FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Laird, JR Katzen, BT Scheinert, D Lammer, J Carpenter, J Buchbinder, M Dave, R Ansel, G Lansky, A Cristea, E Collins, TJ Goldstein, J Jaff, MR AF Laird, John R. Katzen, Barry T. Scheinert, Dierk Lammer, Johannes Carpenter, Jeffrey Buchbinder, Maurice Dave, Rajesh Ansel, Gary Lansky, Alexandra Cristea, Ecaterina Collins, Tyrone J. Goldstein, Jeffrey Jaff, Michael R. CA RESILIENT Investigators TI Response to Letter Regarding Article, "Nitinol Stent Implantation Versus Balloon Angioplasty for Lesions in the Superficial Femoral Artery and Proximal Popliteal Artery: Twelve-Month Results From the RESILIENT Randomized Trial" SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Letter C1 [Laird, John R.] UC Davis Hlth Syst, Sacramento, CA USA. [Katzen, Barry T.] Baptist Heart & Vasc Ctr, Miami, FL USA. [Scheinert, Dierk] Leipzig Heart Ctr, Leipzig, Germany. [Lammer, Johannes] Med Univ Vienna, Vienna, Austria. [Carpenter, Jeffrey] Univ Penn, Philadelphia, PA 19104 USA. [Buchbinder, Maurice] Scripps Clin, San Diego, CA USA. [Dave, Rajesh] Pinnacle Hlth Syst, Harrisburg, PA USA. [Ansel, Gary] Riverside Methodist Hosp, Columbus, OH 43214 USA. [Lansky, Alexandra; Cristea, Ecaterina] Cardiovasc Res Fdn, New York, NY USA. [Collins, Tyrone J.] Oschner Clin Fdn, New Orleans, LA USA. [Goldstein, Jeffrey] Prairie Educ & Res Ctr, Springfield, IL USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Laird, JR (reprint author), UC Davis Hlth Syst, Sacramento, CA USA. RI Collins, Tyrone/H-1695-2014 NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD OCT PY 2010 VL 3 IS 5 BP E23 EP E23 DI 10.1161/CIRCINTERVENTIONS.110.958181 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666ZA UT WOS:000283160500003 ER PT J AU Tsai, TT Maddox, TM Rumsfeld, JS Ho, PM Magid, DJ Xu, S Powers, JD Carroll, NM Shetterly, SM Margolis, K Go, AS AF Tsai, Thomas T. Maddox, Thomas M. Rumsfeld, John S. Ho, P. Michael Magid, David J. Xu, Stanley Powers, J. David Carroll, Nikki M. Shetterly, Susan M. Margolis, Karen Go, Alan S. TI Response to Letter Regarding Article, "Increased Risk of Bleeding in Patients on Clopidogrel Therapy After Drug-Eluting Stents Implantation: Insights From the HMO Research Network-Stent Registry (HMORN-Stent)" SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Letter ID LONG-TERM OUTCOMES; THROMBOSIS C1 [Tsai, Thomas T.; Maddox, Thomas M.; Rumsfeld, John S.; Ho, P. Michael; Magid, David J.] Univ Colorado, Denver VA Med Ctr, Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80202 USA. [Margolis, Karen] HealthPartners Res Fdn, Minneapolis, MN USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Go, Alan S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Tsai, TT (reprint author), Univ Colorado, Denver VA Med Ctr, Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80202 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD OCT PY 2010 VL 3 IS 5 BP E25 EP E25 DI 10.1161/CIRCINTERVENTIONS.110.958587 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666ZA UT WOS:000283160500005 ER PT J AU Mullins, RJ Clark, S Camargo, CA AF Mullins, R. J. Clark, S. Camargo, C. A., Jr. TI Socio-economic status, geographic remoteness and childhood food allergy and anaphylaxis in Australia SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE anaphylaxis; Australia; epidemiology; EpiPen; food allergy; geographic remoteness; infant hypoallergenic formula; rural; socio-economic status ID RISK-FACTORS; VITAMIN-D; ASTHMA; SENSITIZATION; PREVALENCE; CHILDREN; TRENDS; ASSOCIATION; ECZEMA; HOSPITALIZATIONS AB Background The risk factors for food allergy (FA) and anaphylaxis remain uncertain. Objective We examined the association between socio-economic status (SES), geographic remoteness and childhood FA and anaphylaxis in Australia. Methods Sales of infant hypoallergenic formulae (IHF; 2008-2009) and EpiPens (2006-2007) in children aged 0-4 years and hospital anaphylaxis admission rates (2002-2006) in age groups 0-4, 5-14, 15-24, 25-64 and 651 years were used as proxy markers of FA and anaphylaxis in Australia. Government and commercially derived data were analysed by SES and geographic remoteness (very remote, remote, outer regional, inner regional and major cities). Results Annual IHF sales rates were higher in those with the greatest compared with the least socio-economic advantage (47 830 vs. 21 384 tins/100 000 population; P<0.001). EpiPen sales trends were also higher in those with the greatest socio-economic advantage in all age groups, most marked in those aged 0-4 (1713 vs. 669/100 000; P = 0.002) and 5-14 years (1628 vs. 600/100 000; P = 0.001). Formula sales rates were higher in major cities than remote/very remote regions (37 421 vs. 6704/100 000; P<0.001) with similar EpiPen sales trends, particularly in ages 0-4 (1166 vs. 601/100 000; P = 0.045) and 5-14 years (1099 vs. 588/100 000; P<0.001). Socio-economic advantage and geographic remoteness remained statistically significant in multivariable analysis of prescription rates (P<0.01) and were unchanged by adjustment for health services access. While anaphylaxis admission rates were higher in those with the greatest compared with the least socio-economic advantage in children aged 0-4 years (129 vs. 92/100 000 population/year; P = 0.03), the opposite was observed in older age groups (e. g. aged 25-64 years: 43 vs. 76, P = 0.01). There was no association between geographic remoteness and anaphylaxis admissions. Conclusion Socio-economic advantage and residence in major cities may be risk factors for developing childhood FA and anaphylaxis. Further study will determine the extent to which economic factors and location of residence also influence access to health services. C1 [Mullins, R. J.] John James Med Ctr, Deakin, ACT 2600, Australia. [Mullins, R. J.] Australian Natl Univ, Sch Med, Canberra, ACT, Australia. [Mullins, R. J.] Univ Canberra, Fac Hlth, Canberra, ACT 2601, Australia. [Clark, S.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Camargo, C. A., Jr.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, C. A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Mullins, RJ (reprint author), John James Med Ctr, Suite 1,175 Strickland Crescent, Deakin, ACT 2600, Australia. EM rmullins@allergycapital.com.au OI Mullins, Raymond/0000-0002-0267-1591 FU Commonwealth Serum Laboratories Australia; Alpha-pharm Australia; Ilhan Food Allergy Foundation, Melbourne, Australia; Dey (Basking Ridge, NJ, USA) FX Dr Mullins received unrestricted investigator-initiated grants for data purchase from Commonwealth Serum Laboratories Australia and Alpha-pharm Australia (the past and current Australian distributors of EpiPen) and the Ilhan Food Allergy Foundation, Melbourne, Australia. Dr Camargo has received consulting funds and an investigator-initiated research grant from Dey (Basking Ridge, NJ, USA). Dr Clark declares no conflict of interest.; Data purchase was funded with unrestricted investigator-initiated grants from Commonwealth Serum Laboratories Australia and Alphapharm Australia (the past and current Australian distributors of EpiPen) and the Ilhan Food Allergy Foundation, Melbourne, Australia. Study sponsors had no input into study design, data interpretation or the contents of this manuscript. NR 45 TC 17 Z9 17 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD OCT PY 2010 VL 40 IS 10 BP 1523 EP 1532 DI 10.1111/j.1365-2222.2010.03573.x PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 647RJ UT WOS:000281636000012 PM 20636400 ER PT J AU Anders, CK Winer, EP Ford, JM Dent, R Silver, DP Sledge, GW Carey, LA AF Anders, Carey K. Winer, Eric P. Ford, James M. Dent, Rebecca Silver, Daniel P. Sledge, George W. Carey, Lisa A. TI Poly(ADP-Ribose) Polymerase Inhibition: "Targeted" Therapy for Triple-Negative Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Review ID BASAL-LIKE SUBTYPE; HOMOLOGOUS RECOMBINATION; PARP INHIBITORS; DNA-DAMAGE; BRCA1; REPAIR; TUMORS; EXPRESSION; SENSITIVITY; CARCINOMAS AB In contrast to endocrine-sensitive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer, novel agents capable of treating advanced triple-negative breast cancer (TNBC) are lacking. Poly (ADP-ribose) polymerase (PARP) inhibitors are emerging as one of the most promising "targeted" therapeutics to treat TNBC, with the intended "target" being DNA repair. PARPs are a family of enzymes involved in multiple cellular processes, including DNA repair. TNBC shares multiple clinico-pathologic features with BRCA-mutated breast cancers, which harbor dysfunctional DNA repair mechanisms. Investigators hypothesized that PARP inhibition, in conjunction with the loss of DNA repair via BRCA-dependent mechanisms, would result in synthetic lethality and augmented cell death. This hypothesis has borne out in both preclinical models and in clinical trials testing PARP inhibitors in both BRCA-deficient and triple-negative breast cancer. The focus of this review includes an overview of the preclinical rationale for evaluating PARP inhibitors in TNBC, the presumed mechanism of action of this novel therapeutic class, promising results from several influential clinical trials of PARP inhibition in advanced breast cancer (both TNBC and BRCA deficient), proposed mechanisms of acquired resistance to PARP inhibitors, and, finally, concludes with current challenges and future directions for the development of PARP inhibitors in the treatment of breast cancer. Clin Cancer Res; 16(19); 4702-10. (C) 2010 AACR. C1 [Anders, Carey K.; Carey, Lisa A.] Univ N Carolina, Chapel Hill, NC 27517 USA. [Winer, Eric P.; Silver, Daniel P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ford, James M.] Stanford Univ, San Francisco, CA USA. [Dent, Rebecca] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Sledge, George W.] Indiana Univ Melvin & Bren Simon Canc Ctr, Indianapolis, IN USA. RP Anders, CK (reprint author), Univ N Carolina, 170 Manning Dr,CB 7305, Chapel Hill, NC 27517 USA. EM carey_anders@med.unc.edu FU Glaxo Smith Klein; Boehringer-Ingelheim; Genentech; Wyeth; Bristol Myers Squibb; BiPAR/Sanofi Aventis; NCI [CA058223]; NIH [R01 CA108794]; Breast Cancer Research Foundation; Susan G. Komen for the Cure; National Cancer Institute at the Dana-Farber/Harvard Cancer Center [CA089393]; Cogan Family Foundation; Canadian Breast Cancer Research Foundation; [5K12CA120780-03] FX L. Carey, commercial research support, Glaxo Smith Klein, Boehringer-Ingelheim, Genentech, Wyeth, Bristol Myers Squibb; consultant, Sanofi-Aventis/BiPar, Wyeth, Pfizer, Genentech, Bristol Myers Squibb, Novartis; C. Anders, consultant and research support, BiPAR/Sanofi Aventis; R. Dent, consultant, AstraZeneca and BiPAR/Sanofi-Aventis. The other authors disclosed no potential conflicts of interest.; 5K12CA120780-03 (C.K. Anders), NCI CA058223 (UNC SPORE, C.K. Anders and L.A. Carey), NIH R01 CA108794 (J.M. Ford), Breast Cancer Research Foundation (J.M. Ford), Susan G. Komen for the Cure (J.M. Ford); National Cancer Institute Program of Research Excellence (SPORE) in Breast Cancer at the Dana-Farber/Harvard Cancer Center CA089393 (D.P. Silver), and the Cogan Family Foundation (D.P. Silver); and Canadian Breast Cancer Research Foundation (R. Dent). NR 51 TC 75 Z9 76 U1 6 U2 23 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2010 VL 16 IS 19 BP 4702 EP 4710 DI 10.1158/1078-0432.CCR-10-0939 PG 9 WC Oncology SC Oncology GA 660MO UT WOS:000282647900004 PM 20858840 ER PT J AU Seeff, LB Everson, GT Morgan, TR Curto, TM Lee, WM Ghany, MG Shiffman, ML Fontana, RJ Di Bisceglie, AM Bonkovsky, HL Dienstag, JL AF Seeff, Leonard B. Everson, Gregory T. Morgan, Timothy R. Curto, Teresa M. Lee, William M. Ghany, Marc G. Shiffman, Mitchell L. Fontana, Robert J. Di Bisceglie, Adrian M. Bonkovsky, Herbert L. Dienstag, Jules L. CA HALT-C Trial Grp TI Complication Rate of Percutaneous Liver Biopsies Among Persons With Advanced Chronic Liver Disease in the HALT-C Trial SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Liver Biopsy; Complications; Adverse Event; Serious Adverse Events; Bleeding; Platelet Count; INR ID CHRONIC HEPATITIS-C; COAGULATION; RISK; INTERFERON; THERAPY; AUDIT; MODEL AB BACKGROUND & AIMS: Although percutaneous liver biopsy is a standard diagnostic procedure, it has drawbacks, including risk of serious complications. It is not known whether persons with advanced chronic liver disease have a greater risk of complications from liver biopsy than patients with more mild, chronic liver disease. The safety and complications of liver biopsy were examined in patients with hepatitis C-related bridging fibrosis or cirrhosis who were enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial. METHODS: Standard case report forms from 2740 liver biopsies performed at 10 study sites between 2000 and 2006 were reviewed for serious adverse events, together with information from questionnaires completed by investigators about details of biopsy techniques used at each hospital. RESULTS: There were 29 serious adverse events (1.1%); the most common was bleeding (16 cases; 0.6%). There were no biopsy-related deaths. The bleeding rare was higher among patients with platelet counts of 60,000/mm(3) or less and among those with an international normalized ratio of 1.3 or greater, although none of the patients with an international normalized ratio greater than 1.5 bled. Excluding subjects with a platelet count of 60,000/mm(3) or less would have reduced the bleeding rate by 25% (4 of 16), eliminating only 2.8% (77 of 2740) of biopsies. Operator experience, the type of needle used, or the performance of the biopsy under ultrasound guidance did not influence the frequencies of adverse events. CONCLUSIONS: Approximately 0.5% of persons with hepatitis C and advanced fibrosis experienced potentially serious bleeding after liver biopsy; risk increased significantly in patients with platelet counts of 60,000/mm(3) or less. C1 [Seeff, Leonard B.] NIDDK, Div Digest Dis & Nutr, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Everson, Gregory T.] Univ Colorado Denver, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Aurora, CO USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Richmond, VA USA. [Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Dienstag, Jules L.] Harvard Univ, Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02115 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Seeff, LB (reprint author), NIDDK, Div Digest Dis & Nutr, NIH, US Dept HHS, 31A Ctr Dr,Room 9A27, Bethesda, MD 20892 USA. EM seeffl@extra.niddk.nih.gov FU National Institute of Diabetes & Digestive & Kidney Diseases; Hoffmann-La Roche, Inc FX This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed above). Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed above). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc, through a Cooperative Research and Development Agreement with the National Institutes of Health. NR 31 TC 96 Z9 100 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2010 VL 8 IS 10 BP 877 EP 883 DI 10.1016/j.cgh.2010.03.025 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 665NM UT WOS:000283042500014 PM 20362695 ER PT J AU Krakower, D Kwan, CK Yassa, DS Colvin, RA AF Krakower, Douglas Kwan, Candice K. Yassa, David S. Colvin, Richard A. TI iAIDS: HIV-Related Internet Resources for the Practicing Clinician SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB In this review, we collate 25 clinically useful human immunodeficiency virus (HIV)-related Web sites to facilitate efficient access to online resources according to themes of clinical inquiry: (1) comprehensive clinical information, (2) opportunistic infections, (3) antiretroviral drug interactions, (4) care of HIV-infected women and children, and (5) continuing medical education. We evaluated these Web sites for clinical content and quality using criteria including the currency of information, inclusion of references, sponsors, whether the site is useful in resource-limited settings, ease of navigation, and content specific for each theme. Using the specified criteria, we provided overall ratings for each Web site. We conclude that the Web sites listed in this review can help extend knowledge about best practices and provide real-time patient care support to clinicians. C1 [Colvin, Richard A.] Massachusetts Gen Hosp, Chelsea Hlth Care Ctr, Div Infect Dis, Dept Med, Chelsea, MA 02150 USA. [Krakower, Douglas; Yassa, David S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Infect Dis,Dept Med, Boston, MA 02215 USA. [Kwan, Candice K.] NYU, Sch Med, Bellevue Hosp Ctr, Div Infect Dis,Dept Med, New York, NY USA. RP Colvin, RA (reprint author), Massachusetts Gen Hosp, Chelsea Hlth Care Ctr, Div Infect Dis, Dept Med, Chelsea, MA 02150 USA. EM rcolvin@partners.org NR 5 TC 10 Z9 10 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 OCT 1 PY 2010 VL 51 IS 7 BP 813 EP 822 DI 10.1086/656237 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 646YX UT WOS:000281583000010 PM 20738185 ER PT J AU Bassett, IV Wang, BX Chetty, S Giddy, J Losina, E Mazibuko, M Bearnot, B Allen, J Walensky, RP Freedberg, KA AF Bassett, Ingrid V. Wang, Bingxia Chetty, Senica Giddy, Janet Losina, Elena Mazibuko, Matilda Bearnot, Benjamin Allen, Jenny Walensky, Rochelle P. Freedberg, Kenneth A. TI Intensive Tuberculosis Screening for HIV-Infected Patients Starting Antiretroviral Therapy in Durban, South Africa SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SUB-SAHARAN AFRICA; PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; RESPIRATORY SPECIMENS; DIAGNOSIS; MORTALITY; PREVALENCE; COMMUNITY; COUNTRIES; TANZANIA AB Background. The World Health Organization (WHO) recommends cough as the trigger for tuberculosis screening in human immunodeficiency virus (HIV)-infected patients, with acid-fast bacillus (AFB) smear as the initial diagnostic test. Our objective was to assess the yield and cost of a more intensive tuberculosis screening in HIV-infected patients starting antiretroviral therapy (ART) in Durban, South Africa. Methods. We prospectively enrolled adults, regardless of tuberculosis signs/symptoms, who were undergoing ART training from May 2007 to May 2008. After the symptom screen, patients expectorated sputum for AFB smear, tuberculosis polymerase chain reaction (PCR), and mycobacterial culture. Sensitivity and specificity of different symptoms and tests, alone and in combination, were compared with the reference standard of 6-week tuberculosis culture results. Program costs included personnel, materials, and cultures. Results. Of 1035 subjects, 487 (59%) were female; median CD4 cell count was 100 cells/mu L. A total of 210 subjects (20%) were receiving tuberculosis treatment and were excluded. Of the remaining 825 subjects, 158 (19%) had positive sputum cultures, of whom 14 (9%) had a positive AFB smear and 82 (52%) reported cough. The combination of cough, other symptoms, AFB smear, and chest radiograph had 93% sensitivity (95% confidence interval, 88%-97%) and 15% specificity (95% confidence interval, 13%-18%). The incremental cost of intensive screening including culture was $360 per additional tuberculosis case identified. Conclusions. Nearly 20% of patients starting ART in Durban, South Africa, had undiagnosed, culture-positive pulmonary tuberculosis. Despite WHO recommendations, neither cough nor AFB smear were adequately sensitive for screening. Tuberculosis sputum cultures should be performed before ART initiation, regardless of symptoms, in areas with a high prevalence of HIV and tuberculosis. C1 [Bassett, Ingrid V.; Walensky, Rochelle P.] Harvard Univ, Div Infect Dis, Boston, MA 02115 USA. [Bassett, Ingrid V.; Wang, Bingxia; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Div Gen Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wang, Bingxia; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Harvard Ctr AIDS Res, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Chetty, Senica; Giddy, Janet; Mazibuko, Matilda; Bearnot, Benjamin] McCord Hosp, Durban, South Africa. [Allen, Jenny] Univ KwaZulu, Natal Microbiol Lab, Durban, South Africa. [Allen, Jenny] MRC, Durban, South Africa. RP Bassett, IV (reprint author), 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM ibassett@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Disease [K23 AI 068458, R01 AI058736, K24 AI062476]; National Institute of Mental Health [R01 MH073445]; Harvard University Center for AIDS Research [P30 AI060354]; Doris Duke Charitable Foundation; ORACTA FX National Institute of Allergy and Infectious Disease: K23 AI 068458 (IVB); R01 AI058736 (KAF); K24 AI062476 (KAF); the National Institute of Mental Health: R01 MH073445 (RPW); the Harvard University Center for AIDS Research P30 AI060354; the Doris Duke Charitable Foundation, Clinical Scientist Development Award (RPW) and ORACTA (KAF). NR 31 TC 86 Z9 88 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2010 VL 51 IS 7 BP 823 EP 829 DI 10.1086/656282 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 646YX UT WOS:000281583000011 PM 20735240 ER PT J AU Boyajian, R AF Boyajian, Richard TI Depression's Impact on Survival in Patients With Cancer SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; CORONARY-ARTERY-DISEASE; MENTAL STRESS; MYOCARDIAL-ISCHEMIA; HEART-DISEASE; DAILY-LIFE; RISK; ASSOCIATION; PROGRESSION; MECHANISMS AB Healthcare professionals spend a great deal of time evaluating prognostic indicators to improve the treatment and survival of patients. With the building evidence that depression is an independent prognostic factor, they should look to do what those in cardiology are attempting intervention trials to treat depression and lower its risk. As patient advocates, oncology nurses should look at their practice and make sure they incorporate psychosocial assessment as a standard component of cancer care. C1 Dana Farber Canc Inst, Adult Survivorship Program, Boston, MA 02115 USA. RP Boyajian, R (reprint author), Dana Farber Canc Inst, Adult Survivorship Program, Boston, MA 02115 USA. EM rboyajian@partners.org NR 33 TC 0 Z9 1 U1 0 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD OCT PY 2010 VL 14 IS 5 BP 649 EP 652 DI 10.1188/10.CJON.649-652 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA 672WM UT WOS:000283617700015 PM 20880822 ER PT J AU Treon, SP AF Treon, Steven P. TI Fc gamma Receptor Predictive Genomic Testing and the Treatment of Indolent Non-Hodgkin Lymphoma SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Editorial Material ID MONOCLONAL-ANTIBODY; CLINICAL-RESPONSE; RIIIA; POLYMORPHISMS; RITUXIMAB; THERAPY; LINKAGE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 15 TC 3 Z9 3 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD OCT PY 2010 VL 10 IS 5 BP 321 EP 322 DI 10.3816/CLML.2010.n.063 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 672TR UT WOS:000283610300001 PM 21030343 ER PT J AU Wierda, WG Chiorazzi, N Dearden, C Brown, JR Montserrat, E Shpall, E Stilgenbauer, S Muneer, S Greyer, M AF Wierda, William G. Chiorazzi, Nicholas Dearden, Claire Brown, Jennifer R. Montserrat, Emili Shpall, Elizabeth Stilgenbauer, Stephan Muneer, Sabeeha Greyer, Michael TI Chronic Lymphocytic Leukemia: New Concepts for Future Therapy SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Review DE Alemtuzumab; Bendamustine; Flavopiridol; Lenalidomide; Ofatumumab ID PROGRESSION-FREE SURVIVAL; PREVIOUSLY UNTREATED PATIENTS; STEM-CELL TRANSPLANTATION; CXCR4 CHEMOKINE RECEPTOR; CLL STUDY-GROUP; PHASE-II TRIAL; B-CELLS; ANTITUMOR-ACTIVITY; ANTIBODY THERAPY; PLUS FLUDARABINE AB Over the past several years, we have witnessed rapid advances in our understanding of the biology and treatment of chronic lymphocytic leukemia (CLL). New prognostic factors have been characterized that help identify patients at high risk of rapid disease progression, refractoriness to treatment, and short overall survival (OS). These advances have led to a significant paradigm shift in the management of CLL. Novel therapeutic strategies, including combinations of monoclonal antibodies with conventional chemotherapy, have dramatically improved response rates, remission duration, and recently, OS. However, these benefits do not appear to extend to certain patient subsets, especially those with unfavorable clinical or cytogenetic risk factors. The majority of patients with CLL will invariably relapse following first-line therapy and can acquire high-risk genetic abnormalities. Repeated treatment leads to eventual therapeutic refractoriness and shortened survival compared with age-matched healthy individuals. Several novel agents and strategies, including next-generation anti-CD20 monoclonal antibodies, the alkylating agent bendamustine, the immunomodulatory agent lenalidomide, the cyclin-dependent kinase inhibitor flavopiridol, and small-molecule Bcl2 inhibitors, are currently under clinical investigation as novel agents that will hopefully improve treatment outcomes for CLL. Though allogeneic stem cell transplantation offers curative potential, it also presents clinical challenges in terms of patient appropriateness, donor availability, and timing. The merits and challenges of incorporating these treatment modalities into the treatment algorithm for patients with CLL, as discussed by a panel of experts in CLL, are outlined in this article. C1 [Wierda, William G.; Shpall, Elizabeth] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Chiorazzi, Nicholas] Feinstein Inst Med Res, Manhasset, NY USA. [Dearden, Claire] Royal Marsden Hosp, Surrey, England. [Dearden, Claire] Inst Canc Res, Surrey, England. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Montserrat, Emili] Univ Barcelona, E-08007 Barcelona, Spain. [Stilgenbauer, Stephan] Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany. [Muneer, Sabeeha] Phys Educ Resource, Dallas, TX USA. [Greyer, Michael] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. RP Wierda, WG (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM wwierda@mdanderson.org FU Abbott Laboratories; Berlex Oncology/Bayer Pharmaceuticals Corporation; Genmab; GlaxoSmithKline; Memgen; LLC; sanofi-aventis, U.S.; Sunesis Pharmaceuticals, Inc.; Roche Pharmaceuticals; Celgene Corporation; Genzyme Corporation; Amgen; Bayer Healthcare AG; Mundipharma Laboratories GmbH; sanofi-aventis FX William G. Wierda has served as a consultant or been on an advisory board for Berlex Oncology/Bayer Pharmaceuticals Corporation, Biogen Idec, Celgene Corporation, Cephalon, Inc., Genentech, Inc., Genzyme Corporation, Ligand Pharmaceuticals, Inc., MedImmune, Inc., Micromet, Inc., and Schering-Plough Corporation; has served on a Speaker's Bureau for Celgene Corporation, Cephalon, Inc., Genzyme Corporation, GlaxoSmithKline, and Roche Pharmaceuticals; and has received research funding from Abbott Laboratories, Berlex Oncology/Bayer Pharmaceuticals Corporation, Genmab, GlaxoSmithKline, Memgen, LLC, sanofi-aventis, U.S., and Sunesis Pharmaceuticals, Inc. Emili Montserrat has received research funding from GlaxoSmithKline and Roche Pharmaceuticals, and has served as a consultant or been on an advisory/research panel for Roche Pharmaceuticals. Claire Dearden has served as a consultant or been on an advisory/research panel for Genzyme Corporation, GlaxoSmithKline, and Roche Pharmaceuticals. Jennifer R. Brown has received research funding from Celgene Corporation and Genzyme Corporation, and has served as a consultant or been on an advisory/research panel for Calistoga Pharmaceuticals, Inc. and Celgene Corporation. Stephan Stilgenbauer has received research funding from Amgen, Bayer Healthcare AG, Celgene Corporation, Genzyme Corporation, GlaxoSmithKline, Mundipharma Laboratories GmbH, Roche Pharmaceuticals, and sanofi-aventis. The remaining authors have no relevant relationships to disclose. NR 95 TC 8 Z9 10 U1 0 U2 6 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD OCT PY 2010 VL 10 IS 5 BP 369 EP 378 DI 10.3816/CLML.2010.n.070 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 672TR UT WOS:000283610300007 PM 21030350 ER PT J AU Sure, D Dunn, I Norden, A Anderson, WS AF Sure, Durga Dunn, Ian Norden, Andrew Anderson, William S. TI Intracerebral hemorrhage secondary to thrombocytopenia in a patient treated with temozolomide SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Letter DE Temozolomide; Thrombocytopenia; Intracerebral hemorrhage; Myelotoxicity ID GLIOMAS AB Thrombocytopenia related intracerebral hemorrhage (ICH) secondary to chemotherapy induced myelosuppression can be very difficult to manage and may result in the death of the patient. We present the case of a 26-year-old male suffering a fatal ICH in the context of treatment of a high grade glioma with temozolomide. The clinician should be aware that a dose dependent severe and possible irreversible myelotoxicity can occur with temozolomide treatment resulting in substantial morbidity. (C) 2010 Elsevier B.V. All rights reserved. C1 [Anderson, William S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Norden, Andrew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dunn, Ian] Univ Arkansas Med Sci, Dept Neurosurg, Little Rock, AR 72205 USA. [Sure, Durga] Louisiana State Univ, Sch Med, Dept Neurosurg, Marrero, LA 70072 USA. RP Anderson, WS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, 75 Francis St CA 138F, Boston, MA 02115 USA. EM dsure@lsuhsc.edu; idunn@partners.org; anorden@partners.org; wsanderson@partners.org NR 5 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD OCT PY 2010 VL 112 IS 8 BP 741 EP 742 DI 10.1016/j.clineuro.2010.04.005 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 651ZG UT WOS:000281967300023 PM 20434832 ER PT J AU Bourgeois, FC Linder, J Johnson, SA Co, JPT Fiskio, J Ferris, TG AF Bourgeois, Fabienne C. Linder, Jeffrey Johnson, Sarah A. Co, John Patrick T. Fiskio, Julie Ferris, Timothy G. TI Impact of a Computerized Template on Antibiotic Prescribing for Acute Respiratory Infections in Children and Adolescents SO CLINICAL PEDIATRICS LA English DT Article AB Background. Computerized decision support (CDS) can potentially improve patient safety and guideline adherence. The authors developed an acute respiratory illness interactive template (ARI-IT) within an electronic health record (EHR) to manage pediatric ARIs and assessed the impact on antibiotic prescribing. Methods. They randomized 12 practices either to receive the ARI-IT or to the control group. Antibiotic rates among all eligible ARI diagnoses were compared among control and intervention ARI visits, controlling for clustering by clinician. Results. There was no difference in total antibiotic prescriptions between control and intervention clinics. Use of the ARI-IT significantly reduced antibiotic prescriptions (31.7% vs 39.9%; P = .02) and use of macrolides (6.2% vs 9.5%; P = .02) among visits compared with those eligible visits where it was not used. Conclusion. Use of the CDS reduced antibiotic prescribing and macrolide prescriptions among children with an ARI. Nonetheless, the low overall use resulted in an ineffective intervention. C1 [Bourgeois, Fabienne C.] Childrens Hosp, Boston, MA 02115 USA. [Bourgeois, Fabienne C.; Linder, Jeffrey; Co, John Patrick T.; Ferris, Timothy G.] Harvard Univ, Sch Med, Boston, MA USA. [Linder, Jeffrey; Fiskio, Julie] Brigham & Womens Hosp, Boston, MA 02115 USA. [Johnson, Sarah A.; Ferris, Timothy G.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Co, John Patrick T.; Ferris, Timothy G.] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. RP Bourgeois, FC (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM fabienne.bourgeois@childrens.harvard.edu FU Agency for Healthcare Research and Quality [NCT00134823] FX This study was funded by the Agency for Healthcare Research and Quality grant Improving Pediatric Safety and Quality With Health Care IT Registration Number: NCT00134823 http://clinicaltrials.gov/ct2/show/NCT00134823. NR 46 TC 12 Z9 12 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD OCT PY 2010 VL 49 IS 10 BP 976 EP 983 DI 10.1177/0009922810373649 PG 8 WC Pediatrics SC Pediatrics GA V28KQ UT WOS:000208680100008 PM 20724348 ER PT J AU Eickhoff, JC Kim, K Beach, J Kolesar, JM Gee, JR AF Eickhoff, Jens C. Kim, KyungMann Beach, Jason Kolesar, Jill M. Gee, Jason R. TI A Bayesian adaptive design with biomarkers for targeted therapies SO CLINICAL TRIALS LA English DT Article; Proceedings Paper CT Annual Conference on Statistical Issues on Clinical Trials - Statistical Issues in Developing Targeted Therapies CY APR 29, 2009 CL Univ Pennsylvania, Philadelphia, PA SP Amer Stat Assoc, Soc Clinical Trials HO Univ Pennsylvania ID CLINICAL-TRIAL DESIGNS; PARTIAL LEAST-SQUARES; CANCER; CLASSIFICATION; RANDOMIZATION; VALIDATION; REGRESSION; EFFICIENCY AB Background Targeted therapies are becoming increasingly important for the treatment of various diseases. Biomarkers are a critical component of a targeted therapy as they can be used to identify patients who are more likely to benefit from a treatment. Targeted therapies, however, have created major challenges in the design, conduct, and analysis of clinical trials. In traditional clinical trials, treatment effects for various biomarkers are typically evaluated in an exploratory fashion and only limited information about the predictive values of biomarkers obtained. Purpose New study designs are required, which effectively evaluate both the diagnostic and the therapeutic implication of biomarkers. Methods The Bayesian approach provides a useful framework for optimizing the clinical trial design by directly integrating information about biomarkers and clinical outcomes as they become available. We propose a Bayesian covariate-adjusted response-adaptive randomization design, which utilizes individual biomarker profiles and patient's clinical outcomes as they become available during the course of the trial, to assign the most efficacious treatment to individual patients. Predictive biomarker subgroups are determined adaptively using a partial least squares regression approach. Results A series of simulation studies were conducted to examine the operating characteristics of the proposed study design. The simulation studies show that the proposed design efficiently identifies patients who benefit most from a targeted therapy and that there are substantial savings in the sample size requirements when compared to alternative designs. Limitations The design does not control for the type I error in the traditional sense and a positive result should be confirmed by conducting an independent phase III study focusing on the selected biomarker profile groups. Conclusions We conclude that the proposed design may serve a useful role in the early efficacy phase of targeted therapy development. Clinical Trials 2010; 7: 546-556. http://ctj.sagepub.com C1 [Eickhoff, Jens C.; Kim, KyungMann; Beach, Jason] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. [Eickhoff, Jens C.; Kim, KyungMann; Kolesar, Jill M.] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI USA. [Gee, Jason R.] William S Middleton Mem Vet Adm Med Ctr, Urol Sect, Madison, WI USA. [Gee, Jason R.] Lahey Clin Med Ctr, Sophia Gordon Canc Ctr, Inst Urol, Burlington, MA 01803 USA. RP Eickhoff, JC (reprint author), Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. EM eickhoff@biostat.wisc.edu FU NCI NIH HHS [P30 CA014520, P30 CA14520] NR 27 TC 13 Z9 14 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2010 VL 7 IS 5 BP 546 EP 556 DI 10.1177/1740774510372657 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 653KK UT WOS:000282089800005 PM 20571131 ER PT J AU Young, KY Laird, A Zhou, XH AF Young, K. Y. Laird, A. Zhou, X. H. TI The efficiency of clinical trial designs for predictive biomarker validation SO CLINICAL TRIALS LA English DT Article; Proceedings Paper CT Annual Conference on Statistical Issues on Clinical Trials - Statistical Issues in Developing Targeted Therapies CY APR 29, 2009 CL Univ Pennsylvania, Philadelphia, PA SP Amer Stat Assoc, Soc Clinical Trials HO Univ Pennsylvania ID BREAST-CANCER; CHEMOTHERAPY AB Background The rapid advance of molecular genetic technology and of molecular diagnostics companies have set the stage for a new era in personalized treatments. Biomarkers such as gene expressions may be integrated into the anatomically based tumor-node-metastasis staging system to provide information for risk stratification and treatment selection. With the assumption that preliminary results show evidence that a biomarker has predictive value, the marker-based designs are geared to assess the purported predictive value in a clinical trial. Purpose In this article, we compared the efficiency of the traditional design, which does not involve a biomarker, to several alternative designs in terms of the sample size required in each trial. Methods We first derived the variance formulas for the two-sample t-tests under the various designs when the biomarker assay is imperfect, and then conducted numerical and simulation studies to evaluate the performance of the various designs. Results Based on numerical and simulation studies, we conclude that the marker-based strategy designs are less efficient than the traditional design in general. Since the biomarker assay is imperfect in a realistic setting, the estimated sample size for each alternative design is influenced by the sensitivity and specificity of the assay and the prevalence of the biomarker in the population of interest as well as the parameters involved in a standard sample size calculation. Limitations Due to limitations of a simulation study, it is not clear whether our results can be generalized to other parameter settings that are different from the ones used in the simulation study. Conclusions The marker-based strategy designs are less efficient than the traditional design in general. If there is no treatment effect among marker-negative patients, it is still feasible to use the marker-based strategy design I if the assay sensitivity is high. If the treatment effect among marker-negative patients is half of the effect among marker-positive patients, the marker prevalence must be relatively high and the sensitivity of the assay must be very high for the marker-based strategy design I to approximate the efficiency of the traditional design. The efficiency of the marker-based strategy design II relative to the traditional design is low in all scenarios considered under the current study. Clinical Trials 2010; 7: 557-566. http://ctj.sagepub.com C1 [Young, K. Y.; Laird, A.; Zhou, X. H.] Univ Washington, Dept Biostat, Seattle, WA 98198 USA. [Zhou, X. H.] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, HSB Box 357232, Seattle, WA 98198 USA. EM azhou@u.washington.edu NR 12 TC 14 Z9 14 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2010 VL 7 IS 5 BP 557 EP 566 DI 10.1177/1740774510370497 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 653KK UT WOS:000282089800006 PM 20571132 ER PT J AU Ellenbecker, TS Reinold, M Nelson, CO AF Ellenbecker, Todd S. Reinold, Michael Nelson, Cory O. TI Clinical Concepts for Treatment of the Elbow in the Adolescent Overhead Athlete SO CLINICS IN SPORTS MEDICINE LA English DT Article DE Injury; Elbow; Adolescent; Overhead athlete ID IDENTIFYING SCAPULAR DYSKINESIS; VALGUS EXTENSION OVERLOAD; YOUTH BASEBALL PITCHERS; TENNIS PLAYERS; ELECTROMYOGRAPHIC ANALYSIS; UPPER EXTREMITY; REHABILITATION PROGRAM; COLLATERAL LIGAMENT; GLENOHUMERAL JOINT; SHOULDER FUNCTION AB Injuries to the adolescent elbow are common because of the repetitive overuse inherent in many overhead sport activities. The management of these patients is greatly facilitated through a greater understanding of the demands placed on the upper extremity kinetic chain during these overhead activities as well as a detailed examination and rehabilitation for the entire upper extremity kinetic chain. Particular emphasis on improving rotator cuff strength and muscular endurance, along with scapular stabilization, is a critical part of elbow rehabilitation in these patients. In addition, the use of a strategic and progressive interval sport return program is necessary to minimize reinjury and return the adolescent overhead athlete to full function. C1 [Ellenbecker, Todd S.] Scottsdale Sports Clin, Physiotherapy Associates, Scottsdale, AZ USA. [Ellenbecker, Todd S.] ATP World Tours, Ponte Vedra Beach, FL USA. [Ellenbecker, Todd S.] Physiotherapy Associates, Exton, PA USA. [Reinold, Michael] Massachusetts Gen Hosp, Dept Orthopaed Surg, Div Sports Med, Boston, MA 02114 USA. [Nelson, Cory O.] Spine & Orthoped Specialists, Sports Med Arthroscop Surg, Scottsdale, AZ USA. RP Ellenbecker, TS (reprint author), Scottsdale Sports Clin, Physiotherapy Associates, Scottsdale, AZ USA. EM ellenbeckerpt@cox.net NR 61 TC 4 Z9 4 U1 4 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-5919 J9 CLIN SPORT MED JI Clin. Sports Med. PD OCT PY 2010 VL 29 IS 4 BP 705 EP + DI 10.1016/j.csm.2010.06.006 PG 21 WC Sport Sciences SC Sport Sciences GA 672DA UT WOS:000283562000012 PM 20883905 ER PT J AU Lam, HY Wiggs, JL Jurkunas, UV AF Lam, Helene Y. Wiggs, Janey L. Jurkunas, Ula V. TI Unusual Presentation of Presumed Posterior Polymorphous Dystrophy Associated With Iris Heterochromia, Band Keratopathy, and Keratoconus SO CORNEA LA English DT Article DE posterior polymorphous dystrophy; keratoconus; band keratopathy; VSX-1 ID IRIDOCORNEAL ENDOTHELIAL SYNDROME; CORNEAL-DYSTROPHY; SPECULAR MICROSCOPY; GENE; MUTATIONS; CHROMOSOME-20; LINKAGE; ATROPHY; MAPS; VSX1 AB Purpose: To report an unusual presentation of posterior polymorphous corneal dystrophy (PPCD) associated with band keratopathy, iridocorneal adhesions, heterochromia, keratoconus, and confocal microscopic findings suggestive of iridocorneal endothelial syndrome. Methods: Confocal microscopy, corneal topography, electroretinography, and genetic analysis were performed in the proband and his siblings. Results: A 23-year-old man presented with decreased vision in both eyes over 9 months. Examination revealed bilateral alterations in corneal endothelial mosaic with corneal edema and beaten metal appearance in the right eye and cystoid endothelial opacities in the left eye. Marked heterochromia, band keratopathy, and broad peripheral anterior synechiae were present in both eyes. Topographic features of keratoconus were noted. Electroretinography did not detect abnormal retinal function, as has been described with PPCD associated with VSX1 mutations. Diagnosis of PPCD was postulated on the basis of the examination of 3 of proband's brothers by confocal microscopy. Genetic analysis of 3 known PPCD genes, VSX1, COL8A2, and TCF8, did not detect any mutations. Conclusions: In severe cases, PPCD can resemble iridocorneal endothelial syndromes in both clinical appearance and imaging studies (confocal microscopy). There was a strong genetic phenotypic penetrance in the family, which was essential in the diagnostic decision making. A yet undetermined genotype is contributing to this unusual PPCD phenotype. C1 [Lam, Helene Y.; Wiggs, Janey L.; Jurkunas, Ula V.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Lam, Helene Y.; Wiggs, Janey L.; Jurkunas, Ula V.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Wiggs, Janey L.; Jurkunas, Ula V.] Schepens Eye Res Inst, Boston, MA USA. RP Lam, HY (reprint author), Dedham Med Associates, 1 Lyons St, Dedham, MA 02026 USA. EM helene_lam@vmed.org FU [NEI K12 EY016335] FX Supported by NEI K12 EY016335 (U. V. Jurkunas). NR 26 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD OCT PY 2010 VL 29 IS 10 BP 1180 EP 1185 DI 10.1097/ICO.0b013e3181d007e1 PG 6 WC Ophthalmology SC Ophthalmology GA 653YA UT WOS:000282133100019 PM 20567203 ER PT J AU Kacmarek, RM Villar, J AF Kacmarek, Robert M. Villar, Jesus TI Clinical repercussions of high-frequency percussive ventilation: A burning issue SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE HFPV; barotrauma; ARDS; burn patients ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; CONVENTIONAL VENTILATION; OSCILLATORY VENTILATION; CONTROLLED-TRIAL; LUNG INJURY; METAANALYSIS; MORTALITY; STRATEGY; BENCH C1 [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Villar, Jesus] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Spain. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2010 VL 38 IS 10 BP 2069 EP 2070 DI 10.1097/CCM.0b013e3181f178cb PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 652XB UT WOS:000282043800026 PM 20855997 ER PT J AU Palilla, DS Alston, TA AF Palilla, David S. Alston, Theodore A. TI Caspase: The unfriendly "meat tenderizer" of sepsis SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE apoptosis; caspase; endotoxin; lipopolysaccharide; protease; sarcoplasmic reticulum ID DISEASE; DEATH; APOPTOSIS; SURVIVAL; ENZYME; CED-3 C1 [Palilla, David S.; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. RP Palilla, DS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2010 VL 38 IS 10 BP 2075 EP 2076 DI 10.1097/CCM.0b013e3181f3dd8f PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 652XB UT WOS:000282043800029 PM 20856000 ER PT J AU Simunovic, VJ Hozo, I Rakic, M Jukic, M Tomic, S Kokic, S Ljutic, D Druzijanic, N Grkovic, I Simunovic, F Marasovic, D AF Simunovic, Vladimir J. Hozo, Izet Rakic, Mladen Jukic, Marko Tomic, Snjezana Kokic, Slaven Ljutic, Dragan Druzijanic, Nikica Grkovic, Ivica Simunovic, Filip Marasovic, Dujomir TI New Paradigm in Training of Undergraduate Clinical Skills the NEPTUNE-CS project at the Split University School of Medicine SO CROATIAN MEDICAL JOURNAL LA English DT Article ID EDUCATION; STUDENTS; PROFESSIONALISM; CONTINUITY; EXPERIENCE; PHYSICIAN; PATIENT; REFORM; ART C1 [Simunovic, Vladimir J.] Univ Hosp Split, Unit Sci & Res, Split 21000, Croatia. [Simunovic, Filip] Split Univ, Sch Med, Dept Anat, Split, Croatia. [Hozo, Izet] Univ Hosp Ctr Split, Dept Gastroenterol, Split, Croatia. [Rakic, Mladen; Jukic, Marko] Univ Hosp Ctr Split, Dept Anaesthesiol, Split, Croatia. [Tomic, Snjezana] Univ Hosp Ctr Split, Dept Pathol, Split, Croatia. [Kokic, Slaven] Univ Hosp Ctr Split, Dept Endocrinol, Split, Croatia. [Ljutic, Dragan] Univ Hosp Ctr Split, Dept Nephrol, Split, Croatia. [Druzijanic, Nikica] Univ Hosp Ctr Split, Dept Surg, Split, Croatia. [Simunovic, Filip] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Marasovic, Dujomir] Univ Hosp Ctr Split, Dept Dermatol, Split, Croatia. RP Simunovic, VJ (reprint author), Univ Hosp Split, Unit Sci & Res, Split 21000, Croatia. RI Grkovic, Ivica/D-8728-2017 OI Grkovic, Ivica/0000-0001-9010-2091 NR 36 TC 1 Z9 1 U1 0 U2 3 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-9504 J9 CROAT MED J JI Croat. Med. J. PD OCT PY 2010 VL 51 IS 5 BP 373 EP 380 DI 10.3325/cmj.2010.51.323 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 689ZN UT WOS:000284969700001 PM 20960586 ER PT J AU Raje, N Vallet, S AF Raje, Noopur Vallet, Sonia TI Sotatercept, a soluble activin receptor type 2A IgG-Fc fusion protein for the treatment of anemia and bone loss SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article ID MULTIPLE-MYELOMA; OSTEOCLAST DIFFERENTIATION; POSTMENOPAUSAL WOMEN; HUMAN ERYTHROPOIESIS; SIGNALING PATHWAYS; TUMOR PROGRESSION; GENE-EXPRESSION; CANCER; DISEASE; INHIBIN AB Sotatercept (ACE-011), under development by Acceleron Pharma Inc in collaboration with Celgene Corp, is a chimeric protein containing the extracellular domain of the activin receptor 2A (ACVR2A) fused to the Fc domain of human IgG1. Sotatercept contains the binding site of ACVR2A and interferes with downstream signaling cascades, in particular the SMAD pathway, by sequestering activin. The murine counterpart of sotatercept, referred to as RAP-011, has been extensively evaluated in preclinical studies, in particular in models of cancer-and osteoporosis-related bone loss, and the developing companies envisage that sotatercept may also have potential for the treatment of cancer and cancer-related bone loss. In a phase I clinical trial in postmenopausal females, sotatercept increased hematocrit levels, and, in a phase II trial in patients with multiple myeloma, a trend toward improvement in osteolytic lesions as well as antitumor activity was observed. At the time of publication, phase II trials in patients with anemia were ongoing. Future clinical development will rely on an evaluation of the benefits and complications of sotatercept administration, focusing in particular on suppression of ovarian function and increases in hematocrit levels without a consequent risk of hypertension and thrombosis. C1 [Raje, Noopur; Vallet, Sonia] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Div Hematol Oncol, Boston, MA 02114 USA. RP Raje, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Div Hematol Oncol, POB 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org NR 80 TC 40 Z9 42 U1 0 U2 2 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD OCT PY 2010 VL 12 IS 5 BP 586 EP 597 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 657DL UT WOS:000282392900011 PM 20886391 ER PT J AU Guinan, JJ AF Guinan, John J., Jr. TI Cochlear efferent innervation and function SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY LA English DT Article DE auditory development; auditory psychophysics; descending control; hearing; medial olivocochlear ID CONTRALATERAL ACOUSTIC STIMULATION; PRODUCT OTOACOUSTIC EMISSIONS; MEDIAL OLIVOCOCHLEAR REFLEX; AUDITORY-NERVE RESPONSES; INNER HAIR-CELLS; MASKED TONES; NOISE; RECEPTOR; SYSTEM; INHIBITION AB Purpose of review This review covers topics relevant to olivocochlear-efferent anatomy and function for which there are new findings in papers from 2009 to early 2010. Recent findings Work within the review period has increased our understanding of medial olivocochlear (MOC) mechanisms in outer hair cells, MOC-reflex tuning, MOC effects on distortion product otoacoustic emissions, the time course of MOC effects, MOC effects in psychophysical tests and on understanding speech, MOC effects in attention and learning, and lateral efferent function in binaural hearing. In addition, there are new insights into efferent molecular mechanisms and their effect on cochlear development. Summary Techniques for measuring efferent effects using otoacoustic emissions are now well developed and have promise in clinical applications ranging from predicting which patients are susceptible to acoustic trauma to characterizing relationships between efferent activation and learning disabilities. To realize this promise, studies are needed in which these techniques are applied with high standards. C1 [Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm,Eaton Peabody Labs, Boston, MA 02114 USA. [Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Guinan, John J., Jr.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Guinan, JJ (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm,Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu FU NIH NIDCD [RO1 DC005977, RO1 DC000235, P30 DC005209] FX I thank Dr Jeffery Lichtenhan and Ms Maria Berezina for comments on the manuscript. This study was supported by NIH NIDCD RO1 DC005977, RO1 DC000235, and P30 DC005209. NR 72 TC 70 Z9 71 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1068-9508 EI 1531-6998 J9 CURR OPIN OTOLARYNGO JI Curr. Opin. Otolaryngol. Head Neck Surg. PD OCT PY 2010 VL 18 IS 5 BP 447 EP 453 DI 10.1097/MOO.0b013e32833e05d6 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 647KU UT WOS:000281618200017 PM 20717032 ER PT J AU Mizoguchi, A Mizoguchi, E AF Mizoguchi, Atsushi Mizoguchi, Emiko TI Animal models of IBD: linkage to human disease SO CURRENT OPINION IN PHARMACOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; MEDIATED INTESTINAL INFLAMMATION; TRANSCRIPTION FACTOR FOXP3; T-CELL SUBSET; CROHNS-DISEASE; ULCERATIVE-COLITIS; B-CELLS; INNATE IMMUNITY; MOUSE MODEL AB Spontaneous development of intestinal inflammation in many different kinds of genetically engineered mice as well as the presence of numerous susceptibility genes in humans suggests that inflammatory bowel disease (IBD) is mediated by more complicated mechanisms than previously predicted. The human genetic studies implicate some major pathways in the pathogenesis of IBD, including epithelial defense against commensal microbiota, the IL-23/Th17 axis, and immune regulation. Murine IBD models, which are genetically engineered to lack some susceptibility genes, have been generated, and have provided useful insights into the therapeutic potential of targeting the susceptibility genes directly or their downstream pathways indirectly for IBD. This review summarizes current information related to the function of IBD-associated genes as derived from genetically engineered mouse models. C1 [Mizoguchi, Atsushi] Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. [Mizoguchi, Emiko] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Mizoguchi, Atsushi] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Mizoguchi, Emiko] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mizoguchi, Atsushi; Mizoguchi, Emiko] Ctr Study Inflammatory Bowel Dis, Boston, MA USA. RP Mizoguchi, A (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. EM amizoguchi@partners.org FU NIH [RC1DK086242, RO1DK064351, DK80070, DK74454, DK64289]; Crohn's and Colitis Foundation of America; American Gastroenterological Association Foundation; Eli & Edythe Broad Medical Research Foundation FX We thank Mr Terry Danford Lott for his excellent editorial assistance and Ms Cindy Lau for her technical assistance. This study has been supported by NIH RC1DK086242, RO1DK064351 and Crohn's and Colitis Foundation of America (AM), and NIH DK80070, DK74454, DK64289 and grants from American Gastroenterological Association Foundation and Eli & Edythe Broad Medical Research Foundation (EM). NR 119 TC 40 Z9 44 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD OCT PY 2010 VL 10 IS 5 BP 578 EP 587 DI 10.1016/j.coph.2010.05.007 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 657BB UT WOS:000282384800012 PM 20860919 ER PT J AU Kapoor, R Elston, DM AF Kapoor, Roger Elston, Dirk M. TI What's Eating You? Ixodes Ticks SO CUTIS LA English DT Editorial Material ID HUMAN GRANULOCYTIC EHRLICHIOSIS; LYME-DISEASE; BORRELIA-BURGDORFERI; SCAPULARIS; DURATION; BABESIOSIS; ATTACHMENT; IXODIDAE; ACARI; BIRDS C1 [Elston, Dirk M.] Geisinger Med Ctr, Dept Dermatol, Danville, PA 17822 USA. [Elston, Dirk M.] Geisinger Med Ctr, Dept Lab Med, Danville, PA 17822 USA. [Kapoor, Roger] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Elston, DM (reprint author), Geisinger Med Ctr, Dept Dermatol, 100 N Acad Ave, Danville, PA 17822 USA. EM dmelston@geisinger.edu NR 21 TC 0 Z9 0 U1 0 U2 2 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 J9 CUTIS JI Cutis PD OCT PY 2010 VL 86 IS 4 BP 178 EP 180 PG 3 WC Dermatology SC Dermatology GA 680RD UT WOS:000284251200003 PM 21140924 ER PT J AU Kalapatapu, RK Patil, U Goodman, MS AF Kalapatapu, Raj K. Patil, Uday Goodman, Marianne S. TI Using the Internet to Assess Perceptions of Patients with Borderline Personality Disorder: What Do Patients Want in the DSM-V? SO CYBERPSYCHOLOGY BEHAVIOR AND SOCIAL NETWORKING LA English DT Article ID CLASSIFICATION; FAMILIES; STIGMA AB Objectives: This study was an anonymous Internet survey of individuals currently diagnosed with borderline personality disorder (BPD), where participants gave opinions about BPD criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR), and suggested modifications for BPD criteria to appear in the DSM-V (5th edition). Methods: Survey links were posted on 24 websites/Internet blogs that offered advice, education, or treatment of BPD. Demographic and clinical data pertaining to each participant were collected. Free-text responses were analyzed by frequencies of keywords and key phrases. Results: A total of 1,832 responses were downloaded between March 7 and June 6, 2009, and 646 responses were analyzable. Results indicated that the majority of the DSM-IV-TR criteria appeared to capture what participants were experiencing, even though a significant percentage of participants felt that something was missing from the current criteria. A significant percentage of participants felt that BPD should be renamed in the DSM-V; some combination of "emotion(al)'' and "(dys)regulation'' was most commonly suggested to include in an alternative name. Conclusions: This Internet study highlighted the enthusiasm of individuals diagnosed with BPD to share their opinions on the DSM criteria with mental-health professionals. A significant percentage of participants in this study felt that BPD should be renamed in the DSM-V. Patient involvement during the DSM-V revision process remains controversial. C1 [Kalapatapu, Raj K.] Columbia Univ, New York State Psychiat Inst, Subst Use Res Ctr, Unit 120, New York, NY 10032 USA. [Patil, Uday] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Goodman, Marianne S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Goodman, Marianne S.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Kalapatapu, RK (reprint author), Columbia Univ, New York State Psychiat Inst, Subst Use Res Ctr, Unit 120, 1051 Riverside Dr, New York, NY 10032 USA. EM kalapat@pi.cpmc.columbia.edu NR 33 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 2152-2715 EI 2152-2723 J9 CYBERPSYCH BEH SOC N JI Cyberpsychology Behav. Soc. Netw. PD OCT PY 2010 VL 13 IS 5 BP 483 EP 494 DI 10.1089/cyber.2009.0351 PG 12 WC Psychology, Social SC Psychology GA 665PR UT WOS:000283048400001 PM 20950172 ER PT J AU Leitner, NR Kolbe, T Lassnig, C Hochedlinger, K Rulicke, T Muller, M AF Leitner, Nicole R. Kolbe, Thomas Lassnig, Caroline Hochedlinger, Konrad Ruelicke, Thomas Mueller, Mathias TI Inducible STAT1 protein in mice SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Leitner, Nicole R.; Lassnig, Caroline; Mueller, Mathias] Univ Vet Med Vienna, Inst Genet & Anim Breeding, Vienna, Austria. [Kolbe, Thomas; Lassnig, Caroline; Ruelicke, Thomas; Mueller, Mathias] Univ Vet Med Vienna, Univ Ctr Biomodels Austria, Vienna, Austria. [Kolbe, Thomas] Univ Nat Resources & Appl Life Sci, Dept IFA Tulln, Inst Biotechnol Anim Prod, Tulln, Austria. [Hochedlinger, Konrad] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Canc, Boston, MA 02114 USA. [Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA 02114 USA. [Ruelicke, Thomas] Univ Vet Med Vienna, Inst Lab Anim Sci, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 31 EP 32 DI 10.1016/j.cyto.2010.07.141 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400123 ER PT J AU Chan, O Murooka, TT Fish, EN AF Chan, Olivia Murooka, Thomas T. Fish, Eleanor N. TI The role of CCL5/RANTES in regulating nutrient receptor trafficking, metabolism and protein expression in activated T cell SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Chan, Olivia; Murooka, Thomas T.; Fish, Eleanor N.] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A1, Canada. [Murooka, Thomas T.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Fish, Eleanor N.] Toronto Gen Hosp Res Inst, Div Cellular Mol Biol, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 95 EP 95 DI 10.1016/j.cyto.2010.07.403 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400367 ER PT J AU Keuthen, NJ Rothbaum, BO Welch, SS Taylor, C Falkenstein, M Heekin, M Jordan, CA Timpano, K Meunier, S Fama, J Jenike, MA AF Keuthen, Nancy J. Rothbaum, Barbara O. Welch, Stacy Shaw Taylor, Caitlin Falkenstein, Martha Heekin, Mary Jordan, Cathrine Arndt Timpano, Kiara Meunier, Suzanne Fama, Jeanne Jenike, Michael A. TI PILOT TRIAL OF DIALECTICAL BEHAVIOR THERAPY-ENHANCED HABIT REVERSAL FOR TRICHOTILLOMANIA SO DEPRESSION AND ANXIETY LA English DT Article DE trichotillomania; hair pulling; habit reversal; dialectical behavior therapy ID FUNCTIONAL IMPAIRMENT; EXPLORING DIFFERENCES; EMOTION REGULATION; SYMPTOM SEVERITY; DOUBLE-BLIND; PHENOMENOLOGY; IMPACT; SCALE; STYLES; MODEL AB Background: Not all hair pullers improve acutely with cognitive-behavioral treatment (CBT) and few maintain their gains over time. Methods: We conducted an open clinical trial of a new treatment that addresses affectively triggered pulling and emphasizes relapse prevention in addition to standard CBT approaches. Ten female participants satisfying DSM-IV criteria for trichotillomania (TTM) at two study sites received Dialectical Behavior Therapy (DBT)-enhanced CBT consisting of 11 weekly sessions and 4 maintenance sessions over the following 3 months. Independent assessors rated hair pulling impairment and global improvement at several study time points. Participants completed self-report measures of hair pulling severity and emotion regulation. Results: Significant improvement in hair pulling severity and emotion regulation, as well as hair pulling impairment and anxiety and depressive symptoms, occurred during acute treatment and were maintained during the subsequent 3 months. Significant correlations were reported between changes in emotion regulation and hair pulling severity during both the acute treatment and maintenance phases. Conclusions: This study offers preliminary evidence for the efficacy of DBT-enhanced CBT for TTM and suggests the importance of addressing emotion regulation during TTM treatment. Depression and Anxiety 27:953-959, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Keuthen, Nancy J.] Harvard Univ, Massachusetts Gen Hosp, Trichotillomania Clin & Res Unit, Sch Med, Boston, MA 02114 USA. [Rothbaum, Barbara O.; Heekin, Mary; Jordan, Cathrine Arndt] Emory Univ, Sch Med, Atlanta, GA USA. [Welch, Stacy Shaw] Univ Washington, Anxiety & Stress Reduct Ctr, Seattle, WA 98195 USA. RP Keuthen, NJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Trichotillomania Clin & Res Unit, Sch Med, Simches 2,185 Cambridge St, Boston, MA 02114 USA. EM nkeuthen@partners.org RI Citations, TLC SAB/C-4006-2011; Timpano, Kiara/C-8760-2012; OI Falkenstein, Martha/0000-0001-5074-3409; Timpano, Kiara/0000-0002-0665-8722 FU David Judah Fund FX We acknowledge the David Judah Fund for its financial support of this research. We also express our heartfelt thanks to all study participants and to Christina Pearson, Jennifer Raikes, and the Trichotillomania Learning Center staff who assisted with study recruitment. We also wish to recognize Susan Sprich Ph.D., for her helpful feedback on our treatment manual. NR 37 TC 29 Z9 29 U1 1 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2010 VL 27 IS 10 BP 953 EP 959 DI 10.1002/da.20732 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 661PR UT WOS:000282740700006 PM 20721929 ER PT J AU Selim, MA Hoang, MP AF Selim, Maria Angelica Hoang, Mai P. TI A Histologic Review of Vulvar Inflammatory Dermatoses and Intraepithelial Neoplasm SO DERMATOLOGIC CLINICS LA English DT Review DE Vulva; External genitalia; Dermatitis; VIN; ISSVD classification ID SQUAMOUS-CELL CARCINOMA; IGA BULLOUS DERMATOSIS; HAILEY-HAILEY DISEASE; IRRITANT CONTACT-DERMATITIS; LICHEN SIMPLEX CHRONICUS; CROHNS-DISEASE; HUMAN-PAPILLOMAVIRUS; BEHCETS-DISEASE; ACANTHOLYTIC DERMATOSIS; DIAGNOSTIC-CRITERIA AB Patients with urogenital complaints are frequently encountered by family practitioners, gynecologists, and dermatologists. This review article provides practical information regarding normal anatomy and embryology of the vulva, followed by a summary of procedural techniques. The new classifications of vulvar inflammatory and intraepithelial neoplasm proposed by the ISSVD are used as guidelines to review the wide spectrum of diseases involving this organ. C1 [Selim, Maria Angelica] Duke Univ, Med Ctr, Dept Pathol, Dermatopathol Unit, Durham, NC 27710 USA. [Hoang, Mai P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit,Dept Pathol, Boston, MA 02114 USA. RP Selim, MA (reprint author), Duke Univ, Med Ctr, Dept Pathol, Dermatopathol Unit, POB 3712, Durham, NC 27710 USA. EM selim001@mc.duke.edu NR 105 TC 6 Z9 9 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD OCT PY 2010 VL 28 IS 4 BP 649 EP + DI 10.1016/j.det.2010.07.005 PG 20 WC Dermatology SC Dermatology GA 676XT UT WOS:000283953100003 PM 20883910 ER PT J AU Whalen, FM Jambusaria-Pahlajani, A Speck, RM Schmitz, K Schmults, CD AF Whalen, Faith Miller Jambusaria-Pahlajani, Anokhi Speck, Rebecca M. Schmitz, Kathryn Schmults, Chrysalyne D. TI Effect of Physical Activity on Nonmelanoma Skin Cancer Risk in Kidney, Liver, and Pancreatic Transplant Patients SO DERMATOLOGIC SURGERY LA English DT Article ID EXERCISE; MELANOMA; ALUMNI; MICE AB BACKGROUND Physical activity has been associated with a lower risk of cancer, including melanoma, but the effect has not yet been assessed for nonmelanoma skin cancer (NMSC). OBJECTIVE To determine whether the risk of skin cancer differs according to physical activity level in patients at high risk for NMSC. METHODS We conducted a retrospective cohort study in kidney, liver, and pancreatic transplant patients via telephone interview. Physical activity scores were calculated for each patient using a previously validated questionnaire. Sun exposure history and skin type were also recorded. The outcome of interest was a biopsy-proven diagnosis of at least one NMSC. RESULTS Of 142 subjects, 45 (32%) developed NMSC. There was no significant effect of physical activity on the development of NMSC. CONCLUSIONS Physical activity level may not be a major predictor of skin cancer risk in organ transplant patients. Controlled trials and population-based studies are needed to determine whether exercise can decrease the risk of NMSC in the general population. The authors have indicated no significant interest with commercial supporters. C1 [Schmults, Chrysalyne D.] Dana Farber Brigham & Womens Canc Ctr, Dept Dermatol, Jamaica Plain, MA USA. [Whalen, Faith Miller] Crozer Chester Med Ctr, Dept Med, Upland, PA USA. [Jambusaria-Pahlajani, Anokhi] Hosp Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Jambusaria-Pahlajani, Anokhi; Speck, Rebecca M.; Schmitz, Kathryn; Schmults, Chrysalyne D.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Schmults, CD (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Dermatol, 1153 Ctr St,Suite 4349, Jamaica Plain, MA USA. EM cschmults@partners.org NR 13 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD OCT PY 2010 VL 36 IS 10 BP 1510 EP 1513 DI 10.1111/j.1524-4725.2010.01674.x PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 656IX UT WOS:000282324800003 PM 20698873 ER PT J AU Martin, JE Speyer, LA Schmults, CD AF Martin, Julie E. Speyer, Lark-Aeryn Schmults, Chrysalyne D. TI Heightened Infection-Control Practices are Associated with Significantly Lower Infection Rates in Office-Based Mohs Surgery SO DERMATOLOGIC SURGERY LA English DT Article ID DERMATOLOGICAL SURGERY; MICROGRAPHIC SURGERY; BACTERIAL-CONTAMINATION; COMPLICATIONS; RINGS AB BACKGROUND Reported infection rates for Mohs micrographic surgery (MMS) range from less than 1% to 3.5%. OBJECTIVE To determine whether lower infection rates are possible for MMS with a consistently applied infection-control regimen. METHODS A series of 832 consecutive patients with 950 tumors undergoing MMS formed the cohort for a retrospective study of infections before and after a program of heightened infection-control practices at a single-surgeon academic Mohs practice. The sterility upgrade included jewelry restrictions, alcohol hand scrub before stages and reconstruction, sterile gloves and (during reconstruction) sterile gowns for staff, and sterile towels and dressings for patients during Mohs stages. RESULTS Infection rate was 2.5% (9 infections/365 tumors) before the sterility upgrade and 0.9% (5 infections/585 tumors) after, a statistically significant difference (p=.04). CONCLUSION MMS already has low rates of infection, but this study shows that rigorous infection-control practices can significantly affect infection rates. The authors have indicated no significant interest with commercial supporters. C1 [Martin, Julie E.] Univ Texas Med Branch, Dept Dermatol, Galveston, TX USA. [Speyer, Lark-Aeryn; Schmults, Chrysalyne D.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. RP Schmults, CD (reprint author), Dana Farber Brigham & Womens Canc Ctr, Mohs Microg Surg Ctr, 1153 Ctr St,Suite 4349, Jamaica Plain, MA 02130 USA. EM cschmults@partners.org NR 16 TC 14 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD OCT PY 2010 VL 36 IS 10 BP 1529 EP 1536 DI 10.1111/j.1524-4725.2010.01677.x PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 656IX UT WOS:000282324800006 PM 20698870 ER PT J AU Bonner-Weir, S Li, WC Ouziel-Yahalom, L Guo, LL Weir, GC Sharma, A AF Bonner-Weir, Susan Li, Wan-Chun Ouziel-Yahalom, Limor Guo, Lili Weir, Gordon C. Sharma, Arun TI beta-Cell Growth and Regeneration: Replication Is Only Part of the Story SO DIABETES LA English DT Article ID PANCREATIC-DUCT CELLS; 60-PERCENT PARTIAL-PANCREATECTOMY; ENDOCRINE PROGENITOR CELLS; CARBONIC-ANHYDRASE-II; ADULT-MOUSE PANCREAS; RAT PANCREAS; ISLET REGENERATION; TRANSGENIC MICE; LIFE-SPAN; COMPENSATORY GROWTH C1 [Bonner-Weir, Susan; Li, Wan-Chun; Ouziel-Yahalom, Limor; Guo, Lili; Weir, Gordon C.; Sharma, Arun] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA. EM susan.bonner-weir@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU National Institute of Diabetes and Digestive and Kidney Diseases; Juvenile Diabetes Research Foundation FX This research has been supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the Juvenile Diabetes Research Foundation, and an important group of private donors. NR 96 TC 120 Z9 124 U1 2 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2010 VL 59 IS 10 BP 2340 EP 2348 DI 10.2337/db10-0084 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667PJ UT WOS:000283205700002 PM 20876724 ER PT J AU Jablonski, KA McAteer, JB de Bakker, PIW Franks, PW Pollin, TI Hanson, RL Saxena, R Fowler, S Shuldiner, AR Knowler, WC Altshuler, D Florez, JC AF Jablonski, Kathleen A. McAteer, Jarred B. de Bakker, Paul I. W. Franks, Paul W. Pollin, Toni I. Hanson, Robert L. Saxena, Richa Fowler, Sarah Shuldiner, Alan R. Knowler, William C. Altshuler, David Florez, Jose C. CA Diabet Prevention Program Res Grp TI Common Variants in 40 Genes Assessed for Diabetes Incidence and Response to Metformin and Lifestyle Intervention in the Diabetes Prevention Program SO DIABETES LA English DT Article ID WIDE ASSOCIATION SCAN; CATION TRANSPORTER 1; ADMIXTURE MAP; LOCI; DISEASE; REQUIREMENT; DISCOVERY; MELLITUS AB OBJECTIVE-Genome-wide association studies have begun to elucidate the genetic architecture of type 2 diabetes. We examined whether single nucleotide polymorphisms (SNPs) identified through targeted complementary approaches affect diabetes incidence in the at-risk population of the Diabetes Prevention Program (DPP) and whether they influence a response to preventive interventions. RESEARCH DESIGN AND METHODS-We selected SNPs identified by prior genome-wide association studies for type 2 diabetes and related traits, or capturing common variation in 40 candidate genes previously associated with type 2 diabetes, implicated in monogenic diabetes, encoding type 2 diabetes drug targets or drug-metabolizing/transporting enzymes, or involved in relevant physiological processes. We analyzed 1,590 SNPs for association with incident diabetes and their interaction with response to metformin or lifestyle interventions in 2,994 DPP participants. We controlled for multiple hypothesis testing by assessing false discovery rates. RESULTS-We replicated the association of variants in the metformin transporter gene SLC47A1 with metformin response and detected nominal interactions in the AMP kinase (AMPK) gene STK11, the AMPK subunit genes PRKAA1 and PRK4.A2, and a missense SNP in SLC22A1, which encodes another metformin transporter. The most significant association with diabetes incidence occurred in the AMPK subunit gene PRKAG2 (hazard ratio 1.24, 95% CI 1.09-1.40, P = 7 x 10(-4)). Overall, there were nominal associations with diabetes incidence at 85 SNPs and nominal interactions with the metformin and lifestyle interventions at 91 and 69 mostly nonoverlapping SNPs, respectively. The lowest P values were consistent with experiment-wide 33% false discovery rates. CONCLUSIONS-We have identified potential genetic determinants of metformin response. These results merit confirmation in independent samples. Diabetes 59:2672-2681, 2010 C1 [McAteer, Jarred B.; Saxena, Richa; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Jablonski, Kathleen A.; Fowler, Sarah] George Washington Univ, Ctr Biostat, Rockville, MD USA. [McAteer, Jarred B.; de Bakker, Paul I. W.; Saxena, Richa; Altshuler, David; Florez, Jose C.] Broad Inst, Prograrn Med & Populat Genet, Cambridge, MA USA. [de Bakker, Paul I. W.; Altshuler, David; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [de Bakker, Paul I. W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Franks, Paul W.] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Div Med, S-90185 Umea, Sweden. [Franks, Paul W.] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Pollin, Toni I.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Hanson, Robert L.; Knowler, William C.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Dept Med, Boston, MA 02114 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM dppmail@biostat.bsc.gwu.edu RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009; Hanson, Robert/O-3238-2015; OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Hanson, Robert/0000-0002-4252-7068; Franks, Paul/0000-0002-0520-7604 FU Doris Duke Charitable Foundation; Novo Nordisk; Swedish Heart-Lung Foundation; Swedish Diabetes Association; Pahlssons Foundation; Swedish Research Council; Umea University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Office of Research on Women's Health; Centers for Disease Control and Prevention; American Diabetes Association; [R01 DK072041] FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the coordinating center for the design and conduct of the study and collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Office of Research on Women's Health, the Centers for Disease Control and Prevention, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported in part by the intramural research program of the NIDDK. Life Scan, Health O Meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck and Company, Nike Sports Marketing, Slim Fast Foods, and Quaker Oats donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices, Matthews Media Group, and the Henry M. Jackson Foundation provided support services under subcontract with the coordinating center. A complete list of centers, investigators, and staff can be found in the online appendix.; This work was funded by R01 DK072041 to K.A.J., T.I.P., A.R.S., D.A., and J.C.F. J.C.F. is also supported by the Massachusetts General Hospital and a Clinical Scientist Development Award by the Doris Duke Charitable Foundation. This work was partially supported by a Doris Duke Charitable Foundation Distinguished Scientist Clinical Award to D.A. P.W.F. was supported in part by grants from Novo Nordisk, the Swedish Heart-Lung Foundation, the Swedish Diabetes Association, Pahlssons Foundation, the Swedish Research Council, and a Career Development Award from Umea University. J.C.F. received consulting honoraria from Publicis Healthcare, Merck, bioStrategies, XOMA, and Daiichi-Sankyo and has been a paid invited speaker at internal scientific seminars hosted by Pfizer and Alnylam Pharmaceuticals. NR 35 TC 106 Z9 111 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2010 VL 59 IS 10 BP 2672 EP 2681 DI 10.2337/db10-0543 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667PJ UT WOS:000283205700042 PM 20682687 ER PT J AU Lazo, M Solga, SF Horska, A Bonekamp, S Diehl, AM Brancati, FL Wagenknecht, LE Pi-Sunyer, FX Kahn, SE Clark, JM AF Lazo, Mariana Solga, Steven F. Horska, Alena Bonekamp, Susanne Diehl, Anna Mae Brancati, Frederick L. Wagenknecht, Lynne E. Pi-Sunyer, F. Xavier Kahn, Steven E. Clark, Jeanne M. CA Fatty Liver Subgrp Look AHEAD Res TI Effect of a 12-Month Intensive Lifestyle Intervention on Hepatic Steatosis in Adults With Type 2 Diabetes SO DIABETES CARE LA English DT Article ID NONALCOHOLIC FATTY LIVER; WEIGHT-LOSS; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; CRYPTOGENIC CIRRHOSIS; CALORIE RESTRICTION; NATURAL-HISTORY; RISK-FACTORS; STEATOHEPATITIS; EXERCISE AB OBJECTIVE - Weight loss through lifestyle changes is recommended for nonalcoholic fatty liver disease (NAFLD). However, its efficacy in patients with type 2 diabetes is unproven. RESEARCH DESIGN AND METHODS - Look AHEAD (Action for Health in Diabetes) is a 16-center clinical trial with 5,145 overweight or obese adults with type 2 diabetes, who were randomly assigned to an intensive lifestyle intervention (ILI) to induce a minimum weight loss of 7% or a control group who received diabetes support and education (DSE). In the Fatty Liver Ancillary Study, 96 participants completed proton magnetic resonance spectroscopy to quantify hepatic steatosis and tests to exclude other causes of liver disease at baseline and 12 months. We defined steatosis >5.5% as NAFLD. RESULTS - Participants were 49% women and 68% white. The mean age was 61 years, mean BMI was 35 kg/m(2), mean steatosis was 8.0%, and mean aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 20.5 and 24.2 units/l, respectively. After 12 months, participants assigned to ILI (n = 46) lost more weight (-8.5 vs. -0.05%; P<0.01) than those assigned to DSE and had a greater decline in steatosis (-50.8 vs. -22.8%, P=0.04) and in AI C (-0.7 vs. -0.2%, P=0.04). There were no significant 12-month changes in AST or ALT levels. At 12 months, 26% of DSE participants and 3% (1 of 31) of ILI participants without NAFLD at baseline developed NAFLD (P<0.05). CONCLUSIONS - A 12-month intensive lifestyle intervention in patients with type 2 diabetes reduces steatosis and incident NAFLD. C1 [Lazo, Mariana; Brancati, Frederick L.; Clark, Jeanne M.] Welch Ctr Prevent Epidemiol & Clin Res, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Horska, Alena] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD USA. [Diehl, Anna Mae] Duke Univ, Med Ctr, Durham, NC USA. [Wagenknecht, Lynne E.] Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Pi-Sunyer, F. Xavier] Columbia Univ, St Lukes Roosevelt Hosp Ctr, Coll Phys & Surg, Div Endocrinol Diabet & Nutr, New York, NY USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. RP Lazo, M (reprint author), Welch Ctr Prevent Epidemiol & Clin Res, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. EM mlazo@jhsph.edu OI Bonekamp, Susanne/0000-0001-5847-5656; Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK-060427, U01-DK-57149]; Johns Hopkins University School of Medicine General Clinical Research Center [M01-RR-00052]; Department of Veterans Affairs FX The study was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (grants R01-DK-060427 and U01-DK-57149), The Johns Hopkins University School of Medicine General Clinical Research Center (grant M01-RR-00052), and the Department of Veterans Affairs. NR 24 TC 103 Z9 108 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2010 VL 33 IS 10 BP 2156 EP 2163 DI 10.2337/dc10-0856 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667PD UT WOS:000283205100005 PM 20664019 ER PT J AU Wexler, DJ Shrader, P Burns, SM Cagliero, E AF Wexler, Deborah J. Shrader, Peter Burns, Sean M. Cagliero, Enrico TI Effectiveness of a Computerized Insulin Order Template in General Medical Inpatients With Type 2 Diabetes A cluster randomized trial SO DIABETES CARE LA English DT Article ID GLUCOSE MANAGEMENT; GLYCEMIC CONTROL; HYPERGLYCEMIA; PROTOCOL; HYPOGLYCEMIA; QUALITY; SET AB OBJECTIVE - To determine whether an electronic order template for basal-bolus insulin ordering improves mean blood glucose in hospitalized general medical patients with hyperglycemia and type 2 diabetes. RESEARCH DESIGN AND METHODS - We randomly assigned internal medicine resident teams on acute general medical floors to the use of an electronic insulin order template or usual insulin ordering. We measured diabetes care parameters for 1 month on all patients with type 2 diabetes and blood glucose <60 mg/dl or >180 mg/dl treated by these physicians. RESULTS - Intervention group patients (n = 65) had mean glucose or 195 +/- 66 mg/dl. Control group patients (n = 63) had mean glucose of 224 +/- 57 mg/dl (P = 0.004). In the intervention group, there was no increase in hypoglycemia. CONCLUSIONS - Access to a computer insulin order template was associated with improved mean glucose levels without increasing hypoglycemia in patients with type 2 diabetes. C1 [Wexler, Deborah J.; Burns, Sean M.; Cagliero, Enrico] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Wexler, Deborah J.; Burns, Sean M.; Cagliero, Enrico] Harvard Univ, Sch Med, Boston, MA USA. [Shrader, Peter] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Wexler, DJ (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. EM dwexler@partners.org FU Massachusetts General Hospital (NIGH); National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK 080 228]; National Institutes of Health [T32 DK007028-34] FX This research study was funded by the Massachusetts General Hospital (NIGH) Clinical Innovation Award program, an initiative of the MGH Quality and Safety Program. D.J.W. is supported by a National Institute of Diabetes and Digestive and Kidney Diseases Career Development Award (K23 DK 080 228). S.B. is supported in part by a National Institutes of Health institutional training grant (T32 DK007028-34). NR 15 TC 29 Z9 29 U1 0 U2 3 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 OCT PY 2010 VL 33 IS 10 BP 2181 EP 2183 DI 10.2337/dc10-0964 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667PD UT WOS:000283205100010 PM 20664017 ER PT J AU Pearson, JF Bachireddy, C Shyamprasad, S Goldfine, AB Brownstein, JS AF Pearson, John F. Bachireddy, Chethan Shyamprasad, Sangameswaran Goldfine, Allison B. Brownstein, John S. TI Association Between Fine Particulate Matter and Diabetes Prevalence in the U.S. SO DIABETES CARE LA English DT Article ID AIR-POLLUTION; INSULIN-RESISTANCE; POPULATION; MODEL AB OBJECTIVE - Recent studies have drawn attention to the adverse effects of ambient air pollutants such as particulate matter 2.5 (PM2.5) on human health. We evaluated the association between PM2.5 exposure and diabetes prevalence in the U.S. and explored factors that may influence this relationship. RESEARCH DESIGN AND METHODS - The relationship between PM2.5 levels and diagnosed diabetes prevalence in the U.S. was assessed by multivariate regression models at the county level using data obtained from both the Centers for Disease Control and Prevention (CDC) and U.S. Environmental Protection Agency (EPA) for years 2004 and 2005. Covariates including obesity rates, population density, ethnicity, income, education, and health insurance were collected from the U.S. Census Bureau and the CDC. RESULTS - Diabetes prevalence increases with increasing PM2.5 concentrations, with a 1% increase in diabetes prevalence seen with a 10 mu g/m(3) increase in PM2.5 exposure (2004: beta = 0.77[95% CI 0.39-1.25], P<0.001; 2005:beta = 0.81 [0.48-1.07], P<0.001). This finding was confirmed for each study year in both univariate and multivariate models. The relationship remained consistent and significant when different estimates of PM2.5 exposure were used. Even for counties within guidelines for EPA PM2.5 exposure limits, those with the highest exposure showed a >20% increase in diabetes prevalence compared with that for those with the lowest levels of PM2.5, an association that persisted after controlling for diabetes risk factors. CONCLUSIONS - Our results suggest PM2.5 may contribute to increased diabetes prevalence in the adult U.S. population. These findings add to the growing evidence that air pollution is a risk factor for diabetes. C1 [Pearson, John F.; Bachireddy, Chethan; Shyamprasad, Sangameswaran; Brownstein, John S.] Harvard MIT, Childrens Hosp Informat Program, Div Hlth Sci & Technol, Boston, MA USA. [Pearson, John F.] St Georges Univ, Sch Med, St Georges, Grenada. [Bachireddy, Chethan] Yale Univ, Sch Med, New Haven, CT USA. [Goldfine, Allison B.] Partners Healthcare, Boston, MA USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA USA. [Brownstein, John S.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Brownstein, John S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. RP Brownstein, JS (reprint author), Harvard MIT, Childrens Hosp Informat Program, Div Hlth Sci & Technol, Boston, MA USA. EM john_brownstein@harvard.edu OI Pearson, John/0000-0001-5607-4517 FU National Institutes of Health National Center for Biomedical Computing [5U54-LM-008748] FX This study was funded by National Institutes of Health National Center for Biomedical Computing (grant 5U54-LM-008748). NR 25 TC 93 Z9 97 U1 5 U2 28 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 OCT PY 2010 VL 33 IS 10 BP 2196 EP 2201 DI 10.2337/dc10-0698 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667PD UT WOS:000283205100013 PM 20628090 ER PT J AU Kahn, SE AF Kahn, S. E. TI Beta-cell loss in type 2 diabetes SO DIABETES OBESITY & METABOLISM LA English DT Meeting Abstract C1 [Kahn, S. E.] Univ Washington, Seattle, WA 98195 USA. [Kahn, S. E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD OCT PY 2010 VL 12 SU 1 BP 12 EP 12 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 656XE UT WOS:000282373600017 ER PT J AU Chartoumpekis, D Ziros, P Psyrogiannis, A Kyriazopoulou, V Sykiotis, G Habeos, I AF Chartoumpekis, D. Ziros, P. Psyrogiannis, A. Kyriazopoulou, V Sykiotis, G. Habeos, I TI The role of Nrf2 in high fat diet induced obesity in mice the FGF21 connection SO DIABETES OBESITY & METABOLISM LA English DT Meeting Abstract C1 [Chartoumpekis, D.; Ziros, P.; Psyrogiannis, A.; Kyriazopoulou, V; Habeos, I] Univ Patras, GR-26110 Patras, Greece. [Sykiotis, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI ziros, panos/C-7289-2009 NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD OCT PY 2010 VL 12 SU 1 BP 35 EP 35 DI 10.1111/j.1463-1326.2010.01300.x PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 656XE UT WOS:000282373600039 ER PT J AU Kajimura, S Andreucci, A Koncarevic, A Cornwall-Brady, M Davies, M Sako, D Liu, J Kumar, R Tomkinson, K Baker, T Umiker, B Monnell, T Grinberg, A Liharska, K Underwood, K Ucran, J Spaits, M Spiegelman, B Seehra, J Lachey, J AF Kajimura, S. Andreucci, A. Koncarevic, A. Cornwall-Brady, M. Davies, M. Sako, D. Liu, J. Kumar, R. Tomkinson, K. Baker, T. Umiker, B. Monnell, T. Grinberg, A. Liharska, K. Underwood, K. Ucran, J. Spaits, M. Spiegelman, B. Seehra, J. Lachey, J. TI Characterization of the thermogenic program induced in white adipose tissue of HFD-fed mice treated with a soluble ACVR2B and identification of ligands potentially mediating this effect SO DIABETES OBESITY & METABOLISM LA English DT Meeting Abstract C1 [Kajimura, S.; Spiegelman, B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD OCT PY 2010 VL 12 SU 1 BP 52 EP 53 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 656XE UT WOS:000282373600074 ER PT J AU Lynch, CP Strom, JL Egede, LE AF Lynch, Cheryl P. Strom, Joni L. Egede, Leonard E. TI Variation in Quality of Care Indicators for Diabetes in a National Sample of Veterans and Non-Veterans SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID AFFAIRS HEALTH-CARE; PREVALENCE; ADULTS; SYSTEM AB Background: Veterans have a disproportionately higher burden of type 2 diabetes. It is unclear whether veterans with diabetes have better self-care behaviors or receive better quality of care than non-veterans. The objective was to examine differences in diabetes care between veterans and non-veterans. Methods: Data analysis was performed with respondents from the 2003 Behavioral Risk Factor Surveillance Survey (n-21,111 with diabetes). Veterans were those who reported U. S. military service and no longer on active duty. Self-care behaviors included daily fruit and vegetable intake, physical activity level, self-foot checks, and home glucose testing. Quality of care indicators included provider actions over the past 12 months (2+ office visits, 2+ glycosylated hemoglobin checks, 1+ foot exams, 1+ dilated eye exams, daily aspirin use, receiving flu or pneumonia vaccine). Multiple logistic regression using STATA version 10 (Stata Corp., College Station, TX) analyzed differences by veteran status on each quality indicator, controlling for sociodemographics and diabetes education. Results: Veterans comprised 14.2% of the sample, and 12.4% had diabetes compared to 6.7% of non-veterans. In final adjusted models, veterans were significantly more likely to check their feet (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.09, 1.64), get a dilated eye exam (OR 1.36, 95% CI 1.11, 1.66), receive aspirin (OR 1.31, 95% CI 1.04, 1.65), get a flu shot (OR 1.32, 95% CI 1.09, 1.61), and ever get a pneumonia shot (OR 1.38, 95% CI 1.12, 1.70). Conclusions: Veterans appear to have better self-care behaviors and receive better preventive care than non-veterans. However, future efforts need to focus on boosting self-care to improve diabetes outcomes. C1 [Lynch, Cheryl P.; Strom, Joni L.; Egede, Leonard E.] Med Univ S Carolina, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Lynch, Cheryl P.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29425 USA. RP Lynch, CP (reprint author), Med Univ S Carolina, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Ctr Hlth Dispar Res, 135 Rutledge Ave,MSC 250593, Charleston, SC 29425 USA. EM lynchcp@musc.edu FU Center for Disease Prevention and Health Interventions for Diverse Populations [REA 08-261] FX This work was supported by the use of facilities at the Charleston VA Health Services Research & Development-funded Center for Disease Prevention and Health Interventions for Diverse Populations (REA 08-261). NR 25 TC 5 Z9 5 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD OCT PY 2010 VL 12 IS 10 BP 785 EP 790 DI 10.1089/dia.2010.0040 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 659UC UT WOS:000282591400006 PM 20809677 ER PT J AU Faquin, WC Baloch, ZW AF Faquin, William C. Baloch, Zubair W. TI Fine-Needle Aspiration of Follicular Patterned Lesions of the Thyroid: Diagnosis, Management, and Follow-Up According to National Cancer Institute (NCI) Recommendations SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE thyroid; FNA; follicular lesion of undetermined significance; follicular neoplasm; repeat FNA ID PAPILLARY CARCINOMA; COMPLETION THYROIDECTOMY; INTEROBSERVER VARIABILITY; OBSERVER VARIATION; NODULES; CYTOLOGY; VARIANT; BIOPSY; MALIGNANCY; NEOPLASMS AB The National Cancer Institute (NCI) State of the Science Conference on thyroid fine-needle aspiration (FNA) proposed that follicular patterned lesions can be divided into two diagnostic categories; follicular lesion of undetermined significance/Atypia of undetermined significance (FLUS/AUS) and suspicious for follicular neoplasm/follicular neoplasm (SFON/FON). The former group can benefit from repeat FNA (RFNA) to achieve a more definitive diagnosis and the latter should undergo surgical excision for histologic characterization (adenoma vs. carcinoma). In this study, we report the combined experience from our institutions with thyroid FNA cases that can be placed into NCI-designated thyroid FNA diagnostic categories for follicular patterned lesions. The case cohort comprised of 857 cases in 645 females and 212 males; 509 cases could be classified as FLUS/AUS and 348 as SFON/FON. Histologic follow-up was available in 273/509 (54%) cases diagnosed as FLUS/AUS and 251/348 (72%) cases diagnosed as SFON/FON. RFNA was performed in 203/509 (40%) patients classified as FLUS/AUS. RFNA diagnoses were: benign (125 cases), FLUS (46 cases), SFON/FON (20 cases), suspicious for papillary carcinoma (7 cases), papillary carcinoma (3 cases) and non-diagnostic (2 cases). The malignancy rate on surgical excision in the FLUS/AUS group was 27 and 15% with and without RFNA, respectively; and 25% in cases diagnosed as SFON/FON. RFNA is effective in managing thyroid nodules diagnosed as FLUS/AUS since the malignancy rates are different in cases with or without RFNA (27% vs. 15%). The malignancy rate (25%) in cases diagnosed as SFON/FON is similar to reported by other authors. Diagn. Cytopathol. 2010;38:731-739. (C) 2010 Wiley-Liss, Inc. C1 [Baloch, Zubair W.] Univ Penn, Med Ctr, Dept Pathol & Lab, Div Cytopathol, Philadelphia, PA 19104 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Div ENT Pathol, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Div Cytopathol, Boston, MA 02114 USA. RP Baloch, ZW (reprint author), Univ Penn, Med Ctr, Dept Pathol & Lab, Div Cytopathol, Philadelphia, PA 19104 USA. EM baloch@mail.med.upenn.edu NR 69 TC 113 Z9 113 U1 1 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD OCT PY 2010 VL 38 IS 10 BP 731 EP 739 DI 10.1002/dc.21292 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 660SJ UT WOS:000282664000006 PM 20049964 ER PT J AU Yaeger, KA Hysell, C Pitman, MB AF Yaeger, Kurt A. Hysell, Chris Pitman, Martha Bishop TI Amyloid Goiter SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Editorial Material C1 [Pitman, Martha Bishop] Harvard Univ, Sch Med, FNA Serv, Massachusetts Gen Hosp,Dept Pathol, Boston, MA 02114 USA. [Yaeger, Kurt A.] Lafayette Coll, Easton, PA 18042 USA. RP Pitman, MB (reprint author), Harvard Univ, Sch Med, FNA Serv, Massachusetts Gen Hosp,Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM mpitman@partners.org NR 3 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD OCT PY 2010 VL 38 IS 10 BP 742 EP 743 DI 10.1002/dc.21250 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 660SJ UT WOS:000282664000008 PM 19937940 ER PT J AU Shi, HX Ren, JL Xu, HZ Pan, JS Hao, XY Barlow, LL Dong, WG AF Shi, Huaxiu Ren, Jianlin Xu, Hongzhi Pan, Jinshui Hao, Xiaoyan Barlow, Lydia Leyland Dong, Weiguo TI Upregulated Expression of hITF in Crohn's Disease and Screening of hITF Interactant by a Yeast Two-Hybrid System SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Human intestinal trefoil factor; Crohn's disease; Yeast two-hybrid system ID INTESTINAL TREFOIL FACTOR; DOUBLE-BALLOON ENTEROSCOPY; PROTEIN-PROTEIN INTERACTIONS; INDUCED COLITIS; KAPPA-B; MICE; MUCOSA; TFF3; LOCALIZATION; PEPTIDE AB To study the expression of human intestinal trefoil factor (hITF) mRNA in Crohn's disease and to screen the cellular proteins that can interact with the hITF protein by a yeast two-hybrid system in order to explore the mechanism of hITF in protecting intestinal mucosa from injury. Seventy-eight patients underwent double-balloon enteroscopy (DBE). Expression of hITF mRNA was detected by quantitative real-time polymerase chain reaction analysis (qRT-PCR). The hITF gene was amplified by PCR and cloned into vector pDEST32. The yeast cells cotransformed with pDEST32-hITF and the human jejunal cDNA library were plated in a selective SC-Leu-Trp-His-Ura medium. The subsequent screen was performed with chi-gal detection, and true-positive clones were sequenced and analyzed with bioinformatics. Co-immunoprecipitation (Co-IP) was performed to confirm the binding of putative proteins to the hITF protein. Thirty-nine patients were diagnosed with Crohn's disease. We found that the expression of hITF mRNA is significantly increased in Crohn's disease compared to normal controls. A total of ten colonies were selected and sequenced. Among these, six colonies were Homo sapiens zinc finger protein 193 (ZNF193), three colonies were Homo sapiens Aldo-keto reductase family 1C 1 (AKR1C1), and one colony was of an unknown gene. A reverse two-hybrid experiment and Co-IP indicated that ZNF193 and AKR1C1 might interact with hITF. The expression of hITF mRNA is increased in Crohn's disease. ZNF193 and AKR1C1 are proteins that can interact with the hITF protein by a yeast two-hybrid system and Co-IP, hITF may contribute to the mucosal repair through this interaction. C1 [Shi, Huaxiu; Dong, Weiguo] Wuhan Univ, Renmin Hosp, Dept Gastroenterol, Wuhan 430060, Hubei Province, Peoples R China. [Shi, Huaxiu; Ren, Jianlin; Xu, Hongzhi; Pan, Jinshui; Hao, Xiaoyan] Xiamen Univ, Zhongshan Hosp, Dept Gastroenterol, Xiamen 361004, Fujian Province, Peoples R China. [Shi, Huaxiu; Barlow, Lydia Leyland] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. [Shi, Huaxiu; Barlow, Lydia Leyland] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Dong, WG (reprint author), Wuhan Univ, Renmin Hosp, Dept Gastroenterol, 238 JieFang Rd, Wuhan 430060, Hubei Province, Peoples R China. EM dongwg66@yahoo.com.cn FU Science and Technology Innovation Foundation of Fujian Province, China [WQK05022005] FX This work was supported in part by grant WQK05022005 from the Science and Technology Innovation Foundation of Fujian Province, China. The authors are grateful to the Department of Gastroenterology, Zhongshan Hospital, Xiamen University and the Department of Surgery, Renji Hospital of Shanghai Jiaotong Medical University. We thank Ms. Lydia Leyland Barlow and Dr. Wenyu Lin for their help in this manuscript edition. NR 32 TC 2 Z9 3 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2010 VL 55 IS 10 BP 2929 EP 2939 DI 10.1007/s10620-010-1227-0 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 653LU UT WOS:000282093700050 PM 20499178 ER PT J AU Mendez-Navarro, J Chirino, RA Corey, KE Gorospe, EC Zheng, H Moran, S Juarez, JA Chung, RT Dehesa-Violante, M AF Mendez-Navarro, Jorge Chirino, Ruby A. Corey, Kathleen E. Gorospe, Emmanuel C. Zheng, Hui Moran, Segundo Juarez, Jesus A. Chung, Raymond T. Dehesa-Violante, Margarita TI A Randomized Controlled Trial of Double Versus Triple Therapy with Amantadine for Genotype 1 Chronic Hepatitis C in Latino Patients (vol 55, pg 2629, 2010) SO DIGESTIVE DISEASES AND SCIENCES LA English DT Correction C1 [Mendez-Navarro, Jorge; Chirino, Ruby A.; Moran, Segundo; Juarez, Jesus A.] Hosp Especialidades Ctr Med La Raza, Dept Gastroenterol, Ctr Med Nacl Siglo XXI, IMSS, Mexico City 06725, DF, Mexico. [Mendez-Navarro, Jorge; Corey, Kathleen E.; Chung, Raymond T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Gorospe, Emmanuel C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD USA. [Zheng, Hui] Harvard Univ, Sch Med, MGH Biostat Ctr, Boston, MA USA. RP Mendez-Navarro, J (reprint author), Hosp Especialidades Ctr Med La Raza, Dept Gastroenterol, Ctr Med Nacl Siglo XXI, IMSS, Av Cuauhtemoc 330, Mexico City 06725, DF, Mexico. EM jmndoc@yahoo.com NR 1 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2010 VL 55 IS 10 BP 3010 EP 3010 DI 10.1007/s10620-009-1114-8 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 653LU UT WOS:000282093700063 ER PT J AU Lillehei, CW Masek, BJ Shamberger, RC AF Lillehei, Craig W. Masek, Bruce J. Shamberger, Robert C. TI Prospective Study of Health-Related Quality of Life and Restorative Proctocolectomy in Children SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Health-related Quality of Life; Ulcerative colitis; Pediatric; Restorative proctocolectomy ID POUCH-ANAL ANASTOMOSIS; COLITIS ACTIVITY INDEX; ULCERATIVE-COLITIS; FUNCTIONAL OUTCOMES AB PURPOSE: Although restorative proctocolectomy has become the standard surgical treatment for ulcerative colitis and familial adenomatous polyposis, there are no prospective studies in children of the impact of this intervention on health-related quality of life. METHODS: A prospective study of health-related quality of life in children with ulcerative colitis or familial adenomatous polyposis undergoing restorative proctocolectomy was performed. Patients and their parents who agreed to participate completed standardized health-related quality-of-life surveys (Medical Outcomes Study Short Form-36 and Child Health Questionnaire Parent Form) within one month before colectomy and approximately one year after completion of their surgery. RESULTS: Of the 60 patients who agreed to participate, 44 completed surveys at the appropriate time periods allowing comparison. The parents of 28 of these subjects also completed paired surveys. Before colectomy, patients with ulcerative colitis had substantially lower health-related quality-of-life scores, which were also mirrored in parental surveys. Following surgery patients with ulcerative colitis had significant improvement in 7 of 8 Medical Outcomes Study Short Form-36 patient subscales and all 6 corresponding Child Health Questionnaire Parent Form parental subscales of health-related quality of life. Patients with familial adenomatous polyposis showed improvement in the bodily pain subscale alone, whereas their corresponding parental surveys only showed improvement in the mental health subscale. CONCLUSION: There are clearly significant adverse affects on health-related quality of life in children with ulcerative colitis that dramatically improved following restorative proctocolectomy. C1 [Lillehei, Craig W.; Shamberger, Robert C.] Childrens Hosp Boston, Dept Surg, Boston, MA 02115 USA. [Masek, Bruce J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Lillehei, CW (reprint author), Childrens Hosp Boston, Dept Surg, Fegan 3,300 Longwood Ave, Boston, MA 02115 USA. EM Craig.lillehei@childrens.harvard.edu NR 23 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD OCT PY 2010 VL 53 IS 10 BP 1388 EP 1392 DI 10.1007/DCR.0b013e3181e8efc5 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 655HA UT WOS:000282238500007 PM 20847620 ER PT J AU Chu, JW Picard, MH Agnihotri, AK Fitzsimons, MG AF Chu, John W. Picard, Michael H. Agnihotri, Arvind K. Fitzsimons, Michael G. TI Diagnosis of Congenital Unicuspid Aortic Valve in Adult Population: The Value and Limitation of Transesophageal Echocardiography SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE unicuspid aortic valve; diagnosis; transesophageal echocardiography ID QUALITY-OF-LIFE; 3-DIMENSIONAL ECHOCARDIOGRAPHY; IMPROVED SURVIVAL; STENOSIS; DISEASE; REPLACEMENT; DISSECTION; MORPHOLOGY; FEATURES; AGE AB Background: This study aimed to assess the accuracy of two-dimensional echocardiography (echo) in diagnosing unicuspid aortic valve (UAV) and to determine echo features that could improve the diagnosis. Method: We reviewed transthoracic/transesophageal echoes (TTE/TEE) from our hospital database for adult patients who had aortic valve surgery with a preoperative echo diagnosis of UAV or equivocal diagnosis of bicuspid aortic valve (BAV) BAV/UAV. Morphological characteristics of AV and ascending aortic dimensions were evaluated. Results: Nineteen patients were identified, 13 (11 Male, 2 Female, mean age 47 +/- 10 years) had surgically confirmed diagnosis of UAV, six had BAV. The incidence of UAV was 2.6%. For diagnosing UAV, the sensitivity and specificity of TIE was 27% and 50% and those of TEE was 75% and 86%, respectively. For TTE, positive predictive value (PPV) was 60% and negative predictive value (NPV) was 20%. By TEE, PPV was 90% and the NPV was 67%. In UAV patients, 85% had severe aortic stenosis (mean gradient 45 +/- 16 mmHg, AVA: 0.9 +/- 0.2 cm(2)). 46% had ascending aorta aneurysm (mean aortic root, sinutubular junction, ascending aorta dimensions: 36 +/- 3 mm, 31 +/- 4 mm and 41 +/- 8 mm). Patients with ascending aortic aneurysm were younger (41 +/- 11 years vs. 52 +/- 5 years, P < 0.05) All UAV were unicommissural with a posteriorly positioned commissural attachment, 69% were heavily calcified. Diagnostic accuracy was limited by quality of images, severity, and distribution of calcification. Conclusion: TEE is the diagnostic modality of choice in UAV. Identifying several echo features may improve its diagnostic accuracy. (Echocardiography 2010;27:1107-1112) C1 [Chu, John W.; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Dept Cardiol, Boston, MA USA. [Agnihotri, Arvind K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiac Surg, Boston, MA USA. [Fitzsimons, Michael G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Chu, JW (reprint author), Univ Otago, Dunedin Sch Med, Dunedin, New Zealand. EM john.chu@healthotago.co.nz OI Picard, Michael/0000-0002-9264-3243 FU National Heart Foundation of New Zealand, Auckland, New Zealand FX Dr. John W. Chu was supported in part by a grant from the National Heart Foundation of New Zealand, Auckland, New Zealand. NR 21 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD OCT PY 2010 VL 27 IS 9 BP 1107 EP 1112 DI 10.1111/j.1540-8175.2010.01209.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 673UW UT WOS:000283690100011 PM 20553323 ER PT J AU Amorosa, V MacNeil, A McConnell, R Patel, A Dillon, KE Hamilton, K Erickson, BR Campbell, S Knust, B Cannon, D Miller, D Manning, C Rollin, PE Nichol, ST AF Amorosa, Valerianna MacNeil, Adam McConnell, Ryan Patel, Ami Dillon, Katherine E. Hamilton, Keith Erickson, Bobbie Rae Campbell, Shelley Knust, Barbara Cannon, Deborah Miller, David Manning, Craig Rollin, Pierre E. Nichol, Stuart T. TI Imported Lassa Fever, Pennsylvania, USA, 2010 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID EPIDEMIC; LIBERIA AB We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in country, sought medical care upon return to the United States, and subsequently had his illness laboratory confirmed. The patient recovered with supportive therapy. No secondary cases occurred. C1 [Amorosa, Valerianna; McConnell, Ryan; Dillon, Katherine E.; Hamilton, Keith] Univ Penn, Philadelphia, PA 19104 USA. [Amorosa, Valerianna] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [MacNeil, Adam; Patel, Ami; Erickson, Bobbie Rae; Campbell, Shelley; Knust, Barbara; Cannon, Deborah; Miller, David; Manning, Craig; Rollin, Pierre E.; Nichol, Stuart T.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Patel, Ami] Philadelphia Dept Hlth, Philadelphia, PA USA. RP Amorosa, V (reprint author), Philadelphia VAMC Med, Philadelphia, PA 19104 USA. EM valerianna.amorosa@uphs.upenn.edu OI Cameron, Katherine/0000-0002-0859-0741 NR 14 TC 25 Z9 27 U1 0 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD OCT PY 2010 VL 16 IS 10 BP 1598 EP 1600 DI 10.3201/eid1610.100774 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 657EA UT WOS:000282394800014 PM 20875288 ER PT J AU Miedlich, SU Zhu, ED Sabbagh, Y Demay, MB AF Miedlich, Susanne U. Zhu, Eric D. Sabbagh, Yves Demay, Marie B. TI The Receptor-Dependent Actions of 1,25-Dihydroxyvitamin D Are Required for Normal Growth Plate Maturation in NPt2a Knockout Mice SO ENDOCRINOLOGY LA English DT Article ID VITAMIN-D-RECEPTOR; MINERAL ION HOMEOSTASIS; HYPERTROPHIC CHONDROCYTES; EPIPHYSEAL CHONDROCYTES; SKELETAL PHENOTYPE; ABLATED MICE; RICKETS; APOPTOSIS; ALOPECIA; RESCUE AB Rickets is a growth plate abnormality observed in growing animals and humans. Rachitic expansion of the hypertrophic chondrocyte layer of the growth plate, in the setting of hypophosphatemia, is due to impaired apoptosis of these cells. Rickets is observed in humans and mice with X-linked hypophosphatemia that is associated with renal phosphate wasting secondary to elevated levels of fibroblast growth factor-23. Rickets is also seen in settings of impaired vitamin D action, due to elevated PTH levels that increase renal phosphate excretion. However, mice with hypophosphatemia secondary to ablation of the renal sodium-dependent phosphate transport protein 2a (Npt2a), have not been reported to develop rickets. Because activation of the mitochondrial apoptotic pathway by phosphate is required for hypertrophic chondrocyte apoptosis in vivo, investigations were undertaken to address this paradox. Analyses of the Npt2a null growth plate demonstrate expansion of the hypertrophic chondrocyte layer at 2 wk of age, with resolution of this abnormality by 5 wk of age. This is temporally associated with an increase in circulating levels of 1,25-dihydroxyvitamin D. To address whether the receptor-dependent actions of this steroid hormone are required for normalization of the growth plate phenotype, the Npt2a null mice were mated with mice lacking the vitamin D receptor or were rendered vitamin D deficient. These studies demonstrate that the receptor-dependent actions of 1,25-dihydroxyvitamin D are required for maintenance of a normal growth plate phenotype in the Npt2a null mice. (Endocrinology 151: 4607-4612, 2010) C1 [Miedlich, Susanne U.; Zhu, Eric D.; Sabbagh, Yves; Demay, Marie B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Demay, MB (reprint author), 50 Blossom St,Thier 11, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu OI Sabbagh, Yves/0000-0001-5339-6705 FU National Institutes of Health [R01 DK 46974, P50 AR054086] FX This work was supported by Grants R01 DK 46974 and P50 AR054086 from the National Institutes of Health. NR 21 TC 17 Z9 17 U1 1 U2 2 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 OCT PY 2010 VL 151 IS 10 BP 4607 EP 4612 DI 10.1210/en.2010-0354 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652KQ UT WOS:000282005700003 PM 20685875 ER PT J AU Sacco, A Ghobrial, IM Roccaro, AM AF Sacco, Antonio Ghobrial, Irene M. Roccaro, Aldo M. TI Epigenetics in Waldenstrom's macroglobulinemia SO EPIGENOMICS LA English DT Article DE histone acetylation; miRNA; Waldenstrom's macroglobulinemia ID NF-KAPPA-B; MULTIPLE-MYELOMA; MICRORNA EXPRESSION; HUMAN CANCERS; GENE; MODULATION; EPIGENOME; LEUKEMIA; THERAPY; REVEALS AB Waldenstrom's macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by the presence of lymphoplasmacytic cells in the bone marrow and a serum monoclonal immunoglobulin, known as IgM, in the circulation. Although indolent, it remains incurable with a median overall survival of 5-6 years, and most patients succumb to disease progression. Cytogenetic and molecular studies on gene-expression analysis at the mRNA level have demonstrated minimal changes in WM cells. Therefore, multilevel characterization of this disease at the genetic and epigenetic level is required to improve our understanding of the underlying molecular changes that lead to the initiation and progression of this disease. In this study it has been demonstrated that WM patients present with a specific miRNA signature. Among deregulated miRNAs, miR-155 and miR-9 star play a pivotal role in the pathogenesis of this disease. C1 [Sacco, Antonio; Ghobrial, Irene M.; Roccaro, Aldo M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Roccaro, AM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128 NR 36 TC 1 Z9 1 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-1911 J9 EPIGENOMICS-UK JI Epigenomics PD OCT PY 2010 VL 2 IS 5 BP 691 EP 696 DI 10.2217/EPI.10.42 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 687ZJ UT WOS:000284817000012 PM 22122052 ER PT J AU Ramsay, E Faught, E Krumholz, A Naritoku, D Privitera, M Schwarzman, L Mao, L Wiegand, F Hulihan, J AF Ramsay, Eugene Faught, Edward Krumholz, Allan Naritoku, Dean Privitera, Michael Schwarzman, Lesley Mao, Lian Wiegand, Frank Hulihan, Joseph CA Capss-272 Study Group TI Efficacy, tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new-onset epilepsy: A randomized double-blind clinical trial SO EPILEPSIA LA English DT Article DE Complex partial seizures; Epilepsy; Generalized tonic-clonic seizures; Phenytoin; Rapid-initiation; Topiramate ID NEWLY-DIAGNOSED EPILEPSY; 1ST UNPROVOKED SEIZURE; TONIC CLONIC SEIZURES; UNTREATED EPILEPSY; CARBAMAZEPINE; LAMOTRIGINE; MONOTHERAPY; RISK; VALPROATE; ADULTS AB P>Purpose: To evaluate topiramate (TPM) and phenytoin (PHT) monotherapy following rapid oral initiation in new-onset epilepsy. Methods: Randomized, double-blind, 28-day trial of TPM (100 mg/day beginning on day 1) versus PHT (1,000 mg on day 1 followed by 300 mg/day maintenance dosing) in 261 patients with new-onset epilepsy. The primary end point was time to seizure, and the primary objective was to establish noninferiority of TPM to PHT in the risk of seizure. Results: At day 28, the estimated seizure-free rate was 81.1% for TPM treatment in comparison with 90.3% for PHT treatment. Noninferiority of TPM to PHT (primary objective) could not be established [hazard ratio (HR) 2.0, 95% confidence interval (CI), 0.98 to 4.12, p = 0.366), and PHT could not be shown to be superior to TPM. A higher percentage discontinued with PHT compared to TPM for all reasons (21.1 vs. 12.8%) and due to adverse events (13.4 vs. 6.8%). The most common treatment-related adverse events in both groups were dizziness, paresthesia, and somnolence. A post hoc analysis showed that TPM was superior to PHT in time to discontinuation (retention rate) for all causes (89.4% vs. 80.3%, p = 0.047). Conclusion: This study was inconclusive in establishing noninferiority of TPM 100 mg/day compared to a standard regimen of oral PHT in seizure risk in this population of patients with new-onset epilepsy. Given the superiority of TPM in overall retention and favorable tolerability without titration, it may nonetheless be an appropriate option in some patients with new-onset epilepsy requiring rapid treatment initiation. C1 [Ramsay, Eugene] Ochsner Baptist Med Ctr, Epilepsy Inst, New Orleans, LA 70115 USA. [Faught, Edward] Univ Alabama, Sch Med, Birmingham, AL USA. [Faught, Edward] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Krumholz, Allan] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Naritoku, Dean] So Illinois Univ, Springfield, IL USA. [Privitera, Michael] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Schwarzman, Lesley; Mao, Lian; Wiegand, Frank; Hulihan, Joseph] LLC, Ortho McNeil Janssen Sci Affairs, Titusville, NJ USA. RP Ramsay, E (reprint author), Ochsner Baptist Med Ctr, Epilepsy Inst, 4299 Clara St,MacFarland Bldg,Suite 440, New Orleans, LA 70115 USA. EM eramsay@epiworld.com RI Ramsay, R. Eugene/D-4491-2011 FU Ortho-McNeil Janssen Scientific Affairs, LLC.; Abbott Laboratories; Bertex; Carter-Wallace; Cephalon; Cyberonics; Eisai; GlaxoSmithKline; IVAX; Marion Merrell Dow; Novartis; Ortho-McNeil Pharmaceuticals; Ovation Pharmaceuticals; Pfizer; RW Johnson; Schwarz Pharma; SmithKline Beecham; UCB Pharma; X-cel Pharma; Ortho-McNeil/JohnsonJohnson; Schwarz Pharma/UCB; American Epilepsy Society; EpiFellows Foundation; Janssen-Cilag; National Institutes of Health; Pfizer Inc FX Funding for this study was provided by Ortho-McNeil Janssen Scientific Affairs, LLC.; Eugene Ramsay has received support from, and/or has served as a paid consultant for Abbott Laboratories, Bertex, Carter-Wallace, Cephalon, Cyberonics, Eisai, GlaxoSmithKline, IVAX, Marion Merrell Dow, Novartis, Ortho-McNeil Pharmaceuticals, Ovation Pharmaceuticals, Pfizer, RW Johnson, Schwarz Pharma, SmithKline Beecham, UCB Pharma, and X-cel Pharma.; Edward Faught has received support from, and/or has served as a paid consultant for Ortho-McNeil/Johnson&Johnson.; Allan Krumholz has received support from, and/or has served as a paid consultant for Ortho-McNeil Pharmaceuticals, Ovation Pharmaceuticals, and UCB Pharma.; Dean Naritoku has received support from, and/or has served as a paid consultant for Abbott Laboratories, Eisai, GlaxoSmithKline, Ortho-McNeil Pharmaceuticals, and Schwarz Pharma/UCB.; Michael Privitera has received support from, and/or has served as a paid consultant for the American Epilepsy Society, epiFellows Foundation, GlaxoSmithKline, Janssen-Cilag, National Institutes of Health, Ortho-McNeil Pharmaceuticals, Pfizer Inc, and UCB Pharma. NR 35 TC 17 Z9 17 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2010 VL 51 IS 10 BP 1970 EP 1977 DI 10.1111/j.1528-1167.2010.02670.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 660KE UT WOS:000282639700006 PM 20633037 ER PT J AU Zukotynski, KA Fahey, FH Laffin, S Davis, R Treves, ST Grant, FD Drubach, LA AF Zukotynski, Katherine A. Fahey, Frederic H. Laffin, Stephen Davis, Royal Treves, S. Ted Grant, Frederick D. Drubach, Laura A. TI Seasonal variation in the effect of constant ambient temperature of 24A degrees C in reducing FDG uptake by brown adipose tissue in children SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE Seasonal variation; (18)F-FDG uptake; Brown adipose tissue; Children ID POSITRON-EMISSION-TOMOGRAPHY; UPPER CHEST REGION; F-18-FDG PET/CT; ADULT HUMANS; USA-FAT; OBESITY; CANCER; PROPRANOLOL; REDUCTION; SCANS AB It has been shown that warming patients prior to and during (18)F-FDG uptake by controlling the room temperature can decrease uptake by brown adipose tissue (BAT). The aim of this study is to determine if this effect is subject to seasonal variation. A retrospective review was conducted of all patients referred for whole-body (18)F-FDG PET between December 2006 and December 2008. After December 2007, all patients were kept in the PET injection room at a constant 24A degrees C for 30 min before and until 1 h following FDG administration. Patients over 22 years of age and those who received pre-medication known to reduce FDG uptake by BAT were excluded. One hundred and three patients were warmed to 24A degrees C prior to scanning. The number of patients showing uptake by BAT in this group was compared to a control group of 99 patients who underwent PET prior to December 2007 when the injection room temperature was 21A degrees C. Uptake by BAT occurred in 9% of studies performed after patient warming (24A degrees C), compared to 27% of studies performed on the control group (21A degrees C) (p < 0.00001). The effect of warming on decreasing FDG accumulation in BAT was statistically significant in the winter (p < 0.005) and summer (p < 0.001). However, in the spring and autumn, though the effect of warming on decreasing FDG accumulation in BAT was evident, it was not statistically significant (p > 0.05). Maintaining room temperature at a constant 24A degrees C for 30 min prior to and 1 h after IV tracer administration significantly decreases FDG uptake by BAT in children. This effect is greatest in the summer and winter. C1 [Fahey, Frederic H.; Laffin, Stephen; Davis, Royal; Treves, S. Ted; Grant, Frederick D.; Drubach, Laura A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Radiol,Div Nucl Med PET, Boston, MA 02115 USA. [Zukotynski, Katherine A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging,Div Nucl Med, Boston, MA 02115 USA. RP Drubach, LA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Radiol,Div Nucl Med PET, 300 Longwood Ave, Boston, MA 02115 USA. EM kzukotynski@partners.org; laura.drubach@childrens.harvard.edu NR 32 TC 16 Z9 16 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2010 VL 37 IS 10 BP 1854 EP 1860 DI 10.1007/s00259-010-1485-2 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 647DX UT WOS:000281597700006 PM 20505932 ER PT J AU Giesel, FL Mehndiratta, A Essig, M AF Giesel, Frederik L. Mehndiratta, Amit Essig, Marco TI High-relaxivity contrast-enhanced magnetic resonance neuroimaging: a review SO EUROPEAN RADIOLOGY LA English DT Article DE Contrast media; Magnetic resonance imaging; Neuroimaging; Protein affinity; Relaxivity ID NEPHROGENIC SYSTEMIC FIBROSIS; 1.0 M GADOBUTROL; AORTOILIAC OCCLUSIVE DISEASE; HIGH-DOSE GADOTERIDOL; GADOBENATE-DIMEGLUMINE; GADOPENTETATE DIMEGLUMINE; MR-ANGIOGRAPHY; 3 TESLA; BRAIN-TUMORS; PHASE-III AB Evaluation of brain lesions using magnetic resonance imaging (MRI) provides information that is critical for accurate diagnosis, prognosis, therapeutic intervention and monitoring response. Conventional contrast-enhanced MR neuroimaging using gadolinium (Gd) contrast agents primarily depicts disruption of the blood-brain barrier, demonstrating location and extent of disease, and also the morphological details at the lesion site. However, conventional imaging results do not always accurately predict tumour aggressiveness. Advanced functional MRI techniques such as dynamic contrast-enhanced perfusion-weighted imaging utilise contrast agents to convey physiological information regarding the haemodynamics and neoangiogenic status of the lesion that is often complementary to anatomical information obtained through conventional imaging. Most of the Gd contrast agents available have similar T1 and T2 relaxivities, and thus their contrast-enhancing capabilities are comparable. Exceptions are gadobenate-dimeglumine, Gd-EOB-DTPA, Gadobutrol and gadofosveset, which, owing to their transient-protein-binding capability, possess almost twice (and more) the T1 and T2 relaxivities as other agents at all magnetic field strengths. Numerous comparative studies have demonstrated the advantages of the increased relaxivity in terms of enhanced image contrast, image quality and diagnostic confidence. Here we summarise the benefits of higher relaxivity for the most common neuroimaging applications including MRI, perfusion-weighted imaging and MRA for evaluation of brain tumours, cerebrovascular disease and other CNS lesions. C1 [Giesel, Frederik L.; Mehndiratta, Amit; Essig, Marco] German Canc Res Ctr, Dept Radiol E010, D-69120 Heidelberg, Germany. [Giesel, Frederik L.] Univ Heidelberg, Heidelberg, Germany. [Mehndiratta, Amit] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Essig, M (reprint author), German Canc Res Ctr, Dept Radiol E010, D-69120 Heidelberg, Germany. EM m.essig@dkfz.de NR 79 TC 26 Z9 28 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD OCT PY 2010 VL 20 IS 10 BP 2461 EP 2474 DI 10.1007/s00330-010-1805-8 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 651SR UT WOS:000281947900019 PM 20567832 ER PT J AU de Molina, RM Mortensen, EM Restrepo, MI Copeland, LA Pugh, MJV Anzueto, A AF de Molina, R. Malo Mortensen, E. M. Restrepo, M. I. Copeland, L. A. Pugh, M. J. V. Anzueto, A. TI Inhaled corticosteroid use is associated with lower mortality for subjects with COPD and hospitalised with pneumonia SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Chronic obstructive pulmonary disease; inhaled corticosteroids; mortality; pneumonia ID OBSTRUCTIVE PULMONARY-DISEASE; COMMUNITY-ACQUIRED PNEUMONIA; SALMETEROL/FLUTICASONE PROPIONATE; FLUTICASONE PROPIONATE; UNITED-STATES; RISK-FACTORS; PROPENSITY SCORE; LUNG-DISEASE; SALMETEROL; EXACERBATIONS AB Recent studies suggest that use of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) may be associated with a higher incidence of pneumonia. However, it is unclear whether COPD subjects on ICS who develop pneumonia have worse outcomes. Therefore, our aim was to examine the association of prior outpatient ICS therapy with mortality in hospitalised COPD subjects with pneumonia. We included subjects >= 64 yrs of age, hospitalised with pneumonia in US Veterans Affairs hospitals, and assessed the association of ICS exposure with mortality for hospitalised COPD subjects with pneumonia in a covariate-adjusted regression model. We identified 6,353 subjects with a diagnosis of pneumonia and prior COPD, of whom 38% were on ICS. Mortality was 9% at 30 days and 16% at 90 days. In regression analyses, outpatient ICS therapy was associated with lower mortality at both 30 days (OR 0.76, 95% CI 0.70-0.83), and 90 days (OR 0.80, 95% CI 0.75-0.86). Outpatient therapy with ICS was associated with a significantly lower 30- and 90-day mortality in hospitalised COPD patients with pneumonia. C1 [Restrepo, M. I.] UTHSCSA, ALMD, VERDICT Res Programme,S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX 78229 USA. [de Molina, R. Malo; Restrepo, M. I.; Anzueto, A.] UTHSCSA, Div Pulm & Crit Care Med, Dept Med, San Antonio, TX 78229 USA. [Mortensen, E. M.] UTHSCSA, Div Gen Internal Med, Dept Med, San Antonio, TX 78229 USA. [Copeland, L. A.] UTHSCSA, Dept Psychiat, San Antonio, TX 78229 USA. [Pugh, M. J. V.] UTHSCSA, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. RP Restrepo, MI (reprint author), UTHSCSA, ALMD, VERDICT Res Programme,S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, 11C6,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu OI Mortensen, Eric/0000-0002-3880-5563; Copeland, Laurel/0000-0002-9478-0209 FU Spanish Pulmonary Society (SEPAR) [757]; Dept of Veterans Affairs [IIR 02-076, MREP 02-267] FX R. Malo de Molina received funding from the Spanish Pulmonary Society (SEPAR), project 757. M.J. Pugh received funding from the Dept of Veterans Affairs IIR 02-076 and MREP 02-267. L. A. Copeland was supported by the Dept of Veterans Affairs MREP 05-145. M. I. Restrepo is supported by a Dept of Veteran Affairs Veterans Integrated Service Network 17 new faculty grant and National Health Institute KL2 Grant 9CTSA Award Number (KL2 RR025766). This material is the result of work supported with resources and the use of facilities at the South Texas Veterans Health Care System. The funding agencies had no role in conducting the study, or role in the preparation, review, or approval of the manuscript. 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 52 TC 39 Z9 39 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD OCT PY 2010 VL 36 IS 4 BP 751 EP 757 DI 10.1183/09031936.00077509 PG 7 WC Respiratory System SC Respiratory System GA 658ER UT WOS:000282473700014 ER PT J AU Rasmusson, AM Schnurr, PP Zukowska, Z Scioli, E Forman, DE AF Rasmusson, Ann M. Schnurr, Paula P. Zukowska, Zofia Scioli, Erica Forman, Daniel E. TI Adaptation to extreme stress: post-traumatic stress disorder, neuropeptide Y and metabolic syndrome SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Annual FASEB Experimental Biology Meeting CY APR 21, 2009 CL San Diego, CA DE metabolic syndrome; post-traumatic stress disorder; neuropeptide Y; obesity hypertension; neurosteroids; depression; dehydroepiandrosterone; testosterone; cortisol; allopregnanolone ID ALPHA(2C)-ADRENORECEPTOR GENE POLYMORPHISM; AMBULATORY CARDIOVASCULAR ACTIVITY; CONGENITAL ADRENAL-HYPERPLASIA; CORTICOTROPIN-RELEASING-FACTOR; RECEPTOR ANTAGONIST BIBP3226; NUCLEUS-TRACTUS-SOLITARIUS; POLYCYSTIC-OVARY-SYNDROME; MALE MILITARY VETERANS; MAJOR DEPRESSION; DEHYDROEPIANDROSTERONE-SULFATE AB The prevalence rates of obesity and metabolic syndrome are on the rise in the United States. Epidemiological surveys suggest that the rates of these medical conditions are especially high among persons with psychiatric disorders, including post-traumatic stress disorder (PTSD). A variety of factors are thought to contribute to the risk for metabolic syndrome, including excessive caloric intake, decreased activity and energy expenditure, use of certain medications, stress and genetic influences. Recent research demonstrates that stress, acting through the neuropeptide Y (NPY) and glucocorticoid systems, potentiates the development of obesity and other aspects of metabolic syndrome in mice fed a high caloric, fat and sugar diet. Alterations in the NPY and glucocorticoid systems also impact behavioral adaptation to stress, as indicated by studies in animals and persons exposed to severe, life-threatening or traumatic stress. The following review examines the biology of the NPY and neuroactive steroid systems as physiological links between metabolic syndrome and PTSD, a paradigmatic neuropsychiatric stress disorder. Hopefully, understanding the function of these systems from both a translational and systems biology point of view in relation to stress will enable development of more effective methods for preventing and treating the negative physical and mental health consequences of stress. C1 [Rasmusson, Ann M.; Scioli, Erica; Forman, Daniel E.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Rasmusson, Ann M.; Scioli, Erica] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Rasmusson, Ann M.; Scioli, Erica] Boston Univ, Sch Med, Boston, MA 02118 USA. [Schnurr, Paula P.] Natl Ctr PTSD, Execut Div, White River Jct, VT 05009 USA. [Schnurr, Paula P.] Dartmouth Med Sch, Hanover, NH 03755 USA. [Zukowska, Zofia] Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20057 USA. [Zukowska, Zofia] Georgetown Univ, Med Ctr, Stress Physiol & Res Ctr, Washington, DC 20057 USA. [Forman, Daniel E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Forman, Daniel E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rasmusson, AM (reprint author), VA Boston Healthcare Syst, 116B3,150 S Huntington Ave, Boston, MA 02130 USA. EM ann.rasmusson@gmail.com FU NHLBI NIH HHS [HL055310, HL067357] NR 161 TC 51 Z9 52 U1 6 U2 18 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1535-3702 EI 1535-3699 J9 EXP BIOL MED JI Exp. Biol. Med. PD OCT PY 2010 VL 235 IS 10 BP 1150 EP 1162 DI 10.1258/ebm.2010.009334 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 670VN UT WOS:000283455500003 PM 20881319 ER PT J AU Stengel, A Tache, Y AF Stengel, Andreas Tache, Yvette TI Corticotropin-releasing factor signaling and visceral response to stress SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Annual FASEB Experimental Biology Meeting CY APR 21, 2009 CL San Diego, CA DE cardiovascular system; corticotropin-releasing factor (CRF); irritable bowel syndrome (IBS); stress; urocortin (Ucn) ID IRRITABLE-BOWEL-SYNDROME; ENTERIC NERVOUS-SYSTEM; EXPERIMENTAL HEART-FAILURE; MESSENGER-RNA EXPRESSION; FUNCTIONAL GASTROINTESTINAL DISORDERS; HORMONE-RECEPTOR ANTAGONIST; WATER-AVOIDANCE STRESS; COLONIC MOTOR RESPONSE; TYPE-2 CRF RECEPTORS; ISOLATED RAT-HEART AB Stress may cause behavioral and/or psychiatric manifestations such as anxiety and depression and also impact on the function of different visceral organs, namely the gastrointestinal and cardiovascular systems. During the past years substantial progress has been made in the understanding of the underlying mechanisms recruited by stressors. Activation of the corticotropin-releasing factor (CRF) signaling system is recognized to be involved in a large number of stress-related behavioral and somatic disorders. This review will outline the present knowledge on the distribution of the CRF system (ligands and receptors) expressed in the brain and peripheral viscera and its relevance in stress-induced alterations of gastrointestinal and cardiovascular functions and the therapeutic potential of CRF(1) receptor antagonists. C1 [Tache, Yvette] VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Div Digest Dis, Los Angeles, CA 90095 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU NIDDK NIH HHS [R01 DK033061, R01 DK 33061, R01 DK 57238, R01 DK057238, R37 DK033061] NR 171 TC 54 Z9 59 U1 0 U2 7 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD OCT PY 2010 VL 235 IS 10 BP 1168 EP 1178 DI 10.1258/ebm.2010.009347 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 670VN UT WOS:000283455500005 PM 20881321 ER PT J AU Ananthakrishnan, AN Binion, DG AF Ananthakrishnan, Ashwin N. Binion, David G. TI Impact of Clostridium difficile on inflammatory bowel disease SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE Clostridium difficile; Crohn's disease; inflammatory bowel disease; metronidazole; ulcerative colitis; vancomycin ID ANTIBIOTIC-ASSOCIATED DIARRHEA; PSEUDOMEMBRANOUS ENTERITIS; INTRAVENOUS IMMUNOGLOBULIN; TREATMENT STRATEGIES; NORTH-AMERICA; RISK-FACTORS; TOXIN-A; INFECTION; COLITIS; COLECTOMY AB Clostridium difficile infection (CDI) has been increasing in incidence among those with underlying inflammatory bowel disease (IBD) and is associated with substantial morbidity, the need for surgery and even mortality. The similar clinical presentation between CDI and a flare of underlying IBD makes prompt diagnosis essential to prevent deterioration which would accompany an escalation of immunosuppression in the absence of appropriate antibiotic therapy. Classical risk factors (antibiotic or healthcare exposure) or clinical findings (pseudomembranes) may not be found in many IBD patients with CDI and should not be considered essential for entertaining the diagnosis. Enzyme immunoassays detecting both toxins A and B remain the most widely used test for diagnosis and have acceptable sensitivity, but may require testing of multiple samples in select situations. Both vancomycin and metronidazole appear to be effective and treatment with oral vancomycin is preferred in those with severe disease, including those who require hospitalization. Appropriate infection control measures are essential to restrict patient-to-patient spread within healthcare environments and to prevent recurrences. Several novel therapies are currently under study, including new antibiotic agents and monoclonal antibodies targeted against the toxins. There is a need to broaden these studies to the IBD population. There is also the need to prospectively examine whether CDI has long-term disease-modifying consequences in those with underlying IBD. C1 [Binion, David G.] Univ Pittsburgh, Sch Med, UPMC Presbyterian Hosp, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15216 USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Binion, DG (reprint author), Univ Pittsburgh, Sch Med, UPMC Presbyterian Hosp, Div Gastroenterol Hepatol & Nutr, 200 Lothrop St, Pittsburgh, PA 15216 USA. EM binion@pitt.edu FU NIH; UCB Pharma; Abbott Laboratories FX Ashwin N Ananthakrishnan reports no conflicts related to this work. David Binion has research support from the NIH and ongoing research collaboration with UCB Pharma and Abbott Laboratories and has received consulting fees from these entities as well. 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 105 TC 11 Z9 11 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4124 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD OCT PY 2010 VL 4 IS 5 BP 589 EP 600 DI 10.1586/EGH.10.55 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 860YF UT WOS:000297983700014 PM 20932144 ER PT J AU Sher, DJ AF Sher, David J. TI Cost-effectiveness studies in radiation therapy SO EXPERT REVIEW OF PHARMACOECONOMICS & OUTCOMES RESEARCH LA English DT Review DE cancer; cost-effectiveness analysis; decision analysis; health services research; radiation oncology; radiation therapy; utilities ID CELL LUNG-CANCER; STAGE BREAST-CANCER; PROPHYLACTIC CRANIAL IRRADIATION; INTENSITY-MODULATED RADIOTHERAPY; RANDOMIZED CONTROLLED-TRIAL; TOTAL MESORECTAL EXCISION; PAINFUL BONE METASTASES; UTILITY ANALYSIS; PROSTATE-CANCER; RECTAL-CANCER AB The field of radiation therapy has made dramatic technical advances over the past 20 years. 3D conformal radiotherapy, intensity-modulated radiation therapy and proton beam therapy have all been developed in an attempt to improve the therapeutic ratio: higher cure rates with lower toxicity. Unfortunately, although the costs of radiation therapy are certainly increasing, it is unclear whether its clinical benefit has also improved. Cost-effectiveness analyses are designed to formally evaluate the cost of a treatment relative to an associated change in quality-adjusted survival. As the cost of oncologic care is increasing, it is critically important to assess the cost-effectiveness of radiation therapy. This article will describe the issues surrounding the delivery and cost of radiation therapy, and it will summarize the work that has been done to evaluate the use of cost-effectiveness in radiation oncology. C1 [Sher, David J.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Sher, David J.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Sher, DJ (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM dsher@lroc.harvard.edu NR 109 TC 17 Z9 17 U1 0 U2 8 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7167 J9 EXPERT REV PHARM OUT JI Expert Rev. Pharmacoecon. Outcomes Res. PD OCT PY 2010 VL 10 IS 5 BP 567 EP 582 DI 10.1586/ERP.10.51 PG 16 WC Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 847XY UT WOS:000297010200014 PM 20950072 ER PT J AU Mukherjee, R Colbath, GP Justus, CD Bruce, JA Allen, CM Hewett, KW Saul, JP Gourdie, RG Spinale, FG AF Mukherjee, Rupak Colbath, Gregory P. Justus, Charles D. Bruce, James A. Allen, Claire M. Hewett, Kenneth W. Saul, J. Philip Gourdie, Robert G. Spinale, Francis G. TI Spatiotemporal induction of matrix metalloproteinase-9 transcription after discrete myocardial injury SO FASEB JOURNAL LA English DT Article DE myocardial injury; structure; remodeling ID MATRIX-METALLOPROTEINASE INHIBITION; LEFT-VENTRICULAR ENLARGEMENT; GAP-JUNCTION; HEART-FAILURE; ATRIAL-FIBRILLATION; TARGETED DELETION; TISSUE INHIBITOR; CARDIAC-FUNCTION; INFARCTION; EXPRESSION AB Radiofrequency (RF) ablation of the myocardium causes discrete sites of injury. RF scars can expand, altering the extracellular matrix (ECM) structure and the continuity of the electrical syncytium of the adjacent myocardium. Matrix metalloproteinases (MMPs), such as MMP-9, contribute to ECM remodeling. However, whether and to what degree transcriptional induction of MMP-9 occurs after myocardial RF injury and the association with electrical conduction patterns after RF injury remains unexplored. This study examined MMP-9 gene promoter (M9PROM) activation after myocardial RF injury using mice in which the M9PROM was fused to a beta-galactosidase (beta-gal) reporter. RF lesions (0.5-mm probe, 80 degrees C, 30 s) were created on the left ventricular (LV) epicardium of M9PROM mice (n=62) and terminally studied at 1 h, 1 d, 3 d, 7 d, 14 d, and 28 d after RF injury. M9PROM activation was localized through beta-gal staining. The RF scar area and the area of beta-gal staining were measured and normalized to LV area (planimetry). RF scar size increased from 1 h post-RF-injury values by 7 d and remained higher at 28 d. M9PROM activation became evident at 3 d and peaked at 7 d. Electrical conduction was measured (potentiometric dye mapping) at 7 d after RF injury. Heterogeneities in action potentials and electrical impulse propagation coincident with M9PROM activation were observed after RF injury. For example, conduction proximal to the RF site was slower than that in the remote myocardium (0.15+/-0.02 vs. 0.83+/-0.08 mm/ms, P<0.05). Thus, a unique spatiotemporal pattern of MMP-9 transcriptional activation occurred after discrete myocardial injury, which was associated with the development of electrical heterogeneity. Therefore, these findings suggest that changes in a key determinant of extracellular matrix remodeling, in addition to changes in myocardial structure, can contribute to arrhythmogenesis around the region of myocardial injury.-Mukherjee, R., Colbath, G. P., Justus, C. D., Bruce, J. A., Allen, C. M., Hewett, K. W., Saul, J. P., Gourdie, R. G., Spinale, F. G. Spatiotemporal induction of matrix metalloproteinase-9 transcription following discrete myocardial injury. FASEB J. 24, 3819-3828 (2010). www.fasebj.org C1 [Mukherjee, Rupak; Colbath, Gregory P.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Mukherjee, Rupak; Bruce, James A.; Allen, Claire M.; Saul, J. Philip; Spinale, Francis G.] Med Univ S Carolina, Div Pediat Cardiol, Charleston, SC 29425 USA. [Justus, Charles D.; Hewett, Kenneth W.; Gourdie, Robert G.] Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. [Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Mukherjee, R (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Strom Thurmond Res Bldg,770 MUSC Complex,Ste 625, Charleston, SC 29425 USA. EM mukherr@musc.edu FU U.S. National Institutes of Health [HL-66029, HL-45024, HL-97012, P01-48788, HL-56728] FX This study was supported by U.S. National Institutes of Health grants HL-66029 (to R.M.), HL-45024, HL-97012, and P01-48788 (to F.G.S.), and HL-56728 (to R.G.G.). NR 41 TC 6 Z9 6 U1 0 U2 2 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 OCT PY 2010 VL 24 IS 10 BP 3819 EP 3828 DI 10.1096/fj.10-155531 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 690LI UT WOS:000285005900020 PM 20530752 ER PT J AU Grover, S Syngal, S AF Grover, Shilpa Syngal, Sapna TI Hereditary Pancreatic Cancer SO GASTROENTEROLOGY LA English DT Review ID PEUTZ-JEGHERS-SYNDROME; PAPILLARY MUCINOUS NEOPLASMS; BRCA1 MUTATION CARRIERS; GERMLINE P16 MUTATIONS; STRONG FAMILY-HISTORY; INTRAEPITHELIAL NEOPLASIA; PRONE FAMILIES; HIGH-RISK; DUCTAL ADENOCARCINOMAS; CLINICAL-PERSPECTIVE C1 [Grover, Shilpa; Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02114 USA. [Grover, Shilpa; Syngal, Sapna] Brigham & Womens Hosp, Dept Gastroenterol, Boston, MA 02115 USA. [Grover, Shilpa; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Grover, Shilpa] Massachusetts Gen Hosp, Program Canc Outcomes Res Training, Boston, MA 02114 USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, 44 Binney St,Smith 209, Boston, MA 02114 USA. EM ssyngal@partners.org FU NIH/NCI [R25 CA092203, K24 CA113433-05, R01CA97075-07] FX Dr Grover is funded by an NIH grant (NIH/NCI R25 CA092203). Dr Syngal is the recipient of NIH grants (NIH/NCI K24 CA113433-05, NIH/NCI R01CA97075-07). NR 85 TC 30 Z9 31 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2010 VL 139 IS 4 BP 1076 EP + DI 10.1053/j.gastro.2010.08.012 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 656WV UT WOS:000282372700010 PM 20727885 ER PT J AU Goyal, RK Chaudhury, A AF Goyal, Raj K. Chaudhury, Arun TI Pathogenesis of Achalasia: Lessons From Mutant Mice SO GASTROENTEROLOGY LA English DT Editorial Material ID SMOOTH-MUSCLE; CGMP KINASE; DISEASE; NEURONS; MODEL; GUT C1 VA Boston HealthCare Syst, Ctr Swallowing & Motil Disorders, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goyal, RK (reprint author), VA Med Ctr, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM raj_goyal@hms.harvard.edu FU NIDDK NIH HHS [DK062867] NR 21 TC 14 Z9 15 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2010 VL 139 IS 4 BP 1086 EP 1090 DI 10.1053/j.gastro.2010.08.013 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 656WV UT WOS:000282372700013 PM 20800108 ER PT J AU Leung, FW Harker, JO Jackson, G Okamoto, KE Behbahani, OM Jamgotchian, NJ Aharonian, HS Guth, PH Mann, SK Leung, JW AF Leung, Felix W. Harker, Judith O. Jackson, Guy Okamoto, Kate E. Behbahani, Omid M. Jamgotchian, Nora J. Aharonian, H. Steven Guth, Paul H. Mann, Surinder K. Leung, Joseph W. TI A proof-of-principle, prospective, randomized, controlled trial demonstrating improved outcomes in scheduled unsedated colonoscopy by the water method SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week/111th Annual Meeting of the American-Gastroenterological-Association CY MAY 01-06, 2010 CL New Orleans, LA SP Amer Gastroenterol Assoc ID SEDATION-FREE COLONOSCOPY; SCREENING COLONOSCOPY; COLORECTAL-CANCER; PATIENT; VETERANS; PERFORMANCE; POPULATION; DISCOMFORT; ENDOSCOPY; TIME AB Background: An observational study in veterans showed that a novel water method (water infusion in lieu of air insufflation) enhanced cecal intubation and willingness to undergo a repeat scheduled unsedated colonoscopy. Objective: To confirm these beneficial effects and significant attenuation of discomfort in a randomized, controlled trial (RCT). Design: Prospective RCT, intent-to-treat analysis. Setting: Veterans Affairs ambulatory care facility. Patients: Veterans undergoing scheduled unsedated colonoscopy. Interventions: During insertion, the water and traditional air methods were compared. Main Outcome Measurements: Discomfort and procedure-related outcomes. Results: Eighty-two veterans were randomized to the air (n = 40) or water (n = 42) method. Cecal intubation (78% vs 98%) and willingness to repeat (78% vs 93%) were significantly better with the water method (P < .05; Fisher exact test). The mean (standard deviation) of maximum discomfort (0 = none, 10 = most severe) during colonoscopy was 5.5 (3.0) versus 3.6 (2.1) P = .002 (Student t test), and the median overall discomfort after colonoscopy was 3 versus 2, P = .052 (Mann-Whitney U test), respectively. The method, but not patient characteristics, was a predictor of discomfort (t = -1.998, P = .049, R(2) = 0.074). The odds ratio for failed cecal intubation was 2.09 (95% CI, 1.49-2.93) for the air group. Fair/poor previous experience increased the risk of failed cecal intubation in the air group only. The water method numerically increased adenoma yield. Limitations: Single site, small number of elderly men, unblinded examiner, possibility of unblinded subjects, restricted generalizability. Conclusions: The RCT data confirmed that the water method significantly enhanced cecal intubation and willingness to undergo a repeat colonoscopy. The decrease in maximum discomfort was significant; the decrease in overall discomfort approached significance. The method, but not patient characteristics, was a predictor of discomfort. (Clinical trial registration number NCT00747084). (Gastrointest Endosc 2010;72:693-700.) C1 [Leung, Felix W.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, David Geffen Sch Med,Div Gastroenterol 111G, Res Serv,Sepulveda Ambulatory Care Ctr, North Hills, CA 91343 USA. [Leung, Felix W.; Aharonian, H. Steven; Guth, Paul H.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Mann, Surinder K.; Leung, Joseph W.] Vet Affairs No Calif Healthcare Syst, Sacramento VAMC, Mather, CA USA. [Mann, Surinder K.; Leung, Joseph W.] UC Davis Med Ctr, Sacramento, CA USA. [Leung, Felix W.; Harker, Judith O.; Jackson, Guy; Okamoto, Kate E.; Behbahani, Omid M.; Jamgotchian, Nora J.; Aharonian, H. Steven; Guth, Paul H.] Vet Affairs Greater Los Angeles Healthcare Syst, Med Serv, Sepulveda Ambulatory Care Ctr, North Hills, CA USA. RP Leung, FW (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, David Geffen Sch Med,Div Gastroenterol 111G, Res Serv,Sepulveda Ambulatory Care Ctr, 16111 Plummer St, North Hills, CA 91343 USA. EM felix.leung@va.gov NR 42 TC 49 Z9 50 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2010 VL 72 IS 4 BP 693 EP 700 DI 10.1016/j.gie.2010.05.020 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663ZB UT WOS:000282927600004 PM 20619405 ER PT J AU Turner, BG Gee, DW Cizginer, S Kim, MC Mino-Kenudson, M Sylla, P Brugge, WR Rattner, DW AF Turner, Brian G. Gee, Denise W. Cizginer, Sevdenur Kim, Min-Chan Mino-Kenudson, Mari Sylla, Patricia Brugge, William R. Rattner, David W. TI Endoscopic transesophageal mediastinal lymph node dissection and en bloc resection by using mediastinal and thoracic approaches (with video) SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID SURGERY NOTES; LUNG-CANCER; SURVIVAL; THORACOSCOPY AB Background: The criterion standard for sampling mediastinal lymph nodes is cervical mediastinoscopy. Current methods that require transthoracic or cervical incisions can result in significant postoperative pain. Objective: To determine the feasibility of a novel, transesophageal endoscopic technique for mediastinal lymph node dissection and en bloc resection. Design: Nonsurvival and survival animal study. Setting: Animal trial at a tertiary-care academic center. Subjects: This study involved 12 Yorkshire swine. Intervention: An endoscopic cap band mucosectomy device was used to create an esophageal mucosal defect. By using the tip of the endoscope and biopsy forceps, a submucosal tunnel was fashioned, and, within the submucosal space, a hook-knife incised the muscular esophageal wall. The endoscope was then advanced into the mediastinum and chest. Mediastinoscopy and thoracoscopy were performed to identify lymph node stations. Prototype endoscopic devices permitted lymph node dissection prior to removal with an electrocautery snare. A covered prototype stent was placed over the mucosectomy site. Main Outcome Measurements: Feasibility of endoscopic transesophageal lymphadenectomy. Results: Three lymph nodes (1 para-aortic and 2 right paratracheal) were removed in the 3 nonsurvival swine. Nine swine were survived for 14 days (range 13-14 days) and had a total of 7 lymph nodes (2 para-aortic and 5 paratracheal) removed. Two swine had no endoscopically visible lymph nodes in the mediastinum or chest. Lymph node dissection and resection was successful in all cases where lymph nodes were identified. Lymphadenectomy was completed in a median time of 20.0 minutes (range 8-60 minutes); median total procedure time was 70.0 minutes (range 28-105 minutes). Median lymph node size was 1.1 cm (range 0.6-1.4 cm). Limitations: Animal study. Conclusion: An endoscopic transesophageal approach can accomplish mediastinal lymph node dissection and en bloc resection and provides architecturally intact lymph node specimens for histologic examination. C1 [Gee, Denise W.; Kim, Min-Chan; Sylla, Patricia; Rattner, David W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kim, Min-Chan] Dong A Univ, Coll Med, Minimally Invas & Robot Ctr, Dept Surg, Pusan, South Korea. [Turner, Brian G.; Cizginer, Sevdenur; Brugge, William R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. FU Center for Integrative Medicine and Technology FX Funding for this project was provided by the Center for Integrative Medicine and Technology (B. T., D. G., S. C., P. S. W. R. B., D. W. R.). Ethicon Endo-Surgery donated instruments for this project, and Cook Medical donated endoscopic supplies. W. R. Brugge disclosed a consultant relationship with Boston Scientific, and D. W. Rattner disclosed a speaker relationship with Olympus for which he has received an honorarium. No other disclosures of financial relationships relevant to this publication were made. NR 8 TC 6 Z9 7 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2010 VL 72 IS 4 BP 831 EP 835 DI 10.1016/j.gie.2010.04.019 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663ZB UT WOS:000282927600026 PM 20573345 ER PT J AU DeWitt, J DiMaio, CJ Brugge, WR AF DeWitt, John DiMaio, Christopher J. Brugge, William R. TI Long-term follow-up of pancreatic cysts that resolve radiologically after EUS-guided ethanol ablation SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID PAPILLARY MUCINOUS NEOPLASMS; UPDATED EXPERIENCE; RESECTION; ESOPHAGUS; LESIONS; LAVAGE; TUMORS AB Background: EUS-guided ablation of pancreatic cysts is a minimally invasive technique with reported short-term, CT-defined cyst resolution rates of 33% to 79%. Follow-up results of image-defined, successful pancreatic cyst ablation are not known. Objective: To determine the durability of successful cyst resolution after EUS-guided ethanol lavage. Design: Prospective cohort study. Setting: Two tertiary-care referral hospitals in the United States. Patients: This study involved 12 patients with 1-to-5-cm, unilocular, pancreatic cysts that had previously resolved after ethanol lavage. Interventions: Follow-up CT after cyst resolution. Main Outcome Measurements: The presence or absence of residual pancreatic cysts by CT scanning after previous successful ablation. Results: In a previously reported trial, we found that CT scanning documented pancreatic cyst resolution in 12 patients (33%) after one (n = 6) or two (n = 6) ethanol lavages. These 12 cysts (median diameter 18 mm; range 10-34 mm) were located in the head/uncinate of the pancreas in 6 patients (50%) and in the body of the pancreas in 6 patients (50%). The median cyst fluid carcinoembryonic antigen (CEA) level (available in 11 patients) was 463 ng/mL (range 1.6-64,550 ng/mL; normal, 0-2.5 ng/mL). Clinical diagnoses were mucinous cystic neoplasm (MCN) in 9 patients, intraductal papillary mucinous neoplasm in 1 patient, pseudocyst in 1 patient, and serous cystadenoma (SCA) in 1 patient. Follow-up CT in 3 patients (one each of MCN, SCA, and pseudocyst) after the initial diagnosis of cyst resolution was not available. For the remaining 9 patients (75%), follow-up CT performed in a median of 26 months (range 13-39 months) after initial documentation of cyst resolution demonstrated no evidence of cyst recurrence in any patient. Limitations: Loss to follow-up of some of the cohort. Conclusions: Follow-up after successful EUS-guided ethanol ablation of pancreatic cysts, including suspected mucinous cysts, suggests a durable, image-defined resolution. Longer follow-up in these patients is needed before considering these patients "cured" of their disease. C1 [DeWitt, John] Indiana Univ, Med Ctr, Div Gastroenterol & Hepatol, Dept Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. [DiMaio, Christopher J.] Mem Sloan Kettering Canc Ctr, Dept Gastroenterol, New York, NY 10021 USA. [Brugge, William R.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. RP DeWitt, J (reprint author), Indiana Univ, Med Ctr, Div Gastroenterol & Hepatol, Dept Gastroenterol & Hepatol, 550 N Univ Blvd,UH 4100, Indianapolis, IN 46202 USA. NR 19 TC 27 Z9 28 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2010 VL 72 IS 4 BP 862 EP 866 DI 10.1016/j.gie.2010.02.039 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663ZB UT WOS:000282927600042 PM 20883866 ER PT J AU Becker, PS Taylor, JA Trobridge, GD Zhao, X Beard, BC Chien, S Adair, J Kohn, DB Wagner, JE Shimamura, A Kiem, HP AF Becker, P. S. Taylor, J. A. Trobridge, G. D. Zhao, X. Beard, B. C. Chien, S. Adair, J. Kohn, D. B. Wagner, J. E. Shimamura, A. Kiem, H-P TI Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector SO GENE THERAPY LA English DT Article DE gene therapy; mitomycin C; reducing agent; hypoxia ID HEMATOPOIETIC STEM-CELLS; NATURAL GENE-THERAPY; FUNCTIONAL CORRECTION; REPOPULATING CELLS; REVERSE MOSAICISM; PROGENITOR CELLS; ENGRAFTMENT; VIRUS AB One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA. Gene Therapy (2010) 17, 1244-1252; doi:10.1038/gt.2010.62; published online 20 May 2010 C1 [Becker, P. S.; Zhao, X.; Chien, S.] Univ Washington, Div Hematol, Dept Med, Seattle, WA 98109 USA. [Taylor, J. A.] Oregon Hlth & Sci Univ, Div Hematol Oncol, Dept Med, Portland, OR USA. [Taylor, J. A.] Portland VA Med Ctr, Portland, OR USA. [Trobridge, G. D.; Beard, B. C.; Adair, J.; Shimamura, A.; Kiem, H-P] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Trobridge, G. D.; Kiem, H-P] Univ Washington, Div Med Oncol, Dept Med, Seattle, WA 98109 USA. [Kohn, D. B.] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90024 USA. [Kohn, D. B.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Wagner, J. E.] Univ Minnesota, Dept Pediat, Div Pediat Hematol Oncol, Minneapolis, MN 55455 USA. [Shimamura, A.] Seattle Childrens Hosp, Dept Pediat, Div Pediat Hematol Oncol, Seattle, WA USA. [Kiem, H-P] Univ Washington, Dept Pathol, Seattle, WA 98109 USA. RP Becker, PS (reprint author), Univ Washington, Div Hematol, Dept Med, Campus Box 358056,815 Mercer St N415, Seattle, WA 98109 USA. EM pbecker@u.washington.edu RI Kohn, Donald/N-5085-2016 OI Kohn, Donald/0000-0003-1840-6087 FU NIH [HL085693, DK56465, DK47754]; National Institutes of Health FX This work was supported by NIH Grants HL085693, DK56465 and DK47754 to HPK. We thank Helen Crawford and Bonnie Larson for help with the preparation of the article. HPK is a Molecular Medicine Investigator and the recipient of the Jose Carreras/E. Donnall Thomas Endowed Chair for Cancer Research. We received grant support from National Institutes of Health. NR 27 TC 12 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 2010 VL 17 IS 10 BP 1244 EP 1252 DI 10.1038/gt.2010.62 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 664GO UT WOS:000282948600008 PM 20485382 ER PT J AU Chen, G Buck, KJ AF Chen, G. Buck, K. J. TI Rostroventral caudate putamen involvement in ethanol withdrawal is influenced by a chromosome 4 locus SO GENES BRAIN AND BEHAVIOR LA English DT Article DE c-Fos; lesion; Mpdz; MUPP1 seizure; striatum ID PDZ DOMAIN PROTEIN; C-FOS EXPRESSION; ACUTE ALCOHOL-WITHDRAWAL; BASAL GANGLIA; STRIATOPALLIDAL NEURONS; INDUCED CONVULSIONS; NMDA RECEPTORS; NERVOUS-SYSTEM; C57BL/6J MICE; NR2B SUBUNIT AB Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains alcohol use and abuse and may contribute to relapse in dependent individuals. Although no animal model duplicates alcoholism, models for specific factors, like withdrawal, are useful for identifying potential genetic and neural determinants of liability in humans. Previously, we identified a quantitative trait locus (QTL) and gene (Mpdz, which encodes the multi-PDZ domain protein) on chromosome 4 with a large effect on alcohol withdrawal in mice. Using congenic mice that confirm this QTL and c-Fos expression as a high-resolution marker of neuronal activation, we report that congenic mice show significantly less neuronal activity associated with alcohol withdrawal in the rostroventral caudate putamen (rvCP), but not other parts of the striatum, compared with background strain mice. Moreover, bilateral rvCP lesions significantly increase alcohol withdrawal severity. Using retrograde (fluorogold) and anterograde (Texas Red conjugated dextran amine) tract tracing, we found that similar to 25% of c-Fos immunoreactive rvCP neurons project to caudolateral substantia nigra pars reticulata (clSNr), which we previously found is crucially involved in withdrawal following acute and repeated alcohol exposure. Our results expand upon work suggesting that this QTL impacts alcohol withdrawal via basal ganglia circuitry associated with limbic function, and indicate that an rvCP-clSNr projection plays a critical role. Given the growing body of evidence that the syntenic region of human chromosome 9p and human MPDZ gene are associated with alcohol abuse, our results may facilitate research on alcohol dependence and associated withdrawal in clinical populations. C1 [Buck, K. J.] Portland VA Med Ctr, Dept Behav Neurosci, Portland, OR 97239 USA. Portland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland, OR 97239 USA. RP Buck, KJ (reprint author), Portland VA Med Ctr, Dept Behav Neurosci, Portland, OR 97239 USA. EM buckk@ohsu.edu FU VA; [AA011114]; [AA10760]; [DA05228] FX Supported by AA011114, AA10760, DA05228, and the VA. We are grateful to Drs. Laura Kozell, Robert Hitzemann, Charles Meshul, John Belknap and John Crabbe for helpful discussions of these experiments and their comments on a draft of this manuscript. NR 60 TC 6 Z9 6 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD OCT PY 2010 VL 9 IS 7 BP 768 EP 776 DI 10.1111/j.1601-183X.2010.00611.x PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 660IT UT WOS:000282634300011 PM 20608999 ER PT J AU Stegh, AH Brennan, C Mahoney, JA Forloney, KL Jenq, HT Luciano, JP Protopopov, A Chin, L DePinho, RA AF Stegh, Alexander H. Brennan, Cameron Mahoney, John A. Forloney, Kristin L. Jenq, Harry T. Luciano, Janina P. Protopopov, Alexei Chin, Lynda DePinho, Ronald A. TI Glioma oncoprotein Bcl2L12 inhibits the p53 tumor suppressor SO GENES & DEVELOPMENT LA English DT Article DE Glioblastoma multiforme; Bcl2L12; p53 ID GROWTH-FACTOR RECEPTOR; DNA-DAMAGE; MALIGNANT GLIOMAS; APOPTOTIC PATHWAYS; INK4A LOCUS; CELL-DEATH; BAX GENE; IN-VITRO; MDM2; GLIOBLASTOMA AB Glioblastoma multiforme (GBM) is a lethal brain tumor characterized by intense apoptosis resistance and extensive necrosis. Bcl2L12 (for Bcl2-like 12) is a cytoplasmic and nuclear protein that is overexpressed in primary GBM and functions to inhibit post-mitochondrial apoptosis signaling. Here, we show that nuclear Bcl2L12 physically and functionally interacts with the p53 tumor suppressor, as evidenced by the capacity of Bcl2L12 to (1) enable bypass of replicative senescence without concomitant loss of p53 or p19 Arf, (2) inhibit p53-dependent DNA damage-induced apoptosis, (3) impede the capacity of p53 to bind some of its target gene promoters, and (4) attenuate endogenous p53-directed transcriptomic changes following genotoxic stress. Correspondingly, The Cancer Genome Atlas profile and tissue protein analyses of human GBM specimens show significantly lower Bcl2L12 expression in the setting of genetic p53 pathway inactivation. Thus, Bcl2L12 is a multifunctional protein that contributes to intense therapeutic resistance of GBM through its ability to operate on two key nodes of cytoplasmic and nuclear signaling cascades. C1 [Stegh, Alexander H.; Mahoney, John A.; Forloney, Kristin L.; Protopopov, Alexei; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Stegh, Alexander H.; Luciano, Janina P.] Northwestern Univ, Ken & Ruth Davee Dept Neurol, Robert H Lurie Comprehens Canc Ctr, Brain Tumor Inst,Ctr Genet Med, Chicago, IL 60611 USA. [Brennan, Cameron] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, Dept Neurosurg, New York, NY 10021 USA. [Jenq, Harry T.] Harvard Univ, Sch Med, Div Hlth Sci & Technol, Boston, MA 02114 USA. [Jenq, Harry T.] MIT, Boston, MA 02114 USA. [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. RP Stegh, AH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. EM a-stegh@northwestern.edu; ron_depinho@dfci.harvard.edu FU NIH [5R00CA129172-04, RO1CA99041, 5P01CA95616]; Zell Scholar award; NIOH [5P01CA95616, U24 CA126543-01]; Ben and Catherine Ivy Foundation; Goldhirsh Foundation; Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science FX We thank Dr. William Kaelin (Dana-Farber Cancer Institute [DFCI], Boston) for providing us with cDNAs encoding various p53 deletion mutants, and Dr. Stanley Korsmeyer (DFCI, Boston) for the GST-Bcl-xL and Bad expression constructs. A. H. S. was supported by NIH grant 5R00CA129172-04 and a Zell Scholar award. C. B. was supported by the NIOH grants 5P01CA95616 and U24 CA126543-01. Grant support derives from the Ben and Catherine Ivy Foundation (to R. A. D. and L. C.), the Goldhirsh Foundation (to R. A. D.), and NIH grants RO1CA99041 (to L. C) and 5P01CA95616 (to L. C. and R. A. D.). R. A. D. is an American Cancer Society Research Professor, and is supported by the Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science. The results published here are based in part upon data generated by The Cancer Genome Atlas pilot project established by the NCI and National Human Genome Research Institute. Information about TCGA and the investigators and institutions who constitute the The Cancer Genome Atlas Research Network can be found at http://www.cancergenome.nih.gov. A. H. S. dedicates this study to the memory of his father, Theodor Stegh, who passed away in May 2009 after a brave battle with ALS. NR 74 TC 36 Z9 37 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 1 PY 2010 VL 24 IS 19 BP 2194 EP 2204 DI 10.1101/gad.1924710 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 656YE UT WOS:000282376200009 PM 20837658 ER PT J AU Lupien, M Meyer, CA Bailey, ST Eeckhoute, J Cook, J Westerling, T Zhang, XY Carroll, JS Rhodes, DR Liu, XS Brown, M AF Lupien, Mathieu Meyer, Clifford A. Bailey, Shannon T. Eeckhoute, Jerome Cook, Jennifer Westerling, Thomas Zhang, Xiaoyang Carroll, Jason S. Rhodes, Daniel R. Liu, X. Shirley Brown, Myles TI Growth factor stimulation induces a distinct ER alpha cistrome underlying breast cancer endocrine resistance SO GENES & DEVELOPMENT LA English DT Article DE ERBB2; breast cancer; cistrome; estrogen receptor; growth factors; transcription ID ESTROGEN-RECEPTOR-ALPHA; GENE-EXPRESSION SIGNATURE; ACTIVATED PROTEIN-KINASE; SIGNALING PATHWAYS; HISTOLOGIC GRADE; BINDING-SITES; MCF-7 CELLS; CROSS-TALK; TAMOXIFEN; PHOSPHORYLATION AB Estrogen receptor alpha (ER alpha) expression in breast cancer is predictive of response to endocrine therapy; however, resistance is common in ER alpha-positive tumors that overexpress the growth factor receptor ERBB2. Even in the absence of estrogen, ER alpha can be activated by growth factors, including the epidermal growth factor (EGF). EGF induces a transcriptional program distinct from estrogen; however, the mechanism of the stimulus-specific response is unknown. Here we show that the EGF-induced ER alpha genomic targets, its cistromes, are distinct from those induced by estrogen in a process dependent on the transcription factor AP-1. The EGF-induced ER alpha cistrome specifically regulates genes found overexpressed in ERBB2-positive human breast cancers. This provides a potential molecular explanation for the endocrine therapy resistance seen in ER alpha-positive breast cancers that overexpress ERBB2. These results suggest a central role for ER alpha in hormone-refractory breast tumors dependent on growth factor pathway activation and favors the development of therapeutic strategies completely antagonizing ER alpha, as opposed to blocking its estrogen responsiveness alone. C1 [Lupien, Mathieu; Bailey, Shannon T.; Cook, Jennifer; Westerling, Thomas; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. [Lupien, Mathieu; Bailey, Shannon T.; Cook, Jennifer; Westerling, Thomas; Liu, X. Shirley; Brown, Myles] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Lupien, Mathieu; Zhang, Xiaoyang] Dartmouth Med Sch, Norris Cotton Canc Ctr, Dept Genet, Lebanon, NH 03756 USA. [Meyer, Clifford A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Meyer, Clifford A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Eeckhoute, Jerome] Univ Rennes 1, CNRS, UMR 6026, F-35042 Rennes, France. [Carroll, Jason S.] Cambridge Res Inst, Canc Res UK, Cambridge CB2 0RE, England. [Rhodes, Daniel R.] Compendia Biosci Inc, Ann Arbor, MI 48104 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. EM xsliu@jimmy.harvard.edu; myles_brown@dfci.harvard.edu RI Bailey, Shannon/B-8045-2014; OI Brown, Myles/0000-0002-8213-1658 FU NIDDK [R01DK074967]; NCI [P01 CA8011105, P50C89393]; DFCI; US Department of Defense [W81XWH-08-1-0214] FX We thank Dr. Nancy Colburn (NCI-Frederick) for providing the dominant-negative AP-1 construct (TAM67). This work was supported by grants from the NIDDK (R01DK074967 to M. B.), the NCI (P01 CA8011105, and the DF/HCC Breast Cancer SPORE Grant P50C89393 to M. B.), the DFCI Women's Cancers Program, and the US Department of Defense Breast Cancer Research Program Awards (W81XWH-08-1-0214 to M.L.). NR 69 TC 70 Z9 71 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 1 PY 2010 VL 24 IS 19 BP 2219 EP 2227 DI 10.1101/gad.1944810 PG 9 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 656YE UT WOS:000282376200011 PM 20889718 ER PT J AU Surakka, I Kristiansson, K Anttila, V Inouye, M Barnes, C Moutsianas, L Salomaa, V Daly, M Palotie, A Peltonen, L Ripatti, S AF Surakka, Ida Kristiansson, Kati Anttila, Verneri Inouye, Michael Barnes, Chris Moutsianas, Loukas Salomaa, Veikko Daly, Mark Palotie, Aarno Peltonen, Leena Ripatti, Samuli TI Founder population-specific HapMap panel increases power in GWA studies through improved imputation accuracy and CNV tagging SO GENOME RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; COPY-NUMBER; LINKAGE DISEQUILIBRIUM; DISEASE HERITAGE; POLYMORPHISMS; COMMON AB The combining of genome-wide association (GWA) data across populations represents a major challenge for massive global meta-analyses. Genotype imputation using densely genotyped reference samples facilitates the combination of data across different genotyping platforms. HapMap data is typically used as a reference for single nucleotide polymorphism (SNP) imputation and tagging copy number polymorphisms (CNPs). However, the advantage of having population-specific reference panels for founder populations has not been evaluated. We looked at the properties and impact of adding 81 individuals from a founder population to HapMap3 reference data on imputation quality, CNP tagging, and power to detect association in simulations and in an independent cohort of 2138 individuals. The gain in SNP imputation accuracy was highest among low-frequency markers (minor allele frequency [MAF] < 5%), for which adding the population-specific samples to the reference set increased the median R(2) between imputed and genotyped SNPs from 0.90 to 0.94. Accuracy also increased in regions with high recombination rates. Similarly, a reference set with population-specific extension facilitated the identification of better tag-SNPs for a subset of CNPs; for 4% of CNPs the R(2) between SNP genotypes and CNP intensity in the independent population cohort was at least twice as high as without the extension. We conclude that even a relatively small population-specific reference set yields considerable benefits in SNP imputation, CNP tagging accuracy, and the power to detect associations in founder populations and population isolates in particular. C1 [Surakka, Ida; Anttila, Verneri; Palotie, Aarno; Peltonen, Leena; Ripatti, Samuli] Univ Helsinki, FIMM, Inst Mol Med Finland, FI-00014 Helsinki, Finland. [Surakka, Ida; Kristiansson, Kati; Peltonen, Leena; Ripatti, Samuli] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, FI-00271 Helsinki, Finland. [Kristiansson, Kati; Anttila, Verneri; Inouye, Michael; Barnes, Chris; Palotie, Aarno; Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Inouye, Michael] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Moutsianas, Loukas] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Hlth Promot & Chron Dis Prevent, FI-00271 Helsinki, Finland. [Daly, Mark; Palotie, Aarno; Peltonen, Leena] Harvard & Massachusetts Inst Technol, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Daly, Mark] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Palotie, Aarno; Peltonen, Leena] Univ Helsinki, Helsinki Univ Hosp, Dept Med Genet, FI-00014 Helsinki, Finland. RP Ripatti, S (reprint author), Univ Helsinki, FIMM, Inst Mol Med Finland, FI-00014 Helsinki, Finland. EM samuli.ripatti@fimm.fi RI Ripatti, Samuli/H-9446-2014; OI Ripatti, Samuli/0000-0002-0504-1202; Anttila, Verneri/0000-0002-0073-4675; Kristiansson, Kati/0000-0003-4688-107X FU Wellcome Trust [WT089062/Z/09/Z, WT089061/Z/09/Z]; Center of Excellence for Complex Disease Genetics of the Academy of Finland [213506, 129680]; Biocentrum Helsinki Foundation; Nordic Center of Excellence in Disease Genetics; Academy of Finland [129494, 125973]; Finnish Foundation for Cardiovascular Research; Sigrid Juselius Foundation; Orion-Farmos Research Foundation; EPSRC; Finnish Cultural Foundation FX This work was supported by the Wellcome Trust (WT089062/Z/09/Z, WT089061/Z/09/Z). L.P., S.R., and A.P. are supported by the Center of Excellence for Complex Disease Genetics of the Academy of Finland (grant nos. 213506 and 129680). L.P. is supported by the Biocentrum Helsinki Foundation and The Nordic Center of Excellence in Disease Genetics. V.S. is supported by the Academy of Finland (grant no. 129494), the Finnish Foundation for Cardiovascular Research, and the Sigrid Juselius Foundation. K.K. is supported by the Academy of Finland (grant no. 125973) and the Orion-Farmos Research Foundation. L.M. is supported by the EPSRC. V.A. is supported by the Finnish Cultural Foundation. We thank Peter Wagner for language revision of this manuscript. NR 21 TC 27 Z9 27 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2010 VL 20 IS 10 BP 1344 EP 1351 DI 10.1101/gr.106534.110 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 656XS UT WOS:000282375000004 PM 20810666 ER PT J AU Seo, SJ Fisher, DE AF Seo, S. -J. Fisher, D. E. TI Melanocyte photobiology, ultraviolet radiation and melanoma SO GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA LA English DT Article DE Melanocytes; Melanoma; Ultraviolet rays; Skin pigmentation; Skin neoplasms ID CULTURED HUMAN MELANOCYTES; INDUCED DNA-DAMAGE; CYCLOBUTANE PYRIMIDINE DIMERS; STIMULATING-HORMONE-RECEPTOR; IRRADIATED MOUSE SKIN; MALIGNANT-MELANOMA; HUMAN-EPIDERMIS; HUMAN KERATINOCYTES; INDUCED APOPTOSIS; RED HAIR AB Of all the organs of the human body, the skin is most commonly affected by malignancy, and ultraviolet radiation has long been implicated as the primary mutagenic exposure leading to the development of many cutaneous cancers. However, as research in this field has continued, it has become clear that the effect of ultraviolet radiation on the skin is quite complex. Distinct cell types within the skin exhibit differing responses to ultraviolet radiation, and even within the same cell type, divergent effects may be observed; depending on the dose or wavelength of the radiation, or the maturational state of the affected cell, unique responses can be elicited. Melanocytes form a minor component of the outermost layer of skin, but they have an enormous impact on not only the appearance of the skin, but also the ability of the skin to withstand exposure to ultraviolet radiation. In addition, melanocytes give rise to melanoma, one of the most deadly types of skin cancer. Clearly, it is critical that we achieve a better understanding of the effect of ultraviolet radiation on melanocytes, and that we clarify its role in the oncogenesis of melanoma. Although the picture is far from complete, the mechanisms by which melanocytes respond to ultraviolet radiation are beginning to be elucidated, and, as these pathways emerge, they offer new targets for chemopreventive and chemotherapeutic intervention. C1 [Fisher, D. E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Seo, S. -J.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Seo, S. -J.; Fisher, D. E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Fisher, D. E.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. EM dfisher3@partners.org FU NIAMS NIH HHS [R01 AR043369] NR 100 TC 2 Z9 2 U1 0 U2 2 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0026-4741 J9 GIORN ITAL DERMAT V JI G. Ital. Dermatol. Venereol. PD OCT PY 2010 VL 145 IS 5 BP 603 EP 611 PG 9 WC Dermatology SC Dermatology GA 658FZ UT WOS:000282477200005 PM 20930695 ER PT J AU Wexler, TL Durst, R McCarty, D Picard, MH Gunnell, L Omer, Z Fazeli, P Miller, KK Klibanski, A AF Wexler, Tamara L. Durst, Ronen McCarty, David Picard, Michael H. Gunnell, Lindsay Omer, Zehra Fazeli, Pouneh Miller, Karen K. Klibanski, Anne TI Growth hormone status predicts left ventricular mass in patients after cure of acromegaly SO GROWTH HORMONE & IGF RESEARCH LA English DT Article DE Acromegaly; Growth hormone deficiency; Left ventricular mass ID CARDIOVASCULAR RISK-FACTORS; ADULT GH DEFICIENCY; SOMATOSTATIN ANALOGS; HYPOPITUITARY ADULTS; CARDIAC-PERFORMANCE; BODY-COMPOSITION; MORTALITY; HEART; REPLACEMENT; ATHEROSCLEROSIS AB Context: Growth hormone excess and growth hormone deficiency (GHD) are both associated with increased cardiovascular morbidity. A specific acromegaly-related cardiomyopathy has been described, characterized in part by increased left ventricular mass (LVM). Growth hormone deficiency is associated with reduced LVM. Following cure of acromegaly with surgery or radiation therapy, GHD may develop; however, its effects on cardiac morphology and function in this population are not established. Objective: We hypothesized that the development of GHD in patients with prior acromegaly would be associated with cardiac morphologic and functional changes that differ from those in patients who are GH sufficient following cure of acromegaly. Design: A cross-sectional study was conducted in a Clinical Research Center. Study participants consisted of three groups of subjects (n=34): I. Cured acromegaly with GHD (n=15), II. Cured acromegaly with GH sufficiency (n=8), and III. Active acromegaly (n=11). Main outcome measures included cardiac morphology and function, using echocardiography parameters. Results: Mean age and BMI, 44.6 +/- 2.3 years (SEM) and 30.7 +/- 13 kg/m(2), respectively, were not different among the three groups. Mean peak GH values were: I. 2.8 +/- 0.4 ng/ml; II. 30.1 +/- 9.1 ng/ml (p = 0.0002.) In group I, left ventricular mass, indexed to body surface area (LVMi), was within the normal range in all patients; moreover, left ventricular (LV) geometry was normal. At least 50% of patients in groups II and III had elevated LVMi, and in 50% of patients, LV geometry was abnormal, indicating pathologic hypertrophy. Ejection fraction was similar between all three groups. There were no significant differences in diastolic function. Conclusions: Patients who develop GHD following cure of acromegaly do not demonstrate elevated LV mass, in contrast to patients with a history of acromegaly but normal GH levels or to patients with active acromegaly. This suggests that GH status after treatment of acromegaly correlates with LV mass, and that, in GH sufficient patients, reversal of remodeling may be slower than previously thought. These data suggest that it will be important to determine whether GH replacement alters left ventricular morphology over time. (C) 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved. C1 [Wexler, Tamara L.; Gunnell, Lindsay; Omer, Zehra; Fazeli, Pouneh; Miller, Karen K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Wexler, Tamara L.; Durst, Ronen; McCarty, David; Picard, Michael H.; Gunnell, Lindsay; Omer, Zehra; Fazeli, Pouneh; Miller, Karen K.; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA USA. [Durst, Ronen; McCarty, David; Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM AKlibanski@partners.org OI Picard, Michael/0000-0002-9264-3243 FU National Institutes of Health [MO1 RR01066, ULI RR0257801, T32 DK007028]; Pfizer; Guthart Family Foundation FX This work was supported in part by the following grants from the National Institutes of Health: MO1 RR01066, ULI RR0257801, and T32 DK007028, an investigator-initiated research grant from Pfizer and a grant from the Guthart Family Foundation. NR 46 TC 7 Z9 7 U1 0 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 1096-6374 EI 1532-2238 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD OCT PY 2010 VL 20 IS 5 BP 333 EP 337 DI 10.1016/j.ghir.2010.05.003 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 672UD UT WOS:000283611500001 PM 20598930 ER PT J AU Fontana, RJ Dienstag, JL Bonkovsky, HL Sterling, RK Naishadham, D Goodman, ZD Lok, ASF Wright, EC Su, GL AF Fontana, Robert J. Dienstag, Jules L. Bonkovsky, Herbert L. Sterling, Richard K. Naishadham, Deepa Goodman, Zachary D. Lok, Anna S. F. Wright, Elizabeth C. Su, Grace L. CA HALT-C Trial Grp TI Serum fibrosis markers are associated with liver disease progression in non-responder patients with chronic hepatitis C SO GUT LA English DT Article ID COMPENSATED CIRRHOSIS; INTERFERON THERAPY; RANDOMIZED-TRIAL; HYALURONIC-ACID; YKL-40; STEATOSIS; RIBAVIRIN; VIRUS; PEGINTERFERON; VARIABILITY AB Objectives The aim of this study was to explore the association of serum fibrosis marker levels with the risk of clinical and histological disease progression in a large cohort of patients with chronic hepatitis C (CHC). Methods 462 prior non-responders to peginterferon and ribavirin enrolled in the randomised phase of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial had baseline and annual serum samples tested for hyaluronic acid (HA), N-terminal peptide of procollagen type 3, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and YKL-40. All patients underwent a pretreatment liver biopsy and follow-up biopsies at years 2 and 4. Histological progression was defined as a >= 2 point increase in Ishak fibrosis score in patients without cirrhosis. Clinical outcomes included development of decompensation, hepatocellular cancer, death or an increase in the CTP (Child-Turcotte-Pugh) score to >= 7. Results Mean patient age was 49.5 years and 39% had histological cirrhosis at entry. Baseline HA, YKL-40 and TIMP-1 levels combined with other laboratory parameters were all significantly associated with clinical outcomes in the 69 (15%) patients with disease progression (p<0.0001). The best multivariate model to predict clinical outcomes included baseline bilirubin, albumin, international normalised ratio (INR) and YKL-40 levels. All of the baseline serum fibrosis marker levels were also significantly associated with histological fibrosis progression that developed in 70 (33%) of the 209 patients with cirrhosis (p<0.0001). However, baseline HA and platelet counts were best at predicting histological progression (area under the curve (AUC)=0.663). Conclusion Pretreatment serum fibrosis marker levels are significantly increased in patients with CHC at risk of clinical and histological disease progression. If validated in additional cohorts, measurement of these markers could help identify patients with CHC who would benefit from more frequent and intensive monitoring. C1 [Fontana, Robert J.] Univ Michigan, Dept Internal Med, Taubman Ctr 3912, Sch Med, Ann Arbor, MI 48109 USA. [Dienstag, Jules L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Med Serv, Boston, MA USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Storrs, CT 06269 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Storrs, CT 06269 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Storrs, CT 06269 USA. [Sterling, Richard K.] Virginia Commonwealth Univ Med Ctr, Hepatol Sect, Richmond, VA USA. [Naishadham, Deepa] Tufts Univ New England Med Ctr, Boston, MA USA. [Wright, Elizabeth C.] NIDDKD, NIH, Dept Hlth & Human Serv, Baltimore, MD USA. RP Fontana, RJ (reprint author), Univ Michigan, Dept Internal Med, Taubman Ctr 3912, Sch Med, Ann Arbor, MI 48109 USA. EM rfontana@med.umich.edu OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes & Digestive & Kidney Diseases; National Center for Research Resources, National Institutes of Health; Hoffmann-La Roche; National Institutes of Health; University of Massachusetts Medical Center, Worcester, Massachusetts [N01-DK-9-2326]; University of Connecticut Health Center, Farmington, Connecticut [M01RR-06192]; Massachusetts General Hospital, Boston, Massachusetts (Harvard Clinical and Translational Science Center) [N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; University of Michigan Medical Center, Ann Arbor, Michigan (Michigan Center for Clinical and Health Research) [N01-DK-9-2323, M01RR-00042, 1 UL1 RR024986]; Virginia Commonwealth University Health System, Richmond, Virginia [N01-DK-9-2322, M01RR-00065]; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, Maryland; New England Research Institutes, Watertown, Massachusetts [N01-DK-9-2328]; Armed Forces Institute of Pathology, Washington, DC FX This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. In addition to the authors of this manuscript, the following individuals were instrumental in the planning, conduct and/or care of patients enrolled in this study at each of the participating institutions as follows: University of Massachusetts Medical Center, Worcester, Massachusetts (contract N01-DK-9-2326), Gyongyi Szabo, Barbara F Banner, Maureen Cormier, Donna Giansiracusa; University of Connecticut Health Center, Farmington, Connecticut (grant M01RR-06192), Gloria Borders, Michelle Kelley; Massachusetts General Hospital, Boston, Massachusetts (contract N01-DK-9-2319, grant M01RR-01066; grant 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center), Raymond T Chung, Andrea E Reid, Atul K Bhan, Wallis A Molchen, Cara C Gooch; University of Michigan Medical Center, Ann Arbor, Michigan (contract N01-DK-9-2323, grant M01RR-00042, grant 1 UL1 RR024986, Michigan Center for Clinical and Health Research), Joel K Greenson, Pamela A Richtmyer, R Tess Bonham; Virginia Commonwealth University Health System, Richmond, Virginia (contract N01-DK-9-2322, grant M01RR-00065), Mitchell L Shiffman, Melissa J Contos, A Scott Mills, Charlotte Hofmann, Paula Smith; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, Maryland, James E. Everhart, Leonard B Seeff, Patricia R Robuck, Jay H Hoofnagle; New England Research Institutes, Watertown, Massachusetts (contract N01-DK-9-2328), Kristin K Snow, Margaret C Bell, Teresa M Curto; Armed Forces Institute of Pathology, Washington, DC, Fanny Monge, Michelle Parks; Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, Guadalupe Garcia-Tsao, Michael Kutner, Stanley M. Lemon, Robert P. Perrillo. NR 44 TC 52 Z9 53 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD OCT PY 2010 VL 59 IS 10 BP 1401 EP 1409 DI 10.1136/gut.2010.207423 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 660RN UT WOS:000282661300020 PM 20675691 ER PT J AU Schorge, JO Modesitt, SC Coleman, RL Cohn, DE Kauff, ND Duska, LR Herzog, TJ AF Schorge, John O. Modesitt, Susan C. Coleman, Robert L. Cohn, David E. Kauff, Noah D. Duska, Linda R. Herzog, Thomas J. TI SGO White Paper on Ovarian Cancer: Etiology, Screening and Surveillance SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Hereditary breast ovarian cancer syndrome; Risk-reducing salpingo-oophorectomy; Ovarian cancer screening ID REDUCING SALPINGO-OOPHORECTOMY; PAPILLARY SEROUS CARCINOMA; SERUM CA-125 LEVELS; MENOPAUSAL HORMONE-THERAPY; GYNECOLOGIC-ONCOLOGY-GROUP; MUTATION CARRIERS; BRCA2 MUTATIONS; UNITED-STATES; PROPHYLACTIC OOPHORECTOMY; TRANSVAGINAL ULTRASOUND AB Ovarian cancer is a heterogeneous, rapidly progressive, highly lethal disease of low prevalence. The etiology remains poorly understood. Numerous risk factors have been identified, the most prominent involving an inherited predisposition in 10% of cases. Women with germline mutations associated with Hereditary Breast/Ovarian Cancer and Lynch syndromes have dramatically elevated risks (up to 46% and 12%, respectively). Risk-reducing salpingo-oophorectomy is the best method to prevent ovarian cancer in these high-risk women. Significant risk reduction is also seen in the general population who use oral contraceptives. Since up to 89% patients with early-stage disease have symptoms prior to diagnosis, increased awareness of the medical community may facilitate further workup in patients who otherwise would have had a delay. Despite enormous effort, there is no proof that routine screening for ovarian cancer in either the high-risk or general populations with serum markers, sonograms, or pelvic examinations decreases mortality. Further evaluation is needed to determine whether any novel biomarkers, or panels of markers, have clinical utility in early detection. Prospective clinical trials have to be designed and completed prior to offering of any of these new diagnostic tests. CA125 is currently the only biomarker recommended for monitoring of therapy as well as detection of recurrence. This commentary provides an overview on the background, screening and surveillance of ovarian cancer. (C) 2010 Elsevier Inc. All rights reserved. C1 [Herzog, Thomas J.] Columbia Univ, Coll Phys & Surg NY Prebyterian New York, New York, NY 10027 USA. [Schorge, John O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Modesitt, Susan C.; Duska, Linda R.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Coleman, Robert L.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cohn, David E.] Ohio State Univ, Columbus, OH 43210 USA. [Kauff, Noah D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Herzog, TJ (reprint author), Columbia Univ, Coll Phys & Surg NY Prebyterian New York, New York, NY 10027 USA. EM th2135@columbia.edu OI Kauff, Noah/0000-0001-7242-6156 NR 117 TC 57 Z9 58 U1 3 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2010 VL 119 IS 1 BP 7 EP 17 DI 10.1016/j.ygyno.2010.06.003 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 657AN UT WOS:000282382500002 PM 20692025 ER PT J AU Ghosh, S Albitar, L LeBaron, R Welch, WR Samimi, G Birrer, MJ Berkowitz, RS Mok, SC AF Ghosh, Sue Albitar, Lina LeBaron, Richard Welch, William R. Samimi, Goli Birrer, Michael J. Berkowitz, Ross S. Mok, Samuel C. TI Up-regulation of stromal versican expression in advanced stage serous ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Versican; Stroma; Ovarian cancer ID EXTRACELLULAR-MATRIX; DIFFERENTIAL EXPRESSION; CELL INVASION; TUMORS; HYALURONAN; ISOFORMS AB Objective. The purpose of this study is to examine the role of versican (VCAN) in advanced stage serous ovarian cancer by investigating its expression, its function, and its correlation with clinical outcomes. Methods. Microarray analysis was performed on RNA isolated from tumor and stromal components of advanced stage serous ovarian cancer and normal ovarian epithelial tissue to identify genes up-regulated in ovarian tumor stroma. Validation studies using immunohistochemistry and quantitative real-time PCR (Q-RTPCR) was performed on one of the up-regulated genes, VCAN. Immunolocalization of VCAN (n = 111) and CD31 (n = 56) was done on serous ovarian tumors. CD31 staining was performed to examine microvessel density (MVD). Q-RT-PCR was performed on 65 samples to evaluate the differential expression of VCAN isoforms. Cell proliferation and invasion assays were performed to examine how V1-treated ovarian cancer cell lines and an endothelial cell line would differ from controls. Univariate survival analyses were done with VCAN expression. Correlation analysis was done with CD31, platinum resistance, and clinical data. Results. Validation studies using Q-RT-PCR and immunohistochemistry showed significantly higher VCAN V1 isoform expression in ovarian cancer stroma compared with normal ovarian stroma and ovarian cancer cells. Correlation studies showed stromal VCAN expression was associated with poorer overall and progression-free survival, platinum resistance, and increased MVD. VCAN-treated ovarian cancer and endothelial cells showed increased invasion potential. Conclusions. VCAN overexpression is associated with increased MVD and invasion potential, which may lead to poorer overall and progression-free survival and platinum resistance. (C) 2010 Elsevier Inc. All rights reserved. C1 [Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Ghosh, Sue; Berkowitz, Ross S.] Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Albitar, Lina] Brigham & Womens Hosp, Dept Med, Genet Lab, Boston, MA 02115 USA. [LeBaron, Richard] Univ Texas San Antonio, Dept Biol, San Antonio, TX USA. [Welch, William R.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Samimi, Goli] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Mok, SC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, T4-3908,1515 Holcombe Blvd, Houston, TX 77030 USA. EM scmok@mdanderson.org RI LeBaron, Richard/K-4722-2013 OI LeBaron, Richard/0000-0002-7770-305X FU Dana-Farber/Harvard Cancer Center [P50CA165009]; National Institute of Health [P50CA083639, RO1CA133057, R33CA103595]; Department of Health and Human Services; Gillette Center For Women's Cancer; Adler Foundation, Inc.; Edgar Astrove Fund; Ovarian Cancer Research Fund, Inc.; Morse Family Fund; Natalie Pihl Fund; Ruth N. White Research Fellowship; Friends of Dana-Farber Cancer Institute; Robert and Deborah First Fund; National Cancer Institute FX This study was supported in part by the Dana-Farber/Harvard Cancer Center Ovarian Cancer SPORE grant P50CA165009, the M.D. Anderson Ovarian Cancer SPORE grant P50CA083639, RO1CA133057 and R33CA103595 from National Institute of Health, Department of Health and Human Services, Gillette Center For Women's Cancer, Adler Foundation, Inc., Edgar Astrove Fund, the Ovarian Cancer Research Fund, Inc., the Morse Family Fund, the Natalie Pihl Fund, the Ruth N. White Research Fellowship, Friends of Dana-Farber Cancer Institute, the Robert and Deborah First Fund, and the intramural research program of the National Cancer Institute. NR 26 TC 24 Z9 26 U1 0 U2 2 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 OCT PY 2010 VL 119 IS 1 BP 114 EP 120 DI 10.1016/j.ygyno.2010.05.029 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 657AN UT WOS:000282382500020 PM 20619446 ER PT J AU Koo, S Huntly, BJ Wang, YA Chen, J Brumme, K Ball, B McKinney-Freeman, SL Yabuuchi, A Scholl, C Bansa, D Zon, LI Frohling, S Daley, GQ Gilliland, DG Mercher, T AF Koo, Sumin Huntly, Brian J. Wang, Yuan Chen, Jing Brumme, Kristina Ball, Brian McKinney-Freeman, Shannon L. Yabuuchi, Akiko Scholl, Claudia Bansa, Dimple Zon, Leonard I. Froehling, Stefan Daley, George Q. Gilliland, D. Gary Mercher, Thomas TI Cdx4 is dispensable for murine adult hematopoietic stem cells but promotes MLL-AF9-mediated leukemogenesis SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE Cdx4; homeobox; leukemia; MLL-AF9; hematopoietic stem cell; Hox ID ACUTE MYELOID-LEUKEMIA; HOMEOBOX GENE CDX2; ACUTE LYMPHOBLASTIC-LEUKEMIA; ECTOPIC EXPRESSION; HOX EXPRESSION; PROGENITORS; MOUSE; MENIN; T(12/13)(P13,Q12); ELONGATION AB Background Cdx4 is a homeobox gene essential for normal blood formation during embryonic development in the zebrafish, through activation of posterior Hox genes. However, its role in adult mammalian hematopoiesis has not been extensively studied and its requirement in leukemia associated with Hox gene expression alteration is unclear. Design and Methods We inactivated Cdx4 in mice through either a germline or conditional knockout approach and analyzed requirement for Cdx4 in both normal adult hematopoiesis and leukemogenesis initiated by the MLL-AF9 fusion oncogene. Results Here, we report that loss of Cdx4 had a minimal effect on adult hematopoiesis. Indeed, although an increase in white blood cell counts was observed, no significant differences in the distribution of mature blood cells, progenitors or stem cells were observed in Cdx4-deficient animals. In addition, long-term repopulating activity in competitive transplantation assays was not significantly altered. In vitro, B-cell progenitor clonogenic potential was reduced in Cdx4-deficient animals but no significant alteration of mature B cells was detected in vivo. Finally, induction of acute myeloid leukemia in mice by MLL-AF9 was significantly delayed in the absence of Cdx4 in a retroviral transduction/bone marrow transplant model. Conclusions These observations indicate that Cdx4 is dispensable for the establishment and maintenance of normal hematopoiesis in adult mammals. These results, therefore, outline substantial differences in the Cdx-Hox axis between mammals and zebrafish and support the hypothesis that Cdx factors are functionally redundant during mammalian hematopoietic development under homeostatic conditions. In addition, our results suggest that Cdx4 participates in MLL-AF9-mediated leukemogenesis supporting a role for Cdx factors in the pathogenesis of myeloid leukemia. C1 [Mercher, Thomas] Univ Paris 11, INSERM, U985, Inst Gustave Roussy, F-94800 Villejuif, France. [Koo, Sumin; Huntly, Brian J.; Chen, Jing; Brumme, Kristina; Ball, Brian; Scholl, Claudia; Bansa, Dimple; Froehling, Stefan; Gilliland, D. Gary; Mercher, Thomas] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. [Huntly, Brian J.] Univ Cambridge, Dept Hematol, Cambridge, England. [Wang, Yuan; McKinney-Freeman, Shannon L.; Yabuuchi, Akiko; Zon, Leonard I.; Daley, George Q.] Childrens Hosp, Div Hematol Oncol, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Wang, Yuan] E China Normal Univ, Inst Biomed Res, Shanghai 200062, Peoples R China. [Chen, Jing] Emory Univ Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA USA. [Scholl, Claudia; Froehling, Stefan] Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany. [Zon, Leonard I.] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. RP Mercher, T (reprint author), Univ Paris 11, INSERM, U985, Inst Gustave Roussy, 39 Rue Camille Desmoulins, F-94800 Villejuif, France. EM thomas.mercher@inserm.fr RI Mercher, Thomas/J-2446-2014 OI Mercher, Thomas/0000-0003-1552-087X FU NIH; Leukemia and Lymphoma Society [3431-06]; EHA FX we are very grateful to Mahnaz Paktinat for flow cytometty analyses and Rachel Okabe and Maricel Gozo for technical assistance. This work was supported in part by NIH grants (DGG), and the Leukemia and Lymphoma Society (DGG).; BJH was supported by an EHA Jose Carreras Young Investigator Fellowship and is an MRC (UK) senior clinical fellow. SF is the recipient of an EHA Jose Carreras Young Investigator Fellowship. TM was supported by a Leukemia and Lymphoma Society Special Fellow Award (#3431-06), is the recipient of an EHA Jose Carreras Young Investigator Fellowship and is an INSERM investigator. NR 30 TC 5 Z9 8 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD OCT PY 2010 VL 95 IS 10 BP 1642 EP 1650 DI 10.3324/haematol.2010.023168 PG 9 WC Hematology SC Hematology GA 668MV UT WOS:000283275000006 PM 20494928 ER PT J AU Wu, CW Lu, IC Randolph, GW Kuo, WR Lee, KW Chen, CL Chiang, FY AF Wu, Che-Wei Lu, I-Cheng Randolph, Gregory W. Kuo, Wen-Rei Lee, Ka-Wo Chen, Chang-Lin Chiang, Feng-Yu TI INVESTIGATION OF OPTIMAL INTENSITY AND SAFETY OF ELECTRICAL NERVE STIMULATION DURING INTRAOPERATIVE NEUROMONITORING OF THE RECURRENT LARYNGEAL NERVE: A PROSPECTIVE PORCINE MODEL SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE intraoperative neuromonitoring; recurrent laryngeal nerve; safety; thyroid surgery; porcine model ID THYROID-SURGERY; EVOKED ELECTROMYOGRAPHY; ENDOTRACHEAL-TUBE; IDENTIFICATION; RISK; PARATHYROIDECTOMY; PRESERVATION; INJURY; PALSY; PIG AB Background. Intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) has recently been more frequently applied in thyroid surgery. However, concerns have been raised regarding the safety and optimal intensity of electrical nerve stimulation. Methods. Eight piglets were enrolled, and electrically evoked electromyography (EMG) was recorded from the vocalis muscles via endotracheal surface electrodes. The baseline EMG was measured and continuous pulsatile stimulations were performed on the vagus nerve and RLN for 10 minutes. Changes of EMG waveform and cardiopulmonary status were analyzed. Results. A dose-response curve existed with increasing EMG amplitude as stimulating current was increased, with maximum amplitude elicited on vagal and RLN stimulation at <1 mA. No obvious EMG changes and untoward cardiopulmonary effects were observed after the stimulation. Conclusions. Electrical stimulation is safe during IONM in this porcine model. Minimal current that required generating the maximal evoked EMG, approximately 1 mA in this study, can be selected to minimize the risk of nerve damage and cardiopulmonary effects. (C) 2010 Wiley Periodicals, Inc. Head Neck 32: 1295-1301, 2010 C1 [Wu, Che-Wei; Kuo, Wen-Rei; Lee, Ka-Wo; Chiang, Feng-Yu] Kaohsiung Med Univ Hosp, Dept Otolaryngol Head & Neck Surg, Kaohsiung, Taiwan. [Wu, Che-Wei] Kaohsiung Med Univ, Dept Otolaryngol, Kaohsiung Municipal Hsaio Kang Hosp, Kaohsiung, Taiwan. [Lu, I-Cheng] Kaohsiung Med Univ Hosp, Dept Anesthesiol, Kaohsiung, Taiwan. [Kuo, Wen-Rei; Lee, Ka-Wo; Chiang, Feng-Yu] Kaohsiung Med Univ, Dept Otolaryngol Head & Neck Surg, Fac Med, Coll Med, Kaohsiung, Taiwan. [Wu, Che-Wei; Lu, I-Cheng] Kaohsiung Med Univ, Grad Inst Med, Kaohsiung, Taiwan. [Chen, Chang-Lin] Kaohsiung Municipal Minsheng Hosp, Dept Ophthalmol, Kaohsiung, Taiwan. [Randolph, Gregory W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Chiang, FY (reprint author), Kaohsiung Med Univ Hosp, Dept Otolaryngol Head & Neck Surg, Kaohsiung, Taiwan. EM fychiang@kmu.edu.tw OI Wu, Che-Wei/0000-0003-1052-5348 FU Institutional Animal Care and Use Committee of Kaohsiung Medical University [97146] FX The animal use protocol was approved by the Institutional Animal Care and Use Committee of Kaohsiung Medical University (protocol no. 97146). NR 30 TC 19 Z9 19 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2010 VL 32 IS 10 BP 1295 EP 1301 DI 10.1002/hed.21324 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 661ER UT WOS:000282707500003 PM 20091689 ER PT J AU Silber, JH Rosenbaum, PR Brachet, TJ Ross, RN Bressler, LJ Even-Shoshan, O Lorch, SA Volpp, KG AF Silber, Jeffrey H. Rosenbaum, Paul R. Brachet, Tanguy J. Ross, Richard N. Bressler, Laura J. Even-Shoshan, Orit Lorch, Scott A. Volpp, Kevin G. TI The Hospital Compare Mortality Model and the Volume-Outcome Relationship SO HEALTH SERVICES RESEARCH LA English DT Article DE Hospital Compare; mortality; acute myocardial infarction; random effects model ID ACUTE MYOCARDIAL-INFARCTION; REPORT CARDS; HEALTH-CARE; QUALITY; SURVIVAL AB Objective We ask whether Medicare's Hospital Compare random effects model correctly assesses acute myocardial infarction (AMI) hospital mortality rates when there is a volume-outcome relationship. Data Sources/Study Setting Medicare claims on 208,157 AMI patients admitted in 3,629 acute care hospitals throughout the United States. Study Design We compared average-adjusted mortality using logistic regression with average adjusted mortality based on the Hospital Compare random effects model. We then fit random effects models with the same patient variables as in Medicare's Hospital Compare mortality model but also included terms for hospital Medicare AMI volume and another model that additionally included other hospital characteristics. Principal Findings Hospital Compare's average adjusted mortality significantly underestimates average observed death rates in small volume hospitals. Placing hospital volume in the Hospital Compare model significantly improved predictions. Conclusions The Hospital Compare random effects model underestimates the typically poorer performance of low-volume hospitals. Placing hospital volume in the Hospital Compare model, and possibly other important hospital characteristics, appears indicated when using a random effects model to predict outcomes. Care must be taken to insure the proper method of reporting such models, especially if hospital characteristics are included in the random effects model. C1 [Silber, Jeffrey H.; Brachet, Tanguy J.; Ross, Richard N.; Bressler, Laura J.; Even-Shoshan, Orit; Lorch, Scott A.] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.; Brachet, Tanguy J.] Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Silber, Jeffrey H.; Rosenbaum, Paul R.; Brachet, Tanguy J.; Even-Shoshan, Orit; Lorch, Scott A.; Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Rosenbaum, Paul R.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Lorch, Scott A.] Childrens Hosp Philadelphia, Dept Pediat, Div Neonatol, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Vet Adm Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Volpp, Kevin G.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Silber, JH (reprint author), Childrens Hosp Philadelphia, Ctr Outcomes Res, 3535 Market St,Suite 1029, Philadelphia, PA 19104 USA. EM silberj@wharton.upenn.edu RI Rosenbaum, Paul/H-8687-2012 FU NHLBI [R01 HL082637, R01 HL094593]; NSF [0849370] FX This work was supported by NHLBI grants R01 HL082637 and R01 HL094593 and NSF grant 0849370. Portions of this work were presented at the 2009 Academy Health Annual Meeting. We thank Traci Frank, A. A., for her assistance with preparing this manuscript. NR 33 TC 39 Z9 39 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2010 VL 45 IS 5 BP 1148 EP 1167 DI 10.1111/j.1475-6773.2010.01130.x PN 1 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 648RU UT WOS:000281712400002 PM 20579125 ER PT J AU Meterko, M Wright, S Lin, H Lowy, E Cleary, PD AF Meterko, Mark Wright, Steven Lin, Hai Lowy, Elliott Cleary, Paul D. TI Mortality among Patients with Acute Myocardial Infarction: The Influences of Patient-Centered Care and Evidence-Based Medicine SO HEALTH SERVICES RESEARCH LA English DT Article DE Patient assessment; satisfaction; patient outcomes; functional status; ADLs; IADLs; quality of care; patient safety (measurement) ID MEDICARE MANAGED CARE; HEALTH-CARE; HOSPITAL-CARE; OUTCOMES; QUALITY; SATISFACTION; ADHERENCE; CAHPS(R); PERFORMANCE; PHYSICIAN AB Background Recent studies have suggested that there is a positive impact of patient-centered care (PCC) on both the patient-physician relationship and subsequent patient health-related behaviors. One recent prospective study reported a significant relationship between the degree of PCC experienced by patients during their hospitalization for acute myocardial infarction (AMI) and their postdischarge cardiac symptoms. A limitation of this study, however, was a lack of information regarding the technical quality of the AMI care, which might have explained at least part of the differences in outcomes. The present study was undertaken to test the influence of both PCC and technical care quality on outcomes among AMI patients. Methods We analyzed data from a national sample of 1,858 veterans hospitalized for an initial AMI in a Department of Veterans Affairs medical center during fiscal years 2003 and 2004 for whom data had been compiled on evidence-based treatment and who had also completed a Picker questionnaire assessing perceptions of PCC. Cox proportional hazards models were used to estimate the relationship between PCC and survival 1-year postdischarge, controlling for technical quality of care, patient clinical condition and history, admission process characteristics, and patient sociodemographic characteristics. We hypothesized that better PCC would be associated with a lower probability of death 1-year postdischarge, even after controlling for patient characteristics and the technical quality of care. Results Better PCC was associated with a significantly but modestly lower hazard of death over the 1-year study period (hazard ratio 0.992, 95 percent confidence interval 0.986-0.999). Conclusions Providing PCC may result in important clinical benefits, in addition to meeting patient needs and expectations. C1 [Meterko, Mark] VA Boston Healthcare Syst 152 M, HSR&D Ctr Org Leadership & Management Res, Boston, MA USA. [Meterko, Mark] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Wright, Steven] VA Off Qual & Performance, Washington, DC USA. [Lin, Hai] Women & Infants Hosp Rhode Isl, Brown Ctr Study Children Risk, Providence, RI 02908 USA. [Lowy, Elliott] VA Puget Sound Healthcare Syst, HSR&D NW Ctr Excellence, Seattle, WA USA. [Cleary, Paul D.] Yale Univ, Sch Med, Sch Publ Hlth, New Haven, CT 06520 USA. RP Cleary, PD (reprint author), Yale Univ, Sch Med, Sch Publ Hlth, 60 Coll St,LEPH 210,POB 208034, New Haven, CT 06520 USA. EM paul.cleary@yale.edu FU Picker Institute FX This research was supported by a grant from the Picker Institute. Marjorie Nealon-Seibert, M.B.A., Survey Administrator at COLMR, assisted with preparation and submission of the study for IRB review by the VA Boston Healthcare System. There are no financial or other disclosures. NR 46 TC 61 Z9 62 U1 5 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2010 VL 45 IS 5 BP 1188 EP 1204 DI 10.1111/j.1475-6773.2010.01138.x PN 1 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 648RU UT WOS:000281712400004 PM 20662947 ER PT J AU Liu, CF Chapko, M Bryson, CL Burgess, JF Fortney, JC Perkins, M Sharp, ND Maciejewski, ML AF Liu, Chuan-Fen Chapko, Michael Bryson, Chris L. Burgess, James F., Jr. Fortney, John C. Perkins, Mark Sharp, Nancy D. Maciejewski, Matthew L. TI Use of Outpatient Care in Veterans Health Administration and Medicare among Veterans Receiving Primary Care in Community-Based and Hospital Outpatient Clinics SO HEALTH SERVICES RESEARCH LA English DT Article DE Access; demand; utilization of services; Medicare; VA health care system; cohort analysis ID PERFORMANCE-MEASURES; DUAL-USE; VA; AFFAIRS; SERVICES; QUALITY; ACCESS; COVERAGE; SYSTEM AB Objective To examine differences in use of Veterans Health Administration (VA) and Medicare outpatient services by VA primary care patients. Data Sources/Study Setting VA administrative and Medicare claims data from 2001 to 2004. Study Design Retrospective cohort study of outpatient service use by 8,964 community-based and 6,556 hospital-based VA primary care patients. Principal Findings A significant proportion of VA patients used Medicare-reimbursed primary care (> 30 percent) and specialty care (> 60 percent), but not mental health care (3-4 percent). Community-based patients had 17 percent fewer VA primary care visits (p <.001), 9 percent more Medicare-reimbursed visits (p <.001), and 6 percent fewer total visits (p <.05) than hospital-based patients. Community-based patients had 22 percent fewer VA specialty care visits (p <.0001) and 21 percent more Medicare-reimbursed specialty care visits (p <.0001) than hospital-based patients, but no difference in total visits (p=.80). Conclusions Medicare-eligible VA primary care patients followed over 4 consecutive years used significant primary care and specialty care outside of VA. Community-based patients offset decreased VA use with increased service use paid by Medicare, suggesting that increasing access to VA primary care via community clinics may fragment veteran care in unintended ways. Coordination of care between VA and non-VA providers and health care systems is essential to improve the quality and continuity of care. C1 [Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, HSR&D, Dept Vet Affairs, NW Ctr Outcomes Res Older Adults, Seattle, WA 98101 USA. [Liu, Chuan-Fen; Chapko, Michael; Sharp, Nancy D.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bryson, Chris L.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. [Burgess, James F., Jr.] Ctr Org Leadership & Management Res, Dept Vet Affairs, Boston, MA USA. [Burgess, James F., Jr.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Fortney, John C.] S Cent Mental Hlth Illness Res & Educ & Clin Ctr, N Little Rock, AR USA. [Fortney, John C.] Cent Arkansas Vet Healthcare Syst, HSR&D Ctr Mental Healthcare & Outcomes Res, N Little Rock, AR USA. [Fortney, John C.] Univ Arkansas Med Sci, Dept Psychiat & Behav Sci, Div Hlth Serv Res, N Little Rock, AR USA. [Maciejewski, Matthew L.] Vet Adm Med Ctr, Ctr Hlth Serv Res Primary Care, Dept Vet Affairs, Durham, NC 27705 USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. RP Liu, CF (reprint author), VA Puget Sound Hlth Care Syst, HSR&D, Dept Vet Affairs, NW Ctr Outcomes Res Older Adults, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM chuan-fen.liu@va.gov OI Burgess, James/0000-0002-6646-7071 FU Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs [IIR 04-292] FX This work was supported by the Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs, project number IIR 04-292. Drs. Liu, Chapko, Bryson, Sharp, and Perkins are at the Northwest Center for Outcomes Research in Older Adults at the Seattle VA. Dr. Burgess is at the Center for Organization, Leadership & Management Research at the Boston VA. Dr. Fortney is at the Center for Mental Healthcare and Outcomes Research at the Little Rock VA. Dr. Maciejewski is at the Center for Health Services Research in Primary Care at the Durham VA. The authors are grateful for helpful comments from Will Manning. The views expressed herein are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs and other affiliated institutions. NR 31 TC 25 Z9 25 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2010 VL 45 IS 5 BP 1268 EP 1286 DI 10.1111/j.1475-6773.2010.01123.x PN 1 PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 648RU UT WOS:000281712400008 PM 20831716 ER PT J AU Iezzoni, LI AF Iezzoni, Lisa I. TI Multiple Chronic Conditions and Disabilities: Implications for Health Services Research and Data Demands SO HEALTH SERVICES RESEARCH LA English DT Article DE Chronic conditions; disability; functional status; comparative effectiveness research; quality measurement; health information technology; coding nomenclatures ID PAY-FOR-PERFORMANCE; QUALITY-OF-CARE; INFORMATION-TECHNOLOGY; UNITED-KINGDOM; RECORDS; IMPROVE; PREVALENCE; PHYSICIANS; MEDICARE; CENTERS AB Increasing numbers of Americans are living with multiple chronic conditions (MCCs) and disabilities. Addressing health care needs of persons with MCCs or disabilities presents challenges on many levels. For health services researchers, priorities include (1) considering MCCs and disabilities in comparative effectiveness research (CER) and assessing quality of care; and (2) identifying and evaluating the data needed to conduct CER, performance measure development, and other research to inform health policy and public health decisions concerning persons with MCCs or disabilities. Little information is available to guide CER or treatment choices for persons with MCCs or disabilities, however, because they are typically excluded from clinical trials that produce the scientific evidence base. Furthermore, most research funding flows through public and private agencies oriented around single organ systems or diseases. Likely changes in the data landscape-notably wider dissemination of electronic health records (EHRs) and moving toward updated coding nomenclatures-may increase the information available to monitor health care service delivery and quality for persons with MCCs and disabilities. Generating this information will require new methods to extract and code information about MCCs and functional status from EHRs, especially narrative texts, and incorporating coding nomenclatures that capture critical dimensions of functional status and disability. C1 Massachusetts Gen Hosp, James J Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, James J Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@partners.org FU AcademyHealth FX AcademyHealth provided support for preparation of this manuscript. NR 58 TC 12 Z9 12 U1 2 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2010 VL 45 IS 5 BP 1523 EP 1540 DI 10.1111/j.1475-6773.2010.01145.x PN 2 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 648RX UT WOS:000281712700007 PM 21054370 ER PT J AU Songer, JE Rosowski, JJ AF Songer, Jocelyn E. Rosowski, John J. TI A superior semicircular canal dehiscence-induced air-bone gap in chinchilla SO HEARING RESEARCH LA English DT Article ID CONDUCTIVE HEARING-LOSS; MIDDLE-EAR; SOUND; ADMITTANCE; MECHANISMS; COCHLEA; VERTIGO; MODEL AB An SCD is a pathologic hole (or dehiscence) in the bone separating the superior semicircular canal from the cranial cavity that has been associated with a conductive hearing loss in patients with SCD syndrome. The conductive loss is defined by an audiometrically determined air-bone gap that results from the combination of a decrease in sensitivity to air-conducted sound and an increase in sensitivity to bone-conducted sound. Our goal is to demonstrate, through physiological measurements in an animal model, that mechanically altering the superior semicircular canal (SC) by introducing a hole (dehiscence) is sufficient to cause such an air-bone gap. We surgically introduced holes into the SC of chinchilla ears and evaluated auditory sensitivity (cochlear potential) in response to both air- and bone-conducted stimuli. The introduction of the SC hole led to a low-frequency (<2000 Hz) decrease in sensitivity to air-conducted stimuli and a low-frequency (<1000 Hz) increase in sensitivity to bone-conducted stimuli resulting in an air-bone gap. This result was consistent and reversible. The air-bone gaps in the animal results are qualitatively consistent with findings in patients with SCD syndrome. (C) 2010 Elsevier B.V. All rights reserved. C1 [Songer, Jocelyn E.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Songer, Jocelyn E.; Rosowski, John J.] Harvard MIT, Cambridge, MA 02138 USA. [Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Songer, JE (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM jocelyns@mit.edu FU NSF; NIH [T32-DC00038, R01-DC000194] FX This work has been supported by an NSF graduate student fellowship. NIH training grant T32-DC00038, and an additional NIH research grant R01-DC000194. S. Merchant and W. Peake, and M.E. Ravicz provided insights and suggestions. M. Wood assisted with data collection and animal surgery. NR 32 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD OCT 1 PY 2010 VL 269 IS 1-2 BP 70 EP 80 DI 10.1016/j.heares.2010.07.002 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 658ON UT WOS:000282499400008 PM 20638462 ER PT J AU Blosser, CD Ayehu, G Wu, S Lomagro, RM Malone, E Brunelli, SM Itkin, M Golden, M McCombs, P Lipschutz, JH AF Blosser, Christopher D. Ayehu, Gashu Wu, Sam Lomagro, Ruth M. Malone, Ellen Brunelli, Steven M. Itkin, Max Golden, Michael McCombs, Peter Lipschutz, Joshua H. TI High rate of fistula placement in a cohort of dialysis patients in a single payer system SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE Fistula; hemodialysis; health care economics ID VEIN ARTERIOVENOUS-FISTULAS; VASCULAR ACCESS; HEMODIALYSIS-PATIENTS; OUTCOMES; TRANSPOSITION; PATENCY; IMPACT; CARE C1 [Blosser, Christopher D.; Ayehu, Gashu; Wu, Sam; Lipschutz, Joshua H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Lomagro, Ruth M.; Lipschutz, Joshua H.] Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. [Malone, Ellen; Golden, Michael; McCombs, Peter] Vet Affairs Med Ctr, Dept Surg, Vasc Surg Sect, Philadelphia, PA USA. [Brunelli, Steven M.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. [Itkin, Max] Vet Affairs Med Ctr, Dept Radiol, Intervent Radiol Sect, Philadelphia, PA USA. RP Lipschutz, JH (reprint author), 431 Hill Pavilion,380 S Univ Ave, Philadelphia, PA 19104 USA. EM jhlipsch@mail.med.upenn.edu FU National Institutes of Health [DK069909, DK070980, K23DK079056]; Satellite Healthcare FX The authors and this work were supported in part by the National Institutes of Health (DK069909 and DK070980 to J.H.L.; K23DK079056 to S.M.B.) and Satellite Healthcare (Norman S. Coplon Extramural Research Grant to J.H.L). NR 25 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1492-7535 J9 HEMODIAL INT JI Hemodial. Int. PD OCT PY 2010 VL 14 IS 4 BP 393 EP 397 DI 10.1111/j.1542-4758.2010.00479.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 667DY UT WOS:000283174100009 PM 20812959 ER PT J AU Sterling, RK Wright, EC Morgan, TR Seeff, LB Hoefs, JC Di Bisceglie, AM Dienstag, JL Lok, AS AF Sterling, Richard K. Wright, Elizabeth C. Morgan, Timothy R. Seeff, Leonard B. Hoefs, John C. Di Bisceglie, Adrian M. Dienstag, Jules L. Lok, Anna S. TI FREQUENCY OF ELEVATED HEPATOCELLULAR CARCINOMA (HCC) BIOMARKERS (AFP, AFP-L3, AND DCP) IN PATIENTS WITH CHRONIC HEPATITIS C (CHC)AND ADVANCED FIBROSIS WITH AND WITHOUT HCC SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Sterling, Richard K.] Virginia Commonwealth Univ, Div Gastroenterol & Hepatol, Richmond, VA USA. [Wright, Elizabeth C.; Seeff, Leonard B.] NIDDK, NIH, Bethesda, MD USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Long Beach, CA USA. [Hoefs, John C.] Univ Calif Irvine, Ann Arbor, MI USA. [Di Bisceglie, Adrian M.] St Louis Univ, St Louis, MO 63103 USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Lok, Anna S.] Univ Michagan, Ann Arbor, MI USA. NR 0 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 18 BP 328A EP 328A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600019 ER PT J AU O'Brien, TR Everhart, JE Chung, RT Morgan, TR Bonkovsky, HL Shao, YW Lok, AS Shiffman, ML Sninsky, J Pfeiffer, R AF O'Brien, Thomas R. Everhart, James E. Chung, Raymond T. Morgan, Timothy R. Bonkovsky, Herbert L. Shao, Yongwu Lok, Anna S. Shiffman, Mitchell L. Sninsky, John Pfeiffer, Ruth TI AN IL28B GENOTYPE-BASED MODEL FOR PERSONALIZED PREDICTION OF RESPONSE TO PEGYLATED-INTERFERON-ALFA AND RIBAVIRIN IN THE TREATMENT OF CHRONIC HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [O'Brien, Thomas R.; Pfeiffer, Ruth] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Shao, Yongwu] Informat Management Serv Inc, Silver Spring, MD USA. [Lok, Anna S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. [Sninsky, John] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA. [Sninsky, John] Celera Corp, Alameda, CA USA. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 127 BP 382A EP 382A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600128 ER PT J AU Cusi, K Lomonaco, R Ortiz-Lopez, C Webb, A Orsak, B Darland, CM Finch, J Kaminski-Graham, R AF Cusi, Kenneth Lomonaco, Romina Ortiz-Lopez, Carolina Webb, Amy Orsak, Beverly Darland, Celia M. Finch, Joan Kaminski-Graham, Rosemarie TI ASSESSMENT OF ETHNIC AND METABOLIC FACTORS IN THE DEVELOPMENT OF NASH IN A PREDOMINANTLY HISPANIC POPULATION: THE UNIVERSITY OF TEXAS AT SAN ANTONIO NASH TRIAL SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Cusi, Kenneth; Lomonaco, Romina; Ortiz-Lopez, Carolina; Orsak, Beverly] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Cusi, Kenneth; Lomonaco, Romina; Webb, Amy; Darland, Celia M.; Finch, Joan; Kaminski-Graham, Rosemarie] Vet Adm Med Ctr, Diabet Div, San Antonio, TX USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 698 BP 653A EP 654A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601017 ER PT J AU Louvet, A Artru, F Wartel, F O'Grady, JG Carithers, RL Phillips, M Mendenhall, CL Naveau, S Canva-Delcambre, V Morgan, TR Mathurin, P AF Louvet, Alexandre Artru, Florent Wartel, Faustine O'Grady, John G. Carithers, Robert L. Phillips, Martin Mendenhall, Charles L. Naveau, Sylvie Canva-Delcambre, Valerie Morgan, Timothy R. Mathurin, Philippe TI A RESPONSE-GUIDED THERAPY FOR A BETTER MANAGEMENT OF PATIENTS SEVERE ALCOHOLIC HEPATITIS TREATED WITH CORTICOSTEROIDS SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Louvet, Alexandre; Artru, Florent; Wartel, Faustine; Canva-Delcambre, Valerie; Mathurin, Philippe] Ctr Hosp Reg & Univ Lille, Hop Huriez, F-59037 Lille, France. [O'Grady, John G.; Phillips, Martin] Kings Coll London, London WC2R 2LS, England. [Mendenhall, Charles L.] Vet Affairs Med Ctr, Cincinnati, OH 45267 USA. [Carithers, Robert L.] Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol, Seattle, WA USA. [Naveau, Sylvie] Hop Antoine Beclere, Clamart, France. [Morgan, Timothy R.] Vet Affairs Long Beach Healthcare Syst, Gastroenterol Sect, Long Beach, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1652 BP 1109A EP 1109A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602272 ER PT J AU Speliotes, EK Massaro, JM O'Donnell, CJ Fox, CS AF Speliotes, Elizabeth K. Massaro, Joseph M. O'Donnell, Christopher J. Fox, Caroline S. TI Uric Acid Potentially Links Fatty Liver and High Blood Pressure Reply SO HEPATOLOGY LA English DT Letter C1 [Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Speliotes, Elizabeth K.] Harvard & Massachusetts Inst technol, Dept Med & Populat Genet, Broad Inst, Cambridge, MA USA. [Speliotes, Elizabeth K.; Massaro, Joseph M.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham, MA USA. [Speliotes, Elizabeth K.; Massaro, Joseph M.; O'Donnell, Christopher J.; Fox, Caroline S.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. RP Speliotes, EK (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 BP 1519 EP 1519 DI 10.1002/hep.23887 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 660BK UT WOS:000282613000044 ER PT J AU Trovik, J Wik, E Stefansson, I Carter, SL Beroukhim, R Oyan, AM Kalland, KH Akslen, LA Salvesen, HB AF Trovik, Jone Wik, Elisabeth Stefansson, Ingunn Carter, Scott L. Beroukhim, Rameen Oyan, Anne M. Kalland, Karl-Henning Akslen, Lars A. Salvesen, Helga B. TI Stathmin is superior to AKT and phospho-AKT staining for the detection of phosphoinositide 3-kinase activation and aggressive endometrial cancer SO HISTOPATHOLOGY LA English DT Letter ID BREAST-CANCER; EXPRESSION; CARCINOMA; SIGNATURE; SURVIVAL; P53 C1 [Trovik, Jone; Salvesen, Helga B.] Haukeland Hosp, Dept Obstet & Gynaecol, N-5021 Bergen, Norway. [Trovik, Jone; Wik, Elisabeth; Salvesen, Helga B.] Univ Bergen, Dept Clin Med, Bergen, Norway. [Stefansson, Ingunn; Kalland, Karl-Henning; Akslen, Lars A.] Univ Bergen, Gade Inst, Sect Pathol, Bergen, Norway. [Stefansson, Ingunn; Akslen, Lars A.] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. [Carter, Scott L.] Harvard & MIT, Div Hlth Sci & Technol, Cambridge, MA USA. [Carter, Scott L.; Beroukhim, Rameen] Harvard & MIT, Broad Inst, Cambridge, MA USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Beroukhim, Rameen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Oyan, Anne M.; Kalland, Karl-Henning] Haukeland Hosp, Dept Microbiol, N-5021 Bergen, Norway. RP Trovik, J (reprint author), Haukeland Hosp, Dept Obstet & Gynaecol, N-5021 Bergen, Norway. RI Kalland, Karl-Henning/B-9445-2017; Akslen, Lars /C-1202-2017; salvesen, Helga/C-1187-2017 OI Kalland, Karl-Henning/0000-0003-4486-2334; Akslen, Lars /0000-0003-2710-9543; salvesen, Helga/0000-0002-4438-8831 NR 15 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD OCT PY 2010 VL 57 IS 4 BP 641 EP 646 DI 10.1111/j.1365-2559.2010.03661.x PG 6 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 666AB UT WOS:000283078300020 PM 20955391 ER PT J AU Chien, KR AF Chien, Kenneth R. TI Regeneration Next: Towards Heart Stem Cell Therapeutics SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 18th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY OCT 22-25, 2010 CL Milan, ITALY C1 [Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Chien, Kenneth R.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2010 VL 21 IS 10 BP 1386 EP 1386 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 664JF UT WOS:000282955500090 ER PT J AU Kahraman, S Dirice, E Elpek, O Ertosun, MG Balci, MK Omer, A Sanlioglu, S Sanlioglu, AD AF Kahraman, S. Dirice, E. Elpek, O. Ertosun, M. G. Balci, M. K. Omer, A. Sanlioglu, S. Sanlioglu, A. D. TI Spontaneous type 1 diabetes in NOD mice is related to an increase in DcR1 expression SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 18th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY OCT 22-25, 2010 CL Milan, ITALY C1 [Kahraman, S.; Sanlioglu, A. D.] Akdeniz Univ Hosp & Clin, Human Gene & Cell Therapy Ctr, Dept Med Biol & Genet, TR-07058 Antalya, Turkey. [Dirice, E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Med, Boston, MA 02115 USA. [Elpek, O.] Akdeniz Univ, Fac Med, Dept Pathol, TR-07058 Antalya, Turkey. [Balci, M. K.] Akdeniz Univ, Fac Med, Div Endocrinol & Metab, TR-07058 Antalya, Turkey. [Omer, A.] Sn Vincent Hosp, Worcester, MA USA. [Sanlioglu, S.] Akdeniz Univ Hosp & Clin, Dept Med Genet, Human Gene & Cell Therapy Ctr, TR-07058 Antalya, Turkey. RI BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Salih/F-9305-2016 OI BALCI, Mustafa Kemal/0000-0002-6494-3249; NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2010 VL 21 IS 10 BP 1447 EP 1448 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 664JF UT WOS:000282955500260 ER PT J AU Kahraman, S Dirice, E Hapil, FZ Ertosun, MG Ozturk, S Griffith, TS Sanlioglu, S Sanlioglu, AD AF Kahraman, S. Dirice, E. Hapil, F. Z. Ertosun, M. G. Ozturk, S. Griffith, T. S. Sanlioglu, S. Sanlioglu, A. D. TI In vivo fluorescence imaging of xenogeneic islet graft survival SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 18th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY OCT 22-25, 2010 CL Milan, ITALY C1 [Dirice, E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Med, Boston, MA 02215 USA. [Dirice, E.] Akdeniz Univ, Human Gene & Cell Therapy Ctr, TR-07058 Antalya, Turkey. [Hapil, F. Z.; Sanlioglu, A. D.] Akdeniz Univ Hosp & Clin, Human Gene & Cell Therapy Ctr, Dept Med Biol & Genet, TR-07058 Antalya, Turkey. [Ozturk, S.] Akdeniz Univ, Fac Med, Dept Histol & Embryol, TR-07070 Antalya, Turkey. [Griffith, T. S.] Univ Iowa, Gene Therapy Ctr, Iowa City, IA 52242 USA. [Sanlioglu, S.] Akdeniz Univ Hosp & Clin, Human Gene & Cell Therapy Ctr, Dept Med Genet, TR-07058 Antalya, Turkey. RI Ozturk, Saffet/C-1239-2016; Sanlioglu, Salih/F-9305-2016 NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2010 VL 21 IS 10 BP 1451 EP 1451 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 664JF UT WOS:000282955500269 ER PT J AU Eijgelsheim, M Newton-Cheh, C Sotoodehnia, N de Bakker, PIW Muller, M Morrison, AC Smith, AV Isaacs, A Sanna, S Dorr, M Navarro, P Fuchsberger, C Nolte, IM de Geus, EJC Estrada, K Hwang, SJ Bis, JC Ruckert, IM Alonso, A Launer, LJ Hottenga, JJ Rivadeneira, F Noseworthy, PA Rice, KM Perz, S Arking, DE Spector, TD Kors, JA Aulchenko, YS Tarasov, KV Homuth, G Wild, SH Marroni, F Gieger, C Licht, CM Prineas, RJ Hofman, A Rotter, JI Hicks, AA Ernst, F Najjar, SS Wright, AF Peters, A Fox, ER Oostra, BA Kroemer, HK Couper, D Volzke, H Campbell, H Meitinger, T Uda, M Witteman, JCM Psaty, BM Wichmann, HE Harris, TB Kaab, S Siscovick, DS Jamshidi, Y Uitterlinden, AG Folsom, AR Larson, MG Wilson, JF Penninx, BW Snieder, H Pramstaller, PP van Duijn, CM Lakatta, EG Felix, SB Gudnason, V Pfeufer, A Heckbert, SR Stricker, BHC Boerwinkle, E O'Donnell, CJ AF Eijgelsheim, Mark Newton-Cheh, Christopher Sotoodehnia, Nona de Bakker, Paul I. W. Mueller, Martina Morrison, Alanna C. Smith, Albert V. Isaacs, Aaron Sanna, Serena Doerr, Marcus Navarro, Pau Fuchsberger, Christian Nolte, Ilja M. de Geus, Eco J. C. Estrada, Karol Hwang, Shih-Jen Bis, Joshua C. Rueckert, Ina-Maria Alonso, Alvaro Launer, Lenore J. Hottenga, Jouke Jan Rivadeneira, Fernando Noseworthy, Peter A. Rice, Kenneth M. Perz, Siegfried Arking, Dan E. Spector, Tim D. Kors, Jan A. Aulchenko, Yurii S. Tarasov, Kirill V. Homuth, Georg Wild, Sarah H. Marroni, Fabio Gieger, Christian Licht, Carmilla M. Prineas, Ronald J. Hofman, Albert Rotter, Jerome I. Hicks, Andrew A. Ernst, Florian Najjar, Samer S. Wright, Alan F. Peters, Annette Fox, Ervin R. Oostra, Ben A. Kroemer, Heyo K. Couper, David Voelzke, Henry Campbell, Harry Meitinger, Thomas Uda, Manuela Witteman, Jacqueline C. M. Psaty, Bruce M. Wichmann, H-Erich Harris, Tamara B. Kaeaeb, Stefan Siscovick, David S. Jamshidi, Yalda Uitterlinden, Andre G. Folsom, Aaron R. Larson, Martin G. Wilson, James F. Penninx, Brenda W. Snieder, Harold Pramstaller, Peter P. van Duijn, Cornelia M. Lakatta, Edward G. Felix, Stephan B. Gudnason, Vilmundur Pfeufer, Arne Heckbert, Susan R. Stricker, Bruno H. Ch. Boerwinkle, Eric O'Donnell, Christopher J. TI Genome-wide association analysis identifies multiple loci related to resting heart rate SO HUMAN MOLECULAR GENETICS LA English DT Article ID RECTIFIER POTASSIUM CHANNEL; CARDIAC-PACEMAKER CELLS; QT INTERVAL DURATION; MYOSIN HEAVY-CHAIN; MIDDLE-AGED MEN; COMMON VARIANTS; FUNCTIONAL EXPRESSION; ADRENERGIC-RECEPTOR; GENETIC-VARIANTS; RISK-FACTOR AB Higher resting heart rate is associated with increased cardiovascular disease and mortality risk. Though heritable factors play a substantial role in population variation, little is known about specific genetic determinants. This knowledge can impact clinical care by identifying novel factors that influence pathologic heart rate states, modulate heart rate through cardiac structure and function or by improving our understanding of the physiology of heart rate regulation. To identify common genetic variants associated with heart rate, we performed a meta-analysis of 15 genome-wide association studies (GWAS), including 38 991 subjects of European ancestry, estimating the association between age-, sex- and body mass-adjusted RR interval (inverse heart rate) and similar to 2.5 million markers. Results with P < 5 x 10(-8) were considered genome-wide significant. We constructed regression models with multiple markers to assess whether results at less stringent thresholds were likely to be truly associated with RR interval. We identified six novel associations with resting heart rate at six loci: 6q22 near GJA1; 14q12 near MYH7; 12p12 near SOX5, c12orf67, BCAT1, LRMP and CASC1; 6q22 near SLC35F1, PLN and c6orf204; 7q22 near SLC12A9 and UfSp1; and 11q12 near FADS1. Associations at 6q22 400 kb away from GJA1, at 14q12 MYH6 and at 1q32 near CD34 identified in previously published GWAS were confirmed. In aggregate, these variants explain similar to 0.7% of RR interval variance. A multivariant regression model including 20 variants with P < 10(-5) increased the explained variance to 1.6%, suggesting that some loci falling short of genome-wide significance are likely truly associated. Future research is warranted to elucidate underlying mechanisms that may impact clinical care. C1 [Eijgelsheim, Mark; Isaacs, Aaron; Rivadeneira, Fernando; Aulchenko, Yurii S.; Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Stricker, Bruno H. Ch.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Estrada, Karol; Rivadeneira, Fernando; Uitterlinden, Andre G.; Stricker, Bruno H. Ch.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Kors, Jan A.; Stricker, Bruno H. Ch.] Erasmus MC, Dept Med Informat, NL-3000 CA Rotterdam, Netherlands. [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands. [Newton-Cheh, Christopher; Noseworthy, Peter A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher; de Bakker, Paul I. W.] Broad Inst Harvard & MIT, Program Med Populat Genet, Cambridge, MA USA. [Newton-Cheh, Christopher; Hwang, Shih-Jen; Larson, Martin G.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Sotoodehnia, Nona] Univ Washington, Sch Med, Dept Med, Div Cardiol, Seattle, WA 98195 USA. [Sotoodehnia, Nona; Bis, Joshua C.; Psaty, Bruce M.; Siscovick, David S.; Heckbert, Susan R.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.; Siscovick, David S.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [de Bakker, Paul I. W.] Brighams & Womens Hosp, Div Genet, Dept Med, Boston, MA USA. [Mueller, Martina; Wichmann, H-Erich; Kaeaeb, Stefan] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol, Neuherberg, Germany. [Mueller, Martina; Rueckert, Ina-Maria; Gieger, Christian; Peters, Annette; Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Univ Hosp Grosshadern, Munich, Germany. [Mueller, Martina] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavogur, Iceland. [Sanna, Serena; Uda, Manuela] Cittadella Univ Monserrato, Ist Neurogenet & Neurofarmacol, Consiglio Nazl Ric, Cagliari, Italy. [Doerr, Marcus; Felix, Stephan B.] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany. [Homuth, Georg; Ernst, Florian] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Navarro, Pau; Wright, Alan F.] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Fuchsberger, Christian; Marroni, Fabio; Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy. [Nolte, Ilja M.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Unit Genet Epidemiol & Bioinformat, Dept Epidemiol, NL-9713 AV Groningen, Netherlands. [de Geus, Eco J. C.; Hottenga, Jouke Jan] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Alonso, Alvaro; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Perz, Siegfried] Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Munich, Germany. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Spector, Tim D.; Jamshidi, Yalda; Snieder, Harold] St Thomas Hosp, Dept Twin Res, Kings Coll London, London, England. [Spector, Tim D.; Jamshidi, Yalda; Snieder, Harold] St Thomas Hosp, Genet Epidemiol Unit, Kings Coll London, London, England. [Tarasov, Kirill V.; Najjar, Samer S.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Wild, Sarah H.; Campbell, Harry; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Marroni, Fabio] Inst Appl Genom, Udine, Italy. [Licht, Carmilla M.; Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Prineas, Ronald J.] EPICARE Ctr, Salem, NC USA. [Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Stricker, Bruno H. Ch.] Netherlands Genom Initiat Sponsored Netherlands C, Rotterdam, Netherlands. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Fox, Ervin R.] Univ Mississippi, Med Ctr, Div Cardiol, Jackson, MS 39216 USA. [Kroemer, Heyo K.] Ctr Pharmacol & Expt Therapeut, Dept Pharmacol, Greifswald, Germany. [Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Meitinger, Thomas; Pfeufer, Arne] Helmholtz Ctr Munich, Inst Human Genet, Munich, Germany. [Meitinger, Thomas; Pfeufer, Arne] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany. [Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Res Inst, Seattle, WA USA. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Jamshidi, Yalda] St Georges Univ London, London, England. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Stricker, Bruno H. Ch.] Inspectorate Hlth Care, The Hague, Netherlands. [O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA. RP Stricker, BHC (reprint author), Erasmus MC, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM b.stricker@erasmusmc.nl; odonnellc@nhlbi.nih.gov RI Aulchenko, Yurii/M-8270-2013; de Bakker, Paul/B-8730-2009; Pramstaller, Peter/C-2357-2008; Peters, Annette/A-6117-2011; Gudnason, Vilmundur/K-6885-2015; Alonso, Alvaro/A-4917-2010; Fuchsberger, Christian/C-9646-2010; Max, Mad/E-5238-2010; Kaab, Stefan/H-3915-2012; Rice, Kenneth/A-4150-2013; Pfeufer, Arne/B-6634-2013; Wilson, James F/A-5704-2009; de Geus, Eco/M-9318-2015; Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015; Hicks, Andrew/E-9518-2017; OI Aulchenko, Yurii/0000-0002-7899-1575; de Bakker, Paul/0000-0001-7735-7858; Gudnason, Vilmundur/0000-0001-5696-0084; Alonso, Alvaro/0000-0002-2225-8323; Max, Mad/0000-0001-6966-6829; Rice, Kenneth/0000-0001-5779-4495; Wilson, James F/0000-0001-5751-9178; de Geus, Eco/0000-0001-6022-2666; Gieger, Christian/0000-0001-6986-9554; Rivadeneira, Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845; Hicks, Andrew/0000-0001-6320-0411; Larson, Martin/0000-0002-9631-1254; Marroni, Fabio/0000-0002-1556-5907; Fuchsberger, Christian/0000-0002-5918-8947; sanna, serena/0000-0002-3768-1749; Jamshidi, Yalda/0000-0003-0151-6482 FU Chief Scientist Office [CZB/4/710]; Medical Research Council [MC_U127561128, MC_U127592696]; None [NIH2000501635]; PHS HHS [2000501635] NR 65 TC 62 Z9 63 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 2010 VL 19 IS 19 BP 3885 EP 3894 DI 10.1093/hmg/ddq303 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 648UD UT WOS:000281718900017 PM 20639392 ER PT J AU Johnston, JJ Sapp, JC Turner, JT Amor, D Aftimos, S Aleck, KA Bocian, M Bodurtha, JN Cox, GF Curry, CJ Day, R Donnai, D Field, M Fujiwara, I Gabbett, M Gal, M Graham, JM Hedera, P Hennekam, RCM Hersh, JH Hopkin, RJ Kayserili, H Kidd, AMJ Kimonis, V Lin, AE Lynch, SA Maisenbacher, M Mansour, S McGaughran, J Mehta, L Murphy, H Raygada, M Robin, NH Rope, AF Rosenbaum, KN Schaefer, GB Shealy, A Smith, W Soller, M Sommer, A Stalker, HJ Steiner, B Stephan, MJ Tilstra, D Tomkins, S Trapane, P Tsai, ACH Van Allen, MI Vasudevan, PC Zabel, B Zunich, J Black, GCM Biesecker, LG AF Johnston, Jennifer J. Sapp, Julie C. Turner, Joyce T. Amor, David Aftimos, Salim Aleck, Kyrieckos A. Bocian, Maureen Bodurtha, Joann N. Cox, Gerald F. Curry, Cynthia J. Day, Ruth Donnai, Dian Field, Michael Fujiwara, Ikuma Gabbett, Michael Gal, Moran Graham, John M., Jr. Hedera, Peter Hennekam, Raoul C. M. Hersh, Joseph H. Hopkin, Robert J. Kayserili, Hulya Kidd, Alexa M. J. Kimonis, Virginia Lin, Angela E. Lynch, Sally Ann Maisenbacher, Melissa Mansour, Sahar McGaughran, Julie Mehta, Lakshmi Murphy, Helen Raygada, Margarita Robin, Nathaniel H. Rope, Alan F. Rosenbaum, Kenneth N. Schaefer, G. Bradley Shealy, Amy Smith, Wendy Soller, Maria Sommer, Annmarie Stalker, Heather J. Steiner, Bernhard Stephan, Mark J. Tilstra, David Tomkins, Susan Trapane, Pamela Tsai, Anne Chun-Hui Van Allen, Margot I. Vasudevan, Pradeep C. Zabel, Bernhard Zunich, Janice Black, Graeme C. M. Biesecker, Leslie G. TI Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations SO HUMAN MUTATION LA English DT Article DE GLI3; Greig syndrome; Pallister-Hall syndrome; oral-facial-digital syndrome ID PALLISTER-HALL-SYNDROME; FACIAL-DIGITAL SYNDROME; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; MORPHOLOGY STANDARD TERMINOLOGY; POLYDACTYLY TYPE-IV; SYNDROME TYPE-VI; HYPOTHALAMIC HAMARTOMA; ACROCALLOSAL SYNDROME; GENE; PATIENT AB A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial- digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Johnston, Jennifer J.; Sapp, Julie C.; Turner, Joyce T.; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Amor, David] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Aftimos, Salim] Auckland City Hosp, No Reg Genet Serv, Auckland, New Zealand. [Aleck, Kyrieckos A.] St Josephs Hosp, Phoenix, AZ USA. [Bocian, Maureen; Kimonis, Virginia] Univ Calif Irvine, Dept Pediat, Med Ctr, Div Genet & Metab, Orange, CA 92668 USA. [Bodurtha, Joann N.] Virginia Commonwealth Univ, Dept Human & Mol Genet Pediat Obstet Gynecol Epid, Richmond, VA USA. [Cox, Gerald F.] Harvard Univ, Sch Med, Div Genet, Boston, MA USA. [Cox, Gerald F.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Cox, Gerald F.] Genzyme Corp, Clin Res, Cambridge, MA USA. [Curry, Cynthia J.] Genet Med Cent Calif Univ Calif, San Francisco, CA USA. [Day, Ruth] Cheshire & Merseyside Clin Genet Serv, Liverpool, Merseyside, England. [Donnai, Dian; Murphy, Helen; Black, Graeme C. M.] Univ Manchester, Manchester Acad Heath Sci Ctr, Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England. [Field, Michael] Nepean Hosp, Dept Clin Genet, Penrith, NSW, Australia. [Fujiwara, Ikuma] Tohoku Univ Sch Med, Tohoku Univ Hosp, Dept Pediat, Sendai, Miyagi, Japan. [Gabbett, Michael; McGaughran, Julie] Univ Queensland, Sch Med, Brisbane, Qld, Australia. [Gabbett, Michael; McGaughran, Julie] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. [Gal, Moran] Shaare Zedek Med Ctr, Inst Med Genet, Jerusalem, Israel. [Graham, John M., Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Med Genet Inst,Cedars Sinai Med Ctr, Los Angeles, CA 90095 USA. [Hedera, Peter] Vanderbilt Univ, Dept Neurol, Nashville, TN USA. [Hennekam, Raoul C. M.] Univ Amsterdam, Acad Med Ctr, Dept Pediat, Meibergdreef, Az Amsterdam, Netherlands. [Hersh, Joseph H.] Univ Louisville, Sch Med, Dept Pediat, Louisville, KY 40292 USA. [Hopkin, Robert J.] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH USA. [Kayserili, Hulya] Istanbul Univ, Istanbul Fac Med, Dept Med Genet, Istanbul, Turkey. [Kidd, Alexa M. J.] Canterbury Hlth Labs, Christchurch, New Zealand. [Lin, Angela E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lynch, Sally Ann] Our Ladys Childrens Hosp, Natl Ctr Med Genet, Dublin 12, Ireland. [Maisenbacher, Melissa; Stalker, Heather J.] Univ Florida, Dept Pediat, Div Genet & Metab, Gainesville, FL USA. [Mansour, Sahar] Univ London, SW Thames Reg Genet Serv, London, England. [Mehta, Lakshmi] Mt Sinai Sch Med, Dept Genet & Genom Sci, Div Med Genet, New York, NY USA. [Raygada, Margarita] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Clin & Dev Genom, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Robin, Nathaniel H.] Univ Alabama, Dept Genet & Pediat, Birmingham, AL USA. [Rope, Alan F.] Univ Utah Sch Med, Div Med Genet, Salt Like City, UT USA. [Rosenbaum, Kenneth N.] Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. [Schaefer, G. Bradley] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Genet & Pediat, Sect Genet & Metab,Dept Pediat, Little Rock, AR 72205 USA. [Shealy, Amy] Cleveland Clin, Genom Med Inst, Cleveland, OH 44106 USA. [Smith, Wendy] Barbara Bush Childrens Hosp Maine Med Ctr, Portland, ME USA. [Soller, Maria] Univ Lund Hosp, Div Clin Genet, Univ & Reg Labs Reg Skane, S-22185 Lund, Sweden. [Sommer, Annmarie] Ohio State Univ Coll Med, Dept Pediat, Columbus, OH USA. [Sommer, Annmarie] Nationwide Childrens Hosp, Columbus, OH USA. [Steiner, Bernhard] Univ Zurich, Inst Med Genet, CH-8603 Schwerzenbach, Switzerland. [Stephan, Mark J.] Madigan Army Med Ctr, Dept Pediat, Tacoma, WA 98431 USA. [Tilstra, David] CentraCare Clin, Dept Pediat, St Cloud, MN USA. [Tomkins, Susan] Univ Hosp Bristol, Bristol, Avon, England. [Trapane, Pamela] Univ Iowa Hosp & Clin, Dept Pediat, Iowa City, IA 52242 USA. [Tsai, Anne Chun-Hui] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. [Van Allen, Margot I.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Vasudevan, Pradeep C.] Univ Leicester, Univ Hosp Leicester NHS Trust, Leicester, Leics, England. [Zabel, Bernhard] Univ Hosp Freiburg, Dept Pediat, Freiburg, Germany. [Zunich, Janice] Indiana Univ Sch Med NW, Genet Ctr, Gary, IN USA. RP Johnston, JJ (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bldg 49,Room 4C64, Bethesda, MD 20892 USA. EM jjohnsto@mail.nih.gov RI Gabbett, Michael/C-3228-2012; McGaughran, Julie/A-2563-2012; OI Black, Graeme/0000-0001-8727-6592; Hopkin, Robert/0000-0003-0770-5516 FU SHARE's Childhood Disability Center; Steven Spielberg Pediatric Research Center; NIH/NICHD [HD22657]; Medical Genetics NIH/NIGMS [5-T32-GM08243]; National Human Genome Research Institute of the National Institutes of Health FX The authors thank the following genetic professionals for referring patients to our study: William P. Allen, David J. Aughton, Christopher Cunniff, Sally Davies, William B. Dobyns, Linda Genen, Daniel Gruskin, Ketil Heimdal, Gail Herman, Jodi Hoffman, Helen Hughes, LaDonna Immken, Jeffrey Innis, Ian Krantz, David Manchester, Elizabeth McPherson, Thomas Morgan, Maximilian Muenke, Tracy Oh, Melissa Parisi, Betsy Peach, Lynda Pollack, Nazneen Rahman, Miranda Splitt and LuAnn Weik. Grant sponsors: SHARE's Childhood Disability Center, the Steven Spielberg Pediatric Research Center, the NIH/NICHD Program Project Grant; grant number: HD22657; the Medical Genetics NIH/NIGMS Training Program Grant; grant number: 5-T32-GM08243 (all to J. M. G). Grant sponsor: funding from the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health. We also acknowledge the Manchester NIHR Biomedical research Centre. Disclaimer: The opinions and assertions contained herein are the views of the authors and are not to be construed as official or as reflecting the views of the United States Department of Defense. NR 35 TC 33 Z9 33 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD OCT PY 2010 VL 31 IS 10 BP 1142 EP 1154 DI 10.1002/humu.21328 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 660OW UT WOS:000282653900008 PM 20672375 ER PT J AU Dorfman, DM Hornick, JL Shahsafaei, A Freeman, GJ AF Dorfman, David M. Hornick, Jason L. Shahsafaei, Aliakbar Freeman, Gordon J. TI The phosphatidylserine receptors, T cell immunoglobulin mucin proteins 3 and 4, are markers of histiocytic sarcoma and other histiocytic and dendritic cell neoplasms SO HUMAN PATHOLOGY LA English DT Article DE Interdigitating dendritic cell sarcoma; Follicular dendritic cell sarcoma; Juvenile xanthogranuloma; Blastic plasmacytoid dendritic cell neoplasm; Leukemia cutis; Langerhans cell histiocytosis; T cell immunoglobulin mucin protein ID APOPTOTIC CELLS; TRANSCRIPTION FACTORS; BONE-MARROW; TIM-3; EXPRESSION; DISORDERS; PHAGOCYTOSIS; PROGENITORS; LYMPHOMAS; SUBSET AB The T cell immunoglobulin mucin (TIM) proteins are a family of cell surface phosphatidyserine receptors that are important for the recognition and phagocytosis of apoptotic cells. Because TIM-4 is expressed by macrophages and dendritic cells in human tissue, we examined its expression in a range of histiocytic and dendritic cell neoplasms and found moderate to strong immunohistochemical staining in cases of juvenile xanthogranuloma and histiocytic sarcoma, and lower level staining in interdigitating dendritic cell sarcoma, Langerhans cell histiocytosis, acute monocytic leukemia (leukemia cutis), and blastic plasmacytoid dendritic cell neoplasm (hematodermic tumor). TIM-3 was first described on activated T(H)1 cells but was recently shown to also be a phosphatidylserine receptor and mediate phagocytosis. We found TIM-3 was expressed by peritoneal macrophages, monocytes and splenic dendritic cells. We found that it, like TIM-4, is expressed in a range of histiocytic and dendritic cell neoplasms, typically with strong immunohistochemical staining. Cases of diffuse large B cell lymphoma, anaplastic large cell lymphoma, metastatic malignant melanoma, and metastatic poorly differentiated carcinoma generally exhibited negative to minimal heterogenous staining for TIM-4 and TIM-3. We conclude that histiocytic and dendritic cell neoplasms consistently express TIM-3 and TIM-4 and that these molecules are new markers of neoplasms derived from histiocytic and dendritic cells. (C) 2010 Elsevier Inc. All rights reserved. C1 [Dorfman, David M.; Hornick, Jason L.; Shahsafaei, Aliakbar] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Dorfman, David M.; Hornick, Jason L.; Shahsafaei, Aliakbar] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Dorfman, DM (reprint author), Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. EM ddorfman@partners.org FU NIH [P01 AI054456] FX This work was supported in part by NIH P01 AI054456 (G.F.). NR 26 TC 12 Z9 13 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 2010 VL 41 IS 10 BP 1486 EP 1494 DI 10.1016/j.humpath.2010.04.005 PG 9 WC Pathology SC Pathology GA 658OF UT WOS:000282498600015 PM 20656318 ER PT J AU Chirinos, JA Segers, P AF Chirinos, Julio A. Segers, Patrick TI Noninvasive Evaluation of Left Ventricular Afterload Part 1: Pressure and Flow Measurements and Basic Principles of Wave Conduction and Reflection SO HYPERTENSION LA English DT Article DE afterload; noninvasive; input impedance; arterial load ID MIDDLE-AGED MEN; ARTERIAL STIFFNESS; AUGMENTATION INDEX; INPUT IMPEDANCE; PULSE; VELOCITY; QUANTIFICATION; AMPLIFICATION; HYPERTENSION; VALIDATION AB The mechanical load imposed by the systemic circulation to the left ventricle is an important determinant of normal and abnormal cardiovascular function. Left ventricular afterload is determined by complex time-varying phenomena, which affect pressure and flow patterns generated by the pumping ventricle and cannot be expressed as a single numeric measure or described in terms of pressure alone. Left ventricular afterload is best described in terms of pressure-flow relations. High-fidelity arterial applanation tonometry can be used to record time-resolved central pressure noninvasively, whereas contemporary noninvasive imaging techniques, such as Doppler echocardiography and phase-contrast MRI, allow for accurate assessments of aortic flow. Central pressure and flow can be analyzed using simplified biomechanical models to characterize various components of afterload, with great potential for mechanistic understanding of the role of central hemodynamics in cardiovascular disease and the effects of therapeutic interventions. In the first part of this tutorial, we review noninvasive techniques for central pressure and flow measurements and basic concepts of wave conduction and reflection as they relate to the interpretation of central pressure-flow relations. Conceptual descriptions of various models and methods are emphasized over mathematical ones. Our review is aimed at helping researchers and clinicians apply and interpret results obtained from analyses of left ventricular afterload in clinical and epidemiological settings. (Hypertension. 2010;56:555-562.) C1 [Chirinos, Julio A.] Univ Penn, Dept Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Segers, Patrick] Univ Ghent, IBiTech, B-9000 Ghent, Belgium. RP Chirinos, JA (reprint author), Room 8B-111,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu NR 23 TC 43 Z9 45 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2010 VL 56 IS 4 BP 555 EP U30 DI 10.1161/HYPERTENSIONAHA.110.157321 PG 18 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 650VL UT WOS:000281881400001 PM 20733089 ER PT J AU Chirinos, JA Segers, P AF Chirinos, Julio A. Segers, Patrick TI Noninvasive Evaluation of Left Ventricular Afterload Part 2: Arterial Pressure-Flow and Pressure-Volume Relations in Humans SO HYPERTENSION LA English DT Article DE afterload; noninvasive; input impedance; arterial load ID HEART-FAILURE; HYPERTENSION; WINDKESSEL; LOAD AB The mechanical load imposed by the systemic circulation to the left ventricle is an important determinant of normal and abnormal cardiovascular function. Left ventricular afterload is determined by complex time-varying phenomena, which affect pressure and flow patterns generated by the pumping ventricle. Left ventricular afterload is best described in terms of pressure-flow relations, allowing for quantification of various components of load using simplified biomechanical models of the circulation, with great potential for mechanistic understanding of the role of central hemodynamics in cardiovascular disease and the effects of therapeutic interventions. In the second part of this tutorial, we review analytic methods used to characterize left ventricular afterload, including analyses of central arterial pressure-flow relations and windkessel modeling (pressure-volume relations). Conceptual descriptions of various models and methods are emphasized over mathematical ones. Our review is aimed at helping researchers and clinicians obtain and interpret results from analyses of left ventricular afterload in clinical and epidemiological settings. (Hypertension. 2010;56:563-570.) C1 [Chirinos, Julio A.] Univ Penn, Dept Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Segers, Patrick] Univ Ghent, IBiTech, B-9000 Ghent, Belgium. RP Chirinos, JA (reprint author), Room 8B-111,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu NR 24 TC 48 Z9 51 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2010 VL 56 IS 4 BP 563 EP 570 DI 10.1161/HYPERTENSIONAHA.110.157339 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 650VL UT WOS:000281881400002 PM 20733088 ER PT J AU Chirinos, JA Townsend, R AF Chirinos, Julio A. Townsend, Raymond TI Sodium, Potassium, and Target Organ Damage A Case for Central Hemodynamics SO HYPERTENSION LA English DT Editorial Material ID ESSENTIAL-HYPERTENSION; RATS C1 [Chirinos, Julio A.; Townsend, Raymond] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Chirinos, Julio A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Chirinos, JA (reprint author), Room 8B-111,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu NR 11 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2010 VL 56 IS 4 BP 578 EP 580 DI 10.1161/HYPERTENSIONAHA.110.159046 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 650VL UT WOS:000281881400006 PM 20733084 ER PT J AU Selby, JV Lee, J Swain, BE Tavel, HM Ho, PM Margolis, KL O'Connor, PJ Fine, L Schmittdiel, JA Magid, DJ AF Selby, Joe V. Lee, Janelle Swain, Bix E. Tavel, Heather M. Ho, P. Michael Margolis, Karen L. O'Connor, Patrick J. Fine, Lawrence Schmittdiel, Julie A. Magid, David. J. TI Trends in Time to Confirmation and Recognition of New-Onset Hypertension, 2002-2006 SO HYPERTENSION LA English DT Article DE hypertension; electronic health records; registries; early detection; screening ID AMBULATORY BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; RISK; MANAGEMENT; CARE; VARIABILITY; POPULATION; ADULTS; TRIAL AB Achieving full benefits of blood pressure control in populations requires prompt recognition of previously undetected hypertension. In 2003, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure provided definitions of hypertension and recommended that single elevated readings be confirmed within 1 to 2 months. We sought to determine whether the time required to confirm and recognize (ie, diagnose and/or treat) new-onset hypertension decreased from 2002 to 2006 for adult members of 2 large integrated healthcare delivery systems, Kaiser Permanente Northern California and Colorado. Using electronically stored office blood pressure readings, physician diagnoses, and pharmacy prescriptions, we identified 200 587 patients with new-onset hypertension (2002-2006) marked by 2 consecutive elevated blood pressure readings in previously undiagnosed, untreated members. Mean confirmation intervals (time from the first to second consecutive elevated reading) declined steadily from 103 to 89 days during this period. For persons recognized within 12 months after confirmation, the mean interval to recognition declined from 78 to 61 days. However, only 33% of individuals were recognized within 12 months. One third were never recognized during observed follow-up. For these patients, most subsequent blood pressure recordings were not elevated. Higher initial blood pressure levels, history of previous cardiovascular disease, and older age were associated with shorter times to recognition. Times to confirmation and recognition of new-onset hypertension have become shorter in recent years, especially for patients with higher cardiovascular disease risk. Variability in office-based blood pressure readings suggests that further improvements in recognition and treatment may be achieved with more specific automated approaches to identifying hypertension. (Hypertension. 2010;56:605-611.) C1 [Selby, Joe V.; Lee, Janelle; Swain, Bix E.; Schmittdiel, Julie A.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Tavel, Heather M.; Magid, David. J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Ho, P. Michael] Denver Vet Affairs Med Ctr, Denver, CO USA. [Ho, P. Michael] Univ Colorado, Denver, CO 80202 USA. [Margolis, Karen L.; O'Connor, Patrick J.] HealthPartners Res Fdn, Minneapolis, MN USA. [Fine, Lawrence] NHLBI, NIH, Bethesda, MD 20892 USA. RP Selby, JV (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM joe.selby@kp.org FU National Heart, Lung, and Blood Institute [U19HL091179]; Office of Research in Women's Health Building Interdisciplinary Careers [K12HD052163]; Veterans' Affairs Research and Development [05-026-2] FX This study was supported by the National Heart, Lung, and Blood Institute (award No. U19HL091179). J.A.S. is supported by the Office of Research in Women's Health Building Interdisciplinary Careers in Women's Health K12 Career Development Award (K12HD052163). P.M.H. is supported by a Veterans' Affairs Research and Development Career Development Award (05-026-2). NR 27 TC 21 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2010 VL 56 IS 4 BP 605 EP 611 DI 10.1161/HYPERTENSIONAHA.110.153528 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 650VL UT WOS:000281881400011 PM 20733092 ER PT J AU Shahid, M Shen, L Seldin, DC Lu, B Ustyugova, IV Chen, XY Zapol, WM Wu, MX AF Shahid, Mohd Shen, Li Seldin, David C. Lu, Bao Ustyugova, Irina V. Chen, Xinyuan Zapol, Warren M. Wu, Mei X. TI Impaired 3 ',5 '-Cyclic Adenosine Monophosphate-Mediated Signaling in Immediate Early Responsive Gene X-1-Deficient Vascular Smooth Muscle Cells SO HYPERTENSION LA English DT Article DE hypertension; IEX-1; ROS; G alpha(i2); mitochondria ID SPONTANEOUSLY HYPERTENSIVE-RATS; HIGH BLOOD-PRESSURE; OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; CARDIAC-HYPERTROPHY; ENHANCED EXPRESSION; IEX-1; MECHANISMS; PROTEINS; OXIDASE AB Gene-targeted deletion of the immediate early responsive gene X-1 (IEX-1) results in a significant increase in systemic arterial blood pressure, but the underlying mechanism is not understood. Studies of arterial reactivity in isolated aortas revealed normal endothelium-dependent and -independent vasorelaxation and vasoconstriction but reduced cAMP-dependent vasorelaxation in the absence of IEX-1. This defect in cAMP signaling was also evident in endothelium-denuded aortic rings, consistent with the enhancement of mitochondrial O(2)(center dot-) production only in IEX-1-deficient vascular smooth muscle cells, not in endothelial cells. Excessive production of reactive oxygen species at mitochondria augmented the expression of G alpha(i2), suppressing cAMP production in vascular smooth muscle cells. The role of mitochondrial reactive oxygen species in the upregulation of G alpha(i2) leading to the development of hypertension was supported by the ability of antioxidant or pertussis toxin to restore the cAMP-dependent vasorelaxation to a normal level and reverse established hypertension in IEX-1 homozygous knockout mice. Our results suggest that hypertension in IEX-1 knockout mice may arise primarily from impaired cAMP signaling induced by overproduction of mitochondrial reactive oxygen species in vascular smooth muscle cells and demonstrate a causal relationship between mitochondrial dysfunction and cAMP-dependent vasorelaxation. (Hypertension. 2010;56:705-712.) C1 [Shahid, Mohd; Shen, Li; Ustyugova, Irina V.; Chen, Xinyuan; Wu, Mei X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. [Zapol, Warren M.] Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med,Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Zapol, Warren M.; Wu, Mei X.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Boston, MA USA. [Seldin, David C.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Lu, Bao] Harvard Univ, Sch Med, Childrens Hosp, Div Pulm, Boston, MA 02114 USA. RP Wu, MX (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM mwu5@partners.org RI chen, xinyuan/B-8505-2012 FU National Institutes of Health [AI050822, AI070785, CA75796]; American Heart Association [0855762D] FX This work is supported by National Institutes of Health grants AI050822 and AI070785 and a Grant-in-Aid (0855762D) from the American Heart Association (to M.X.W.) and National Institutes of Health grant CA75796 (to D.C.S.) NR 41 TC 10 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2010 VL 56 IS 4 BP 705 EP U265 DI 10.1161/HYPERTENSIONAHA.110.154880 PG 20 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 650VL UT WOS:000281881400025 PM 20713914 ER PT J AU Powe, CE Seely, EW Rana, S Bhan, I Ecker, J Karumanchi, SA Thadhani, R AF Powe, Camille E. Seely, Ellen W. Rana, Sarosh Bhan, Ishir Ecker, Jeffrey Karumanchi, S. Ananth Thadhani, Ravi TI First Trimester Vitamin D, Vitamin D Binding Protein, and Subsequent Preeclampsia SO HYPERTENSION LA English DT Article DE vitamin D; vitamin D binding protein; preeclampsia; pregnancy ID PARATHYROID-HORMONE; WHITE WOMEN; 25-HYDROXYVITAMIN-D LEVELS; INSULIN-RESISTANCE; ENDOTHELIAL-CELLS; HUMAN-SERUM; BODY-FAT; 1,25-DIHYDROXYVITAMIN-D; CALCIUM; RISK AB Previous studies report an association between vitamin D deficiency and hypertension, including the pregnancy-specific disorder preeclampsia. Circulating vitamin D is almost entirely bound to vitamin D binding protein, which increases 2-fold during pregnancy and previous studies have not examined vitamin D binding protein or free vitamin D levels. We performed a nested case-control study within the Massachusetts General Hospital Obstetric Maternal Study, measuring first trimester total 25-hydroxyvitamin D (25[OH] D) and vitamin D binding protein and calculating free 25(OH) D levels. We compared these levels from pregnancies complicated by subsequent preeclampsia (cases, n=39) with those from normotensive pregnancies (controls, n=131). First trimester total 25(OH) D levels were similar in cases and controls (27.4 +/- 1.9 versus 28.8 +/- 0.80 ng/mL; P=0.435). Despite an association between higher first trimester blood pressures and subsequent preeclampsia, first trimester total 25(OH) D was not associated with first trimester systolic (r=0.11; P=0.16) or diastolic blood pressures (r=0.03; P=0.72). Although there was a trend toward increased risk of preeclampsia with 25(OH) D levels <15 ng/mL (odds ratio: 2.5 [95% CI: 0.89 to 6.90]), this was attenuated after adjustment for body mass index and other covariates (odds ratio: 1.35 [95% CI: 0.40 to 4.50]). First trimester vitamin D binding protein and free 25(OH) D levels were similar in cases and controls and were not associated with first trimester blood pressures. These data suggest that first trimester total and free 25(OH) D levels are not independently associated with first trimester blood pressure or subsequent preeclampsia. (Hypertension. 2010;56:758-763.) C1 [Powe, Camille E.; Bhan, Ishir; Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Ecker, Jeffrey] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Seely, Ellen W.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Rana, Sarosh; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, 55 Fruit St,Bullfinch 127, Boston, MA 02114 USA. EM rthadhani@partners.org FU National Institutes of Health/National Heart, Lung, and Blood Institute [K24HL096141]; American Diabetes Association; Women's Reproductive Health [K12HD001255]; Abbott Laboratories FX This research was partly supported by K24HL096141 (National Institutes of Health/National Heart, Lung, and Blood Institute) to E.W.S. J.E. has received support from the American Diabetes Association for the MGH Maternal Obstetrical Study. C.E.P. is a Howard Hughes Medical Institute Medical Research Training Fellow. S.R. is supported by Women's Reproductive Health Research grant (K12HD001255-National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development). S.A.K. is an investigator of the Howard Hughes Medical Institute.; R.T. has a grant from Abbott Laboratories to study vitamin D in kidney disease. R.T. has filed patents on the use of biomarkers for the prediction and diagnosis of preeclampsia through the Massachusetts General Hospital. R.T. is a consultant to Beckman Coulter and Roche Diagnostics in the area of preeclampsia biomarkers. S.A.K. is a coinventor on multiple patents related to angiogenic proteins for the diagnosis/therapy of preeclampsia. S.A.K. is a consultant to Abbott, Beckman Coulter, Roche, and Johnson & Johnson, which are developing angiogenic markers for use in preeclampsia diagnosis/prediction. NR 42 TC 75 Z9 78 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD OCT PY 2010 VL 56 IS 4 BP 758 EP 763 DI 10.1161/HYPERTENSIONAHA.110.158238 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 650VL UT WOS:000281881400032 PM 20733087 ER PT J AU You, LW Brusic, V Gallagher, M Boden, M AF You, Liwen Brusic, Vladimir Gallagher, Marcus Boden, Mikael TI Using Gaussian Process with Test Rejection to Detect T-Cell Epitopes in Pathogen Genomes SO IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS LA English DT Article DE Immunology; amino acid sequence; epitope; machine learning; Gaussian processes; regression; false positives ID I-BINDING PEPTIDES; SUPPORT VECTOR MACHINES; INDEPENDENT BINDING; PREDICTION; MOLECULES; RESPONSES; MODELS AB A major challenge in the development of peptide-based vaccines is finding the right immunogenic element, with efficient and long-lasting immunization effects, from large potential targets encoded by pathogen genomes. Computer models are convenient tools for scanning pathogen genomes to preselect candidate immunogenic peptides for experimental validation. Current methods predict many false positives resulting from a low prevalence of true positives. We develop a test reject method based on the prediction uncertainty estimates determined by Gaussian process regression. This method filters false positives among predicted epitopes from a pathogen genome. The performance of stand-alone Gaussian process regression is compared to other state-of-the-art methods using cross validation on 11 benchmark data sets. The results show that the Gaussian process method has the same accuracy as the top performing algorithms. The combination of Gaussian process regression with the proposed test reject method is used to detect true epitopes from the Vaccinia virus genome. The test rejection increases the prediction accuracy by reducing the number of false positives without sacrificing the method's sensitivity. We show that the Gaussian process in combination with test rejection is an effective method for prediction of T-cell epitopes in large and diverse pathogen genomes, where false positives are of concern. C1 [You, Liwen] Lund Univ, Dept Theoret Phys, S-22362 Lund, Sweden. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Gallagher, Marcus] Univ Queensland, Sch Informat Technol & Elect Engn, Brisbane, Qld 4072, Australia. [Boden, Mikael] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia. RP You, LW (reprint author), Lund Univ, Dept Theoret Phys, Solvegatan 14A, S-22362 Lund, Sweden. EM liwenyou@gmail.com; vladimir_brusic@dfci.harvard.edu; marcusg@itee.uq.edu.au; m.boden@uq.edu.au RI Boden, Mikael/A-6030-2010; OI Boden, Mikael/0000-0003-3548-268X; Gallagher, Marcus/0000-0002-6694-9572 FU National Research School in Genomics and Bioinformatics; EC [028069]; ARC Centre of Excellence in Bioinformatics FX Liwen You was funded within the National Research School in Genomics and Bioinformatics hosted by Goteborg University, Sweden. This project was supported in part (Liwen You and Vladimir Brusic) by the ImmunoGrid project, under EC contract FP6-2004-IST-4, No. 028069. Mikael Boden was supported by the ARC Centre of Excellence in Bioinformatics. The authors are grateful for constructive advice from three anonymous reviewers and Dr. Timothy Bailey. NR 23 TC 5 Z9 8 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1545-5963 J9 IEEE ACM T COMPUT BI JI IEEE-ACM Trans. Comput. Biol. Bioinform. PD OCT-DEC PY 2010 VL 7 IS 4 BP 741 EP 751 DI 10.1109/TCBB.2008.131 PG 11 WC Biochemical Research Methods; Computer Science, Interdisciplinary Applications; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Biochemistry & Molecular Biology; Computer Science; Mathematics GA 672BX UT WOS:000283559100017 PM 21030740 ER PT J AU Sabuncu, MR Yeo, BTT Van Leemput, K Fischl, B Golland, P AF Sabuncu, Mert R. Yeo, B. T. Thomas Van Leemput, Koen Fischl, Bruce Golland, Polina TI A Generative Model for Image Segmentation Based on Label Fusion SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Image parcellation; image registration; image segmentation ID ATLAS BASED SEGMENTATION; TISSUE CLASSIFICATION; ALZHEIMERS-DISEASE; MR-IMAGES; REGISTRATION ALGORITHM; NONRIGID REGISTRATION; BRAIN IMAGES; EM ALGORITHM; INFORMATION; FRAMEWORK AB We propose a nonparametric, probabilistic model for the automatic segmentation of medical images, given a training set of images and corresponding label maps. The resulting inference algorithms rely on pairwise registrations between the test image and individual training images. The training labels are then transferred to the test image and fused to compute the final segmentation of the test subject. Such label fusion methods have been shown to yield accurate segmentation, since the use of multiple registrations captures greater inter-subject anatomical variability and improves robustness against occasional registration failures. To the best of our knowledge, this manuscript presents the first comprehensive probabilistic framework that rigorously motivates label fusion as a segmentation approach. The proposed framework allows us to compare different label fusion algorithms theoretically and practically. In particular, recent label fusion or multiatlas segmentation algorithms are interpreted as special cases of our framework. We conduct two sets of experiments to validate the proposed methods. In the first set of experiments, we use 39 brain MRI scans-with manually segmented white matter, cerebral cortex, ventricles and subcortical structures-to compare different label fusion algorithms and the widely-used FreeSurfer whole-brain segmentation tool. Our results indicate that the proposed framework yields more accurate segmentation than FreeSurfer and previous label fusion algorithms. In a second experiment, we use brain MRI scans of 282 subjects to demonstrate that the proposed segmentation tool is sufficiently sensitive to robustly detect hippocampal volume changes in a study of aging and Alzheimer's Disease. C1 [Sabuncu, Mert R.; Yeo, B. T. Thomas; Van Leemput, Koen; Fischl, Bruce; Golland, Polina] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Sabuncu, Mert R.; Van Leemput, Koen; Fischl, Bruce] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Van Leemput, Koen] Aalto Univ, Dept Informat & Comp Sci, Sch Sci & Technol, FI-00076 Aalto, Finland. RP Sabuncu, MR (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RI Van Leemput, Koen/A-9197-2009; OI Van Leemput, Koen/0000-0001-6466-5309; Yeo, B.T. Thomas/0000-0002-0119-3276 FU NAMIC [NIH NIBIB NAMIC U54-EB005149]; NAC [NIH NCRR NAC P41-RR13218]; mBIRN [NIH NCRR mBIRN U24-RR021382]; NIH NINDS [R01-NS051826]; NSF [0642971]; NCRR [P41-RR14075, R01 RR16594-01A1]; NIBIB [R01 EB001550, R01EB006758]; NINDS [R01 NS052585-01]; MIND Institute; Ellison Medical Foundation; A*STAR, Singapore; Academy of Finland [133611] FX Support for this research is provided in part by: NAMIC (NIH NIBIB NAMIC U54-EB005149), the NAC (NIH NCRR NAC P41-RR13218), the mBIRN (NIH NCRR mBIRN U24-RR021382), the NIH NINDS R01-NS051826 grant, the NSF CAREER 0642971 grant, NCRR (P41-RR14075, R01 RR16594-01A1), the NIBIB (R01 EB001550, R01EB006758), the NINDS (R01 NS052585-01), the MIND Institute, and the Autism and Dyslexia Project funded by the Ellison Medical Foundation. B. T. T. Yeo is funded by the A*STAR, Singapore. K. Van Leemput was supported in part by the Academy of Finland, grant number 133611. M. R. Sabuncu and B. T. T. Yeo contributed equally to this work. NR 74 TC 214 Z9 218 U1 4 U2 26 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 OCT PY 2010 VL 29 IS 10 BP 1714 EP 1729 DI 10.1109/TMI.2010.2050897 PG 16 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 669LR UT WOS:000283352700002 PM 20562040 ER PT J AU Heliot, R Ganguly, K Jimenez, J Carmena, JM AF Heliot, Rodolphe Ganguly, Karunesh Jimenez, Jessica Carmena, Jose M. TI Learning in Closed-Loop Brain-Machine Interfaces: Modeling and Experimental Validation SO IEEE TRANSACTIONS ON SYSTEMS MAN AND CYBERNETICS PART B-CYBERNETICS LA English DT Article DE Brain-machine interfaces (BMIs); internal model; macaque monkey; motor learning ID DIRECT CORTICAL CONTROL; PRIMATE MOTOR CORTEX; ARM MOVEMENTS; PROSTHETIC DEVICES; INTERNAL-MODELS; TETRAPLEGIA; FEEDFORWARD; KINEMATICS; DIRECTION; NETWORKS AB Closed-loop operation of a brain-machine interface (BMI) relies on the subject's ability to learn an inverse transformation of the plant to be controlled. In this paper, we propose a model of the learning process that undergoes closed-loop BMI operation. We first explore the properties of the model and show that it is able to learn an inverse model of the controlled plant. Then, we compare the model predictions to actual experimental neural and behavioral data from nonhuman primates operating a BMI, which demonstrate high accordance of the model with the experimental data. Applying tools from control theory to this learning model will help in the design of a new generation of neural information decoders which will maximize learning speed for BMI users. C1 [Heliot, Rodolphe; Carmena, Jose M.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Program Cognit Sci, Berkeley, CA 94720 USA. [Heliot, Rodolphe; Ganguly, Karunesh; Carmena, Jose M.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Ganguly, Karunesh] San Francisco VA Med Ctr, Neurol & Rehabil Serv, San Francisco, CA 94121 USA. [Ganguly, Karunesh] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Heliot, R (reprint author), Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Program Cognit Sci, Berkeley, CA 94720 USA. EM carmena@eecs.berkeley.edu FU French "Delegation generale pour l'armement' [PDE 07C0067]; American Heart Association; Graduate Assistance in Areas of National Need Fellowship; Christopher and Dana Reeve Foundation FX The work of R. Heliot was supported by the French "Delegation generale pour l'armement' under Grant PDE 07C0067. The work of K. Ganguly was supported by the American Heart Association. The work of J. Jimenez was supported by the Graduate Assistance in Areas of National Need Fellowship. The work of J. M. Carmena was supported by the Christopher and Dana Reeve Foundation. This paper was recommended by Associate Editor J. D. R. Millan. NR 42 TC 25 Z9 25 U1 1 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1083-4419 J9 IEEE T SYST MAN CY B JI IEEE Trans. Syst. Man Cybern. Part B-Cybern. PD OCT PY 2010 VL 40 IS 5 BP 1387 EP 1397 DI 10.1109/TSMCB.2009.2036931 PG 11 WC Automation & Control Systems; Computer Science, Artificial Intelligence; Computer Science, Cybernetics SC Automation & Control Systems; Computer Science GA 668TI UT WOS:000283292800014 PM 20007050 ER PT J AU Berglund, M Melgar, S Kobayashi, KS Flavell, RA Hornquist, EH Hultgren, OH AF Berglund, Martin Melgar, Silvia Kobayashi, Koichi S. Flavell, Richard A. Hornquist, Elisabeth Hultgren Hultgren, Olof H. TI IL-1 Receptor-associated Kinase M Downregulates DSS-induced Colitis SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE IRAK-M; TLR signaling; colitis; proinflammatory cytokines ID DEXTRAN SULFATE SODIUM; INFLAMMATORY-BOWEL-DISEASE; INTESTINAL EPITHELIAL-CELLS; TOLL-LIKE RECEPTORS; IRAK-M; ULCERATIVE-COLITIS; NEGATIVE REGULATOR; THYMIC INVOLUTION; INNATE IMMUNITY; UP-REGULATION AB Background: Ulcerative colitis is associated with increased colon permeability resulting in bacterial translocation into the lamina propria. We investigate the importance of the Toll-like receptor (TLR) regulating protein IL-1 receptor-associated kinase M (IRAK-M) using the erosive dextran sulfate sodium (DSS)-induced model of colitis. Methods: IRAK-M-competent and -incompetent mice were treated with 3% DSS for 5 days followed by 2 days of regular drinking water. Clinical signs of disease were followed for 7 days. At day 7 the mice were sacrificed and plasma and tissue were collected for histopathological examination and analyses of the production of cytokines and chemokines as well as expression of T-cell transcription factors. Results: At day 7 IRAK-M-deficient mice display a reduced total body weight (77.1 +/- 2.1 versus 88.5 +/- 2.0, *P=0.002) and an increased macroscopical (2.7 +/- 0.2 versus 1.6 +/- 0.1, *P 0.002) and histopathological (6.0 +/- 0 versus 3.3 +/- 60.5, *P < 0.001) colon score compared to wildtype mice. Furthermore, IRAK-M-deficient mice have increased colon mRNA expression of proinflammatory cytokines and increased tumor necrosis factor concentrations (41.1 +/- 13.5 versus 12.8 +/- 2.0 pg/mL, *P = 0.010) in plasma. Conclusions: This is the first report examining the role of IRAK-M in colitis. We find that IRAK-M is of critical importance in downregulating induction and progression of DSS colitis, and thereby suggesting that IRAK-M might be a target for future interventional therapies. (Inflamm Bowel Dis 2010; 16: 1778-1786) C1 [Berglund, Martin] Univ Gothenburg, Dept Microbiol & Immunol, Inst Biomed, Sahlgrenska Acad, S-40530 Gothenburg, Sweden. [Melgar, Silvia] Natl Univ Ireland, Alimentary Pharmabiot Ctr, Univ Coll Cork, Cork, Ireland. [Melgar, Silvia] Immunoinflammat CEDD GlaxoSmithKline, Stevenage, Herts, England. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. [Hornquist, Elisabeth Hultgren; Hultgren, Olof H.] Univ Orebro, Dept Med, Sch Hlth & Med Sci, Orebro, Sweden. [Hultgren, Olof H.] Orebro Univ Hosp, Dept Clin Microbiol, Orebro, Sweden. RP Berglund, M (reprint author), Univ Gothenburg, Dept Microbiol & Immunol, Inst Biomed, Sahlgrenska Acad, Box 435, S-40530 Gothenburg, Sweden. EM martin.berglund@immuno.gu.se OI melgar, silvia/0000-0001-7463-3343 FU Goteborg Medical Society; Swedish Medical Society; Olle Engkvist Foundation; Karl and Annie Leon Foundation; Swedish Research Council-Medicine and Health; Swedish Cancer Society; Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (LUA-ALF); Bengt Ihre's Foundation; University of Goteborg; Mucosal Immunology and Vaccine Center (MIVAC); Science Foundation Ireland; GlaxoSmithKline FX Supported by grants from the Goteborg Medical Society, the Swedish Medical Society, the Olle Engkvist Foundation, the Karl and Annie Leon Foundation, the Swedish Research Council-Medicine and Health, the Swedish Cancer Society, the Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (LUA-ALF), the Bengt Ihre's Foundation, the University of Goteborg, and the Mucosal Immunology and Vaccine Center (MIVAC). The Alimentary Pharmabiotic Centre is supported, in part, by Science Foundation Ireland and GlaxoSmithKline. R.A. Flavell is an investigator of the Howard Hughes Medical Institute. NR 51 TC 15 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD OCT PY 2010 VL 16 IS 10 BP 1778 EP 1786 DI 10.1002/ibd.21287 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 660EV UT WOS:000282623700021 PM 20848470 ER PT J AU Rhemrev, SJ Beeres, FJP van Leerdam, RH Hogervorst, M Ring, D AF Rhemrev, S. J. Beeres, F. J. P. van Leerdam, R. H. Hogervorst, M. Ring, D. TI Clinical prediction rule for suspected scaphoid fractures A Prospective Cohort Study SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Scaphoid; Scaphoid fractures; Wrist; Fractures of the wrist ID BONE-SCINTIGRAPHY; SKELETAL SCINTIGRAPHY; COMPUTED-TOMOGRAPHY; MANAGEMENT; MRI AB Background: The low prevalence of true fractures amongst suspected fractures magnifies the shortcomings of the diagnostic tests used to triage suspected scaphoid fractures. Purpose: The objective was to develop a clinical prediction rule that would yield a subset of patients who were more likely to have a scaphoid fracture than others who lacked the subset criteria. Methods: Seventy-eight consecutive patients diagnosed with a suspected scaphoid fracture were included. Standardised patient history, physical examination, range of motion (ROM) and strength measurements were studied. The reference standard for a true fracture was based on the results of magnetic resonance imaging, bone scintigraphy, follow-up radiographs and examination. Results: Analysis revealed three significant independent predictors: extension < 50%, supination strength <= 10% and the presence of a previous fracture. Conclusion: Clinical prediction rules have the potential to increase the prevalence of true fractures amongst patients with suspected scaphoid fractures, which can increase the diagnostic performance characteristics of radiological diagnostic tests used for triage. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Rhemrev, S. J.; Beeres, F. J. P.; van Leerdam, R. H.] Med Ctr Haaglanden, Dept Surg, NL-2501 CK The Hague, Netherlands. [Hogervorst, M.] Gelre Ziekenhuizen, Dept Surg, NL-7300 DS Apeldoorn, Netherlands. [Ring, D.] Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA. RP van Leerdam, RH (reprint author), Med Ctr Haaglanden, Dept Surg, Postbus 432, NL-2501 CK The Hague, Netherlands. EM r.leerdam@gmail.com OI Beeres, Frank/0000-0002-7277-3438 NR 21 TC 10 Z9 10 U1 1 U2 9 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 OCT PY 2010 VL 41 IS 10 BP 1026 EP 1030 DI 10.1016/j.injury.2010.03.029 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 647AJ UT WOS:000281587300009 PM 20510414 ER PT J AU Weiser, TG Haynes, AB Lashoher, A Dziekan, G Boorman, DJ Berry, WR Gawande, AA AF Weiser, Thomas G. Haynes, Alex B. Lashoher, Angela Dziekan, Gerald Boorman, Daniel J. Berry, William R. Gawande, Atul A. TI Perspectives in quality: designing the WHO Surgical Safety Checklist SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE quality improvement; quality management; consensus methods; general methodology; surgery; teamwork; human resources AB The World Health Organization's Patient Safety Programme created an initiative to improve the safety of surgery around the world. In order to accomplish this goal the programme team developed a checklist with items that could and, if at all possible, should be practised in all settings where surgery takes place. There is little guidance in the literature regarding methods for creating a medical checklist. The airline industry, however, has more than 70 years of experience in developing and using checklists. The authors of the WHO Surgical Safety Checklist drew lessons from the aviation experience to create a safety tool that supports essential clinical practice. In order to inform the methodology for development of future checklists in health care, we review how we applied lessons learned from the aviation experience in checklist development to the development of the Surgical Safety Checklist and also discuss the differences that exist between aviation and medicine that impact the use of checklists in health care. C1 [Lashoher, Angela] Johns Hopkins Univ, Dept Surg, Baltimore, MD 21218 USA. [Weiser, Thomas G.; Haynes, Alex B.; Berry, William R.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Weiser, Thomas G.; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lashoher, Angela; Dziekan, Gerald] WHO, Patient Safety Programme, CH-1211 Geneva, Switzerland. [Boorman, Daniel J.] Boeing Corp, Seattle, WA USA. RP Lashoher, A (reprint author), Johns Hopkins Univ, Dept Surg, Baltimore, MD 21218 USA. EM alashoher@gmail.com OI Gawande, Atul/0000-0002-1824-9176 FU WHO FX The study was supported by WHO as part of the Safe Surgery Saves Lives project led by A. A. G. The sponsor approved this work but had no responsibility for the decision to submit for publication. NR 20 TC 87 Z9 88 U1 1 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD OCT PY 2010 VL 22 IS 5 BP 365 EP 370 DI 10.1093/intqhc/mzq039 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 651WN UT WOS:000281958200020 PM 20702569 ER PT J AU Faustman, DL Davis, M AF Faustman, Denise L. Davis, Miriam TI Stem cells in the spleen: Therapeutic potential for Sjogren's syndrome, type I diabetes, and other disorders SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Spleen; Stem cells; Regeneration; Sjogrens; Type 1 diabetes ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; NOD MICE; DEVELOPMENTAL EXPRESSION; REVERSAL; HOX11; IDENTIFICATION; ACTIVATION; HYPOTHESIS; RECOVERY AB The view of the spleen as an unnecessary organ has been shattered. The evidence shows the spleen to be a source of naturally-occurring multipotent stem cells with possibly pluripotent potential. The stem cells are sequestered in the spleen of not only of animals but also of normal human adults. The reservoir of cells is set for differentiation and they need not be manipulated in vitro or ex vivo before autologous or heterologous use. Splenic stem cells, of Hox11 lineage, have been found in disease or injury to differentiate into pancreatic islets, salivary epithelial cells and osteoblast-like cells, cranial neurons, cochlea, lymphocytes, and more differentiated immune cells that repair injured heart cells. Injury or disease in target tissues induces these stem cells, still in the spleen, to upregulate the same embryonic transcription factors artificially introduced into induced pluripotent stem cells (iPS). Splenic stem cells may have broad pluripotent potential, but unlike iPS cells, possess low oncogenic risk. (c) 2010 Elsevier Ltd. All rights reserved. C1 [Faustman, Denise L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Faustman, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bldg 149,13th St,Room 3602, Charlestown, MA 02129 USA. EM faustman@helix.mgh.harvard.edu FU NIDDK NIH HHS [P30 DK057521] NR 31 TC 12 Z9 13 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD OCT PY 2010 VL 42 IS 10 BP 1576 EP 1579 DI 10.1016/j.biocel.2010.06.012 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 656PZ UT WOS:000282350200002 PM 20601088 ER PT J AU Dieguez-Acuna, F Kodama, S Okubo, Y Paz, AC Gygi, SP Faustman, DL AF Dieguez-Acuna, Francisco Kodama, Shohta Okubo, Yoshiaki Paz, Ana Cristina Gygi, Steven P. Faustman, Denise L. TI Proteomics identifies multipotent and low oncogenic risk stem cells of the spleen SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Stem cells; Proteomics; Multipotency; Mass spectrometry; Regeneration; Spleen; Hox11; Cancer stem cells ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DIRECTED DIFFERENTIATION; DISTAL PANCREATECTOMY; CHRONIC-PANCREATITIS; GENE-EXPRESSION; TRANSGENIC MICE; DIABETIC MICE; MOUSE; CANCER; GENERATION AB The adult spleen harbors a population of naturally occurring multipotent stem cells of non-lymphoid lineage (CD45-). In animal models, these splenic stem cells can directly or indirectly contribute to regeneration of bone, inner ear, cranial nerves, islets, hearts and salivary glands. Here we characterize the CD45- stem cell proteome to determine its potential broader multipotency versus its protection from malignant transformation. Using state-of-the-art proteomics and in vivo testing, we performed functional analyses of unique proteins of CD45- (non-lymphoid) splenic stem cells, as compared with CD45+ (lymphoid) cells. CD45- stem cell-specific proteins were identical to those in iPS, including OCT3/4, SOX2, KLF4, c-MYC and NANOG. They also expressed Hox11, Gli3, Wnt2, and Adam12, the benchmark transcription factors of embryonic stem cells. These transcription factors were functional because their mRNA was upregulated in the spleen in association with ongoing damage to the pancreas and salivary glands, organs to which they normally contribute stem cells. We also show low likelihood of malignant transformation. Our proteomic and functional analyses reveals that naturally occurring CD45- stem cells of the spleen are the first-ever candidates for naturally occurring population of embryonic and iPS cells with low oncogenic risk. Given their presence in normal humans and mice, splenic stem cells are poised for translational research. (c) 2009 Elsevier Ltd. All rights reserved. C1 [Dieguez-Acuna, Francisco; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Dieguez-Acuna, Francisco; Kodama, Shohta; Okubo, Yoshiaki; Faustman, Denise L.] Massachusetts Gen Hosp, Immunobiol Lab, Charlestown, MA 02129 USA. [Dieguez-Acuna, Francisco; Kodama, Shohta; Okubo, Yoshiaki; Faustman, Denise L.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Kodama, Shohta; Paz, Ana Cristina] Brigham & Womens Hosp, Tissue Engn & Regenerat Med, Boston, MA 02115 USA. [Kodama, Shohta; Gygi, Steven P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Faustman, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Bldg 149,13th St,Room 3602, Charlestown, MA 02129 USA. EM faustman@helix.mgh.harvard.edu RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NIH [HG003456, TGT32DK07028]; The Iacocca Foundation FX This work was funded by the NIH Grants HG003456 (to S.P.G.) and TGT32DK07028 (to D.F.) and The Iacocca Foundation. We thank Dr Miriam Davis for her editing and Ms Lynne Murphy for her secretarial assistance. NR 58 TC 5 Z9 5 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD OCT PY 2010 VL 42 IS 10 BP 1651 EP 1660 DI 10.1016/j.biocel.2009.12.001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 656PZ UT WOS:000282350200014 PM 20005973 ER PT J AU Durazzo, TC Meyerhoff, DJ Nixon, SJ AF Durazzo, Timothy C. Meyerhoff, Dieter J. Nixon, Sara Jo TI Chronic Cigarette Smoking: Implications for Neurocognition and Brain Neurobiology SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE chronic cigarette smoking; neurocognition; neurobiology; neuroimaging; genetics ID CEREBRAL-BLOOD-FLOW; MAGNETIC-RESONANCE SPECTROSCOPY; MIDDLE-AGED ADULTS; BODY-MASS INDEX; MILD COGNITIVE IMPAIRMENT; WHITE-MATTER LESIONS; YOUNG-WOMEN SMOKE; RISK TASK BART; NICOTINE DEPENDENCE; CARDIOVASCULAR HEALTH AB Compared to the substantial volume of research on the general health consequences associated with chronic smoking, little research has been specifically devoted to the investigation of its effects on human neurobiology and neurocognition. This review summarizes the peer-reviewed literature on the neurocognitive and neurobiological implications of chronic cigarette smoking in cohorts that were not seeking treatment for substance use or psychiatric disorders. Studies that specifically assessed the neurocognitive or neurobiological (with emphasis on computed tomography and magnetic resonance-based neuroimaging studies) consequences of chronic smoking are highlighted. Chronic cigarette smoking appears to be associated with deficiencies in executive functions, cognitive flexibility, general intellectual abilities, learning and/or memory processing speed, and working memory. Chronic smoking is related to global brain atrophy and to structural and biochemical abnormalities in anterior frontal regions, subcortical nuclei and commissural white matter. Chronic smoking may also be associated with an increased risk for various forms of neurodegenerative diseases. The existing literature is limited by inconsistent accounting for potentially confounding biomedical and psychiatric conditions, focus on cross-sectional studies with middle aged and older adults and the absence of studies concurrently assessing neurocognitive, neurobiological and genetic factors in the same cohort. Consequently, the mechanisms promoting the neurocognitive and neurobiological abnormalities reported in chronic smokers are unclear. Longitudinal studies are needed to determine if the smoking-related neurobiological and neurocognitive abnormalities increase over time and/or show recovery with sustained smoking cessation. C1 [Durazzo, Timothy C.; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Durazzo, Timothy C.; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Nixon, Sara Jo] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. [Nixon, Sara Jo] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. RP Durazzo, TC (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 505 Parnassus Ave,M-391, San Francisco, CA 94143 USA. EM timothy.durazzo@ucsf.edu; dieter.meyerhoff@ucsf.edu; sjnixon@ufl.edu RI Nixon, Sara/L-1369-2014 OI Nixon, Sara/0000-0003-1179-2851 FU NIH [DA 024136, AA10788, DA 13677, U54 RR025208] FX This material is the result of work supported by NIH DA 024136 (TCD), AA10788 (DJM) and DA 13677 and U54 RR025208 (Nelson, PI; SJN, Co-Investigator) with resources and the use of facilities at the San Francisco Veterans Administration Medical Center, San Francisco, CA, USA. NR 195 TC 69 Z9 70 U1 2 U2 18 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD OCT PY 2010 VL 7 IS 10 BP 3760 EP 3791 DI 10.3390/ijerph7103760 PG 32 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 672IO UT WOS:000283576600011 PM 21139859 ER PT J AU Denninger, JW AF Denninger, John W. TI Group and the Social Brain: Speeding Toward a Neurobiological Understanding of Group Psychotherapy SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Editorial Material ID RELAXATION RESPONSE; NEURAL BASIS; BEHAVIOR; CORTEX; TRUST C1 [Denninger, John W.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Denninger, John W.] Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. [Denninger, John W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Denninger, JW (reprint author), Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, 151 Merrimac St,Suite 400, Boston, MA 02114 USA. EM jdenninger@partners.org NR 20 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 2010 VL 60 IS 4 SI SI BP 595 EP 604 DI 10.1521/ijgp.2010.60.4.595 PG 10 WC Psychology, Clinical SC Psychology GA 656TC UT WOS:000282358500008 PM 21028978 ER PT J AU Ford, JM Roach, BJ Miller, RM Duncan, CC Hoffman, RE Mathalon, DH AF Ford, Judith M. Roach, Brian J. Miller, Ryan M. Duncan, Connie C. Hoffman, Ralph E. Mathalon, Daniel H. TI When it's time for a change: Failures to track context in schizophrenia SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE P300; Schizophrenia; Context ID CONTINGENT NEGATIVE-VARIATION; EVENT-RELATED POTENTIALS; AUDITORY EVOKED-RESPONSE; LATE POSITIVE WAVE; STIMULUS SEQUENCE; P300 AMPLITUDE; MISMATCH NEGATIVITY; BRAIN POTENTIALS; SCALP TOPOGRAPHY; CNV AB Introduction: Reduction of P300 event-related potential amplitude in schizophrenia is perhaps the most replicated biological reflection of the illness. P300 is typically elicited by infrequent deviant events that are imbedded in a series of identical frequent standard events. Deviants have features that explicitly distinguish them from standards, whereas standards can be distinguished from each other based on their local sequential probabilities within the stimulus series. The improbable occurrence of a standard should generate a P300, but only if the implicit local context generated by the recent stimulus history is processed. Method: To assess the ability of schizophrenia patients to process this implicit contextual information, ERPs were elicited from 22 controls and 16 schizophrenia patients during an auditory oddball task containing infrequent target tones (15%) and novel distracter sounds (15%) imbedded pseudo-randomly in a series of standard tones (70%). Consecutively presented standards following deviant stimuli varied in sequential probability from p = 1.0 for the 1st standard to p = 0.16 for the 4th consecutive standard. Results: Patients compared to controls demonstrated smaller P300 (P3a) to the fourth consecutive standard. However, in controls but not patients a contingent negative variation (CNV) was observed prior to the fourth standard, and an N2b/mismatch negativity (MMN) was observed following it. Conclusions: These outcomes suggest that patients are deficient in using the implicit context established by recent stimulus history to anticipate that an otherwise standard stimulus was unlikely and its occurrence unexpected. (C) 2010 Published by Elsevier B.V. C1 [Ford, Judith M.; Roach, Brian J.; Miller, Ryan M.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA 94121 USA. [Ford, Judith M.; Roach, Brian J.; Miller, Ryan M.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Duncan, Connie C.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. [Hoffman, Ralph E.] Yale Univ, Dept Psychiat, Sch Med, New Haven, CT 06520 USA. RP Ford, JM (reprint author), San Francisco VA Med Ctr, Psychiat Serv, 116D,4150 Clement St, San Francisco, CA 94121 USA. EM judith.ford@ucsf.edu OI Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974 FU VA Schizophrenia Biological Research Center; Research Career Scientist; VA Merit Review; NIMH; NARSAD; VA Career Award FX This work was supported by the VA Schizophrenia Biological Research Center (JMF), Research Career Scientist (JMF), VA Merit Review (JMF), NIMH (JMF, DHM, REH), NARSAD (JMF, DHM, REH), VA Career Award (DHM). NR 69 TC 19 Z9 19 U1 4 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD OCT PY 2010 VL 78 IS 1 SI SI BP 3 EP 13 DI 10.1016/j.ijpsycho.2010.05.005 PG 11 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 657IR UT WOS:000282406900002 PM 20580752 ER PT J AU El-Din, MAA Taghian, AG AF El-Din, Mohamed A. Alm Taghian, Alphonse G. TI OPTIMIZING BENEFITS OF LOCAL CONTROL IN BREAST CANCER REPLY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter ID ADJUVANT CHEMOTHERAPY; POSTOPERATIVE RADIOTHERAPY; RADIATION-THERAPY; RANDOMIZED-TRIAL; RISK; IRRADIATION; TAMOXIFEN C1 [El-Din, Mohamed A. Alm; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [El-Din, Mohamed A. Alm] Tanta Univ Hosp, Tanta Fac Med, Tanta, Egypt. RP El-Din, MAA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. NR 9 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2010 VL 78 IS 2 BP 638 EP 638 DI 10.1016/j.ijrobp.2010.03.034 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 654CV UT WOS:000282147000049 ER PT J AU Downes, J Tanner, ACR Dewhirst, FE Wade, WG AF Downes, Julia Tanner, Anne C. R. Dewhirst, Floyd E. Wade, William G. TI Prevotella saccharolytica sp. nov., isolated from the human oral cavity SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID ACIDS AB Two strains of anaerobic, Gram-stain-negative bacilli isolated from the human oral cavity (D033B-12-2(T) and D080A-01) were subjected to a comprehensive range of phenotypic and genotypic tests and were found to be distinct from any previously described species. 16S rRNA gene sequence analysis revealed that the strains were related most closely to the type strain of Prevotella marshii (93.5% sequence identity). The novel strains were saccharolytic and produced acetic acid and succinic acid as end products of fermentation. The principal cellular long-chain fatty acids were C(16:0), iso-C(14:0), C(14:0), anteiso-C(15:0), iso-C(16:0) and C(16:0) 3-OH. The G + C content of the DNA of strain D033B-12-2(T) was 44 mol%. Strains D033B-12-2(T) and D080A-01 are considered to represent a single novel species of the genus Prevotella, for which the name Prevotella saccharolytica sp. nov. is proposed. The type strain is D033B-12-2(T) (=DSM 22473(T) =CCUG 57944(T)). C1 [Downes, Julia; Wade, William G.] Kings Coll London, Kings Coll London Dent Inst Guys, London SE1 9RT, England. [Downes, Julia; Wade, William G.] St Thomas Hosp, Infect Res Grp, London SE1 9RT, England. [Tanner, Anne C. R.; Dewhirst, Floyd E.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Wade, WG (reprint author), Kings Coll London, Kings Coll London Dent Inst Guys, London SE1 9RT, England. EM william.wade@kcl.ac.uk OI Wade, William/0000-0003-2685-826X FU Guy's and St Thomas' Charity [R050724]; US National Institutes of Health [DE015847, DE016937]; Department of Health via the National Institute for Health Research (NIHR); King's College London FX This research was supported by grants from the Guy's and St Thomas' Charity (ref. R050724) and the US National Institutes of Health (DE015847 and DE016937). The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London. NR 19 TC 6 Z9 7 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD OCT PY 2010 VL 60 BP 2458 EP 2461 DI 10.1099/ijs.0.014720-0 PN 10 PG 4 WC Microbiology SC Microbiology GA 675KT UT WOS:000283830300035 PM 19946051 ER PT J AU Wu, J Henderson, C Feun, L Van Veldhuizen, P Gold, P Zheng, H Ryan, T Blaszkowsky, LS Chen, HB Costa, M Rosenzweig, B Nierodzik, M Hochster, H Muggia, F Abbadessa, G Lewis, J Zhu, AX AF Wu, Jennifer Henderson, Charles Feun, Lynn Van Veldhuizen, Peter Gold, Philip Zheng, Hui Ryan, Theresa Blaszkowsky, Lawrence S. Chen, HaoBin Costa, Max Rosenzweig, Barry Nierodzik, MaryLynn Hochster, Howard Muggia, Franco Abbadessa, Giovanni Lewis, Jonathan Zhu, Andrew X. TI Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Darinaparsin; Hepatocellular carcinoma; Clinical trials; Phase II study ID ARSENIC TRIOXIDE; DNA METHYLATION; UNITED-STATES; APOPTOSIS; HEPATOCARCINOGENESIS; CANCER; MICE AB Background Darinaparsin is a novel organic arsenic that reaches higher intracellular concentration with decreased toxicity compared to inorganic arsenic. We conducted a multi-center phase II study with darinaparsin in patients with advanced HCC. Methods Eligibility criteria included unresectable or metastatic measurable HCC, up to two prior systemic treatments, ECOG performance status a parts per thousand currency sign2, Child Pugh Class A or B and adequate organ functions. Darinaparsin was administered at 420 mg/m(2) intravenously, twice weekly at least 72 h apart for 3 weeks in a 4-week cycle. The primary end point was response rate. A Simon two-stage design was used. Results Among 15 patients in the first stage, no objective responses were observed. Two patients had stable disease. The median number of cycles on study per patient was 2 (1-6). The median progression free survival and overall survival were 55 days (95% confidence interval: 50-59) and 190 days (95% confidence interval: 93-227), respectively. No treatment related hospitalizations or deaths occurred. Treatment related grade 1-2 toxicities included nausea, vomiting (26.7% each), fatigue (20%), anorexia and diarrhea (13.3% each). Grade 3 anorexia, wheezing, agitation, abdominal pain and SGPT were observed in 1 patient each (6.7%). One patient experienced grade 4 hypoglycemia (6.7%). Conclusions Darinaparsin could be safely administered with tolerable toxicity profiles, and no QTc prolongation in patients with advanced HCC. However, at this dose and schedule, it has shown no objective responses in HCC and this trial was terminated as planned after the first stage of efficacy analysis. C1 [Wu, Jennifer] NYU, Inst Canc, Bellevue Hosp, New York, NY 10016 USA. [Nierodzik, MaryLynn] NYU, Sch Med, Dept Hematol & Med Oncol, New York, NY 10016 USA. [Rosenzweig, Barry] NYU, Sch Med, Dept Cardiol, New York, NY 10016 USA. [Chen, HaoBin; Costa, Max] NYU, Sch Med, Dept Environm Med, New York, NY 10016 USA. [Blaszkowsky, Lawrence S.; Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Wu, Jennifer; Ryan, Theresa; Hochster, Howard; Muggia, Franco] NYU, Sch Med, Dept Med Oncol, New York, NY 10016 USA. [Henderson, Charles] Piedmont Hosp, Res Inst, Dept Med Oncol, Atlanta, GA USA. [Feun, Lynn] Univ Miami, Hosp & Clin, Dept Med Oncol, Miami, FL USA. [Van Veldhuizen, Peter] Kansas City Vet Adm Med Ctr, Dept Hematol & Med Oncol, Kansas City, MO USA. [Gold, Philip] Swedish Canc Inst Res, Dept Med Oncol, Seattle, WA USA. [Abbadessa, Giovanni; Lewis, Jonathan] Ziopharm Oncol Inc, Res, Boston, MA USA. RP Wu, J (reprint author), NYU, Inst Canc, Bellevue Hosp, BCD 556,462 1st Ave, New York, NY 10016 USA. EM Jennifer.wu@nyumc.org RI costa, max/H-1754-2012; OI Muggia, Franco/0000-0003-0703-9146 NR 32 TC 23 Z9 23 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD OCT PY 2010 VL 28 IS 5 BP 670 EP 676 DI 10.1007/s10637-009-9286-9 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 627UV UT WOS:000280069800015 PM 19565187 ER PT J AU Dumas, S Jacques, V Sun, WC Troughton, JS Welch, JT Chasse, JM Schmitt-Willich, H Caravan, P AF Dumas, Stephane Jacques, Vincent Sun, Wei-Chuan Troughton, Jeffrey S. Welch, Joel T. Chasse, Jaclyn M. Schmitt-Willich, Heribert Caravan, Peter TI High Relaxivity Magnetic Resonance Imaging Contrast Agents Part 1 Impact of Single Donor Atom Substitution on Relaxivity of Serum Albumin-Bound Gadolinium Complexes SO INVESTIGATIVE RADIOLOGY LA English DT Article DE relaxivity; gadolinium; protein binding; water exchange; NMRD ID WATER EXCHANGE-RATE; NEPHROGENIC SYSTEMIC FIBROSIS; ELECTRON-SPIN RELAXATION; GADOLINIUM COMPLEXES; LANTHANIDE(III) COMPLEXES; MACROCYCLIC GADOLINIUM; ENDOR SPECTROSCOPY; RATIONAL DESIGN; PROTEIN-BINDING; GD3+ COMPLEXES AB Rationale and Objectives: The donor atoms that bind to gadolinium in contrast agents influence inner-sphere water exchange and electronic relaxation, both of which determine observed relaxivity. The effect of these molecular parameters on relaxivity is greatest when the contrast agent is protein bound. We sought to determine an optimal donor atom set to yield high relaxivity compounds. Methods: A total of 38 gadolinium-1,4,7,10-tetraazacyclo-dodecane-N, N',N '', N'''-tetraacetato derivatives were prepared and relaxivity was determined in the presence and absence of human serum albumin as a function of temperature and magnetic field. Each compound had a common albumin-binding group and differed only by substitution of different donor groups at one of the macrocycle nitrogens. Oxygen-17 isotope relaxometry at 7.05 T was performed to estimate water exchange rates. Results: Changing a single donor atom resulted in changes in water exchange rates ranging across 3 orders of magnitude. Donor groups increased water exchange rate in the order: phosphonate > phenolate > alpha-substituted acetate > acetate > hydroxamate > sulfonamide > amide > pyridyl > imidazole. Relaxivites at 0.47 and 1.4 T, 37 degrees C, ranged from 12.3 to 55.6 mM(-1)s(-1) and from 8.3 to 32.6 mM(-1)s(-1) respectively. Optimal relaxivities were observed when the donor group was an alpha-substituted acetate. Electronic relaxation was slowest for the acetate derivatives as well. Conclusions: Water exchange dynamics and relaxivity can be predictably tuned by choice of donor atoms. C1 [Caravan, Peter] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. [Dumas, Stephane; Jacques, Vincent; Sun, Wei-Chuan; Troughton, Jeffrey S.; Welch, Joel T.; Chasse, Jaclyn M.; Caravan, Peter] Epix Pharmaceut, Cambridge, MA USA. [Schmitt-Willich, Heribert] Bayer Schering Pharma AG, Berlin, Germany. RP Caravan, P (reprint author), Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp,Dept Radiol, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU National Institutes of Health [R01EB009062, R21EB009738] FX PC acknowledges financial support from the National Institutes of Health through grants R01EB009062 and R21EB009738. NR 60 TC 36 Z9 36 U1 0 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD OCT PY 2010 VL 45 IS 10 BP 600 EP 612 DI 10.1097/RLI.0b013e3181ee5a9e PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 652KL UT WOS:000282005200005 PM 20808235 ER PT J AU Jacques, V Dumas, S Sun, WC Troughton, JS Greenfield, MT Caravan, P AF Jacques, Vincent Dumas, Stephane Sun, Wei-Chuan Troughton, Jeffrey S. Greenfield, Matthew T. Caravan, Peter TI High-Relaxivity Magnetic Resonance Imaging Contrast Agents Part 2 Optimization of Inner- and Second-Sphere Relaxivity SO INVESTIGATIVE RADIOLOGY LA English DT Article DE relaxivity; gadolinium; second-sphere; protein binding; water exchange; NMRD ID PROTON RELAXATION ENHANCEMENT; NEPHROGENIC SYSTEMIC FIBROSIS; ELECTRON-SPIN RELAXATION; HUMAN SERUM-ALBUMIN; WATER EXCHANGE-RATE; MRI CONTRAST; GD3+ COMPLEXES; LANTHANIDE(III) COMPLEXES; GADOLINIUM(III) COMPLEXES; ENDOR SPECTROSCOPY AB Rationale and Objectives: The observed relaxivity of gadolinium-based contrast agents has contributions from the water molecule(s) that bind directly to the gadolinium ion (inner-sphere water), long-lived water molecules and exchangeable protons that make up the second-sphere of coordination, and water molecules that diffuse near the contrast agent (outersphere). Inner-and second-sphere relaxivity can both be increased by optimization of the lifetimes of the water molecules and protons in these coordination spheres, the rotational motion of the complex, and the electronic relaxation of the gadolinium ion. We sought to identify new high-relaxivity contrast agents by systematically varying the donor atoms that bind directly to gadolinium to increase inner-sphere relaxivity and concurrently including substituents that influence the second-sphere relaxivity. Methods: Twenty gadolinium-1,4,7,10-tetraazacyclo-dodecane-N, N', N '', N'''-tetraacetato derivatives were prepared and their relaxivity determined in presence and absence of human serum albumin as a function of temperature and magnetic field. Data was analyzed to extract the underlying molecular parameters influencing relaxivity. Each compound had a common albumin-binding group and an inner-sphere donor set comprising the 4 tertiary amine N atoms from cyclen, an alpha-substituted acetate oxygen atom, 2 amide oxygen atoms, an inner-sphere water oxygen atom, and a variable donor group. Each amide nitrogen was substituted with different groups to promote hydrogen bonding with second-sphere water molecules. Results: Relativities at 0.47 and 1.4 T, 37 degrees C, in serum albumin ranged from 16.0 to 58.1 mM(-1)s(-1) and from 12.3 to 34.8 mM(-1)s(-1), respectively. The reduction of inner-sphere water exchange typical of amide donor groups could be offset by incorporating a phosphonate or phenolate oxygen atom donor in the first coordination sphere, resulting in higher relaxivity. Amide nitrogen substitution with pendant phosphonate or carboxylate groups increased relaxivity by as much as 88% compared with the N-methyl amide analog. Second-sphere relaxivity contributed as much as 24 and 14 mM(-1)s(-1) at 0.47 and 1.4 T, respectively. Conclusions: Water/proton exchange dynamics in the inner-and second-coordination sphere can be predictably tuned by choice of donor atoms and second-sphere substituents, resulting in high-relaxivity agents. C1 [Caravan, Peter] Harvard Univ, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA. [Jacques, Vincent; Dumas, Stephane; Sun, Wei-Chuan; Troughton, Jeffrey S.; Greenfield, Matthew T.; Caravan, Peter] Epix Pharmaceut, Cambridge, MA USA. RP Caravan, P (reprint author), Harvard Univ, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Med Sch, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU National Institutes of Health [R01EB009062, R21EB009738] FX The author (P.C.) acknowledges financial support from the National Institutes of Health through grants R01EB009062 and R21EB009738. NR 64 TC 41 Z9 42 U1 1 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD OCT PY 2010 VL 45 IS 10 BP 613 EP 624 DI 10.1097/RLI.0b013e3181ee6a49 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 652KL UT WOS:000282005200006 PM 20808234 ER PT J AU Hynes, B Margey, R Kiernan, T Ruggiero, NJ Garasic, J Jaff, MR McCann, AB Drachman, DE Schainfeld, R Ansel, GM Rosenfield, K AF Hynes, B. Margey, R. Kiernan, T. Ruggiero, I. I. N. J. Garasic, J. Jaff, M. R. McCann, A. B. Drachman, D. E. Schainfeld, R. Ansel, G. M. Rosenfield, K. TI EARLY EXPERIENCE WITH PTFE-COVERED STENTS FOR RENAL ARTERY IN-STENT RESTENOSIS SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cardiol Res Fdn, Columbus, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD OCT PY 2010 VL 179 SU 10 MA 63 BP S407 EP S407 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 651UY UT WOS:000281953900064 ER PT J AU Margey, R Hynes, B Witzke, C Ruggerio, N Pomerantsev, E Inglessis, I Palacios, IF AF Margey, R. Hynes, B. Witzke, C. Ruggerio, N. Pomerantsev, E. Inglessis, I. Palacios, I. F. TI PERCUTANEOUS LEFT VENTRICULAR ASSIST DEVICE (PLVAD) THERAPY-THE MASSACHUSETTS GENERAL HOSPITAL EXPERIENCE SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Margey, R.; Hynes, B.; Witzke, C.; Ruggerio, N.; Pomerantsev, E.; Inglessis, I.; Palacios, I. F.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD OCT PY 2010 VL 179 SU 10 MA 27 BP S394 EP S394 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 651UY UT WOS:000281953900028 ER PT J AU Margey, R Suh, W Witzke, C Yeh, R Sahkuja, R Seto, A Palacios, IF AF Margey, R. Suh, W. Witzke, C. Yeh, R. Sahkuja, R. Seto, A. Palacios, I. F. TI PERCUTANEOUS PERICARDIAL BIOPSY-A NOVEL INTERVENTIONAL TECHNIQUE TO AID DIAGNOSIS AND MANAGEMENT OF PERICARDIAL DISEASE SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Margey, R.; Suh, W.; Witzke, C.; Yeh, R.; Sahkuja, R.; Seto, A.; Palacios, I. F.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD OCT PY 2010 VL 179 SU 10 MA 7 BP S386 EP S386 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 651UY UT WOS:000281953900008 ER PT J AU Malmstrom, RR Coe, A Kettler, GC Martiny, AC Frias-Lopez, J Zinser, ER Chisholm, SW AF Malmstrom, Rex R. Coe, Allison Kettler, Gregory C. Martiny, Adam C. Frias-Lopez, Jorge Zinser, Erik R. Chisholm, Sallie W. TI Temporal dynamics of Prochlorococcus ecotypes in the Atlantic and Pacific oceans SO ISME JOURNAL LA English DT Article DE Prochlorococcus; Synechococcus; ecotype; time-series; HOT; BATS ID MARINE CYANOBACTERIUM PROCHLOROCOCCUS; LIGHT-INDUCIBLE POLYPEPTIDES; DISSOLVED ORGANIC-MATTER; NORTH-ATLANTIC; SARGASSO SEA; TIME-SERIES; SYNECHOCYSTIS PCC6803; COMMUNITY STRUCTURE; SUBTROPICAL GYRE; SAR11 BACTERIA AB To better understand the temporal and spatial dynamics of Prochlorococcus populations, and how these populations co-vary with the physical environment, we followed monthly changes in the abundance of five ecotypes-two high-light adapted and three low-light adapted-over a 5-year period in coordination with the Bermuda Atlantic Time Series (BATS) and Hawaii Ocean Time-series (HOT) programs. Ecotype abundance displayed weak seasonal fluctuations at HOT and strong seasonal fluctuations at BATS. Furthermore, stable 'layered' depth distributions, where different Prochlorococcus ecotypes reached maximum abundance at different depths, were maintained consistently for 5 years at HOT. Layered distributions were also observed at BATS, although winter deep mixing events disrupted these patterns each year and produced large variations in ecotype abundance. Interestingly, the layered ecotype distributions were regularly reestablished each year after deep mixing subsided at BATS. In addition, Prochlorococcus ecotypes each responded differently to the strong seasonal changes in light, temperature and mixing at BATS, resulting in a reproducible annual succession of ecotype blooms. Patterns of ecotype abundance, in combination with physiological assays of cultured isolates, confirmed that the low-light adapted eNATL could be distinguished from other low-light adapted ecotypes based on its ability to withstand temporary exposure to high-intensity light, a characteristic stress of the surface mixed layer. Finally, total Prochlorococcus and Synechococcus dynamics were compared with similar time series data collected a decade earlier at each location. The two data sets were remarkably similar-testimony to the resilience of these complex dynamic systems on decadal time scales. The ISME Journal (2010) 4, 1252-1264; doi: 10.1038/ismej.2010.60; published online 13 May 2010 C1 [Malmstrom, Rex R.; Coe, Allison; Martiny, Adam C.; Frias-Lopez, Jorge; Zinser, Erik R.; Chisholm, Sallie W.] MIT, Dept Civil & Environm Engn, Cambridge, MA 02139 USA. [Kettler, Gregory C.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Martiny, Adam C.] Univ Calif Irvine, Dept Earth Syst Sci, Irvine, CA USA. [Martiny, Adam C.] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92717 USA. [Frias-Lopez, Jorge] Forsyth Inst, Boston, MA USA. [Zinser, Erik R.] Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA. RP Chisholm, SW (reprint author), MIT, Dept Civil & Environm Engn, 15 Vassar St, Cambridge, MA 02139 USA. EM chisholm@mit.edu RI Malmstrom, Rex/K-7339-2012 FU National Science Foundation, NSF STC Center for Microbial Oceanography: Research and Education; Gordon and Betty Moore Foundation FX We thank Michael Lomas and the BATS team for sample collection at Bermuda, and David Karl, Matthew Church, and the HOT team for sample collection at Hawaii. We also thank Angel White and Ricardo Letelier for assistance with deriving solar flux data and attenuation coefficients. Norm Nelson and David Court generously provided light data from the Bermuda Bio Optics Program. We thank Daniele Veneziano for advice on statistical analysis. This work was funded by grants from the National Science Foundation, NSF STC Center for Microbial Oceanography: Research and Education, and the Gordon and Betty Moore Foundation. NR 70 TC 75 Z9 75 U1 1 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1751-7362 EI 1751-7370 J9 ISME J JI ISME J. PD OCT PY 2010 VL 4 IS 10 BP 1252 EP 1264 DI 10.1038/ismej.2010.60 PG 13 WC Ecology; Microbiology SC Environmental Sciences & Ecology; Microbiology GA 655LB UT WOS:000282250400004 PM 20463762 ER PT J AU Weiner, RB Hutter, AM Wang, F Kim, J Weyman, AE Wood, MJ Picard, MH Baggish, AL AF Weiner, Rory B. Hutter, Adolph M., Jr. Wang, Francis Kim, Jonathan Weyman, Arthur E. Wood, Malissa J. Picard, Michael H. Baggish, Aaron L. TI The Impact of Endurance Exercise Training on Left Ventricular Torsion SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE exercise; left ventricular torsion; mechanics ID TITIN ISOFORM EXPRESSION; CARDIAC STRUCTURE; APICAL ROTATION; AORTIC-STENOSIS; ATHLETES HEART; ECHOCARDIOGRAPHY; STRAINS AB OBJECTIVES We sought to examine the effect of endurance exercise training (EET) on peak systolic left ventricular torsion (LVT) and peak early diastolic untwisting rate (UTR). BACKGROUND Left ventricular (LV) structural adaptations to EET have been well characterized. LVT, a recognized marker of LV function in numerous cardiac diseases, has recently been investigated in the setting of exercise. However, longitudinal data characterizing the impact of sustained exercise training on LVT have not been reported. METHODS A prospective, longitudinal study design examined the impact of a 90-day period of training on LV twist mechanics in university male rowers (n = 15, mean age 18.6 +/- 0.5 years). Conventional LV structural measurements, LV apical and basal rotation, peak systolic LVT, and peak early diastolic UTR were measured by 2-dimensional and speckle tracking echocardiography before and after the EET study period. RESULTS Participants experienced LV eccentric hypertrophy, characterized by increased LV end-diastolic volume (80.8 +/- 8.7 ml/m(2) vs. 91.3 +/- 8.0 ml/m(2), p < 0.001) and LV mass (101.3 +/- 11.4 g/m(2) vs. 115.7 +/- 12.6 g/m(2), p = 0.001). There was a significant increase in peak systolic apical rotation (8.9 +/- 4.2 degrees vs. 12.7 +/- 3.9 degrees, p = 0.002) but no change in basal rotation. This translated into a highly significant increase in peak systolic LVT after EET (14.1 +/- 5.0 degrees vs. 18.0 +/- 3.6 degrees, p = 0.002). The impact of EET on LV twist mechanics was not confined to ventricular systole, as peak early diastolic UTR (-110.6 +/- 41.8 degrees/s vs. 148.0 +/- 29.8 degrees/s, p = 0.003) and the percentage of untwisting that occurred by the end of isovolumic relaxation (31.2 +/- 12.0% vs. 39.9 +/- 14.9%, p = 0.04) increased. CONCLUSIONS Participation in EET was associated with significant changes in LV twist mechanics characterized by increased apical rotation, LVT, and UTR. These findings suggest that LVT and UTR augmentation may be an important and previously unrecognized component of exercise-induced cardiac remodeling. (J Am Coll Cardiol lmg 2010;3:1001-9) (C) 2010 by the American College of Cardiology Foundation C1 [Weiner, Rory B.; Hutter, Adolph M., Jr.; Kim, Jonathan; Weyman, Arthur E.; Wood, Malissa J.; Picard, Michael H.; Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Wang, Francis] Harvard Univ, Univ Hlth Serv, Cambridge, MA 02138 USA. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM rweiner@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 25 TC 49 Z9 49 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD OCT PY 2010 VL 3 IS 10 BP 1001 EP 1009 DI 10.1016/j.jcmg.2010.08.003 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 672ED UT WOS:000283564900002 PM 20947045 ER PT J AU Bhattacharya, D Umbleja, T Carrat, F Chung, RT Peters, MG Torriani, F Andersen, J Currier, JS AF Bhattacharya, Debika Umbleja, T. Carrat, F. Chung, R. T. Peters, M. G. Torriani, F. Andersen, J. Currier, J. S. TI Women Experience Higher Rates of Adverse Events During Hepatitis C Virus Therapy in HIV Infection: A Meta-Analysis SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 16th Conference on Retroviruses and Opportunistic Infections CY FEB 08-11, 2009 CL Montreal, CANADA DE HIV; hepatitis C virus; sex differences; toxicity; drug therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; INITIAL TREATMENT; SEX-DIFFERENCES; INTERFERON-ALPHA-2B; GENDER; TRIAL; COMBINATION; DEPRESSION; EFAVIRENZ AB Background: In HIV/hepatitis C virus (HCV) coinfection, adverse events (AEs) during HCV therapy account for 12%-39% of treatment discontinuations. It is unknown whether sex influences complications. Methods: Meta-analysis to study the effect of sex and other predictors of AEs in 3 randomized trials, ACTG 5071, APRICOT, and ANRSHCO2-RIBAVIC of Interferon (IFN) and Pegylated IFN (PEG), both with and without Ribavirin, in HIV/HCV coinfection. Primary endpoints were AEs requiring treatment discontinuation (AETD) or first dose modification (AEDM). Multi-covariate stratified logistic regression was used to study predictors and assess interactions with sex. Results: Twenty-one percent of 1376 subjects were women; 61% had undetectable HIV RNA; 14% were antiretroviral (ARV) therapy naive at entry; median CD4 was 485 cells per cubicmillimeter. Seventeen percent had an AETD and 50% AEDM; women had more AETD than men (24% vs. 16% P = 0.003) and AEDM (61% vs. 48% P < 0.0001). AETD and AEDM occurred earlier in women; but the types of AETD and AEDM were similar between sexes. Seventy-four percent of AETDs and 49% of AEDMs involved constitutional AEs; 18% of AETD depression; and 26% of AEDM neutropenia. We identified interactions with sex and body mass index (BMI) (P = 0.04, continuous) and nonnucleoside reverse transcriptase inhibitor (P = 0.03); more AETDs were seen in men with lower BMI (P = 0.01) and in women on nonnucleoside reverse transcriptase inhibitors (P = 0.009). More AEDMs were seen with PEG [ odds ratio (OR) = 2.07]; older age (OR = 1.48 per 10 years); decreasing BMI (OR = 1.04 per kg/m(2)); HCV genotype 1, 4 (OR = 1.31); Ishak 5, 6 (OR = 1.42); decreasing Hgb (OR - 1.23 per g/dL); and decreasing absolute neutrophil count (1.04 per 500 cells/mm(3)). Interactions between sex and ARV-naive status (P = 0.001) and zidovudine (P = 0.001) were identified: There were more AEDMs in ARV-naive women (P = 0.06) and ARV-experienced men (P = 0.001) and higher AEDMs in women with zidovudine (P = 0.0002). Conclusions: Although there was no difference in type of AE, AETD and AEDM were more frequent and occurred earlier in women. In women, ARV regimen may be an important predictor of AETDs during HCV therapy and should be explored as a predictor of AEs in HIV/HCV coinfection trials. C1 [Bhattacharya, Debika] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Umbleja, T.; Andersen, J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Carrat, F.] UPMC Paris 6, UMR S 707, Paris, France. [Carrat, F.] St Antoine Hosp, APHP, Paris, France. [Carrat, F.] INSERM, Paris, France. [Chung, R. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Peters, M. G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Torriani, F.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Bhattacharya, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 10833 Le Conte Ave,37-121 CHS, Los Angeles, CA 90095 USA. EM debikab@mednet.ucla.edu OI CARRAT, fabrice/0000-0002-8672-7918 FU NCRR NIH HHS [M01 RR000044, M01 RR000046, M01 RR000096, RR00044, RR00046, RR00096]; NIAID NIH HHS [AI046376, AI068634, AI25868, AI25897, AI27659, AI27661, AI27670, AI27675, AI46370, AI50410, K23 AI066983, K23 AI066983-01A2, K23 AI066983A, K24 AI 56933, K24 AI056933, K24 AI056933-08, P30 AI027763, P30 AI050410, P30-AI27763D, U01 AI025868, U01 AI025897, U01 AI027659, U01 AI027661, U01 AI027670, U01 AI027675, U01 AI046370, U01 AI046376, U01 AI068634, U01 AI069502, UM1 AI068634]; NICHD NIH HHS [5K12HD01400, K12 HD001400, K12 HD001400-02]; NIDDK NIH HHS [DK078772, K24 DK078772, K24 DK078772-01] NR 27 TC 6 Z9 6 U1 1 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 OCT 1 PY 2010 VL 55 IS 2 BP 170 EP 175 DI 10.1097/QAI.0b013e3181e36420 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 658QI UT WOS:000282504100011 PM 20622678 ER PT J AU Estrella, MM Parekh, RS Abraham, A Astor, BC Szczech, LA Anastos, K Dehovitz, JA Merenstein, DJ Pearce, CL Tien, PC Cohen, MH Gange, SJ AF Estrella, Michelle M. Parekh, Rulan S. Abraham, Alison Astor, Brad C. Szczech, Lynda A. Anastos, Kathryn Dehovitz, Jack A. Merenstein, Daniel J. Pearce, C. Leigh Tien, Phyllis C. Cohen, Mardge H. Gange, Stephen J. TI The Impact of Kidney Function at Highly Active Antiretroviral Therapy Initiation on Mortality in HIV-Infected Women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE kidney disease; mortality; HIV; WIHS; antiretroviral therapy ID DISEASE; DEATH; OUTCOMES; LEVEL; RATES; RISK AB Background: In the early highly active antiretroviral therapy (HAART) era, kidney dysfunction was strongly associated with death among HIV-infected individuals. We re-examined this association in the later HAART period to determine whether chronic kidney disease remains a predictor of death after HAART initiation. Methods: To evaluate the effect of kidney function at the time of HAART initiation on time to all-cause mortality, we evaluated 1415 HIV-infected women initiating HAART in the Women's Interagency HIV Study. Multivariable proportional hazards models with survival times calculated from HAART initiation to death were constructed; participants were censored at the time of the last available visit or December 31, 2006. Results: Chronic kidney disease (estimated glomerular filtration rate less than 60 mL/min/1.73 m(2)) at HAART initiation was associated with higher mortality risk adjusting for age, race, hepatitis C serostatus, AIDS history, and CD4(+) cell count (hazard ratio 2.23, 95% confidence interval: 1.45-3.43). Adjustment for hypertension and diabetes history attenuated this association (hazard ratio = 1.89, confidence interval: 0.94-3.80). Lower kidney function at HAART initiation was weakly associated with increased mortality risk in women with prior AIDS (hazard ratio = 1.09, confidence interval: 1.00-1.19, per 20% decrease in estimated glomerular filtration rate). Conclusions: Kidney function at HAART initiation remains an independent predictor of death in HIV-infected individuals, especially in those with a history of AIDS. Our study emphasizes the necessity of monitoring kidney function in this population. Additional studies are needed to determine mechanisms underlying the increased mortality risk associated with chronic kidney disease in HIV-infected persons. C1 [Estrella, Michelle M.] Johns Hopkins Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21205 USA. [Parekh, Rulan S.] Univ Toronto, Div Nephrol, Toronto, ON, Canada. [Parekh, Rulan S.; Abraham, Alison; Astor, Brad C.; Gange, Stephen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Szczech, Lynda A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Anastos, Kathryn] Montefiore Med Ctr, Dept Med, Washington, DC USA. [Dehovitz, Jack A.] SUNY Hlth Sci Ctr, Sch Publ Hlth, Dept Prevent Med & Community Hlth, Washington, DC USA. [Dehovitz, Jack A.] SUNY Hlth Sci Ctr, Sch Publ Hlth, Dept Med, Washington, DC USA. [Merenstein, Daniel J.] Georgetown Univ, Med Ctr, Dept Family Med, Washington, DC 20007 USA. [Pearce, C. Leigh] Univ So Calif, Norris Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, San Francisco, CA USA. [Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cohen, Mardge H.] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA. RP Estrella, MM (reprint author), Johns Hopkins Sch Med, Dept Med, Div Nephrol, 1830 E Monument St,Suite 416, Baltimore, MD 21205 USA. EM mestrel1@jhmi.edu OI Gange, Stephen/0000-0001-7842-512X FU [UO1-AI-35004]; [UO1-AI-31834]; [UO1-AI-34994]; [UO1-AI-34989]; [UO1-AI-34993]; [UO1-AI-42590]; [UO1-HD-32632]; [UL1 RR024131]; [1K23-DK-081317-01A1]; [5U01DK070657-03]; [1R01-DK-072367]; [R01-DK-07677001]; [R21-DK078218-01A1]; [R01-DK-080094-02] FX The WIHS is funded by UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590, UO1-HD-32632, and UL1 RR024131. Additional support came from 1K23-DK-081317-01A1 to MME, 5U01DK070657-03 and 1R01-DK-072367 to RSP, R01-DK-07677001 and R21-DK078218-01A1 to BCA, and R01-DK-080094-02 to LAS. NR 17 TC 25 Z9 27 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2010 VL 55 IS 2 BP 217 EP 220 DI 10.1097/QAI.0b013e3181e674f4 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 658QI UT WOS:000282504100018 PM 20581688 ER PT J AU Ghotb, A Noworolski, SM Madden, E Scherzer, R Qayyum, A Pannell, J Ferrell, L Peters, M Tien, PC AF Ghotb, Alireza Noworolski, Susan M. Madden, Erin Scherzer, Rebecca Qayyum, Aliya Pannell, Jane Ferrell, Linda Peters, Marion Tien, Phyllis C. TI Adipose Tissue and Metabolic Factors Associated With Steatosis in HIV/HCV Coinfection: Histology Versus Magnetic Resonance Spectroscopy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adipose tissue; HIV; HCV; insulin resistance; magnetic resonance spectroscopy; steatosis ID HEPATITIS-C-VIRUS; HIV-INFECTED PATIENTS; HCV GENOTYPE; LIVER; PREVALENCE; FIBROSIS AB Background: Hepatic steatosis is common in persons with HIV and hepatitis C virus (HCV); yet biopsy measurement of steatosis is prone to sampling error. We compared magnetic resonance spectroscopy (MRS) measurement of steatosis to histology in HIV/HCV-coinfected patients and explored the associated adipose tissue and metabolic factors. Methods: Cross-sectional analysis of 42 HIV/HCV-coinfected men and women. Logistic regression analysis identified factors (MRI-measured visceral adipose tissue and abdominal subcutaneous adipose tissue and Homeostasis Model Assessment-estimated insulin resistance) associated with histologic steatosis (>= 5% of hepatocytes with fat) and MRS steatosis (>= 5% of hepatic fat). Results: MRS steatosis was strongly associated with histologic steatosis, when measured continuously (odds ratio: 10.2 per doubling of MRS-measured hepatic fat; 95% confidence interval: 2.9 to 69.3) and dichotomously (Kappa coefficient = 0.52; P = 0.0007). Four of the 10 with MRS-measured steatosis did not have histologic steatosis; 3 of 9 with histologic steatosis did not have MRS-measured steatosis (67% sensitivity; 88% specificity). Associations of visceral adipose tissue and abdominal subcutaneous adipose tissue were associated with both histologic and MRS-measured steatosis. Insulin resistance was also associated with both. Conclusions: When compared with histology, MRS was similarly associated with adipose tissue and metabolic factors. MRS is a useful noninvasive alternative to biopsy in HIV/HCV coinfection. C1 [Tien, Phyllis C.] Univ Calif San Francisco, VAMC, Infect Dis Sect, Dept Med, San Francisco, CA 94121 USA. [Scherzer, Rebecca; Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ghotb, Alireza] Calif Pacific Med Ctr, Dept Med, San Francisco, CA USA. [Noworolski, Susan M.; Qayyum, Aliya] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94121 USA. [Madden, Erin] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94121 USA. [Pannell, Jane] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94121 USA. [Ferrell, Linda] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94121 USA. RP Tien, PC (reprint author), Univ Calif San Francisco, VAMC, Infect Dis Sect, Dept Med, 111W,4150 Clement St, San Francisco, CA 94121 USA. EM ptien@ucsf.edu FU UCSF Hellman Early Career Faculty Award; National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources [UL1 RR024131]; [K23 AI-66943]; [P01 HD-40543]; [UO1 AI-34989]; [M01 RR-00083] FX Supported in part by grants K23 AI-66943, P01 HD-40543, UO1 AI-34989, M01 RR-00083, and the UCSF Hellman Early Career Faculty Award.; The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). NR 15 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2010 VL 55 IS 2 BP 228 EP 231 DI 10.1097/QAI.0b013e3181e1d963 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 658QI UT WOS:000282504100021 PM 20512045 ER PT J AU Goodrich, DE Lai, ZS Lasky, E Burghardt, AR Kilbourne, AM AF Goodrich, David E. Lai, Zongshan Lasky, Elaine Burghardt, Amy R. Kilbourne, Amy M. TI Access to weight loss counseling services among patients with bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar disorder; Weight loss; Physical activity; Nutritional counseling; Atypical; Antipsychotics; Service access ID CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; UNITED-STATES; SCHIZOPHRENIA; HEALTH; RISK; COMORBIDITY; OBESITY; CARE; INDIVIDUALS AB Background: Cardiovascular disease is the leading cause of mortality in persons with bipolar disorder but little is known about utilization of services for risk reduction. We assessed determinants of access to weight counseling in a sample of patients with bipolar disorder. Methods: Patients enrolled in the Continuous Improvement for Veterans in Care: Mood Disorders (CIVIC-MD), a prospective study conducted from July 2004-July 2006. Patient data were obtained from a baseline questionnaire and chart review. Results: Out of 298 patients, 73% received some weight counseling, with utilization more likely for those with higher BMI (OR = 1.12, p<0.001) or prescribed a second generation antipsychotic (SGA) (OR = 1.80, p = 0.05). About 41% received 2 >= dietary consultations with consults more likely for those reporting illicit substance use (OR = 1.9, p<0.05) or SGA treatment (OR = 2.4, p<0.05). In approximately 25% of patients, increased BMI (OR = 1.06, p = 0.04) and SGA treatment (OR = 2.13, p = 0.04) were associated with greater likelihood of receiving >= 2 exercise consultations. Zero-inflated Poisson regression found SGA treatment was associated with more diet consultations (beta = 35, p<0.05) while SGA treatment (beta = 29, p<0.05) and women (beta = 76, p<0.001) were associated with more exercise consultations. Illicit substance use (beta = -0.36, p<0.05), binge drinking (beta = 32, p<0.05) and other ethnicity (beta = -0.57, p<0.05) were associated with fewer exercise consults. Limitations: Single-site study and limited chart detail. Conclusion: The majority of patients received some weight counseling, with obesity and SGA predicting service use over time. However, low utilization patterns underscore the need for research into determinants of long-term counseling utilization to improve patient health outcomes. Published by Elsevier B.V. C1 [Goodrich, David E.; Kilbourne, Amy M.] VA Ann Arbor Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. [Lasky, Elaine] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Lai, Zongshan; Burghardt, Amy R.; Kilbourne, Amy M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Kilbourne, AM (reprint author), VA Ann Arbor HSR&D 11H,2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM amykilbo@umich.edu OI Goodrich, David/0000-0003-3232-2189 FU Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development Service [IIR 02-283-2, 02-283]; National Institutes of Health [R34 MH74509] FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (IIR 02-283-2; A. Kilbourne, PI) and the National Institutes of Health (R34 MH74509; A. Kilbourne, PI). The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.; This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (02-283) and the National Institute of Mental Health (MH 74509). NR 26 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2010 VL 126 IS 1-2 BP 75 EP 79 DI 10.1016/j.jad.2010.02.138 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 658KD UT WOS:000282488000009 PM 20381155 ER PT J AU Kikura, M Bateman, BT Tanaka, KA AF Kikura, Mutsuhito Bateman, Brian T. Tanaka, Kenichi A. TI Perioperative ischemic stroke in non-cardiovascular surgery patients SO JOURNAL OF ANESTHESIA LA English DT Review DE Ischemic stroke; Cerebral infarction; Perioperative; Non-cardiovascular surgery; Anticoagulant therapy ID ACUTE THROMBOEMBOLISM SYNDROME; PERIPHERAL VASCULAR-SURGERY; RISK-FACTORS; SURGICAL-PROCEDURES; CARDIAC-SURGERY; ANESTHESIA; DEXMEDETOMIDINE; DYSFUNCTION; HEMOSTASIS; MECHANISMS AB Perioperative ischemic stroke occurs in approximately 0.08-0.7% of patients after non-cardiovascular surgery and confers a significant risk of morbidity and mortality. The mortality rate of this major complication is similar in non-cardiovascular and cardiovascular surgery. Its incidence appears to be similar in Japan, Europe, and the United States. Perioperative physicians should be aware of the pathophysiology and predictors of ischemic stroke, and the anti-thrombotic strategies to prevent it. The main causes of perioperative ischemic stroke include cerebral atherothrombosis; lacuna stroke; cardiac thrombi due to atrial fibrillation; dehydration; hypotension; and perioperative systemic hypercoagulability. Perioperative management includes detailed informed consent regarding potential stroke risks, counseling, careful surgical treatment decisions, and identification of the high-risk patient for perioperative antithrombotic strategies. The 2009 Japanese guidelines for the management of stroke recommend using the appropriate intravenous infusions to avoid dehydration and consideration of anticoagulation in the patients who are at high risk for thrombosis and embolism while antithrombotic agents are discontinued. Understanding how to prevent perioperative ischemic stroke remains a challenge. In this article, we review the incidence, timing of the occurrence, mortality, risk factors, and pathophysiology of perioperative ischemic stroke in the non-cardiovascular surgery patient. C1 [Kikura, Mutsuhito] Hamamatsu Med Ctr, Dept Anesthesiol, Hamamatsu, Shizuoka 4328580, Japan. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Tanaka, Kenichi A.] Emory Univ, Sch Med, Dept Anesthesiol, Atlanta, GA 30322 USA. RP Kikura, M (reprint author), Hamamatsu Med Ctr, Dept Anesthesiol, 328 Tomizuka, Hamamatsu, Shizuoka 4328580, Japan. EM mkikura@hotmail.com NR 30 TC 15 Z9 17 U1 0 U2 3 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0913-8668 J9 J ANESTH JI J. Anesth. PD OCT PY 2010 VL 24 IS 5 BP 733 EP 738 DI 10.1007/s00540-010-0969-3 PG 6 WC Anesthesiology SC Anesthesiology GA 661CU UT WOS:000282701400012 PM 20549522 ER PT J AU Moscovitch, DA Suvak, MK Hofmann, SG AF Moscovitch, David A. Suvak, Michael K. Hofmann, Stefan G. TI Emotional response patterns during social threat in individuals with generalized social anxiety disorder and non-anxious controls SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Social phobia; Social anxiety; Emotion; Skin conductance; Heart rate; Negative affect; Positive affect ID DSM-IV ANXIETY; NEGATIVE AFFECT; PSYCHOLOGICAL CONSTRUCTION; DIFFERENTIAL-DIAGNOSIS; MOOD DISORDERS; CORE AFFECT; PHOBIA; FEAR; IMAGERY; SELF AB Patterns of synchrony in repeated measures of heart rate, skin conductance levels, negative affect, and positive affect were investigated in patients with social anxiety disorder and non-anxious controls during a speech task. Despite expected low levels of absolute concordance between measures of affect and arousal overall, results revealed clearly defined and specific patterns of emotional response coherence that distinguished between the two groups and depended on the types of measures used. Specifically, findings demonstrated that (a) for both patients and controls, increased heart rate was significantly synchronized with increased negative affect, with patients showing overall stronger levels of synchrony between these two measures than controls; (b) for controls only, increased heart rate was significantly synchronized with increased positive affect: and (c) for patients only, increased skin conductance was significantly synchronized with both increased negative affect and decreased positive affect. These findings are discussed in relation to current conceptualizations of the construct of emotion as well as directions for future research and potential implications for clinical practice. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Moscovitch, David A.] Univ Waterloo, Dept Psychol, Waterloo, ON N2L 3G1, Canada. [Suvak, Michael K.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Hofmann, Stefan G.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Moscovitch, DA (reprint author), Univ Waterloo, Dept Psychol, 200 Univ Ave W, Waterloo, ON N2L 3G1, Canada. EM dmosco@uwaterloo.ca RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 52 TC 16 Z9 17 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD OCT PY 2010 VL 24 IS 7 BP 785 EP 791 DI 10.1016/j.janxdis.2010.05.013 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 643UT UT WOS:000281325600019 PM 20708493 ER PT J AU Wongviriyawong, C Winkler, T Harris, RS Venegas, JG AF Wongviriyawong, Chanikarn Winkler, Tilo Harris, R. Scott Venegas, Jose G. TI Dynamics of tidal volume and ventilation heterogeneity under pressure-controlled ventilation during bronchoconstriction: a simulation study SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE tidal volume sensitivity; modeling; ventilation distribution; asthma ID AIRWAY SMOOTH-MUSCLE; SELF-ORGANIZED PATCHINESS; CATASTROPHIC SHIFTS; MORPHOMETRY; ASTHMA; MODEL; LUNG; PET AB The difference in effectiveness between volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) on mechanically ventilated patients during bronchoconstriction is not totally clear. PCV is thought to deliver a more uniform distribution of ventilation than VCV, but the delivered tidal volume could be unstable and affected by changes in the degree of constriction. To explore the magnitude of these effects, we ran numerical simulations with both modes of ventilation in a network model of the lung in which we incorporated not only the pressure and flow dynamics along the airways but also the effect of cycling pressures and tissue tethering forces during breathing on the dynamic equilibrium of the airway smooth muscle (ASM) (Venegas et al., Nature 434: 777-782). These simulations provided an illustration of changes in airway radii, the total delivered tidal volume stability, and distribution of ventilation following a transition from VCV to PCV and during progressively increasing ASM activation level. These simulations yielded three major results. First, the ventilation heterogeneity and patchiness in ventilation during steady-state VCV were substantially reduced after the transition to PCV. Second, airway radius, tidal volume, and the distribution of ventilation under severe bronchoconstriction were highly sensitive to the setting of inspiratory pressure selected for PCV and to the degree of activation of the ASM. Third, the dynamic equilibrium of active ASM exposed to cycling forces is the major contributor to these effects. These insights may provide a theoretical framework to guide the selection of ventilation mode, the adjustment of ventilator settings, and the interpretation of clinical observations in mechanically ventilated asthmatic patients. C1 [Wongviriyawong, Chanikarn; Winkler, Tilo; Harris, R. Scott; Venegas, Jose G.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Sch Med, Boston, MA 02114 USA. [Wongviriyawong, Chanikarn] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Wongviriyawong, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Sch Med, Thier 515,55 Fruit St, Boston, MA 02114 USA. EM minto@mit.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU National Heart, Lung, and Blood Institute [HL-068011, HL-087281] FX This work was funded by National Heart, Lung, and Blood Institute Grants HL-068011 and HL-087281. NR 22 TC 6 Z9 8 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD OCT PY 2010 VL 109 IS 4 BP 1211 EP 1218 DI 10.1152/japplphysiol.01401.2009 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 695BF UT WOS:000285344900035 PM 20671035 ER PT J AU Roque, PJ Mankin, HJ Malchau, H AF Roque, Pedro J. Mankin, Henry J. Malchau, Henrik TI Proximal Femoral Allograft: Prognostic Indicators SO JOURNAL OF ARTHROPLASTY LA English DT Article DE proximal femur; allograft; tumors; outcome ID TERM FOLLOW-UP; BONE-TUMORS; PROSTHESIS COMPOSITE; ADJUVANT CHEMOTHERAPY; LIMB-SALVAGE; RECONSTRUCTION; LONG; REPLACEMENT; FEMUR; END AB Between 1972 and 1999, the Orthopedic Oncology Service treated 150 patients with resection and allograft transplantation of the proximal femur. Of the group, 121 patients had malignant tumors of the proximal femur and 29 had benign disorders. Four types of allografts were used: osteoarticular (46 patients), allograft-prosthesis (73), intercalary (20), and allograft-arthrodesis (5). Only 16% of the patients died of disease and 3% required amputation. The overall success rate for the series was 77% with the best results for the allograft prosthetic (82%) and intercalary procedures (87%). Graft infection (15 patients), allograft fracture (26 patients), and local recurrence (11 patients) most markedly affected outcome. With the exception of deaths of disease, no significant outcome difference occurred between the patients with malignant and benign disorders. In conclusion, allograft implantation especially for aggressive or malignant tumors of the proximal femur appears to be a competent system for therapy. C1 [Mankin, Henry J.] Massachusetts Gen Hosp, Orthoped Oncol Serv, Boston, MA 02114 USA. [Malchau, Henrik] Massachusetts Gen Hosp, Orthoped Hip & Implant Serv, Boston, MA 02114 USA. [Roque, Pedro J.] Harvard Univ, Sch Med, Oliver Wendell Holmes Soc Mentee Program, Boston, MA USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthoped Serv, 1122A Jackson Bldg, Boston, MA 02114 USA. NR 44 TC 4 Z9 4 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2010 VL 25 IS 7 BP 1028 EP 1033 DI 10.1016/j.arth.2009.07.018 PG 6 WC Orthopedics SC Orthopedics GA 669FR UT WOS:000283333800004 PM 19879727 ER PT J AU Black, HL Priolo, C Akinyemi, D Gonzalez, R Jackson, DS Garcia, L George, M Apter, AJ AF Black, Heather L. Priolo, Chantel Akinyemi, D'Jahna Gonzalez, Rodalyn Jackson, Danielle S. Garcia, Laura George, Maureen Apter, Andrea J. TI Clearing Clinical Barriers: Enhancing Social Support Using a Patient Navigator for Asthma Care SO JOURNAL OF ASTHMA LA English DT Article DE Asthma; barriers; communication; control; patient navigator; self-management ID DISPARITIES; ADULTS; INTERVENTION; MANAGEMENT; ADHERENCE; NUMERACY; OUTCOMES; QUALITY; SYSTEM; WOMEN AB Background. Patients with moderate or severe asthma, particularly those who are minority or poor, often encounter significant personal, clinical practice, and health system barriers to accessing care. Objective. To explore the ideas of patients and providers for potentially feasible, individualized, cost-effective ways to reduce obstacles to care by providing social support using a patient advocate or navigator. Methods. The authors conducted four focus groups of adults with moderate or severe asthma. Participants were recruited from clinics serving low-income and minority urban neighborhoods. Data from these patient focus groups were shared with two additional focus groups, one of nurses and one of physicians. Researchers independently coded and agreed upon themes from all focus groups, which were categorized by types of social support: instrumental (physical aid), informational (educational), emotional (empathizing), validation (comparisons to others). Results. Patients and providers agreed that a patient navigator could help patients manage asthma by giving social support. Both groups found instrumental and informational support most important. However, patients desired more instrumental help whereas providers focused on informational support. Physicians stressed review of medical information whereas patients wanted information to complete administrative tasks. Providers and patients agreed that the patient navigator's role in asthma would need to address both short-term care of exacerbations and enhance long-term chronic self-management by working with practice personnel. Conclusions. Along with medical information, there is a need for providers to connect patients to instrumental support relevant to acute and long-term asthma-self-management. C1 [Black, Heather L.; Priolo, Chantel; Akinyemi, D'Jahna; Gonzalez, Rodalyn; Jackson, Danielle S.; Garcia, Laura; Apter, Andrea J.] Univ Penn, Div Pulm Allergy & Crit Care Med, Sect Allergy & Immunol, Philadelphia, PA 19104 USA. [George, Maureen] Univ Penn, Sch Nursing, Family & Community Hlth Div, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. RP Apter, AJ (reprint author), Hosp Univ Penn, 829 Gates Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. EM apter@mail.med.upenn.edu FU [HL073932]; [HL088469]; [HL099612]; [K23AT003907] FX This work is support by grants HL073932, HL088469, and HL099612 (A. Apter); HL073932, HL099612 (C. Priolo, L. Garcia, R. Gonzalez, D. Jackson); and K23AT003907 (M. George). NR 33 TC 11 Z9 12 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PD OCT PY 2010 VL 47 IS 8 BP 913 EP 919 DI 10.3109/02770903.2010.506681 PG 7 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 658VB UT WOS:000282516400012 PM 20846085 ER PT J AU Sills, MR Ginde, AA Clark, S Camargo, CA AF Sills, Marion R. Ginde, Adit A. Clark, Sunday Camargo, Carlos A., Jr. TI Multicenter Study of Chronic Asthma Severity Among Emergency Department Patients With Acute Asthma SO JOURNAL OF ASTHMA LA English DT Article DE adolescent; antiasthmatic agents; asthma; asthma (epidemiology); asthma (prevention and control); child; practice guideline; preschool child; severity of illness index ID INHALED CORTICOSTEROIDS; CHILDREN; CARE; MANAGEMENT; GUIDELINES; CLASSIFICATION; PREVENTION; EDUCATION; PROGRAM; ALLIES AB Objective. The initiation of controller therapy for asthma depends on chronic asthma severity. To facilitate initiation of inhaled corticosteroids (ICSs), the preferred controller therapy, in the emergency department (ED), the objective of the study was to describe chronic asthma severity, as defined by the national asthma guidelines, among children presenting to the ED with acute asthma. Methods. Investigators at 14 U. S. sites prospectively enrolled consecutive children 2-17 years presenting to the ED with acute asthma. Three factors (daytime symptoms, nighttime symptoms, and medication usage) were used to categorize children into four chronic asthma severity groups: intermittent, mild persistent, moderate persistent or severe persistent. Results. This multistate cohort of 311 children had a mean age of 7.7 years, was 51% Black, and 89% had a primary care provider (PCP). Regarding chronic severity, 18% were intermittent and 82% persistent: 37% mild persistent, 24% moderate persistent, and 20% severe persistent. Chronic severity groups did not differ by demographics or PCP status. Patients with persistent asthma were more likely to report moderate-severe asthma symptoms (58% versus 19%; p < .001), poor asthma control (2% versus 18%; p = .002), and more ED visits (median, 2 versus 1; p < .001) in the past year. The groups did not differ in acute asthma severity, ED treatment, or admission rate. Rate of discharge prescription for ICSs was low, albeit higher among children with persistent asthma (24% versus 4%; p = .003). Conclusions. The high prevalence of persistent asthma among ED patients exceeds the prevalence reported previously, and supports ED initiation of ICS, as recommended by national guidelines. C1 [Camargo, Carlos A., Jr.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Sills, Marion R.] Univ Colorado Sch Med, Dept Pediat, Aurora, CO USA. [Ginde, Adit A.] Univ Colorado Sch Med, Dept Emergency Med, Aurora, CO USA. [Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. RP Camargo, CA (reprint author), Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@part-ners.org RI Webster, Susan/C-7360-2015; Siry, Bonnie/D-7189-2017; OI Webster, Susan/0000-0002-0684-4226; Sills, Marion/0000-0003-1322-0822 FU AHRQ [R03 HS016418]; NIH [KL2 RR025779, HL-03533, HL-63253]; GlaxoSmithKline (Research Triangle Park, NC); AstraZeneca; Critical Therapeutics; Dey; Genentech; GSK; Merck; Novartis; Respironics; Sanofi-Aventis; Schering-Plough FX Dr. Sills was supported by AHRQ grant R03 HS016418; Dr. Ginde by NIH grant KL2 RR025779; and Dr. Camargo by NIH grant HL-03533. The Multicenter Airway Research Collaboration was supported by NIH grant HL-63253, and by an unrestricted grant from GlaxoSmithKline (Research Triangle Park, NC).; Dr. Camargo has received financial support from a variety of groups for participation in conferences, consulting, and investigator-initiated medical research. During 2007 to 2009, industry sponsors with an interest in asthma were AstraZeneca, Critical Therapeutics, Dey, Genentech, GSK, Merck, Novartis, Respironics, Sanofi-Aventis, and Schering-Plough. Drs. Sills, Ginde, and Clark do not report any potential conflicts of interest. NR 27 TC 5 Z9 5 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PD OCT PY 2010 VL 47 IS 8 BP 920 EP 928 DI 10.3109/02770903.2010.504878 PG 9 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 658VB UT WOS:000282516400013 PM 20831467 ER PT J AU Dewhirst, FE Chen, T Izard, J Paster, BJ Tanner, ACR Yu, WH Lakshmanan, A Wade, WG AF Dewhirst, Floyd E. Chen, Tuste Izard, Jacques Paster, Bruce J. Tanner, Anne C. R. Yu, Wen-Han Lakshmanan, Abirami Wade, William G. TI The Human Oral Microbiome SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RIBOSOMAL-RNA ANALYSIS; GEN. NOV.; MOLECULAR ANALYSIS; BACTEROIDES-UREOLYTICUS; PERIODONTAL INFECTIONS; BACTERIAL DIVERSITY; SUBGINGIVAL PLAQUE; ADULT HUMANS; COMB. NOV; DISEASE AB The human oral cavity contains a number of different habitats, including the teeth, gingival sulcus, tongue, cheeks, hard and soft palates, and tonsils, which are colonized by bacteria. The oral microbiome is comprised of over 600 prevalent taxa at the species level, with distinct subsets predominating at different habitats. The oral microbiome has been extensively characterized by cultivation and culture-independent molecular methods such as 16S rRNA cloning. Unfortunately, the vast majority of unnamed oral taxa are referenced by clone numbers or 16S rRNA GenBank accession numbers, often without taxonomic anchors. The first aim of this research was to collect 16S rRNA gene sequences into a curated phylogeny-based database, the Human Oral Microbiome Database (HOMD), and make it web accessible (www.homd.org). The HOMD includes 619 taxa in 13 phyla, as follows: Actinobacteria, Bacteroidetes, Chlamydiae, Chloroflexi, Euryarchaeota, Firmicutes, Fusobacteria, Proteobacteria, Spirochaetes, SR1, Synergistetes, Tenericutes, and TM7. The second aim was to analyze 36,043 16S rRNA gene clones isolated from studies of the oral microbiota to determine the relative abundance of taxa and identify novel candidate taxa. The analysis identified 1,179 taxa, of which 24% were named, 8% were cultivated but unnamed, and 68% were uncultivated phylotypes. Upon validation, 434 novel, nonsingleton taxa will be added to the HOMD. The number of taxa needed to account for 90%, 95%, or 99% of the clones examined is 259, 413, and 875, respectively. The HOMD is the first curated description of a human-associated microbiome and provides tools for use in understanding the role of the microbiome in health and disease. C1 [Dewhirst, Floyd E.; Chen, Tuste; Izard, Jacques; Paster, Bruce J.; Tanner, Anne C. R.; Yu, Wen-Han; Lakshmanan, Abirami; Wade, William G.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Dewhirst, Floyd E.; Izard, Jacques; Paster, Bruce J.; Tanner, Anne C. R.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Wade, William G.] Kings Coll London, Dent Inst Guys, London SE1 9RT, England. [Wade, William G.] St Thomas Hosp, Infect Res Grp, London SE1 9RT, England. RP Dewhirst, FE (reprint author), Forsyth Inst, Dept Mol Genet, 245 1st St, Cambridge, MA 02142 USA. EM fdewhirst@forsyth.org RI Izard, Jacques/A-6074-2012; OI Izard, Jacques/0000-0002-5904-5436; Wade, William/0000-0003-2685-826X FU National Institute of Dental and Craniofacial Research [U01 DE016937, DE015847, DE017106]; American Recovery and Reinvestment Act of 2009 [DE016937] FX This work has been supported in part by contract U01 DE016937 and grants DE015847 and DE017106 from the National Institute of Dental and Craniofacial Research and a supplement to grant DE016937 from the American Recovery and Reinvestment Act of 2009. NR 70 TC 613 Z9 631 U1 44 U2 236 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 2010 VL 192 IS 19 BP 5002 EP 5017 DI 10.1128/JB.00542-10 PG 16 WC Microbiology SC Microbiology GA 650QW UT WOS:000281866900022 PM 20656903 ER PT J AU Takahashi, TA Maciejewski, ML Bradley, K AF Takahashi, Traci A. Maciejewski, Matthew L. Bradley, Katharine TI US Hospitalizations and Costs for Illicit Drug Users with Soft Tissue Infections SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; SAN-FRANCISCO; INJECTION; CARE; EMERGENCY; ABSCESSES; ABUSE; SKIN; ACCIDENT AB Skin and soft tissue infections (SSTIs) are common complications of illicit drug use. Studies at single, urban hospitals demonstrate high rates of emergency department visits and hospitalizations for these infections. This study sought to estimate nationwide and regional incidence and costs of hospitalizations for illicit drug users with SSTIs in the US. AHRQ's Nationwide Inpatient Sample was used to conduct a retrospective cross-sectional, time-series study. Hospitalizations of illicit drug users with SSTIs were identified using International Classification of Diseases, 9th Revision Clinical Modification codes. An estimated 106,126 hospitalizations for illicit drug users with SSTIs represented 0.07% of all US non-Federal hospitalizations from 1998 to 2001 and cost over 193 million dollars in 2001. Higher rates of hospitalization were found in the West, Northeast, and urban teaching hospitals. Hospitalization rates for illicit drug users with SSTIs vary significantly according to US region. Resources to reduce the incidence and severity of these infections should be targeted accordingly. C1 [Takahashi, Traci A.; Bradley, Katharine] VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA 98108 USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Bradley, Katharine] Univ Washington, Sch Med, Seattle, WA USA. RP Takahashi, TA (reprint author), VA Puget Sound Hlth Care Syst, HSR&D, 1660 S ColumbianWay,S-111 PCC, Seattle, WA 98108 USA. EM traci@u.washington.edu; matthew.maciejewski@va.gov; katharine.bradley@va.gov FU NIDA NIH HHS [R03DA14518] NR 27 TC 8 Z9 8 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD OCT PY 2010 VL 37 IS 4 BP 508 EP 518 DI 10.1007/s11414-009-9177-z PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 652YA UT WOS:000282047300008 PM 19381818 ER PT J AU Juppner, H Wolf, M Salusky, IB AF Jueppner, Harald Wolf, Myles Salusky, Isidro B. TI FGF-23: More Than a Regulator of Renal Phosphate Handling? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE PTH; 1,25(OH)(2)D(3); FGF-23; PHOSPHATE HOMEOSTASIS; CHRONIC KIDNEY DISEASE; BONE MINERALIZATION; CARDIOVASCULAR DISEASE ID FIBROBLAST GROWTH FACTOR-23; CHRONIC KIDNEY-DISEASE; FAMILIAL TUMORAL CALCINOSIS; HYPOPHOSPHATEMIA IN-VIVO; VITAMIN-D; HEMODIALYSIS-PATIENTS; INDUCED OSTEOMALACIA; MINERAL METABOLISM; DIETARY PHOSPHATE; DIALYSIS PATIENTS AB Fibroblast growth factor 23 (FGF-23) is likely to be the most important regulator of phosphate homeostasis, which mediates its functions through FGF receptors and the coreceptor Klotho. Besides reducing expression of the sodium-phosphate cotransporters NPT2a and NPT2c in the proximal tubules, FGF-23 inhibits the renal 1 alpha-hydroxylase and stimulates the 24-hydroxylase, and it appears to reduce parathyroid hormone (PTH) secretion in short-term studies. FGF-23 synthesis and secretion by osteocytes and osteoblasts is upregulated through 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and through an increased dietary phosphate intake. FGF-23 levels are elevated or inappropriately normal in patients with tumor-induced osteomalacia and several inherited hypophosphatemic disorders, but the most significant increases are found in patients with chronic kidney disease (CKD). During the early stages of CKD, increased FGF-23 production enhances urinary phosphate excretion and thus prevents the development of hyperphosphatemia, reduces the circulating levels of 1,25(OH)(2)D(3), and therefore contributes to the development of secondary hyperparathyroidism. In patients with end-stage renal disease (ESRD), FGF-23 levels can be extremely high and were shown to be predictors of bone mineralization, left ventricular hypertrophy, vascular calcification, and mortality. It remains to be determined, however, whether FGF-23 represents simply a sensitive biomarker of an abnormal phosphate homeostasis or has, independent of serum phosphate levels, potentially negative "off-target" effects. Nonetheless, reducing the production and/or the biologic activity of FGF-23 may be an important therapeutic goal for this patient population. (C) 2010 American Society for Bone and Mineral Research. C1 [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. [Salusky, Isidro B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Nephrol, Dept Pediat, Los Angeles, CA 90095 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM hjueppner@partners.org FU NIH [PO1 DK11794, R01DK076116, R01DK081374, RO1DK35423, RO1DK67563, RR00865] FX We would like to thank Dr Takashi Shimada for his insightful comments made during the preparation of this paper. This study was supported by grants from the NIH (PO1 DK11794, Project IV to HJ, R01DK076116 and R01DK081374 to MW, and RO1DK35423, RO1DK67563, and RR00865 to IBS). NR 76 TC 79 Z9 81 U1 3 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2010 VL 25 IS 10 BP 2091 EP 2097 DI 10.1002/jbmr.170 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 662AB UT WOS:000282776100001 PM 20593414 ER PT J AU Makitie, O Pereira, RC Kaitila, I Turan, S Bastepe, M Laine, T Kroger, H Cole, WG Juppner, H AF Makitie, Outi Pereira, Renata C. Kaitila, Ilkka Turan, Serap Bastepe, Murat Laine, Tero Kroger, Heikki Cole, William G. Jueppner, Harald TI Long-Term Clinical Outcome and Carrier Phenotype in Autosomal Recessive Hypophosphatemia Caused by a Novel DMP1 Mutation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE HYPOPHOSPHATEMIA; RICKETS; OSTEOMALACIA; SKELETAL DYSPLASIA; DMP1; FGF-23 ID MATRIX PROTEIN-1 DMP1; IN-VIVO; MARFAN-SYNDROME; BONE; OSTEOMALACIA; RICKETS; FGF23; MICE AB Homozygous inactivating mutations in DMP1 (dentin matrix protein 1), the gene encoding a noncollagenous bone matrix protein expressed in osteoblasts and osteocytes, cause autosomal recessive hypophosphatemia (ARHP). Herein we describe a family with ARHP owing to a novel homozygous DMP1 mutation and provide a detailed description of the associated skeletal dysplasia and carrier phenotype. The two adult patients with ARHP, a 78-year-old man and his 66-year-old sister, have suffered from bone pain and lower extremity varus deformities since early childhood. With increasing age, both patients developed severe joint pain, contractures, and complete immobilization of the spine. Radiographs showed short and deformed long bones, significant cranial hyperostosis, enthesopathies, and calcifications of the paraspinal ligaments. Biochemistries were consistent with hypophosphatemia owing to renal phosphate wasting; markers of bone turnover and serum fibroblast growth factor 23 (FGF-23) levels were increased significantly. Nucleotide sequence analysis of DMP1 revealed a novel homozygous mutation at the splice acceptor junction of exon 6 (IVS5-1G > A). Two heterozygous carriers of the mutation also showed mild hypophosphatemia, and bone biopsy in one of these individuals showed focal areas of osteomalacia. In bone, DMP1 expression was absent in the homozygote but normal in the heterozygote, whereas FGF-23 expression was increased in both subjects but higher in the ARHP patient. The clinical and laboratory observations in this family confirm that DMP1 has an important role in normal skeletal development and mineral homeostasis. The skeletal phenotype in ARHP may be significantly more severe than in other forms of hypophosphatemic rickets. (C) 2010 American Society for Bone and Mineral Research. C1 [Makitie, Outi; Kaitila, Ilkka; Laine, Tero] Univ Helsinki, Hosp Children & Adolescents, FIN-00029 Helsinki, Hus, Finland. [Makitie, Outi] Biomedicum Helsinki, Folkhalsan Inst Genet, Helsinki, Finland. [Pereira, Renata C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Turan, Serap; Bastepe, Murat; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Turan, Serap; Bastepe, Murat; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Kroger, Heikki] Kuopio Univ Hosp, Dept Surg, Bone & Cartilage Res Unit, SF-70210 Kuopio, Finland. [Cole, William G.] Univ Toronto, Hosp Sick Children, Div Orthopaed Surg, Toronto, ON M5G 1X8, Canada. RP Makitie, O (reprint author), Univ Helsinki, Hosp Children & Adolescents, POB 281, FIN-00029 Helsinki, Hus, Finland. EM outi.makitie@helsinki.fi OI Makitie, Outi/0000-0002-4547-001X FU Folkhalsan Research Foundation; Academy of Finland; Sigrid Juselius Foundation; Helsinki University Hospital; NIH [R21 DK075856-01] FX This study was supported by grants from the Folkhalsan Research Foundation, the Academy of Finland, the Sigrid Juselius Foundation, and the Helsinki University Hospital Research Funds, all from Helsinki, Finland, and from the NIH (R21 DK075856-01 to HJ). NR 24 TC 15 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2010 VL 25 IS 10 BP 2165 EP 2174 DI 10.1002/jbmr.105 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 662AB UT WOS:000282776100010 PM 20499351 ER PT J AU Matlock, DD Nowels, CT Bekelman, DB AF Matlock, Dan D. Nowels, Carolyn T. Bekelman, David B. TI Patient Perspectives on Decision Making in Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; patient-centered care; decision making; qualitative ID CARE; DEPRESSION; LIFE; PARTICIPATION; INVOLVEMENT; PREFERENCES; QUALITY AB Background: Patients with heart failure (HF) face an array of challenging decisions involving medications, devices, and transplants. The goal of this qualitative study was to describe patients' perceptions surrounding difficult decisions along with factors that influenced their decisions. Methods and Results: We studied 22 patients with symptomatic HF from the University of Colorado Hospital using in-depth, semistructured interviews. We used descriptive theme analysis in an iterative process to analyze responses to the question: "Can you tell me about any important or difficult decisions you have had to make about your heart condition?" Two distinct decision-making styles emerged: active (55%) and passive (45%). Active decision makers identified interventions such as implantable cardioverter-defibrillators, medications, and transplants to be the most difficult decisions and weighed concerns for side effects, family, and quality of life. Passive decision makers generally did not identify a difficult decision and described factors such as trust in God, trust in the physician, and power of the physician as reasons for their passivity. Conclusions: Patients with HF use active and passive decision styles in their approach to medical decision making. Future work should investigate communication techniques to assure that passive decision makers receive health care that is concordant with their values. (J Cardiac Fail 2010;16:823-826) C1 [Matlock, Dan D.; Nowels, Carolyn T.; Bekelman, David B.] Univ Colorado Denver, Div Gen Internal Med, Acad Off 1, Sch Med, Aurora, CO 80045 USA. [Matlock, Dan D.; Bekelman, David B.] Colorado Cardiovasc Outcomes Res Grp, Denver, CO USA. [Bekelman, David B.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Matlock, DD (reprint author), Univ Colorado Denver, Div Gen Internal Med, Acad Off 1, Sch Med, 12631 E 17th Ave,Campus Box B-180, Aurora, CO 80045 USA. EM daniel.matlock@ucdenver.edu FU University of Colorado Denver (UCD) Hartford/Jahnigen Center for Excellence in Geriatric Medicine; UCD FX This research was conducted while Dan Matlock, MD, was a Hartford Geriatrics Health Outcomes Scholar. This research was funded by the University of Colorado Denver (UCD) Hartford/Jahnigen Center for Excellence in Geriatric Medicine and the UCD Mordecai Palliative Care Grants Fund. NR 19 TC 11 Z9 11 U1 3 U2 6 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2010 VL 16 IS 10 BP 823 EP 826 DI 10.1016/j.cardfail.2010.06.003 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 664XO UT WOS:000282997500004 PM 20932464 ER PT J AU Peal, DS Peterson, RT Milan, D AF Peal, David S. Peterson, Randall T. Milan, David TI Small Molecule Screening in Zebrafish SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Chemical Biology; Zebrafish; Small Molecule Screen ID INHIBITORS; IDENTIFICATION; MUTATION; EMBRYOS; DRUGS; DIFFERENTIATION; CARDIOMYOPATHY; PIGMENTATION; PATHWAYS; MODELS AB Small molecule screens have become useful tools in ongoing efforts to understand complex biologic systems and disease states. These screens can identify compounds that specifically affect signaling pathways, development, and disease processes. The zebrafish Danio rerio has increasingly been used as a whole organism model in which to perform such functional small molecule screens. Here, we review recent advances in screening approaches that focus on modulation of developmental processes and signaling pathways, along with suppressor screens of disease models. The identification of small molecule targets continues to be a challenge, and several recent approaches to this problem are discussed. The promise of chemical screens in zebrafish to identify novel biologic probes and therapeutic compounds continues to drive this rapidly growing field. C1 [Peal, David S.; Peterson, Randall T.; Milan, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Milan, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM DMilan@partners.org NR 38 TC 36 Z9 36 U1 1 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD OCT PY 2010 VL 3 IS 5 SI SI BP 454 EP 460 DI 10.1007/s12265-010-9212-8 PG 7 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 686KH UT WOS:000284694700005 PM 20680709 ER PT J AU Beaujouin, M Prebois, C Derocq, D Laurent-Matha, V Masson, O Pattingre, S Coopman, P Bettache, N Grossfield, J Hollingsworth, RE Zhang, HY Yao, ZM Hyman, BT van der Geer, P Smith, GK Liaudet-Coopman, E AF Beaujouin, Melanie Prebois, Christine Derocq, Danielle Laurent-Matha, Valerie Masson, Olivier Pattingre, Sophie Coopman, Peter Bettache, Nadir Grossfield, Jami Hollingsworth, Robert E. Zhang, Hongyu Yao, Zemin Hyman, Bradley T. van der Geer, Peter Smith, Gary K. Liaudet-Coopman, Emmanuelle TI Pro-cathepsin D interacts with the extracellular domain of the beta chain of LRP1 and promotes LRP1-dependent fibroblast outgrowth SO JOURNAL OF CELL SCIENCE LA English DT Article DE Cathepsin D; LRP1; Tumor microenvironment; Cancer; Fibroblast outgrowth ID RECEPTOR-RELATED PROTEIN; BREAST-CANCER-CELLS; TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODIES; INTRACELLULAR DOMAIN; CYTOPLASMIC DOMAIN; GROWTH-FACTOR; IN-VIVO; METASTASIS; EXPRESSION AB Interactions between cancer cells and fibroblasts are crucial in cancer progression. We have previously shown that the aspartic protease cathepsin D (cath-D), a marker of poor prognosis in breast cancer that is overexpressed and highly secreted by breast cancer cells, triggers mouse embryonic fibroblast outgrowth via a paracrine loop. Here, we show the requirement of secreted cath-D for human mammary fibroblast outgrowth using a three-dimensional co-culture assay with breast cancer cells that do or do not secrete pro-cath-D. Interestingly, proteolytically-inactive pro-cath-D remains mitogenic, indicating a mechanism involving protein-protein interaction. We identify the low-density lipoprotein (LDL) receptor-related protein-1, LRP1, as a novel binding partner for pro-cath-D in fibroblasts. Pro-cath-D binds to residues 349-394 of the beta chain of LRP1, and is the first ligand of the extracellular domain of LRP1 beta to be identified. We show that pro-cath-D interacts with LRP1. in cellulo. Interaction occurs at the cell surface, and overexpressed LRP1 beta directs pro-cath-D to the lipid rafts. Our results reveal that the ability of secreted pro-cath-D to promote human mammary fibroblast outgrowth depends on LRP1 expression, suggesting that pro-cath-D-LRP1 beta interaction plays a functional role in the outgrowth of fibroblasts. Overall, our findings strongly suggest that pro-cath-D secreted by epithelial cancer cells promotes fibroblast outgrowth in a paracrine LRP1-dependent manner in the breast tumor microenvironment. C1 [Beaujouin, Melanie; Prebois, Christine; Derocq, Danielle; Laurent-Matha, Valerie; Masson, Olivier; Pattingre, Sophie; Liaudet-Coopman, Emmanuelle] IRCM, F-34298 Montpellier, France. [Beaujouin, Melanie; Prebois, Christine; Derocq, Danielle; Laurent-Matha, Valerie; Masson, Olivier; Pattingre, Sophie; Liaudet-Coopman, Emmanuelle] INSERM, U896, F-34298 Montpellier, France. [Beaujouin, Melanie; Prebois, Christine; Derocq, Danielle; Laurent-Matha, Valerie; Masson, Olivier; Pattingre, Sophie; Liaudet-Coopman, Emmanuelle] Univ Montpellier 1, F-34298 Montpellier, France. [Beaujouin, Melanie; Prebois, Christine; Derocq, Danielle; Laurent-Matha, Valerie; Masson, Olivier; Pattingre, Sophie; Liaudet-Coopman, Emmanuelle] CRLC Val dAurelle Paul Lamarque, F-34298 Montpellier, France. [Coopman, Peter; Bettache, Nadir] Univ Montpellier 2, CNRS, UMR 5237, Ctr Rech Biochim Macromol, F-34298 Montpellier 5, France. [Grossfield, Jami; Hollingsworth, Robert E.] GlaxoSmithKline Inc, Genet Res, Res Triangle Pk, NC 27709 USA. [Zhang, Hongyu; Yao, Zemin] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1Y 4W7, Canada. [van der Geer, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimer Dis Res Lab, Charlestown, MA 02129 USA. [Smith, Gary K.] GlaxoSmithKline Inc, Screening & Compound Profiling, Res Triangle Pk, NC 27709 USA. RP Liaudet-Coopman, E (reprint author), IRCM, F-34298 Montpellier, France. EM emmanuelle.liaudet-coopman@inserm.fr FU Institut National de la Sante et de la Recherche Medicale; University of Montpellier I; ANR Jeunes Chercheuses, Jeunes Chercheurs; Ligue Nationale contre le Cancer; Association pour la Recherche sur le Cancer FX We thank Nadia Kerdjadj for secretarial assistance, Jean-Yves Cance for the photographs and Chantal Cazevieille (Centre de Ressources en Imagerie Cellulaire, Montpellier) for the immunogold microscopy. We also thank Stephan Jalaguier for helpful discussions regarding the GST pull-down experiments. This work was supported by the 'Institut National de la Sante et de la Recherche Medicale', University of Montpellier I, 'ANR Jeunes Chercheuses, Jeunes Chercheurs' and the 'Ligue Nationale contre le Cancer', and the 'Association pour la Recherche sur le Cancer', which provided a fellowship for Melanie Beaujouin. NR 53 TC 28 Z9 28 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT 1 PY 2010 VL 123 IS 19 BP 3336 EP 3346 DI 10.1242/jcs.070938 PG 11 WC Cell Biology SC Cell Biology GA 651ER UT WOS:000281908400014 PM 20826454 ER PT J AU Wijelath, E Namekata, M Murray, J Furuyashiki, M Zhang, SY Coan, D Wakao, M Harris, RB Suda, Y Wang, LC Sobel, M AF Wijelath, Errol Namekata, Mayumi Murray, Jacqueline Furuyashiki, Mai Zhang, Siyuan Coan, Daniel Wakao, Masahiro Harris, Robert B. Suda, Yasuo Wang, Lianchun Sobel, Michael TI Multiple Mechanisms for Exogenous Heparin Modulation of Vascular Endothelial Growth Factor Activity SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE VEGF-A; VEGFR2; HEPARIN; ENDOTHELIAL CELL; Ndst ID VEGF RECEPTOR; EXTRACELLULAR DOMAIN; BIOLOGICAL-ACTIVITY; BINDING PEPTIDE; SUGAR CHIPS; SULFATE; CELLS; ANGIOGENESIS; NEUROPILIN-1; MIGRATION AB Heparin and heparin-like molecules are known to modulate the cellular responses to vascular endothelial growth factor-A (VEGF-A). In this study, we investigated the likely mechanisms for heparin's influence on the biological activity of VEGF-A. Previous studies have shown that exogenous heparin's effects on the biological activity of VEGF-A are many and varied, in part due to the endogenous cell-surface heparan sulfates. To circumvent this problem, we used mutant endothelial cells lacking cell-surface heparan sulfates. We showed that VEGF-induced cellular responses are dependent in part on the presence of the heparan sulfates, and that exogenous heparin significantly augments VEGF's cellular effects especially when endogenous heparan sulfates are absent. Exogenous heparin was also found to play a cross-bridging role between VEGF-A165 and putative heparin-binding sites within its cognate receptor, VEGFR2 when they were examined in isolation. The cross-bridging appears to be more dependent on molecular weight than on a specific heparin structure. This was confirmed by surface plasmon resonance binding studies using sugar chips immobilized with defined oligosaccharide structures, which showed that VEGF-A165 binds to a relatively broad range of sulfated glycosaminoglycan structures. Finally, studies of the far-UV circular dichroism spectra of VEGF-A165 showed that heparin can also modulate the conformation and secondary structure of the protein. J. Cell. Biochem. 111: 461-468, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Wijelath, Errol; Namekata, Mayumi; Murray, Jacqueline; Coan, Daniel; Sobel, Michael] VA Puget Sound Hlth Care Syst, Dept Surg, Div Vasc Surg, Seattle, WA 98108 USA. [Wijelath, Errol; Namekata, Mayumi; Murray, Jacqueline; Coan, Daniel; Sobel, Michael] Univ Washington, Sch Med, Seattle, WA USA. [Furuyashiki, Mai; Suda, Yasuo] SUDx Biotec Corp, Kobe, Hyogo, Japan. [Zhang, Siyuan; Wang, Lianchun] Univ Georgia, Complex Carbohydrate Res Ctr, Dept Biochem & Mol Biol, Athens, GA 30602 USA. [Wakao, Masahiro; Suda, Yasuo] Kagoshima Univ, Dept Nanostruct & Adv Mat, Grad Sch Sci & Engn, Kagoshima 890, Japan. [Harris, Robert B.] Commonwealth Biotechnol Inc, Richmond, VA USA. RP Wijelath, E (reprint author), VA Puget Sound Hlth Care Syst, Dept Surg, Div Vasc Surg, S151,1660 S Columbian Way, Seattle, WA 98108 USA. EM errolw@u.washington.edu FU NIH [RO1HL097182, P41RR005351]; Japan Science and Technology Agency FX Grant sponsor: NIH; Grant numbers: RO1HL097182, P41RR005351; Grant sponsor: Japan Science and Technology Agency. NR 34 TC 12 Z9 13 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT 1 PY 2010 VL 111 IS 2 BP 461 EP 468 DI 10.1002/jcb.22727 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 658HZ UT WOS:000282482400022 PM 20524207 ER PT J AU Ahmad, S Osei-Bempong, C Dana, R Jurkunas, U AF Ahmad, Sajjad Osei-Bempong, Charles Dana, Reza Jurkunas, Ula TI The Culture and Transplantation of Human Limbal Stem Cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID OCULAR SURFACE RECONSTRUCTION; SINGLE CORNEAL CELLS; EX-VIVO EXPANSION; EPITHELIAL-CELLS; IMPRESSION CYTOLOGY; DEFICIENCY; CONJUNCTIVA; DISORDERS; THERAPY; ORIGIN AB The cornea is the clear front of the eye and its surface is composed of an epithelium. This is renewed by stem cells located at the limbus, which encircles the periphery of the cornea. These limbal stem cells become lost or deficient in the blinding disease of limbal stem cell deficiency. In this review article, we discuss the historical perspective in managing limbal stem cell deficiency as well as describing the more contemporary treatment options, and in particular the culture and transplantation of human limbal stem cells. This treatment was first proposed 13 years ago and many case series have been presented to date showing promising outcomes of this technique. However, challenges still remain in treating the debilitating disease of limbal stem cell deficiency. Here we discuss some of the questions, which remain to be answered in this field. J. Cell. Physiol. 225: 15-19,2010. (C) 2010 Wiley-Liss, Inc. C1 [Ahmad, Sajjad] Newcastle Univ, Int Ctr Life, Inst Human Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Ahmad, Sajjad; Osei-Bempong, Charles] Newcastle Univ, NE England Stem Cell Inst, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Ahmad, Sajjad] Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Dana, Reza; Jurkunas, Ula] Harvard Univ, Schepens Eye Res Inst, Boston, MA 02115 USA. [Dana, Reza; Jurkunas, Ula] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Ahmad, S (reprint author), Newcastle Univ, Int Ctr Life, Inst Human Genet, Cent Pkwy, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. EM sajjad.ahmad@ncl.ac.uk FU Medical Research Council [G0900879] NR 40 TC 19 Z9 21 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 2010 VL 225 IS 1 BP 15 EP 19 DI 10.1002/jcp.22251 PG 5 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 643KK UT WOS:000281295100003 PM 20506173 ER PT J AU Dey, N Ghosh-Choudhury, N Das, F Li, XN Venkatesan, B Barnes, JL Kasinath, BS Choudhury, GG AF Dey, Nirmalya Ghosh-Choudhury, Nandini Das, Falguni Li, Xiaonan Venkatesan, Balachandar Barnes, Jeffrey L. Kasinath, Balakuntalam S. Choudhury, Goutam Ghosh TI PRAS40 Acts as a Nodal Regulator of High Glucose-Induced TORC1 Activation in Glomerular Mesangial Cell Hypertrophy SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RICH AKT-SUBSTRATE; MESSENGER-RNA TRANSLATION; GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR PTEN; INDUCED DNA-SYNTHESIS; 40 KDA PRAS40; DIABETIC-NEPHROPATHY; MAMMALIAN TARGET; RENAL HYPERTROPHY; PHOSPHATIDYLINOSITOL 3-KINASE AB Diabetic nephropathy manifests aberrant activation of TORC1, which senses key signals to modulate protein synthesis and renal hypertrophy. PRAS40 has recently been identified as a raptor-interacting protein and is a component and a constitutive inhibitor of TORC1. The mechanism by which high glucose stimulates TORC1 activity is not known. PRAS40 was identified in the mesangial cells in renal glomeruli and in tubulointerstitium of rat kidney. Streptozotocin-induced diabetic renal hypertrophy was associated with phosphorylation of PRAS40 in the cortex and glomeruli. In vitro, high glucose concentration increased PRAS40 phosphorylation in a PI 3 kinase- and Akt-dependent manner, resulting in dissociation of raptor PRAS40 complex in mesangial cells. High glucose augmented the inactivating and activating phosphorylation of 4EBP-I and S6 kinase, respectively, with concomitant induction of protein synthesis and hypertrophy. Expression of TORC1-nonphosphorylatable mutant of 4EBP-I and dominant-negative S6 kinase significantly inhibited high glucose-induced protein synthesis and hypertrophy. PRAS40 knockdown mimicked the effect of high glucose on phosphorylation of 4EBP-I and S6 kinase, protein synthesis, and hypertrophy. To elucidate the role of PRAS40 phosphorylation, we used phosphorylation-deficient mutant of PRAS40, which in contrast to PRAS40 knockdown inhibited phosphorylation of 4EBP-I and S6 kinase, leading to reduced mesangial cell hypertrophy. Thus, our data identify high glucose-induced phosphorylation and inactivation of PRAS40 as a central node for mesangial cell hypertrophy in diabetic nephropathy. J. Cell. Physiol. 225: 27-41, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Dey, Nirmalya; Das, Falguni; Li, Xiaonan; Venkatesan, Balachandar; Barnes, Jeffrey L.; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Barnes, Jeffrey L.; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, VA Res, San Antonio, TX USA. [Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU NIH [ROI DK50190, ROI AR52425]; Juvenile Diabetes Research Foundation [1-2008-185]; Department of Veterans Affairs; VA Merit Review; VA Research Service; VA Research Service Merit Review FX The authors thank Dr. L. Mahimainathan for his help in animal experiments. The authors wish to acknowledge the University of Texas Health Science Center FACS Core Facility for FACS analysis provided in this article. This work was supported by NIH ROI DK50190, The Juvenile Diabetes Research Foundation 1-2008-185, and VA Research Service Merit Review grants to G.G.C., who is a recipient of Senior Research Career Scientist Award from the Department of Veterans Affairs. N.G.C. is supported by NIH ROI AR52425 and VA Merit Review grants. B.S.K. is supported by grants from NIH, VA Research Service. NR 87 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 2010 VL 225 IS 1 BP 27 EP 41 DI 10.1002/jcp.22186 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 643KK UT WOS:000281295100005 PM 20629086 ER PT J AU Reiser, J Adair, B Reinheckel, T AF Reiser, Jochen Adair, Brian Reinheckel, Thomas TI Specialized roles for cysteine cathepsins in health and disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; CONGENITAL NEPHROTIC SYNDROME; COLLAGEN-INDUCED ARTHRITIS; POLYCYSTIC KIDNEY-DISEASE; DIPEPTIDYL PEPTIDASE-I; HUMAN PROCATHEPSIN L; DEFICIENT MICE; CRYSTAL-STRUCTURE; GENE-EXPRESSION; KNOCKOUT MICE AB Cathepsins were originally identified as proteases that act in the lysosome. Recent work has uncovered nontraditional roles for cathepsins in the extracellular space as well as in the cytosol and nucleus. There is strong evidence that subspecialized and compartmentalized cathepsins participate in many physiologic and pathophysiologic cellular processes, in which they can act as both digestive and regulatory proteases. In this review, we discuss the transcriptional and translational control of cathepsin expression, the regulation of intracellular sorting of cathepsins, and the structural basis of cathepsin activation and inhibition. In particular, we highlight the emerging roles of various cathepsin forms in disease, particularly those of the cardiac and renal systems. C1 [Reiser, Jochen] Univ Miami, Leonard Miller Sch Med, Dept Med, Miami, FL 33136 USA. [Adair, Brian] Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA. [Adair, Brian] Harvard Univ, Sch Med, Charlestown, MA USA. [Reinheckel, Thomas] Univ Freiburg, Inst Mol Med & Cell Res, Freiburg, Germany. [Reinheckel, Thomas] Univ Freiburg, Ctr Biol Signaling Studies BIOSS, Freiburg, Germany. RP Reiser, J (reprint author), Univ Miami, Miller Sch Med, Dept Med, 1580 NW 10th Ave,Batchelor Bldg,6th Floor R-762, Miami, FL 33136 USA. EM jreiser@med.miami.edu RI Silva, Mariana/B-9530-2012 FU US NIH [DK073495]; American Society of Nephrology; Deutsche Forschungsgemeinschaft [SFB 850]; Centre of Chronic Immunodeficiency [TP8]; Excellence Initiative of the German Federal and State Governments [EXC 294]; European Union [201279] FX This work was supported in part by a US NIH grant (DK073495) to J. Reiser, the American Society of Nephrology Carl W. Gottschalk Research Scholar grant to B.D. Adair, and the Deutsche Forschungsgemeinschaft SFB 850 Project B7, the Centre of Chronic Immunodeficiency Freiburg grant (TP8), the Excellence Initiative of the German Federal and State Governments (EXC 294), and the European Union Framework Program (FP7 "MICROENVIMET" no. 201279) to T. Reinheckel. NR 150 TC 208 Z9 216 U1 1 U2 26 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 OCT PY 2010 VL 120 IS 10 BP 3421 EP 3431 DI 10.1172/JCI42918 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 657DN UT WOS:000282393200004 PM 20921628 ER PT J AU Teekakirikul, P Eminaga, S Toka, O Alcalai, R Wang, LB Wakimoto, H Nayor, M Konno, T Gorham, JM Wolf, CM Kim, JB Schmitt, JP Molkentin, JD Norris, RA Tager, AM Hoffman, SR Markwald, RR Seidman, CE Seidman, JG AF Teekakirikul, Polakit Eminaga, Seda Toka, Okan Alcalai, Ronny Wang, Libin Wakimoto, Hiroko Nayor, Matthew Konno, Tetsuo Gorham, Joshua M. Wolf, Cordula M. Kim, Jae B. Schmitt, Joachim P. Molkentin, Jefferey D. Norris, Russell A. Tager, Andrew M. Hoffman, Stanley R. Markwald, Roger R. Seidman, Christine E. Seidman, Jonathan G. TI Cardiac fibrosis in mice with hypertrophic cardiomyopathy is mediated by non-myocyte proliferation and requires Tgf-beta SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR-BETA; ANGIOTENSIN-II; MOUSE MODEL; DILATED CARDIOMYOPATHY; MESENCHYMAL TRANSITION; MYOCARDIAL-INFARCTION; MONOCLONAL-ANTIBODY; CELL-PROLIFERATION; MARFAN-SYNDROME; PERIOSTIN AB Mutations in sarcomere protein genes can cause hypertrophic cardiomyopathy (HCM), a disorder characterized by myocyte enlargement, fibrosis, and impaired ventricular relaxation. Here, we demonstrate that sarcomere protein gene mutations activate proliferative and profibrotic signals in non-myocyte cells to produce pathologic remodeling in HCM. Gene expression analyses of non-myocyte cells isolated from HCM mouse hearts showed increased levels of RNAs encoding cell-cycle proteins, Tgf-beta, periostin, and other profibrotic proteins. Markedly increased BrdU labeling, Ki67 antigen expression, and periostin immunohistochemistry in the fibrotic regions of HCM hearts confirmed the transcriptional profiling data. Genetic ablation of periostin in HCM mice reduced but did not extinguish non-myocyte proliferation and fibrosis. In contrast, administration of Tgf-beta-neutralizing antibodies abrogated non-myocyte proliferation and fibrosis. Chronic administration of the angiotensin II type I receptor antagonist losartan to mutation-positive, hypertrophy-negative (prehypertrophic) mice prevented the emergence of hypertrophy, non-myocyte proliferation, and fibrosis. Losartan treatment did not reverse pathologic remodeling of established HCM but did reduce non-myocyte proliferation. These data define non-myocyte activation of Tgf-beta signaling as a pivotal mechanism for increased fibrosis in HCM and a potentially important factor contributing to diastolic dysfunction and heart failure. Preemptive pharmacologic inhibition of Tgf-beta signals warrants study in human patients with sarcomere gene mutations. C1 [Teekakirikul, Polakit; Eminaga, Seda; Toka, Okan; Alcalai, Ronny; Wang, Libin; Wakimoto, Hiroko; Nayor, Matthew; Konno, Tetsuo; Gorham, Joshua M.; Wolf, Cordula M.; Kim, Jae B.; Schmitt, Joachim P.; Seidman, Christine E.; Seidman, Jonathan G.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Toka, Okan] Univ Erlangen Nurnberg, Childrens Hosp, Dept Pediat Cardiol, Erlangen, Germany. [Alcalai, Ronny] Hadassah Hebrew Univ, Med Ctr, Inst Heart, Jerusalem, Israel. [Wakimoto, Hiroko; Wolf, Cordula M.] Childrens Hosp Boston, Dept Cardiol, Boston, MA USA. [Kim, Jae B.; Seidman, Christine E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Schmitt, Joachim P.] Univ Wurzburg, Inst Pharmacol & Toxicol, Wurzburg, Germany. [Molkentin, Jefferey D.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH USA. [Molkentin, Jefferey D.] Howard Hughes Med Inst, Cincinnati, OH USA. [Norris, Russell A.; Hoffman, Stanley R.; Markwald, Roger R.] Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. [Norris, Russell A.; Hoffman, Stanley R.; Markwald, Roger R.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Tager, Andrew M.] Harvard Univ, Sch Med, Pulm & Crit Care Unit, Boston, MA USA. [Tager, Andrew M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA USA. [Seidman, Christine E.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Seidman, JG (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur,NRB 256, Boston, MA 02115 USA. EM seidman@genetics.med.harvard.edu FU Deutsche Forschungsgemeinschaft; Deutsche Stiftung fur Herzforschung; Leducq Fondation; NHLBI; NIH-NHLBI [HL33756]; NIH-NCRR [P20RR016434, P20RR021949]; Foundation Leducq (Paris, France) [07CVD04]; National Science Foundation [EPS-090279S]; NIH, National Center for Research Resources. [C06 RR018823] FX This work was supported by grants from Deutsche Forschungsgemeinschaft and Deutsche Stiftung fur Herzforschung (to J.P. Schmitt), HHMI (to C.E. Seidman and J.D. Molkentin), the Leducq Fondation (to R Markwald, C.E. Seidman, and J.G. Seidman), NHLBI (to R. Markwald, C.E. Seidman, and J.G. Seidman), and NIH (to J.G. Seidman). R. Markwald, R Norris, and S. Hoffman were supported by the following grants: NIH-NHLBI HL33756, NIH-NCRR COBRE P20RR016434, AREA Administrative Supplement for Translational Research, NIH-NCRR COBRE P20RR021949, the Foundation Leducq (Paris, France) Transatlantic Mitral Network of Excellence Grant 07CVD04, and the National Science Foundation: EPS-090279S. Their work was conducted in a facility constructed with support from NIH C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. NR 72 TC 160 Z9 170 U1 1 U2 26 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 OCT PY 2010 VL 120 IS 10 BP 3520 EP 3529 DI 10.1172/JCI42028 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 657DN UT WOS:000282393200015 PM 20811150 ER PT J AU Marubayashi, S Koppikar, P Taldone, T Abdel-Wahab, O West, N Bhagwat, N Caldas-Lopes, E Ross, KN Gonen, M Gozman, A Ahn, JH Rodina, A Ouerfelli, O Yang, GB Hedvat, C Bradner, JE Chiosis, G Levine, RL AF Marubayashi, Sachie Koppikar, Priya Taldone, Tony Abdel-Wahab, Omar West, Nathan Bhagwat, Neha Caldas-Lopes, Eloisi Ross, Kenneth N. Goenen, Mithat Gozman, Alex Ahn, James H. Rodina, Anna Ouerfelli, Ouathek Yang, Guangbin Hedvat, Cyrus Bradner, James E. Chiosis, Gabriela Levine, Ross L. TI HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; ACTIVATING MUTATION; CYTOKINE RECEPTOR; CANCER XENOGRAFTS; MURINE MODEL; STEM-CELL; INHIBITOR AB JAK2 kinase inhibitors were developed for the treatment of myeloproliferative neoplasms (MPNs), following the discovery of activating JAK2 mutations in the majority of patients with MPN. However, to date JAK2 inhibitor treatment has shown limited efficacy and apparent toxicities in clinical trials. We report here that an HSP90 inhibitor, PU-H71, demonstrated efficacy in cell line and mouse models of the MPN polycythemia vera (PV) and essential thrombocytosis (ET) by disrupting JAK2 protein stability. JAK2 physically associated with both HSP90 and PU-H71 and was degraded by PU-H71 treatment in vitro and in vivo, demonstrating that JAK2 is an HSP90 chaperone client. PU-H71 treatment caused potent, dose-dependent inhibition of cell growth and signaling in JAK2 mutant cell lines and in primary MPN patient samples. PU-H71 treatment of mice resulted in JAK2 degradation, inhibition of JAK-STAT signaling, normalization of peripheral blood counts, and improved survival in MPN models at doses that did not degrade JAK2 in normal tissues or cause substantial toxicity. Importantly, PU-H71 treatment also reduced the mutant allele burden in mice. These data establish what we believe to be a novel therapeutic rationale for HSP90 inhibition in the treatment of JAK2-dependent MPN. C1 [Marubayashi, Sachie; Koppikar, Priya; Abdel-Wahab, Omar; Bhagwat, Neha; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Taldone, Tony; Caldas-Lopes, Eloisi; Gozman, Alex; Ahn, James H.; Rodina, Anna; Chiosis, Gabriela] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA. [Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10065 USA. [West, Nathan; Ross, Kenneth N.; Bradner, James E.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [West, Nathan; Ross, Kenneth N.; Bradner, James E.] MIT, Cambridge, MA 02139 USA. [West, Nathan; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bhagwat, Neha] Gerstner Sloan Kettering Grad Sch Biomed Sci, New York, NY USA. [Goenen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Gozman, Alex] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA. [Ouerfelli, Ouathek; Yang, Guangbin] Mem Sloan Kettering Canc Ctr, Organ Synth Core Facil, New York, NY 10065 USA. [Hedvat, Cyrus] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. RP Levine, RL (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave,Box 20, New York, NY 10065 USA. EM james_Bradner@dfci.harvard.edu; chiosisg@mskcc.org; leviner@mskcc.org RI Gonen, Mithat/E-4826-2012; OI Ouerfelli, Ouathek/0000-0002-7038-0219; HEDVAT, CYRUS/0000-0003-0045-3491; Abdel-Wahab, Omar/0000-0002-3907-6171 FU Leukemia Lymphoma Society; National Institutes of Health; Howard Hughes Medical Institute; Memorial Sloan-Kettering Cancer Center; American Society of Hematology; National Cancer Institute; Burroughs-Wellcome Fund; Clinical and Translation Science Center at Weill Cornell Medical College FX This work was supported by grants from the Leukemia Lymphoma Society to G. Chiosis and R.L. Levine and from the National Institutes of Health and the Howard Hughes Medical Institute to R.L. Levine. O. Abdel-Wahab is supported by the Clinical Scholars Program at Memorial Sloan-Kettering Cancer Center and by the American Society of Hematology. R.L. Levine is an Early Career Award recipient of the Howard Hughes Medical Institute and is the Geoffrey Beene Junior Chair at Memorial Sloan-Kettering Cancer Center. J.E. Bradner and N. West were supported by grants from the National Cancer Institute and the Burroughs-Wellcome Fund. A. Gozman and E. Caldas-Lopes were supported by a grant from the Clinical and Translation Science Center at Weill Cornell Medical College. We thank Neil Rosen and Charles Sawyers for their advice. We thank Agnes Viale and the Memorial Sloan-Kettering Cancer Center Genomics Core Facility for their help in performing the microarray experiments. NR 62 TC 87 Z9 89 U1 0 U2 4 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 OCT PY 2010 VL 120 IS 10 BP 3578 EP 3593 DI 10.1172/JCI42442 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 657DN UT WOS:000282393200020 PM 20852385 ER PT J AU Reyes, NA Fisher, JK Austgen, K VandenBerg, S Huang, EJ Oakes, SA AF Reyes, Nichole A. Fisher, Jill K. Austgen, Kathryn VandenBerg, Scott Huang, Eric J. Oakes, Scott A. TI Blocking the mitochondrial apoptotic pathway preserves motor neuron viability and function in a mouse model of amyotrophic lateral sclerosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROGRAMMED CELL-DEATH; AGGREGATE-PRONE PROTEINS; BCL-2 FAMILY PROTEINS; NEURODEGENERATIVE DISEASES; PROAPOPTOTIC BAX; MUSCULAR-ATROPHY; OXIDATIVE STRESS; AUTOPHAGY; ALS; DYSFUNCTION AB Apoptosis of motor neurons is a well-documented feature in amyotrophic lateral sclerosis (ALS) and related motor neuron diseases (MNDs). However, the role of apoptosis in the pathogenesis of these diseases remains unresolved. One possibility is that the affected motor neurons only succumb to apoptosis once they have exhausted functional capacity. If true, blocking apoptosis should confer no therapeutic benefit. To directly investigate this idea, we tested whether tissue-specific deletion in the mouse CNS of BCL2-associated X protein (BAX) and BCL2-homologous antagonist/killer (BAK), 2 proapoptotic BCL-2 family proteins that together represent an essential gateway to the mitochondrial apoptotic pathway, would protect against motor neuron degeneration. We found that neuronal deletion of Bax and Bak in a mouse model of familial ALS not only halted neuronal loss, but prevented axonal degeneration, symptom onset, weight loss, and paralysis and extended survival. These results show that motor neurons damaged in ALS activate the mitochondrial apoptotic pathway early in the disease process and that apoptotic signaling directly contributes to neuromuscular degeneration and neuronal dysfunction. Hence, inhibiting apoptosis upstream of mitochondrial permeabilization represents a possible therapeutic strategy for preserving functional motor neurons in ALS and other MNDs. C1 [Reyes, Nichole A.; Austgen, Kathryn; Huang, Eric J.; Oakes, Scott A.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Fisher, Jill K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [VandenBerg, Scott] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Huang, Eric J.] Vet Affairs Med Ctr, Pathol Serv, San Francisco, CA 94121 USA. RP Oakes, SA (reprint author), Univ Calif San Francisco, Dept Pathol, 513 Parnassus Ave,HSW 517,Box 0511, San Francisco, CA 94143 USA. EM scott.oakes@ucsf.edu OI Huang, Eric/0000-0002-5381-3801 FU NIH [F31 NS626272, K08 AI054650, RO1 CA136577]; Genentech; HHMI; Steward Trust Foundation; Sandler Program in Basic Sciences FX We thank Feroz Papa, Gerard Evan, Barbara Malynn, Averil Ma, Jay Debnath, Piera Pasinelli, Robert Brown, and Paul Muchowski for scientific advice and encouragement throughout this project. We thank Christine Lin for help with preparing figures for the manuscript. This work was supported by NIH grants F31 NS626272 (to N.A. Reyes), K08 AI054650 (to S.A. Oakes), and RO1 CA136577 (to S.A. Oakes); a Genentech Fellowship (to N.A. Reyes); HHMI Physician-Scientist Early Career Award (to S.A. Oakes); the Steward Trust Foundation (to S.A. Oakes); and the Sandler Program in Basic Sciences (to S.A. Oakes). The authors would like to thank Yien Kuo for assistance with the rotarod studies, Jean Olson for assistance with EM, and Amy Tang, Sherry Kamiya, and Ivy Hsieh for assistance with histology preparations. NR 48 TC 45 Z9 46 U1 1 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2010 VL 120 IS 10 BP 3673 EP 3679 DI 10.1172/JCI42986 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 657DN UT WOS:000282393200029 PM 20890041 ER PT J AU Hemphill, LC AF Hemphill, Linda C. TI Familial hypercholesterolemia: Current treatment options and patient selection for low-density lipoprotein apheresis SO JOURNAL OF CLINICAL LIPIDOLOGY LA English DT Article DE Familial hypercholesterolemia; LDL; Apheresis; Statins; Patient selection ID PLACEBO-CONTROLLED TRIAL; CORONARY HEART-DISEASE; TREATMENT PANEL-III; EFFICACY; ATORVASTATIN; SAFETY; SIMVASTATIN; ROSUVASTATIN; CHOLESTEROL; CHILDREN AB Options for treatment of severe heterozygous and homozygous familial hypercholesterolemia prior to the statin era were limited by significant side effects and morbidity. The advent of both the statins and technology for the selective removal of LDL via apheresis have revolutionized management but challenges remain. (C) 2010 National Lipid Association. All rights reserved. C1 Massachusetts Gen Hosp, Dept Cardiol, Yawkey Ctr, Boston, MA 02114 USA. RP Hemphill, LC (reprint author), Massachusetts Gen Hosp, Dept Cardiol, Yawkey Ctr, Suite 5800,55 Fruit St, Boston, MA 02114 USA. EM lhemphill@partners.org FU ISIS; Genzyme Corporation FX Grant/research support for Dr. Hemphill comes from ISIS and the Genzyme Corporation. NR 18 TC 14 Z9 14 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-2874 J9 J CLIN LIPIDOL JI J. Clin. Lipidol. PD OCT PY 2010 VL 4 IS 5 BP 346 EP 349 DI 10.1016/j.jacl.2010.08.013 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 672ES UT WOS:000283566400006 PM 21122676 ER PT J AU Delpolyi, AR Han, SJ Parsa, AT AF Delpolyi, Amy R. Han, Seunggu J. Parsa, Andrew T. TI Development of a symptomatic intracranial meningioma in a male-to-female transsexual after initiation of hormone therapy SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Meningioma; Sex hormone; Transsexual ID BREAST-CANCER; SEX-HORMONES; PATIENT; RISK; EPIDEMIOLOGY; ASSOCIATION; EXPOSURES AB Transsexual patients are routinely treated with sex hormone therapy, which may be a risk factor for meningiomas, although the data are largely inconclusive. Here we describe a male-to-female transsexual patient treated with estradiol patches, who developed an occipital meningioma causing generalized seizures. This is the second report of a male-to-female transsexual patient who developed a symptomatic meningioma after sex hormone treatment, adding to the growing evidence that sex hormones contribute to the pathogenesis of meningiomas. Meningiomas may therefore complicate hormone therapy and sex hormones may be contraindicated in transsexual candidates with meningiomas identified upon screening. (C) 2010 Elsevier Ltd. All rights reserved, C1 [Han, Seunggu J.; Parsa, Andrew T.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Han, Seunggu J.; Parsa, Andrew T.] Univ Calif San Francisco, Brain Tumor Res Ctr, San Francisco, CA 94143 USA. [Delpolyi, Amy R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Delpolyi, Amy R.] Harvard Univ, Sch Med, Boston, MA USA. RP Parsa, AT (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM parsaa@neurosurg.ucsf.edu OI Deipolyi, Amy/0000-0003-3144-386X NR 26 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD OCT PY 2010 VL 17 IS 10 BP 1324 EP 1326 DI 10.1016/j.jocn.2010.01.036 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 645XQ UT WOS:000281499900027 ER PT J AU Fischer, T Stone, RM DeAngelo, DJ Galinsky, I Estey, E Lanza, C Fox, E Ehninger, G Feldman, EJ Schiller, GJ Klimek, VM Nimer, SD Gilliland, DG Dutreix, C Huntsman-Labed, A Virkus, J Giles, FJ AF Fischer, Thomas Stone, Richard M. DeAngelo, Daniel J. Galinsky, Ilene Estey, Elihu Lanza, Carlo Fox, Edward Ehninger, Gerhard Feldman, Eric J. Schiller, Gary J. Klimek, Virginia M. Nimer, Stephen D. Gilliland, D. Gary Dutreix, Catherine Huntsman-Labed, Alice Virkus, Jodi Giles, Francis J. TI Phase IIB Trial of Oral Midostaurin (PKC412), the FMS-Like Tyrosine Kinase 3 Receptor (FLT3) and Multi-Targeted Kinase Inhibitor, in Patients With Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome With Either Wild-Type or Mutated FLT3 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTERNATIONAL WORKING GROUP; RESPONSE CRITERIA; AML; CHEMOTHERAPY; MODEL AB Purpose Mutations leading to constitutive activation of the FMS-like tyrosine kinase 3 receptor (FLT3) occur in blasts of 30% of patients with acute myeloid leukemia (AML). Midostaurin (PKC412; N-benzoylstaurosporin) is a multitargeted tyrosine kinase inhibitor, with demonstrated activity in patients with AML/myelodysplastic syndrome (MDS) with FLT3 mutations. Patients and Methods Ninety-five patients with AML or MDS with either wild-type (n = 60) or mutated (n = 35) FLT3 were randomly assigned to receive oral midostaurin at 50 or 100 mg twice daily. The drug was discontinued in the absence of response at 2 months, disease progression, or unacceptable toxicity. Response was defined as complete response, partial response (PR), hematologic improvement, or reduction in peripheral blood or bone marrow blasts by >= 50% (BR). Results The rate of BR for the population in whom efficacy could be assessed (n = 92) was 71% in patients with FLT3-mutant and 42% in patients with FLT3 wild-type. One PR occurred in a patient with FLT3-mutant receiving the 100-mg dose regimen. Both doses were well-tolerated; there were no differences in toxicity or response rate according to the dose of midostaurin. Conclusion These results suggest that midostaurin has hematologic activity in both patients with FLT3-mutant and wild-type. The degree of clinical activity observed supports additional studies that combine midostaurin and other agents such as chemotherapy especially in FLT3-mutant AML. C1 [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Magdeburg, D-39106 Magdeburg, Germany. Tech Univ Dresden, Dresden, Germany. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Novartis Pharmaceut, Basel, Switzerland. Novartis Pharmaceut, E Hanover, NJ USA. Cornell Univ, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM rstone@partners.org FU Novartis Pharmaceuticals FX Supported by Novartis Pharmaceuticals. NR 26 TC 160 Z9 164 U1 2 U2 12 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 OCT 1 PY 2010 VL 28 IS 28 BP 4339 EP 4345 DI 10.1200/JCO.2010.28.9678 PG 7 WC Oncology SC Oncology GA 655TP UT WOS:000282272700034 PM 20733134 ER PT J AU Ng, K Meyerhardt, JA Chan, JA Niedzwiecki, D Hollis, DR Saltz, LB Mayer, RJ Benson, AB Schaefer, PL Whittom, R Hantel, A Goldberg, RM Fuchs, CS AF Ng, Kimmie Meyerhardt, Jeffrey A. Chan, Jennifer A. Niedzwiecki, Donna Hollis, Donna R. Saltz, Leonard B. Mayer, Robert J. Benson, Al B., III Schaefer, Paul L. Whittom, Renaud Hantel, Alexander Goldberg, Richard M. Fuchs, Charles S. TI Multivitamin Use Is Not Associated With Cancer Recurrence or Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MINERAL SUPPLEMENT USE; VITAMIN-D STATUS; COLORECTAL-CANCER; FOLLOW-UP; FOLATE; CARCINOGENESIS; PREVENTION; RISK; CALCIUM; CELLS AB Purpose Multivitamin use is widespread in the United States, especially among patients with cancer. However, the influence of multivitamin supplementation on cancer recurrence and death after a curative resection of colon cancer is unknown. Patients and Methods We conducted a prospective, observational study of 1,038 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial. Patients reported on multivitamin use during and 6 months after adjuvant chemotherapy. Patients were observed until March 2009 for disease recurrence and death. To minimize bias by occult recurrence, we excluded patients who recurred or died within 90 days of their multivitamin assessment. Results Among 1,038 patients, 518 (49.9%) reported multivitamin use during adjuvant chemotherapy. Compared with nonusers, the multivariate hazard ratio (HR) for disease-free survival was 0.94 (95% CI, 0.77 to 1.15) for patients who used multivitamins. Similarly, multivitamin use during adjuvant chemotherapy was not significantly associated with recurrence-free survival (multivariate HR, 0.93; 95% CI, 0.75 to 1.15) or overall survival (multivariate HR 0.92; 95% CI, 0.74 to 1.16). Multivitamin use reported 6 months after completion of adjuvant chemotherapy was also not associated with improved patient outcome, and consistent use both during and following adjuvant therapy conferred no benefit. Neither an increasing number of tablets nor increasing duration of use before cancer diagnosis was associated with cancer recurrence or mortality. Multivitamin use also did not improve the rates of grade 3 and higher GI toxicity. Conclusion Multivitamin use during and after adjuvant chemotherapy was not significantly associated with improved outcomes in patients with stage III colon cancer. C1 [Ng, Kimmie] Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Univ, Med Ctr, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Univ N Carolina, Chapel Hill, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Edward Canc Ctr, Naperville, IL USA. Toledo Community Hosp, Oncol Program, Toledo, OH USA. Univ Montreal, Hop Sacre Coeur Montreal, Quebec City, PQ, Canada. RP Ng, K (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kng4@partners.org RI Goldberg , Richard/M-1311-2013; OI Saltz, Leonard/0000-0001-8353-4670 FU National Cancer Institute, National Institutes of Health [P50CA127003, T32CA009001-34]; American Society of Clinical Oncology; Bank of America; Pfizer Oncology; National Cancer Institute [CA31946, CA33601] FX Supported by Grants No. P50CA127003 and T32CA009001-34 from the National Cancer Institute, National Institutes of Health (K.N.); by an American Society of Clinical Oncology Young Investigator Award (K.N.); by the Charles A. King Trust Postdoctoral Fellowship Award, Bank of America, Co-Trustee (K.N.); and by Pharmacia & Upjohn Company, now Pfizer Oncology. The research for CALGB (Cancer and Leukemia Group B) 89803 was also supported, in part, by grants from the National Cancer Institute (CA31946) to CALGB and to the CALGB Statistical Center (CA33601). NR 38 TC 18 Z9 18 U1 0 U2 1 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 OCT 1 PY 2010 VL 28 IS 28 BP 4354 EP 4363 DI 10.1200/JCO.2010.28.0362 PG 10 WC Oncology SC Oncology GA 655TP UT WOS:000282272700036 PM 20805450 ER PT J AU Keating, NL Landrum, MB Arora, NK Malin, JL Ganz, PA van Ryn, M Weeks, JC AF Keating, Nancy L. Landrum, Mary Beth Arora, Neeraj K. Malin, Jennifer L. Ganz, Patricia A. van Ryn, Michelle Weeks, Jane C. TI Cancer Patients' Roles in Treatment Decisions: Do Characteristics of the Decision Influence Roles? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER; HEALTH OUTCOMES; OLDER WOMEN; PARTICIPATION; CARE; QUALITY; COMMUNICATION; PREFERENCES; INFORMATION; LIFE AB Purpose Patients with more active roles in decisions are more satisfied and may have better health outcomes. Younger and better educated patients have more active roles in decisions, but whether patients' roles in decisions differ by characteristics of the decision itself is unknown. Patients and Methods We surveyed a large, population-based cohort of patients with recently diagnosed lung or colorectal cancer about their roles in decisions regarding surgery, radiation therapy, and/or chemotherapy. We used multinomial logistic regression to assess whether characteristics of the decision, including evidence about the treatment's benefit, whether the decision was likely preference-sensitive (palliative therapy for metastatic cancer), and treatment modality, influenced patients' roles in that decision. Results Of 10,939 decisions made by 5,383 patients, 38.9% were patient controlled, 43.6% were shared, and 17.5% were physician controlled. When there was good evidence to support a treatment, shared control was greatest; when evidence was uncertain, patient control was greatest; and when there was no evidence for or evidence against a treatment, physician control was greatest (overall P < .001). Decisions about treatments for metastatic cancers tended to be more physician controlled than other decisions (P < .001). Conclusion Patients making decisions about treatments for which no evidence supports benefit and decisions about noncurative treatments reported more physician control, which suggests that patients may not want the responsibility of deciding on treatments that will not cure them. Better strategies for shared decision making may be needed when there is no evidence to support benefit of a treatment or when patients have terminal illnesses that cannot be cured. C1 [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Hlth Care Ctr, Los Angeles, CA USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU National Cancer Institute (NCI) [U01 CA093344, U01 CA 093332, U01 CA093324, U01 CA093348, U01 CA093329, U01 CA01013, U01 CA093339]; Department of Veterans Affairs [CRS 02-164] FX Supported by Grants No. U01 CA093344 from the National Cancer Institute (NCI) to the Statistical Coordinating Center; U01 CA 093332 from the NCI-supported Primary Data Collection and Research Centers to DanaFarber Cancer Institute/Cancer Research Network; U01 CA093324 to Harvard Medical School/Northern California Cancer Center; U01 CA093348 to RAND/University of California, Los Angeles; U01 CA093329 to the University of Alabama at Birmingham; U01 CA01013 to the University of Iowa; U01 CA093339 to the University of North Carolina; and by Grant No. CRS 02-164 from the Department of Veterans Affairs to the Durham Veterans Affairs Medical Center CRS 02-164. NR 29 TC 52 Z9 52 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2010 VL 28 IS 28 BP 4364 EP 4370 DI 10.1200/JCO.2009.26.8870 PG 7 WC Oncology SC Oncology GA 655TP UT WOS:000282272700037 PM 20713872 ER PT J AU Steensma, DP AF Steensma, David P. TI A Cello for Michayla SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, 44 Binney St,Ste D1B30, Boston, MA 02115 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 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 OCT 1 PY 2010 VL 28 IS 28 BP 4400 EP 4401 DI 10.1200/JCO.2010.30.0681 PG 2 WC Oncology SC Oncology GA 655TP UT WOS:000282272700042 PM 20660826 ER PT J AU Choueiri, TK Schutz, FAB Je, YJ AF Choueiri, Toni K. Schutz, Fabio A. B. Je, Youjin TI Risk of Arterial Thrombosis Not Increased by Sorafenib or Sunitinib Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID ANGIOGENESIS INHIBITOR BEVACIZUMAB; THROMBOEMBOLIC EVENTS; CANCER-PATIENTS; METAANALYSIS C1 [Choueiri, Toni K.; Schutz, Fabio A. B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, Toni K.; Schutz, Fabio A. B.] Harvard Univ, Sch Med, Boston, MA USA. [Je, Youjin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 6 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 OCT PY 2010 VL 28 IS 30 BP E620 EP E620 DI 10.1200/JCO.2010.31.1456 PG 1 WC Oncology SC Oncology GA 665SS UT WOS:000283056400015 ER PT J AU Manne, SL Meropol, NJ Weinberg, DS Vig, H Catts, ZA Manning, C Ross, E Shannon, K Chung, DC AF Manne, Sharon L. Meropol, Neal J. Weinberg, David S. Vig, Hetal Catts, Zohra Alikhan Manning, Cheri Ross, Eric Shannon, Kristen Chung, Daniel C. TI Informed Decisions Regarding Microsatellite Instability Testing: Need for an Intention-to-Screen Analysis Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID COLORECTAL-CANCER C1 [Manne, Sharon L.; Meropol, Neal J.; Weinberg, David S.; Ross, Eric] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Vig, Hetal; Shannon, Kristen; Chung, Daniel C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Catts, Zohra Alikhan] Christiana Care, Helen F Graham Canc Ctr, Newark, DE USA. [Manning, Cheri] Triad Interact Inc, Washington, DC USA. RP Manne, SL (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. NR 3 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 OCT 1 PY 2010 VL 28 IS 28 BP E538 EP E538 DI 10.1200/JCO.2010.29.9677 PG 1 WC Oncology SC Oncology GA 655TP UT WOS:000282272700021 ER PT J AU Zhang, M Li, FM Rasper, M Saad, AG AF Zhang, Meng Li, Fumin Rasper, Michael Saad, Ali G. TI Prolonged Stability of Progressive Multifocal Leukoencephalopathy in a Patient With Chronic Lymphocytic Leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; MIRTAZAPINE; CIDOFOVIR; THERAPY; DISEASE; VIRUS; AIDS C1 [Zhang, Meng] Third Mil Med Univ, Daping Hosp, Chongqing, Peoples R China. [Li, Fumin] SE Univ, Sch Med, Xuzhou Hosp, Jiangsu, Peoples R China. [Rasper, Michael] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rasper, Michael] Tech Univ Munich, Munich, Germany. [Saad, Ali G.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Saad, Ali G.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RP Zhang, M (reprint author), Third Mil Med Univ, Daping Hosp, Chongqing, Peoples R China. RI Kesari, Santosh/E-8461-2013 NR 17 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 OCT 1 PY 2010 VL 28 IS 28 BP E503 EP E506 DI 10.1200/JCO.2009.26.8078 PG 4 WC Oncology SC Oncology GA 655TP UT WOS:000282272700003 PM 20585084 ER PT J AU Gilbertson, MW McFarlane, AC Weathers, FW Keane, TM Yehuda, R Shalev, AY Lasko, NB Goetz, JM Pitman, RK AF Gilbertson, Mark W. McFarlane, Alexander C. Weathers, Frank W. Keane, Terence M. Yehuda, Rachel Shalev, Arieh Y. Lasko, Natasha B. Goetz, Jared M. Pitman, Roger K. CA Harvard VT PTSD Twin Study Investi TI Is Trauma a Causal Agent of Psychopathologic Symptoms in Posttraumatic Stress Disorder? Findings From Identical Twins Discordant for Combat Exposure SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ADMINISTERED PTSD SCALE; WORLD-WAR-II; COMPENSATION-SEEKING; PERSONALITY-TRAITS; MISSISSIPPI SCALE; VIETNAM VETERANS; MAJOR DEPRESSION; RISK-FACTORS; VULNERABILITY; VALIDITY AB Objective: The diagnosis of posttraumatic stress disorder (PTSD) is unique in that its criteria are embedded with a presumed causal agent, viz, a traumatic event. This assumption has come under scrutiny as a number of recent studies have suggested that many symptoms of PTSD may not necessarily be the result of trauma and may merely represent general psychiatric symptoms that would have existed even in the absence of a trauma event but are subsequently misattributed to it. The current study tests this hypothesis. Method: A case-control twin study conducted between 1996-2001 examined psychopathologic symptoms in a national convenience sample of 104 identical twin pairs discordant for combat exposure in Vietnam, with (n = 50) or without (n = 54) combat-related PTSD (DSM-IV-diagnosed) in the exposed twin. Psychometric measures used were the Symptom Checklist-90-Revised, the Clinician-Administered PTSD Scale, and the Mississippi Scale for Combat-Related PTSD. If a psychopathologic feature represents a factor that would have existed even without traumatic exposure, then there is a high chance that it would also be found at elevated rates in the non trauma-exposed, identical cotwins of trauma-exposed twins with PTSD. In contrast, if a psychopathologic feature is acquired as a result of an environmental factor unique to the exposed twin, eg, the traumatic event, their cotwins should not have an increased incidence of the feature. Results: Combat veterans with PTSD demonstrated significantly higher scores (P < .0001) on the Symptom Checklist-90-Revised and other psychometric measures of psychopathology than their own combat-unexposed cotwins (and than combat veterans without PTSD and their cotwins). Conclusions: These results support the conclusion that the majority of psychiatric symptoms reported by combat veterans with PTSD would not have been present were it not for their exposure to traumatic events. J Clin Psychiatry 2010;71(10):1324-1330 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Gilbertson, Mark W.] Manchester VA Med Ctr, Dept Res Serv, Manchester, NH 03104 USA. [Gilbertson, Mark W.; Lasko, Natasha B.; Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA USA. [McFarlane, Alexander C.] Univ Adelaide, Adelaide, SA, Australia. [McFarlane, Alexander C.] Ctr Mil & Vet Hlth, Adelaide, SA, Australia. [Weathers, Frank W.] Auburn Univ, Auburn, AL 36849 USA. [Keane, Terence M.] VA Boston Healthcare Syst, Boston, MA USA. [Keane, Terence M.] Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Yehuda, Rachel] James J Peters VA Med Ctr, Bronx, NY USA. [Yehuda, Rachel] Mt Sinai Sch Med, Bronx, NY USA. [Shalev, Arieh Y.] Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. [Goetz, Jared M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gilbertson, MW (reprint author), Manchester VA Med Ctr, Dept Res Serv, 718 Smyth Rd, Manchester, NH 03104 USA. EM mark.gilbertson@va.gov OI Shalev, Arieh/0000-0001-9425-050X FU United States Public Health Service [MH54636]; US Department of Veterans Affairs; VET Registry FX Supported by United States Public Health Service grant #MH54636. The US Department of Veterans Affairs provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. Through their support of the VET Registry, numerous other US organizations also provided invaluable assistance, including Department of Defense; National Personnel Records Center, National Archives and Records Administration; Internal Revenue Service; National Institutes of Health; National Opinion Research Center; National Research Council; and National Academy of Sciences. NR 52 TC 12 Z9 12 U1 1 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2010 VL 71 IS 10 BP 1324 EP 1330 DI 10.4088/JCP.10m06121blu PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 696LY UT WOS:000285444100008 PM 20868640 ER PT J AU Brooks, AC Comer, SD Sullivan, MA Bisaga, A Carpenter, KM Raby, WM Yu, E O'Brien, CP Nunes, EV AF Brooks, Adam C. Comer, Sandra D. Sullivan, Maria A. Bisaga, Adam Carpenter, Kenneth M. Raby, Wilfrid M. Yu, Elmer O'Brien, Charles P. Nunes, Edward V. TI Long-Acting Injectable Versus Oral Naltrexone Maintenance Therapy With Psychosocial Intervention for Heroin Dependence: A Quasi-Experiment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID OPIOID DEPENDENCE; CONTINGENCY MANAGEMENT; EFFICACY; IMPLANTS; GUIDE AB Objective: To conduct a quasi-experimental comparison of early clinical outcomes between injectable, sustained-release, depot naltrexone formulation versus oral naltrexone maintenance therapy in individuals with opiate dependence. Method: Early retention in treatment and urine-confirmed opiate use in the first 8 weeks postdetoxification were compared between patients (diagnosed as opiate-dependent according to DSM-IV criteria) participating in 2 concurrently run randomized clinical trials of oral (n = 69; patients treated from September 1999 to May 2002) and long-acting injectable (n = 42; patients treated from November 2000 to June 2003) naltrexone maintenance therapy with psychosocial therapy. Results: Long-acting injectable naltrexone produced significantly better outcome than oral naltrexone on days retained in treatment (F(1,106) = 6.49, P = .012) and for 1 measure of opiate use (F(1,106) = 5.26, P = .024); other measures were not significantly different, but differences were in the same direction. In subanalyses, there were interaction effects between baseline heroin use severity and type of treatment. In subanalyses, heroin users with more severe baseline use showed better retention with oral naltrexone maintenance therapy combined with intensive psychotherapy (behavioral naltrexone therapy) as compared to retention shown by severe heroin users treated with long-acting naltrexone injections combined with standard cognitive-behavioral therapy (chi(2)(1) = 9.31, P = .002); less severe heroin users evidenced better outcomes when treated with long-acting injectable naltrexone. Conclusions: This quasi-experimental analysis provides tentative indications of superior outcomes for heroin-dependent patients treated with long-acting injectable naltrexone compared to oral naltrexone. The finding that heroin users with more severe baseline use achieved better outcomes with oral naltrexone is most probably attributable to the intensive nature of the psychosocial treatments provided and points to the opportunity for continued research in augmenting injectable naltrexone with psychosocial strategies to further improve outcome, especially in individuals with more severe use. The results should be considered exploratory given the quasi-experimental nature of the study. J Clin Psychiatry 2010;71(10): 1371-1378 (C) Copyright 2010 Physicians Postgraduate Press, Inc, C1 [Brooks, Adam C.] Treatment Res Inst, Philadelphia, PA 19106 USA. [Brooks, Adam C.; Comer, Sandra D.; Sullivan, Maria A.; Bisaga, Adam; Carpenter, Kenneth M.; Raby, Wilfrid M.; Nunes, Edward V.] New York State Psychiat Inst & Hosp, Div Subst Abuse, New York, NY 10032 USA. [Comer, Sandra D.; Sullivan, Maria A.; Bisaga, Adam; Carpenter, Kenneth M.; Raby, Wilfrid M.; Nunes, Edward V.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Yu, Elmer; O'Brien, Charles P.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Yu, Elmer; O'Brien, Charles P.] Philadelphia Vet Affairs Med Ctr, Dept Behav Hlth, Philadelphia, PA USA. RP Brooks, AC (reprint author), Treatment Res Inst, 600 Publ Ledger Bldg,150 S Independence Mall W, Philadelphia, PA 19106 USA. EM abrooks@tresearch.org FU Schering-Plough; Grunenthal GmbH; Reckitt Benckiser; Johnson Johnson; Alkermes; National Institute on Drug Abuse; [P50 DA09236]; [P60 DA05186]; [R01 DA10746]; [K02 DA00288] FX Dr Corner has been a consultant to Purdue Pharma, Alpharma, King, Inflexxion, Shire, BioDelivery Services, and Analgesics Research; has received grant/research support from Schering-Plough, Grunenthal GmbH, Reckitt Benckiser, and Johnson & Johnson; has received honoraria from the Rehabilitation Institute of Chicago, Yale University, Wake Forest University, and the University of Michigan at Ann Arbor; and has served on the speakers or advisory boards of Alpharma and King. Dr Bisaga has received a grant from Alkermes to conduct a study of depot naltrexone in a clinical trial; Alkermes is providing the medication. Dr O'Brien has an ongoing intermittent consulting relationship with Alkermes. Dr Nunes served on the board of Alkermes/Cephalon until he resigned from that position in November of 2007. Alkermes/Cephalon makes a comparable product to Depotrex, the product used in this study. Drs Brooks, Sullivan, Carpenter, Baby, and Yu have no conflicts to disclose that could affect the reporting of this study.; The authors gratefully acknowledge the support of the National Institute on Drug Abuse. Support for original data collection was drawn from center grants P50 DA09236 and P60 DA05186, as well as R01 DA10746 and K02 DA00288 (Dr Nunes). NR 23 TC 9 Z9 9 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2010 VL 71 IS 10 BP 1371 EP 1378 DI 10.4088/JCP.09m05080ecr PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 696LY UT WOS:000285444100014 PM 20673549 ER PT J AU Biederman, J Mick, E Surman, C Doyle, R Hammerness, P Kotarski, M Spencer, T AF Biederman, Joseph Mick, Eric Surman, Craig Doyle, Robert Hammerness, Paul Kotarski, Meghan Spencer, Thomas TI A Randomized, 3-Phase, 34-Week, Double-Blind, Long-Term Efficacy Study of Osmotic-Release Oral System-Methylphenidate in Adults With Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE adult; ADHD; stimulant; randomized trial; methylphenidate; psychopharmacology ID DEFICIT HYPERACTIVITY DISORDER; PLACEBO-CONTROLLED TRIAL; OROS METHYLPHENIDATE; METAANALYSIS; PREVALENCE; STATES; ADHD AB We conducted a 3-phase, double-blind, placebo-controlled, parallel study design of osmotic-release oral system (OROS)-methylphenidate (MPH) in adults (19-60 years of age) with attention deficit/hyperactivity disorder as classified by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Phase 1 of the study was a 6-week, acute efficacy trial (n = 223), phase 2 was a 24-week, double-blind continuation study of responders (n = 96), and phase 3 was a double-blind, placebo-controlled, 4-week discontinuation study (n = 23). The mean daily dosage at phase 1 endpoint was 78.4 +/- 31.7 mg (0.97 +/- 0.32 mg/kg) OROS-MPH and 96.6 +/- 26.5 mg (1.16 +/- 0.19 mg/kg) placebo (P < 0.0001). Clinical response at phase 1 endpoint was significantly greater in the OROS-MPH group (62%, n = 67 vs 37%, n = 41; P < 0.001) and was maintained throughout 24 weeks of double-blind treatment. With double-blind, placebo-controlled discontinuation, however, there was no statistically significant difference in the rate of relapse between OROS-MPH responders randomized to placebo and those randomized to continue active treatment (18%, n = 2 vs 0%, n = 0; P = 0.1). As expected, decreased appetite, insomnia, being tense/jittery, mucosal dryness, and neurological symptoms were statistically significantly associated with OROS-MPH treatment. More work is needed to be conducted with larger samples being followed to study completion to better understand the long- lasting impact of pharmacotherapy for adult attention-deficit/hyperactivity disorder. C1 [Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145 FU Ortho-McNeil Janssen Scientific Affairs, LLC; Alza; AstraZeneca; Bristol-Myers Squibb; Eli Lilly Company; Janssen Pharmaceuticals Inc; McNeil; Merck; Organon; Otsuka; Shire; National Institutes of Mental Health; NICHD; Fundacion Areces; Medice Pharmaceuticals; Spanish Child Psychiatry Association; Abbott; Celltech, Cephalon; Esai; Forest; Glaxo; Gliatech; Janssen; NARSAD; NIDA; New River; Novartis; Noven; Neurosearch; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma, Inc; Wyeth; Ortho-McNeil Janssen Scientific Affairs; Pfizer; Shire Pharmaceuticals; Cephalon; Elminda; Eli Lilly; National Institutes of Health; Takeda; Glaxo-SmithKline; Johnson & Johnson FX Clinical trials were supported with financial support from Ortho-McNeil Janssen Scientific Affairs, LLC.; Dr Joseph Biederman is currently receiving research support from the following sources: Alza, AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Company, Janssen Pharmaceuticals Inc, McNeil, Merck, Organon, Otsuka, Shire, National Institutes of Mental Health and NICHD. In 2009, Dr Joseph Biederman received a speaker's fee from the following sources: Fundacion Areces, Medice Pharmaceuticals, and the Spanish Child Psychiatry Association. In previous years, Dr Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, AstraZeneca, Celltech, Cephalon, Eli Lilly & Company, Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, NARSAD, NIDA, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc, and Wyeth. Dr Eric Mick receives research support from the following sources: Ortho-McNeil Janssen Scientific Affairs, Pfizer, Shire Pharmaceuticals; and has been an advisory board member for Shire Pharmaceuticals. Dr Surman has received research support from Abbott, Alza, Cephalon, Elminda, Eli Lilly, the Hilda and Preston Davis Foundation, McNeil, Merck, New River, National Institutes of Health, Organon, Pfizer, Shire, and Takeda; has been a speaker for Janssen-Ortho, McNeil, Novartis, and Shire; and has been a consultant/advisor for McNeil, Shire and Takeda. He has also been a speaker for the MGH Academy and Reed Medical Education, which produces programs that are funded by several pharmaceutical companies. Dr Robert Doyle has received speaker honoraria from Shire, Novartis, McNeil, Neuroscience Educational Institute, Continuing Medical Education Outfitters, PriMed, APA, and AACAP. Dr Hammerness has participated, as an investigator, in research studies funded by the following companies: Abbott, Bristol-Myers Squibb, Cephalon, Eli Lilly, Glaxo-SmithKline, Johnson & Johnson, McNeil, Merck, New River, Organon, Pfizer, Shire, and Takeda. In the past 2 years, Dr Hammerness has received research funds or participated in CME activities/professional talks supported by the following companies: Abbott, Eli Lilly, Forest, McNeil, Shire. Dr Hammerness has also received research funds from Elminda Ltd and has participated in speaker training with Shire. Dr Hammerness has also received honoraria from Reed Medical Education (a company working as a logistics collaborator for the MGH Psychiatry Academy); education programs supported through grants from pharmaceutical companies along with participant tuition. Ms Meghan Kotarski reports no competing interests. Dr Thomas Spencer has received research support from the following sources: Shire Laboratories Inc, Cephalon, Eli Lilly & Company, GlaxoSmith Kline, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals, Pfizer, and NIMH. Dr Thomas Spencer has been a speaker for the following speaker's bureaus: Shire Laboratories, Inc, Eli Lilly & Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, and Novartis Pharmaceuticals. Dr Thomas Spencer has been on the advisory board for the following pharmaceutical companies: Shire Laboratories Inc, Cephalon, Eli Lilly & Company, Glaxo-Smith Kline, Janssen, McNeil Pharmaceutical, Novartis Pharmaceuticals, and Pfizer. NR 21 TC 40 Z9 40 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2010 VL 30 IS 5 BP 549 EP 553 DI 10.1097/JCP.0b013e3181ee84a7 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 650JY UT WOS:000281846400010 PM 20814332 ER PT J AU Westra, S Adler, I Batton, D Betz, B Bezinque, S Durfee, S Ecklund, K Feinstein, K Fordham, L Junewick, J Lorenzo, R McCauley, R Miller, C Seibert, J Kuban, K Allred, E Leviton, A AF Westra, Sjirk Adler, Ira Batton, Daniel Betz, Bradford Bezinque, Steven Durfee, Sara Ecklund, Kirsten Feinstein, Kate Fordham, Lynn Junewick, Joseph Lorenzo, Robert McCauley, Roy Miller, Cindy Seibert, Joanna Kuban, Karl Allred, Elizabeth Leviton, Alan TI Reader Variability in the Use of Diagnostic Terms to Describe White Matter Lesions Seen on Cranial Scans of Severely Premature Infants: The ELGAN Study SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Article DE neurosonography; white matter lesions; prematurity; multicenter studies; diagnostic classifications ID PERIVENTRICULAR HEMORRHAGIC INFARCTION; BIRTH-WEIGHT INFANTS; INTENSIVE-CARE UNITS; LOW GESTATIONAL-AGE; BRAIN-INJURY; RISK-FACTORS; NEURODEVELOPMENTAL OUTCOMES; INTRAVENTRICULAR HEMORRHAGE; PRETERM INFANTS; INTRACRANIAL HEMORRHAGE AB Purpose. To evaluate reader variability of white matter lesions seen on cranial sonographic scans of extreme low gestational age neonates (ELGANs). Methods. In 1,452 ELGANs, cranial sonographic scans were obtained in the first and second postnatal weeks, and between the third postnatal week and term. All sets of scans were read independently by two sonologists. We reviewed the use of four diagnostic labels: early periventricular leucomalacia, cystic periventricular leucomalacia, periventricular hemorrhagic infarction (PVHI), and other white matter diagnosis, by 16 sonologists at 14 institutions. We evaluated the association of these labels with location and laterality of hyperechoic and hypoechoic lesions, location of intraventricular hemorrhage, and characteristics of ventricular enlargement. Results. Experienced sonologists differed substantially in their application of the diagnostic labels. Three readers applied early periventricular leucomalacia to more than one fourth of all the scans they read, whereas eight applied this label to <= 5% of scans. Five applied PVHI to >= 10% of scans, while three applied this label to <= 5% of scans. More than one third of scans labeled cystic periventricular leucomalacia had unilateral hypoechoic lesions. White matter abnormalities in PVHI were more extensive than in periventricular leucomalacia and were more anteriorly located. Hypoechoic lesions on late scans tended to be in the same locations, regardless of the diagnostic label applied. Conclusions. Experienced sonologists differ considerably in their tendency to apply diagnostic labels for white matter lesions. This is due to lack of universally agreed-upon definitions. We recommend reducing this variability to improve the validity of large multi-center studies. (C) 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:409-419, 2010; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jcu.20708 C1 [Westra, Sjirk] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Adler, Ira] Eastern Radiologists Inc, Greenville, NC USA. [Batton, Daniel] So Illinois Univ, Sch Med, Springfield, IL USA. [Betz, Bradford; Bezinque, Steven; Junewick, Joseph] DeVos Childrens Hosp, Dept Radiol, Grand Rapids, MI USA. [Durfee, Sara] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Ecklund, Kirsten] Childrens Hosp Boston, Dept Radiol, Boston, MA USA. [Feinstein, Kate] Univ Chicago, Med Ctr, Dept Radiol, Chicago, IL 60637 USA. [Fordham, Lynn] Univ N Carolina, Sch Med, Dept Radiol, Chapel Hill, NC 27514 USA. [Lorenzo, Robert] Childrens Healthcare Atlanta, Dept Radiol, Atlanta, GA USA. [McCauley, Roy] Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA USA. [Miller, Cindy] Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06510 USA. [Seibert, Joanna] Arkansas Childrens Hosp, Dept Radiol, Little Rock, AR 72202 USA. [Kuban, Karl] Boston Med Ctr, Boston, MA USA. [Kuban, Karl] Boston Univ, Dept Pediat, Boston, MA 02215 USA. [Allred, Elizabeth; Leviton, Alan] Childrens Hosp Boston, Dept Neurol, Boston, MA USA. RP Westra, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. OI Kuban, Karl/0000-0001-5299-3567 FU National Institute of Neurologic Diseases and Stroke [5U01NS040069-05]; National Institute of Child Health and Human Development [NIH-P30-HD-18655] FX This study was supported by a cooperative agreement with the National Institute of Neurologic Diseases and Stroke (5U01NS040069-05) and a program project grant from the National Institute of Child Health and Human Development (NIH-P30-HD-18655). The authors gratefully acknowledge the contributions of our subjects and their families, as well as those of our colleagues. NR 33 TC 3 Z9 4 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD OCT PY 2010 VL 38 IS 8 BP 409 EP 419 DI 10.1002/jcu.20708 PG 11 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 653QC UT WOS:000282110700002 PM 20872936 ER PT J AU Long, JA Field, S Armstrong, K Chang, VW Metlay, JP AF Long, Judith A. Field, Sam Armstrong, Katrina Chang, Virginia W. Metlay, Joshua P. TI Social Capital and Glucose Control SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE Diabetes; Veterans; African Americans; Residence characteristics ID CARDIOVASCULAR-DISEASE; RACIAL-DIFFERENCES; DIABETES-MELLITUS; GLYCEMIC CONTROL; HEALTH; MORTALITY; DISPARITIES; POPULATION; COMMUNITIES; POVERTY AB There is a growing diabetes epidemic in the United States and if we are to halt its progress we need to better understand the social determinants of this disease and its control. Social capital, which has been associated with general health and mortality, may be one important mediator of glucose control. In this study we determine if neighborhood social capital is associated with glucose control, independent of individual factors. We performed a cross-sectional study of Black veterans with diabetes living in Philadelphia. We merged individual-level data from surveys and charts with six area-level social capital descriptors. Holding all other variables constant, patients who lived in neighborhoods that scored near the 5th percentile of working together to improve the neighborhood were estimated to have glycosylated hemoglobin (HbA1c) values that were at least one point above a conservative clinical definition of "diabetes control" (HbA1c a parts per thousand currency sign 8%). If these same patients were to live in neighborhoods in the 95th percentile, their expected HbA1c would be over A1/2 a point below the cut-off value 8%. No other measure of social capital was associated with HbA1c. In this study of black veterans with diabetes we observed that living in neighborhoods where people work together is associated with better glucose control. C1 [Long, Judith A.; Chang, Virginia W.; Metlay, Joshua P.] Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Philadelphia, PA 19104 USA. [Long, Judith A.; Armstrong, Katrina; Chang, Virginia W.; Metlay, Joshua P.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Long, Judith A.; Armstrong, Katrina; Chang, Virginia W.; Metlay, Joshua P.] Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA. [Long, Judith A.] Univ Penn, Sch Med, Metab & Diabet Endocrinol Res Ctr, Philadelphia, PA 19104 USA. [Field, Sam] Univ N Carolina, FPG Child Dev Inst, Chapel Hill, NC USA. [Metlay, Joshua P.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Long, JA (reprint author), Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, 1201 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jalong@mail.med.upenn.edu NR 41 TC 8 Z9 8 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD OCT PY 2010 VL 35 IS 5 BP 519 EP 526 DI 10.1007/s10900-010-9222-0 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 661DK UT WOS:000282703000010 PM 20143139 ER PT J AU Hanson, E Nasir, RH Fong, A Lian, A Hundley, R Shen, YP Wu, BL Holm, IA Miller, DT AF Hanson, Ellen Nasir, Ramzi H. Fong, Alexa Lian, Alyss Hundley, Rachel Shen, Yiping Wu, Bai-Lin Holm, Ingrid A. Miller, David T. CA 16p11 2 Study Grp Clinicians TI Cognitive and Behavioral Characterization of 16p11.2 Deletion Syndrome SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE autism spectrum disorders; chromosome 16p11,2; deletion; developmental delay; language delay ID PAROXYSMAL KINESIGENIC DYSKINESIA; COMPARATIVE GENOMIC HYBRIDIZATION; RECURRENT REARRANGEMENTS; MICRODELETION SYNDROME; MENTAL-RETARDATION; FRAGILE-X; AUTISM; PHENOTYPE; DISORDERS; DIAGNOSIS AB Objective: To describe cognitive and behavioral features of patients with chromosome 16p11.2 deletion syndrome, a recently identified and common genetic cause of neurodevelopmental disability, especially autism spectrum disorder (ASD). Method: Twenty-one patients with 16p11.2 deletion were evaluated by medical record review. A subset of 11 patients consented to detailed cognitive, behavioral, and autism diagnostic assessment. Results: Patients with 16p11.2 deletion had varying levels of intellectual disability, variable adaptive skills, and a high incidence of language delay. Attention issues were not as frequent as had been reported in previous clinical reports. Atypical language, reduced social skills, and maladaptive behaviors were common, as was diagnosis of ASD. Based on medical record review, 7 of 21 patients (33%) had an ASD diagnosis. Among patients receiving detailed phenotyping, 3 of 11 (27%) met full criteria (met cutoff scores on both Autism Diagnostic Observation Schedule and Autism Diagnostic Interview) for an ASD diagnosis, whereas 6 other patients (55%) met criteria for ASD on either the Autism Diagnostic Observation Schedule or the Autism Diagnostic Interview, but not both measures. Conclusions: Rates of ASD were similar to previous reports that are based on medical record reviews, but formal assessment revealed that a majority of patients with 16p11.2 deletion demonstrate features of ASD beyond simple language impairment. All patients with 16p11.2 deletion should receive formal neurodevelopmental evaluation including measures to specifically assess cognitive, adaptive, language, and psychiatric/behavioral issues. Clinical evaluation of this patient population should always include assessment by Autism Diagnostic Interview and Autism Diagnostic Observation Schedule to detect behaviors related to ASD and possible ASD diagnosis. C1 [Holm, Ingrid A.; Miller, David T.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Hanson, Ellen; Nasir, Ramzi H.; Fong, Alexa; Lian, Alyss; Hundley, Rachel] Childrens Hosp, Div Dev Med, Boston, MA 02115 USA. [Hanson, Ellen; Nasir, Ramzi H.; Hundley, Rachel; Shen, Yiping; Wu, Bai-Lin; Holm, Ingrid A.; Miller, David T.] Harvard Univ, Sch Med, Boston, MA USA. [Shen, Yiping; Wu, Bai-Lin; Miller, David T.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Shen, Yiping] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Holm, Ingrid A.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. RP Miller, DT (reprint author), Childrens Hosp, Div Genet, Hunnewell 5,300 Longwood Ave, Boston, MA 02115 USA. EM david.miller2@childrens.harvard.edu FU Simons Foundation; Autism Consortium; NIMH [R01MH085143-01, R01MH083565-01] FX Funding support for behavioral phenotyping was provided by the Simons Foundation, the Autism Consortium, and the NIMH (R01MH085143-01 and R01MH083565-01). NR 38 TC 54 Z9 54 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 2010 VL 31 IS 8 BP 649 EP 657 PG 9 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 670AV UT WOS:000283393100004 PM 20613623 ER PT J AU Onishi, Y Hayashi, T Sato, KK Ogihara, T Kuzuya, N Anai, M Tsukuda, K Boyko, EJ Fujimoto, WY Kikuchi, M AF Onishi, Yukiko Hayashi, Tomoshige Sato, Kyoko Kogawa Ogihara, Takehide Kuzuya, Nobuaki Anai, Motonobu Tsukuda, Katsunori Boyko, Edward J. Fujimoto, Wilfred Y. Kikuchi, Masatoshi TI Fasting tests of insulin secretion and sensitivity predict future prediabetes in Japanese with normal glucose tolerance SO JOURNAL OF DIABETES INVESTIGATION LA English DT Article DE Glucose intolerance; Insulin resistance; Epidemiology ID BETA-CELL FUNCTION; VISCERAL ADIPOSITY; DIABETES-MELLITUS; PLASMA-GLUCOSE; RISK-FACTOR; PROGRESSION; PREVALENCE; PROJECTIONS; POPULATION; AMERICANS AB Aims/Introduction: Reduced insulin sensitivity and secretion are important in the pathogenesis of type 2 diabetes. Their relationships to prediabetes, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) have been previously studied with the oral glucose tolerance test (OGTT). We investigated whether or not baseline measures of insulin secretion and sensitivity obtained from fasting blood specimens were related to the development of prediabetes and how these measures compared with those based on the OGTT. Materials and Methods: In 152 Japanese subjects with normal glucose tolerance, we measured baseline plasma glucose and insulin after an overnight fast and during a 75 g OGTT, insulin resistance index (homeostasis model assessment [HOMA-IR]), and insulin secretion (insulinogenic index [30 min insulin - fasting insulin] divided by [30 min glucose - fasting glucose] or HOMA-beta). Results: At a 5-6 year (mean 5.7 years) follow-up examination, we confirmed 36 cases of prediabetes. After adjusting for age, sex, family history of diabetes, body mass index, and 2-h plasma glucose, the odds ratio comparing the lowest tertile (<= 0.82) of insulinogenic index with the highest tertile (>= 1.43) was 6.98 (95% confidence interval, 1.96-24.85) and was 10.72 (2.08-55.3) comparing the lowest tertile (<= 76.3) of HOMA-beta with the highest tertile (>= 122.1), whereas the respective odds ratios of HOMA-IR were 3.74 (1.03-13.57) and 10.89 (1.93-61.41) comparing the highest tertile (>= 1.95) with the lowest tertile (<= 1.25). Conclusions: Lower insulin secretion and sensitivity are independent risk factors for prediabetes. Clinically practical identification of those at risk for prediabetes is obtainable from HOMA-beta and HOMA-IR, both of which are measured in fasting state. (J Diabetes Invest, doi: 10.1111.j.2040-1124.2010.00041.x, 2010) C1 [Onishi, Yukiko; Tsukuda, Katsunori; Kikuchi, Masatoshi] Asahi Life Fdn, Inst Adult Dis, Dept Diabet & Metab, Tokyo, Japan. [Anai, Motonobu] Univ Tokyo, Adv Sci & Technol Res Ctr, Lab Syst Biol & Med, Tokyo, Japan. [Hayashi, Tomoshige; Sato, Kyoko Kogawa] Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Osaka 558, Japan. [Ogihara, Takehide] Hitachi Gen Hosp, Div Internal Med, Ibaraki, Japan. [Kuzuya, Nobuaki] Yokohama Sakae Kyosai Hosp, Dept Endocrinol & Metab, Yokohama, Kanagawa, Japan. [Hayashi, Tomoshige; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Hayashi, Tomoshige; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res Informat Ctr, Seattle, WA USA. [Boyko, Edward J.; Fujimoto, Wilfred Y.] Univ Washington, Dept Med, Seattle, WA USA. RP Onishi, Y (reprint author), Asahi Life Fdn, Inst Adult Dis, Dept Diabet & Metab, Tokyo, Japan. EM y-ohnishi@asahi-life.or.jp RI Hayashi, Tomoshige/N-8508-2015 NR 22 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2040-1116 J9 J DIABETES INVEST JI J. Diabetes Investig. PD OCT PY 2010 VL 1 IS 5 BP 191 EP 195 DI 10.1111/j.2040-1124.2010.00041.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 755DN UT WOS:000289907000006 PM 24843431 ER PT J AU Goldstein, JN Delaney, KE Pelletier, AJ Fisher, J Blanc, PG Halsey, M Pallin, DJ Camargo, CA AF Goldstein, Joshua N. Delaney, Kate E. Pelletier, Andrea J. Fisher, Jonathan Blanc, Phillip G. Halsey, Mark Pallin, Daniel J. Camargo, Carlos A., Jr. TI A BRIEF EDUCATIONAL INTERVENTION MAY INCREASE PUBLIC ACCEPTANCE OF EMERGENCY RESEARCH WITHOUT CONSENT SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Academic-Emergency-Medicine CY MAY 16-19, 2007 CL Chicago, IL SP Soc Acad Emergency Med DE informed consent; public opinion; randomized controlled trial; data collection ID HOSPITAL CARDIAC-ARREST; ACUTE ISCHEMIC-STROKE; INFORMED-CONSENT; COMMUNITY CONSULTATION; RESUSCITATION RESEARCH; MEDICINE RESEARCH; MYOCARDIAL-INFARCTION; DEPARTMENT PATIENTS; ETHICAL ANALYSIS; FINAL RULE AB Objectives: We hypothesized that knowing the regulations regarding emergency research without consent would increase public support for this type of research. Methods: Randomized controlled trial. Consecutive patients presenting during eight 24-h periods received one of two interviews; the intervention interview included an educational paragraph. Results: There were 473 (74% of eligible) patients who participated: 51% (95% confidence interval [CI] 46-55) were willing to be enrolled in a study using exception to informed consent; 84% (95% CI 80-87) believed that current therapy for cardiac arrest offers >= 50% chance of full recovery, and these patients were less willing to enroll (odds ratio [OR] 0.5, 95% CI 0.3-0.9). The educational intervention increased willingness to enroll (OR 13, 95% CI 1.0-1.6, p = 0.03). Conclusions: A brief educational intervention had only a modest effect on willingness to participate in emergency research without consent. It may be more important to educate patients on the shortcomings of current therapy than on the ethical and regulatory justifications for such research. (C) 2010 Elsevier Inc. C1 [Goldstein, Joshua N.; Delaney, Kate E.; Pelletier, Andrea J.; Blanc, Phillip G.; Halsey, Mark; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Goldstein, Joshua N.; Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Goldstein, Joshua N.; Fisher, Jonathan; Pallin, Daniel J.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Fisher, Jonathan] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Pallin, Daniel J.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. RI Pallin, Daniel/H-6382-2013; Goldstein, Joshua/H-8953-2016 OI Pallin, Daniel/0000-0002-8517-9702; NR 55 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2010 VL 39 IS 4 BP 419 EP 435 DI 10.1016/j.jemermed.2007.12.033 PG 17 WC Emergency Medicine SC Emergency Medicine GA 663DC UT WOS:000282862200004 PM 18801638 ER PT J AU Martindale, JL Senecal, EL Obermeyer, Z Nadel, ES Brown, DFM AF Martindale, Jennifer L. Senecal, Emily L. Obermeyer, Ziad Nadel, Eric S. Brown, David F. M. TI ALTERED MENTAL STATUS AND HYPOTHERMIA SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID IMPAIRED WATER-EXCRETION; MYXEDEMA COMA; WERNICKES ENCEPHALOPATHY; HYPOGLYCEMIA; THERAPY; SEPSIS C1 [Senecal, Emily L.; Nadel, Eric S.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Martindale, Jennifer L.; Senecal, Emily L.; Obermeyer, Ziad; Nadel, Eric S.; Brown, David F. M.] Harvard Univ, Sch Med, Div Emergency Med, Harvard Affiliated Emergency Med Residency, Boston, MA USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders 114,Fruit St, Boston, MA 02114 USA. NR 22 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2010 VL 39 IS 4 BP 491 EP 496 DI 10.1016/j.jemermed.2010.03.021 PG 6 WC Emergency Medicine SC Emergency Medicine GA 663DC UT WOS:000282862200013 PM 20537835 ER PT J AU Lerner, LB Tyson, MD Mendoza, PJ AF Lerner, Lori B. Tyson, Mark D. Mendoza, Pierre J. TI Stress Incontinence During the Learning Curve of Holmium Laser Enucleation of the Prostate SO JOURNAL OF ENDOUROLOGY LA English DT Article ID EXPERIENCE; COMPLICATIONS; MORCELLATION; SURGERY AB Background and Purpose: Holmium laser enucleation of the prostate (HoLEP) is an excellent surgical treatment for patients with benign prostatic hyperplasia, but surgical complications are not well described. We set out to determine the predictors of stress incontinence (SUI) after HoLEP during the learning curve. Patients and Methods: A retrospective review of our institution's HoLEP database was performed. Patients were divided into two groups: No pads at 3 months (group 1); SUI and/or mixed incontinence necessitating >= one pad at 3 months (group 2). Results: Seventy-seven patients underwent HoLEP at our institution. Nine (12%) were excluded for pure urge symptoms and two (3%) were lost to follow-up, leaving 66 total patients. No differences were noted as regards age (P = 0.54), operating room time (P = 0.18), prostate size (P = 0.85), prostate-specific antigen level (P = 0.96), or International Prostate Symptom Score (P = 0.11). The number of days between cases, however, was higher in group 2 (44.5 vs 18.1, P = 0.02) and was associated with SUI in simple logistic regression models (odds ratio [OR] 1.25; 95% confidence interval [CI]: 1.04-1.51; P = 0.019). As the interval time between cases increased from 1, 3, and 5 weeks, the strength of the association increased (1 week: OR 2.75; 95% CI: 0.78-9.66; P = 0.12; 3 weeks: OR 2.86; 95% CI: 0.92-8.91; P = 0.07; 5 weeks: OR 4.69; 95% CI: 1.21-18.26; P = 0.026). SUI resolved in all but two patients by 1 year. Conclusions: The major associated risk for SUI, a complication presumably related to surgical technique, was prolonged duration between cases. During the learning curve, surgeons should schedule patients frequently to enhance learning and decrease time to mastery of the technique, thereby reducing SUI. C1 [Lerner, Lori B.] Boston Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA USA. [Tyson, Mark D.] Dartmouth Coll, Hanover, NH 03755 USA. [Mendoza, Pierre J.] Univ Penn, Philadelphia, PA 19104 USA. RP Lerner, LB (reprint author), 12 Water St, Hingham, MA 02043 USA. EM lerner_lori@hotmail.com NR 16 TC 13 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD OCT PY 2010 VL 24 IS 10 BP 1655 EP 1658 DI 10.1089/end.2010.0021 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 661SV UT WOS:000282749300021 PM 20645871 ER PT J AU Bilimoria, KY Cohen, ME Merkow, RP Wang, X Bentrem, DJ Ingraham, AM Richards, K Hall, BL Ko, CY AF Bilimoria, Karl Y. Cohen, Mark E. Merkow, Ryan P. Wang, Xue Bentrem, David J. Ingraham, Angela M. Richards, Karen Hall, Bruce L. Ko, Clifford Y. TI Comparison of Outlier Identification Methods in Hospital Surgical Quality Improvement Programs SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Surgery; Hospital; Quality; Morbidity; Mortality; Morbidity; Complications; Deaths; National surgery quality improvement program; Outlier ID RISK-ADJUSTMENT; PATIENT SAFETY; HEALTH-CARE; OF-CARE; SURGERY; PERFORMANCE AB Surgeons and hospitals are being increasingly assessed by third parties regarding surgical quality and outcomes, and much of this information is reported publicly. Our objective was to compare various methods used to classify hospitals as outliers in established surgical quality assessment programs by applying each approach to a single data set. Using American College of Surgeons National Surgical Quality Improvement Program data (7/2008-6/2009), hospital risk-adjusted 30-day morbidity and mortality were assessed for general surgery at 231 hospitals (cases = 217,630) and for colorectal surgery at 109 hospitals (cases = 17,251). The number of outliers (poor performers) identified using different methods and criteria were compared. The overall morbidity was 10.3% for general surgery and 25.3% for colorectal surgery. The mortality was 1.6% for general surgery and 4.0% for colorectal surgery. Programs used different methods (logistic regression, hierarchical modeling, partitioning) and criteria (P < 0.01, P < 0.05, P < 0.10) to identify outliers. Depending on outlier identification methods and criteria employed, when each approach was applied to this single dataset, the number of outliers ranged from 7 to 57 hospitals for general surgery morbidity, 1 to 57 hospitals for general surgery mortality, 4 to 27 hospitals for colorectal morbidity, and 0 to 27 hospitals for colorectal mortality. There was considerable variation in the number of outliers identified using different detection approaches. Quality programs seem to be utilizing outlier identification methods contrary to what might be expected, thus they should justify their methodology based on the intent of the program (i.e., quality improvement vs. reimbursement). Surgeons and hospitals should be aware of variability in methods used to assess their performance as these outlier designations will likely have referral and reimbursement consequences. C1 [Bilimoria, Karl Y.; Cohen, Mark E.; Merkow, Ryan P.; Wang, Xue; Ingraham, Angela M.; Richards, Karen] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Bilimoria, Karl Y.] Univ Texas Houston, MD Anderson Canc Ctr, Div Surg Oncol, Houston, TX 77030 USA. [Hall, Bruce L.] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Hall, Bruce L.] St Louis & Barnes Jewish Hosp, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO 63110 USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO 63110 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM kbilimoria@facs.org NR 27 TC 10 Z9 10 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD OCT PY 2010 VL 14 IS 10 BP 1600 EP 1606 DI 10.1007/s11605-010-1316-6 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 653OM UT WOS:000282101500025 PM 20824379 ER PT J AU Bradley, KA Williams, EC AF Bradley, Katharine A. Williams, Emily C. TI What Can General Medical Providers Do for Hospitalized Patients with Alcohol Dependence After Discharge? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED-CONTROLLED-TRIAL; DOUBLE-BLIND; BRIEF INTERVENTION; USE DISORDERS; DRINKING; OUTCOMES; CARE; INDIVIDUALS; TOPIRAMATE; SEEKING C1 [Bradley, Katharine A.; Williams, Emily C.] Vet Affairs Puget Sound Hlth Care Syst, HSR&D, Seattle, WA 98101 USA. [Bradley, Katharine A.] Vet Affairs Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA 98101 USA. [Bradley, Katharine A.; Williams, Emily C.] 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 USA. RP Bradley, KA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, HSR&D, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Katharine.bradley@va.gov NR 31 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 2010 VL 25 IS 10 BP 1000 EP 1002 DI 10.1007/s11606-010-1441-7 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 652ZN UT WOS:000282051400003 PM 20632122 ER PT J AU Vig, EK Starks, H Taylor, JS Hopley, EK Fryer-Edwards, K AF Vig, Elizabeth K. Starks, Helene Taylor, Janelle S. Hopley, Elizabeth K. Fryer-Edwards, Kelly TI Why Don't Patients Enroll in Hospice? Can We Do Anything About It? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hospice; decision making; terminally ill; terminal care ID MENTAL STATUS QUESTIONNAIRE; OF-LIFE-CARE; TREATMENT PREFERENCES; BARRIERS; END; DISCUSSIONS; ELIGIBILITY; PHYSICIANS; AMERICAN; SERVICES AB United States hospice organizations aim to provide quality, patient-centered end-of-life care to patients in the last 6 months of life, yet some of these organizations observe that some hospice-eligible patients who are referred to hospice do not initially enroll. Primary objective: To identify reasons that eligible patients do not enroll in hospice (phase 1). Secondary objective: To identify strategies used by hospice providers to address these reasons (phase 2). Semi-structured interviews analyzed using content analysis. In phase 1, we interviewed 30 patients and/or family members of patients who had a hospice admissions visit, but who did not enroll. In phase 2, we interviewed 19 hospice staff and national experts. In phase 1, we asked participants to describe the patient's illness, the hospice referral, and why they had not enrolled. We performed a content analysis to characterize their reasons for not enrolling in hospice. In phase 2, we enrolled hospice admissions staff and hospice experts. We asked them to describe how they would respond to each reason (from phase 1) during an admissions visit with a potential new hospice patient. We identified key phrases, and summarized their recommendations. Reasons that patients hadn't enrolled fell into three broad categories: patient/family perceptions (e.g., "not ready"), hospice specific issues (e.g., variable definitions of hospice-eligible patients), and systems issues (e.g., concerns about continuity of care). Hospice staff/experts had encountered each reason, and offered strategies at the individual and organizational level for responding. In hopes of increasing hospice enrollment among hospice-eligible patients, non-hospice and hospice clinicians may want to adopt some of the strategies used by hospice staff/experts for talking about hospice with patients/families and may want to familiarize themselves with the differences between hospice organizations in their area. Hospices may want to reconsider their admission policies and procedures in light of patients' and families' perceptions and concerns. C1 [Vig, Elizabeth K.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr & Extended Care, Seattle, WA 98108 USA. [Vig, Elizabeth K.; Hopley, Elizabeth K.] Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Starks, Helene; Fryer-Edwards, Kelly] Univ Washington, Dept Bioeth & Humanities, Seattle, WA 98195 USA. [Starks, Helene] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Taylor, Janelle S.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Vig, EK (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr & Extended Care, 1660 S Columbian Way S-182 Eth, Seattle, WA 98108 USA. EM vigster@u.washington.edu FU National Institute on Aging [K23 AG19635] FX This work was supported by the National Institute on Aging (K23 AG19635). This material was presented in part at the Annual Assembly of the American Academy of Hospice and Palliative Medicine in New Orleans, LA in January 2005, and at the Annual Meeting of the Society of General Internal Medicine in Toronto, Ontario, Canada in April 2007. NR 42 TC 22 Z9 22 U1 3 U2 9 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 OCT PY 2010 VL 25 IS 10 BP 1009 EP 1019 DI 10.1007/s11606-010-1423-9 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 652ZN UT WOS:000282051400005 PM 20535577 ER PT J AU Williams, BA McGuire, J Lindsay, RG Baillargeon, J Cenzer, IS Lee, SJ Kushel, M AF Williams, Brie A. McGuire, James Lindsay, Rebecca G. Baillargeon, Jacques Cenzer, Irena Stijacic Lee, Sei J. Kushel, Margot TI Coming Home: Health Status and Homelessness Risk of Older Pre-release Prisoners SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE health status; homelessness risk; pre-release prisoners; older prisoners ID FORMER INMATES; ADULTS; POPULATION; DEATH; CARE; SYSTEM; BOSTON; ILL AB Older adults comprise an increasing proportion of the prison and homeless populations. While older age is associated with adverse post-release health events and incarceration is a risk factor for homelessness, the health status and homelessness risk of older pre-release prisoners are unknown. Moreover, most post-release services are geared towards veterans; it is unknown whether the needs of non-veterans differ from those of veterans. To assess health status and risk of homelessness of older pre-release prisoners, and to compare veterans with non-veterans. Cross-sectional study of 360 prisoners (a parts per thousand yen55 years of age) within 2 years of release from prison using data from the 2004 Survey of Inmates in State and Federal Correctional Facilities. Veteran status, health status (based on self-report), and risk of homelessness (homelessness before arrest). Mean age was 61 years; 93.8% were men and 56.5% were white. Nearly 40% were veterans, of whom 77.2% reported likely VA service eligibility. Veterans were more likely to be white and to have obtained a high school diploma or GED. Overall, 79.1% reported a medical condition and 13.6% reported a serious mental illness. There was little difference in health status between veterans and non-veterans. Although 1 in 12 prisoners reported a risk factor for homelessness, the risk factors did not differ according to veteran status. Older pre-release prisoners had a high burden of medical and mental illness and were at risk for post-release homelessness regardless of veteran status. Reentry programs linking pre-release older prisoners to medical and psychiatric services and to homelessness prevention programs are needed for both veterans and non-veterans. C1 [Williams, Brie A.; Cenzer, Irena Stijacic; Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Williams, Brie A.; Cenzer, Irena Stijacic; Lee, Sei J.] San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco, CA USA. [McGuire, James] Vet Hlth Adm, Healthcare Reentry Vet Program, Durham, NC USA. [Lindsay, Rebecca G.] Univ Calif San Francisco, San Francisco Sch Med, San Francisco, CA 94121 USA. [Lindsay, Rebecca G.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Baillargeon, Jacques] Univ Texas Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX USA. [Baillargeon, Jacques] Univ Texas Med Branch, Div Epidemiol, Galveston, TX USA. [Kushel, Margot] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Williams, BA (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St,Box 181-G, San Francisco, CA 94121 USA. EM brie.williams@ucsf.edu; mkushel@medsfgh.ucsf.edu FU Brookdale Leadership in Aging Fellowship; National Institute of Aging [K23AG033102]; Hellman Family Award; UCSF FX Brie Williams was supported in part by the Brookdale Leadership in Aging Fellowship, the National Institute of Aging (K23AG033102), and the Hellman Family Award. Rebecca Lindsay was supported by the UCSF Dean's Summer Fellowship. Drs. Williams, McGuire, and Lee are employees of the Department of Veterans Affairs. The opinions expressed in this manuscript may not represent those of the VA. NR 58 TC 23 Z9 23 U1 1 U2 18 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 OCT PY 2010 VL 25 IS 10 BP 1038 EP 1044 DI 10.1007/s11606-010-1416-8 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 652ZN UT WOS:000282051400009 PM 20532651 ER PT J AU Hanchate, AD Clough-Gorr, KM Ash, AS Thwin, SS Silliman, RA AF Hanchate, Amresh D. Clough-Gorr, Kerri M. Ash, Arlene S. Thwin, Soe Soe Silliman, Rebecca A. TI Longitudinal Patterns in Survival, Comorbidity, Healthcare Utilization and Quality of Care among Older Women Following Breast Cancer Diagnosis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE survival; case-control; inpatient care; outpatient care; costs; preventive care ID UP CARE; COLORECTAL-CANCER; UNITED-STATES; MORTALITY; MEDICARE; IMPACT; COSTS; MAINTENANCE; POPULATION; TRENDS AB To compare longitudinal patterns of health care utilization and quality of care for other health conditions between breast cancer-surviving older women and a matched cohort without breast cancer. Prospective five-year longitudinal comparison of cases and matched controls. Newly identified breast cancer patients recruited during 1997-1999 from four geographic regions (Los Angeles, CA; Minnesota; North Carolina; and Rhode Island; N = 422) were matched by age, race, baseline comorbidity and zip code location with up to four non-breast-cancer controls (N = 1,656). Survival; numbers of hospitalized days and physician visits; total inpatient and outpatient Medicare payments; guideline monitoring for patients with cardiovascular disease and diabetes, and bone density testing and colorectal cancer screening. Five-year survival was similar for cases and controls (80% and 82%, respectively; p = 0.18). In the first follow-up year, comorbidity burden and health care utilization were higher for cases (p < 0.01), with most differences diminishing over time. However, the number of physician visits was higher for cases (p < 0.01) in every year, driven partly by more cancer and surgical specialist visits. Cases and controls adhered similarly to recommended bone density testing, and monitoring of cardiovascular disease and diabetes; adherence to recommended colorectal cancer screening was better among cases. Breast cancer survivors' health care utilization and disease burden return to pre-diagnosis levels after one year, yet their greater use of outpatient care persists at least five years. Quality of care for other chronic health problems is similar for cases and controls. C1 [Hanchate, Amresh D.; Ash, Arlene S.] Boston Univ, Hlth Care Res Unit, Gen Internal Med Sect, Sch Med, Boston, MA 01532 USA. [Hanchate, Amresh D.] VA Boston Healthcare Syst, COLMR, Boston, MA USA. [Clough-Gorr, Kerri M.; Thwin, Soe Soe; Silliman, Rebecca A.] Boston Univ, Sch Med, Sect Geriatr, Boston, MA 01532 USA. [Clough-Gorr, Kerri M.; Silliman, Rebecca A.] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 01532 USA. [Clough-Gorr, Kerri M.] Univ Zurich, Inst Social & Prevent Med, NICER, CH-8006 Zurich, Switzerland. [Ash, Arlene S.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Thwin, Soe Soe] VA Healthcare Syst, MAVERIC, Boston, MA USA. RP Hanchate, AD (reprint author), Boston Univ, Hlth Care Res Unit, Gen Internal Med Sect, Sch Med, 801 Massachusetts Ave 2077, Boston, MA 01532 USA. EM hanchate@bu.edu OI Hanchate, Amresh/0000-0002-7038-4463 FU National Cancer Institute [CA106979, CA/AG 70818, CA84506, CA92395] FX This work was supported by grants CA106979, CA/AG 70818, CA84506, and CA92395 from the National Cancer Institute. NR 39 TC 17 Z9 17 U1 2 U2 10 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 OCT PY 2010 VL 25 IS 10 BP 1045 EP 1050 DI 10.1007/s11606-010-1407-9 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 652ZN UT WOS:000282051400010 PM 20532657 ER PT J AU Lynch, CP Gebregziabher, M Echols, C Gilbert, GE Zhao, YM Egede, LE AF Lynch, Cheryl P. Gebregziabher, Mulugeta Echols, Carrae Gilbert, Gregory E. Zhao, Yumin Egede, Leonard E. TI Racial Disparities in All-Cause Mortality Among Veterans with Type 2 Diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE race; all-cause mortality; diabetes; veterans ID HEALTH-CARE-SYSTEM; US ADULTS; CARDIOVASCULAR-DISEASE; ADMINISTRATIVE DATA; MEN; METAANALYSIS; HEMOGLOBIN; MELLITUS; OUTCOMES; BLACKS AB Racial differences in mortality among veterans with diabetes are less well characterized than those in the general population. To examine racial differences in all-cause mortality in a large sample of veterans with diabetes. A retrospective cohort. Participants comprised 8,812 veterans with type 2 diabetes. The main outcome measure was time to death. The main predictor was race/ethnicity. Other risk factors (or covariates) included age, gender, marital status, employment, glycosylated hemoglobin (HgbA1c), and several ICD-9 coded physical and mental health comorbidities. Average follow-up was 4.5 years; 64% of veterans were non-Hispanic whites (NHW), 97% male, and 84% at least 50 years old. The overall mortality rate was 15% and was significantly lower for non-Hispanic blacks (NHB). Baseline HgbA1c values also differed for NHW (mean = 7.05) and NHB (mean = 7.65) (p < 0.001). In sequentially-built models NHB race was associated with a lower risk of mortality with HR ranging 0.80-0.92. After adjusting for all significant covariates, the risk of mortality remained lower for NHB (HR = 0.84, 95% CI: 0.75, 0.94). Increased mortality risk was associated with age, not being employed or retired, poor glycemic control, cancer, Coronary Heart Disease (CHD), and anxiety disorder; while a lower risk was associated with being female and ever being married. The risk of death among NHB veterans with diabetes remained significantly lower than that of NHW after controlling for important confounding variables. Future studies in the VA need to examine detailed contributions of patient, provider and system-level factors on racial differences in mortality in adults with diabetes, especially if the findings of this study are replicated at other sites or using national VA data. C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Lynch, Cheryl P.; Zhao, Yumin; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Ralph H Johnson Vet Affairs Med Ctr, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM Egedel@musc.edu RI Gilbert, Gregory/C-7735-2016; OI Gilbert, Gregory/0000-0003-0879-5496; Gebregziabher, Mulugeta/0000-0002-4826-481X FU VA HSRD [REA 08-261] FX This study represents work supported by the use of resources at the VA HSR&D Funded Center for Disease Prevention and Health Interventions for Diverse Populations (REA 08-261) in Charleston, SC. NR 33 TC 8 Z9 8 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2010 VL 25 IS 10 BP 1051 EP 1056 DI 10.1007/s11606-010-1405-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 652ZN UT WOS:000282051400011 PM 20532659 ER PT J AU Bishop, TF Federman, AD Ross, JS AF Bishop, Tara F. Federman, Alex D. Ross, Joseph S. TI Laboratory Test Ordering at Physician Offices with and without On-Site Laboratories SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE physician self-referral; reimbursement/incentive; laboratories/economics; laboratories/utilization ID REFERRING PHYSICIANS; OWNERSHIP; CHARGES; GROWTH; COSTS AB Physician self-referral, ordering a test or procedure or referring to a facility in which a physician has a financial interest, has been associated with increased utilization of health care services. To examine the association between on-site laboratories and laboratory test ordering among visits to group-practice physicians. Cross-sectional study using data from the 2005 and 2006 National Ambulatory Medical Care Surveys. Visits by adults to non-federally-funded, non-hospital-based group practices. Primary analyses focused on visits to physician owners; secondary analyses focused on visits to non-owners. Ordering of five laboratory tests: complete blood count (CBC), electrolytes, glycoslyated hemoglobin A1c (HbA1c), cholesterol, and prostate-specific antigen (PSA). There were 19,163 visits to group-practice owners with 51.9% to a practice with an on-site laboratory. Visits to primary care physicians were more likely to be to a practice with an on-site laboratory when compared with visits to specialists (64.4% vs. 34.0%, p < 0.001). Among visits to specialist group owners, all five tests were ordered more often if there was an on-site laboratory, even after accounting for patient and practice characteristics: CBC: adjusted odds ratio[OR] = 8.01, 95% Confidence Interval [CI], 5.00-12.82, p < 0.001; electrolytes: aOR = 3.51, 95% CI, 1.93-6.40, p < 0.001; HbA1c: aOR = 4.91, 95% CI, 1.75-13.78, p = 0.003; cholesterol: aOR = 3.32, 95% CI, 1.85-5.93, p < 0.001; and PSA: aOR = 3.84, 95% CI, 1.93-7.65, p < 0.001. This association was not found among visits to primary care physician owners and all practice non-owners (both primary care and specialists). The estimated excess spending on these five tests by specialist owners with on-site laboratories was $75 million per 100 million visits. In a nationally representative sample of visits to physician-owned group practices, specialist owners with on-site laboratories were more likely to order five common laboratory tests, potentially resulting in millions in excess healthcare spending. C1 [Bishop, Tara F.; Federman, Alex D.] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Bishop, TF (reprint author), Mt Sinai Sch Med, Div Gen Internal Med, 1 Gustave L Levy Pl,Box 1087, New York, NY 10029 USA. EM taraf@alum.mit.edu FU National Institute on Aging [K08 AG032886, K23 AG028955-01]; American Federation of Aging Research FX This project was not directly supported with external funds. Drs. Ross and Federman are both currently supported by the National Institute on Aging (K08 AG032886 and K23 AG028955-01, respectively) and by the American Federation of Aging Research through the Paul B. Beeson Career Development Award Program. NR 23 TC 6 Z9 6 U1 1 U2 2 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 OCT PY 2010 VL 25 IS 10 BP 1057 EP 1063 DI 10.1007/s11606-010-1409-7 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 652ZN UT WOS:000282051400012 PM 20532656 ER PT J AU Donelan, K Rao, SR Rogers, RS Mailhot, JR Galvin, R AF Donelan, Karen Rao, Sowmya R. Rogers, Robert S. Mailhot, Johanna R. Galvin, Robert TI Experience with Health Coach-Mediated Physician Referral in an Employed Insured Population SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE health coach; physician referral; physician performance data; employee assistance program; survey ID PERFORMANCE REPORTS; PATIENT NAVIGATION; CONSUMER REPORTS; CARDIAC-SURGERY; CARE; QUALITY; DIFFERENCE; IMPACT; TIME AB Given increasing interest in helping consumers choose high-performing (higher quality, lower cost) physicians, one approach chosen by several large employers is to provide assistance in the form of a telephonic "health coach" - a registered nurse who assists with identifying appropriate and available providers. To evaluate the health coach's influence on provider choice and the quality of the user experience in the early introduction of this service. Cross-sectional survey of 3490 employees and covered dependents of a large national firm that offered health coach services to all employees and covered dependents. The survey began in September 2007 with proportionate stratified sampling of 1750 employees and covered dependents who used the services between October 2007 and February 2008, and 1740 non-users. Insured adults (ages 21-64) employed by a large national firm or covered dependents of employees. Awareness of the service, reason for using service, visits to providers recommended by service, use of health advice provided by service, user satisfaction. The primary reason for using the service was to obtain provider referrals (73%). Fifty-two percent of users sought a specialist referral, 33% a PCP referral and 9% a hospital referral. Eighty-nine percent of users seeking a provider referral were referred in-network; 81% of those referred visited the referred provider. Measures of satisfaction with both the service and the care delivered by recommended providers were over 70%. Customers largely follow the provider recommendation of the health coach. Users express general satisfaction with existing health coach services, but differences in performance between vendors highlight the need for the services to be well implemented. C1 [Donelan, Karen; Rao, Sowmya R.; Rogers, Robert S.; Mailhot, Johanna R.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT USA. [Galvin, Robert] Gen Elect, Fairfield, CT USA. RP Donelan, K (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM kdonelan@partners.org FU General Electric; MGH Institute for Health Policy FX This research was funded in its entirety by General Electric through a contract with the Massachusetts General Hospital and the MGH Institute for Health Policy. NR 30 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 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2010 VL 25 IS 10 BP 1071 EP 1077 DI 10.1007/s11606-010-1428-4 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 652ZN UT WOS:000282051400014 PM 20556533 ER PT J AU Balasubramanian, H Banerjee, R Denton, B Naessens, J Stahl, J AF Balasubramanian, Hari Banerjee, Ritesh Denton, Brian Naessens, James Stahl, James TI Improving Clinical Access and Continuity through Physician Panel Redesign SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care access; continuity of care; systems engineering ID PRIMARY-CARE; COMPUTER-SIMULATION; PATIENT; TRIAL; MODEL AB Population growth, an aging population and the increasing prevalence of chronic disease are projected to increase demand for primary care services in the United States. Using systems engineering methods, to re-design physician patient panels targeting optimal access and continuity of care. We use computer simulation methods to design physician panels and model a practice's appointment system and capacity to provide clinical service. Baseline data were derived from a primary care group practice of 39 physicians with over 20,000 patients at the Mayo Clinic in Rochester, MN, for the years 2004-2006. Panel design specifically took into account panel size and case mix (based on age and gender). The primary outcome measures were patient waiting time and patient/clinician continuity. Continuity is defined as the inverse of the proportion of times patients are redirected to see a provider other than their primary care physician (PCP). The optimized panel design decreases waiting time by 44% and increases continuity by 40% over baseline. The new panel design provides shorter waiting time and higher continuity over a wide range of practice panel sizes. Redesigning primary care physician panels can improve access to and continuity of care for patients. C1 [Balasubramanian, Hari] Univ Massachusetts, Dept Mech & Ind Engn, Amherst, MA 01003 USA. [Banerjee, Ritesh; Naessens, James] Mayo Clin, Div Hlth Care Policy & Res, Dept Hlth Sci Res, Rochester, MN USA. [Denton, Brian] N Carolina State Univ, Dept Ind & Syst Engn, Raleigh, NC 27695 USA. [Stahl, James] Massachusetts Gen Hosp, Dept Med, MGH Inst Technol Assessment, Boston, MA 02114 USA. RP Balasubramanian, H (reprint author), Univ Massachusetts, Dept Mech & Ind Engn, 160 Governors Dr, Amherst, MA 01003 USA. EM hbalasubraman@ecs.umass.edu NR 31 TC 10 Z9 12 U1 3 U2 7 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 OCT PY 2010 VL 25 IS 10 BP 1109 EP 1115 DI 10.1007/s11606-010-1417-7 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 652ZN UT WOS:000282051400021 PM 20549379 ER PT J AU Henderson, MC Dhaliwal, G Jones, SR Culbertson, C Bowen, JL AF Henderson, Mark C. Dhaliwal, Gurpreet Jones, Stephen R. Culbertson, Charles Bowen, Judith L. TI RE: Doing What Comes Naturally (vol 25, pg 84, 2010) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Correction C1 [Henderson, Mark C.; Bowen, Judith L.] UC Davis Med Ctr, Dept Internal Med, Sacramento, CA USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. [Jones, Stephen R.; Culbertson, Charles] Legacy Hlth Syst, Dept Internal Med, Portland, OR USA. [Jones, Stephen R.; Culbertson, Charles] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Henderson, MC (reprint author), UC Davis Med Ctr, Dept Internal Med, Sacramento, CA USA. EM MCHenderson@ucdavis.edu NR 1 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 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2010 VL 25 IS 10 BP 1138 EP 1138 DI 10.1007/s11606-010-1339-4 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 652ZN UT WOS:000282051400028 ER PT J AU Trombetta, JM Bradshaw, AD AF Trombetta, Jessica M. Bradshaw, Amy D. TI SPARC/Osteonectin Functions to Maintain Homeostasis of the Collagenous Extracellular Matrix in the Periodontal Ligament SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE SPARC; periodontal ligament; collagen; BM-40; osteonectin; extracellular matrix; matricellular; periodontium; aging ID ALVEOLAR BONE LOSS; MATRICELLULAR PROTEIN; SECRETED PROTEIN; CELL-MATRIX; SPARC; FIBROBLASTS; DISEASE; TISSUES; FIBRILLOGENESIS; REGENERATION AB Expression of secreted protein acidic and rich in cysteine (SPARC)/osteonectin, a collagen-binding matricellular protein, is frequently associated with tissues with high rates of collagen turnover, such as bone. In the oral cavity, expression of SPARC/osteonectin has been localized to the periodontal ligament (PDL), a collagen-rich tissue with high rates of collagen turnover. The PDL is critical for tooth position within the alveolar bone and for absorbing forces generated by chewing. To characterize the function of SPARC/osteonectin in PDL, SPARC/osteonectin expression in murine PDL was evaluated by immunochemistry at 1, 4, 6, and >18 months. Highest levels of SPARC/osteonectin were detected at 1 and >18 months, with decreased levels associated with adult (4-6 months) PDL. To determine whether the absence of SPARC/osteonectin expression influenced cellular and fibrillar collagen content in PDL, PDL of SPARC-null mice was evaluated using histological stains and compared with that of wild-type (WT). Our results demonstrated decreased numbers of nuclei in PDL of SPARC-null mice at 1 month. In addition, decreased collagen volume fractions were found at 1 and >18 months and decreases in thick collagen fiber volume fraction were detected at 4, 6, and >18 months in SPARC-null PDL. The greatest differences in cell number and in collagen content between SPARC-null and WT PDL coincided with ages at which levels of SPARC/osteonectin expression were highest in WT PDL, at 1 and >18 months. These results support the hypothesis that SPARC/osteonectin is critical in the control of tissue collagen content and indicate that SPARC/osteonectin is necessary for PDL homeostasis. (J Histochem Cytochem 58:871-879, 2010) C1 [Bradshaw, Amy D.] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Craniofacial Biol, Charleston, SC 29425 USA. [Trombetta, Jessica M.; Bradshaw, Amy D.] Med Univ S Carolina, Div Cardiol, Dept Med, Charleston, SC 29425 USA. [Bradshaw, Amy D.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Bradshaw, AD (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Craniofacial Biol, 114 Doughty St,Rm 223, Charleston, SC 29425 USA. EM bradshad@musc.edu RI Self, Casey/B-6871-2011 FU National Institutes of Health [T32 DE-017551, 2P20RR017696, HL-094517]; Veterans Administration FX This work was supported by National Institutes of Health Grants T32 DE-017551 (to JMT), 2P20RR017696 (to ADB), and HL-094517 (to ADB) and by a Veterans Administration Merit Award (to ADB). NR 33 TC 18 Z9 19 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD OCT PY 2010 VL 58 IS 10 BP 871 EP 879 DI 10.1369/jhc.2010.956144 PG 9 WC Cell Biology SC Cell Biology GA 652BK UT WOS:000281975100002 PM 20566756 ER PT J AU Tawara, I Shlomchik, WD Jones, A Zou, WP Nieves, E Liu, C Toubai, T Duran-Struuck, R Sun, YP Clouthier, SG Evers, R Lowler, KP Levy, RB Reddy, P AF Tawara, Isao Shlomchik, Warren D. Jones, Angela Zou, Weiping Nieves, Evelyn Liu, Chen Toubai, Tomomi Duran-Struuck, Raimon Sun, Yaping Clouthier, Shawn G. Evers, Rebecca Lowler, Kathleen P. Levy, Robert B. Reddy, Pavan TI A Crucial Role for Host APCs in the Induction of Donor CD4(+) CD25(+) Regulatory T Cell-Mediated Suppression of Experimental Graft-versus-Host Disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ANTIGEN-PRESENTING CELLS; DRAINING LYMPH-NODES; RAT EPIDERMAL-CELLS; DENDRITIC CELLS; IA-ANTIGEN; INDOLEAMINE 2,3-DIOXYGENASE; ALLOANTIGEN EXPRESSION; GUT EPITHELIUM; TOLERANCE AB Allogeneic bone marrow transplantation is an effective treatment for a number of malignant and nonmalignant diseases (Applebaum. 2001. Nature. 411: 385-389 and Copelan. 2006. N Engl JMed. 354: 1813-1826). However, the application of this therapeutic modality has been impeded by a number of confounding side effects, the most frequent and severe of which is the development of graft-versus-host disease (GVHD) (Copelan. 2006. N Engl J Med. 354: 1813-1826 and Blazar and Murphy. 2005. Philos Trans R Soc Lond B Biol Sci. 360: 1747-1767). Alloreactive donor T cells are critical for causing GVHD (Fowler. 2006. Crit Rev Oncol Hematol. 57: 225-244 and Ferrara and Reddy. 2006. Semin Hematol. 43: 3-10), whereas recent data demonstrated a significant role for the naturally occurring thymic-derived donor CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) (Bluestone and Abbas. 2003. Nat Rev Immunol. 3: 253-257 and Shevach. 2006. Immunity. 25: 195-201) in suppressing experimental GVHD after bone marrow transplantation (Blazar and Taylor. 2005. Biol Blood Marrow Transpl. 11: 46-49 and Joffe and van Meerwijk. 2006. Semin Immunol. 18: 128-135). Host APCs are required for induction of GVHD by the conventional donor T cells. However, it is not known whether they are also obligatory for donor Treg-mediated suppression of GVHD. Using multiple clinically relevant MHC-matched and -mismatched murine models of GVHD, we investigated the role of host APCs in the suppression of GVHD by donor Tregs. We found that alloantigen expression by the host APCs is necessary and sufficient for induction of GVHD protection by donor Tregs. This requirement was independent of their effect on the maintenance of Treg numbers and the production of IL-10 or IDO by the host APCs. The Journal of Immunology, 2010, 185: 3866-3872. C1 [Tawara, Isao; Zou, Weiping; Nieves, Evelyn; Toubai, Tomomi; Sun, Yaping; Clouthier, Shawn G.; Evers, Rebecca; Lowler, Kathleen P.; Reddy, Pavan] Univ Michigan, Ctr Comprehens Canc, Dept Internal Med, Ann Arbor, MI 48109 USA. [Shlomchik, Warren D.] Yale Univ, Dept Med, New Haven, CT 06510 USA. [Jones, Angela; Levy, Robert B.] Univ Miami, Miami, FL 33136 USA. [Duran-Struuck, Raimon] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Liu, Chen] Univ Florida, Gainesville, FL 32611 USA. RP Reddy, P (reprint author), Univ Michigan, Ctr Canc, 3312 CCC,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM RLevy@med.miami.edu; reddypr@umich.edu FU National Institutes of Health [AI-075284, HL-090775]; Leukemia Lymphoma Society FX This work was supported by National Institutes of Health Grants AI-075284 and HL-090775 (both to P. R.). P. R. is a recipient of a Clinical Scholar Award from the Leukemia Lymphoma Society. NR 47 TC 32 Z9 34 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2010 VL 185 IS 7 BP 3866 EP 3872 DI 10.4049/jimmunol.1001625 PG 7 WC Immunology SC Immunology GA 653BU UT WOS:000282059500012 PM 20810991 ER PT J AU Renner, B Strassheim, D Amura, CR Kulik, L Ljubanovic, D Glogowska, MJ Takahashi, K Carroll, MC Holers, VM Thurman, JM AF Renner, Brandon Strassheim, Derek Amura, Claudia R. Kulik, Liudmila Ljubanovic, Danica Glogowska, Magdalena J. Takahashi, Kazue Carroll, Michael C. Holers, V. Michael Thurman, Joshua M. TI B Cell Subsets Contribute to Renal Injury and Renal Protection after Ischemia/Reperfusion SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMPLEMENT ACTIVATION; ISCHEMIA-REPERFUSION; MICE DEFICIENT; TISSUE-INJURY; INFLAMMATION; FAILURE; IGM AB Ischemia/reperfusion (I/R) triggers a robust inflammatory response within the kidney. Numerous components of the immune system contribute to the resultant renal injury, including the complement system. We sought to identify whether natural Abs bind to the postischemic kidney and contribute to complement activation after I/R. We depleted peritoneal B cells in mice by hypotonic shock. Depletion of the peritoneal B cells prevented the deposition of IgM within the glomeruli after renal I/R and attenuated renal injury after I/R. We found that glomerular IgM activates the classical pathway of complement, but it does not cause substantial deposition of C3 within the kidney. Furthermore, mice deficient in classical pathway proteins were not protected from injury, indicating that glomerular IgM does not cause injury through activation of the classical pathway. We also subjected mice deficient in all mature B cells (mu MT mice) to renal I/R and found that they sustained worse renal injury than wild-type controls. Serum IL-10 levels were lower in the mu MT mice. Taken together, these results indicate that natural Ab produced by peritoneal B cells binds within the glomerulus after renal I/R and contributes to functional renal injury. However, nonperitoneal B cells attenuate renal injury after I/R, possibly through the production of IL-10. The Journal of Immunology, 2010, 185: 4393-4400. C1 [Renner, Brandon; Strassheim, Derek; Amura, Claudia R.; Kulik, Liudmila; Glogowska, Magdalena J.; Holers, V. Michael; Thurman, Joshua M.] Univ Colorado, Sch Med, Dept Med, Denver, CO 80045 USA. [Ljubanovic, Danica] Univ Hosp Dubrava, Dept Pathol, Zagreb, Croatia. [Takahashi, Kazue] Massachusetts Gen Hosp, Program Dev Immunol, Boston, MA 02115 USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Thurman, JM (reprint author), Univ Colorado Denver, Sch Med, Div Nephrol & Hypertens, B-115,POB 6511, Aurora, CO 80045 USA. EM Joshua.Thurman@UCdenver.edu FU National Institutes of Health [DK076690, DK77661, AI311052, AI077081, AI07450]; Satellite Healthcare FX This work was supported in part by National Institutes of Health Grants DK076690 and DK77661 (to J.M.T.), AI311052 (to V.M.H.), and AI077081 and AI07450 (to K.T.). This work was also supported by a Norman S. Coplon Extramural Grant from Satellite Healthcare (to J.M.T.). NR 18 TC 35 Z9 37 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2010 VL 185 IS 7 BP 4393 EP 4400 DI 10.4049/jimmunol.0903239 PG 8 WC Immunology SC Immunology GA 653BU UT WOS:000282059500067 PM 20810984 ER PT J AU Crum-Cianflone, NF Hullsiek, KH Roediger, M Ganesan, A Patel, S Landrum, ML Weintrob, A Agan, BK Medina, S Rahkola, J Hale, BR Janoff, EN AF Crum-Cianflone, Nancy F. Hullsiek, Katherine Huppler Roediger, Mollie Ganesan, Anuradha Patel, Sugat Landrum, Michael L. Weintrob, Amy Agan, Brian K. Medina, Sheila Rahkola, Jeremy Hale, Braden R. Janoff, Edward N. CA Infect Dis Clinical Res Program HI TI A Randomized Clinical Trial Comparing Revaccination with Pneumococcal Conjugate Vaccine to Polysaccharide Vaccine among HIV-Infected Adults SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; PROTECTIVE ANTIBODY-RESPONSES; CELL TRANSPLANTATION; DOUBLE-BLIND; DISEASE; CHILDREN; IMMUNOGENICITY; IMMUNIZATION; BACTEREMIA; TYPE-1 AB Background. The risk of pneumococcal disease persists, and antibody responses to revaccination with the 23-valent polysaccharide vaccine (PPV) are low among human immunodeficiency virus (HIV)-infected adults. We determined whether revaccination with the 7-valent pneumococcal conjugate vaccine (PCV) would enhance these responses. Methods. In a randomized clinical trial, we compared the immunogenicity of revaccination with PCV (np) or PPV (n = 73) among HIV-infected adults (median CD4 cell count, 533 cells/mm(3)) who had been vaccinated with PPV 3-8 years earlier. HIV-uninfected adults (n = 25) without prior pneumococcal vaccination received 1 dose of PCV. A positive response was defined as a >= 2-fold increase (from baseline to day 60) in capsule-specific immunoglobulin G, with a postvaccination level >= 1000 ng/mL for at least 2 of the 4 serotypes. Results. HIV-infected persons demonstrated a higher frequency of positive antibody responses to PCV than to PPV (57% vs 36%) (Pp. 004) and greater mean changes in the immunoglobulin G concentration from baseline to day 60 for serotypes 4, 9V, and 19F (P<.05, for all), but not for serotype 14. However, by day 180, both outcomes were similar. Responses to PCV were greater in frequency and magnitude for all serotypes in HIV-uninfected adults, compared with those in HIV-infected adults. Conclusions. Among persons with HIV infection, revaccination with PCV was only transiently more immunogenic than PPV, and responses were inferior to those in HIV-uninfected subjects with primary vaccination. Pneumococcal vaccines with more robust and sustained immunogenicity are needed for HIV-infected adults. C1 [Crum-Cianflone, Nancy F.] USN, San Diego Med Ctr, Clin Invest Dept KCA, Infect Dis Clin, San Diego, CA 92134 USA. [Crum-Cianflone, Nancy F.; Hullsiek, Katherine Huppler; Roediger, Mollie; Ganesan, Anuradha; Landrum, Michael L.; Weintrob, Amy; Agan, Brian K.; Medina, Sheila; Hale, Braden R.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Ganesan, Anuradha] USN, Med Ctr, Infect Dis Clin, Bethesda, MD 20814 USA. [Hullsiek, Katherine Huppler; Roediger, Mollie] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Patel, Sugat] USN, Med Ctr Portsmouth, Infect Dis Clin, Portsmouth, VA USA. [Landrum, Michael L.] San Antonio Mil Med Ctr, Infect Dis Serv, San Antonio, TX USA. [Weintrob, Amy] Walter Reed Army Med Ctr, Infect Dis Clin, Washington, DC 20307 USA. [Rahkola, Jeremy; Janoff, Edward N.] Univ Colorado, Div Infect Dis, Mucosal & Vaccine Res Program Colorado, Denver, CO 80202 USA. [Janoff, Edward N.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Crum-Cianflone, NF (reprint author), USN, San Diego Med Ctr, Clin Invest Dept KCA, Infect Dis Clin, 34800 Bob Wilson Dr,Ste 5, San Diego, CA 92134 USA. EM nancy.crum@med.navy.mil; braden.hale@med.navy.mil OI Polis, Michael/0000-0002-9151-2268; Agan, Brian/0000-0002-5114-1669 FU NIAID NIH HHS [Y01 AI005072, Y1-AI-5072] NR 35 TC 42 Z9 44 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2010 VL 202 IS 7 BP 1114 EP 1125 DI 10.1086/656147 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 651FR UT WOS:000281912100016 PM 20795819 ER PT J AU Comeau, AM Hale, JE Pai, SY Bonilla, FA Notarangelo, LD Pasternack, MS Meissner, HC Cooper, ER DeMaria, A Sahai, I Eaton, RB AF Comeau, Anne Marie Hale, Jaime E. Pai, Sung-Yun Bonilla, Francisco A. Notarangelo, Luigi D. Pasternack, Mark S. Meissner, H. Cody Cooper, Ellen Rae DeMaria, Alfred Sahai, Inderneel Eaton, Roger B. TI Guidelines for implementation of population-based newborn screening for severe combined immunodeficiency SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID STEM-CELL TRANSPLANTATION; LYMPHOCYTES; DISEASES; DEFECTS; INFANTS AB Severe combined immunodeficiency (SCID) is a Primary Immune Deficiency that is under consideration for population-based newborn screening (NBS) by many NBS programs, and has recently been recommended for inclusion in the US uniform panel of newborn screening conditions. A marker of SCID, the T cell receptor excision circle (TREC), is detectable in the newborn dried blood spot using a unique molecular assay as a primary screen. The New England Newborn Screening Program developed and validated a multiplex TREC assay in which both the TREC analyte and an internal control are acquired from a single punch and run in the same reaction. Massachusetts then implemented a statewide pilot SCID NBS program. The authors describe the rationale for a pilot SCID NBS program, a comprehensive strategy for successful implementation, the screening test algorithm, the screening follow-up algorithm and preliminary experience based on statewide screening in the first year. The Massachusetts experience demonstrates that SCID NBS is a program that can be implemented on a population basis with reasonable rates of false positives. C1 [Comeau, Anne Marie; Hale, Jaime E.; Sahai, Inderneel; Eaton, Roger B.] UMass Med Sch, New England Newborn Screening Program, Jamaica Plain, MA 02130 USA. [Pai, Sung-Yun; Bonilla, Francisco A.; Notarangelo, Luigi D.] Childrens Hosp, Boston, MA 02115 USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pasternack, Mark S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meissner, H. Cody] Tufts Med Ctr, Boston, MA USA. [Cooper, Ellen Rae] Boston Med Ctr, Boston, MA USA. [DeMaria, Alfred] Massachusetts Dept Publ Hlth, Boston, MA USA. RP Comeau, AM (reprint author), UMass Med Sch, New England Newborn Screening Program, 305 South St, Jamaica Plain, MA 02130 USA. EM anne.comeau@umassmed.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 29 TC 30 Z9 30 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD OCT PY 2010 VL 33 SU 2 BP S273 EP S281 DI 10.1007/s10545-010-9103-9 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 658UT UT WOS:000282515600012 PM 20490925 ER PT J AU Hale, JE Parad, RB Dorkin, HL Gerstle, R Lapey, A O'Sullivan, BP Spencer, T Yee, W Comeau, AM AF Hale, Jaime E. Parad, Richard B. Dorkin, Henry L. Gerstle, Robert Lapey, Allen O'Sullivan, Brian P. Spencer, Terry Yee, William Comeau, Anne Marie TI Cystic fibrosis newborn screening: using experience to optimize the screening algorithm SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID IMPLEMENTATION; GUIDELINES AB Newborn screening (NBS) for cystic fibrosis (CF) offers the opportunity for early diagnosis and improved outcomes in patients with CF and has been universally available in the state of Massachusetts since 1999 using an immunoreactive trypsinogen (IRT)-DNA algorithm. Ideally, CF NBS is incorporated as part of an integrated NBS system that allows for comprehensive and coordinated education, laboratory screening, clinical follow-up, and evaluation so that evidence-based data can be used to maximize quality improvements and optimize the screening algorithm. The New England Newborn Screening Program (NENSP) retrospectively analyzed Massachusetts's CF newborn screening data that yielded decisions to eliminate a screen-positive category, maintain the IRT cutoff value that prompts the second tier DNA testing, and communicate CF relative risk to primary care providers (PCPs) based on categorization of positive CF NBS results. C1 [Hale, Jaime E.; Comeau, Anne Marie] UMass Med Sch, New England Newborn Screening Program, Jamaica Plain, MA 02130 USA. [Parad, Richard B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dorkin, Henry L.; Spencer, Terry] Childrens Hosp, Boston, MA 02115 USA. [Gerstle, Robert] Baystate Med Ctr, Springfield, MA USA. [Lapey, Allen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Sullivan, Brian P.; Comeau, Anne Marie] UMass Med Sch, Dept Pediat, Worcester, MA USA. [Yee, William] Tufts Med Ctr, Boston, MA USA. RP Comeau, AM (reprint author), UMass Med Sch, New England Newborn Screening Program, 305 South St, Jamaica Plain, MA 02130 USA. EM anne.comeau@umassmed.edu RI Parad, Richard/E-8559-2010 FU University of Massachusetts Medical School; HRSA [U22MC03959] FX This work was funded in part by The New England Newborn Screening Program of University of Massachusetts Medical School and HRSA grant U22MC03959 subcontract for Priority Focus 2. NR 11 TC 13 Z9 13 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD OCT PY 2010 VL 33 SU 2 BP S255 EP S261 DI 10.1007/s10545-010-9117-3 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 658UT UT WOS:000282515600010 PM 20521170 ER PT J AU Kumar, P Blendea, D Nandigam, V Moore, SA Heist, EK Singh, JP AF Kumar, Prabhat Blendea, Dan Nandigam, Veena Moore, Stephanie A. Heist, E. Kevin Singh, Jagmeet P. TI Assessment of the post-implant final left ventricular lead position: a comparative study between radiographic and angiographic modalities SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE Cardiac resynchronization therapy; Left ventricular lead position; Chest x-ray; Rotational coronary venous angiography ID CARDIAC-RESYNCHRONIZATION THERAPY; CHRONIC HEART-FAILURE; VENOUS ANGIOGRAPHY; ECHOCARDIOGRAPHY; MORTALITY AB Post-implant lateral and postero-anterior chest X-rays (CXR) are often utilized to determine the final LV lead tip position after cardiac resynchronization therapy (CRT). This study sought to compare post-implant standard CXRs with intra-procedural rotational coronary venous angiography (RCVA) to localize the final LV lead position. Sixty-four patients undergoing CRT (69.2 +/- 11.4 years; males 68.7%; ischemic cardiomyopathy 59.4%; NYHA class 2.9 +/- 0.5 and LV ejection fraction 24% +/- 9%) were included in the study. RCVA was done by recording a rapid 4-second isocentric cine-loop from RAO 55A degrees to LAO 55A degrees (120 frames). Conventional CXR method (CC) and a composite CXR strategy (CM) based on two-view CXR were separately compared with RCVA. The most common pacing site was lateral (64.1%), followed by postero-lateral (23.4%) and antero-lateral (10.9%). In 73.4% (47) cases, the LV lead position was misclassified by CC as compared to RCVA. Among the 47 (73.4%) cases misclassified by CC approach, 35 had lateral LV lead position misclassified by CC as postero-lateral (77%), posterior (20%) and antero-lateral (3%). On the other hand, CM strategy classified the LV lead position correctly in 46 (71.9%) of the patients (p < 0.0001). The composite CXR strategy is a useful method for post-procedure LV lead localization. Due to its simplicity, it can be widely applied in post-implant evaluation of LV lead position in CRT patients. C1 [Kumar, Prabhat; Blendea, Dan; Nandigam, Veena; Moore, Stephanie A.; Heist, E. Kevin; Singh, Jagmeet P.] Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp,Heart Ctr GRB 109, Boston, MA 02412 USA. RP Singh, JP (reprint author), Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp,Heart Ctr GRB 109, 55 Fruit St, Boston, MA 02412 USA. EM jsingh@partners.org FU St. Jude Medical; Biotronik; Medtronic Inc.; Boston Scientific Corp. FX Prabhat Kumar: no potential conflicts of interest; Dan Blendea: no potential conflicts of interest; Veena Nandigam: no potential conflicts of interest; Stephanie Moore receives honoraria from Boston Scientific Corp. and research grants from St. Jude Medical; E. Kevin Heist receives honoraria from Biotronik, Boston Scientific Corp., Medtronic, St. Jude Medical and Sorin group; receives research grants from Biotronik, St. Jude Medical (all modest) and is consultant to St Jude Medical; Jagmeet P Singh has received research grants from St. Jude Medical, Medtronic Inc., Boston Scientific Corp. and Biotronik; has received Honoraria / Speaker Fees from Medtronic Inc., Biotronik, Guidant Corp., St. Jude Medical and has served on advisory Board/Steering Committee and as Consultant to Boston Scientific Corp., Biotronik, St. Jude Medical, Medtronic, Philips Medical Systems. No stocks/No speakers bureau. NR 12 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD OCT PY 2010 VL 29 IS 1 BP 17 EP 22 DI 10.1007/s10840-010-9497-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 652AQ UT WOS:000281972600003 PM 20556496 ER PT J AU Safian, RD Jaff, MR Bresnahan, JF Foster, M Bacharach, JM Yadav, J Joye, J Myla, S Kassab, E Mann, JT Ansel, GM AF Safian, Robert D. Jaff, Michael R. Bresnahan, John F. Foster, Malcolm Bacharach, J. Michael Yadav, Jay Joye, James Myla, Subbarao Kassab, Elias Mann, J. Tift Ansel, Gary M. CA CREATE SpideRX Trial Investigators TI Protected Carotid Stenting in High-Risk Patients: Results of the SpideRX Arm of the Carotid Revascularization with ev3 Arterial Technology Evolution Trial SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID EMBOLIC PROTECTION; CAPTURE REGISTRY; ENDARTERECTOMY; STENOSIS; STROKES AB Purpose: A prospective nonrandomized multicenter registry of 160 patients with severe carotid stenosis and high-risk features for carotid endarterectomy was conducted during the 3-month period from March to May 2005. Methods: Carotid artery stenting (CAS) was performed with the SpideRX (TM) Embolic Protection System (ev3, Inc., Plymouth, MN, USA) as part of an investigational device exemption from the Food and Drug Administration. Results: The primary end-point of major adverse cardiac and cerebrovascular events at 30 days after CAS was observed in nine patients (5.6%), including death in four patients (2.5%), nonfatal stroke in five patients (3.1%), and nonfatal myocardial infarction in one patient (0.6%). A secondary end-point of technical success (defined as successful deployment of all devices, filter retrieval, and final diameter stenosis < 50%) was achieved in 156 of 160 patients (97.5%). The only independent predictor of death or stroke at 30 days was baseline stenosis severity (P < 0.05). Conclusion: CAS with distal embolic protection using the SpideRX (TM) Embolic Protection System is a reasonable alternative for revascularization of some high-risk patients with severe carotid stenosis. (J Interven Cardiol 2010;23:491-498). C1 [Safian, Robert D.] William Beaumont Hosp, Ctr Heart, Royal Oak, MI 48073 USA. [Jaff, Michael R.] Mayo Clin, Rochester, MN USA. [Bresnahan, John F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Foster, Malcolm] Baptist Heart Inst, Nashville, TN USA. [Bacharach, J. Michael] N Cent Heart Hosp S Dakota, Sioux Falls, SD USA. [Yadav, Jay] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Joye, James] El Camino Hosp, Mountain View, CA USA. [Myla, Subbarao] Hoag Mem Hosp, Newport Beach, CA USA. [Kassab, Elias] Oakwood Hosp, Dearborn, MI USA. [Mann, J. Tift] Wake Heart Associates, Raleigh, NC USA. [Ansel, Gary M.] Riverside Methodist Hosp, Columbus, OH 43214 USA. RP Safian, RD (reprint author), William Beaumont Hosp, Ctr Heart, 3rd Floor, Royal Oak, MI 48073 USA. EM rsafian@beaumont.edu FU ev3 Inc (Plymouth, MN, USA) FX This study was supported by an educational research grant from ev3 Inc (Plymouth, MN, USA), which was responsible for data collection and data analysis. NR 19 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0896-4327 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD OCT PY 2010 VL 23 IS 5 BP 491 EP 498 DI 10.1111/j.1540-8183.2010.00578.x PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 658UA UT WOS:000282513700011 PM 20624206 ER PT J AU Pang, YG Greisler, HP AF Pang, Yonggang Greisler, Howard P. TI Using a Type 1 Collagen-Based System to Understand Cell-Scaffold Interactions and to Deliver Chimeric Collagen-Binding Growth Factors for Vascular Tissue Engineering SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE type 1 collagen; growth factor; confocal microscopy; local delivery; scaffold ID SMOOTH-MUSCLE-CELLS; DRUG-DELIVERY; BLOOD-VESSEL; IN-VITRO; MIGRATION; MATRIX; REORGANIZATION; CONSTRUCTION; BIOMATERIALS; VEHICLE AB Vascular tissue engineering should provide more biocompatible and functional conduits than synthetic vascular grafts. Understanding cell-scaffold interactions and developing an efficient delivery system for growth factors and other biomolecules to control the signaling between the cells and the scaffold are fundamental issues in a wide range of tissue engineering research fields. Type 1 collagen is a natural scaffold extensively used in vascular tissue engineering and is a widely used vehicle in biomolecule delivery. In this article, we will discuss type 1 collagen as a vascular tissue engineering scaffold, describe strategies for elucidating the interaction between cells and type 1 collagen scaffolds using various imaging techniques, and summarize our work on the development of a chimeric collagen-binding growth factor-based local delivery system. C1 [Pang, Yonggang; Greisler, Howard P.] Loyola Univ, Dept Surg, Med Ctr, Maywood, IL 60153 USA. [Pang, Yonggang; Greisler, Howard P.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Pang, Yonggang] IIT, Dept Biomed Engn, Chicago, IL 60616 USA. [Greisler, Howard P.] Loyola Univ, Med Ctr, Dept Cell Biol Neurobiol & Anat, Maywood, IL 60153 USA. RP Greisler, HP (reprint author), Loyola Univ, Dept Surg, Med Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA. EM hgreisl@lumc.edu RI Pang, Yonggang/B-2843-2011 FU NIH [R01-HL41272]; Department of Veteran's Affairs; Chicago Association for Research and Education in Science; National Center for Research Resources [R13 RR023236] FX Supported by grants from the NIH R01-HL41272 (HPG), Department of Veteran's Affairs (HPG), and Chicago Association for Research and Education in Science (HPG). This symposium was supported in part by a grant from the National Center for Research Resources (R13 RR023236). NR 33 TC 6 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD OCT PY 2010 VL 58 IS 7 BP 845 EP 848 PG 4 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 653WD UT WOS:000282127700010 PM 20683346 ER PT J AU Kaczorowski, DJ Afrazi, A Scott, MJ Kwak, JH Gill, R Edmonds, RD Liu, YJ Fan, J Billiar, TR AF Kaczorowski, David J. Afrazi, Amin Scott, Melanie J. Kwak, Joon H. Gill, Roop Edmonds, Rebecca D. Liu, Yujian Fan, Jie Billiar, Timothy R. TI Pivotal Advance: The pattern recognition receptor ligands lipopolysaccharide and polyinosine-polycytidylic acid stimulate factor B synthesis by the macrophage through distinct but overlapping mechanisms SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE Toll-like receptors; complement; inflammation ID TOLL-LIKE RECEPTORS; INNATE IMMUNITY; ENDOTHELIAL-CELLS; MOUSE MACROPHAGES; 3RD COMPONENT; EARLY EVENTS; IFN-GAMMA; TNF-ALPHA; COMPLEMENT; PATHWAY AB TLRs and complement are critical to the host response in sepsis, trauma, and ischemia/reperfusion. We hypothesize that TLR stimulation leads to synthesis and release of complement components by macrophages, an important source of extrahepatic complement. RAW264.7 macrophages or peritoneal macrophages from WT and TLR4-, TLR3-, TRIF-, or MyD88-deficient mice were cultured under standard conditions. In some experiments, cells were pretreated with inhibitors of MAPKs or a NF-kappa B inhibitor. Cells were stimulated with TLR ligands at known stimulatory concentrations. Intratracheal and i.p. injections were also performed in mice. RT-PCR, Western blotting, and immunocytochemistry were used for analysis. Using a RT-PCR-based panel, we demonstrate that of 18 complement components tested, factor B of the alternative pathway is the most robustly up-regulated complement component in macrophages in response to LPS. This up-regulation results in release of factor B into the media. Upregulation of factor B by LPS is dependent on TLR4, TRIF, JNK, and NF-kappa B. A screen of other TLR ligands demonstrated that stimulation with poly I: C (dsRNA analog) also results in up-regulation of factor B, which is dependent on JNK and NF-kappa B but independent of TLR3 and TRIF. Up-regulation of factor B is also observed after intratracheal and i.p. injection of LPS or poly I: C in vivo. PRR stimulation profoundly influences production and release of factor B by macrophages. Understanding the mechanisms of PRR-mediated complement production may lead to strategies aimed at preventing tissue damage in diverse settings, including sepsis, trauma, and ischemia/reperfusion. J. Leukoc. Biol. 88: 609-618; 2010. C1 [Kaczorowski, David J.; Afrazi, Amin; Scott, Melanie J.; Kwak, Joon H.; Gill, Roop; Edmonds, Rebecca D.; Liu, Yujian; Fan, Jie; Billiar, Timothy R.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Liu, Yujian; Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Surg Res, Pittsburgh, PA USA. RP Billiar, TR (reprint author), Univ Pittsburgh, Presbyterian Univ Hosp, Dept Surg F1281, Med Ctr, POB 7533,200 Lothrop St, Pittsburgh, PA 15213 USA. EM billiartr@upmc.edu FU National Institutes of Health [P50-GM-53789, R01-HL-079669]; VA Merit Award; American College of Surgeons FX This work was supported by National Institutes of Health grant P50-GM-53789 (T. R. B. and J.F.), National Institutes of Health grant R01-HL-079669 (J. F.), and VA Merit Award (J. F.). D. J. K. and R. D. E. are each recipients of American College of Surgeons Resident Research Scholarships. We thank Meihua Bo, Hong Liao, and Danielle Reiser for technical assistance. NR 33 TC 14 Z9 14 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD OCT PY 2010 VL 88 IS 4 BP 609 EP 618 DI 10.1189/jlb.0809588 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 692ZW UT WOS:000285195400002 PM 20413727 ER PT J AU Shen, LR Lai, CQ Feng, XA Parnell, LD Wan, JB Wang, JD Li, D Ordovas, JM Kang, JX AF Shen, Li Rong Lai, Chao Qiang Feng, Xiang Parnell, Laurence D. Wan, Jian Bo Wang, Jing D. Li, Duo Ordovas, Jose M. Kang, Jing X. TI Drosophila lacks C20 and C22 PUFAs SO JOURNAL OF LIPID RESEARCH LA English DT Article DE D. melanogaster; fatty acid metabolism; desaturases; beta-oxidation; model organism ID LIFE-SPAN; METABOLISM; MELANOGASTER; DIET; NUTRIGENOMICS AB Drosophila melanogaster has been considered a model organism for investigating human diseases and genetic pathways. Whether Drosophila is an ideal model for nutrigenomics, especially for FA metabolism, however, remains to be illustrated. The aim of this study was to examine the metabolism of C20 and C22 PUFAs in Drosophila. Analysis of FA composition revealed a complete lack of C20 and C22 PUFAs in the body tissue of larvae, pupae, and adult flies fed either a base or supplemented diet abundant in the PUFA precursors linoleic acid and alpha-linolenic acid. PUFA with >C20 could only be found in flies supplemented with specific FAs. Interestingly, the supplemented C22 PUFAs docosahexaenoic acid (22:6n-3) and docosatetraenoic acid (22:4n-6) were largely converted to the shorter chain C20 PUFAs eicosapentaenoic acid (20:5n-3) and arachidonic acid (20:4n-6), respectively. Furthermore, a genome sequence scan indicated that no gene encoding Delta-6/Delta-5 desaturases, the key enzymes for the synthesis of C20/C22 PUFA, was present in Drosophila. These findings demonstrate that Drosophila lacks the capability to synthesize the biologically important C20 and C22 PUFAs, and thereby argue that Drosophila is not a valid model for the study of lipid metabolism and related diseases.-Shen, L. R., C. Q. Lai, X. Feng, L. D. Parnell, J. B. Wan, J. D, Wang, D. Li, J. M. Ordovas, and J. X. Kang. Drosophila lacks C20 and C22 PUFAs. J. Lipid Res. 2010. 51: 2985-2992. C1 [Shen, Li Rong; Feng, Xiang; Wan, Jian Bo; Wang, Jing D.; Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Shen, Li Rong; Feng, Xiang; Wan, Jian Bo; Wang, Jing D.; Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Shen, Li Rong; Li, Duo] Zhejiang Univ, Dept Food Sci & Nutr, Hangzhou 310029, Zhejiang, Peoples R China. [Lai, Chao Qiang; Parnell, Laurence D.; Ordovas, Jose M.] Tufts Univ, Nutr & Genom Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Feng, Xiang] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou 510275, Guangdong, Peoples R China. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, Lab Lipid Med & Technol, Boston, MA 02114 USA. EM jxkang@partners.org RI Wan, Jian-Bo/D-8368-2014; OI Wan, Jian-Bo/0000-0002-6750-2617; Ordovas, Jose/0000-0002-7581-5680 FU National Institutes of Health [CA-113605]; Ministry of Science and Technology of China [2007AA10Z324] FX This study was supported by National Institutes of Health Grant CA-113605 and grant 2007AA10Z324 from The Ministry of Science and Technology of China. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or other granting agencies. NR 15 TC 28 Z9 32 U1 0 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD OCT PY 2010 VL 51 IS 10 BP 2985 EP 2992 DI 10.1194/jlr.M008524 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649GS UT WOS:000281756800012 PM 20656917 ER PT J AU Hammad, SM Pierce, JS Soodavar, F Smith, KJ Al Gadban, MM Rembiesa, B Klein, RL Hannun, YA Bielawski, J Bielawska, A AF Hammad, Samar M. Pierce, Jason S. Soodavar, Farzan Smith, Kent J. Al Gadban, Mohammed M. Rembiesa, Barbara Klein, Richard L. Hannun, Yusuf A. Bielawski, Jacek Bielawska, Alicja TI Blood sphingolipidomics in healthy humans: impact of sample collection methodology SO JOURNAL OF LIPID RESEARCH LA English DT Article DE sphingolipid metabolome; sphingomyelin; ceramide; sphingosine ID TANDEM MASS-SPECTROMETRY; APOLIPOPROTEIN-A-I; SPHINGOSINE 1-PHOSPHATE; DENSITY-LIPOPROTEIN; SIGNAL-TRANSDUCTION; SPHINGOSINE-1-PHOSPHATE; CERAMIDE; PLASMA; METABOLISM; CELLS AB We used a HPLC-MS/MS methodology for determination of a basic metabolomic profile (18:1,18:0 sphingoid backbone, C(14)-C(26) N-acyl part) of "normal" sphingolipid levels in human serum and plasma. Blood was collected from healthy males and nonpregnant females under fasting and nonfasting conditions with and without anticoagulants. Sphingolipids analyzed included sphingoid bases, sphingosine and dihydrosphingosine, their 1-phosphates (S1P and dhS1P), molecular species (C(n)-) of ceramide (Cer), sphingomyelin (SM), hexosylceramide (HexCer), lactosylceramide (LacCer), and Cer 1-phosphate (Cer1P). SM, LacCer, HexCer, Cer, and Cer1P constituted 87.7, 5.8, 3.4, 2.8, and 0.15% of total sphingolipids, respectively. The abundant circulating SM was C(16)-SM (64.0 mu M), and it increased with fasting (100 mu M). The abundant LacCer was C(16)-LacCer (10.0 mu M) and the abundant HexCer was C(24)-HexCer (2.5 mu M). The abundant Cer, C(24)-Cer (4.0 mu M), was not influenced by fasting; however, levels of C(16)-C(20) Cers were decreased in response to fasting. S1P levels were higher in serum than plasma (0.68 mu M vs. 0.32 mu M). We also determined levels of sphingoid bases and SM species in isolated lipoprotein classes. HDL(3) was the major carrier of S1P, dhS1P, and Sph, and LDL was the major carrier of Cer and dhSph. Per particle, VLDL contained the highest levels of SM, Cer, and S1P. HPLC-MS/MS should provide a tool for clinical testing of circulating bioactive sphingolipids in human blood.-Hammad, S. M., J. S. Pierce, F. Soodavar, K. J. Smith, M. M. Al Gadban, B. Rembiesa, R. L. Klein, Y. A. Hannun, J. Bielawski, and A. Bielawska. Blood sphingolipidomics in healthy humans:impact of sample collection methodology. J. Lipid Res. 2010. 51: 3074-3087. C1 [Hammad, Samar M.; Soodavar, Farzan; Smith, Kent J.; Al Gadban, Mohammed M.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Pierce, Jason S.; Rembiesa, Barbara; Hannun, Yusuf A.; Bielawski, Jacek; Bielawska, Alicja] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Klein, Richard L.] Med Univ S Carolina, Div Endocrinol, Dept Med, Charleston, SC 29425 USA. [Klein, Richard L.] Ralph H Johnson Vet Affairs Med Ctr, Dept Vet Affairs, Charleston, SC 29401 USA. RP Hammad, SM (reprint author), Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. EM hammadsm@musc.edu FU National Institutes of Health [HL-079274, R0-1HL079274-04S1]; Southeastern Clinical and Translational Research Institute; South Carolina Center of Biomedical Research Excellence (COBRE) in Lipidomics and Pathobiology; National Center for Research Resources (NCCR) [P20 RR17677, CO6RR018823]; Department of Veterans Affairs FX This work was supported by National Institutes of Health Grants HL-079274 and R0-1HL079274-04S1 (American Recovery and Reinvestment Act), The Southeastern Clinical and Translational Research Institute to S.M.H., the South Carolina Center of Biomedical Research Excellence (COBRE) in Lipidomics and Pathobiology (P20 RR17677 from National Center for Research Resources (NCCR) to S.M.H., Y.A.H., A.B., and J.B., the Department of Veterans Affairs Merit Review Program to R.L.K., and NCRR Grant CO6RR018823 for the facility. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or other granting agencies. NR 56 TC 98 Z9 99 U1 4 U2 24 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD OCT PY 2010 VL 51 IS 10 BP 3074 EP 3087 DI 10.1194/jlr.D008532 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649GS UT WOS:000281756800021 PM 20660127 ER PT J AU Johnson, FR Hauber, AB Ozdemir, S Siegel, CA Hass, S Sands, BE AF Johnson, F. Reed Hauber, A. Brett Oezdemir, Semra Siegel, Corey A. Hass, Steven Sands, Bruce E. TI Are Gastroenterologists Less Tolerant of Treatment Risks than Patients? Benefit-Risk Preferences in Crohn's Disease Management SO JOURNAL OF MANAGED CARE PHARMACY LA English DT Article ID ADVERSE EVENT RISKS; ULCERATIVE-COLITIS; TREATMENT EFFICACY; RANDOMIZED-TRIAL; MAINTENANCE; PREVALENCE; AMERICANS AB BACKGROUND: Crohn's disease is a serious and debilitating gastrointestinal disorder with a high, unmet need for new treatments. Biologic agents have the potential to alter the natural course of Crohn's disease but present known risks of potential serious adverse events (SAEs). Previous studies have shown that patients are willing to accept elevated SAE risks in exchange for clinical efficacy. Gastroenterologists and patients may have similar goals of maximizing treatment benefit while minimizing risk; however, gastroenterologists may assess the relative importance of risk differently than patients. OBJECTIVE: To (a) understand how gastroenterologists caring for patients with Crohn's disease balance benefits and risks in their treatment decisions and (b) compare their treatment preferences with those of adult patients with Crohn's disease. METHODS: Both patient and gastroenterologist treatment preferences were elicited using a web-based, choice-format conjoint survey instrument. The conjoint questions required subjects to choose between 2 hypothetical treatment options with differing levels of treatment attributes. Patients evaluated the treatment options for themselves, and gastroenterologists evaluated the treatment options for each of 3 hypothetical patient types: (a) female aged 25 years with no history of Crohn's disease surgery (young), (b) male aged 45 years with 1 Crohn's disease surgery (middle-aged), and (c) female older than 70 years with 4 Crohn's disease surgeries (older). Treatment attributes represented the expected outcomes of treatment: severity of daily symptoms, frequency of flare-ups, serious disease complications, oral steroid use, and the risks of 3 potentially fatal SAEs lymphoma, serious or opportunistic infections, and progressive multifocal leukoencephalopathy (PML) during 10 years of treatment. Maximum acceptable risk (MAR), defined as the highest level of SAE risk that subjects would accept in return for a given improvement in efficacy (i.e., the increase in treatment risk that exactly offsets the hypothetical increase in treatment benefit), was calculated using preference weights (parameter marginal log odds ratios) that were estimated with conjoint analysis (random parameters logit models). Gastroenterologists' and patients' mean MARs for 3 SAE risks were calculated for 6 improvements in Crohn's disease symptoms, and gastroenterologists' preference weights for each of the 3 patient profiles were compared. Gastroenterologists' MARs for a hypothetical middle-aged patient were then compared with predicted MARs derived using data from the patient study for male patients aged 40 to 50 years with 1 surgery. RESULTS: After exclusion of nonrespondents (n=4,021 of 4,422 gastroenterologists; n=681 of 1,285 patients) and nonevaluable respondents (n=86 gastroenterologists; n=24 patients), 315 gastroenterologists and 580 patients were included in the final analytic samples. There were no statistically significant differences in gastroenterologists' preference weights for the middle-aged versus young patient profiles. However, preference weights indicated that gastroenterologists are more concerned about 5% side-effect risks for the older patient profile than for the middle-aged patient profile. For symptomatic improvements from severe symptoms to remission, gastroenterologists' highest MARs were for lymphoma: 6.21%, 8.99%, and 25.00% for the young, middle-aged, and older patient types, respectively. In analyses of improvements from severe to moderate symptoms and from moderate symptoms to remission for hypothetical middle-aged patients, gastroenterologists' 10-year risk tolerance ranged between 1.96% lymphoma risk in return for an improvement from moderate symptoms to remission and 4.93% lymphoma risk for an improvement from severe to moderate symptoms; patients' 10-year risk tolerance for. middle-aged patients ranged between 1.52% PML risk in return for an improvement from severe to moderate symptoms and 5.86% infection risk for an improvement from moderate symptoms to remission. On average, gastroenterologists and patients disagreed about how much risk is tolerable for improvements in efficacy. In exchange for improvements from severe to moderate symptoms for the middle-aged patient profile, gastroenterologists were significantly more tolerant than patients of treatment risks of PML (P<0.001) and serious infection (P=0.001) but not lymphoma (P=0.230). In contrast, in exchange for improvements from moderate symptoms to remission for the same patient profile, patients were significantly more tolerant than gastroenterologists of treatment risks for serious infection (P<0.001) and lymphoma (P<0.001) but not PML (P=0.158). CONCLUSIONS: Gastroenterologists and patients have well-defined preferences among treatment attributes and are willing to accept tradeoffs between efficacy and treatment risks. However, risk tolerance varies depending on the type of patient for whom gastroenterologists are being asked to consider treatment. In rating treatment preferences for patients with a middle-aged profile, gastroenterologists are less tolerant of SAE risks than patients in exchange for improvement from moderate symptoms to remission. C1 [Johnson, F. Reed; Hauber, A. Brett] RTI Int Hlth Solut, Res Triangle Pk, NC 27709 USA. [Oezdemir, Semra] Univ N Carolina, Chapel Hill, NC USA. [Siegel, Corey A.] Dartmouth Hitchcock Med Ctr, Ctr Inflammatory Bowel Dis, Lebanon, NH 03766 USA. [Hass, Steven] Abbott Labs, Abbott Pk, IL 60064 USA. [Sands, Bruce E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sands, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. RP Johnson, FR (reprint author), RTI Int Hlth Solut, 200 Pk Off Dr,APT 204, Res Triangle Pk, NC 27709 USA. EM frjohnson@rti.org OI Hass, Steven/0000-0002-1686-030X FU Elan Pharmaceuticals, San Francisco, California; Biogen ldec, Cambridge, Massachusetts FX This study was funded in part by a contract with Elan Pharmaceuticals, San Francisco, California and Biogen ldec, Cambridge, Massachusetts. NR 25 TC 24 Z9 24 U1 0 U2 4 PU ACAD MANAGED CARE PHARMACY PI ALEXANDRIA PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA SN 1083-4087 J9 J MANAGE CARE PHARM JI J. Manag. Care Pharm. PD OCT PY 2010 VL 16 IS 8 BP 616 EP 628 PG 13 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 672ET UT WOS:000283566500004 PM 20866166 ER PT J AU Panagiotidis, J Lahav, A AF Panagiotidis, John Lahav, Amir TI Simulation of prenatal maternal sounds in NICU incubators: a pilot safety and feasibility study SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article; Proceedings Paper CT 6th International Workshop on Neonatology - Personalized Neonatal Medicine CY OCT 28-30, 2010 CL Cagliari, ITALY SP Union Mediterranean Neonatal Soc, Union European Neonatal Perinatal Soc DE Auditory; preterm; incubator; maternal sounds; developmental care ID PRETERM INFANTS; OUTCOMES; TERM AB Methods. A sample of biological sounds, consisting of voice and heartbeat, were recorded from a mother of a premature infant admitted to our unit. The maternal sounds were then played back inside an unoccupied incubator via a specialized audio system originated and compiled in our lab. We performed a series of evaluations to determine the safety and feasibility of using this system in NICU incubators. Results. The proposed audio system was found to be safe and feasible, meeting criteria for humidly and temperature resistance, as well as for safe noise levels. Simulation of maternal sounds using this system seems achievable and applicable and received local support from medical staff. Conclusion. Further research and technology developments are needed to optimize the design of the NICU incubators to preserve the acoustic environment of the womb. C1 [Lahav, Amir] Brigham & Womens Hosp, Dept Newborn Med, Neonatal Res Lab, Boston, MA 02115 USA. [Lahav, Amir] Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children, Boston, MA 02115 USA. RP Lahav, A (reprint author), Brigham & Womens Hosp, Dept Newborn Med, Neonatal Res Lab, 75 Francis St, Boston, MA 02115 USA. EM amir@hms.harvard.edu NR 17 TC 9 Z9 9 U1 2 U2 9 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 OCT PY 2010 VL 23 SU 3 BP 106 EP 109 DI 10.3109/14767058.2010.512185 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 659TD UT WOS:000282588900031 PM 20836737 ER PT J AU Berry, DL Halpenny, B Wolpin, S Davison, BJ Ellis, WJ Lober, WB McReynolds, J Wulff, J AF Berry, Donna L. Halpenny, Barbara Wolpin, Seth Davison, B. Joyce Ellis, William J. Lober, William B. McReynolds, Justin Wulff, Jennifer TI Development and Evaluation of the Personal Patient Profile-Prostate (P3P), a Web-Based Decision Support System for Men Newly Diagnosed With Localized Prostate Cancer SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Prostate cancer; decision making; computer-assisted; pilot study ID PREFERENCES; INFORMATION AB Background: Given that no other disease with the high incidence of localized prostate cancer (LPC) has so many treatments with so few certainties related to outcomes, many men are faced with assuming some responsibility for the treatment decision along with guidance from clinicians. Men strongly consider their own personal characteristics and other personal factors as important and influential to the decision. Clinical researchers have not developed or comprehensively investigated interventions to facilitate the insight and prioritizing of personal factors along with medical factors that are required of a man in preparation for the treatment decision. Objectives: The purpose of this pilot study was to develop and evaluate the feasibility and usability of a Web-based decision support technology, the Personal Patient Profile-Prostate (P3P), in men newly diagnosed with LPC. Methods: Use cases were developed followed by infrastructure and content application. The program was provided on a personal desktop computer with a touch screen monitor. Participant responses to the query component of P3P determined the content of the multimedia educational and coaching intervention. The intervention was tailored to race, age, and personal factors reported as influencing the decision. Prepilot usability testing was conducted using a "think aloud" interview to identify navigation and content challenges. These issues were addressed prior to deployment in the clinic. A clinical pilot was conducted in an academic medical center where men sought consultation and treatment for LPC. Completion time, missing data, and acceptability were measured. Results: Prepilot testing included 4 men with a past diagnosis of LPC who had completed therapy. Technical navigation issues were documented along with confusing content language. A total of 30 additional men with a recent diagnosis of LPC completed the P3P program in clinic prior to consulting with a urologist regarding treatment options. In a mean time of 46 minutes (SD 13 minutes), participants completed the P3P query and intervention components. Of a possible 4560 items for 30 participants, 22 (0.5%) were missing. Acceptability was reported as high overall. The sections of the intervention reported as most useful were the statistics graphs, priority information topics, and annotated external website links. Conclusions: The P3P intervention is a feasible and usable program to facilitate treatment decision making by men with newly diagnosed LPC. Testing in a multisite randomized trial with a diverse sample is warranted. C1 [Berry, Donna L.; Halpenny, Barbara] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolpin, Seth; Lober, William B.; McReynolds, Justin] Univ Washington, Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Davison, B. Joyce] Univ Saskatchewan, Saskatoon, SK, Canada. [Wulff, Jennifer] Swedish Med Ctr, Swedish Neurosci Inst, Seattle, WA USA. [Ellis, William J.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. RP Berry, DL (reprint author), Dana Farber Canc Inst, 44 Binney St,CP 305, Boston, MA 02115 USA. EM donna_berry@dfci.harvard.edu FU National Institutes of Health [NIH R21 CA 100025] FX The authors wish to thank Martha Foster, RN, for her dedicated assistance in participant recruitment and study deployment. Andrew Ward, Cliff Solomon, Ashley Bond, Alan Gojdics, and John Balzarini were major contributors to video production. Funding was provided by the National Institutes of Health, grant number NIH R21 CA 100025; the sponsor had no role in manuscript preparation or approval. NR 35 TC 13 Z9 13 U1 4 U2 18 PU JOURNAL MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD OCT-DEC PY 2010 VL 12 IS 4 BP 109 EP 121 AR e67 DI 10.2196/jmir.1576 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 699BC UT WOS:000285637900010 PM 21169159 ER PT J AU Garcia, A Siddappa, NB Li, QS Haase, AT Paul, K Stroud, F Zhang, XD Fountain, JA Villinger, F Novembre, FJ Else, JG Secor, WE Ruprecht, RM AF Garcia, Anapatricia Siddappa, Nagadenahalli B. Li, Qingsheng Haase, Ashley T. Paul, Katherine Stroud, Fawn Zhang, Xiaodong Fountain, Jack A. Villinger, Francois Novembre, Francis J. Else, James G. Secor, W. Evan Ruprecht, Ruth M. TI AIDS and optic neuritis in a rhesus monkey infected with the R5 clade C SHIV-1157ipd3N4 SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE neuroAIDS; optic neuropathy; R5 SHIV ID NONHUMAN PRIMATE; HIV; ENV; VIRUSES AB A Chinese rhesus macaque infected with the pathogenic CCR5-tropic clade C simian-human immunodeficiency virus, SHIV-1157ipd3N4, had persistent viremia, depletion of CD4+ T cells to < 200 cells/mu l, opportunistic infections, coagulopathy, and gradual development of bilateral blindness. MRI revealed marked thickening of both optic nerves. Histopathological evaluation showed diffuse cellular infiltration at necropsy and a focus of SHIV-infected cells. This is the first report of CNS pathology following chronic infection with an obligate R5 SHIV. C1 [Garcia, Anapatricia; Stroud, Fawn; Zhang, Xiaodong; Villinger, Francois; Novembre, Francis J.; Else, James G.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Garcia, Anapatricia; Villinger, Francois; Else, James G.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Siddappa, Nagadenahalli B.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Siddappa, Nagadenahalli B.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Qingsheng; Haase, Ashley T.] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. [Paul, Katherine; Secor, W. Evan] Ctr Dis Control & Prevent, Atlanta, GA USA. [Fountain, Jack A.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. RP Garcia, A (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. EM agarci5@emory.edu; ruth_ruprecht@dfci.harvard.edu OI Byrareddy, Siddappa /0000-0002-7423-1763 FU NIH [R56 AI062515, R21 NS063877, PO1 AI 048240, RR-000165] FX The authors thank Dr Peter A. Barry (University of California, Davis) for the kind gift of rabbit anti-monkey CMV antiserum; Drs Prachi Sharma and Daniel Anderson (YNPRC) for their help in the evaluation of the case including CMV IHC; Dr Larry Walker (YN-PRC) for submitting normal control MRI images and Eileen Breding and Evan Dessasau for excellent technical assistance. The work was supported by NIH grants R56 AI062515 and R21 NS063877 to R. M. R., PO1 AI 048240 to R.M.R. and J.G.E., and base grant RR-000165 to the Yerkes National Primate Research Center. NR 12 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2010 VL 39 IS 5 BP 356 EP 360 DI 10.1111/j.1600-0684.2010.00416.x PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 646NP UT WOS:000281549400007 PM 20412378 ER PT J AU Nieuwland, MS Ditman, T Kuperberg, GR AF Nieuwland, Mante S. Ditman, Tali Kuperberg, Gina R. TI On the incrementality of pragmatic processing: An ERP investigation of informativeness and pragmatic abilities SO JOURNAL OF MEMORY AND LANGUAGE LA English DT Article DE Language comprehension; Pragmatics; Scalar quantifiers; Electrophysiology; N400 ERP; Individual differences; Pragmatic abilities; Autism Quotient Communication subscale; Informativeness ID LATENT SEMANTIC ANALYSIS; LANGUAGE COMPREHENSION; BRAIN POTENTIALS; SCALAR IMPLICATURE; EYE-MOVEMENTS; SENTENCE COMPREHENSION; FUNCTIONING AUTISM; WORLD KNOWLEDGE; TIME-COURSE; WRAP-UP AB In two event-related potential (ERP) experiments, we determined to what extent Grice's maxim of informativeness as well as pragmatic ability contributes to the incremental build-up of sentence meaning, by examining the impact of underinformative versus informative scalar statements (e.g. "Some people have lungs/pets, and ...") on the N400 event-related potential (ERP), an electrophysiological index of semantic processing. In Experiment 1, only pragmatically skilled participants (as indexed by the Autism Quotient Communication subscale) showed a larger N400 to underinformative statements. In Experiment 2, this effect disappeared when the critical words were unfocused so that the local underinformativeness went unnoticed (e.g., "Some people have lungs that ..."). Our results suggest that, while pragmatic scalar meaning can incrementally contribute to sentence comprehension, this contribution is dependent on contextual factors, whether these are derived from individual pragmatic abilities or the overall experimental context. (C) 2010 Elsevier Inc. All rights reserved. C1 [Nieuwland, Mante S.] Basque Ctr Cognit Brain & Language, Donostia San Sebastian 20009, Spain. [Nieuwland, Mante S.; Ditman, Tali; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Nieuwland, Mante S.; Ditman, Tali; Kuperberg, Gina R.] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Nieuwland, MS (reprint author), Basque Ctr Cognit Brain & Language, Paseo Mikeletegi 69,2nd Floor, Donostia San Sebastian 20009, Spain. EM m.nieuwland@bcbl.eu FU NWO Rubicon; [NIMH-R01-MH071635] FX We are very grateful to Kana Okano, Liam Clegg and Sarah Cleary for their help with stimulus preparation and data collection, and to Ira Noveck, two anonymous reviewers and Andrea Eyleen Martin-Nieuwland for helpful comments on earlier drafts of this manuscript. This research was supported by an NWO Rubicon Grant to MSN and by NIMH-R01-MH071635 to GRK. NR 108 TC 43 Z9 43 U1 2 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0749-596X J9 J MEM LANG JI J. Mem. Lang. PD OCT PY 2010 VL 63 IS 3 BP 324 EP 346 DI 10.1016/j.jml.2010.06.005 PG 23 WC Linguistics; Psychology; Psychology, Experimental SC Linguistics; Psychology GA 657EZ UT WOS:000282397300005 PM 20936088 ER PT J AU Ergorul, C Ray, A Huang, W Wang, DY Ben, YX Cantuti-Castelvetri, I Grosskreutz, CL AF Ergorul, Ceren Ray, Arjun Huang, Wei Wang, Dan Yi Ben, Yixin Cantuti-Castelvetri, Ippolita Grosskreutz, Cynthia L. TI Hypoxia Inducible Factor-1 alpha (HIF-1 alpha) and Some HIF-1 Target Genes are Elevated in Experimental Glaucoma SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Retinal ganglion cells; Glaucoma; HIF-1 alpha; Muller cells; Astrocytes; qRT-PCR ID ENDOTHELIAL GROWTH-FACTOR; OPEN-ANGLE GLAUCOMA; PLASMINOGEN-ACTIVATOR INHIBITOR-1; FIBRILLARY ACIDIC PROTEIN; HSP27 UP-REGULATION; AQUEOUS-HUMOR; FACTOR-I; INTRAOCULAR-PRESSURE; MICROARRAY ANALYSIS; RETINAL GANGLION AB Low levels of hypoxia have been suggested to be a mechanism of retinal damage in glaucoma. To test the hypothesis that the activation of the hypoxia-responsive transcription factor hypoxia inducible factor-1 alpha (HIF-1 alpha) is involved in the pathophysiology of glaucoma, we used a rat model of glaucoma to study (1) HIF-1 alpha retinal protein levels by immunoblot analysis, (2) cellular localization of HIF-1 alpha in the retina by immunohistochemistry, and (3) expression of retinal HIF-1 gene targets by quantitative real-time polymerase chain reaction. Glaucoma was unilaterally induced in rats by injecting hypertonic saline in episcleral veins. We find that HIF-1 alpha protein was increased in the retina following elevation of intraocular pressure, specifically in Muller glia and astrocytes but not in activated microglia. Eight established HIF-1 target genes were measured in experimental glaucoma. Retinal Epo, Flt-1, Hsp-27, Pai-1, and Vegfa mRNA levels were increased and Et-1, Igf2, and Tgf beta 3 levels were decreased in the glaucomatous retinas. Thus, the increase in HIF-1 alpha levels in Muller glia and astrocytes is accompanied by a marked up regulation of some, but not all, HIF-1 transcriptional targets. These data support the hypothesis that HIF-1 alpha becomes transcriptionally active in astrocytes and Muller cells but not microglia or neurons in glaucoma, arguing against a global hypoxia stimulus to the retina. C1 [Ergorul, Ceren; Ray, Arjun; Huang, Wei; Wang, Dan Yi; Ben, Yixin; Grosskreutz, Cynthia L.] Harvard Univ, Howe Lab Ophthalmol, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Cantuti-Castelvetri, Ippolita] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Howe Lab Ophthalmol, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM cynthia_grosskreutz@meei.harvard.edu FU Massachusetts Lions Grant; MEEI [EY014104]; [R01-EY13399]; [T32-EY07145] FX The authors thank Hisatomo Kowa and Bradley Hyman at MassGeneral Institute for Neurodegeneration, Charlestown, MA for the discussions and for the equipment used in qRT-PCR. The authors also thank Charles Vanderburg, Rachel Diamond, and Ozge Cagsal-Getkin at the Advanced Tissue Resource Center/MGH, Charlestown, MA for their technical help. This work was supported by R01-EY13399 (CLG), T32-EY07145 (CE), Massachusetts Lions Grant (CLG), and MEEI Vision-Core Grant EY014104. NR 53 TC 14 Z9 18 U1 0 U2 1 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 OCT PY 2010 VL 42 IS 2 BP 183 EP 191 DI 10.1007/s12031-010-9343-z PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 636BL UT WOS:000280702700008 PM 20237864 ER PT J AU Kalluri, R Xue, JB Eatock, RA AF Kalluri, Radha Xue, Jingbing Eatock, Ruth Anne TI Ion Channels Set Spike Timing Regularity of Mammalian Vestibular Afferent Neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PERIPHERAL INNERVATION PATTERNS; VENTRAL COCHLEAR NUCLEUS; II HAIR-CELLS; ACTIVATED POTASSIUM CURRENTS; SPIRAL GANGLION NEURONS; TURTLE POSTERIOR CRISTA; SEMICIRCULAR CANALS; NERVE AFFERENTS; SQUIRREL-MONKEY; SENSORY NEURONS AB Kalluri R, Xue J, Eatock RA. Ion channels set spike timing regularity of mammalian vestibular afferent neurons. J Neurophysiol 104: 2034-2051, 2010. First published July 21, 2010; doi:10.1152/jn.00396.2010. In the mammalian vestibular nerve, some afferents have highly irregular interspike intervals and others have highly regular intervals. To investigate whether spike timing is determined by the afferents' ion channels, we studied spiking activity in their cell bodies, isolated from the vestibular ganglia of young rats. Whole cell recordings were made with the perforated-patch method. As previously reported, depolarizing current steps revealed distinct firing patterns. Transient neurons fired one or two onset spikes, independent of current level. Sustained neurons were more heterogeneous, firing either trains of spikes or a spike followed by large voltage oscillations. We show that the firing pattern categories are robust, occurring at different temperatures and ages, both in mice and in rats. A difference in average resting potential did not cause the difference in firing patterns, but contributed to differences in afterhyperpolarizations. A low-voltage-activated potassium current (I(LV)) was previously implicated in the transient firing pattern. We show that I(LV) grew from the first to second postnatal week and by the second week comprised Kv1 and Kv7 (KCNQ) components. Blocking I(LV) converted step-evoked firing patterns from transient to sustained. Separated from their normal synaptic inputs, the neurons did not spike spontaneously. To test whether the firing-pattern categories might correspond to afferent populations of different regularity, we injected simulated excitatory postsynaptic currents at pseudorandom intervals. Sustained neurons responded to a given pattern of input with more regular firing than did transient neurons. Pharmacological block of I(LV) made firing more regular. Thus ion channel differences that produce transient and sustained firing patterns in response to depolarizing current steps can also produce irregular and regular spike timing. C1 [Kalluri, Radha; Xue, Jingbing; Eatock, Ruth Anne] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Kalluri, Radha; Eatock, Ruth Anne] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Xue, Jingbing; Eatock, Ruth Anne] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Eatock, RA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM RKalluri@hei.org; Jingbing_Xue@URMC.Rochester.edu; eatock@meei.harvard.edu RI Eatock, Ruth/F-6404-2013; OI Eatock, Ruth Anne/0000-0001-7547-2051 FU National Research Service Award [F32-DC-93602]; National Institute on Deafness and Other Communication Disorders [R01-DC-02290] FX The research was supported by National Research Service Award Training Grant F32-DC-93602 to R. Kalluri and National Institute on Deafness and Other Communication Disorders Grant R01-DC-02290 to R. A. Eatock. NR 80 TC 39 Z9 40 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2010 VL 104 IS 4 BP 2034 EP 2051 DI 10.1152/jn.00396.2010 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 660NI UT WOS:000282649900020 PM 20660422 ER PT J AU Walker, RH Davies, G Koch, RJ Haack, AK Moore, C Meshul, CK AF Walker, Ruth H. Davies, Georgia Koch, Rick J. Haack, Andrew K. Moore, Cynthia Meshul, Charles K. TI Effects of Zona Incerta Lesions on Striatal Neurochemistry and Behavioral Asymmetry in 6-Hydroxydopamine-Lesioned Rats SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE microdialysis; 6-hydroxydopamine; glutamate; dopamine ID DEEP BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS LESIONS; HIGH-FREQUENCY STIMULATION; ACTIVE ELECTRODE CONTACTS; MEDIAL FRONTAL-CORTEX; PARKINSONS-DISEASE; BASAL GANGLIA; DOPAMINE NEUROTRANSMISSION; NIGROSTRIATAL PATHWAY; 6-OHDA LESION AB Analysis of optimal sites for neurosurgical interventions in patients with Parkinson's disease (PD) suggests that significant clinical benefits may be achieved by involvement of the zona incerta (ZI). Unilateral electrolytic ZI lesions were made in intact and ipsilaterally 6-hydroxydopamine (60HDA)-lesioned rats. Extracellular levels of glutamate, dopamine, and its metabolites in the ipsilateral striatum of awake rats were measured by using microdialysis, and tests of behavioral asymmetry were performed. In intact rats, ZI lesions had no effect on striatal extracellular glutamate or absolute levels of dopamine or metabolites, but dopamine metabolism decreased. After ZI lesions, contralateral forepaw use decreased in the forepaw adjusting steps test, but there was no change in response to vibrissa stimulation or cylinder exploration. There was no development of rotational asymmetry with amphetamine. In 60HDA-lesioned rats, striatal extracellular glutamate levels were elevated compared with controls. ZI lesions reduced the increased levels of glutamate back to normal values. ZI lesions reduced dopamine and homovanillic acid levels and showed a trend toward a decrease in dopamine metabolism. 60HDA-lesioned rats demonstrated the expected asymmetry of motor behaviors. After ZI lesions, ipsilateral turns following amphetamine injection were reduced, and there was a trend toward improved symmetry of forepaw use as determined with the forepaw adjusting steps test. There was no change in forepaw use with vibrissa stimulation or cylinder exploration. These data indicate that lesions of the ZI can affect striatal neurochemistry and motor behavioral asymmetry and suggest potential mechanisms by which ZI lesions may improve symptoms in PD. (C) 2010 Wiley-Liss, Inc. C1 [Walker, Ruth H.; Davies, Georgia; Koch, Rick J.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. [Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Haack, Andrew K.; Moore, Cynthia; Meshul, Charles K.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Neurocytol Lab, Res Serv, Portland, OR 97201 USA. [Meshul, Charles K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci & Pathol, Portland, OR 97201 USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol 127, Bronx, NY 10468 USA. EM ruth.walker@mssm.edu FU U.S. Department of Veterans Affairs FX Contract grant sponsor: U.S. Department of Veterans Affairs (to R.H.W., C.K.M.). NR 52 TC 3 Z9 3 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT PY 2010 VL 88 IS 13 BP 2964 EP 2975 DI 10.1002/jnr.22446 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 642OK UT WOS:000281225100019 PM 20544826 ER PT J AU Bandaru, VVR Mielke, MM Chu, M Lentz, M McArthur, JC Sacktor, N Chang, L Ernst, T Wojna, V Pardo, C Pomper, M Haughey, NJ AF Bandaru, Veera V. R. Mielke, Michelle M. Chu, Michael Lentz, Margaret McArthur, Justin C. Sacktor, Ned Chang, Linda Ernst, Thomas Wojna, Valerie Pardo, Carlos Pomper, Martin Haughey, Norman J. TI CSF sphingomyelin/ceramide C24:1 ratio can predict declines of neurocognitive status in HIV-infected patients SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 10th International Symposium on NeuroVirology CY OCT 12-16, 2010 CL Milan, ITALY C1 [Bandaru, Veera V. R.; Chu, Michael; McArthur, Justin C.; Sacktor, Ned; Pardo, Carlos; Haughey, Norman J.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21218 USA. [Mielke, Michelle M.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21218 USA. [Lentz, Margaret] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Chang, Linda; Ernst, Thomas] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Wojna, Valerie] Univ Puerto Rico, Dept Internal Med, Div Neurol, San Juan, PR 00936 USA. [Pomper, Martin] Johns Hopkins Univ, Sch Med, Dept Radiol, Grp CHARTER, Baltimore, MD 21218 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 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2010 VL 16 SU 1 BP 7 EP 7 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 670GS UT WOS:000283409800015 ER PT J AU Burdo, TH Lentz, MR Krishnan, A Halpern, EF Letendre, S Ellis, RJ Rosenberg, ES Williams, KC AF Burdo, Tricia H. Lentz, Margaret R. Krishnan, Anitha Halpern, Elkan F. Letendre, Scott Ellis, Ronald J. Rosenberg, Eric S. Williams, Kenneth C. TI Soluble CD163 as a plasma marker of HIV disease activation: Implications of macrophage-mediated immune responses SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 10th International Symposium on NeuroVirology CY OCT 12-16, 2010 CL Milan, ITALY C1 [Burdo, Tricia H.; Krishnan, Anitha; Williams, Kenneth C.] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Lentz, Margaret R.; Halpern, Elkan F.] Massachusetts Gen Hosp, Neuroradiol & AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Letendre, Scott; Ellis, Ronald J.] Univ Calif San Diego, HNRC, San Diego, CA 92103 USA. [Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RI Ellis, Ronald/K-3543-2015 OI Ellis, Ronald/0000-0003-4931-752X NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2010 VL 16 SU 1 BP 15 EP 15 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 670GS UT WOS:000283409800032 ER PT J AU Gheuens, S Bord, E Kesari, S Simpson, DM Gandhi, RT Clifford, DB Berger, JR Koralnik, IJ AF Gheuens, Sarah Bord, Evelyn Kesari, Santosh Simpson, David M. Gandhi, Rajesh T. Clifford, David B. Berger, Joseph R. Koralnik, Igor J. TI Role of CD4+and CD8+T cell responses against JC virus in patients with PML SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 10th International Symposium on NeuroVirology CY OCT 12-16, 2010 CL Milan, ITALY C1 [Gheuens, Sarah; Bord, Evelyn; Koralnik, Igor J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div NeuroVirol, Boston, MA 02215 USA. [Gheuens, Sarah; Bord, Evelyn; Koralnik, Igor J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02215 USA. [Kesari, Santosh] Univ Calif San Diego, Dept Neurosci, San Diego Sch Med, Div Neurooncol, San Diego, CA 92103 USA. [Simpson, David M.] Mt Sinai Med Ctr, Dept Neurol, New York, NY 10029 USA. [Gandhi, Rajesh T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA USA. [Clifford, David B.] Washington Univ, Dept Neurol, St Louis, MO USA. [Berger, Joseph R.] Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2010 VL 16 SU 1 BP 34 EP 35 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 670GS UT WOS:000283409800076 ER PT J AU Holman, A Mefford, M Gabuzda, D AF Holman, Alexander Mefford, Megan Gabuzda, Dana TI A unique brain HIV sequence database reveals genetic and biological properties of HIV variants associated with CNS compartmentalization and dementia SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 10th International Symposium on NeuroVirology CY OCT 12-16, 2010 CL Milan, ITALY C1 [Holman, Alexander; Mefford, Megan; Gabuzda, Dana] Dana Farber Canc Inst, Boston, MA USA. [Mefford, Megan; Gabuzda, Dana] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2010 VL 16 SU 1 BP 38 EP 39 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 670GS UT WOS:000283409800084 ER PT J AU Lentz, MR Kim, WK Kim, H Lee, V Venna, N Halpern, E Rosenberg, ES Williams, K Gonzalez, RG AF Lentz, Margaret R. Kim, Woong-Ki Kim, Hyun Lee, Vallent Venna, Nagagopal Halpern, Elkan Rosenberg, Eric S. Williams, Kenneth Gonzalez, R. G. TI Alterations in Brain Metabolism during the First Year of HIV-Infection SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract CT 10th International Symposium on NeuroVirology CY OCT 12-16, 2010 CL Milan, ITALY C1 [Lentz, Margaret R.; Kim, Hyun; Lee, Vallent; Venna, Nagagopal; Halpern, Elkan; Rosenberg, Eric S.; Gonzalez, R. G.] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Lentz, Margaret R.; Kim, Hyun; Lee, Vallent; Venna, Nagagopal; Halpern, Elkan; Rosenberg, Eric S.; Gonzalez, R. G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lentz, Margaret R.; Kim, Hyun; Lee, Vallent; Venna, Nagagopal; Halpern, Elkan; Rosenberg, Eric S.; Gonzalez, R. G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kim, Woong-Ki] Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA USA. [Williams, Kenneth] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2010 VL 16 SU 1 BP 49 EP 49 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 670GS UT WOS:000283409800107 ER PT J AU Lentz, MR Degaonkar, M Mohamed, MA Kim, H Conant, K Halpern, EF Sacktor, N Barker, PB Pomper, MG AF Lentz, Margaret R. Degaonkar, Mahaveer Mohamed, Mona A. Kim, Hyun Conant, Katherine Halpern, Elkan F. Sacktor, Ned Barker, Peter B. Pomper, Martin G. TI Exploring the relationship of macrophage colony-stimulating factor levels on neuroaxonal metabolism and cognition during chronic human immunodeficiency virus infection SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE HAD; M-CSF; MRS; MSK; NAA; NPZ 8 ID MAGNETIC-RESONANCE-SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; NAIVE HIV PATIENTS; M-CSF; BRAIN-METABOLITES; DEMENTIA; AIDS; ABNORMALITIES; QUANTITATION; MULTICENTER AB Macrophage colony stimulating factor (M-CSF) promotes macrophage differentiation, increases susceptibility of macrophages to viral infection, and enhances human immunodeficiency virus (HIV) replication in infected macro phages Given the current model of HIV neuropathogenesis, which involves monocyte trafficking into the central nervous system, immune factors linked with macrophage maturation and survival may be associated with cognitive decline (measured by neuropsychological z score [NPZ-8] or Memorial Sloan-Kettering [MSK] score) and alterations in a marker of neuronal integrity, N acetylaspartate (NAA) Fifty-four chronically infected HIV+ subjects under went neuropsychological assessment, magnetic resonance spectroscopic imaging, and quantification of M-CSF in plasma and cerebrospinal fluid (CSF) at baseline Thirty nine of those subjects underwent further examination at 3 and 10 months after initiation of combination antiretroviral therapy (ART) regimens Within 3 months of therapy use, CSF M-CSF and viral RNA levels were reduced, whereas NAA concentrations in many brain regions were increased Neither baseline levels nor the change in M-CSF levels had the ability to predict changes in NAA levels observed after 10 months of combination ART use At study entry those with the lowest M-CSF levels in the CSF had the least cognitive impairment (NPZ 8) Those who had higher baseline CSF M-CSF levels and exhibited larger decreases in M-CSF after therapy, tended to have greater cognitive improvement after 10 months Increased prevalence of M CSF in the setting of HIV infection could contribute to neuronal injury and may be predictive of cognitive impairment Journal of Neuro Virology (2010) 16, 368-376 C1 [Degaonkar, Mahaveer; Mohamed, Mona A.; Barker, Peter B.; Pomper, Martin G.] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21231 USA. [Conant, Katherine; Sacktor, Ned] Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21231 USA. [Lentz, Margaret R.; Kim, Hyun; Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Neuroradiol, Charlestown, MA USA. [Lentz, Margaret R.; Kim, Hyun; Halpern, Elkan F.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Pomper, MG (reprint author), Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, 1550 Orleans St,492 CRB 2, Baltimore, MD 21231 USA. FU NIH [R01 MH61438, K25 NS051129] FX This work was funded by NIH grants R01 MH61438 (to M G P) and K25 NS051129 (to M R L) NR 31 TC 5 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2010 VL 16 IS 5 BP 368 EP 376 DI 10.3109/13550284.2010.513029 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 679AT UT WOS:000284132500004 PM 20839921 ER PT J AU Murphy, MK Brady, TJ Nasir, K Gazelle, GS Bamberg, F Truong, QA Mamuya, WS Abbara, S Lee, TH Blankstein, R AF Murphy, Meagan K. Brady, Thomas J. Nasir, Khurram Gazelle, G. Scott Bamberg, Fabian Truong, Quynh A. Mamuya, Wilfred S. Abbara, Suhny Lee, Thomas H. Blankstein, Ron TI Appropriateness and utilization of cardiac CT: Implications for development of future criteria SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Computed tomography (CT); coronary artery disease; diagnostic; prognostic application ID PERIOPERATIVE CARDIOVASCULAR EVALUATION; CORONARY-ARTERY DISEASE; NONCARDIAC SURGERY AB Background. The cardiac CT (CCT) appropriateness criteria (AC) were jointly published by multiple societies to ensure effective utilization of CCT. We sought to determine how these criteria apply to CCT scans performed at a tertiary-care hospital. Methods and Results. Data were collected from medical records and interviews of 267 consecutive patients referred for CCT. Two physicians designated exam indication as appropriate, inappropriate, or uncertain as per AC, or "not known" if not listed in AC. CCT exam indication was appropriate in 47%, inappropriate in 9%, uncertain in 15%, and not known in 29%. The most common appropriate indication was evaluation of CAD in symptomatic patients with equivocal stress test, whereas the most common inappropriate referral was evaluation of asymptomatic patients with low pretest probability of CAD. Most exams (69%) were for evaluation of CAD, with the remaining exams performed to evaluate other elements of cardiac structure or function. Exams for these non-CAD indications were more likely to be appropriate and less likely to have an undetermined (uncertain or not known) level of appropriateness than those for CAD indications. There was no difference in exam appropriateness whether ordered by cardiologists or internists, but providers who completed training >25 years ago ordered fewer appropriate and more inappropriate exams than younger providers. Conclusions. In applying the AC to a large academic medical center, few CCT exams were inappropriate; however, many patients referred for CCT, particularly for evaluation of CAD, had an indication for which the level of appropriateness remained undetermined. Given the rapid adoption of CCT, these results emphasize the need to refine current criteria for appropriate utilization. (J Nucl Cardiol 2010; 17: 881-9.) C1 [Murphy, Meagan K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Brady, Thomas J.; Gazelle, G. Scott; Bamberg, Fabian; Truong, Quynh A.; Mamuya, Wilfred S.; Abbara, Suhny; Blankstein, Ron] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Brady, Thomas J.; Gazelle, G. Scott; Bamberg, Fabian; Truong, Quynh A.; Mamuya, Wilfred S.; Abbara, Suhny; Blankstein, Ron] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Nasir, Khurram] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. [Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Lee, Thomas H.] Partners HealthCare, Boston, MA USA. [Blankstein, Ron] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, Dept Med & Radiol, Boston, MA 02115 USA. RP Murphy, MK (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM mmurphy22@partners.org FU NIH [1T32 HL076136-02]; Partners HealthCare, Boston, MA, USA FX Drs Blankstein, Nasir, and Truong have received support from NIH Grant 1T32 HL076136-02. This study was partially funded by an internal grant from Partners HealthCare, Boston, MA, USA. NR 10 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD OCT PY 2010 VL 17 IS 5 BP 881 EP 889 DI 10.1007/s12350-010-9252-0 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 651SQ UT WOS:000281947800019 PM 20552311 ER PT J AU Christoffersen, J Barron, AM Lynch, M Caroline, H AF Christoffersen, Jean Barron, Anne-Marie Lynch, Marla Caroline, Harlene TI Integrating Psychosocial Skills into a Medical-Surgical Curriculum in a Baccalaureate Nursing Program SO JOURNAL OF NURSING EDUCATION LA English DT Article ID EDUCATION; THEATER AB With the increasing acuity levels of hospitalized patients, faculty members struggle with accessing clinical sites for undergraduate students. Teaching students how to interact with patients and their families can often take second place to attending to the many needs and safety issues in caring for acutely ill individuals, particularly in medical-surgical settings. Over the past several years, the psychiatric and medical-surgical faculty members in the nursing department of a college in Boston have struggled with how best to prepare students for both the physical and psychosocial aspects of care. In this article, the evolution of our psychiatric consultation-liaison model is discussed. C1 [Christoffersen, Jean; Barron, Anne-Marie; Lynch, Marla] Simmons Coll, Dept Nursing, Boston, MA 02458 USA. [Caroline, Harlene] Curry Coll, Milton, MA USA. [Christoffersen, Jean] Beth Israel Deaconness Med Ctr, Boston, MA USA. [Barron, Anne-Marie] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Christoffersen, J (reprint author), Simmons Coll, Dept Nursing, 300 Fenway, Boston, MA 02458 USA. EM jean.christoffersen@simmons.edu NR 16 TC 1 Z9 1 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0148-4834 J9 J NURS EDUC JI J. Nurs. Educ. PD OCT PY 2010 VL 49 IS 10 BP 573 EP 577 DI 10.3928/01484834-20100730-03 PG 5 WC Nursing SC Nursing GA 720BX UT WOS:000287256300006 PM 20669875 ER PT J AU Smith, KW Proctor, SR Ozonoff, A McClean, MD AF Smith, Kristen W. Proctor, Susan R. Ozonoff, Al McClean, Michael D. TI Inhalation Exposure to Jet Fuel (JP8) Among US Air Force Personnel SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article DE exposure assessment; inhalation exposure; jet fuel; JP8 ID DERMAL EXPOSURE; JP-8; NAPHTHALENE; WORKERS AB As jet fuel is a common occupational exposure among military and civilian populations, this study was conducted to characterize jet fuel (JP8) exposure among active duty U.S. Air Force personnel. Personnel (n = 24) were divided a priori into high, moderate, and low exposure groups. Questionnaires and personal air samples (breathing zone) were collected from each worker over 3 consecutive days (72 worker-days) and analyzed for total hydrocarbons (THC), benzene, toluene, ethylbenzene, xylenes, and naphthalene. Air samples were collected from inside the fuel tank and analyzed for the same analytes. Linear mixed-effects models were used to evaluate the exposure data. Our results show that the correlation of THC (a measure of overall JP8 inhalation exposure) with all other analytes was moderate to strong in the a priori high and moderate exposure groups combined. Inhalation exposure to all analytes varied significantly by self-reported JP8 exposure (THC levels higher among workers reporting JP8 exposure), a priori exposure group (THC levels in high group > moderate group > low group), and more specific job task groupings (THC levels among workers in fuel systems hangar group > refueling maintenance group > fuel systems office group > fuel handling group > clinic group), with task groupings explaining the most between-worker variability. Among highly exposed workers, statistically significant job task-related predictors of inhalation exposure to THC indicated that increased time in the hangar; working close to the fuel tank (inside > less than 25 ft > greater than 25 ft), primary job (entrant > attendant/runner/fireguard > outside hangar), and performing various tasks near the fuel tank, such as searching for a leak, resulted in higher JP8 exposure. This study shows that while a priori exposure groups were useful in distinguishing JP8 exposure levels, job task-based categories should be considered in epidemiologic study designs to improve exposure classification. Finally, the strong correlation of THC with naphthalene suggests that naphthalene may be an appropriate surrogate of JP8 exposure. C1 [Smith, Kristen W.; Proctor, Susan R.; McClean, Michael D.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Smith, Kristen W.; Proctor, Susan R.] USA, Environm Med Res Inst, Mil Performance Div, Natick, MA 01760 USA. [Proctor, Susan R.] VA Boston Healthcare Syst, Boston, MA USA. [Ozonoff, Al] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Smith, KW (reprint author), Harvard Univ, Sch Med, 655 Huntington Ave,Bldg 1,Room 1402, Boston, MA 02115 USA. EM ksmith@hsph.harvard.edu RI McClean, Michael/J-2934-2015; OI McClean, Michael/0000-0002-3902-8823; Ozonoff, Al/0000-0003-4233-5899 FU U.S. Army Medical Research and Materiel Command [W81XWH-06-1-0105] FX The authors gratefully acknowledge the Air Force personnel who participated in this study. This work was supported by the U.S. Army Medical Research and Materiel Command, grant number W81XWH-06-1-0105. NR 24 TC 12 Z9 12 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PD OCT PY 2010 VL 7 IS 10 BP 563 EP 572 DI 10.1080/15459624.2010.503755 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 659AB UT WOS:000282538100003 PM 20694886 ER PT J AU Vo, NV Sowa, GA Kang, JD Seidel, C Studer, RK AF Vo, Nam V. Sowa, Gwendolyn A. Kang, James D. Seidel, Christopher Studer, Rebecca K. TI Prostaglandin E2 and Prostaglandin F2 alpha Differentially Modulate Matrix Metabolism of Human Nucleus Pulposus Cells SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE nucleus pulposus cells; prostaglandins; PGE(2); PGF(2 alpha); intervertebral disc matrix ID INTERVERTEBRAL DISC DEGENERATION; NECROSIS-FACTOR-ALPHA; HUMAN ARTICULAR CHONDROCYTES; IN-VITRO; NITRIC-OXIDE; EXPRESSION; CYCLOOXYGENASE-2; ACTIVATION; HERNIATION; MEDIATORS AB Prostaglandin (PG) actions on disc metabolism are unclear even though certain PGs are highly expressed by disc cells under inflammatory conditions and nonsteroidal anti-inflammatory drugs (NSAI Ds) are frequently used to block PG production to treat back pain. Hence this study aimed to (1) quantify gene expression of arachiclonic acid cascade components responsible for PG synthesis and (2) examine the effects of key PGs on disc matrix homeostasis Microarray analysis revealed that inflammatory stress increases expression of synthases and receptors for prostaglandin E2 (PGE(2)) and prostaglandin F2 alpha (PGF(2 alpha)), resulting in elevated PGE(2) and PGF(2 alpha) production in conditioned mocha of disc cells PGE(2) diminished disc cell proteoglycan synthesis, in a dose-dependent manner Semiquantitative RT-PGR revealed differential effects of PGE(2) and PGF(2 alpha) on disc cell expression of key matrix structural genes. aggrecan, versican, collagens type I and II PGE(2) and PGF(2 alpha) also decreased message for the anabolic factor, IGF-1 PGE2 decreased mRNA expression for the anti-catabolic factor TIMP-1 while PGF(2 alpha) increased mRNAs for catabolic factors MMP-1 and MMP-3 Thus, PGE(2) and PGF(2 alpha) may have an overall negative impact on disc matrix homeostasis, and the use of NSAIDs may impact disc metabolism is well as treat back pain (C) 2010 Orthopaedic Research Society Published by Wiley Periodicals, Inc J Orthop Res 28 1259-1266, 2010 C1 [Vo, Nam V.; Sowa, Gwendolyn A.; Kang, James D.; Studer, Rebecca K.] Univ Pittsburgh, Sch Med, Ferguson Lab Orthopaed Res, Pittsburgh, PA 15260 USA. [Vo, Nam V.; Sowa, Gwendolyn A.; Kang, James D.; Studer, Rebecca K.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Pittsburgh, PA 15261 USA. [Sowa, Gwendolyn A.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA 15261 USA. [Studer, Rebecca K.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Seidel, Christopher] Stowers Inst Med Res, Kansas City, MO USA. RP Vo, NV (reprint author), Univ Pittsburgh, Sch Med, Ferguson Lab Orthopaed Res, Pittsburgh, PA 15260 USA. FU VA Rehabilitation Research and Development [B4-3894RA]; Pittsburgh Foundation; Ferguson Laboratory FX This work supported by VA Rehabilitation Research and Development Grant B4-3894RA and the Albert B. Ferguson, Jr, MD Orthopaedic Fund of the Pittsburgh Foundation. The work was approved by the IRB of the University of Pittsburgh The authors gratefully acknowledge the technical support of SuLan Huang, Elizabeth Christian, Geoffrey Sirockman, and the staff of the Ferguson Laboratory NR 40 TC 8 Z9 9 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD OCT PY 2010 VL 28 IS 10 BP 1259 EP 1266 DI 10.1002/joi.21157 PG 8 WC Orthopedics SC Orthopedics GA 647YQ UT WOS:000281657200001 PM 20839316 ER PT J AU Ullrich, CK Dussel, V Hilden, JM Sheaffer, JW Moore, CL Berde, CB Wolfe, J AF Ullrich, Christina K. Dussel, Veronica Hilden, Joanne M. Sheaffer, Jan W. Moore, Caron L. Berde, Charles B. Wolfe, Joanne TI Fatigue in Children with Cancer at the End of Life SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Fatigue; cancel; symptoms; child; palliative care; end-of-life care ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; RECEIVING PALLIATIVE CARE; PEDIATRIC-PATIENTS; SYMPTOMS; PATIENT; PARENTS; METHYLPHENIDATE; CHEMOTHERAPY; ADOLESCENTS AB Context. Fatigue is a prevalent source of suffering in children with advanced cancer; yet, little is known about it. Objectives. This study aimed to describe fatigue experienced by children with advanced cancer and to identify the factors associated with suffering from fatigue and its treatment. Methods. A retrospective cross-sectional study of 141 parents of children who died of cancer (response rate: 64%) was conducted in two tertiary-level U.S. pediatric hospitals. Results. By parent report, 96% of children experienced fatigue in the last month of life. Nearly 50% experienced significant suffering from fatigue; this was associated with suffering from pain, dyspnea, anorexia, nausea/vomiting, diarrhea, anxiety, sadness, or fear (P < 0.05), and with side effects from pain or dyspnea treatment (P < 0.05). In multivariate analysis of symptom-related factors, suffering from nausea/vomiting (odds ratio [OR] = 3.93, 95% confidence interval [CI] = 1.23-12.61, P = 0.02); anorexia (OR = 7.52, 95% CI = 1.87-30.25, P = 0.005); and fear (OR = 5.13, 95% CI = 2.03-12.96, P <= 0.001) remained independently associated with fatigue. Children suffering from fatigue had primary oncologists with fewer years' experience than children who did not suffer from fatigue (mean = 7.7 years, standard deviation [SD] = 4.9 vs. mean of 9.9 years, SD = 6.0, P = 0.02). Among children with fatigue, 17 of 129 (13%) received fatigue-directed treatment, which was successful in 3 of 12 (25%). Children experiencing side effects from dyspnea or pain treatment were more likely to be treated for fatigue (relative risk = 1.25, 95% CI = 1.06-1.47, P = 0.009). Conclusion. Fatigue is a common source of suffering in children with cancer at the end of life. Palliation of this symptom is rarely successful. Increased attention to factors associated with fatigue and effective interventions to ameliorate fatigue are needed. J Pain Symptom Manage 2010;40:483-494. (C) 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Ullrich, Christina K.; Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Ullrich, Christina K.; Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Ullrich, Christina K.; Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Berde, Charles B.] Childrens Hosp Boston, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Hilden, Joanne M.] Peyton Manning Childrens Hosp St Vincent, Dept Pediat, Indianapolis, IN USA. [Sheaffer, Jan W.; Moore, Caron L.] Childrens Hosp & Clin Minnesota, Dept Pediat Hematol Oncol, St Paul, MN USA. [Sheaffer, Jan W.; Moore, Caron L.] Childrens Hosp & Clin Minnesota, Dept Pediat Hematol Oncol, Minneapolis, MN USA. RP Ullrich, CK (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Smith 221,44 Binney St, Boston, MA 02115 USA. EM christina_ullrich@dfci.harvard.edu; joanne_wolfe@dfci.harvard.edu FU AHRQ [T32 PE10018]; American Cancer Society; Pine Tree Apple Tennis Classic Oncology Research Fund FX Christina K. Ullrich is an Olive Branch Foundation Scholar of the National Palliative Care Research Center. Christina K. Ullrich and Veronica Dussel were supported by AHRQ Grant No. T32 PE10018 to the Harvard Pediatric Health Services Research Fellowship Program. Joanne Wolfe is the recipient of a grant from the American Cancer Society. Jan W. Sheaffer was supported by the Pine Tree Apple Tennis Classic Oncology Research Fund. NR 63 TC 16 Z9 16 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD OCT PY 2010 VL 40 IS 4 BP 483 EP 494 DI 10.1016/j.jpainsymman.2010.02.020 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 671CA UT WOS:000283476200001 PM 20678889 ER PT J AU Loprinzi, CL Schapira, L Moynihan, T Kalemkerian, GP von Gunten, C Steensma, D AF Loprinzi, Charles L. Schapira, Lidia Moynihan, Timothy Kalemkerian, Gregory P. von Gunten, Charles Steensma, David TI Compassionate Honesty SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material ID BAD-NEWS; COMMUNICATION-SKILLS; DISCUSSING PROGNOSIS; ADVANCED CANCER; ONCOLOGY; TELL; WANT; INFORMATION; EXPERIENCE; COLLUSION C1 [Loprinzi, Charles L.; Moynihan, Timothy; Steensma, David] Mayo Clin, Rochester, MN 55905 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kalemkerian, Gregory P.] Univ Michigan, Ann Arbor, MI 48109 USA. [von Gunten, Charles] San Diego Hosp, Ctr Palliat Studies, San Diego, CA USA. RP Loprinzi, CL (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM cloprinzi@mayo.edu OI Steensma, David/0000-0001-5130-9284 NR 38 TC 3 Z9 3 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD OCT PY 2010 VL 13 IS 10 BP 1187 EP 1191 DI 10.1089/jpm.2010.9777 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 664IP UT WOS:000282953900005 PM 20846004 ER PT J AU Rabow, MW Pantilat, SZ Kerr, K Enguidanos, S Ferrell, B Goldstein, R Pankratz, C Picchi, T Rosenfeld, KE Stone, SC AF Rabow, Michael W. Pantilat, Steven Z. Kerr, Kathleen Enguidanos, Susan Ferrell, Bruce Goldstein, Rebecca Pankratz, Charles Picchi, Tina Rosenfeld, Kenneth E. Stone, Susan C. TI The Intersection of Need and Opportunity: Assessing and Capitalizing on Opportunities To Expand Hospital-Based Palliative Care Services SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID METRICS CONSENSUS RECOMMENDATIONS; UNITED-STATES; PROGRAMS; LIFE AB Background: To develop and grow most effectively, palliative care programs must consider how best to align their mission with that of their institution. To do so, programs must identify their institutional mission and needs, what palliative care can do to address those needs given available resources, and how the palliative care team can measure and document its value. Such an approach encourages the palliative care team to think strategically and to see themselves and their service as a solution to issues and concerns within the institution. It also helps a palliative care team decide which, among many potential opportunities and possible initiatives, is the one most likely to be supported by the institution and have a recognized and significant impact. Subjects and Methods: We present five case studies to demonstrate how successful programs identify and address institutional needs to create opportunities for palliative care program growth. These case studies can serve as models for other programs seeking to develop or expand their palliative care services. C1 [Rabow, Michael W.; Pantilat, Steven Z.; Kerr, Kathleen] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Enguidanos, Susan] Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA USA. [Ferrell, Bruce] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Goldstein, Rebecca] Downey Med Ctr Kaiser Downey, Dept Med, Downey, CA USA. [Pankratz, Charles] St Johns Reg Med Ctr, Dept Med, Oxnard, CA USA. [Pankratz, Charles] St Johns Pleasant Valley Hosp, Dept Med, Camarillo, CA USA. [Picchi, Tina] St Johns Reg Med Ctr, Dept Spiritual Care, Oxnard, CA USA. [Picchi, Tina] St Johns Pleasant Valley Hosp, Dept Spiritual Care, Camarillo, CA USA. [Rosenfeld, Kenneth E.] VA Greater Angeles Hlth Syst, Dept Med, Los Angeles, CA USA. [Stone, Susan C.] Univ So Calif, Dept Emergency Med, Los Angeles, CA USA. RP Rabow, MW (reprint author), Univ Calif San Francisco, Dept Med, 1701 Divisadero St 500, San Francisco, CA 94143 USA. EM mrabow@medicine.ucsf.edu OI Enguidanos, Susan/0000-0002-5112-288X FU Archstone Foundation Hospital-Based Palliative Care Service Innovation Initiative FX All authors have received support from the Archstone Foundation Hospital-Based Palliative Care Service Innovation Initiative. NR 13 TC 4 Z9 5 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD OCT PY 2010 VL 13 IS 10 BP 1205 EP 1210 DI 10.1089/jpm.2010.0112 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 664IP UT WOS:000282953900008 PM 20831435 ER PT J AU Jackson, V Arnold, RM AF Jackson, Vicki Arnold, Robert M. TI Starting a New Job SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 [Jackson, Vicki] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jackson, V (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM VJackson@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD OCT PY 2010 VL 13 IS 10 BP 1277 EP 1277 DI 10.1089/jpm.2010.9776 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 664IP UT WOS:000282953900018 ER PT J AU Winter, HS AF Winter, Harland S. TI Pantoprazole or Symptoms of Infant GERD: Clothing the Emperor! SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Letter ID NORTH-AMERICAN-SOCIETY; GASTROESOPHAGEAL-REFLUX; PEDIATRIC-GASTROENTEROLOGY; RECOMMENDATIONS; GUIDELINES; NUTRITION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Winter, HS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD OCT PY 2010 VL 51 IS 4 BP 537 EP 539 PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 653UU UT WOS:000282123600032 ER PT J AU Raval, MV Sturgeon, C Bentrem, DJ Elaraj, DM Stewart, AK Winchester, DJ Ko, CY Reynolds, M AF Raval, Mehul V. Sturgeon, Cord Bentrem, David J. Elaraj, Dina M. Stewart, Andrew K. Winchester, David J. Ko, Clifford Y. Reynolds, Marleta TI Influence of lymph node metastases on survival in pediatric medullary thyroid cancer SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Medullary thyroid cancer; Thyroid neoplasm; Pediatric surgery; Pathology; Epidemiology; National cancer data base ID MULTIPLE ENDOCRINE NEOPLASIA; STANDARDIZED SURGICAL APPROACH; 80 CONSECUTIVE PATIENTS; DATA-BASE REPORT; CLINICAL-CHARACTERISTICS; CONTEMPORARY SERIES; PROGNOSTIC-FACTORS; RET PROTOONCOGENE; BIOCHEMICAL CURE; UNITED-STATES AB Purpose: Lymph node metastases (LNM) from medullary thyroid cancer (MTC) are common in adults and are a poor prognostic factor. Less is known about LNM in children, who often have hereditary forms of MTC. Guidelines recommend prophylactic thyroidectomy in early childhood, but randomized prospective trials are not feasible. We hypothesized that LNM is associated with poor prognosis in children. Methods: Patients with MTC 21 years or younger from the National Cancer Data Base from 1985 to 2007 were studied. Multivariable logistic regression was used to identify factors associated with lymph node evaluation. Survival was estimated using the Kaplan-Meier method. Results: Of 430 patients, 276 (64.2%) had nodal evaluation with LNM present in 121 (28.1%). Older patients, those with tumors larger than 2 cm, and those with involved margins were more likely to have LNM (all P < .05). Patients undergoing total thyroidectomy, those with involved margins, and older patients were more likely to undergo lymph node evaluation after controlling for patient, tumor, and hospital factors (all P < .05). Over time an increasing number of patients with MTC have undergone total thyroidectomy. Patients 16 to 21 years of age had lower 10-year overall survival compared to patients 0 to 15 years old (88.7% vs 98.1%, P = .005). Lymph node metastases were also associated with decreased 10-year overall survival (84.4% vs 100%, P < .001). Conclusions: In pediatric MTC, LNM predict poorer overall survival. Adequate lymph node assessment can provide valuable prognostic information for the pediatric MTC patient. Lymph node assessment should be considered for older pediatric patients undergoing surgery for hereditary MTC or biopsy confirmed MTC. (C) 2010 Elsevier Inc. All rights reserved. C1 [Raval, Mehul V.; Stewart, Andrew K.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Canc Programs, Chicago, IL 60611 USA. [Raval, Mehul V.; Reynolds, Marleta] Childrens Mem Hosp, Div Pediat Surg, Chicago, IL 60614 USA. [Raval, Mehul V.; Sturgeon, Cord; Bentrem, David J.; Elaraj, Dina M.] Northwestern Univ, Feinberg Sch Med, Div Gastrointestinal & Oncol Surg, Dept Surg, Chicago, IL 60611 USA. [Bentrem, David J.] Jesse Brown VA Med Ctr, Chicago, IL 60612 USA. [Winchester, David J.] NorthShore Univ HealthSyst, Dept Surg, Evanston, IL 60201 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90073 USA. [Ko, Clifford Y.] VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Raval, MV (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, Canc Programs, Chicago, IL 60611 USA. EM m-raval@md.northwestern.edu OI Raval, Mehul/0000-0002-1527-2661 FU John Gray Research Fellowship; Daniel F and Ada L Rice Foundation; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service; American College of Surgeons, Commission on Cancer; American Cancer Society FX MVR participates in the American College of Surgeons Clinical Scholars in Residence Program and is supported by the John Gray Research Fellowship and the Daniel F and Ada L Rice Foundation. DJB is supported by a career development award from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service. The National Cancer Data Base is supported by the American College of Surgeons, Commission on Cancer, and the American Cancer Society. NR 42 TC 9 Z9 9 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD OCT PY 2010 VL 45 IS 10 BP 1947 EP 1954 DI 10.1016/j.jpedsurg.2010.06.013 PG 8 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 656WC UT WOS:000282370800010 PM 20920711 ER PT J AU Goodman, E Must, A Daniels, SR Dolan, LM AF Goodman, Elizabeth Must, Aviva Daniels, Stephen R. Dolan, Lawrence M. TI Hostility and Adiposity Mediate Disparities in Insulin Resistance among Adolescents and Young Adults SO JOURNAL OF PEDIATRICS LA English DT Article ID CORONARY-HEART-DISEASE; SOCIOECONOMIC-STATUS; RISK-FACTORS; METABOLIC SYNDROME; PSYCHOSOCIAL CHARACTERISTICS; HEALTH BEHAVIORS; PHYSICAL HEALTH; US ADOLESCENTS; CHILDREN; ASSOCIATION AB Objective This study explores whether the relationship between lower socioeconomic status and insulin resistance in adolescents is mediated by both physiological and psychological factors associated with increased cardiometabolic risk Study design School-based longitudinal cohort study of 1222 healthy, non-Hispanic black and white teens. Parent education (PE), youth-specific Cook-Medley hostility scale, waist circumference, height, weight, pubertal status, and fasting plasma insulin (FPI) were measured and FPI reassessed 1 year later. Regression analyses utilizing bootstrapping (n = 2000) were used to estimate the direct and indirect effects of PE on FPI and assess the role of hostility and adiposity while adjusting for covariates. Results Lower PE predicted higher FPI (B = -1.52, P =.003), as did hostility (B =.19, P =.002) and adiposity (waist circumference B =.44, P <.001, BMI B =.98, P <.001). The effect of PE on FPI was mediated by both hostility and adiposity. When adiposity and hostility were accounted for, the effect of PE on FPI decreased by 32% (B = -1.04, P =.04); the total indirect estimate was -.485 (95% CI, -.652, -.041). Hostility accounted for 36% of the meditational effect. Conclusions Lower PE influences insulin resistance through adiposity and hostility. Thus, interventions to reduce health disparities associated with insulin resistance should consider both physiological and psychological approaches. (J Pediatr 2010; 157:572-7). C1 [Goodman, Elizabeth] Tufts Med Ctr, Floating Hosp Children, Boston, MA USA. [Must, Aviva] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA. [Daniels, Stephen R.] Denver Childrens Hosp, Dept Pediat, Denver, CO USA. Univ Colorado, Sch Med, Denver, CO USA. [Dolan, Lawrence M.] Cincinnati Childrens Hosp Med Ctr, Div Endocrinol, Cincinnati, OH USA. RP Goodman, E (reprint author), MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM egoodman3@partners.org OI Goodman, Elizabeth/0000-0002-9640-9884 FU NIH [HD41527, DK59183, M01RR 08084] FX Supported by NIH grants HD41527, DK59183, and M01RR 08084. S.D. is a consultant to Abbott and Schering-Plough. The other authors declare no conflicts of interest. NR 38 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2010 VL 157 IS 4 BP 572 EP U84 DI 10.1016/j.jpeds.2010.04.048 PG 7 WC Pediatrics SC Pediatrics GA 647YM UT WOS:000281656800014 PM 20542297 ER PT J AU Biederman, J Spencer, TJ Monuteaux, MC Faraone, SV AF Biederman, Joseph Spencer, Thomas J. Monuteaux, Michael C. Faraone, Stephen V. TI A Naturalistic 10-Year Prospective Study of Height and Weight in Children with Attention-Deficit Hyperactivity Disorder Grown Up: Sex and Treatment Effects SO JOURNAL OF PEDIATRICS LA English DT Article ID FOLLOW-UP; DEFICIT/HYPERACTIVITY DISORDER; STIMULANTS AB Objective To assess the effect of attention-deficit/hyperactivity disorder (ADHD) and its treatment on growth outcomes in children followed into adulthood. Study design Two identically designed, longitudinal, case-control studies of males and females with and without ADHD were combined; 124 and 137 control and subjects with ADHD, respectively, provided growth information at the 10- to 11-year follow-up. We used linear growth curve models to estimate the effect of time on change in height and whether this effect differed by sex and ADHD status. We also examined the effect of stimulant treatment on growth outcomes. Results We found no evidence that ADHD was associated with trajectories of height over time or differences at follow-up in any growth outcomes. Similarly, we found no evidence that stimulant treatment was associated with differences in growth. However, among subjects with ADHD, major depression was associated with significantly larger weight in females and smaller height in males. Conclusions Our results do not support an association between deficits in growth outcomes and either ADHD or psychostimulant treatment for ADHD. These findings extend the literature on this topic into young adulthood and should assist clinicians and parents in formulating treatment plans for children with ADHD. (J Pediatr 2010;157:635-40). C1 [Biederman, Joseph; Spencer, Thomas J.; Monuteaux, Michael C.] Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Pediat Psychiat, Boston, MA 02114 USA. [Biederman, Joseph; Spencer, Thomas J.; Monuteaux, Michael C.] Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Spencer, Thomas J.; Monuteaux, Michael C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Dept Pediat Psychopharmacol, Boston, MA USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Pediat Psychiat, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [5R01 HD-36317-07, R01 HD036317] NR 18 TC 32 Z9 34 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 2010 VL 157 IS 4 BP 635 EP U158 DI 10.1016/j.jpeds.2010.04.025 PG 7 WC Pediatrics SC Pediatrics GA 647YM UT WOS:000281656800027 PM 20605163 ER PT J AU Ross, JH Hardy, DC Schuyler, CA Slate, EH Mize, TW Huang, Y AF Ross, J. H. Hardy, D. C. Schuyler, C. A. Slate, E. H. Mize, T. W. Huang, Y. TI Expression of periodontal interleukin-6 protein is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE periodontal diseases; diabetes mellitus; interleukin-6 (IL-6); gene expression ID MATRIX METALLOPROTEINASE-1 EXPRESSION; CARDIOVASCULAR-DISEASE; IL-6; LIPOPOLYSACCHARIDE; INFLAMMATION; TISSUE; RISK; POLYMORPHISMS; FIBROBLASTS; MELLITUS AB Background and Objective: Epidemiological studies have established that patients with diabetes have an increased prevalence and severity of periodontal disease. Interleukin (IL)-6, a multifunctional cytokine, plays a role in the tissue inflammation that characterizes periodontal disease. Our recent study has shown a trend of increase in periodontal IL-6 expression at the mRNA level across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. However, the periodontal IL-6 expression at the protein level in these patients has not been investigated. Material and Methods: Periodontal tissue specimens were collected from eight patients without periodontal disease and diabetes (group 1), from 17 patients with periodontal disease alone (group 2) and from 10 patients with both periodontal disease and diabetes (group 3). The frozen sections were prepared from these tissue specimens and IL-6 protein expression was detected and quantified. Results: The nonparametric Kruskal-Wallis test showed that the difference in IL-6 protein levels among the three groups was statistically significant (p = 0.035). Nonparametric analysis using the Jonckheere-Terpstra test showed a tendency of increase in periodontal IL-6 protein levels across group 1 to group 2 to group 3 (p = 0.006). Parametric analysis of variance (ANOVA) on IL-6 protein levels showed that neither age nor gender significantly affected the difference of IL-6 levels among the groups. Conclusion: Periodontal IL-6 expression at the protein level is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. C1 [Huang, Y.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Ross, J. H.; Hardy, D. C.; Mize, T. W.] Med Univ S Carolina, Div Periodont, Dept Stomatol, Coll Dent Med, Charleston, SC 29403 USA. [Slate, E. H.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29403 USA. [Huang, Y.] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, 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 NIH [DE16353]; Department of Veterans Affairs; COBRE, NIH [P20RR017696] FX This work was supported by NIH grant DE16353 and by a Merit Review Grant from the Department of Veterans Affairs (to Y.H.). This work was also partially supported by COBRE grant P20RR017696 from NIH. NR 29 TC 11 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD OCT PY 2010 VL 45 IS 5 BP 688 EP 694 DI 10.1111/j.1600-0765.2010.01286.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 641PR UT WOS:000281141500013 PM 20682019 ER PT J AU Sloan, DM Sege, CT McSweeney, LB Suvak, MK Shea, MT Litz, BT AF Sloan, Denise M. Sege, Christopher T. McSweeney, Lauren B. Suvak, Michael K. Shea, M. Tracie Litz, Brett T. TI DEVELOPMENT OF A BORDERLINE PERSONALITY DISORDER-RELEVANT PICTURE STIMULUS SET SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; STARTLE REFLEX; MODULATION; EMOTION; IMPULSIVITY; WOMEN AB Individuals with borderline personality disorder (BPD) report erratic and poorly regulated emotional behavior. However, these abnormalities have not been confirmed in laboratory studies. This may be because the emotional stimuli employed have not been sufficiently relevant or evocative of psychological themes germane to BPD (e.g., threats to attachment). The aim of this study was to develop a picture stimulus set relevant to BPD that could be employed in research to examine emotion dysregulation thought to be central to BPD. Ninety pictures were initially selected from the International Affective Picture System that had putative interpersonal and social content across a range of pleasantness and intensity. The set was then rated by 19 clinical BPD research experts on two dimensions: How self-referential the picture would be to someone with BPD and the extent to which the picture represented an ideal-other to a prototypic BPD case. Two sets of pictures were generated for future research with BPD participants. C1 [Sloan, Denise M.; Sege, Christopher T.; Suvak, Michael K.; Litz, Brett T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Sloan, Denise M.; Suvak, Michael K.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Shea, M. Tracie] Brown Univ, Warren Alpert Med Sch, Dept Vet Affairs Providence, Providence, RI 02912 USA. [Shea, M. Tracie] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B-2, Boston, MA 02130 USA. EM Denise.Sloan@va.gov FU NIMH NIH HHS [MH069444] NR 29 TC 8 Z9 8 U1 2 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD OCT PY 2010 VL 24 IS 5 BP 664 EP 675 PG 12 WC Psychiatry SC Psychiatry GA 660TY UT WOS:000282669900007 PM 20958174 ER PT J AU Zhou, JY Afjehi-Sadat, L Asress, S Duong, DM Cudkowicz, M Glass, JD Peng, J AF Zhou, Jian-Ying Afjehi-Sadat, Leila Asress, Seneshaw Duong, Duc M. Cudkowicz, Merit Glass, Jonathan D. Peng, Junmin TI Galectin-3 Is a Candidate Biomarker for Amyotrophic Lateral Sclerosis: Discovery by a Proteomics Approach SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE Motor neuron disease; galectin-3; human; biomarkers ID CEREBROSPINAL-FLUID; SHOTGUN PROTEOMICS; MASS-SPECTROMETRY; SPINAL-CORD; MOUSE MODEL; ALS; CHROMATOGRAPHY; DEGENERATION; PROTEINS; TDP-43 AB The discovery of biomarkers for neurodegenerative diseases will have a major impact on the efficiency of therapeutic clinical trials and may be important for understanding basic pathogenic mechanisms. We have approached the discovery of protein biomarkers for amyotrophic lateral sclerosis (ALS) by profiling affected tissues in a relevant animal model and then validating the findings in human tissues. Ventral roots from SOD1(G93A) "ALS" mice were analyzed by label-free quantitative mass spectrometry, and the resulting data were compared with data for matched samples from nontransgenic littermates and transgenic mice carrying wild-type human SOD1 (SOD1(WT)). Of 1299 proteins, statistical inference of the data in the three groups identified 14 proteins that were dramatically altered in the ALS mice compared with the two control groups. The protein galectin-3 emerged as a lead biomarker candidate on the basis of its differential expression as assessed by immunoblot and immunocytochemistry in SOD1G93A mice as compared to controls and because it is a secreted protein that could potentially be measured in human biofluids. Spinal cord tissue from ALS patients also exhibited increased levels of galectin-3 when compared to controls. Further measurement of galectin-3 in cerebrospinal fluid samples showed that ALS patients had approximately twice as much galectin-3 as normal and disease controls. These results provide the proof of principle that biomarker identification in relevant and well-controlled animal models can be translated to human disease. The challenge is to validate our biomarker candidate proteins as true biomarkers for ALS that will be useful for diagnosis and/or monitoring disease activity in future clinical trials. C1 [Glass, Jonathan D.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Glass, Jonathan D.] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. [Zhou, Jian-Ying; Afjehi-Sadat, Leila; Duong, Duc M.; Peng, Junmin] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. [Zhou, Jian-Ying; Afjehi-Sadat, Leila; Asress, Seneshaw; Duong, Duc M.; Glass, Jonathan D.; Peng, Junmin] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Atlanta, GA 30322 USA. [Asress, Seneshaw; Glass, Jonathan D.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Emory Prote Serv Ctr, Atlanta, GA 30322 USA. [Cudkowicz, Merit] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cudkowicz, Merit] Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. RP Glass, JD (reprint author), Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. EM jglas03@emory.edu; jpeng@emory.edu RI Zhou, Jian-Ying/B-1336-2011; Zhou, Jian-Ying/D-1308-2012 FU National Institutes of Health [P50AG025688, R21NS060182, P30NS055077]; Amyotrophic Lateral Sclerosis Association FX We thank Drs. A. Levey, P. Xu, and N. T. Seyfried for valuable comments regarding the manuscript, Matt Jaffa for assistance with CSF samples, and Dr. Marla Gearing and Deborah Cooper for providing the human spinal cord tissues. We also thank Dr. H. Cummings for providing purified Gal3 proteins. This work was supported by National Institutes of Health Grants P50AG025688, R21NS060182, and P30NS055077 and the Amyotrophic Lateral Sclerosis Association. Importantly, we thank the patients and families who contributed tissues and CSF samples, without which this kind of research could not be accomplished. NR 31 TC 33 Z9 34 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD OCT PY 2010 VL 9 IS 10 BP 5133 EP 5141 DI 10.1021/pr100409r PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 655NX UT WOS:000282257800023 PM 20698585 ER PT J AU D'Hertog, W Maris, M Ferreira, GB Verdrengh, E Lage, K Hansen, DA Cardozo, AK Workman, CT Moreau, Y Eizirik, DL Waelkens, E Overbergh, L Mathieu, C AF D'Hertog, Wannes Maris, Michael Ferreira, Gabriela B. Verdrengh, Eefje Lage, Kasper Hansen, Daniel A. Cardozo, Alessandra K. Workman, Christopher T. Moreau, Yves Eizirik, Decio L. Waelkens, Etienne Overbergh, Lutgart Mathieu, Chantal TI Novel Insights into the Global Proteome Responses of Insulin-Producing INS-1E Cells To Different Degrees of Endoplasmic Reticulum Stress SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE Type 1 diabetes; 2D-DIGE; INS-1E; endoplasmic reticulum stress ID PANCREATIC BETA-CELLS; 14-3-3 PROTEINS; HNRNP-K; GENE-EXPRESSION; MESSENGER-RNA; DEATH; BAD; SECRETION; SURVIVAL; BINDING AB Exposure of insulin-secreting beta-cells to inflammatory cytokines or high concentrations of free fatty acids, factors involved in the pathogenesis of type 1 and type 2 diabetes, leads to endoplasmic reticulum (ER) stress, beta-cell dysfunction, and eventually apoptotic beta-cell death. The aim of this study was to investigate the impact of ER stress on beta-cells at the protein level to evaluate the contribution of post-transcriptional and post-translational changes in ER stress-induced beta-cell damage. INS-1E cells were exposed in vitro to the ER-stress inducer cyclopiazonic acid (CPA) at two concentrations, and protein changes were evaluated using 2D-DIGE. CPA, 25 mu M, led to massive apoptosis, accompanied by a near complete protein translation shut-down. CPA, 6.25 mu M, led to adaptation of the beta-cells to ER stress. Identification of the differentially expressed proteins in the two conditions led to the discovery of a clear pattern of defense pathways, with post-translational modifications playing a crucial role. Key alterations included inhibition of insulin translation and post-translational modifications in ER chaperones HYOU1 and HSPA5. Also, a central role for 14-3-3 proteins is suggested. In conclusion, INS-1E cells are highly sensitive to ER stress, leading to important post-transcriptional and post-translational modifications that may contribute to beta-cell dysfunction and death. C1 [D'Hertog, Wannes; Maris, Michael; Ferreira, Gabriela B.; Verdrengh, Eefje; Overbergh, Lutgart; Mathieu, Chantal] Catholic Univ Louvain, Univ Hosp Gasthuisberg, Lab Expt Med & Endocrinol LEGENDO, B-3000 Louvain, Belgium. [Lage, Kasper; Hansen, Daniel A.; Workman, Christopher T.] Tech Univ Denmark, Ctr Biol Sequence Anal, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Lage, Kasper] Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Surg Res Labs, Boston, MA 02114 USA. [Lage, Kasper] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lage, Kasper; Overbergh, Lutgart; Mathieu, Chantal] MIT, Broad Inst, Cambridge, MA 02142 USA. [Lage, Kasper] Harvard Univ, Cambridge, MA 02142 USA. [Cardozo, Alessandra K.; Eizirik, Decio L.] Free Univ Brussels, Expt Med Lab, B-1070 Brussels, Belgium. [Moreau, Yves] Catholic Univ Louvain, Dept Elect Engn, ESAT SDC, B-3001 Heverlee, Belgium. [Waelkens, Etienne] Catholic Univ Louvain, Univ Hosp Gasthuisberg, ProMeta, B-3000 Louvain, Belgium. [Waelkens, Etienne] Catholic Univ Louvain, Univ Hosp Gasthuisberg, Biochem Lab, B-3000 Louvain, Belgium. RP Overbergh, L (reprint author), Catholic Univ Louvain, Univ Hosp Gasthuisberg, Lab Expt Med & Endocrinol LEGENDO, Herestr 49,Box 902, B-3000 Louvain, Belgium. EM lut.overbergh@med.kuleuven.be RI Bomfim Ferreira, Gabriela/L-8343-2014; Workman, Christopher/K-1066-2015 OI Workman, Christopher/0000-0002-2210-3743 FU Catholic University of Leuven (GOA) [2004/10, 2009/10]; Flemish Research Foundation (FWO) [G.0552.06, G.0649.08]; Belgium Program on Interuniversity Poles of Attraction initiated by the Belgian State [IUAP P5/17, P6/40]; Centre of Excellence SymBioSys [EF/05/007]; Juvenile Diabetes Research Foundation International [1-2008-536]; European Union; European Community; NAIMIT; Forskningsradet for Sunned og Sygdom; NICHD [HD055150-03]; [E06D100904BR] FX This work was supported by the Catholic University of Leuven (GOA 2004/10 and 2009/10), the Flemish Research Foundation (FWO G.0552.06 G.0649.08), the Belgium Program on Interuniversity Poles of Attraction initiated by the Belgian State (IUAP P5/17 and P6/40), the Centre of Excellence SymBioSys (Research Council K.U.Leuven EF/05/007), the Juvenile Diabetes Research Foundation International (1-2008-536), and the European Union (projects Savebeta, in the Framework Program 6 of the European Community, and NAIMIT, in the Framework Program 7 of the European Community). K.L. is supported by a grant from 'Forskningsradet for Sunned og Sygdom' and by NICHD ROI grant HD055150-03. G.B.F. is supported by a doctoral fellowship (Alban, no. E06D100904BR), A.K.C. by a Research Associate of the Fonds National de la Recherche Scientifique, and C.M. by a clinical research fellowship (FWO). We gratefully acknowledge the technical assistance of Karin Schildermans, Sandy Vandoninck, Nursen Gol, Jos Depovere, and Jos Laureys. NR 50 TC 11 Z9 11 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD OCT PY 2010 VL 9 IS 10 BP 5142 EP 5152 DI 10.1021/pr1004086 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 655NX UT WOS:000282257800024 PM 20839851 ER PT J AU Ehrlich, S Weiss, D Burghardt, R Infante-Duarte, C Brockhaus, S Muschler, MA Bleich, S Lehmkuhl, U Frieling, H AF Ehrlich, Stefan Weiss, Deike Burghardt, Roland Infante-Duarte, Carmen Brockhaus, Simone Muschler, Marc A. Bleich, Stefan Lehmkuhl, Ulrike Frieling, Helge TI Promoter specific DNA methylation and gene expression of POMC in acutely underweight and recovered patients with anorexia nervosa SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Proopiomelanocortin (POMC); alpha-MSH; Leptin; Cortisol; Anorexia nervosa; mRNA expression; Promoter specific DNA methylation; CpG residues ID MELANOCYTE-STIMULATING HORMONE; PROOPIOMELANOCORTIN MESSENGER-RNA; AGOUTI-RELATED PROTEIN; EATING-DISORDERS; HAIR PIGMENTATION; ACTH EXPRESSION; BETA-ENDORPHIN; NEUROPEPTIDE-Y; FOOD-INTAKE; IN-VIVO AB Proopiomelanocortin (POMC) and its derived peptides, in particular alpha-MSH, have been shown to play a crucial role in the regulation of hunger, satiety and energy homeostasis. Studies in patients with anorexia nervosa (AN) suggest an abnormal expression of appetite-regulating hormones. Hormone expression levels may be modulated by epigenetic mechanisms, which were recently shown to be implicated in the pathophysiology of eating disorders. We hypothesised that POMC promoter specific DNA methylation and gene expression will be affected by malnutrition and therefore differ in AN patients at distinct stages of the disorder. Promoter specific DNA methylation of the POMC gene and expression of POMC mRNA variants were determined in peripheral blood mononuclear cells (PBMC) of 30 healthy control women (HCW), 31 underweight (acAN) and 30 weight-recovered patients with AN (recAN). Malnutrition was characterized by plasma leptin. Expression of the functionally relevant long POMC mRNA transcript was significantly correlated with leptin levels and higher in acAN compared to recAN and HCW. Expression of the truncated form and mean promoter DNA methylation was similar in all three subgroups. Methylation of single CpG residues in the E2F binding site was inversely related to POMC expression. Our preliminary data on pattern of POMC regulation suggests an association with the underweight state rather than with persisting trait markers of AN. In contrast to POMC expression in the central nervous system, peripheral POMC mRNA expression decreased with malnutrition and hypoleptinemia. This may represent a counterregulatory mechanism as part of the crosstalk between the immune and neuroendocrine systems. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Ehrlich, Stefan] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Psychiat Neuroimaging Res Program,Med Sch,Gollub, Charlestown, MA 02129 USA. [Ehrlich, Stefan; Weiss, Deike; Burghardt, Roland; Brockhaus, Simone; Lehmkuhl, Ulrike] Charite, CVK, Dept Child & Adolescent Psychiat Psychosomat & Ps, Berlin, Germany. [Ehrlich, Stefan] Charite, CCM, Dept Psychiat & Psychotherapy, Berlin, Germany. [Infante-Duarte, Carmen] Charite, CCM, Cecilie Vogt Clin, Berlin, Germany. [Muschler, Marc A.; Bleich, Stefan; Frieling, Helge] Hannover Med Sch, Mol Neurosci Lab, Dept Psychiat Socialpsychiat & Psychotherapy, D-3000 Hannover, Germany. [Frieling, Helge] Univ Hosp Erlangen, Dept Psychiat & Psychotherapy, Erlangen, Germany. RP Ehrlich, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Psychiat Neuroimaging Res Program,Med Sch,Gollub, CNY Bldg 120,Suite 100, Charlestown, MA 02129 USA. EM stefan@nmr.mgh.harvard.edu RI Frieling, Helge/C-5299-2015; OI Frieling, Helge/0000-0001-5146-9720; Ehrlich, Stefan/0000-0003-2132-4445 FU Charite Research Fund; DFG; German federal ministry of education and research (BMBF); Beyer Vital AG; Astra Zeneca Germany FX Funding for this study was provided by the Charite Research Fund, the German Research Fund (DFG) and the German federal ministry of education and research (BMBF). The aforementioned funding organizations had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.; S.B. and H.F. are holding grants from Beyer Vital AG and previously from Astra Zeneca Germany. S.B. has consulted for Astra Zeneca, Janssen, Lundbeck, Merz, Beyer, Servier Germany, BMS and Ostuka. H.F. has consulted for Astra Zeneca, Merz, Otsuka and Servier Germany. All other authors declare no biomedical financial interests or potential conflicts of interest. NR 64 TC 43 Z9 43 U1 3 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2010 VL 44 IS 13 BP 827 EP 833 DI 10.1016/j.jpsychires.2010.01.011 PG 7 WC Psychiatry SC Psychiatry GA 657FO UT WOS:000282398800004 PM 20176366 ER PT J AU Agnati, LF Guidolin, D Vilardaga, JP Ciruela, F Fuxe, K AF Agnati, Luigi F. Guidolin, Diego Vilardaga, Jean Pierre Ciruela, Francisco Fuxe, Kjell TI On the expanding terminology in the GPCR field: The meaning of receptor mosaics and receptor heteromers SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Article DE Oligomerization; receptor-receptor interactions; stoichiometry; spatial arrangement ID PROTEIN-COUPLED RECEPTORS; ADENOSINE A(2A) RECEPTORS; CENTRAL-NERVOUS-SYSTEM; METABOTROPIC GLUTAMATE-RECEPTOR; BETA-ADRENERGIC-RECEPTORS; HIGHER-ORDER OLIGOMERS; LIVING CELLS; DOPAMINE-D-2 RECEPTORS; NEGATIVE COOPERATIVITY; CONFORMATIONAL-CHANGES AB The oligomerization of G protein-coupled receptors (GPCRs) is a fact that deserves further attention as increases both the complexity and diversity of the receptor-mediated signal transduction, thus enriching the cell signaling. Consequently, in the present review we tackle among others the problems concerning the terminology used to describe aspects surrounding the GPCRs oligomerization phenomenon. Therefore, the theoretical implications of the GPCR oligomerization will be briefly discussed together with possible implications of this phenomenon especially for new strategies in drug development. C1 [Agnati, Luigi F.] IRCCS San Camillo, Lido Venezia, Italy. [Guidolin, Diego] Univ Padua, Dept Human Anat & Physiol, Padua, Italy. [Vilardaga, Jean Pierre] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Vilardaga, Jean Pierre] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Vilardaga, Jean Pierre] Harvard Univ, Sch Med, Boston, MA USA. [Ciruela, Francisco] IDIBELL Univ Barcelona, Fac Med, Dept Patol & Terapeut Expt, Unitat Farmacol, Barcelona, Spain. [Fuxe, Kjell] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Agnati, LF (reprint author), IRCCS San Camillo, Via Alberoni 70, Lido Venezia, Italy. EM luigiagnati@tin.it RI Ciruela, Francisco/A-5096-2013 OI Fuxe, Kjell/0000-0001-8491-4288; Guidolin, Diego/0000-0003-2133-3552; Ciruela, Francisco/0000-0003-0832-3739 FU IRCCS San Camillo; Swedish Research Council; Swedish Brain Fund; Torsten and Ragnar Soderberg's Foundation; Ministerio de Ciencia e Innovacion [SAF2008-01462, CSD2008-00005] FX This work was supported by IRCCS San Camillo (L.F.A.), Swedish Research Council, Swedish Brain Fund and Torsten and Ragnar Soderberg's Foundation (K.F.) and by grants SAF2008-01462 and Consolider-Ingenio CSD2008-00005 from Ministerio de Ciencia e Innovacion to F.C. who belong to the "Neuropharmacology and Pain" accredited research group (Generalitat de Catalunya, 2009 SGR 232). NR 132 TC 17 Z9 17 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1079-9893 EI 1532-4281 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PD OCT PY 2010 VL 30 IS 5 SI SI BP 287 EP 303 DI 10.3109/10799891003786226 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 671CD UT WOS:000283476500004 PM 20429829 ER PT J AU Vilardaga, JP AF Vilardaga, Jean-Pierre TI Theme and variations on kinetics of GPCR activation/deactivation SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Review DE GPCR; kinetics; FRET ID PROTEIN-COUPLED RECEPTORS; BETA(2) ADRENERGIC-RECEPTOR; RESONANCE ENERGY-TRANSFER; PARATHYROID-HORMONE RECEPTOR; GAMMA COMPLEX TRANSLOCATION; HETEROTRIMERIC G-PROTEINS; LIVING CELLS; CONFORMATIONAL-CHANGES; ALLOSTERIC MODULATION; MUSCARINIC RECEPTOR AB G protein-coupled receptors (GPCRs) initiate intracellular signaling pathways in response to physiologically and medically important extracellular ligands such as peptide and large glycoprotein hormones, neurotransmitters, sensory stimuli (odorant and taste molecules, light), calcium, L-amino acids, and are the target of many clinical drugs. The conversion of these extracellular stimuli into intracellular signals involves sequential and reversible reactions that initially take place at the plasma membrane. These reactions are mediated not only by dynamic interactions between ligands, receptors and heterotrimeric G proteins, but also by conformational changes associated with the activation/deactivation process of each protein. This review discusses the kinetic characteristics and rate-limiting reactions engaged in signal propagation that are involved in systems as diverse as neurotransmitter and hormonal signaling, and that have been recorded in live cells by Forster resonance energy transfer (FRET) approaches. C1 [Vilardaga, Jean-Pierre] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Sch Med, Pittsburgh, PA 15261 USA. [Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Vilardaga, JP (reprint author), Univ Pittsburgh, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Sch Med, E1357,200 Lothrop St, Pittsburgh, PA 15261 USA. EM jpv@pitt.edu FU National Institutes of Health (NIH) [DK087688] FX This work was supported by the National Institutes of Health (NIH) grant DK087688. I thank Tim Feinstein for critical comments. NR 73 TC 12 Z9 12 U1 0 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PD OCT PY 2010 VL 30 IS 5 SI SI BP 304 EP 312 DI 10.3109/10799893.2010.509728 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 671CD UT WOS:000283476500005 PM 20836728 ER PT J AU Petri, M Naqibuddin, M Carson, KA Wallace, DJ Weisman, MH Holliday, SL Sampedro, M Padilla, PA Brey, RL AF Petri, Michelle Naqibuddin, Mohammad Carson, Kathryn A. Wallace, Daniel J. Weisman, Michael H. Holliday, Stephen L. Sampedro, Margaret Padilla, Patricia A. Brey, Robin L. TI Depression and Cognitive Impairment in Newly Diagnosed Systemic Lupus Erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE SYSTEMIC LUPUS ERYTHEMATOSUS; DEPRESSION; AUTOMATED NEUROPSYCHOLOGICAL ASSESSMENT METRICS ID RATING-SCALE; DISEASE-ACTIVITY; PSYCHIATRIC-SYMPTOMS; REVISED CRITERIA; FATIGUE; CLASSIFICATION; SCHIZOPHRENICS; ANTIBODIES; DISORDERS; MOOD AB Objective. Cognitive impairment is present in 80% of patients with systemic lupus erythematosus (SLE) 10 years after diagnosis. The natural history of cognitive dysfunction in newly diagnosed SLE is unknown. We examined the association of depression and cognitive performance in newly diagnosed SLE. Methods. A multicenter cohort of 111 patients newly diagnosed (within 9 months) with SLE underwent cognitive function testing using an automated battery [Automated Neuropsychological Assessment Metrics (ANAM)] with 9 subtests. Depression was measured using the Calgary Depression Scale (CDS). Results. The patient cohort was 97.3% female, 55.9% white, 15.3% African American, 20.7% Hispanic, mean age 37.8 years, mean education 15.2 years. CDS score ranged from 0 to 18 (mean 5.0 +/- 4.6). CDS score did not differ by age, sex, ethnicity, or prednisone dose. Higher Krupp Fatigue Severity Scale scores and presence of fibromyalgia were significantly associated with higher CDS score (p < 0.001 p = 0.006, respectively). Depressed patients, defined by a CDS score > 6, had significantly poorer performance on 5 ANAM throughput measures: code substitution (p = 0.03), continuous performance (p = 0.02), matching-to-sample (p = 0.04), simple reaction time (p = 0.02), and the Sternberg memory test (p = 0.04). Adjusting for age, sex, ethnicity, education, and prednisone dose, a higher CDS score remained significantly associated with poorer performance on 3 measures, but the association was slightly attenuated for code substitution and matching-to-sample. Depression was not associated with mathematical or spatial processing. Conclusion. Depression, a modifiable risk factor, is associated with significantly poorer function in several cognitive domains in patients newly diagnosed with SLE. Treatment of depression when the CDS score is greater than 6 may improve cognitive functioning and should be further studied. (First Release July 15 2010; J Rheumatol 2010;37:2032-8; doi:10.3899/jrheum.091366) C1 [Petri, Michelle; Naqibuddin, Mohammad; Carson, Kathryn A.; Sampedro, Margaret] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Wallace, Daniel J.; Weisman, Michael H.] Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Los Angeles, CA 90095 USA. [Holliday, Stephen L.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Padilla, Patricia A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Petri, M (reprint author), Johns Hopkins Univ, 1830 E Monument St,Suite 7500, Baltimore, MD 21205 USA. EM mpetri@jhmi.edu FU NIH [RO1 AR049125]; Johns Hopkins Institute for Clinical and Translational Research [UL1 RR 025005]; University of Texas Health Science Center at San Antonio Frederic C. Bartter General Clinical Research Center [MO1-RR-01346] FX The Brain CONECTIONS study is supported by NIH RO1 AR049125 and the Johns Hopkins Institute for Clinical and Translational Research (K. Carson is supported by UL1 RR 025005) and the University of Texas Health Science Center at San Antonio Frederic C. Bartter General Clinical Research Center (MOI-RR-01346). NR 46 TC 35 Z9 36 U1 3 U2 8 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2010 VL 37 IS 10 BP 2032 EP 2038 DI 10.3899/jrheum.091366 PG 7 WC Rheumatology SC Rheumatology GA 663DY UT WOS:000282864400010 PM 20634244 ER PT J AU Maserejian, NN Shifren, JL Parish, SJ Braunstein, GD Gerstenberger, EP Rosen, RC AF Maserejian, Nancy N. Shifren, Jan L. Parish, Sharon J. Braunstein, Glenn D. Gerstenberger, Eric P. Rosen, Raymond C. TI The Presentation of Hypoactive Sexual Desire Disorder in Premenopausal Women SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Hypoactive Sexual Desire Disorder; Female; Sexual Dysfunction; Premenopausal ID NATIONALLY REPRESENTATIVE SAMPLE; MENOPAUSAL STATUS; UNITED-STATES; INDEX FSFI; PREVALENCE; VALIDATION; DISTRESS; INSTRUMENT; HSDD AB Introduction. Little is known about the clinical presentation of hypoactive sexual desire disorder (HSDD) in premenopausal women or their perceptions of sexual problems. Aim. Describe characteristics of premenopausal women with clinically diagnosed acquired, generalized HSDD, and investigate factors perceived to contribute to desire problems. Methods. Cross-sectional analysis of baseline data from premenopausal women with clinically diagnosed and confirmed HSDD enrolled during the first year of the HSDD Registry for Women (N = 400). Main Outcome Measures. Relationship, demographic, and clinical characteristics were assessed by clinician's medical history review and self-administered questionnaire. Sexual desire function was measured by the validated Female Sexual Function Index (FSFI). Results. Over 85% of women cited multiple factors that contributed to ongoing decreased desire (mean 2.9 +/- 2.3 factors, range 0-12). Most commonly cited contributing factors were "stress or fatigue" (60.0%), "dissatisfaction with my physical appearance" (40.8%), and other sexual difficulties (e.g., inability to reach orgasm) (33.5%). Exploratory analyses of the FSFI score confirmed that self-image (P = 0.002) and other sexual problems (P < 0.001) were significantly associated with decreased desire. Almost all (96%) participants were currently in a partner relationship. Antidepressant medication was currently used by 18.0% of women, hormonal contraceptives by 28.5%, and hormonal medications (for noncontraceptive reasons) by 7.3%. Physical functioning was consistent with general population norms (SF-36 mean +/- standard deviation, 53.3 +/- 7.6 vs. norm of 50 +/- 10), while overall mental functioning was slightly lower (SF-36, 44.7 +/- 10.6). Conclusions. Within this sample of premenopausal women with clinically diagnosed HSDD, decreased sexual desire was associated with multiple factors, including poor self-image and stress or fatigue. Clinicians presented with premenopausal women expressing sexual desire problems should assess patients' perceptions of their condition to develop a comprehensive, patient-oriented management plan. Therapy may need to address issues with low self-esteem and mood and offer practical coping mechanisms for stress and fatigue. Maserejian NN, Shifren JL, Parish SJ, Braunstein GD, Gerstenberger EP, and Rosen RC. The presentation of hypoactive sexual desire disorder in premenopausal women. J Sex Med 2010;7:3439-3448. C1 [Maserejian, Nancy N.; Gerstenberger, Eric P.; Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA USA. [Shifren, Jan L.] Massachusetts Gen Hosp, Vincent OB GYN Serv, Boston, MA 02114 USA. [Parish, Sharon J.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Braunstein, Glenn D.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. RP Rosen, RC (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM rrosen@neriscience.com FU Boehringer Ingelheim Pharmaceuticals, Inc.; Proctor and Gamble Pharmaceuticals FX This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc.; Dr Maserejian, Dr Braunstein and Mr. Gerstenberger have no conflicts of interest to declare. Dr Parish has served as a consultant to Boehringer Ingelheim Pharmaceuticals, Inc. Dr Shifren has served as a consultant to Boehringer Ingelheim Pharmaceuticals, Inc. and as a consultant to New England Research Institutes, Inc. She has research support from Proctor and Gamble Pharmaceuticals. Dr Rosen is a board member for Boehringer Ingelheim Pharmaceuticals, Inc. He has served as a consultant/advisor to Eli Lilly, Bayer-Schering Pharma, Sanofi-Aventi, Johnson & Johnson, and Endo Pharmaceuticals. He serves as an investigator for Eli Lilly, Bayer-Schering Pharma, Boehringer Ingelheim Pharmaceuticals, Inc. and Endo Pharmaceuticals. NR 33 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD OCT PY 2010 VL 7 IS 10 BP 3439 EP 3448 DI 10.1111/j.1743-6109.2010.01934.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 658UC UT WOS:000282513900020 PM 20646184 ER PT J AU Dhikav, V Karmarkar, G Verma, M Gupta, R Gupta, S Mittal, D Anand, K AF Dhikav, Vikas Karmarkar, Girish Verma, Myank Gupta, Ruchi Gupta, Supriya Mittal, Deeksha Anand, Kuljeet TI Yoga in Male Sexual Functioning: A Noncompararive Pilot Study SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Yoga; Male Sexual Functions; Male Sexual Quotient; Male Sexual Dysfunctions; Male Sexuality; Physical Exercises ID PREMATURE EJACULATION; ERECTILE DYSFUNCTION; ALTERNATIVE THERAPIES; CLINICAL-APPLICATIONS; COMPLEMENTARY; SATISFACTION; DEPRESSION; PREVALENCE; ANXIETY; STRESS AB Introduction. Yoga is practiced both in developing and developed countries. Many patients and yoga protagonists claim that it is useful in improving sexual functions and treating sexual disorders. Aim. We wanted to study the effect of yoga on male sexual functioning. Methods. We studied 65 males (age range = 24-60 years, average age = 40 +/- 8.26 years) who were enrolled in a yoga camp and administered a known questionnaire, i.e., Male Sexual Quotient (MSQ) before and after 12 weeks session of yoga. Main Outcome Measures. MSQ scores before and after yoga sessions. Results. It was found that after the completion of yoga sessions, the sexual functions scores were significantly improved (P < 0.0001). The improvement occurred in scores of all the domains of sexual functions as studied by MSQ (desire, intercourse satisfaction, performance, confidence, partner synchronization, erection, ejaculatory control, orgasm). Conclusions. Yoga appears to be an effective method of improving all domains of sexual functions in men as studied by MSQ. Dhikav V, Karmarkar G, Verma M, Gupta R, Gupta S, Mittal D, and Anand K. Yoga in male sexual functioning: A noncompararive pilot study. J Sex Med 2010;7:3460-3466. C1 [Dhikav, Vikas] Guru Gobind Singh Indraprastha Univ, Dept Neurol, Dr RML Hosp, Postgrad Inst Med Educ & Res, Delhi 110085, Rohini, India. [Karmarkar, Girish] Sexol Clin, Dept Physiol, Thana, Maharashtra, India. [Verma, Myank] Postgrad Inst Med Sci, Rohtak, Haryana, India. [Gupta, Ruchi] Mt Sinai Sch Med, New York, NY USA. [Gupta, Supriya] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mittal, Deeksha] Manipal Acad Higher Educ, Gangktok, Sikkim, India. [Anand, Kuljeet] Guru Gobind Singh Indraprastha Univ, Dr Ram Manohar Lohia Hosp Neurol, Postgrad Inst Med Educ & Res, Delhi 110085, Rohini, India. RP Dhikav, V (reprint author), Guru Gobind Singh Indraprastha Univ, Dept Neurol, Dr RML Hosp, Postgrad Inst Med Educ & Res, E-3,Flat 280,Sector 18, Delhi 110085, Rohini, India. EM vikasdhikav@hotmail.com NR 32 TC 3 Z9 3 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD OCT PY 2010 VL 7 IS 10 BP 3460 EP 3466 DI 10.1111/j.1743-6109.2010.01930.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 658UC UT WOS:000282513900022 PM 20646186 ER PT J AU Guitton, TG van der Werf, HJ Ring, D AF Guitton, Thierry G. van der Werf, Huub J. Ring, David TI Quantitative three-dimensional computed tomography measurement of radial head fractures SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Computed tomography: fractures; morphology; quantitative; radial head; surface; three-dimensional; volume ID INTERNAL-FIXATION; OPEN REDUCTION; SURFACE; VOLUME AB Background: We developed a method to quantitatively analyze fracture fragment morphology on quantitative 3-dimensional computed tomography (3DCT) images in terms of size, shape. and articular surface area Materials and methods: We analyzed 46 adult patients with a computed tomography scan of a fractured radial head with quantitative 3DCT We defined an unstable fracture as complete loss of cortical contact of at least 1 fragment Of the patients. 3 had a Mason type I fracture (all stable), 26 had a type 2 fractures (7 stable [27%] and 19 unstable [73%]), and 17 had a type 3 fracture (all unstable) The volume and articular surface area of each articular fracture fragment were measured A small fragment was defined as having a volume of less than 100 mm(3) or an articular surface of less than 100 mm(2). Results: Partial head fractures (Mason type 2) (26 fractures) are usually multi-fragmented (19 of 26 [73%]) and often have small fragments by volume (32 fragments) and surface area (46 fragments) criteria. particularly when the fracture is displaced and unstable Only 4 of the 17 patients (25%) with whole-head fractures (Mason type 3) had greater than 3 fragments, but 9 of 17 fractures (69%) with 3 or fewer fragments had small fragments Conclusions: According to this initial application of quantitative 3DCT analysis, partial-head fractures are often complex and difficult to repair (small fragments). and most whole-head fractures have 3 or fewer fragments, but many of those fragments are small and may be difficult to repair Level of evidence: Level IV, Diagnostic Study. Nonconsecutive Patients, No Reference Standard (C) 2010 Journal of Shoulder and Elbow Surgery Board of Trustees C1 [Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Ste 2100,55 Fruit St, Boston, MA 02114 USA. OI Guitton, Thierry/0000-0002-2599-1985 FU Stryker; Joint Active Systems; Biomet FX David Ring. MD, PhD. has received research-specific grants from Stryker, Joint Active Systems, and Biomet; has received honoraria/travel expenses from AO North America and AO International; is a consultant for Wright Medical. Skeletal Dynamics, Acumed, and Tormer, has received royalties from Hand Innovations, Wright Medical, and Skeletal Dynamics; and has received stock options from Illuminos and Mimedex. NR 14 TC 18 Z9 18 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD OCT PY 2010 VL 19 IS 7 BP 973 EP 977 DI 10.1016/j.jse.2010.03.013 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 669JY UT WOS:000283344900004 PM 20566295 ER PT J AU Rosmarin, DH Pirutinsky, S Siev, J AF Rosmarin, David H. Pirutinsky, Steven Siev, Jedidiah TI RECOGNITION OF SCRUPULOSITY AND NON-RELIGIOUS OCD BY ORTHODOX AND NON-ORTHODOX JEWS SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; RESPONSE PREVENTION; CONTROLLED TRIAL; EXPOSURE; ATTITUDES; SYMPTOMS; THERAPY AB Perceptions of psychological symptoms may be influenced by religiousness, particularly when symptom presentation is shaped by a socio-religious context. We therefore examined whether among Jews, Orthodox affiliation was related to recognition of scrupulosity as obsessive compulsive disorder (OCD). Seventy Orthodox and 23 non-Orthodox Jews were randomized to view one of two matched vignettes describing religious or non-religious OCD. Whereas Orthodox Jews were equally likely to recognize both vignettes as OCD, non-Orthodox Jews were less likely to recognize the religious than the non-religious presentation as OCD. Furthermore, Orthodox Jews were equally likely to recommend professional treatment for both scrupulosity and non-religious OCD, whereas non-Orthodox Jews were less likely to recommend professional treatment for scrupulosity compared to non-religious OCD. These findings may suggest that familiarity with Orthodox practices increases sensitivity to distinctions between scrupulosity and normative religion, thereby increasing recognition of the need for professional treatment. C1 [Rosmarin, David H.] McLean Hosp, Belmont, MA 02478 USA. [Rosmarin, David H.; Siev, Jedidiah] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Pirutinsky, Steven] Columbia Univ, Teachers Coll, New York, NY 10027 USA. [Siev, Jedidiah] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosmarin, DH (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM drosmarin@mclean.harvard.edu NR 28 TC 3 Z9 3 U1 1 U2 2 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0736-7236 J9 J SOC CLIN PSYCHOL JI J. Soc. Clin. Psychol. PD OCT PY 2010 VL 29 IS 8 BP 930 EP 944 PG 15 WC Psychology, Clinical; Psychology, Social SC Psychology GA 658EK UT WOS:000282472900004 ER PT J AU Stepp, CE Hillman, RE Heaton, JT AF Stepp, Cara E. Hillman, Robert E. Heaton, James T. TI The Impact of Vocal Hyperfunction on Relative Fundamental Frequency During Voicing Offset and Onset SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE vocal hyperfunction; muscle tension dysphonia; vocal nodules; vocal polyps; acoustic measures; fundamental frequency ID MUSCLE TENSION DYSPHONIA; PARKINSON-DISEASE; BEHAVIOR AB Purpose: This study tested the hypothesis that individuals with vocal hyperfunction would show decreases in relative fundamental frequency (RFF) surrounding a voiceless consonant. Method: This retrospective study of 2 clinical databases used speech samples from 15 control participants and women with hyperfunction-related voice disorders: 82 prior to treatment (muscle tension dysphonia, n = 22; vocal fold nodules, n = 30; vocal fold polyps, N = 30) and 18 before and after surgical removal of vocal fold nodules or polyps. Acoustic samples were analyzed with respect to the RFF at the offset and onset of voicing surrounding a voiceless consonant. Results: Individuals with vocal hyperfunction in a large clinical sample showed significant lowering of offset and onset RFF compared with controls. Voicing offset and onset RFFs were not significantly changed by the removal of vocal fold lesions in the surgical group. Conclusions: Altered offset and onset RFF in patients with hyperfunction-related voice disorders can be interpreted as a by-product of heightened levels of laryngeal muscle tension. Measurement of RFF during voice offset and onset has potential for use as a simple, noninvasive measure of vocal hyperfunction. C1 [Stepp, Cara E.; Hillman, Robert E.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Stepp, Cara E.; Hillman, Robert E.; Heaton, James T.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Hillman, Robert E.; Heaton, James T.] Harvard Univ, Sch Med, Boston, MA USA. RP Stepp, CE (reprint author), Univ Washington, Dept Comp Sci, Box 352350, Seattle, WA 98195 USA. EM cstepp@alum.mit.edu NR 25 TC 16 Z9 16 U1 0 U2 6 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD OCT 1 PY 2010 VL 53 IS 5 BP 1220 EP 1226 DI 10.1044/1092-4388(2010/09-0234) PG 7 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 655UX UT WOS:000282279100012 PM 20643798 ER PT J AU Mehta, DD Deliyski, DD Hillman, RE AF Mehta, Daryush D. Deliyski, Dimitar D. Hillman, Robert E. TI Commentary on Why Laryngeal Stroboscopy Really Works: Clarifying Misconceptions Surrounding Talbot's Law and the Persistence of Vision SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Letter DE stroboscopy; endoscopy; vocal fold; voice; assessment ID MOTION AB Purpose: The purpose of this article is to clear up misconceptions that have propagated in the clinical voice literature that inappropriately cite Talbot's law (1834) and the theory of persistence of vision as the scientific principles that underlie laryngeal stroboscopy. Method: After initial research into Talbot's (1834) original studies, it became clear that his experiments were not designed to explain why stroboscopy works. Subsequently, a comprehensive literature search was conducted for the purpose of investigating the general principles of stroboscopic imaging from primary sources. Results: Talbot made no reference to stroboscopy in designing his experiments, and the notion of persistence of vision is not applicable to stroboscopic motion. Instead, two visual phenomena play critical roles: (a) the flicker-free perception of light and (b) the perception of apparent motion. In addition, the integration of stroboscopy with video-based technology in today's voice clinic requires additional complexities to include synchronization with camera frame rates. Conclusions: References to Talbot's law and the persistence of vision are not relevant to the generation of stroboscopic images. The critical visual phenomena are the flicker-free perception of light intensity and the perception of apparent motion from sampled images. A complete understanding of how laryngeal stroboscopy works will aid in better interpreting clinical findings during voice assessment. C1 [Mehta, Daryush D.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Mehta, Daryush D.; Hillman, Robert E.] MIT, Cambridge, MA 02139 USA. [Deliyski, Dimitar D.] Univ S Carolina, Columbia, SC 29208 USA. [Hillman, Robert E.] Harvard Univ, Sch Med, Boston, MA USA. RP Mehta, DD (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM daryush.mehta@alum.mit.edu FU NIDCD NIH HHS [T32 DC000038, T32 DC00038, R01 DC007640] NR 27 TC 5 Z9 5 U1 0 U2 4 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD OCT 1 PY 2010 VL 53 IS 5 BP 1263 EP 1267 DI 10.1044/1092-4388(2010/09-0241) PG 5 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 655UX UT WOS:000282279100017 PM 20881095 ER PT J AU Schoenfeld, AJ Wood, KB Fisher, CF Fehlings, M Oner, FC Bouchard, K Arnold, P Vaccaro, AR Sekhorn, L Harris, MB Bono, CM AF Schoenfeld, Andrew J. Wood, Kirkham B. Fisher, Charles F. Fehlings, Michael Oner, F. C. Bouchard, Kim Arnold, Paul Vaccaro, Alexander R. Sekhorn, Lali Harris, Mitchel B. Bono, Christopher M. TI Posttraumatic Kyphosis: Current State of Diagnosis and Treatment: Results of a Multinational Survey of Spine Trauma Surgeons SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES LA English DT Article DE posttraumatic kyphosis; thoracolumbar spine; trauma; survey ID WEDGE OSTEOTOMY; SURGICAL-TREATMENT; THORACOLUMBAR; INSTRUMENTATION; MANAGEMENT; DEFORMITY AB Study Design: Multinational survey of spine trauma surgeons. Objectives: To survey a multinational group of spine trauma surgeons and develop an updated consensus definition of posttraumatic kyphosis (PTK), and the most current methods for diagnosis and treatment. Summary of Background Data: PTK remains a potential problematic sequela of thoracolumbar trauma. Although most surgeons have devised their own approaches for detecting and treating this condition, broad agreement in terms of the diagnosis and management of PTK has not been achieved. There is a lack of consensus-based guidelines, as the current literature largely consists of small case series or anecdotal expert opinions. Methods: A survey questionnaire was circulated among 35 multinational spine trauma surgeons. The questionnaire consisted of 29 questions divided into 8 domains: definition, diagnosis, risk factors, symptoms, radiographic evaluation, surgical indications, treatment, and expected outcome. Answers from respondents were compiled and evaluated to generate a consensus. Results: All 35 surgeons completed the survey. Consensus was achieved that PTK represents "a painful kyphotic angulation that can occur anywhere in the posttraumatic spine.'' Agreement was also reached that asymptomatic PTK can exist, although no true consensus could be reached on the extent of angular deformity that results in PTK. Untreated or maltreated flexion-distraction injuries, or severe burst fractures of the thoracolumbar spine, were felt to be the 2 injuries most likely to produce PTK. Computed tomography, magnetic resonance, and dynamic radiographs were all recommended for evaluation. If surgery is necessary, posteriorly based osteotomies, especially pedicle subtraction osteotomies, have become the principal means of correction. Conclusions: An updated understanding of PTK and its treatment has been achieved. Posterior osteotomies seem to be the most popular means of surgical correction. In the future, multicenter prospective studies are necessary to ascertain, with greater precision, the most appropriate treatment for this condition. C1 [Schoenfeld, Andrew J.; Wood, Kirkham B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02215 USA. [Bouchard, Kim] Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. [Harris, Mitchel B.; Bono, Christopher M.] Brigham & Womens Hosp, Dept Orthopaed, Boston, MA 02115 USA. [Fisher, Charles F.] Vancouver Gen Hosp, VGH, Vancouver, BC, Canada. [Fehlings, Michael] Toronto Western Hosp, Div Neurosurg, Toronto, ON M5T 2S8, Canada. [Arnold, Paul] Univ Kansas, Dept Neurosurg, Kansas City, MO USA. [Vaccaro, Alexander R.] Rothman Inst, Philadelphia, PA USA. [Sekhorn, Lali] Spine Nevada, Reno, NV USA. [Oner, F. C.] Univ Utrecht Hosp, Dept Orthopaed, Utrecht, Netherlands. RP Schoenfeld, AJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, 75 Peterborough St,Apt 505, Boston, MA 02215 USA. EM ajschoen@neoucom.edu RI Oner, FC/L-7769-2013; OI Oner, FC/0000-0003-0858-8243; Schoenfeld, Andrew/0000-0002-3691-1215 NR 21 TC 9 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1536-0652 J9 J SPINAL DISORD TECH JI J. Spinal Disord. Tech. PD OCT PY 2010 VL 23 IS 7 BP E1 EP E8 DI 10.1097/BSD.0b013e3181c03517 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 657VZ UT WOS:000282448200009 PM 20124914 ER PT J AU Mankin, HJ Hornicek, FJ Springfield, DS AF Mankin, Henry J. Hornicek, Francis J. Springfield, Dempsey S. TI Extra-Abdominal Desmoid Tumors: A Report of 234 Cases SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE extra-abdominal; desmoid; tumors ID RADIATION-THERAPY; AGGRESSIVE FIBROMATOSIS; GARDNERS-SYNDROME; COMBINED SURGERY; LOCAL-CONTROL; RADIOTHERAPY; TRISOMY-8; BONE AB Background/Objectives: To report on the clinical presentation and outcome for 234 patients with extra-abdominal desmoids tumors Methods: Since 1977, the authors have treated 234 patients with extra-abdominal desmoid tumors The patients had an average age of 36 7 and 61% were female The tumors arose adjacent to muscles or bones and the largest number were m the foot, shoulder thigh and calf All of the patients were treated by primary surgery Thirty-seven had additional radiation and eight had chemotherapy Results: Local recurrence occurred in 39 patients and 23% of the patients required additional surgery Of great concern were 24 patients who developed multiple sites metachronously. which required further surgery and in many cases caused disability None of the patients died of disease hut 5 required amputations Conclusions: The authors concluded that despite the benign nature of the disease, these patients are difficult to treat and the results are sometimes considerably less than optimal J Surg Oncol 2010.102 380-384 (C) 2009 Wiley-Liss. Inc C1 [Mankin, Henry J.; Hornicek, Francis J.; Springfield, Dempsey S.] Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Serv, 1122A Jackson Bldg, Boston, MA 02114 USA. NR 47 TC 19 Z9 21 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD OCT 1 PY 2010 VL 102 IS 5 BP 380 EP 384 DI 10.1002/jso.21433 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 669HX UT WOS:000283339600006 PM 19877160 ER PT J AU Kaafarani, HMA Kaufman, D Reda, D Itani, KMF AF Kaafarani, Haytham M. A. Kaufman, Derrick Reda, Domenic Itani, Kamal M. F. TI Predictors of Surgical Site Infection in Laparoscopic and Open Ventral Incisional Herniorrhaphy SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE surgical wound infection; ventral hernia; randomized controlled trial ID HERNIA REPAIR; LOGISTIC-REGRESSION AB Background. Surgical site infection (SSI) after ventral incisional hernia repair (VIH) can result in serious consequences. We sought to identify patient, procedure, and/or hernia characteristics that are associated with SSI in VIH. Methods. Between 2004 and 2006, patients were randomized in four Veteran Affairs (VA) hospitals to undergo laparoscopic or open VIH. Patients who developed SSI within eight weeks postoperatively were compared to those who did not. A bivariate analysis for each factor and a multiple logistic regression analysis were performed to determine factors associated with SSI. The variables studied included patient characteristics and co-morbidities (e.g., age, gender, race, ethnicity, body mass index, ASA classification, diabetes, steroid use), hernia characteristics (e.g., size, duration, number of previous incisions), procedure characteristics (e.g., open versus laparoscopic, blood loss, use of postoperative drains, operating room temperature) and surgeons' experience (resident training level, number of open VIH previously performed by the attending surgeon). Antibiotic prophylaxis, anticoagulation protocols, preparation of the skin, draping of the wound, body temperature control, and closure of the surgical site were all standardized and monitored throughout the study period. Results. Out of 145 patients who underwent VIII, 21 developed a SSI (14.5%). Patients who underwent open VIH had significantly more SSIs than those who underwent laparoscopic VIH (22.1% versus 3.4%; P = 0.002). Among patients who underwent open VIII, those who developed SSI had a recorded intraoperative blood loss greater than 25 mL (68.4% versus 40.3%; P = 0.030), were more likely to have a drain placed (79.0% versus 49.3%; P = 0.021) and were more likey to be operated on by surgeons with less than 75 open VIH case experience (52.6% versus 28.4%; P = 0.048). Patient and hernia characteristics were similar between the two groups. In a multiple logistic regression analysis, the open surgical technique was associated with SSI (OR 8.03, 95% CI 2.03, 31.72; P = 0.003) while controlling for the VA medical center where the procedure was performed (P = 0.041). Conclusion. Open surgical technique and the medical center rather than patient co-morbidities or hernia characteristics are associated with the formation of postoperative SSI in VIH. Published by Elsevier Inc. C1 [Itani, Kamal M. F.] VA Boston Healthcare Syst, Dept Surg, W Roxbury, MA 02132 USA. [Kaafarani, Haytham M. A.] Tufts Med Ctr, Dept Surg, Boston, MA USA. [Kaufman, Derrick; Reda, Domenic] Vet Affairs Cooperat Studies Program Coordinating, Hines, IL USA. [Itani, Kamal M. F.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Itani, KMF (reprint author), VA Boston Healthcare Syst, Dept Surg, W Roxbury, MA 02132 USA. EM kitani@med.va.gov NR 17 TC 29 Z9 30 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2010 VL 163 IS 2 BP 229 EP 234 DI 10.1016/j.jss.2010.03.019 PG 6 WC Surgery SC Surgery GA 653SB UT WOS:000282115900012 PM 20605590 ER PT J AU Bichara, DA Zhao, X Hwang, NS Bodugoz-Senturk, H Yaremchuk, MJ Randolph, MA Muratoglu, OK AF Bichara, David A. Zhao, Xing Hwang, Nathaniel S. Bodugoz-Senturk, Hatice Yaremchuk, Michael J. Randolph, Mark A. Muratoglu, Orhun K. TI Porous Poly(vinyl alcohol)-Alginate Gel Hybrid Construct for Neocartilage Formation Using Human Nasoseptal Cells SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE poly(vinyl alcohol); hydrogel; cartilage; nasoseptal chondrocytes; tissue engineering ID EAR-SHAPED CARTILAGE; HYDROGELS; RECONSTRUCTION; CHONDROCYTES; SCAFFOLDS AB Background. Limited options exist for the restoration of craniofacial cartilage. Autologous tissue or porous polyethylene is currently used for nasal and auricular reconstruction. Both options are associated with drawbacks, including donor site morbidity and implant extrusion. Poly(vinyl alcohol) (PVA) is a non-degradable flexible biocompatible polymer than can be engineered to mimic the properties of cartilage. The goal of this study was to engineer a biosynthetic hybrid construct using a combination of PVA-alginate hydrogels and human nasal septum chondrocytes. Materials and Methods. Chondrocytes isolated from human nasal septum cartilage were expanded and mixed with 2% sodium alginate hydrogel. The chondrocyte-alginate mix was injected into a non-degradable porous PVA hydrogel, creating biosynthetic constructs. A group of these constructs were implanted into the subcutaneous environment of nude mice, while the other group was cultured in a spinner flask bioreactor system for 10 d and then implanted. After 6 wk in vivo, the histologic, biochemical, and biomechanical properties were examined. Results. Histological analysis demonstrated sulfated glycosaminoglycans and deposition of collagen type II in constructs from both groups. Constructs cultured in the bioreactor system prior in vivo implantation demonstrated higher levels of DNA, glycosaminoglycans, and hydroxyproline. An increase of 22% in the compressive strength of the engineered constructs exposed to the bioreactor was also observed. Conclusion. A novel porous PVA-alginate gel hybrid was used to successfully engineer human cartilage in vivo. A 10-d period of bioreactor culturing increased levels of DNA, glycosaminoglycans, hydroxyproline, and the compressive modulus of the constructs. (C) 2010 Elsevier Inc. All rights reserved. C1 [Bichara, David A.; Zhao, Xing; Yaremchuk, Michael J.; Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab,Div Plast Surg, Boston, MA 02114 USA. [Hwang, Nathaniel S.] MIT, Koch Inst Innovat Canc Res, Cambridge, MA 02139 USA. [Bodugoz-Senturk, Hatice; Muratoglu, Orhun K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab,Div Plast Surg, Room WAC 435,15 Parkman St, Boston, MA 02114 USA. EM marandolph@partners.org FU American Society of Maxillofacial; Massachusetts General Hospital FX This study was supported in part by the American Society of Maxillofacial Surgeons Research Grant and the Department of Orthopaedic Surgery Academic Enrichment Fund of the Massachusetts General Hospital. NR 24 TC 30 Z9 31 U1 1 U2 24 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 OCT PY 2010 VL 163 IS 2 BP 331 EP 336 DI 10.1016/j.jss.2010.03.070 PG 6 WC Surgery SC Surgery GA 653SB UT WOS:000282115900029 PM 20538292 ER PT J AU Pinsky, E AF Pinsky, Elizabeth TI When a Child Dies: How Pediatric Physicians and Nurses Cope. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Pinsky, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pinsky, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM epinsky@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2010 VL 49 IS 10 BP 1084 EP 1085 DI 10.1016/j.jaac.2010.07.006 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 655ZQ UT WOS:000282295600013 ER PT J AU Kolman, O Hoang, MP Piris, A Mihm, MC Duncan, LM AF Kolman, Olga Hoang, Mai P. Piris, Adriano Mihm, Martin C., Jr. Duncan, Lyn M. TI Histologic processing and reporting of cutaneous pigmented lesions: Recommendations based on a survey of 94 dermatopathologists SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE dysplastic nevus; histology; margins; melanoma; processing ID MELANOCYTIC LESIONS; SURGICAL MARGINS; DERMATOLOGISTS; MELANOMA; SKIN AB Background: Standard operating procedures for laboratory processing and reporting of margins of cutaneous pigmented lesions do not exist. We conducted a survey of 94 dermatopathologists to evaluate these practices. Objectives: We sought to: (1) identify dominant practices among dermatopathologists; (2) determine the impact of the procedure, intent to excise, and histologic diagnosis on the process of margin evaluation; and (3) propose guidelines based on these findings. Methods: The survey consisted of 44 questions focused on the impact of procedure (punch, shave, or ellipse), intent (excision or biopsy), and histologic diagnosis (common nevus, congenital nevus, atypical nevus. melanoma) on processing and margin reporting. Results: For ellipses, or specimens indicated as excisions, the majority practice (76%-98%) was to ink the specimens. Although more than 90% of observers report the margins on all melanomas and atypical nevi, fewer than 50% of respondents report margins on all nonatypical nevi. Limitations: The study consists of a survey sample of dermatopathologists and does not represent the practices of those who did not respond to the survey. Conclusions: Based on the results of this survey We have arrived at the following recommendations: (1) ink all specimens that are ellipses or designated as excisions; (2) tips should be evaluated separately if the specimen is an ellipse; (3) obtain levels in cases with tumor in the tip but not at ink if the specimen is an ellipse or excision and the diagnosis is atypical nevus or melanoma; and (4) report margins on all atypical nevi and melanomas. (J Am Acad Dermatol 2010;63:661-7.) C1 [Kolman, Olga; Hoang, Mai P.; Piris, Adriano; Mihm, Martin C., Jr.; Duncan, Lyn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, Boston, MA 02114 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM lduncan@partners.org NR 15 TC 4 Z9 4 U1 0 U2 0 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 OCT PY 2010 VL 63 IS 4 BP 661 EP 667 DI 10.1016/j.jaad.2009.09.047 PG 7 WC Dermatology SC Dermatology GA 653DZ UT WOS:000282069400012 PM 20846568 ER PT J AU Emmons, RR Garber, CE Cirnigliaro, CM Moyer, JM Kirshblum, SC Galea, MD Spungen, AM Bauman, WA AF Emmons, Racine R. Garber, Carol Ewing Cirnigliaro, Christopher M. Moyer, Jeremy M. Kirshblum, Steven C. Galea, Marinella D. Spungen, Ann M. Bauman, William A. TI The Influence of Visceral Fat on the Postprandial Lipemic Response in Men with Paraplegia SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE spinal cord injury; postprandial lipemia; triglyceride clearance; abdominal adiposity ID DENSITY-LIPOPROTEIN CHOLESTEROL; SPINAL-CORD-INJURY; METABOLIC SYNDROME; ULTRASONOGRAPHY; ATHEROGENESIS; OBESITY; PLASMA AB Background: Postprandial lipemia (PPL) is associated with vascular dysfunction and may be an etiologic factor in the progression of atherogenic cardiovascular disease. Objective: In 10 men with paraplegia and 10 able-bodied men, the magnitude of the PPL responses and the relationship of abdominal adiposity and the PPL responses were determined. Methods: Anthropometrics, dual energy x-ray absorptiometry, and abdominal ultrasonography were performed to determine visceral fat and total body fat. A fasting lipid profile was performed. A high-fat milkshake (1.3 g fat/kg body mass) was administered with serum collected at baseline and at 2, 4, and 6 hours after the test meal for subsequent measurement of triglyceride. The triglyceride response was determined by the area under the triglyceride curve. Results: No significant differences were noted between the groups in fasting lipid values or in measures of visceral fat. Total body fat tended to be higher in men with paraplegia than in able-bodied men (34.9 +/- 10.0 vs. 27.3 +/- 6.7%, p = 0.07). No significant difference between the groups was observed in triglyceride response. In men with paraplegia, visceral fat was strongly associated with the triglyceride (r = 0.8, p = 0.005), fasting low-density lipoprotein (r = 0.66, p = 0.04), and triglyceride responses (r = 0.80, p = 0.005); a significant relationship was not found between fasting high-density lipoprotein and any measure of adiposity. In men with paraplegia, triglyceride response was positively related to all measures of abdominal adiposity. Conclusion: Visceral abdominal fat was related to delayed triglyceride clearance after a fat load, which may contribute to coronary heart disease (CHD) risk and progression of vascular disease in men with paraplegia. C1 [Emmons, Racine R.; Cirnigliaro, Christopher M.; Moyer, Jeremy M.; Galea, Marinella D.; Spungen, Ann M.; Bauman, William A.] US Dept Vet Affairs, Rehabil Res & Dev Ctr Excellence Med Consequences, James J Peters VA Med Ctr, Bronx, NY USA. [Emmons, Racine R.; Garber, Carol Ewing] Columbia Univ Teachers Coll, New York, NY 10027 USA. [Spungen, Ann M.; Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Spungen, Ann M.; Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven C.] Univ Med Sch New Jersey, Dept Phys Med & Rehabil, Newark, NJ USA. RP Emmons, RR (reprint author), James J Peters VA Med Ctr, VA Ctr Excellence Med Consequences SCI, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM racine.emmons@va.gov OI Garber, Carol/0000-0002-1268-576X FU Department of Veterans Affairs Rehabilitation Research and Development Center of Excellence for the Medical Consequences of Spinal Cord Injury [B4162C] FX This work was supported by the Department of Veterans Affairs Rehabilitation Research and Development Center of Excellence for the Medical Consequences of Spinal Cord Injury (#B4162C). NR 25 TC 8 Z9 8 U1 0 U2 2 PU AMER COLLEGE NUTRITION PI CLEARWATER PA 300 SOUTH DUNCAN AVENUE, STE 225, CLEARWATER, FL 33755 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD OCT PY 2010 VL 29 IS 5 BP 476 EP 481 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 716YX UT WOS:000287010500005 PM 21504974 ER PT J AU Patti, JA AF Patti, John A. TI The Saga of Our Times-Government Inaction on Self-Referral: Are We Getting Closer to a Solution? SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM jpatti@partners.org NR 1 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD OCT PY 2010 VL 7 IS 10 BP 743 EP 744 DI 10.1016/j.jacr.2010.08.029 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23ST UT WOS:000208363200001 PM 20889099 ER PT J AU Hempton, TJ Dominici, JT AF Hempton, Timothy J. Dominici, John T. TI MORE ABOUT CROWN LENGTHENING Response SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter C1 [Hempton, Timothy J.] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. [Dominici, John T.] Michael E DeBakey Vet Adm Med Ctr, Prosthodont Residency Programs, Houston, TX USA. RP Hempton, TJ (reprint author), Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 2010 VL 141 IS 10 BP 1184 EP 1185 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 662XJ UT WOS:000282847300009 ER PT J AU Duru, OK Sarkisian, CA Leng, M Mangione, CM AF Duru, O. Kenrik Sarkisian, Catherine A. Leng, Mei Mangione, Carol M. TI Sisters in Motion: A Randomized Controlled Trial of a Faith-Based Physical Activity Intervention SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE physical activity; African Americans; randomized controlled trial ID AMERICAN-HEART-ASSOCIATION; OLDER-ADULTS; CARDIOVASCULAR-DISEASE; HEALTH-PROMOTION; PUBLIC-HEALTH; WOMEN; EXERCISE; OUTCOMES; RECOMMENDATIONS; QUESTIONNAIRE AB OBJECTIVES To evaluate a faith-based intervention (Sisters in Motion) intended to increase walking in older, sedentary African-American women. DESIGN Randomized controlled trial using within-church randomization. SETTING Three Los Angeles churches. PARTICIPANTS Sixty-two African-American women aged 60 and older who reported being active less than 30 minutes three times per week and walked less than 35,000 steps per week as measured using a baseline pedometer reading. INTERVENTION Intervention participants received a multicomponent curriculum including scripture readings, prayer, goal-setting, a community resource guide, and walking competitions. Intervention and control participants both participated in physical activity sessions. MEASUREMENTS The primary outcome was change in weekly steps walked as measured using the pedometer. Secondary outcomes included change in systolic blood pressure (SBP). Outcomes were assessed at baseline and 6 months after the intervention. RESULTS Eighty-five percent of participants attended at least six of eight sessions. Intervention participants averaged 12,727 steps per week at baseline, compared with 13,089 steps in controls. Mean baseline SBP was 156 mmHg for intervention participants and 147 mmHg for controls (P=.10). At 6 months, intervention participants had increased their weekly steps by 9,883 on average, compared with an increase of 2,426 for controls (P=.02); SBP decreased on average by 12.5 mmHg in intervention participants and only 1.5 mmHg in controls (P=.007). CONCLUSION The Sisters in Motion intervention led to an increase in walking and a decrease in SBP at 6 months. This is the first randomized controlled trial of a faith-based physical activity program to increase physical activity in older African-American women and represents an attractive approach to stimulate lifestyle change in this population. C1 [Duru, O. Kenrik; Leng, Mei; Mangione, Carol M.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Sarkisian, Catherine A.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Div Geriatr, Los Angeles, CA 90095 USA. RP Duru, OK (reprint author), Univ Calif Los Angeles, Div Gen Internal Med Hlth Serv Res, 911 Broxton Plaza, Los Angeles, CA 90095 USA. EM kduru@mednet.ucla.edu FU Institute for Health and Aging, University of California at San Francisco; National Institutes on Aging [R01-AG024460]; University of California at Los Angeles (UCLA); National Center on Minority Health and Health Disparities [2P20MD000182]; UCLA Center for Health Improvement of Minority Elderly/Resource Centers for Minority Aging Research; National Institutes of Health (NIH); NIA [2P30AG021684, P30-AG028748] FX The authors gratefully acknowledge the support and guidance of Dr. Anita Stewart and Ms. Dawn Gillis at the Institute for Health and Aging, University of California at San Francisco, who graciously shared their experiences in developing a physical activity intervention for translation in a community setting. The authors would also like to thank the program participants in the Seniors in Motion for Health program in San Francisco, sponsored by the Network for Elders.; This study was funded by a diversity supplement awarded to Dr. Duru by the National Institutes on Aging, to Grant R01-AG024460. Dr. Mangione was supported by University of California at Los Angeles (UCLA)/Drew Project Export, National Center on Minority Health and Health Disparities, 2P20MD000182. Dr. Mangione also received support from the UCLA Center for Health Improvement of Minority Elderly/Resource Centers for Minority Aging Research, National Institutes of Health (NIH), NIA under Grant 2P30AG021684. Drs. Duru, Sarkisian, and Mangione received support from the UCLA Older Americans Independence Center, NIH, NIA Grant P30-AG028748. The content of this article does not necessarily represent the official views of the NIA or the NIH. NR 33 TC 43 Z9 44 U1 2 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2010 VL 58 IS 10 BP 1863 EP 1869 DI 10.1111/j.1532-5415.2010.03082.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 660ZP UT WOS:000282690900005 PM 20929464 ER PT J AU Palmer, RF Royall, DR AF Palmer, Raymond F. Royall, Donald R. TI Missing Data? Plan on It! SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE missing data methods; statistical measurement; longitudinal aging research ID FREEDOM HOUSE; MODELS; GROWTH; ASSOCIATION; DECLINE; TIME AB Longitudinal study designs are indispensable for investigating age-related functional change. There now are well-established methods for addressing missing data in longitudinal studies. Modern missing data methods not only minimize most problems associated with missing data (e.g., loss of power and biased parameter estimates), but also have valuable new applications such as research designs that use modern missing data methods to plan missing data purposefully. This article describes two state-of-the-art statistical methodologies for addressing missing data in longitudinal research: growth curve analysis and statistical measurement models. How the purposeful planning of missing data in research designs can reduce subject burden, improve data quality and statistical power, and manage costs is then described. J Am Geriatr Soc 58:S343-S348, 2010. C1 [Palmer, Raymond F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78284 USA. [Palmer, Raymond F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biostat & Epidemiol, San Antonio, TX 78284 USA. [Royall, Donald R.] S Texas Vet Hlth Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, Dept Family & Community Med, San Antonio, TX USA. [Royall, Donald R.] S Texas Vet Hlth Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, Dept Psychiat, San Antonio, TX USA. [Royall, Donald R.] S Texas Vet Hlth Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, Dept Med, San Antonio, TX USA. [Royall, Donald R.] S Texas Vet Hlth Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, Dept Pharmacol, San Antonio, TX USA. RP Palmer, RF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM palmerr@uthscsa.edu FU Robert Wood Johnson Foundation FX This paper is based on a January 2009 conference on Longitudinal Studies in Aging, Boca Raton, Florida, supported by a grant from the Robert Wood Johnson Foundation. NR 44 TC 23 Z9 24 U1 0 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2010 VL 58 SU 2 BP S343 EP S348 DI 10.1111/j.1532-5415.2010.03053.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 656YJ UT WOS:000282376700014 PM 21029065 ER PT J AU Hanlon, JT Perera, S Sevick, MA Rodriguez, KL Jaffe, EJ AF Hanlon, Joseph T. Perera, Subashan Sevick, Mary Ann Rodriguez, Keri L. Jaffe, Emily J. TI Pain and Its Treatment in Older Nursing Home Hospice/Palliative Care Residents SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Aged; nursing home; hospice; palliative care; analgesics ID NONMALIGNANT PAIN; HOSPICE CARE; MANAGEMENT; ADULTS AB Objectives: The objectives of this study were to determine the prevalence of pain, describe its treatment, and determine factors associated with any pain in older residents assigned to a hospice specialty unit bed or receiving services from a hospice/palliative care/end-of-life special program in US nursing homes. Design: Cross-sectional study of data from the 2004 National Nursing Home Survey. Setting: The setting was 1174 US nursing homes. Participants: Participants were 303 sampled patients, 65 years or older, representing 33,413 individuals receiving hospice/palliative care. Measurements: Facility staff was asked if, in the past 7 days, the resident had reported or shown evidence of pain. Medication use data were derived from medication administration records. Information about demographics and health status was derived from Minimum Data Set records. Results: Cancer was the primary diagnosis in only 11.4% of residents. Overall 36.6% had any pain in the previous week. Among those with any pain, 86.4% received some analgesic; specifically, 65.5% received opioids, whereas 31.7% received acetaminophen. Those with any pain compared with those without pain had shorter lengths of stay in hospice/palliative care (mean 123 days versus 161 days, P < .01), were more likely to be incontinent of bowel (76.2%, versus 60.3%, P < 0.01) and bladder (84.5% versus 71.8%, P = 0.01). Conclusions: Pain symptoms were present in more than one third of older nursing home hospice/palliative care residents despite the use of opioids in two thirds of those who had reported or shown evidence of any pain. Additional future studies are needed to improve the management of pain in older residents receiving hospice/palliative care in US nursing homes. (J Am Med Dir Assoc 2010; 11: 579-583) C1 [Hanlon, Joseph T.; Perera, Subashan] Univ Pittsburgh, Dept Med, Div Geriatr Med, Sch Med, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Pharm & Therapeut, Sch Pharm, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Sevick, Mary Ann; Rodriguez, Keri L.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Hanlon, Joseph T.; Sevick, Mary Ann; Rodriguez, Keri L.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Perera, Subashan] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Sevick, Mary Ann; Rodriguez, Keri L.; Jaffe, Emily J.] Univ Pittsburgh, Div Gen Internal Med, Dept Med, Sch Med, Pittsburgh, PA 15213 USA. [Sevick, Mary Ann] Univ Pittsburgh, Dept Behav & Community Hlth Sci, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Med, Div Geriatr Med, Sch Med, Kaufman Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA. EM jth14@pitt.edu RI Perera, Subashan/D-7603-2014 FU National Institute of Aging [R01AG027017, P30AG024827]; VA Health Services Research grant [IIR-06-062] FX This study was supported by National Institute of Aging grants (R01AG027017; P30AG024827), and a VA Health Services Research grant (IIR-06-062). NR 21 TC 16 Z9 18 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD OCT PY 2010 VL 11 IS 8 BP 579 EP 583 DI 10.1016/j.jamda.2009.11.014 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 669FO UT WOS:000283333500007 PM 20889094 ER PT J AU Lable, I Kelley, JM Ackerman, J Levy, R Waldron, S Ablon, JS AF Lable, Ira Kelley, John M. Ackerman, Julie Levy, Raymond Waldron, Sherwood, Jr. Ablon, J. Stuart TI THE ROLE OF THE COUCH IN PSYCHOANALYSIS: PROPOSED RESEARCH DESIGNS AND SOME PRELIMINARY DATA SO JOURNAL OF THE AMERICAN PSYCHOANALYTIC ASSOCIATION LA English DT Article ID COLLABORATIVE RESEARCH-PROGRAM; FACIAL EXPRESSIONS; FREE ASSOCIATION; ANALYTIC PROCESS; PSYCHOTHERAPY; PROTOTYPES; THERAPY; VIEW AB Ever since Freud, the couch has been viewed as an important-some would argue essential-component of psychoanalysis. Although many theoretical papers and case reports have addressed the use of the couch in psychoanalysis, no empirical study has investigated its effect on psychoanalytic process or outcome. After a review of the literature, a number of research designs are proposed that might be used in such an investigation. Finally, preliminary empirical data are presented from archived audiotapes of two psychoanalyses: one in which the patient switched from lying down to sitting up, and one in which the opposite occurred. The aim is to stimulate research-oriented psychoanalysts to undertake empirical investigations of the theoretical concepts underlying use of the couch and, more generally, to present a specific example of research as a paradigm for a broader research agenda for empirical investigation of the key theoretical ideas underlying psychoanalysis. C1 [Lable, Ira] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kelley, John M.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Kelley, John M.] Endicott Coll, Beverly, MA USA. [Kelley, John M.; Levy, Raymond; Ablon, J. Stuart] Massachusetts Gen Hosp, Psychotherapy Res Program, Boston, MA 02114 USA. [Ackerman, Julie] UCL, Anna Freud Ctr, London WC1E 6BT, England. [Waldron, Sherwood, Jr.] Mt Sinai Hosp, New York, NY USA. [Waldron, Sherwood, Jr.] New York Psychoanalyt Inst, New York, NY USA. RP Lable, I (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St WACC812, Boston, MA 02114 USA. EM ira_lable@hms.harvard.edu NR 55 TC 2 Z9 2 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-0651 J9 J AM PSYCHOANAL ASS JI J. Am. Psychoanal. Assoc. PD OCT PY 2010 VL 58 IS 5 BP 861 EP 887 DI 10.1177/0003065110390210 PG 27 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 717WY UT WOS:000287079400002 PM 21300629 ER PT J AU Demenais, F Mohamdi, H Chaudru, V Goldstein, AM Bishop, JAN Bishop, DT Kanetsky, PA Hayward, NK Gillanders, E Elder, DE Avril, MF Azizi, E van Belle, P Bergman, W Bianchi-Scarra, G Bressac-de Paillerets, B Calista, D Carrera, C Hansson, J Harland, M Hogg, D Hoiom, V Holland, EA Ingvar, C Landi, MT Lang, JM Mackie, RM Mann, GJ Ming, ME Njauw, CJ Olsson, H Palmer, J Pastorino, L Puig, S Randerson-Moor, J Stark, M Tsao, H Tucker, MA van der Velden, P Yang, XR Gruis, N AF Demenais, F. Mohamdi, H. Chaudru, V. Goldstein, A. M. Bishop, J. A. Newton Bishop, D. T. Kanetsky, P. A. Hayward, N. K. Gillanders, E. Elder, D. E. Avril, M. F. Azizi, E. van Belle, P. Bergman, W. Bianchi-Scarra, G. Bressac-de Paillerets, B. Calista, D. Carrera, C. Hansson, J. Harland, M. Hogg, D. Hoiom, V. Holland, E. A. Ingvar, C. Landi, M. T. Lang, J. M. Mackie, R. M. Mann, G. J. Ming, M. E. Njauw, C. J. Olsson, H. Palmer, J. Pastorino, L. Puig, S. Randerson-Moor, J. Stark, M. Tsao, H. Tucker, M. A. van der Velden, P. Yang, X. R. Gruis, N. CA Melanoma Genetics Consortium TI Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN MELANOCORTIN-1 RECEPTOR; MULTIPLE PRIMARY MELANOMAS; STIMULATING HORMONE; CUTANEOUS MELANOMA; PRONE FAMILIES; GENE VARIANTS; RED HAIR; SKIN PIGMENTATION; HUMAN MELANOCYTES; WIDE ASSOCIATION AB Background Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited. Methods We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, >= 2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided. Results Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 x 10(-6) < P < .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; P(trend) = 1.86 x 10(-8)). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 <= P <= .04), hair color (.006 <= P <= .06), and number of nevi (6.9 x 10(-6) <= P <= .02). Conclusion Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings. C1 [Demenais, F.; Mohamdi, H.; Chaudru, V.; Bressac-de Paillerets, B.] Fdn Jean Dausset CEPH, INSERM, U946, F-75010 Paris, France. [Demenais, F.; Mohamdi, H.] Univ Paris Diderot, Inst Univ Hematol, Paris, France. [Chaudru, V.] Univ Evry Val Essonne, Evry, France. [Goldstein, A. M.; Landi, M. T.; Tucker, M. A.; Yang, X. R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Bishop, J. A. Newton; Bishop, D. T.; Harland, M.; Randerson-Moor, J.] St James Univ Hosp, Epidemiol & Biostat Sect, Leeds Inst Mol Med, Canc Res UK Clin Ctr, Leeds LS9 7TF, W Yorkshire, England. [Kanetsky, P. A.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Kanetsky, P. A.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Hayward, N. K.; Palmer, J.; Stark, M.] Queensland Inst Med Res, Oncogen Lab, Brisbane, Qld 4006, Australia. [Gillanders, E.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. [Elder, D. E.; van Belle, P.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Avril, M. F.] Univ Paris 05, Serv Dermatol, Hop Cochin, AP HP, Paris, France. [Azizi, E.] Tel Aviv Univ, Dept Dermatol, Sheba Med Ctr, Sackler Fac Med, Tel Aviv, Israel. [Bergman, W.; van der Velden, P.; Gruis, N.] Leiden Univ Med Ctr, Dept Dermatol, Leiden, Netherlands. [Bianchi-Scarra, G.; Pastorino, L.] Univ Genoa, Dept Oncol Biol & Genet, I-16126 Genoa, Italy. [Bianchi-Scarra, G.] San Martino Hosp, Lab Genet Rare Hereditary Canc, Genoa, Italy. [Bressac-de Paillerets, B.] Inst Canc Gustave Roussy, Dept Mol Genet, Villejuif, France. [Calista, D.] Maurizio Bufalini Hosp, Dermatol Unit, Cesena, Italy. [Gillanders, E.] Hosp Clin Barcelona, Dept Dermatol, Melanoma Unit, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain. [Carrera, C.; Puig, S.] Ctr Invest Biomed Red CIBER Enfermedades Rares, Barcelona, Spain. [Hansson, J.; Hoiom, V.] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Hogg, D.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Hogg, D.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Holland, E. A.; Mann, G. J.] Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Westmead, NSW 2145, Australia. [Holland, E. A.; Mann, G. J.] Melanoma Inst Australia, Westmead, NSW, Australia. [Ingvar, C.] Univ Lund Hosp, Dept Surg, S-22185 Lund, Sweden. [Lang, J. M.; Mackie, R. M.] Univ Glasgow, Dept Med Genet, Glasgow, Lanark, Scotland. [Lang, J. M.; Mackie, R. M.] Univ Glasgow, Dept Publ Hlth, Glasgow, Lanark, Scotland. [Ming, M. E.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Ming, M. E.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Njauw, C. J.; Tsao, H.] Massachusetts Gen Hosp, Wellman Ctr Photomed, MGH Melanoma & Pigmented Les Ctr, Boston, MA 02114 USA. [Njauw, C. J.; Tsao, H.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Olsson, H.] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. RP Demenais, F (reprint author), Fdn Jean Dausset CEPH, INSERM, U946, 27 Rue Juliette Dodu, F-75010 Paris, France. EM florence.demenais@inserm.fr RI Stark, Mitchell/E-3542-2010; Mann, Graham/G-4758-2014; Bianchi Scarra, Giovanna/G-8933-2014; Demenais, Florence/G-3298-2013; Tucker, Margaret/B-4297-2015; hayward, nicholas/C-1367-2015; Duffy, David/B-7392-2013; Marti, Rosa/A-2256-2010; Bruno, William/N-7477-2013; Hoiom, Veronica/F-4153-2012; bertazzi, pietro alberto/D-5039-2017 OI Bishop, Tim/0000-0002-8752-8785; Newton Bishop, Julia/0000-0001-9147-6802; Puig, Susana/0000-0003-1337-9745; CARRERA, CRISTINA/0000-0003-1608-8820; Badenas, Celia/0000-0002-0621-0477; Gruis, Nelleke/0000-0002-5210-9150; Stark, Mitchell/0000-0002-4510-2161; Mann, Graham/0000-0003-1301-405X; Bianchi Scarra, Giovanna/0000-0002-6127-1192; Demenais, Florence/0000-0001-8361-0936; hayward, nicholas/0000-0003-4760-1033; Duffy, David/0000-0001-7227-632X; Marti, Rosa/0000-0001-6866-6114; Bruno, William/0000-0002-0337-0168; bertazzi, pietro alberto/0000-0003-3475-2449 FU European Community [LSH-CT-2006-018702]; National Institutes of Health [RO1 CA83115, RO1 CA88363, RO1 CA5558-01A2]; Ligue Nationale contre le Cancer [PRE05/FD, PRE09/FD]; Programme Hospitalier de Recherche Clinique [PHRC 2007-AOM-07-195]; French Institut National du Cancer [13]; National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Institutes of Health; Cancer Research UK Programme [C588/A4994]; Australian National Health and Medical Research Council; Cancer Councils of New South Wales, Victoria and Queensland; Cancer Institute NSW; Italian Ministry of Health [DGRST. 4/4235-P1.9. A. B]; Swedish Cancer Society; Radiumhemmet Research Funds; Swedish Research Council; Swedish Cancer foundation; Regional funds in Skane; University Hospital in Lund; Fondo de Investigaciones Sanitarias, Spain [03/0019, 05/0302, 06/0265] FX European Community FP6 Network of Excellence Award (LSH-CT-2006-018702 to J.A.N.B. and N.G.); the National Institutes of Health (RO1 CA83115 to D. E. E., RO1 CA88363 to N.K.H., RO1 CA5558-01A2 to M. T. L.); the Ligue Nationale contre le Cancer (PRE05/FD and PRE09/FD to F. D.); the Programme Hospitalier de Recherche Clinique (PHRC 2007-AOM-07-195 to F. D. and M. F. A.); the French Institut National du Cancer (Melanoma Network RS Number 13 to BB-dP); the Intramural Research Program of the National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Institutes of Health to A. M. G, M. T. L., M. A. T and X.R.Y.; the Cancer Research UK Programme Award (C588/A4994 to J.A.N.B. and D. T. B.); the Australian National Health and Medical Research Council (to N.K.H. and to G.J.M.); the Cancer Councils of New South Wales, Victoria and Queensland to N.K.H. and G.J.M.; the Cancer Institute NSW to N.K.H. and G.J.M.; the Italian Ministry of Health (DGRST. 4/4235-P1.9. A. B to G. B-S.); the Swedish Cancer Society to J.H.: the Radiumhemmet Research Funds to J.H.; the Swedish Research Council to J.H; the Swedish Cancer foundation to C. I and H.O.; the Regional funds in Skane to C. I and H.O.; the funds at the University Hospital in Lund to C. I and H.O.; and Fondo de Investigaciones Sanitarias, Spain (03/0019, 05/0302, 06/0265 to S.P.). NR 59 TC 38 Z9 40 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT PY 2010 VL 102 IS 20 BP 1568 EP 1583 DI 10.1093/jnci/djq363 PG 16 WC Oncology SC Oncology GA 673PS UT WOS:000283676000010 PM 20876876 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Board Recertification SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2010 VL 8 IS 10 BP 1111 EP 1111 PG 1 WC Oncology SC Oncology GA 670EG UT WOS:000283403400001 PM 20971837 ER PT J AU Carlson, RW Allred, DC Anderson, BO Burstein, HJ Carter, WB Edge, SB Erban, JK Farrar, WB Forero, A Giordano, SH Goldstein, LJ Gradishar, WJ Hayes, DF Hudis, CA Ljung, BM Marcom, PK Mayer, IA McCormick, B Pierce, LJ Reed, EC Smith, ML Som, G Topham, NS Ward, JH Winer, EP Wolff, AC AF Carlson, Robert W. Allred, D. Craig Anderson, Benjamin O. Burstein, Harold J. Carter, W. Bradford Edge, Stephen B. Erban, John K. Farrar, William B. Forero, Andres Giordano, Sharon Hermes Goldstein, Lori J. Gradishar, William J. Hayes, Daniel F. Hudis, Clifford A. Ljung, Britt-Marie Marcom, P. Kelly Mayer, Ingrid A. McCormick, Beryl Pierce, Lori J. Reed, Elizabeth C. Smith, Mary Lou Som, George Topham, Neal S. Ward, John H. Winer, Eric P. Wolff, Antonio C. TI Breast Cancer: Noninvasive and Special Situations SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; noninvasive breast cancer; breast-conserving therapy; mastectomy; endocrine therapy; tamoxifen; radiation therapy; lobular carcinoma in situ; ductal carcinoma in situ ID CARCINOMA-IN-SITU; SURGICAL ADJUVANT BREAST; LYMPH-NODE BIOPSY; RANDOMIZED CONTROLLED-TRIAL; AMERICAN-JOINT-COMMITTEE; NUYS PROGNOSTIC INDEX; BOWEL PROJECT P-1; PAGETS-DISEASE; LOCAL RECURRENCE; PHYLLODES TUMORS C1 [Carlson, Robert W.] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Allred, D. Craig] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Allred, D. Craig] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Anderson, Benjamin O.] Univ Washington, Seattle, WA 98195 USA. [Burstein, Harold J.; Winer, Eric P.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Buffalo, NY USA. [Erban, John K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Farrar, William B.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Forero, Andres] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL USA. [Giordano, Sharon Hermes] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pierce, Lori J.; Topham, Neal S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Gradishar, William J.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Hayes, Daniel F.; Pierce, Lori J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Hudis, Clifford A.; McCormick, Beryl] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Reed, Elizabeth C.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE 68198 USA. [Ward, John H.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Wolff, Antonio C.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. RP Carlson, RW (reprint author), Stanford Comprehens Canc Ctr, Stanford, CA USA. OI Wolff, Antonio/0000-0003-3734-1063 NR 115 TC 1 Z9 1 U1 0 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2010 VL 8 IS 10 BP 1182 EP 1207 PG 26 WC Oncology SC Oncology GA 670EG UT WOS:000283403400006 PM 20971842 ER PT J AU Trimarchi, S Eagle, KA Nienaber, CA Rampoldi, V Jonker, FHW De Vincentiis, C Frigiola, A Menicanti, L Tsai, T Froehlich, J Evangelista, A Montgomery, D Bossone, E Cooper, JV Li, J Deeb, MG Meinhardt, G Sundt, TM Isselbacher, EM AF Trimarchi, Santi Eagle, Kim A. Nienaber, Christoph A. Rampoldi, Vincenzo Jonker, Frederik H. W. De Vincentiis, Carlo Frigiola, Alessandro Menicanti, Lorenzo Tsai, Thomas Froehlich, Jim Evangelista, Arturo Montgomery, Daniel Bossone, Eduardo Cooper, Jeanna V. Li, Jin Deeb, Michael G. Meinhardt, Gabriel Sundt, Thoralf M. Isselbacher, Eric M. CA Intl Registry Acute Aortic Dissect TI Role of age in acute type A aortic dissection outcome: Report from the International Registry of Acute Aortic Dissection (IRAD) SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID SURGICAL-TREATMENT; CARDIAC-SURGERY; MORTALITY; OCTOGENARIANS; EXPERIENCE; OLDER; NONAGENARIANS; INTERVENTION; REPAIR; VALVE AB Objective: The increasing life expectancy of the population will likely be accompanied by a rise in the incidence of acute type A aortic dissection. However, because of an increased risk of cardiac surgery in an elderly population, it is important to define when, if at all, the risks of aortic repair outweigh the risk of death from unoperated type A aortic dissection. Methods: We analyzed 936 patients with type A aortic dissection enrolled in the International Registry of Acute Aortic Dissection from 1996 to 2004. Patients with type A aortic dissection were categorized according to patient age by decade and by surgical versus medical management, and outcomes of both management types were investigated in the different age groups. Results: The rate of surgical aortic repair decreased progressively with age, whereas surgical mortality significantly increased with age. Age 70 years or more was an independent predictor for mortality ( 38.2% vs 26.0%; P < .0001, odds ratio 1.73). The in-hospital mortality rate was significantly lower after surgical management compared with medical management until the age of 80 years. For patients aged 80 to 90 years, the in-hospital mortality appeared to be lower after surgical management (37.9% vs 55.2%; P = .188); however, this failed to reach clinical significance owing to the limited patient number in this age group. Conclusions: Although the surgical mortality significantly increased with increased age, surgical management was still associated with significantly lower in-hospital mortality rates compared with medical management until the age of 80 years. Surgery may decrease the in-hospital mortality rate for octogenarians with type A aortic dissection and might be considered in all patients with type A aortic dissection regardless of age. (J Thorac Cardiovasc Surg 2010;140:784-9) C1 [Trimarchi, Santi] Univ Milan, Policlin San Donato IRCCS, Cardiovasc Ctr E Malan, I-20097 San Donato Milanese, Italy. [Eagle, Kim A.; Tsai, Thomas; Froehlich, Jim; Montgomery, Daniel; Cooper, Jeanna V.; Li, Jin; Deeb, Michael G.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nienaber, Christoph A.] Univ Rostock, Rostock, Germany. [Jonker, Frederik H. W.] Yale Univ, New Haven, CT USA. [Evangelista, Arturo] Hosp Gen Univ Valle Hebron, Barcelona, Spain. [Bossone, Eduardo] CNR, Lecce, Italy. [Meinhardt, Gabriel] Robert Bosch Krankenhaus, Stuttgart, Germany. [Sundt, Thoralf M.] Mayo Clin, Rochester, MN USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Trimarchi, S (reprint author), Univ Milan, Policlin San Donato IRCCS, Cardiovasc Ctr E Malan, Piazza Malan 2, I-20097 San Donato Milanese, Italy. EM santi.trimarchi@unimi.it RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 FU Varbedian Fund for Aortic Research; Mardigian Foundation; Gore Inc.; University of Michigan Health System FX IRAD is supported by grants from the University of Michigan Health System, the Varbedian Fund for Aortic Research, the Mardigian Foundation, and Gore Inc. NR 25 TC 75 Z9 80 U1 1 U2 7 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 OCT PY 2010 VL 140 IS 4 BP 784 EP 789 DI 10.1016/j.jtcvs.2009.11.014 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 651YO UT WOS:000281965300010 PM 20176372 ER PT J AU Heist, RS Fain, J Chinnasami, B Khan, W Molina, JR Sequist, LV Temel, JS Fidias, P Brainerd, V Leopold, L Lynch, TJ AF Heist, Rebecca Suk Fain, Jerry Chinnasami, Bernard Khan, Waseem Molina, Julian R. Sequist, Lecia V. Temel, Jennifer S. Fidias, Panos Brainerd, Valari Leopold, Lance Lynch, Thomas J. TI Phase I/II Study of AT-101 with Topotecan in Relapsed and Refractory Small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Small cell lung cancer; BCL-2 inhibitor; Chemotherapy ID BCL-2 ANTISENSE OLIGONUCLEOTIDE; ETOPOSIDE; CYCLOPHOSPHAMIDE; VINCRISTINE; CARBOPLATIN; INHIBITION; CISPLATIN; TRIAL; G3139 AB Introduction: AT-101 is an oral, pan Bcl-2 family protein inhibitor that has demonstrated activity in small cell lung cancer (SCLC) models. A phase I/II study was conducted combining AT-101 with topotecan in relapsed and refractory SCLC. Methods: An open-labeled multicenter phase I/II study was conducted of oral AT-101 with intravenous topotecan in patients with SCLC who had progressed on prior platinum-containing chemotherapy. The phase II portion was a two-stage design, and two cohorts of patients, sensitive relapsed and refractory, were analyzed. Primary endpoint in the two-stage phase II portion was response rate; secondary endpoints were duration of response and time to progression. Results: Thirty-six patients were enrolled. The most common toxicities were hematologic, as would be expected with topotecan and AT-101. The recommended phase II dose was 40 mg AT-101 days 1 to 5 with topotecan 1.25 mg/m(2) days 1 to 5 on a 21-day cycle. In the sensitive-relapsed cohort (n = 18), there were 0 complete response (CR), three partial response (PR), 10 stable disease (SD), and four progressive disease (PD). In the refractory cohort (n = 12), there were 0 CR/PR, five SD, and five PD. The study did not meet its prespecified endpoints to continue enrollment in the second stage of the phase II study. Median time to progression in the sensitive-relapsed cohort was 17.4 weeks and 11.7 weeks in the refractory cohort. Conclusions: AT-101 can be safely combined with topotecan at a reduced dose of 1.25 mg/m2. The response rates observed did not meet the criteria for additional enrollment; however, many patients had a best response of SD and the median time to progression in both cohorts was favorable. Additional trials of AT-101 in SCLC are ongoing. C1 [Heist, Rebecca Suk; Sequist, Lecia V.; Temel, Jennifer S.; Fidias, Panos] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fain, Jerry] Texas Oncol, Austin, TX USA. [Chinnasami, Bernard] Emerywood Hematol Oncol, High Point, NC USA. [Khan, Waseem] Canc Care N Florida PA, Lake City, FL USA. [Molina, Julian R.] Mayo Clin, Rochester, MN USA. [Brainerd, Valari; Leopold, Lance] Ascenta Therapeut Inc, Malvern, PA USA. [Lynch, Thomas J.] Yale Canc Ctr, New Haven, CT USA. RP Heist, RS (reprint author), Massachusetts Gen Hosp, Yawkey 7B,32 Fruit St, Boston, MA 02114 USA. EM rheist@partners.org NR 29 TC 29 Z9 33 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD OCT PY 2010 VL 5 IS 10 BP 1637 EP 1643 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 653UI UT WOS:000282122000022 PM 20808253 ER PT J AU Dubey, S Janne, PA Krug, L Pang, H Wang, XF Heinze, R Watt, C Crawford, J Kratzke, R Vokes, E Kindler, HL AF Dubey, Sarita Jaenne, Pasi A. Krug, Lee Pang, Herbert Wang, Xiaofei Heinze, Robin Watt, Colleen Crawford, Jeff Kratzke, Robert Vokes, Everett Kindler, Hedy Lee TI A Phase II Study of Sorafenib in Malignant Mesothelioma Results of Cancer and Leukemia Group B 30307 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Mesothelioma; Sorafenib; Vascular endothelial growth factor; Tyrosine kinase inhibitor; Clinical trial ID ADVANCED HEPATOCELLULAR-CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; PLEURAL-MESOTHELIOMA; ANGIOGENESIS; CANCER; CELLS; VINORELBINE; PROGRESSION; CISPLATIN; PATHWAY AB Hypothesis: Malignant mesotheliomas (MMs) express vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and cKIT. Sorafenib is a potent inhibitor of the ras/raf/MEK pathway and also targets VEGFR and cKIT. We evaluated the activity of sorafenib in patients with unresectable mesothelioma. Methods: MM patients who had received 0 to 1 prior chemotherapy regimens were treated with sorafenib 400 mg orally twice daily continuously. The primary end point was objective response. ERK1/2 phosphorylation in archival tissues was correlated with response and survival. Results: A total of 51 patients were enrolled, 50 were evaluable and included in the analysis. Three patients had a partial response (6% [95% confidence interval = 1.3-16.6%]), and 27 (54% [95% confidence interval = 39.3-68.2%]) had stable disease. Median progression-free survival and median overall survival (OS) were 3.6 and 9.7 months, respectively. Median survival was superior in epithelioid histology versus other types (10.7 versus 3.7 months, p = 0.0179). The difference in median OS between pretreated and chemonaive patients was not statistically significant (13.2 versus 5 months, p = 0.3117). Low/negative baseline tumor phospho-ERK1/2 levels were associated with improved OS (13.9 versus 5.2 months, p = 0.0066). Conclusion: Sorafenib has limited activity in advanced MM patients, similar to that seen with other VEGFR tyrosine kinase inhibitors. Additional studies of sorafenib in MM are not warranted. C1 [Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dubey, Sarita] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Krug, Lee] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Pang, Herbert; Wang, Xiaofei; Heinze, Robin] Duke Univ, Med Ctr, Canc & Leukemia Grp Stat Ctr B, Durham, NC USA. [Watt, Colleen] Canc & Leukemia Grp B Cent Off, Chicago, IL USA. [Kratzke, Robert] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. [Vokes, Everett; Kindler, Hedy Lee] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, 44 Binney St,D820B, Boston, MA 02115 USA. EM pjanne@partners.org FU National Cancer Institute [CA31946, CA33601]; NCI CTEP Translational Research Initiative [25XS051] FX Supported, in part, by grants CA31946 (to Richard L. Schilsky, MD, Chairman, Cancer and Leukemia Group B) and CA33601 (to Stephen George, PhD, CALGB Statistical Center) from the National Cancer Institute. Support for the correlative science studies was provided through the NCI CTEP Translational Research Initiative administered by SAIC-Frederick (25XS051). NR 29 TC 49 Z9 49 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD OCT PY 2010 VL 5 IS 10 BP 1655 EP 1661 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 653UI UT WOS:000282122000025 PM 20736856 ER PT J AU Wright, CD AF Wright, Cameron D. TI Extended Resections for Thymic Malignancies SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article; Proceedings Paper CT 1st International Conference Thymic Malignancies CY AUG 20-21, 2009 CL Bethesda, MD DE Thymic malignancy; Superior vena cava resection; Pleuropneumonectomy ID SUPERIOR VENA-CAVA; STAGE IVA THYMOMA; MEDIASTINAL MALIGNANCIES; MULTIMODALITY THERAPY; TUMORS; MANAGEMENT; RECURRENCE; REPLACEMENT; PREDICTORS; INVASION AB Almost all series reporting on the results of resection in thymic tumors indicate that the performance of a complete resection is probably the most important prognostic factor. This issue is not a factor in Masaoka stage I and II tumors that are almost always easily completely resected and have an excellent prognosis. Masaoka stage III tumors that invade the pericardium, lungs, or great vessels have relatively higher incomplete resection rates, significantly higher recurrence rates, and thus a worse prognosis. There are several small reports on the efficacy of resection of the great veins when involved by a thymic malignancy with low morbidity and meaningful long-term survival. Superior vena cava reconstruction is commonly performed by a polytetrafluroethylene, venous, or pericardial graft. These cases can usually be identified preoperatively and, thus, considered for induction therapy. Because these types of cases are almost always of marginal respectability in terms of obtaining a true en bloc resection, there is an increasing enthusiasm for offering induction therapy in an effort to enhance resectability. Preliminary results suggest increased R0 resection rates and improved survival with induction therapy for locally advanced tumors. The optimal induction treatment is unknown. The ultimate extended surgery for advanced thymic tumors is an extrapleural pneumonectomy performed for extensive pleural disease (Masaoka stage IVA). These rarely performed operations are done for IVA disease found at initial presentation and for recurrent disease as a salvage procedure. Again these advanced patients are probably best managed by induction chemotherapy followed by resection. C1 [Wright, Cameron D.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Wright, Cameron D.] NCI, Dept Med Oncol, Bethesda, MD 20892 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,32 Fruit St, Boston, MA 02114 USA. EM cdwright@partners.org NR 22 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD OCT PY 2010 VL 5 SU 4 BP S344 EP S347 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 658PV UT WOS:000282502800016 PM 20859130 ER PT J AU Mannucci, PM Asselta, R Duga, S Guella, I Spreafico, M Lotta, L Merlini, PA Peyvandi, F Kathiresan, S Ardissino, D AF Mannucci, P. M. Asselta, R. Duga, S. Guella, I. Spreafico, M. Lotta, L. Merlini, P. A. Peyvandi, F. Kathiresan, S. Ardissino, D. TI The association of factor V Leiden with myocardial infarction is replicated in 1880 patients with premature disease SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE acute myocardial infarction; association study; factor V Leiden; plasminogen activator inhibitor (PAI-1); prothrombin ID GENE POLYMORPHISMS; RISK-FACTORS; METAANALYSIS AB Aims: Gain-of-function variants of genes encoding coagulation factor V (F5 G1691A) and prothrombin (F2 G20210A) cause hypercoagulability and are established risk factors for venous thrombosis. A meta-analysis of 66 155 cases and 91 307 controls found that either polymorphism is associated with a moderately increased risk of coronary artery disease (CAD). Because genetic factors play a particularly important role when acute myocardial infarction (AMI) occurs in the young, we chose to replicate these results by investigating, in the frame of a case-control study, a large cohort of Italian patients who had AMI before the age of 45 years. Methods and Results: In 1880 patients with AMI (1680 men and 210 women) and an equal number of controls, the minor A allele of F5 G1691A (2.6% frequency in cases and 1.7% in controls) was associated with an increased risk of AMI, the association remaining significant after adjustment for traditional risk factors (OR, 1.66; 95% CI, 1.15-2.38; P = 0.006). The positive association with AMI for the minor A allele of F2 G20210A (2.5% frequency in cases and 1.9% in controls) did not reach statistical significance (OR, 1.32; 95% CI, 0.96-1.80; P = 0.159). Conclusions: In a large cohort of young AMI patients the gain-of-function variant F5 G1691A was associated with an increased risk of AMI. The findings on the variant F2 G20210A confirmed the previously reported results, but the association was statistically not significant. These data suggest that a number of young patients with AMI carry gene variants associated with a procoagulant phenotype. C1 [Mannucci, P. M.; Spreafico, M.; Lotta, L.; Peyvandi, F.] Univ Milan, IRCCS Fdn Ca Granda Osped Maggiore, Sci Direct, Ctr Emofilia & Trombosi A Bianchi Bonomi, I-20122 Milan, Italy. [Asselta, R.; Duga, S.; Guella, I.] Univ Milan, Dipartimento Biol & Genet Sci Med, I-20122 Milan, Italy. [Merlini, P. A.] Osped Niguarda Ca Granda, Dipartimento Cardiol, Milan, Italy. [Kathiresan, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Kathiresan, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Kathiresan, S.] Broad Inst, Cambridge, MA USA. [Ardissino, D.] Azienda Osped Univ Parma, Dipartimento Cardiopolmonare, Unita Operativa Cardiol, Parma, Italy. RP Mannucci, PM (reprint author), Univ Milan, IRCCS Fdn Ca Granda Osped Maggiore, Sci Direct, Ctr Emofilia & Trombosi A Bianchi Bonomi, Via Pace 9, I-20122 Milan, Italy. EM piermannuccio.mannucci@unimi.it RI Mannucci, Pier/C-3102-2014; Duga, Stefano/F-8173-2014; OI Asselta, Rosanna/0000-0001-5351-0619; Peyvandi, Flora/0000-0001-7423-9864; Duga, Stefano/0000-0003-3457-1410 FU Italian Health Ministry; FIRST (Finanziamenti per l'Innovazione, la Ricerca e lo Sviluppo Tecnologico) FX This study was supported by 'Progetto Finalizzato' from the Italian Health Ministry to P. M. Mannucci and 'Progetto a Concorso' to R. Asselta. The financial support of FIRST (Finanziamenti per l'Innovazione, la Ricerca e lo Sviluppo Tecnologico, for years 2005-2007) is also gratefully acknowledged. NR 22 TC 20 Z9 22 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD OCT PY 2010 VL 8 IS 10 BP 2116 EP 2121 DI 10.1111/j.1538-7836.2010.03982.x PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 660KV UT WOS:000282642500004 PM 20626623 ER PT J AU Yoon, JH Yeh, RW Nam, KH Hoffman, WD Agnihotri, AK Jang, IK AF Yoon, Joo Heung Yeh, Robert W. Nam, Kyung Hun Hoffman, William D. Agnihotri, Arvind K. Jang, Ik-Kyung TI Safety and efficacy of the argatroban therapy during the early post-cardiac surgery period SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Argatroban; Bleeding; Cardiac surgery; Direct thrombin inhibitor; Heparin-induced thrombocytopenia ID HEPARIN-INDUCED THROMBOCYTOPENIA; CARDIOPULMONARY BYPASS AB Heparin-induced thrombocytopenia (HIT) is associated with a high incidence of vein graft occlusion after cardiac surgery. When HIT is suspected during the post-operative period, current guideline recommends a direct thrombin inhibitor such as argatroban to be started immediately. The aim of this retrospective study was to evaluate the safety and efficacy of argatroban in the early period after cardiac surgery. All patients who received argatroban within 72 h after cardiac surgery from September 2005 to June 2009 from a single center were included. Patient demographics, pre-operative relevant history, intra-operative events and post-operative data were collected and analyzed. The primary endpoints were bleeding, thrombotic complication during or after argatroban administration, and in-hospital mortality. The study population comprised 31 patients administered argatroban within 72 h after cardiac surgery. Argatroban was started a mean of 1.7 days after surgery (median dose, 0.66 mu g/kg/min; median duration, 5.9 days). Twenty patients (64.5%) experienced bleeding; episode driven entirely by the need for blood transfusion. No new thromboembolic complication occurred during or after argatroban infusion. One patient died from aspiration pneumonia. Compared to those without bleeding complications, patients who bled had longer operation times and increased use of intra-aortic balloon pump. However, argatroban therapy including the starting time, median dose, infusion duration, and activated partial thromboplastin times showed no difference between the two groups. In cardiac surgery patients with clinical suspicion of HIT, early postoperative use of argatroban seems well-tolerated and associated with a low risk of thrombotic events. C1 [Yoon, Joo Heung; Yeh, Robert W.; Nam, Kyung Hun; Jang, Ik-Kyung] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Hoffman, William D.; Agnihotri, Arvind K.] Harvard Univ, Cardiac Surg Div, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org FU GlaxoSmithKline FX Dr. Jang has received grant support from GlaxoSmithKline. NR 10 TC 5 Z9 5 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 OCT PY 2010 VL 30 IS 3 BP 276 EP 280 DI 10.1007/s11239-010-0485-1 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 655BD UT WOS:000282215300003 PM 20449633 ER PT J AU Jonker, MA Sano, Y Hermsen, JL Lan, JG Kudsk, KA AF Jonker, Mark A. Sano, Yoshifumi Hermsen, Joshua L. Lan, Jinggang Kudsk, Kenneth A. TI Proinflammatory Cytokine Surge After Injury Stimulates an Airway Immunoglobulin A Increase SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT Annual Meeting of the Surgical-Infection-Society CY MAY09, 2009 CL Chicago, IL SP Surg Infection Soc DE Pro-inflammatory cytokines; Mucosal immunity; Airway; Injury; Kinetics; Intraperitoneal ID TUMOR-NECROSIS-FACTOR; VENTILATOR-ASSOCIATED PNEUMONIA; CRITICALLY-ILL PATIENTS; EPITHELIAL-CELL LINE; FACTOR-KAPPA-B; NOSOCOMIAL PNEUMONIA; FACTOR-ALPHA; SECRETORY COMPONENT; TRAUMA PATIENTS; MUCOSAL IMMUNITY AB Background: Injury stimulates an innate airway IgA response in severely injured patients, which also occurs in mice. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta stimulate the production of polymeric immunoglobulin receptor, the protein required to transport immunoglobulin A (IgA) to mucosal surfaces. Blockade of TNF-alpha and IL-1 beta eliminates the airway IgA response to injury. IL-6 stimulates differentiation of B cells into IgA-secreting plasma cells at mucosal sites. We investigated the local and systemic kinetics of TNF-alpha, IL-1 beta, and IL-6 after injury in mice. We also hypothesized that injection of exogenous TNF-alpha, IL-1 beta, and IL-6 would replicate the airway IgA response to injury. Methods: Experiment 1: male Institute of Cancer Research mice were randomized to uninjured controls (n = 8) or to surgical stress with laparotomy and neck incisions, with killing at 1, 2, 3, 5, or 8 hours after injury (n = 8/group). Bronchoalveolar lavage (BAL) and serum levels of TNF-alpha, IL-1 beta, and IL-6 were analyzed by enzyme-linked immunosorbent assay. Experiment 2: male Institute of Cancer Research mice were randomized to uninjured controls (n = 6), injury (surgical stress that was similar to experiment 1 except the peritoneum was left intact, n = 6), or cytokine injection with intraperitoneal injection of recombinant TNF-alpha, IL-1 beta, and IL-6. Animals were killed at 2 hours after injury, and nasal airway lavage and BAL IgA were analyzed by enzyme-linked immunosorbent assay. Results: Experiment 1: BAL TNF-alpha, IL-1 beta, and IL-6 levels increased in bimodal pattern after injury at 3 hours and 8 hours versus controls (p < 0.05). Serum IL-6 did not increase at 3 hours, but did show a significant increase by 5 hours versus control (p < 0.05). Serum levels of TNF-alpha and IL-1 beta did not change. Experiment 2: both Injury and combination TNF-alpha, IL-1 beta, and IL-6 cytokine injection significantly increased IgA levels in airway lavage (BAL + nasal airway lavage) compared with control (p < 0.01 for both). Conclusions: Airway levels of TNF-alpha, IL-1 beta, and IL-6 increase in a bimodal pattern after injury with peaks at 3 hours and 8 hours, which do not correspond to serum changes. The peak at 8 hours is consistent with the known increase in airway IgA after injury. Intraperitoneal injection of a combination exogenous TNF-alpha, IL-1 beta, and IL-6 replicates the airway IgA increase after injury. This effect is not seen with individual cytokine injections. C1 [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. [Jonker, Mark A.; Sano, Yoshifumi; Hermsen, Joshua L.; Lan, Jinggang; Kudsk, Kenneth A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU NIGMS NIH HHS [R01 GM053439-13, R01 GM053439-09, R01 GM053439-07, R01 GM053439-12, R01 GM053439-02, R01 GM053439, R01 GM53439, R01 GM053439-05, R01 GM053439-11, R01 GM053439-03, R01 GM053439-04, R01 GM053439-08, R01 GM053439-06A1, R01 GM053439-10A2] NR 51 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD OCT PY 2010 VL 69 IS 4 BP 843 EP 848 DI 10.1097/TA.0b013e3181c45284 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 664KP UT WOS:000282959100036 PM 20173656 ER PT J AU Kalantar, BS Hipp, JA Reitman, CA Dreiangel, N Ben-Galim, P AF Kalantar, Babak S. Hipp, John A. Reitman, Charles A. Dreiangel, Niv Ben-Galim, Peleg TI Diagnosis of Unstable Cervical Spine Injuries: Laboratory Support for the Use of Axial Traction to Diagnose Cervical Spine Instability SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Cervical spine; Trauma; Instability; Diagnosis; Traction ID COMPUTED-TOMOGRAPHY SCAN; BLUNT TRAUMA PATIENTS; INTERVERTEBRAL MOTION; PLAIN RADIOGRAPHY; JACKSON TABLE; DISLOCATIONS; CLEARANCE; PATIENT; SERIES; HEAD AB Background: The ability to detect damage to the intervertebral structures is critical in the management of patients after blunt trauma. A practical and inexpensive method to identify severe structural damage not clearly seen on computed tomography would be of benefit. The objective of this study was to assess whether ligamentous injury in the subaxial cervical spine can be reliably detected by analysis of lateral radiographs taken with and without axial traction. Methods: Twelve fresh, whole, postrigor-mortis cadavers were used for this study. Lateral cervical spine radiographs were obtained during the application of 0 N, 89 N, and 178 N of axial traction applied to the head. Progressive incremental sectioning of posterior structures was then performed at C4 C5 with traction imaging repeated after each intervention. Intervertebral distraction was analyzed using computer-assisted software. Results: Almost imperceptible intervertebral separation was found when traction was applied to intact spines. In the subaxial cervical spine, the average posterior disc height consistently increased under traction in severely injured spines. The average disc height increase was 14% of the C4 upper endplate width, compared with an average of 2% in the noninjured spines. A change of more than 5% in posterior disc height under traction was above the 95% confidence interval for intact spines, with sensitivity of 83% and specificity of 80%. Applied force of 89 N (20 lb) was sufficient to demonstrate injury. The combination of assessing alignment and distraction under traction increased both the sensitivity and specificity to nearly 100%. Conclusion: This study supports further clinical investigations to determine whether low-level axial traction may be a useful adjunct for detecting unstable subaxial cervical spine injuries in an acute setting. C1 [Hipp, John A.] Baylor Coll Med, Dept Orthoped Surg, Houston, TX 77030 USA. Michael E DeBakey Vet Adm Med Ctr, Spine Res Lab, Houston, TX USA. RP Hipp, JA (reprint author), Baylor Coll Med, Dept Orthoped Surg, 6620 Main St,11th Floor, Houston, TX 77030 USA. EM jhipp@bcm.edu NR 34 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD OCT PY 2010 VL 69 IS 4 BP 889 EP 895 DI 10.1097/TA.0b013e3181bbd660 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 664KP UT WOS:000282959100047 PM 20130489 ER PT J AU Forbes, D Creamer, M Bisson, JI Cohen, JA Crow, BE Foa, EB Friedman, MJ Keane, TM Kudler, HS Ursano, RJ AF Forbes, David Creamer, Mark Bisson, Jonathan I. Cohen, Judith A. Crow, Bruce E. Foa, Edna B. Friedman, Mathew J. Keane, Terence M. Kudler, Harold S. Ursano, Robert J. TI A Guide to Guidelines for the Treatment of PTSD and Related Conditions SO JOURNAL OF TRAUMATIC STRESS LA English DT Article AB In recent years, several practice guidelines have appeared to inform clinical work in the assessment and treatment of posttraumatic stress disorder. Although there is a high level of consensus across these documents, there are also areas of apparent difference that may lead to confusion among those to whom the guidelines are targeted providers, consumers, ant/purchasers of mental health services for people affected by trauma. The authors have been responsible for developing guidelines across three continents (North America, Europe, and Australia). The aim of this article is to examine the various guidelines and to compare and contrast their methodologies and recommendations to aid clinicians in making decisions about their use. C1 [Forbes, David; Creamer, Mark] Univ Melbourne, ACPMH, Melbourne, Vic 3002, Australia. [Bisson, Jonathan I.] Cardiff Univ, Dept Psychol Med, Cardiff, S Glam, Wales. [Cohen, Judith A.] Allegheny Gen Hosp, Dept Psychiat, Pittsburgh, PA 15212 USA. [Cohen, Judith A.] Drexel Univ, Coll Med, Philadelphia, PA USA. [Foa, Edna B.] Univ Penn, Dept Psychiat, Ctr Treatment & Study Anxiety, Philadelphia, PA 19104 USA. [Friedman, Mathew J.] Dartmouth Med Sch, Dept Psychiat, Hanover, NH USA. [Friedman, Mathew J.] Dartmouth Med Sch, Dept Pharmacol, Hanover, NH USA. [Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Kudler, Harold S.] US Dept Vet Affairs, Mid Atlantic Mental Illness Res Educ & Clin Ctr, Washington, DC USA. [Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, Bethesda, MD USA. RP Forbes, D (reprint author), Univ Melbourne, ACPMH, Level 1,340 Albert St, Melbourne, Vic 3002, Australia. EM dforbes@unimelb.edu.au RI turton, miranda/F-4682-2011 NR 14 TC 93 Z9 94 U1 6 U2 27 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2010 VL 23 IS 5 BP 537 EP 552 DI 10.1002/jts.20565 PG 16 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 674PF UT WOS:000283758900001 PM 20839310 ER PT J AU Marshall-Berenz, EC Vujanovic, AA Bonn-Miller, MO Bernstein, A Zvolensky, MJ AF Marshall-Berenz, Erin C. Vujanovic, Anka A. Bonn-Miller, Marcel O. Bernstein, Amit Zvolensky, Michael J. TI Multimethod Study of Distress Tolerance and PTSD Symptom Severity in a Trauma-Exposed Community Sample SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE PROCESSING THERAPY; EARLY SMOKING LAPSE; DISCOMFORT INTOLERANCE; SCALE; BEHAVIORS; RELEVANT; VETERANS; SMOKERS AB Despite initial evidence linking distress tolerance to posttraumatic stress disorder (PTSD) symptom severity, there is a need for the investigation of interrelations among multiple measures of distress tolerance and PTSD symptom severity. Therefore, the present study investigated concurrent relations among multiple measures of distress tolerance, as well as the relations between these measures and PTSD symptom severity, within a trauma-exposed community sample. The sample consisted of 81 trauma-exposed adults (63.1% women). Results indicated that Distress Tolerance Scale (Simons & Gaher, 2005) scores, but no other measures of distress tolerance were significantly related to PTSD symptom severity above and beyond the variance accounted for by number of traumas, trait-level neuroticism, and participant sex. Implications and future directions are discussed. C1 [Marshall-Berenz, Erin C.; Zvolensky, Michael J.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Vujanovic, Anka A.] VA Boston Hlth Care Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. [Vujanovic, Anka A.] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02215 USA. [Bernstein, Amit] Univ Haifa, Dept Psychol, IL-31999 Haifa, Israel. RP Zvolensky, MJ (reprint author), Univ Vermont, Dept Psychol, John Dewey Hall,2 Colchester Ave, Burlington, VT 05405 USA. EM Michael.Zvolensky@uvm.edu FU NIDA NIH HHS [1 R01 DA027533-01, R01 DA027533]; NIMH NIH HHS [1 F31 MH080453-01A1, 1 R01 MH076629-01, F31 MH080453, R01 MH076629] NR 32 TC 50 Z9 50 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2010 VL 23 IS 5 BP 623 EP 630 DI 10.1002/jts.20568 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 674PF UT WOS:000283758900010 PM 20848616 ER PT J AU Miller, MW Wolf, EJ Harrington, KM Brown, TA Kaloupek, DG Keane, TM AF Miller, Mark W. Wolf, Erika J. Harrington, Kelly M. Brown, Timothy A. Kaloupek, Danny G. Keane, Terence M. TI An Evaluation of Competing Models for the Structure of PTSD Symptoms Using External Measures of Comorbidity SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSIS; RESTRUCTURED CLINICAL-SCALES; COMBAT-RELATED PTSD; WORLD-TRADE-CENTER; DSM-IV ANXIETY; MOOD DISORDERS; HIERARCHICAL MODEL; RC SCALES; MMPI-2 AB Research on the structure of posttraumatic stress disorder (PTSD) symptoms has yielded support for two 4-factor models: the King (King, Leskin, King, er Weathers, 1998) and Simms/Watson models (Simms, Watson, & Doebbeling, 2002). This study evaluated them using data drawn from 1,128 Vietnam veterans by comparing associations with a latent internalizing comorbidity variable and five scales from the MMPI-2 Restructured Clinical (RC) Scales (Tellegen et al., 2003). The Simms/Watson dysphoria factor failed to show evidence of superior convergent or discriminant validity in association with external measures relative to the numbing or hyperarousal factors of the King model. Findings raise questions about proposals to abandon the distinction between numbing and hyperarousal symptoms in favor of a dysphoria-based model. C1 [Miller, Mark W.; Wolf, Erika J.; Harrington, Kelly M.; Kaloupek, Danny G.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Miller, Mark W.; Harrington, Kelly M.; Kaloupek, Danny G.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Wolf, Erika J.; Brown, Timothy A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435; Kaloupek, Danny/0000-0002-0795-593X FU CSRD VA [I01 CX000431]; NIMH NIH HHS [5F31MH074267, 5R01MH079806] NR 50 TC 40 Z9 40 U1 2 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2010 VL 23 IS 5 BP 631 EP 638 DI 10.1002/jts.20559 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 674PF UT WOS:000283758900011 PM 20839312 ER PT J AU Calohan, J Peterson, K Peskind, ER Raskind, MA AF Calohan, Jess Peterson, Kris Peskind, Elaine R. Raskind, Murray A. TI Prazosin Treatment of Trauma Nightmares and Sleep Disturbance in Soldiers Deployed in Iraq SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COMBAT VETERANS; PTSD; SYMPTOMS; BRAIN AB Trauma nightmares and sleep disturbance impair combat soldiers' functioning. The alpha-1 adrenoreceptor antagonist prazosin has been demonstrated effective for these symptoms in Vietnam veterans. Thirteen soldiers seeking relief from distressing trauma nightmares impairing military function in northern Iraq in 2006 received prazosin alone or in combination with other psychotropics. Mean prazosin dose was 4.1 (SD = 2.2) mg before bed. Six soldiers improved markedly and 3 moderately on the Clinical Global Impression of Change Ratings of distressing dreams decreased from an average of 7.0 (SD = 0.7) to 2.9 (SD = 3.0, p < .001) and those of disturbed sleep from 67 (SD = 0.9) to 3.7 (SD = 2.4, p < .001). Prazosin appears effective and well tolerated in the desert warfare environment. RP Raskind, MA (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S116 6 E, Seattle, WA 98108 USA. EM murray.raskind@va.gov NR 10 TC 18 Z9 19 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2010 VL 23 IS 5 BP 645 EP 648 DI 10.1002/jts.20570 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 674PF UT WOS:000283758900014 PM 20931662 ER PT J AU Shipp, TD Bromley, B Benacerraf, BR AF Shipp, Thomas D. Bromley, Bryann Benacerraf, Beryl R. TI The Width of the Uterine Cavity is Narrower in Patients With an Embedded Intrauterine Device (IUD) Compared to a Normally Positioned IUD SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE intrauterine device; 3-dimensional sonography; uterus ID CONTRACEPTIVE-DEVICES; UTERUS; SONOGRAPHY AB Objective. The purpose of this study was to determine whether women with intrauterine devices (IUDs) embedded in the myometrium or cervix have a narrower fundal transverse endometrial diameter as seen on 3-dimensional (3D) sonography compared to women whose IUDs are in a normal location. Methods. A sonographer blinded to the study hypothesis retrospectively evaluated the 3D images and reconstructed coronal views of the uterine cavity in 172 consecutive women who had an IUD in the uterus. The width of the endometrial cavity at the fundus of the uterus was measured transversely on the rendered coronal sonogram using the calipers on a picture archiving and communications system. The measurements obtained from women who had nonembedded IUDs were compared to those with embedded IUDs. Results. Measurement of the width of the endometrial cavity at the fundus was successfully performed in 132 patients with nonembedded IUDs and 29 with embedded IUDs. The mean +/- SD values of the fundal uterine cavity for the nonembedded and embedded IUDs were 3.2 +/- 1.0 and 2.5 +/- 0.8 mm, respectively (P = .0003). Conclusions. Patients with embedded IUDs have a smaller fundal endometrial cavity diameter compared to those with normally placed IUDs as documented using 3D rendering of the uterus. Whether preprocedural 3D sonography for women who are IUD candidates would be useful deserves further study. C1 [Shipp, Thomas D.; Bromley, Bryann; Benacerraf, Beryl R.] Diagnost Ultrasound Associates PC, Boston, MA 02115 USA. [Shipp, Thomas D.; Bromley, Bryann; Benacerraf, Beryl R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Shipp, Thomas D.; Bromley, Bryann; Benacerraf, Beryl R.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Benacerraf, Beryl R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Shipp, Thomas D.; Bromley, Bryann; Benacerraf, Beryl R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Shipp, TD (reprint author), Diagnost Ultrasound Associates PC, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. EM tshipp@partners.org NR 10 TC 12 Z9 12 U1 1 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 OCT PY 2010 VL 29 IS 10 BP 1453 EP 1456 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 663FL UT WOS:000282868300009 PM 20876899 ER PT J AU O'Regan, KN Nishino, M Armand, P Kelly, PJ Hwang, DGI Di Salvo, D AF O'Regan, Kevin N. Nishino, Mizuki Armand, Philippe Kelly, Paul J. Hwang, Dick Guang-Iong Di Salvo, Donald TI Sonographic Features of Pectoralis Muscle Necrosis Secondary to Gemcitabine-Induced Radiation Recall Case Report and Review of Current Literature SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Review ID TISSUE AB Radiation recall is defined as an inflammatory reaction within a previously treated radiation field during chemotherapy treatment.(1) Gemcitabine is one of the most common cytotoxic agents implicated in the development of this condition, and for the most part it manifests clinically as a skin reaction (radiation recall dermatitis [RRD]).(2) Radiation recall can however manifest in other tissues such as the central nervous system and the gastrointestinal tract,3 and rare cases of gemcitabine-induced radiation recall muscle necrosis have been described.(4-7) We present a case of bilateral pectoralis muscle necrosis secondary to radiation recall in a patient treated with gemcitabine in which sonography and computed tomography (CT) provided substantial clinical assistance. C1 [O'Regan, Kevin N.; Nishino, Mizuki; Di Salvo, Donald] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Armand, Philippe] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kelly, Paul J.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Hwang, Dick Guang-Iong] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP O'Regan, KN (reprint author), Dana Farber Canc Inst, Dept Imaging, 44 Binney St, Boston, MA 02115 USA. EM knoregan@partners.org NR 13 TC 5 Z9 5 U1 0 U2 0 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 OCT PY 2010 VL 29 IS 10 BP 1499 EP 1502 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 663FL UT WOS:000282868300017 PM 20876906 ER PT J AU Smith, MR Morton, RA Barnette, KG Sieber, PR Malkowicz, SB Rodriguez, D Hancock, ML Steiner, MS AF Smith, Matthew R. Morton, Ronald A. Barnette, K. Gary Sieber, Paul R. Malkowicz, S. Bruce Rodriguez, Domingo Hancock, Michael L. Steiner, Mitchell S. TI Toremifene to Reduce Fracture Risk in Men Receiving Androgen Deprivation Therapy for Prostate Cancer SO JOURNAL OF UROLOGY LA English DT Article DE osteoporosis; prostatic neoplasms; selective estrogen receptor modulators; toremifene ID RANDOMIZED CONTROLLED-TRIAL; BONE LOSS; VERTEBRAL FRACTURES; HORMONE AGONISTS; OSTEOPOROSIS; RALOXIFENE; ESTROGEN; DISEASE AB Purpose: Androgen deprivation therapy is associated with fracture risk in men with prostate cancer. We assessed the effects of toremifene, a selective estrogen receptor modulator, on fracture incidence in men receiving androgen deprivation therapy during a 2-year period. Materials and Methods: In this double-blind, placebo controlled phase III study 646 men receiving androgen deprivation therapy for prostate cancer were assigned to toremifene (80 mg by mouth daily) and 638 were assigned to placebo. Subjects were followed for 2 years. The primary study end point was new vertebral fractures. Secondary end points included fragility fractures, bone mineral density and lipid changes. Results: The 2-year incidence of new vertebral fractures was 4.9% in the placebo group vs 2.5% in the toremifene group, a significant relative risk reduction of 50% (95% CI-1.5 to 75.0, p = 0.05). Toremifene significantly increased bone mineral density at the lumbar spine, hip and femoral neck vs placebo (p < 0.0001 for all comparisons). There was a concomitant decrease in markers of bone turnover (p < 0.05 for all comparisons). Toremifene also significantly improved lipid profiles. Venous thromboembolic events occurred more frequently with toremifene than placebo with 7 subjects (1.1%) in the placebo group experiencing a venous thromboembolic event vs 17 (2.6%) in the toremifene group. Other adverse events were similar between the groups. Conclusions: Toremifene significantly decreased the incidence of new vertebral fractures in men receiving androgen deprivation therapy for prostate cancer. It also significantly improved bone mineral density, bone turnover markers and serum lipid profiles. C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Morton, Ronald A.; Barnette, K. Gary; Rodriguez, Domingo; Hancock, Michael L.; Steiner, Mitchell S.] GTx Inc, Memphis, TN USA. [Sieber, Paul R.] Urol Associates Lancaster, Lancaster, PA USA. [Malkowicz, S. Bruce] Univ Penn, Dept Surg, Div Urol, Philadelphia, PA 19104 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU GTx Inc.; National Institutes of Health [5K24CA121990-02]; Prostate Cancer Foundation; Amgen; Astellas; Endo Pharma; Tengion; GTx FX Supported by GTx Inc.; Recipient of a National Institutes of Health K24 Midcareer Investigator Award (5K24CA121990-02) and awards from the Prostate Cancer Foundation.; Financial interest and/or other relationship with GTx and Amgen.; Financial interest and/or other relationship with Astellas, Endo Pharma, Tengion and GTx. NR 28 TC 66 Z9 67 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 OCT PY 2010 VL 184 IS 4 BP 1316 EP 1321 DI 10.1016/j.juro.2010.06.022 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 660CB UT WOS:000282615400026 PM 20723926 ER PT J AU Churchill, BM Bergman, J Kristo, B Gore, JL AF Churchill, Bernard M. Bergman, Jonathan Kristo, Blaine Gore, John L. TI Improved Continence in Patients With Neurogenic Sphincteric Incompetence With Combination Tubularized Posterior Urethroplasty and Fascial Wrap: The Lengthening, Narrowing and Tightening Procedure SO JOURNAL OF UROLOGY LA English DT Article DE urethra; urinary bladder, neurogenic; meningomyelocele; urinary incontinence; reconstructive surgical procedures ID BLADDER NECK REPAIR; URINARY-INCONTINENCE; CHILDREN; 10-YEAR AB Purpose: We evaluated the outcome in 19 patients who underwent bladder neck reconstruction by lengthening, narrowing and tightening the bladder neck with a combined tubularized posterior urethroplasty and circumferential fascial wrap. Materials and Methods: We reviewed the records of all patients who underwent bladder neck lengthening, narrowing and tightening between April 1996 and November 2002. Preoperative urodynamic and radiographic data were available on all patients. The surgical technique involved retroperitoneal exposure of the bladder neck with a tubularized posterior urethroplasty over a urethral catheter. The reconstructed urethra was then circumferentially wrapped with a fitted piece of cadaveric fascia. Results: Of the 19 patients 15 remain completely continent at a mean +/- SD followup of 35.5 +/- 29.1 months. Three patients underwent secondary reconstruction, including bladder neck ligation in all 3 and secondary enterocystoplasty in 2. No patient experienced difficult intermittent catheterization via the urethra postoperatively. Conclusions: Bladder neck lengthening, narrowing and tightening is effective for managing neurogenic sphincteric incontinence. Outcomes are comparable with those of other reconstructive procedures. C1 [Gore, John L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Gore, JL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Box 951738,CHS 66-124, Los Angeles, CA 90095 USA. EM jgore@mednet.ucla.edu OI Gore, John/0000-0002-2847-5062 NR 13 TC 5 Z9 5 U1 0 U2 1 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 OCT PY 2010 VL 184 IS 4 SU 1 BP 1763 EP 1767 DI 10.1016/j.juro.2010.03.080 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 660DC UT WOS:000282618600065 PM 20728163 ER PT J AU Eisner, BH AF Eisner, Brian H. TI Pediatric Urolithiasis-Does Body Mass Index Influence Stone Presentation and Treatment? EDITORIAL COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02163 USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02163 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2010 VL 184 IS 4 SU 1 BP 1815 EP 1815 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 660DC UT WOS:000282618600081 PM 20728186 ER PT J AU Jaff, MR Katzen, BT AF Jaff, Michael R. Katzen, Barry T. TI Two-year Clinical Evaluation of the Zilver Vascular Stent for Symptomatic Iliac Artery Disease SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; RANDOMIZED CONTROLLED-TRIAL; INTERMITTENT CLAUDICATION; OCCLUSIVE DISEASE; FOLLOW-UP; ENDOVASCULAR REVASCULARIZATION; PLACEMENT; EXERCISE; FEMOROPOPLITEAL; PREVALENCE AB PURPOSE: To evaluate the 2-year outcomes of safety and effectiveness for iliac artery stent placement and examine the effects of placement in the common iliac artery (CIA) and external iliac artery (EIA), the degree of initial stenosis, and patient gender on success. MATERIALS AND METHODS: Zilver vascular stents (Cook Inc., Bloomington, Indiana) were placed in 151 consecutive patients whose iliac arteries remained stenotic after percutaneous transluminal angioplasty (PTA). Success at 2 years was determined by patency, ankle-brachial index (ABI) scores, and Walking Impairment Questionnaire (WIQ) scores. RESULTS: Patency, ABI measurements, and WIQ scores showed improvement at 2 years, compared with preprocedure measurements. Kaplan-Meier estimate of overall patency at 2 years was 90% (n = 117). Significant improvement in ABI and WIQ scores was seen at 2 years, compared with preprocedural values (P < .01). The 2-year overall success rate was 91%. The degree of initial stenosis, stent location, and patient gender did not affect the success of the Zilver stent (P = .65, P = .58, and P = .77). The Kaplan-Meier estimate of the probability of experiencing a major adverse event (MAE) related to the device or stent placement procedure by the 2-year follow-up was 2.7%. CONCLUSIONS: The Zilver vascular stent remains durable at 2 years in regard to safety and clinical effectiveness, and is effective in the CIA and EIA both in male and female patients. C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. [Katzen, Barry T.] Baptist Cardiac & Vasc Inst, Miami, FL USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Vasc Ctr, 55 Fruit St,GB 800, Boston, MA 02114 USA. EM mjaff@partners.org NR 22 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 2010 VL 21 IS 10 BP 1489 EP 1494 DI 10.1016/j.jvir.2010.06.013 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 663TE UT WOS:000282912000004 PM 20801673 ER PT J AU Ma, XZ Arellano, RS Gervais, DA Hahn, PF Mueller, PR Sahani, DV AF Ma, Xiaozhou Arellano, Ronald S. Gervais, Debra A. Hahn, Peter F. Mueller, Peter R. Sahani, Dushyant V. TI Success of Image-guided Biopsy for Small (<= 3 cm) Focal Liver Lesions in Cirrhotic and Noncirrhotic Individuals SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID SMALL HEPATOCELLULAR-CARCINOMA; ETHANOL-INJECTION-THERAPY; CT HEPATIC ARTERIOGRAPHY; LONG-TERM SURVIVAL; ARTERIAL PORTOGRAPHY; RADIOFREQUENCY ABLATION; MICROWAVE COAGULATION; PERCUTANEOUS BIOPSY; UNITED-STATES; HELICAL CT AB PURPOSE: Imaging techniques can detect small liver lesions, although these are a challenge to biopsy, particularly in cirrhotic liver. The authors assessed the diagnostic success of image-guided biopsies collected from small (<= 3 cm) focal liver lesions. MATERIALS AND METHODS: This single-center, retrospective study included 374 patients (199 men; mean age, 62 +/- 15). Eighteen-gauge core biopsy and 22-gauge fine needle aspiration (FNA) samples were collected from small focal liver lesions. Samples were compared by histology versus cytology, malignant versus benign, from lesions smaller versus larger than 1.5 cm, from livers with versus without cirrhosis, collected by computed tomography (CT) guidance versus ultrasound, and from different locations in the liver. RESULTS: The combined accuracy of core biopsy plus FNA analysis was 95.5%; core biopsy alone characterized 93.3% of samples, and FNA alone characterized 72.5% (P < .001). Biopsy successfully characterized 94.5% of malignant lesions and 98.8% of benign lesions (P > .05). Biopsy characterized 95.3% (102 of 107) lesions <= 1.5 cm. The success in cirrhotic livers was 94.8%, for CT-guided biopsies was 95%, and for ultrasound-guided biopsies was 95.8% (P > .05). The success rate was lower in liver caudate lobe than in other locations (P < .05). CONCLUSIONS: Image-guided biopsy of small (<= 3 cm) focal liver lesions is highly reliable with the use of core biopsy alone. Neither size <= 1.5 cm nor presence of cirrhosis is an impediment to biopsy. CT and ultrasound guidance produce similar rates of success. C1 [Ma, Xiaozhou; Arellano, Ronald S.; Gervais, Debra A.; Hahn, Peter F.; Mueller, Peter R.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 42 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 2010 VL 21 IS 10 BP 1539 EP 1547 DI 10.1016/j.jvir.2010.05.025 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 663TE UT WOS:000282912000012 PM 20801683 ER PT J AU Saxena, A Hakimelahi, R Jha, RM Hirsch, AE Growney, M Yoo, AJ AF Saxena, Akriti Hakimelahi, Reza Jha, Ruchira M. Hirsch, Ariel E. Growney, Marion Yoo, Albert J. TI The Safety and Effectiveness of a Curved Needle for Vertebral Augmentation: Comparison with Traditional Techniques SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID PERCUTANEOUS VERTEBROPLASTY; COMPRESSION FRACTURES; RADIATION-EXPOSURE; RANDOMIZED-TRIAL; SINGLE-CENTER; PAIN RELIEF; KYPHOPLASTY; OUTCOMES; EXPERIENCE; OPERATORS AB PURPOSE: To evaluate the safety and effectiveness of a curved needle compared with traditional (noncurved needle) techniques in a large single-center experience. MATERIALS AND METHODS: This study was a retrospective analysis of 243 consecutive vertebral augmentation procedures over a 17-month period. Curved needle procedures were compared with noncurved needle procedures for baseline clinical variables, complication rate, pain relief, and improvement in disability. Procedure duration and fluoroscopy time were compared between the two cohorts. RESULTS: Between curved needle and noncurved needle procedures, there were no statistically significant differences in the baseline clinical variables, fracture location, and fracture etiology. No complications were noted in either group. In both groups, there was a median improvement in the visual analog scale (VAS) score of 2.0 points (P = .62). More than 90% of procedures in both groups resulted in some pain improvement (P = .78). For both groups, the median improvement in disability on the Roland Morris Disability Questionnaire (RMDQ) was 4.0 points (P = .69). Approximately 70% of procedures in both groups resulted in improvement in disability (P = 1.00). In single-level cases, there were shorter procedure times (51.8 min +/- 2.7 vs 62.8 min +/- 2.2, P = .002) and shorter fluoroscopy times (P = .31) for curved needle procedures. CONCLUSIONS: The curved needle is as safe and effective as traditional vertebral augmentation techniques in treating the pain and disability related to vertebral compression fractures. Additionally, the curved needle is associated with shorter procedure duration and reduced fluoroscopy time. C1 [Hakimelahi, Reza; Growney, Marion; Yoo, Albert J.] Harvard Univ, Sch Med, Div Intervent Neuroradiol, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jha, Ruchira M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Ariel E.] Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Saxena, Akriti] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Yoo, AJ (reprint author), Harvard Univ, Sch Med, Div Intervent Neuroradiol, Dept Radiol,Massachusetts Gen Hosp, 55 Fruit St,Gray 241, Boston, MA 02114 USA. EM ajyoo@partners.org NR 21 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 2010 VL 21 IS 10 BP 1548 EP 1553 DI 10.1016/j.jvir.2010.06.015 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 663TE UT WOS:000282912000013 PM 20801677 ER PT J AU Houbballah, R Majewski, M Becquemin, JP AF Houbballah, Rabih Majewski, Marek Becquemin, Jean-Pierre TI Significant sac retraction after endovascular aneurysm repair is a robust indicator of durable treatment success SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ABDOMINAL AORTIC-ANEURYSM; ENDOLUMINAL EXCLUSION; REPORTING STANDARDS; DIAMETER; SIZE; REGRESSION; DEVICE; TRIAL; THROMBUS; REGISTRY AB Objectives: The principal aim of this study was to demonstrate that significant sac retraction (SSR) was a predictive marker of durable success after endovascular aortic repair (EVAR). If verified, follow-up (FU) of patients with SSR may become unnecessary. In addition, the clinical features of the patients and aneurysms were analyzed to identify predictive factors of SSR. Methods: A group of 371 patients treated by EVAR had a complete clinical exam, computed tomography (CT) scan, and duplex scan follow-up. Data were collected prospectively and analyzed retrospectively. We assessed the difference between the largest diameter of the aneurysm (D) and the diameter of the stent-graft body (DI) on each postoperative CT scan. SSR was defined as a minimum of 75% reduction of this difference between the first and any of the following CT scans. Treatment success was defined as survival free of aneurysm-related death, type I or III endoleak, aneurysm expansion exceeding 5 mm, rupture, surgical conversion, migration, and graft occlusion. To assess the predictive factors of SSR, we performed a multivariable analysis and a logistic regression of the most significant variables. Results: SSR was observed in 24.8% (92/371) of the patients after an average of 26 +/- 21 months of FU. The mean duration of FU in this group was 50 +/- 26 months (vs 45 +/- 25 months; P = NS). Survival was significantly longer in the SSR group (96 +/- 3 months vs 93 +/- 3 months; P < .05). No rupture, surgical, or endovascular conversion was reported in the SSR group. The frequency of type I (2.2% vs 15.4%; P < .001), type II (3.3% vs 29.4%; P < 10(-6)), and secondary interventions (3.3% vs 13.3%;P < .05) was lower in the SSR group. All type I and III endoleaks were diagnosed and treated before SSR detection. Since SSR was detected, treatment success remained until last follow-up in 98.9% (91 of 92) of the patients. The independent predictive factors of SSR were abdominal aortic aneurysm (AAA) diameter <55 mm (odds ratio [OR] 3.91; 95% confidence interval [CI]: 2.16-7.11), infra renal aorta diameter <23 mm (OR 2.96; 95% CI: 1.74-5.03), and a proximal neck length >22 mm (OR 2.41; 95% CI: 1.42-4.10). Conclusion: In this series, SSR was accurately predictive of a durable success after EVAR. It occurred mostly in patients with a favorable anatomy. Less intensive follow-up work up seems to be safe in patients with SSR. (J Vase Surg 2010; 52:878-83.) C1 [Houbballah, Rabih; Majewski, Marek; Becquemin, Jean-Pierre] Univ Paris, Dept Vasc & Endovasc Surg, Henri Mondor Hosp, Creteil, France. RP Houbballah, R (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Edwards 307A, Boston, MA 02114 USA. EM docrabih@gmail.com NR 32 TC 17 Z9 19 U1 1 U2 11 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 OCT PY 2010 VL 52 IS 4 BP 878 EP 883 DI 10.1016/j.jvs.2010.04.069 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 660RF UT WOS:000282660300009 PM 20638230 ER PT J AU Patel, VI Lancaster, RT Conrad, MF LaMu-Raglia, GM Kwolek, CJ Brewster, DC Cambria, RP AF Patel, Virendra I. Lancaster, Robert T. Conrad, Mark F. LaMu-raglia, Glenn M. Kwolek, Christopher J. Brewster, David C. Cambria, Richard P. TI Complex Aortic Aneurysm Repair Compares Favorably to Open Infra-renal Abdominal Aortic Aneurysm Repair SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract C1 [Patel, Virendra I.; Lancaster, Robert T.; Conrad, Mark F.; LaMu-raglia, Glenn M.; Kwolek, Christopher J.; Brewster, David C.; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2010 VL 52 IS 4 BP 1116 EP 1116 DI 10.1016/j.jvs.2010.06.116 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 660RF UT WOS:000282660300049 ER PT J AU Nguyen, BNH Conrad, MF Guest, JM Hackney, L Paruchuri, V Patel, VI Rosenfield, K Cambria, RP AF Nguyen, Bao-Ngoc H. Conrad, Mark F. Guest, Julie M. Hackney, Lauren Paruchuri, Vikram Patel, Viendra I. Rosenfield, Kenneth Cambria, Richard P. TI Angioplasty (POBA) Versus Stenting for Superficial Femoral/Popliteal Disease: Late Outcomes Are Equivalent SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract C1 [Nguyen, Bao-Ngoc H.; Conrad, Mark F.; Guest, Julie M.; Hackney, Lauren; Paruchuri, Vikram; Patel, Viendra I.; Rosenfield, Kenneth; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2010 VL 52 IS 4 BP 1119 EP 1119 DI 10.1016/j.jvs.2010.06.124 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 660RF UT WOS:000282660300057 ER PT J AU Lancaster, RT Conrad, MF Patel, VI Cambria, RP LaMuraglia, GL AF Lancaster, Robert T. Conrad, Mark F. Patel, Virendra I. Cambria, Richard P. LaMuraglia, Glenn L. TI Predictors of Early Graft Failure After Infrainguinal Bypass Surgery: A Risk-Adjusted Analysis From the NSQIP SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2010 VL 52 IS 4 BP 1120 EP 1120 DI 10.1016/j.jvs.2010.06.126 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 660RF UT WOS:000282660300059 ER PT J AU Haurani, MJ Albadawi, H Houbballah, R Nguyen, BN Yoo, HJ LaMuraglia, GM Watkins, MT AF Haurani, Mounir J. Albadawi, Hassan Houbballah, Rabih Nguyen, Bao-Ngoc Yoo, Hyung-Jin LaMuraglia, Glen M. Watkins, Michael T. TI Continuous Inhibition of Poly-ADP Ribose Polymerase Improves Functional Recovery and Modulates Skeletal Muscle Regeneration Following Hind Limb Ischemia and Reperfusion SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract C1 [Haurani, Mounir J.; Albadawi, Hassan; Houbballah, Rabih; Nguyen, Bao-Ngoc; Yoo, Hyung-Jin; LaMuraglia, Glen M.; Watkins, Michael T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2010 VL 52 IS 4 BP 1122 EP 1122 DI 10.1016/j.jvs.2010.06.130 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 660RF UT WOS:000282660300063 ER PT J AU Lin, NH Negusse, DM Beroukhim, R Giguel, F Lockman, S Essex, M Kuritzkes, DR AF Lin, Nina H. Negusse, Daniel M. Beroukhim, Rameen Giguel, Francoise Lockman, Shahin Essex, Myron Kuritzkes, Daniel R. TI The design and validation of a novel phenotypic assay to determine HIV-1 coreceptor usage of clinical isolates SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Chemokine receptor; Luciferase; Pseudovirus; Viral fitness; HIV; Viral tropism; Coreceptor usage; CCR5; CXCR4 ID IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VITRO; DNA RECOMBINATION; CCR5 INHIBITOR; INFECTION; TROPISM; AIDS; REPLICATION; PROGRESSION; SEQUENCE AB A phenotypic assay to determine coreceptor usage of HIV-1 has been developed for rapid testing of clinical samples. The assay is based on the synthesis of viral stock from full-length env amplicons isolated from patient's plasma. Pseudoviral stock is generated rapidly by using an overlapping PCR method to assemble a CMV promoter to env, followed by co-transfection into producer cells with a HIV plasmid (pNL4-3.Luc.R(-)E(-)) containing a non-functional env. The coreceptor used by the viral quasispecies is tested by infection into U87.CD4.CCR5 and U87.CD4.CXCR4 cells. Viral entry is indicated by the expression of the luciferase gene in relative light units (RLU). The use of CXCR4 coreceptor by minor variants is confirmed with sufficient suppression of RLU by a CXCR4 inhibitor. Two statistical tests are employed to confirm viral entry. This assay accurately assigned coreceptor usage of isolates of various subtypes and in the majority of samples of various viral loads. The sensitivity to detect minor species of CXCR4-using env is 1% at higher viral loads and 5% at less than 1000 copies/ml. This assay provides a sensitive, efficient and relatively low-cost approach suitable for use by research laboratories for assessing HIV-1 coreceptor usage of plasma samples. (c) 2010 Elsevier B.V. All rights reserved. C1 [Lin, Nina H.; Giguel, Francoise; Lockman, Shahin; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Sect Retroviral Therapeut, Cambridge, MA 02139 USA. [Lin, Nina H.; Giguel, Francoise; Lockman, Shahin; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Div Infect Dis, Cambridge, MA 02139 USA. [Lin, Nina H.; Giguel, Francoise] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Lin, Nina H.; Giguel, Francoise; Lockman, Shahin; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Negusse, Daniel M.; Lockman, Shahin; Essex, Myron] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, AIDS Initiat, Boston, MA 02115 USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol & Canc Biol, Boston, MA 02215 USA. [Beroukhim, Rameen] 7 Cambridge Ctr, Broad Inst, Cambridge, MA 02142 USA. RP Kuritzkes, DR (reprint author), Brigham & Womens Hosp, Sect Retroviral Therapeut, 65 Landsdowne St,Rm 449, Cambridge, MA 02139 USA. EM nhlin@partners.org; dnegusse@hsph.harvard.edu; rameen@broad.mit.edu; fgiguel@partners.org; slockman@hsph.harvard.edu; messex@hsph.harvard.edu; dkuritzkes@partners.org FU NIH [U87-CD4-CCR5, U87-CD4-CXCR4, RR016482, U01 A1068636, R01 HD037793, R01 HD044391]; Harvard Center for AIDS Research Grant; Burroughs-Wellcome-ASTMH Tropical Research Fellowship FX To the contributions of Drs. Vladimir Novitsky and Joseph Makhema for the subtype C clinical samples from Botswana: the ACTG A5211 protocol team for the use of clinical isolates and their corresponding Trofile assay data; and Drs. Martin Hirsch and Cecil Trembley for the subtype B acute infection isolates are gratefully acknowledged. Dr. Manish Sagar and Dr. Zixin Hu provided valuable scientific advice throughout the study. The following reagents were obtained from the NIH AIDS Research and Reference Reagent Program: U87-CD4-CCR5 and U87-CD4-CXCR4 cells from H. Deng and D.R. Littman, and AMD3100. The generous donation of TAK779 by Takeda Pharmaceuticals is also acknowledged. This work was supported by NIH grants RR016482 and U01 A1068636 (an ACTG Virology Support Laboratory contract) (DRK), R01 HD037793 (ME), R01 HD044391 (SL), and the Harvard Center for AIDS Research Grant and Burroughs-Wellcome-ASTMH Tropical Research Fellowship (NHL). NR 27 TC 17 Z9 17 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD OCT PY 2010 VL 169 IS 1 BP 39 EP 46 DI 10.1016/j.jviromet.2010.06.012 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 657FM UT WOS:000282398600007 PM 20599562 ER PT J AU Dieltjens, T Willems, B Coppens, S Van Nieuwenhove, L Humbert, M Dietrich, U Heyndrickx, L Vanham, G Janssens, W AF Dieltjens, Tessa Willems, Betty Coppens, Sandra Van Nieuwenhove, Lies Humbert, Michael Dietrich, Ursula Heyndrickx, Leo Vanham, Guido Janssens, Wouter TI Unravelling the antigenic landscape of the HIV-1 subtype A envelope of an individual with broad cross-neutralizing antibodies using phage display peptide libraries SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Human immunodeficiency virus; M13 bacteriophage; Phage display; Neutralizing antibodies; Mimotopes ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCLONAL-ANTIBODIES; IMMUNODOMINANT EPITOPE; VACCINE DESIGN; TYPE-1; REGION; SERA; IDENTIFICATION; MIMOTOPES; GP120 AB Broad cross-neutralizing antibodies from persons infected with HIV-1 target a variety of epitopes. Identification of these HIV-1 epitopes may result in an optimal panel of antigenic peptides to be included in a prophylactic vaccine. Phage display peptide libraries were used to unravel the antigenic landscape of an individual (ITM1) infected with HIV-1 subtype A with broad cross-neutralizing antibodies. A stringent selection strategy resulted in the identification of 60 unique HIV-1 peptide phage, which were subjected to sequence analysis and mapped onto the ITM1 envelope sequences. Four groups of peptide phages were found: the first group (n = 11) were similar with the tip of the V3 loop (KxxHxGPxxxF); the second group (n = 11) represented the gp41 principal immunodominant domain (CxGxLxCTxNxP); the third group (n = 16) could be localized in the V2 loop (KxxxHxxxY); and the fourth group (n = 22) mimicked a conformational epitope (Hxx(s)/(T)NxK). All but the V2-binding antibodies were conserved over the 11 years of follow-up. A neutralization inhibition assay revealed the contribution of the V3 antibodies to the neutralizing capacity of the ITM1 plasma. Overall, the ITM1 immunogenic landscape was mapped and a part of the origin of this broad cross-neutralizing activity was demonstrated. (c) 2010 Elsevier B.V. All rights reserved. C1 [Dieltjens, Tessa; Willems, Betty; Coppens, Sandra; Heyndrickx, Leo; Vanham, Guido; Janssens, Wouter] Inst Trop Med, Dept Microbiol, B-2000 Antwerp, Belgium. [Van Nieuwenhove, Lies] Inst Trop Med, Dept Parasitol, Unit Parasite Diagnost, B-2000 Antwerp, Belgium. [Humbert, Michael; Dietrich, Ursula] Inst Biomed Res, Frankfurt, Germany. [Humbert, Michael] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vanham, Guido] Univ Antwerp, Dept Biomed Sci, B-2020 Antwerp, Belgium. [Vanham, Guido] Free Univ Brussels, Fac Med & Pharm, B-1050 Brussels, Belgium. RP Dieltjens, T (reprint author), Inst Trop Med, Dept Microbiol, Natl Str 155, B-2000 Antwerp, Belgium. EM tdieltjens@itg.be FU Research Foundation, Flanders (FWO) [G 0302.01]; European Community [201433]; Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT) FX The study was funded by the Research Foundation, Flanders (FWO Project G 0302.01) and from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 201433. Tessa Dieltjens is supported by a Ph.D. scholarship from the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT). We thank the ITM AIDS Reference Centre (ARC) and Laboratory (ARL) for patient follow-up and clinical data. NR 32 TC 10 Z9 11 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD OCT PY 2010 VL 169 IS 1 BP 95 EP 102 DI 10.1016/j.jviromet.2010.07.004 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 657FM UT WOS:000282398600015 PM 20637241 ER PT J AU Leslie, A Matthews, PC Listgarten, J Carlson, JM Kadie, C Ndung'u, T Brander, C Coovadia, H Walker, BD Heckerman, D Goulder, PJR AF Leslie, Alasdair Matthews, Philippa C. Listgarten, Jennifer Carlson, Jonathan M. Kadie, Carl Ndung'u, Thumbi Brander, Christian Coovadia, Hoosen Walker, Bruce D. Heckerman, David Goulder, Philip J. R. TI Additive Contribution of HLA Class I Alleles in the Immune Control of HIV-1 Infection SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; DISEASE PROGRESSION; VIRAL LOAD; AIDS; ASSOCIATIONS; REPLICATION; ADVANTAGE; SUPERTYPE; GENOTYPE AB Previous studies have identified a central role for HLA-B alleles in influencing control of HIV infection. An alternative possibility is that a small number of HLA-B alleles may have a very strong impact on HIV disease outcome, dominating the contribution of other HLA alleles. Here, we find that even following the exclusion of subjects expressing any of the HLA-B class I alleles (B*57, B*58, and B*18) identified to have the strongest influence on control, the dominant impact of HLA-B alleles on virus set point and absolute CD4 count variation remains significant. However, we also find that the influence of HLA on HIV control in this C-clade-infected cohort from South Africa extends beyond HLA-B as HLA-Cw type remains a significant predictor of virus and CD4 count following exclusion of the strongest HLA-B associations. Furthermore, there is evidence of interdependent protective effects of the HLA-Cw*0401-B*8101, HLA-Cw*1203-B*3910, and HLA-A*7401-B*5703 haplotypes that cannot be explained solely by linkage to a protective HLA-B allele. Analysis of individuals expressing both protective and detrimental alleles shows that even the strongest HLA alleles appear to have an additive rather than dominant effect on HIV control at the individual level. Finally, weak but significant frequency-dependent effects in this cohort can be detected only by looking at an individual's combined HLA allele frequencies. Taken together, these data suggest that although individual HLA alleles, particularly HLA-B, can have a strong impact, HIV control overall is likely to be influenced by the additive effect of some or all of the other HLA alleles present. C1 [Matthews, Philippa C.; Goulder, Philip J. R.] Univ Oxford, Nuffield Dept Med, Dept Paediat, Oxford OX1 3SY, England. [Leslie, Alasdair] Univ Oxford, Weatherall Inst Mol Med, Oxford OX1 3SY, England. [Listgarten, Jennifer; Carlson, Jonathan M.; Kadie, Carl; Heckerman, David] Microsoft Res, Machine Learning & Appl Stat Grp, Redmond, WA USA. [Ndung'u, Thumbi; Coovadia, Hoosen; Walker, Bruce D.; Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Brander, Christian] Hosp Badalona Germans Trias & Pujol, Fundacio IrsiCaixa HIVACAT, Badalona, Spain. [Brander, Christian] Inst Catalana Recerca & Estudis Avancats, Barcelona 08916, Spain. [Walker, Bruce D.; Goulder, Philip J. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Goulder, PJR (reprint author), Univ Oxford, Nuffield Dept Med, Dept Paediat, Peter Medawar Bldg Pathogen Res, Oxford OX1 3SY, England. EM philip.goulder@paediatrics.ox.ac.uk OI Brander, Christian/0000-0002-0548-5778; Matthews, Philippa/0000-0002-4036-4269; Ndung'u, Thumbi/0000-0003-2962-3992 FU National Institutes of Health [2RO1AI46995]; South African AIDS Vaccine Initiative; Wellcome Trust FX This work was funded by the National Institutes of Health (2RO1AI46995), the South African AIDS Vaccine Initiative, and the Wellcome Trust (to A. L. and P.J.R.G.). P.J.R.G. is an Elizabeth Glaser Pediatric AIDS Foundation Scientist. T.N. holds the South African Research Chair in Systems Biology of HIV/AIDS. NR 28 TC 87 Z9 88 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2010 VL 84 IS 19 BP 9879 EP 9888 DI 10.1128/JVI.00320-10 PG 10 WC Virology SC Virology GA 660KQ UT WOS:000282641800021 PM 20660184 ER PT J AU Doores, KJ Burton, DR AF Doores, Katie J. Burton, Dennis R. TI Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; N-LINKED GLYCOSYLATION; BUTYLDEOXYNOJIRIMYCIN-MEDIATED INHIBITION; TYPE-1 ENVELOPE GLYCOPROTEIN; COMPLEMENT COMPONENT C3; SITE-SPECIFIC ANALYSIS; NEUTRALIZING ANTIBODIES; SYNCYTIUM FORMATION; AIDS VACCINE; BINDING-SITE AB The HIV-1-specific antibodies PG9 and PG16 show marked cross-isolate neutralization breadth and potency. Antibody neutralization has been shown to be dependent on the presence of N-linked glycosylation at position 160 in gp120. We show here that (i) the loss of several key glycosylation sites in the V1, V2, and V3 loops; (ii) the generation of pseudoviruses in the presence of various glycosidase inhibitors; and (iii) the growth of pseudoviruses in a mutant cell line (GnT1(-/-)) that alters envelope glycosylation patterns all have significant effects on the sensitivity of virus to neutralization by PG9 and PG16. However, the interaction of antibody is not inhibited by sugar monosaccharides corresponding to those found in glycans on the HIV surface. We show that some of the glycosylation effects described are isolate dependent and others are universal and can be used as diagnostic for the presence of PG9 and PG16-like antibodies in the sera of HIV-1-infected patients. The results suggest that PG9 and PG16 recognize a conformational epitope that is dependent on glycosylation at specific variable loop N-linked sites. This information may be valuable for the design of immunogens to elicit PG9 and PG16-like antibodies, as well as constructs for cocrystallization studies. C1 [Doores, Katie J.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Doores, Katie J.; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Doores, Katie J.; Burton, Dennis R.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM burton@scripps.edu OI Doores, Katie/0000-0002-5507-1725 FU International AIDS Vaccine Initiative through the Neutralizing Antibody Consortium, National Institute of Allergy and Infectious Diseases, National Institutes of Health [AI33292]; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Harvard. FX This study was funded by the International AIDS Vaccine Initiative through the Neutralizing Antibody Consortium, National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant AI33292 [D.R.B.]), and the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard. NR 63 TC 116 Z9 118 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2010 VL 84 IS 20 BP 10510 EP 10521 DI 10.1128/JVI.00552-10 PG 12 WC Virology SC Virology GA 660KW UT WOS:000282642600008 PM 20686044 ER PT J AU Payne, RP Kloverpris, H Sacha, JB Brumme, Z Brumme, C Buus, S Sims, S Hickling, S Riddell, L Chen, F Luzzi, G Edwards, A Phillips, R Prado, JG Goulder, PJR AF Payne, Rebecca P. Kloverpris, Henrik Sacha, Jonah B. Brumme, Zabrina Brumme, Chanson Buus, Soren Sims, Stuart Hickling, Stephen Riddell, Lynn Chen, Fabian Luzzi, Graz Edwards, Anne Phillips, Rodney Prado, Julia G. Goulder, Philip J. R. TI Efficacious Early Antiviral Activity of HIV Gag- and Pol-Specific HLA-B*2705-Restricted CD8(+) T Cells SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LYMPHOCYTE RESPONSE; INFECTED-CELLS; CTL EPITOPES; VIRAL LOAD; ESCAPE; REPLICATION; PROTEINS; FITNESS; POLYFUNCTIONALITY AB The association between HLA-B*2705 and the immune control of human immunodeficiency virus type 1 (HIV-1) has previously been linked to the targeting of the HLA-B*2705-restricted Gag epitope KRWIILGLNK (KK10) by CD8(+) T cells. In order to better define the mechanisms of the HLA-B*2705 immune control of HIV, we first characterized the CD8(+) T-cell responses of nine highly active antiretroviral therapy (HAART)-naive B*2705-positive subjects. Unexpectedly, we observed a strong response to an HLA-B*2705-restricted Pol epitope, KRKGGIGGY (KY9), in 8/9 subjects. The magnitude of the KY9 response was only marginally lower than that of the KK10-specific response (median, 695 versus 867 spot-forming cells [SFC]/million peripheral blood mononuclear cells [PBMCs]; not significant [NS]), and viral escape mutants were observed in both KY9 and KK10, resulting from selection pressure driven by the respective CD8(+) T-cell response. By comparing inhibitions of viral replication by CD8(+) T cells specific for the Gag KK10, Pol KY9, and Vpr VL9 HLA-B*2705-restricted epitopes, we observed a consistent hierarchy of antiviral efficacy (Gag KK10 > Pol KY9 > Vpr VL9). This hierarchy was associated with early recognition of HIV-1-infected cells, within 6 h of infection, by KK10- and KY9-specific CD8(+) T cells but not until 18 h postinfection by VL9-specific CD8(+) T cells. There was no association between antiviral efficacy and proliferative capacity, cytotoxicity, polyfunctionality, or T-cell receptor (TCR) avidity. These data are consistent with previous studies indicating an important role for the B*2705-Gag KK10 response in the control of HIV but also suggest a previously unrecognized role played by the subdominant Pol-specific KY9 response in HLA-B*2705-mediated control of HIV and that the recognition of HIV-infected cells by CD8(+) T cells early in the viral life cycle may be important for viral containment in HIV-infected individuals. C1 [Payne, Rebecca P.; Kloverpris, Henrik; Prado, Julia G.; Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England. [Sacha, Jonah B.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53711 USA. [Brumme, Zabrina] Simon Fraser Univ, Fac Hlth Sci, Vancouver, BC, Canada. [Brumme, Zabrina; Brumme, Chanson] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Buus, Soren] Univ Copenhagen, Expt Immunol Lab, Copenhagen, Denmark. [Sims, Stuart; Hickling, Stephen; Phillips, Rodney] Univ Oxford, Nuffield Dept Med, Oxford OX1 3SY, England. [Hickling, Stephen] James Martin 21st Century Sch, Dept Zool, Oxford OX1 3SY, England. [Riddell, Lynn] Northampton Healthcare NHS Fdn Trust, Northampton NN1 5BD, England. [Chen, Fabian] Royal Berkshire NHS Fdn Trust, Reading RG1 5AN, Berks, England. [Luzzi, Graz] Wycombe Gen Hosp, High Wycombe HP11 2TT, Bucks, England. [Edwards, Anne] Churchill Hosp, Oxford OX3 7LJ, England. [Goulder, Philip J. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. [Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. RP Payne, RP (reprint author), Univ Oxford, Dept Paediat, Peter Medawar Bldg Pathogen Res, Oxford OX1 3SY, England. EM rebecca.payne@paediatrics.ox.ac.uk RI Buus, Soren/F-5446-2010; OI Buus, Soren/0000-0001-8363-1999; Brumme, Chanson/0000-0003-2722-5288 FU National Institutes of Health [RO1AI46995]; Wellcome Trust; UK Medical Research Council; Canadian Institutes of Health Research FX This work is funded by grants from the National Institutes of Health (grant RO1AI46995) (P.J.R.G.), the Wellcome Trust (P.J.R.G.), and the UK Medical Research Council (R.P.P.). Z.B. is supported by a new investigator award from the Canadian Institutes of Health Research. NR 37 TC 48 Z9 48 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2010 VL 84 IS 20 BP 10543 EP 10557 DI 10.1128/JVI.00793-10 PG 15 WC Virology SC Virology GA 660KW UT WOS:000282642600011 PM 20686036 ER PT J AU Doores, KJ Fulton, Z Huber, M Wilson, IA Burton, DR AF Doores, Katie J. Fulton, Zara Huber, Michael Wilson, Ian A. Burton, Dennis R. TI Antibody 2G12 Recognizes Di-Mannose Equivalently in Domain- and Nondomain-Exchanged Forms but Only Binds the HIV-1 Glycan Shield if Domain Exchanged SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODIES; CARBOHYDRATE-RECOGNITION; ENVELOPE GLYCOPROTEIN; VACCINE DESIGN; B-CELLS; DC-SIGN; GP120; EPITOPE AB The broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibody 2G12 targets the high-mannose cluster on the glycan shield of HIV-1. 2G12 has a unique V(H) domain-exchanged structure, with a multivalent binding surface that includes two primary glycan binding sites. The high-mannose cluster is an attractive target for HIV-1 vaccine design, but so far, no carbohydrate immunogen has elicited 2G12-like antibodies. Important questions remain as to how this domain exchange arose in 2G12 and how this unusual event conferred unexpected reactivity against the glycan shield of HIV-1. In order to address these questions, we generated a nondomain-exchanged variant of 2G12 to produce a conventional Y/T-shaped antibody through a single amino acid substitution (2G12 I19R) and showed that, as for the 2G12 wild type (2G12 WT), this antibody is able to recognize the same Man alpha 1,2Man motif on recombinant gp120, Candida albicans, and synthetic glycoconjugates. However, the nondomain-exchanged variant of 2G12 is unable to bind the cluster of mannose moieties on the surface of HIV-1. Crystallographic analysis of 2G12 I19R in complex with Man alpha 1,2Man revealed an adaptable hinge between V(H) and C(H)1 that enables the V(H) and V(L) domains to assemble in such a way that the configuration of the primary binding site and its interaction with disaccharide are remarkably similar in the nondomain-exchanged and domain-exchanged forms. Together with data that suggest that very few substitutions are required for domain exchange, the results suggest potential mechanisms for the evolution of domain-exchanged antibodies and immunization strategies for eliciting such antibodies. C1 [Doores, Katie J.; Huber, Michael; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Doores, Katie J.; Huber, Michael; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Fulton, Zara; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Doores, Katie J.; Huber, Michael; Burton, Dennis R.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM wilson@scripps.edu; burton@scripps.edu RI Huber, Michael/B-8509-2015; OI Doores, Katie/0000-0002-5507-1725 FU International AIDS Vaccine Initiative (IAVI) through the Neutralizing Antibody Consortium, NIH [AI33292, U01 AI078224]; NIH [GM46192, AI84817]; Ragon Institute of MGH; Swiss National Foundation [PBEZB-119694]; Skaggs Institute for Chemical Biology; Ragon Institute of MIT; Ragon Institute of Harvard FX This work was funded by the International AIDS Vaccine Initiative (IAVI) through the Neutralizing Antibody Consortium, NIH grants AI33292 and U01 AI078224 (to D. R. B.), NIH grants GM46192 and AI84817 (to I. A. W.), the Ragon Institute of MGH, MIT, and Harvard (funding to D. R. B., K.J.D., and M. H.), the Swiss National Foundation (grant PBEZB-119694 to M. H.), and the Skaggs Institute for Chemical Biology. NR 54 TC 40 Z9 40 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2010 VL 84 IS 20 BP 10690 EP 10699 DI 10.1128/JVI.01110-10 PG 10 WC Virology SC Virology GA 660KW UT WOS:000282642600024 PM 20702629 ER PT J AU Huber, M Le, KM Doores, KJ Fulton, Z Stanfield, RL Wilson, IA Burton, DR AF Huber, Michael Le, Khoa M. Doores, Katie J. Fulton, Zara Stanfield, Robyn L. Wilson, Ian A. Burton, Dennis R. TI Very Few Substitutions in a Germ Line Antibody Are Required To Initiate Significant Domain Exchange SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; CROSS-CLADE NEUTRALIZATION; HIV VACCINES; B-CELLS; AIDS VACCINE; 2G12; GP120; EXPRESSION; GLYCOPROTEIN AB 2G12 is a broadly neutralizing anti-HIV-1 monoclonal human IgG1 antibody reactive with a high-mannose glycan cluster on the surface of glycoprotein gp120. A key feature of this very highly mutated antibody is domain exchange of the heavy-chain variable region (V(H)) with the V(H) of the adjacent Fab of the same immunoglobulin, which assembles a multivalent binding interface composed of two primary binding sites in close proximity. A non-germ line-encoded proline in the elbow between V(H) and C(H)1 and an extensive network of hydrophobic interactions in the V(H)/V(H)' interface have been proposed to be crucial for domain exchange. To investigate the origins of domain exchange, a germ line version of 2G12 that behaves as a conventional antibody was engineered. Substitution of 5 to 7 residues for those of the wild type produced a significant fraction of domain-exchanged molecules, with no evidence of equilibrium between domain-exchanged and conventional forms. Two substitutions not previously implicated, A(H14) and E(H75), are the most crucial for domain exchange, together with I(H19) at the V(H)/V(H)' interface and P(H113) in the elbow region. Structural modeling gave clues as to why these residues are essential for domain exchange. The demonstration that domain exchange can be initiated by a small number of substitutions in a germ line antibody suggests that the evolution of a domain-exchanged antibody response in vivo may be more readily achieved than considered to date. C1 [Huber, Michael; Le, Khoa M.; Doores, Katie J.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Huber, Michael; Le, Khoa M.; Doores, Katie J.; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Fulton, Zara; Stanfield, Robyn L.; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Huber, Michael; Doores, Katie J.; Burton, Dennis R.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM burton@scripps.edu RI Huber, Michael/B-8509-2015; OI Doores, Katie/0000-0002-5507-1725 FU International AIDS Vaccine Initiative (IAVI) through the Neutralizing Antibody Consortium; National Institutes of Allergy and Infectious Diseases, NIH [AI33292, U01 AI078224, GM46192, AI84817]; Ragon Institute of MGH; Swiss National Science Foundation [PBEZB-119694]; Skaggs Institute for Chemical Biology; Ragon Institute of MIT; Ragon Institute of Harvard FX This work was supported by the International AIDS Vaccine Initiative (IAVI) through the Neutralizing Antibody Consortium; the National Institutes of Allergy and Infectious Diseases, NIH (grants AI33292 and U01 AI078224 to D. R. B. and grants GM46192 and AI84817 to I. A. W.); the Ragon Institute of MGH, MIT, and Harvard (support given to D. R. B., M. H., and K.J.D.); the Swiss National Science Foundation (grant PBEZB-119694 to M. H.); and the Skaggs Institute for Chemical Biology. NR 46 TC 25 Z9 25 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2010 VL 84 IS 20 BP 10700 EP 10707 DI 10.1128/JVI.01111-10 PG 8 WC Virology SC Virology GA 660KW UT WOS:000282642600025 PM 20702640 ER PT J AU Huang, JH Burke, P Yang, Y Seiss, K Beamon, J Cung, T Toth, I Pereyra, F Lichterfeld, M Yu, XG AF Huang, Jinghe Burke, Patrick Yang, Yue Seiss, Katherine Beamon, Jill Cung, Thai Toth, Ildiko Pereyra, Florencia Lichterfeld, Mathias Yu, Xu G. TI Soluble HLA-G Inhibits Myeloid Dendritic Cell Function in HIV-1 Infection by Interacting with Leukocyte Immunoglobulin-Like Receptor B2 SO JOURNAL OF VIROLOGY LA English DT Article ID PERIPHERAL-BLOOD; G MOLECULE; T-CELLS; ACTIVATION; DYSFUNCTION; ANTIGEN; CD4(+); LYMPHOCYTES; EXPRESSION; MATURATION AB Dendritic cells represent a specialized class of professional antigen-presenting cells that are responsible for priming and maintaining antigen-specific effector cell responses and regulating immune activation by cytokine secretion. In HIV-1 infection, myeloid dendritic cells are highly dysfunctional, but mechanisms contributing to their functional alterations are not well defined. Here, we show that soluble molecules of the nonclassical major histocompatibility complex class Ib (MHC-Ib) antigen HLA-G are highly upregulated in the plasma during progressive HIV-1 infection, while levels of membrane-bound HLA-G surface expression on dendritic cells, monocytes, and T cells only slightly differ among HIV-1 progressors, HIV-1 elite controllers, and HIV-1-negative persons. These elevated levels of soluble HLA-G in progressive HIV-1 infection likely result from increased secretion of intracellularly stored HLA-G molecules in monocytes and dendritic cells and contribute to a functional disarray of dendritic cells by inhibiting their antigen-presenting properties, while simultaneously enhancing their secretion of proinflammatory cytokines. Interestingly, we observed that these immunoregulatory effects of soluble HLA-G were mainly mediated by interactions with the myelomonocytic HLA class I receptor leukocyte immunoglobulin-like receptor B2 (LILRB2; ILT4), while binding of soluble HLA-G to its alternative high-affinity receptor, LILRB1 (ILT2), appeared to be less relevant for its immunomodulatory functions on dendritic cells. Overall, these results demonstrate a critical role for soluble HLA-G in modulating the functional characteristics of professional antigen-presenting cells in progressive HIV-1 infection and suggest that soluble HLA-G might represent a possible target for immunotherapeutic interventions in HIV-1-infected persons. C1 [Huang, Jinghe; Burke, Patrick; Yang, Yue; Seiss, Katherine; Beamon, Jill; Cung, Thai; Toth, Ildiko; Pereyra, Florencia; Yu, Xu G.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Yu, XG (reprint author), Harvard Univ, MIT, Ragon Inst MGH, 149,13th St, Charlestown, MA 02129 USA. EM xyu@partners.org RI Huang, Jinghe/O-1986-2015 FU U.S. National Institutes of Health [AI078799, AI074415]; Doris Duke Clinical Scientist Development Award; William and Melinda Gates Foundation; Mark and Lisa Schwartz Foundation FX This study was supported by the U.S. National Institutes of Health (to X.G.Y., AI078799 and AI074415). X.G.Y. and M.L. are both recipients of the Doris Duke Clinical Scientist Development Award. The recruitment of study patients was supported by the William and Melinda Gates Foundation and the Mark and Lisa Schwartz Foundation. NR 32 TC 21 Z9 24 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2010 VL 84 IS 20 BP 10784 EP 10791 DI 10.1128/JVI.01292-10 PG 8 WC Virology SC Virology GA 660KW UT WOS:000282642600032 PM 20702625 ER PT J AU Wright, JK Brumme, ZL Carlson, JM Heckerman, D Kadie, CM Brumme, CJ Wang, BX Losina, E Miura, T Chonco, F van der Stok, M Mncube, Z Bishop, K Goulder, PJR Walker, BD Brockman, MA Ndung'u, T AF Wright, Jaclyn K. Brumme, Zabrina L. Carlson, Jonathan M. Heckerman, David Kadie, Carl M. Brumme, Chanson J. Wang, Bingxia Losina, Elena Miura, Toshiyuki Chonco, Fundisiwe van der Stok, Mary Mncube, Zenele Bishop, Karen Goulder, Philip J. R. Walker, Bruce D. Brockman, Mark A. Ndung'u, Thumbi TI Gag-Protease-Mediated Replication Capacity in HIV-1 Subtype C Chronic Infection: Associations with HLA Type and Clinical Parameters SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; VIRAL LOAD; DISEASE PROGRESSION; ESCAPE MUTATIONS; SET-POINT; LYMPHOCYTE RESPONSES; ELITE CONTROLLERS; IMMUNE ESCAPE; HOST FACTORS AB The mechanisms underlying HIV-1 control by protective HLA class I alleles are not fully understood and could involve selection of escape mutations in functionally important Gag epitopes resulting in fitness costs. This study was undertaken to investigate, at the population level, the impact of HLA-mediated immune pressure in Gag on viral fitness and its influence on HIV-1 pathogenesis. Replication capacities of 406 recombinant viruses encoding plasma-derived Gag-protease from patients chronically infected with HIV-1 subtype C were assayed in an HIV-1-inducible green fluorescent protein reporter cell line. Viral replication capacities varied significantly with respect to the specific HLA-B alleles expressed by the patient, and protective HLA-B alleles, most notably HLA-B*81, were associated with lower replication capacities. HLA-associated mutations at low-entropy sites, especially the HLA-B*81-associated 186S mutation in the TL9 epitope, were associated with lower replication capacities. Most mutations linked to alterations in replication capacity in the conserved p24 region decreased replication capacity, while most in the highly variable p17 region increased replication capacity. Replication capacity also correlated positively with baseline viral load and negatively with baseline CD4 count but did not correlate with the subsequent rate of CD4 decline. In conclusion, there is evidence that protective HLA alleles, in particular HLA-B*81, significantly influence Gag-protease function by driving sequence changes in Gag and that conserved regions of Gag should be included in a vaccine aiming to drive HIV-1 toward a less fit state. However, the long-term clinical benefit of immune-driven fitness costs is uncertain given the lack of correlation with longitudinal markers of disease progression. C1 [Wright, Jaclyn K.; Chonco, Fundisiwe; van der Stok, Mary; Mncube, Zenele; Bishop, Karen; Goulder, Philip J. R.; Walker, Bruce D.; Ndung'u, Thumbi] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, ZA-4013 Durban, South Africa. [Brumme, Zabrina L.; Brockman, Mark A.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Brumme, Zabrina L.; Brumme, Chanson J.; Brockman, Mark A.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Carlson, Jonathan M.; Heckerman, David; Kadie, Carl M.] Microsoft Res, eSci Grp, Redmond, WA USA. [Wang, Bingxia; Losina, Elena] Massachusetts Gen Hosp, Program HIV Outcomes Res, Boston, MA 02114 USA. [Miura, Toshiyuki] Univ Tokyo, Inst Med Sci, Tokyo, Japan. [Goulder, Philip J. R.] Univ Oxford, Nuffield Dept Med, Dept Paediat, Oxford, England. [Goulder, Philip J. R.; Walker, Bruce D.; Ndung'u, Thumbi] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Goulder, Philip J. R.; Walker, Bruce D.; Ndung'u, Thumbi] Harvard Univ, Boston, MA 02115 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Ndung'u, T (reprint author), Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, 719 Umbilo Rd, ZA-4013 Durban, South Africa. EM ndungu@ukzn.ac.za OI Bishop, Karen/0000-0003-4935-7708; Ndung'u, Thumbi/0000-0003-2962-3992; Brumme, Chanson/0000-0003-2722-5288; Brockman, Mark/0000-0001-6432-1426 FU NIH [ROI-AI067073, NOI-AI-15422]; South African AIDS Vaccine Initiative; Ragon Institute Fund for Innovation and New International Initiatives; National Research Foundation; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology; Harvard University; Canadian Institutes for Health Research (CIHR) FX This research was funded by the NIH (grant ROI-AI067073, contract NOI-AI-15422), the South African AIDS Vaccine Initiative, and the Ragon Institute Fund for Innovation and New International Initiatives. J.K.W. was funded by the National Research Foundation and the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University. Z.L.B. was supported by a New Investigator Award from the Canadian Institutes for Health Research (CIHR). T.N. holds the South African Department of Science and Technology/National Research Foundation Research Chair in Systems Biology of HIV/AIDS. NR 47 TC 44 Z9 44 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2010 VL 84 IS 20 BP 10820 EP 10831 DI 10.1128/JVI.01084-10 PG 12 WC Virology SC Virology GA 660KW UT WOS:000282642600036 PM 20702636 ER PT J AU Kopcow, HD Cerdeira, S Husain, Z Stillman, I Lo, A Royle, C Thadhani, R Sukhatme, V Karumanchi, A AF Kopcow, Hernan D. Cerdeira, Sofia Husain, Zaheed Stillman, Isaac Lo, Agnes Royle, Caroline Thadhani, Rabi Sukhatme, Vikas Karumanchi, Ananth TI Hypoxia and TGF-beta 1 Turn NK Cells into Cells with Enhanced Angiogenic Potential and Limited Cytotoxicity SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Kopcow, Hernan D.; Cerdeira, Sofia; Husain, Zaheed; Stillman, Isaac; Lo, Agnes; Royle, Caroline; Sukhatme, Vikas; Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Thadhani, Rabi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kopcow, Hernan D.; Cerdeira, Sofia; Husain, Zaheed; Stillman, Isaac; Lo, Agnes; Royle, Caroline; Thadhani, Rabi; Sukhatme, Vikas; Karumanchi, Ananth] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Karumanchi, Ananth] Howard Hughes Med Inst, Chevy Chase, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2010 VL 19 IS 10 BP 1788 EP 1788 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 660WF UT WOS:000282676500038 ER PT J AU Holsen, LM Lawson, EA Ko, E Blum, J Klibanksi, A Goldstein, JM AF Holsen, Laura M. Lawson, Elizabeth A. Ko, Eunice Blum, Justine Klibanksi, Anne Goldstein, Jill M. TI Subcortical Food Reward Circuitry Deficits and Appetite-Regulatory Peptide Abnormalities in Women With Anorexia Nervosa SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Holsen, Laura M.; Ko, Eunice; Goldstein, Jill M.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Dept Med, Boston, MA 02115 USA. [Holsen, Laura M.; Goldstein, Jill M.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Holsen, Laura M.; Ko, Eunice; Goldstein, Jill M.] Harvard Univ, Sch Med, Connors Ctr Womens Hlth & Gender Biol, Dept Med, Cambridge, MA 02138 USA. [Lawson, Elizabeth A.; Blum, Justine; Klibanksi, Anne] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Goldstein, Jill M.] MIT, Athinoula Martinos Ctr Biomed Imaging, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2010 VL 19 IS 10 BP 1798 EP 1798 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 660WF UT WOS:000282676500070 ER PT J AU Holsen, LM Klibanski, A Hornig, M Whitfield-Gabrieli, S Goldstein, JM AF Holsen, Laura M. Klibanski, Anne Hornig, Mady Whitfield-Gabrieli, Susan Goldstein, Jill M. TI Stress Response Circuitry Hypoactivation, Hormonal Dysfunction, and Inflammation: Implications for Understanding Sex Differences in Depression SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Med, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Klibanski, Anne] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Klibanski, Anne] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hornig, Mady] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. [Hornig, Mady] Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY 10027 USA. [Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, Susan; Goldstein, Jill M.] MIT, Athinoula Martinos Ctr Biomed Imaging, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2010 VL 19 IS 10 BP 1802 EP 1802 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 660WF UT WOS:000282676500084 ER PT J AU Doty, ND Willoughby, BLB Lindahl, KM Malik, NM AF Doty, Nathan Daniel Willoughby, Brian L. B. Lindahl, Kristin M. Malik, Neena M. TI Sexuality Related Social Support Among Lesbian, Gay, and Bisexual Youth SO JOURNAL OF YOUTH AND ADOLESCENCE LA English DT Article DE Gay; Lesbian; Bisexual; Sexual minority; Stress; Social support; Resilience; Matching theory ID MENTAL-HEALTH; YOUNG-ADULTS; MINORITY ADOLESCENTS; BUFFERING HYPOTHESIS; LIFE STRESS; VICTIMIZATION; ORIENTATION; FAMILY; FRIENDS; SCHOOL AB Lesbian, gay, and bisexual ("LGB") youth may face significant stressors related to their sexual orientation. Few studies, however, have examined youth's experiences of support for coping with these stressors. The current study compared LGB youth's perceptions of support for sexuality stress to their support for other types of problems. The links between sexuality stress, sexuality support, and emotional distress were also examined. Ninety-eight LGB youth (ages 18-21, 33% female) rated support from family, heterosexual friends, and sexual minority friends for dealing with problems related, and not related, to their sexuality. From family and heterosexual friends, support for sexuality stress was less available than support for other stressors. Sexual minority friends provided the highest levels of sexuality support. In regression analyses, higher levels of sexuality support related to decreased emotional distress and buffered against the negative effects of sexuality stress on emotional distress. Sexuality support, although less available than other types of support, may be especially relevant to mental health among LGB youth. C1 [Doty, Nathan Daniel] Learning & Emot Assessment Program, Boston, MA 02114 USA. [Malik, Neena M.] Univ Miami, Dept Pediat, Coral Gables, FL 33124 USA. [Lindahl, Kristin M.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Doty, Nathan Daniel; Willoughby, Brian L. B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Doty, Nathan Daniel; Willoughby, Brian L. B.] Harvard Univ, Sch Med, Boston, MA USA. RP Doty, ND (reprint author), Learning & Emot Assessment Program, 5th Floor,151 Merrimac St, Boston, MA 02114 USA. EM ndoty@partners.org FU NICHD NIH HHS [R01 HD055372] NR 59 TC 49 Z9 49 U1 4 U2 22 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0047-2891 J9 J YOUTH ADOLESCENCE JI J. Youth Adolesc. PD OCT PY 2010 VL 39 IS 10 BP 1134 EP 1147 DI 10.1007/s10964-010-9566-x PG 14 WC Psychology, Developmental SC Psychology GA 635UG UT WOS:000280681600002 PM 20593304 ER PT J AU Brunelli, SM Chertow, GM Ankers, ED Lowrie, EG Thadhani, R AF Brunelli, Steven M. Chertow, Glenn M. Ankers, Elizabeth D. Lowrie, Edmund G. Thadhani, Ravi TI Importance of 3 h when dialyzing daily Reply SO KIDNEY INTERNATIONAL LA English DT Letter C1 [Brunelli, Steven M.] Brigham & Womens Hosp, Div Renal, Dept Med, Boston, MA 02115 USA. [Brunelli, Steven M.; Thadhani, Ravi] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Dept Med, Div Nephrol, Palo Alto, CA 94304 USA. [Ankers, Elizabeth D.; Thadhani, Ravi] Massachusetts Gen Hosp, Renal Unit, Dept Med, Boston, MA 02114 USA. RP Brunelli, SM (reprint author), Brigham & Womens Hosp, Div Renal, Dept Med, 75 Francis St,MRB 4, Boston, MA 02115 USA. EM sbrunelli@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2010 VL 78 IS 7 BP 710 EP 711 DI 10.1038/ki.2010.249 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 650CA UT WOS:000281824200020 ER PT J AU Kumbhani, DJ Bhatt, DL AF Kumbhani, Dharam J. Bhatt, Deepak L. TI Secondary prevention of stroke: can we do better than aspirin? SO LANCET NEUROLOGY LA English DT Editorial Material ID ANTIPLATELET THERAPY; ISCHEMIC-STROKE; METAANALYSIS; RISK C1 [Kumbhani, Dharam J.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kumbhani, DJ (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, 75 Francis St, Boston, MA 02115 USA. EM dlbhattmd@post.harvard.edu NR 11 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 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD OCT PY 2010 VL 9 IS 10 BP 942 EP 943 DI 10.1016/S1474-4422(10)70217-9 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 672WC UT WOS:000283616700002 PM 20833590 ER PT J AU Marsh, L AF Marsh, Laura TI Treatment of Lewy-body dementias and psychopathology SO LANCET NEUROLOGY LA English DT Editorial Material ID PARKINSONS-DISEASE; BODIES; SYSTEM C1 [Marsh, Laura] Baylor Coll Med, Dept Psychiat, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Marsh, Laura] Baylor Coll Med, Dept Neurol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Marsh, L (reprint author), Baylor Coll Med, Dept Psychiat, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. EM laura.marsh2@va.gov NR 9 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD OCT PY 2010 VL 9 IS 10 BP 943 EP 945 DI 10.1016/S1474-4422(10)70208-8 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 672WC UT WOS:000283616700003 PM 20729149 ER PT J AU Heinrich, MC AF Heinrich, Michael C. TI Imatinib treatment of metastatic GIST: don't stop (believing) SO LANCET ONCOLOGY LA English DT Editorial Material ID GASTROINTESTINAL STROMAL TUMORS; STEM-CELLS; LEUKEMIA C1 Portland VA Med Ctr, Portland, OR USA. [Heinrich, Michael C.] OHSU Knight Canc Inst, Portland, OR USA. RP Heinrich, MC (reprint author), Portland VA Med Ctr, Portland, OR USA. EM heinrich@ohsu.edu NR 6 TC 6 Z9 7 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 OCT PY 2010 VL 11 IS 10 BP 910 EP 911 DI 10.1016/S1470-2045(10)70225-4 PG 2 WC Oncology SC Oncology GA 667RE UT WOS:000283210600004 PM 20864404 ER PT J AU Lipshultz, SE Scully, RE Lipsitz, SR Sallan, SE Silverman, LB Miller, TL Borry, EV Asselin, BL Athale, U Clavell, LA Larsen, E Moghrabi, A Samson, Y Michon, B Schorin, MA Cohen, HJ Neuberg, DS Orav, EJ Colan, SD AF Lipshultz, Steven E. Scully, Rebecca E. Lipsitz, Stuart R. Sallan, Stephen E. Silverman, Lewis B. Miller, Tracie L. Borry, Elly V. Asselin, Barbara L. Athale, Uma Clavell, Luis A. Larsen, Eric Moghrabi, Albert Samson, Yvan Michon, Bruno Schorin, Marshall A. Cohen, Harvey J. Neuberg, Donna S. Orav, E. John Colan, Steven D. TI Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial SO LANCET ONCOLOGY LA English DT Article ID CHILDHOOD-CANCER SURVIVOR; PEDIATRIC HODGKINS-DISEASE; CARDIAC TROPONIN-T; PROSPECTIVE (PCHIV)-C-2-H-2 MULTICENTER; ANTHRACYCLINE CARDIOTOXICITY; SECONDARY MALIGNANCIES; 5-YEAR SURVIVORS; ADULT SURVIVORS; LATE MORTALITY; CLINICAL-IMPLICATIONS AB Background Doxorubicin chemotherapy is associated with cardiomyopathy. Dexrazoxane reduces cardiac damage during treatment with doxorubicin in children with acute lymphoblastic leukaemia (ALL). We aimed to establish the long-term effect of dexrazoxane on the subclinical state of cardiac health in survivors of childhood high-risk ALL 5 years after completion of doxorubicin treatment. Methods Between January, 1996, and September, 2000, children with high-risk ALL were enrolled from nine centres in the USA, Canada, and Puerto Rico. Patients were assigned by block randomisation to receive ten doses of 30 mg/m(2) doxorubicin alone or the same dose of doxorubicin preceded by 300 mg/m(2) dexrazoxane. Treatment assignment was obtained through a telephone call to a centralised registrar to conceal allocation. Investigators were masked to treatment assignment but treating physicians and patients were not; however, investigators, physicians, and patients were masked to study serum cardiac troponin-T concentrations and echocardiographic measurements. The primary endpoints were late left ventricular structure and function abnormalities as assessed by echocardiography; analyses were done including all patients with data available after treatment completion. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00165087. Findings 100 children were assigned to doxorubicin (66 analysed) and 105 to doxorubicin plus dexrazoxane (68 analysed). 5 years after the completion of doxorubicin chemotherapy, mean left ventricular fractional shortening and end-systolic dimension Z scores were significantly worse than normal for children who received doxorubicin alone (left ventricular fractional shortening: -0.82, 95% CI -1.31 to -0.33; end-systolic dimension: 0.57, 0.21-0-93) but not for those who also received dexrazoxane (-0.41, -0-88 to 0.06; 0.15, -0.20 to 0.51). The protective effect of dexrazoxane, relative to doxorubicin alone, on left ventricular wall thickness (difference between groups: 0.47, 0.46-0.48) and thickness-to-dimension ratio (0.66, 0.64-0.68) were the only statistically significant characteristics at 5 years. Subgroup analysis showed dexrazoxane protection (p=0.04) for left ventricular fractional shortening at 5 years in girls (1.17, 0.24-2.11), but not in boys (-0.10, -0.87 to 0.68). Similarly, subgroup analysis showed dexrazoxane protection (p=0.046) for the left ventricular thickness-to-dimension ratio at 5 years in girls (1.15, 0.44-1.85), but not in boys (0.19, -0.42 to 0.81). With a median follow-up for recurrence and death of 8.7 years (range 1.3-12.1), event-free survival was 77% (95% CI 67-84) for children in the doxorubicin-alone group, and 76% (67-84) for children in the doxorubicin plus decrazoxane group (p=0.99). Interpretation Dexrazoxane provides long-term cardioprotection without compromising oncological efficacy in doxorubicin-treated children with high-risk ALL. Dexrazoxane exerts greater long-term cardioprotective effects in girls than in boys. C1 [Lipshultz, Steven E.] Univ Miami, Leonard M Miller Sch Med, Dept Pediat D820, Miami, FL 33101 USA. [Lipshultz, Steven E.; Scully, Rebecca E.; Miller, Tracie L.] Univ Miami, Jackson Mem Med Ctr, Holtz Childrens Hosp, Miami, FL USA. [Lipshultz, Steven E.; Scully, Rebecca E.; Miller, Tracie L.] Univ Miami Sylvester Comprehens Canc Ctr, Miami, FL USA. [Lipsitz, Stuart R.; Orav, E. John] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sallan, Stephen E.; Silverman, Lewis B.; Neuberg, Donna S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Borry, Elly V.] Genzyme Corp, Cambridge, MA USA. [Asselin, Barbara L.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Athale, Uma] McMaster Univ, Hamilton, ON, Canada. [Clavell, Luis A.] San Jorge Childrens Hosp, San Juan, PR USA. [Larsen, Eric] Maine Childrens Canc Program, Portland, ME USA. [Moghrabi, Albert] Hop St Justine, Montreal, PQ H3T 1C5, Canada. [Samson, Yvan; Michon, Bruno] Ctr Hosp Univ Quebec, Quebec City, PQ, Canada. [Schorin, Marshall A.] Inova Fairfax Hosp Children, Falls Church, VA USA. [Cohen, Harvey J.] Stanford Univ, Sch Med, Stanford, CA USA. [Sallan, Stephen E.; Silverman, Lewis B.; Colan, Steven D.] Childrens Hosp, 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 US 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; Roche Diagnostics; Pfizer; Novartis FX US National Institutes of Health, Children's Cardiomyopathy Foundation, University of Miami Women's Cancer Association, Lance Armstrong Foundation, Roche Diagnostics, Pfizer, and Novartis.; This study was supported by grants from the US National Institutes of Health (HL072705, HL078522, HL053392, CA127642, CA068484, HD052104, AI50274, CA068484, HD052102, HL087708, HL079233, HL004537, HL087000, HL007188, HL094100, HL095127, and HD80002), Children's Cardiomyopathy Foundation, University of Miami Women's Cancer Association, Lance Armstrong Foundation, Roche Diagnostics, Pfizer, and Novartis. We thank Suzanne E Dahlberg for her statistical advice; and Vivian I Franco and Jacqueline M Henkel for their editorial assistance. NR 91 TC 123 Z9 129 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2010 VL 11 IS 10 BP 950 EP 961 DI 10.1016/S1420-2045(10)70204-7 PG 12 WC Oncology SC Oncology GA 667RE UT WOS:000283210600021 PM 20850381 ER PT J AU Friedman, AD Burns, JA Heaton, JT Zeitels, SM AF Friedman, Aaron D. Burns, James A. Heaton, James T. Zeitels, Steven M. TI Early Versus Late Injection Medialization for Unilateral Vocal Cord Paralysis SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Conference on Triological-Society/Combined Otolaryngology Spring Meeting/143rd Annual Meeting of the American-Otological-Society CY APR 28-MAY 02, 2010 CL Las Vegas, NV SP Amer Otolog Soc DE Vocal cord paralysis; injections; dysphonia; larynx/surgery ID FOLD PARALYSIS; ADDUCTION ARYTENOPEXY; LARYNGOPLASTY; IMMOBILITY AB Objectives: To evaluate whether the timing of early (<6 months from time of nerve injury) vs. late (>6 months) injection medialization laryngoplasty impacts the need for subsequent open-neck reconstruction to restore vocal function in patients with unilateral vocal cord paralysis. Study Design: Retrospective chart review. Methods: A total of 112 outpatient or hospitalized adults with dysphonia resulting from postsurgical or idiopathic unilateral vocal cord paralysis were identified who were injected as initial treatment within 1 year of onset of their paralysis. All subjects underwent awake, transoral, paraglottic injection with absorbable hyaluronic-acid gel. Patients with documented recovery of vocal cord mobility (22), active disease directly affecting the recurrent laryngeal nerve (8), <3 months of follow-up after injection (time for gel to be reabsorbed) (34), or deaths within 1 year after the onset of paralysis (13) were excluded, leaving a study population of 35 patients. Results: Twenty of 32 (62.5%) patients with early injection medialization maintained an adequate voice, obviating the need for open-neck phonosurgical reconstruction; their follow-up from onset of paralysis ranged from 4.0 to 41.8 months (mean 15.2). None of the three patients undergoing late injection (>6 months postparalysis) avoided phonosurgical reconstruction (P = .03, chi(2) test). Conclusions: Patients receiving early injection medialization for vocal cord paralysis were less likely to require transcervical reconstruction. We believe that early medialization creates a more favorable vocal cord position for phonation that can be maintained by synkinetic reinnervation, in contrast to the final position of a lateralized vocal cord being determined solely by reinnervation. C1 [Friedman, Aaron D.; Burns, James A.; Heaton, James T.; Zeitels, Steven M.] Harvard Univ, Ctr Laryngeal Surg & Voice Rehabil, Massachusetts Gen Hosp, Dept Surg,Med Sch, Boston, MA 02114 USA. RP Friedman, AD (reprint author), Harvard Univ, Ctr Laryngeal Surg & Voice Rehabil, Massachusetts Gen Hosp, Dept Surg,Med Sch, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM afriedman3@partners.org NR 12 TC 51 Z9 52 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2010 VL 120 IS 10 BP 2042 EP 2046 DI 10.1002/lary.21097 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 661QP UT WOS:000282743100024 PM 20824787 ER PT J AU Chan, NPY Ho, SGY Shek, SYN Yeung, CK Chan, HH AF Chan, Nicola P. Y. Ho, Stephanie G. Y. Shek, Samantha Y. N. Yeung, Chi K. Chan, Henry H. TI A Case Series of Facial Depigmentation Associated With Low Fluence Q-Switched 1,064 nm Nd/YAG Laser for Skin Rejuvenation and Melasma SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE laser toning; laser facial; depigmentation; leucoderma punctata; Q-switched 1,064 nm Nd:YAG; laser; non-ablative; skin rejuvenation; melasma ID INTENSE PULSED-LIGHT; ND-YAG LASER; REFRACTORY MELASMA; NDYAG LASER; LEUKODERMA PUNCTATA; ALEXANDRITE LASER; PHOTOTHERMOLYSIS; HYPOPIGMENTATION; CO2-LASER; DESIGN AB Background and Objective: In recent years, "laser toning" using low fluence, large spot size, multiple passed Q-switched 1,064 nm Nd:YAG laser has gained much popularity in Asian countries for non-ablative skin rejuvenation and the treatment of melasma. This case series highlights one of the complications associated with laser toning, which is facial depigmentation. Materials and Methods: Fourteen patients with laser toning-associated facial depigmentation were assessed with cross-polarized and ultraviolet (UV) photographic images. The laser toning regimens received by these patients, as well as the treatment given for depigmentation, were analyzed retrospectively. Results: All 14 patients were Chinese females, 9 of whom received laser toning for non-ablative skin rejuvenation and the other 5 for melasma. The treatment regimens received by these patients were highly variable. The total number of treatments received ranged from 6 to 50 (mean 22.07). In all cases, UV photographic images demonstrated facial mottled depigmentation. Laser toning failed to significantly improve melasma in all five patients. Five patients received targeted narrowband UVB for depigmentation with good clinical results. Conclusions: Laser toning with low fluence Q-switched 1,064 nm Nd:YAG laser for skin rejuvenation and melasma can be associated with mottled depigmentation. With laser toning being frequently performed, this complication may become more commonly encountered in clinical practice. The depigmentation can appear after only a few treatment sessions, and can cause much disfigurement, especially in cases with background melasma. Further studies on laser toning are needed with the view to optimizing efficacy and minimizing side-effects. Lasers Surg. Med. 42:712- 719, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Chan, Nicola P. Y.; Ho, Stephanie G. Y.; Shek, Samantha Y. N.; Yeung, Chi K.; Chan, Henry H.] Univ Hong Kong, Div Dermatol, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Chan, Henry H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Chan, HH (reprint author), Hong Kong Dermatol & Laser Ctr, 13th Floor,Club Lusitano,16 Ice House St, Hong Kong, Hong Kong, Peoples R China. EM hhlchan@hku.hk RI Yeung, Chi Keung/L-4795-2013; Chan, Henry Hin Lee/L-2267-2013 NR 34 TC 48 Z9 51 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD OCT PY 2010 VL 42 IS 8 BP 712 EP 719 DI 10.1002/lsm.20956 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 663VH UT WOS:000282917800004 PM 20848553 ER PT J AU Terpos, E Dimopoulos, MA Sezer, O Roodman, D Abildgaard, N Vescio, R Tosi, P Garcia-Sanz, R Davies, F Chanan-Khan, A Palumbo, A Sonneveld, P Drake, MT Harousseau, JL Anderson, KC Durie, BGM AF Terpos, E. Dimopoulos, M. A. Sezer, O. Roodman, D. Abildgaard, N. Vescio, R. Tosi, P. Garcia-Sanz, R. Davies, F. Chanan-Khan, A. Palumbo, A. Sonneveld, P. Drake, M. T. Harousseau, J-L Anderson, K. C. Durie, B. G. M. CA Int Myeloma Working Grp TI The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group SO LEUKEMIA LA English DT Review DE myeloma; bone markers; NTX; CTX; ICTP ID CARBOXY-TERMINAL TELOPEPTIDE; RESISTANT ACID-PHOSPHATASE; I COLLAGEN ICTP; NONCOLLAGENOUS MATRIX PROTEINS; SERUM OSTEOPROTEGERIN LEVELS; STEM-CELL TRANSPLANTATION; SKELETAL-RELATED EVENTS; ZOLEDRONIC ACID; RESORPTION MARKERS; ISOFORM 5B AB Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic lesions rarely heal and X-rays are of limited value in monitoring bone destruction during anti-myeloma or anti-resorptive treatment. Biochemical markers of bone resorption (amino-and carboxy-terminal cross-linking telopeptide of type I collagen (NTX and CTX, respectively) or CTX generated by matrix metalloproteinases (ICTP)) and bone formation provide information on bone dynamics and reflect disease activity in bone. These markers have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX and serum ICTP are elevated in myeloma patients with osteolytic lesions and correlate with advanced disease stage. Furthermore, urinary NTX and serum ICTP correlate with risk for skeletal complications, disease progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti-myeloma therapies and provides information on novel markers that may be of particular interest in the near future. Leukemia (2010) 24, 1700-1712; doi:10.1038/leu.2010.173; published online 2 September 2010 C1 [Terpos, E.; Dimopoulos, M. A.; Int Myeloma Working Grp] Univ Athens, Sch Med, Dept Clin Therapeut, Athens 11528, Greece. [Sezer, O.] Univ Med Ctr Hamburg, Dept Hematol Oncol & Stem Cell Transplantat, Hamburg, Germany. [Roodman, D.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. [Abildgaard, N.] Odense Univ, Dept Hematol, Odense, Denmark. [Vescio, R.; Durie, B. G. M.] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. [Tosi, P.] Univ Bologna, Inst Hematol & Oncol, Bologna, Italy. [Garcia-Sanz, R.] Hosp Univ Salamanca, Dept Hematol, Salamanca, Spain. [Davies, F.] Inst Canc Res, Sutton, Surrey, England. [Davies, F.] Royal Marsden Hosp, Sect Haematooncol, Sutton, Surrey, England. [Chanan-Khan, A.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Palumbo, A.] Univ Turin, Div Ematol, Turin, Italy. [Sonneveld, P.] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Drake, M. T.] Mayo Clin, Div Endocrinol, Rochester, MN USA. [Harousseau, J-L] Inst Biol, Hematol Lab, Nantes, France. [Anderson, K. C.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. RP Terpos, E (reprint author), Univ Athens, Sch Med, Alexandra Gen Hosp, Dept Clin Therapeut, 80 Vas Sofias Ave, Athens 11528, Greece. EM eterpos@med.uoa.gr RI IBSAL, Secretaria/H-3719-2011; Waage, Anders/D-7705-2013; Garcia-Sanz, Ramon/B-7986-2017; OI Garcia-Sanz, Ramon/0000-0003-4120-2787; SAN MIGUEL, JESUS/0000-0002-9183-4857 NR 97 TC 37 Z9 42 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2010 VL 24 IS 10 BP 1700 EP 1712 DI 10.1038/leu.2010.173 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA 665SQ UT WOS:000283056200005 PM 20811404 ER PT J AU Rourke, M Anderson, KC Ghobrial, IM AF Rourke, Meghan Anderson, Kenneth C. Ghobrial, Irene M. TI Review of clinical trials conducted in Waldenstrom macroglobulinemia and recommendations for reporting clinical trial responses in these patients SO LEUKEMIA & LYMPHOMA LA English DT Review DE Lymphoma and Hodgkin disease; prognostication; chemotherapeutic approaches ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; PHASE-II TRIAL; EXTENDED RITUXIMAB THERAPY; PROGNOSTIC-FACTORS; FLUDARABINE THERAPY; MULTIPLE-MYELOMA; CYCLOPHOSPHAMIDE; COMBINATION; 2-CHLORODEOXYADENOSINE AB Many novel therapeutic agents are being tested in clinical trials for Waldenstrom macroglobulinemia (WM). However, given the paucity of large clinical trials in WM, the establishment of a standard treatment regimen that can be used for comparison of response has become challenging. We therefore performed a review of published clinical trials in WM. Systematic searches of the PubMed and Medline databases, including The Cochrane Library, were performed for the search terms: clinical trials, Waldenstrom, macroglobulinemia, and lymphoplasmacytic lymphoma. Studies of transplant in WM are beyond the scope of this review and were excluded. A total of 44 clinical trials were found in this search (38 full articles, six abstracts). Of these, 11 were performed in patients with untreated WM, 14 in patients with relapsed or refractory WM, 17 in both upfront and relapsed or refractory WM, and two studies did not provide this information. Based on this review, we recommend new response criteria and definitions of time to event analysis to be used in future clinical trials of WM. This review of the published literature would serve as a reference for comparison of response and survival analysis in current clinical trials. C1 [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Kirsch Lab WM, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Kirsch Lab WM, 44 Binney St,D1B27, Boston, MA 02115 USA. EM Irene_ghobrial@dfci.harvard.edu FU Kirsch Laboratory for Waldenstrom Macroglobulinemia; Heje Fellowship for WM FX This study was supported in part by the Kirsch Laboratory for Waldenstrom Macroglobulinemia and the Heje Fellowship for WM. NR 71 TC 12 Z9 12 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 2010 VL 51 IS 10 BP 1779 EP 1792 DI 10.3109/10428194.2010.499977 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 663NS UT WOS:000282895200007 PM 20795787 ER PT J AU Musunuru, K AF Musunuru, Kiran TI Atherogenic Dyslipidemia: Cardiovascular Risk and Dietary Intervention SO LIPIDS LA English DT Review DE Lipids; Lipoproteins; Cardiovascular diseases; Genetics ID LOW-DENSITY-LIPOPROTEIN; LDL PARTICLE-SIZE; CORONARY-HEART-DISEASE; LOW-FAT DIET; FAMILIAL COMBINED HYPERLIPIDEMIA; MAGNETIC-RESONANCE SPECTROSCOPY; APOLIPOPROTEIN-A-I; ARTERY-DISEASE; GENETIC-DETERMINANTS; PLASMA TRIGLYCERIDE AB Atherogenic dyslipidemia comprises a triad of increased blood concentrations of small, dense low-density lipoprotein (LDL) particles, decreased high-density lipoprotein (HDL) particles, and increased triglycerides. A typical feature of obesity, the metabolic syndrome, insulin resistance, and type 2 diabetes mellitus, atherogenic dyslipidemia has emerged as an important risk factor for myocardial infarction and cardiovascular disease. A number of genes have now been linked to this pattern of lipoprotein changes. Low-carbohydrate diets appear to have beneficial lipoprotein effects in individuals with atherogenic dyslipidemia, compared to high-carbohydrate diets, whereas the content of total fat or saturated fat in the diet appears to have little effect. Achieving a better understanding of the genetic and dietary influences underlying atherogenic dyslipidemia may provide clues to improved interventions to reduce the risk of cardiovascular disease in high-risk individuals. C1 [Musunuru, Kiran] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Musunuru, Kiran] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Musunuru, K (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, 185 Cambridge St,CPZN 5th floor, Boston, MA 02114 USA. EM kmusunuru@partners.org NR 49 TC 70 Z9 72 U1 2 U2 19 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 J9 LIPIDS JI Lipids PD OCT PY 2010 VL 45 IS 10 BP 907 EP 914 DI 10.1007/s11745-010-3408-1 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 670IU UT WOS:000283415600004 PM 20524075 ER PT J AU Naugler, WE Sonnenberg, A AF Naugler, Willscott E. Sonnenberg, Amnon TI Survival and Cost-Effectiveness Analysis of Competing Strategies in the Management of Small Hepatocellular Carcinoma SO LIVER TRANSPLANTATION LA English DT Article ID HEPATITIS-C VIRUS; RADIOFREQUENCY ABLATION; COMPUTED-TOMOGRAPHY; NATURAL-HISTORY; GROWTH-RATE; COMPENSATED CIRRHOSIS; CLINICAL-TRIALS; UNITED-STATES; LIVER-TUMORS; COMPLICATIONS AB The aim of the present study is to compare the survival rates and cost-effectiveness of different treatment strategies for small (<2 cm) hepatocellular carcinoma (HCC). Markov chains are developed to model different management strategies for patients with compensated cirrhosis and small HCC. Probabilities of progression and survival and the likelihood of orthotopic liver transplantation are taken from the literature and incorporated into the models. As a starting population, 1000 patients are followed over a period of 10 years. Patients treated immediately with transarterial chemoembolization (TACE) or radiofrequency ablation (RFA) live as long as or longer than patients who are monitored expectantly with the intention of liver transplantation once the HCC has grown larger than 2 cm and a higher transplant priority score becomes available. With TACE, immediate treatment results in an average survival time of 4.269 years versus 4.324 years with the monitoring strategy. With RFA, immediate treatment results in an average survival time of 5.273 years versus 5.236 years with the monitoring strategy. In addition, the cost analysis shows that immediate treatment with either TACE or RFA is less expensive than monitoring. The better cost-effectiveness of immediate therapy versus the monitoring strategy remains robust and unaffected by variations of the assumptions built into the model. In conclusion, in patients with compensated cirrhosis and small HCC, a strategy of immediate treatment with either TACE or RFA prevails over a strategy of expectant monitoring with the intention of transplantation. Liver Transpl 16: 1186-1194, 2010. (C) 2010 AASLD. C1 [Naugler, Willscott E.] Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Naugler, WE (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM nauglers@ohsu.edu NR 39 TC 27 Z9 28 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD OCT PY 2010 VL 16 IS 10 BP 1186 EP 1194 DI 10.1002/lt.22129 PG 9 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 665XH UT WOS:000283070000009 PM 20879017 ER PT J AU Keith, RL Karoor, V Mozer, AB Hudish, TM Le, M Miller, YE AF Keith, Robert L. Karoor, Vijaya Mozer, Anthony B. Hudish, Tyler M. Le, Mysan Miller, York E. TI Chemoprevention of murine lung cancer by gefitinib in combination with prostacyclin synthase overexpression SO LUNG CANCER LA English DT Article DE Chemoprevention; Lung cancer; Transgenic mice; Src; EGFR; Gefitinib; Prostacyclin ID GROWTH-FACTOR RECEPTOR; PULMONARY PROSTACYCLIN; TRANSGENIC MICE; TUMOR-GROWTH; CELL-LINES; EXPRESSION; ADENOCARCINOMA; INHIBITION; SRC; TUMORIGENESIS AB Introduction: We hypothesized that the combination of the EGFR tyrosine kinase inhibitor (TKI) gefitinib with the powerful chemopreventive manipulation of lung-specific transgenic prostacyclin synthase (PGIS) overexpression on tumorigenesis in FVB/N mice would result in augmented chemoprevention. Materials and methods: Wildtype and littermate PGIS overexpressors (OE) were given urethane, 1 mg/kg i.p. followed by thrice weekly i.p. injections of gefitinib, 50 mg/kg or 100 mg/kg, or vehicle. Pulmonary adenomas were enumerated and measured. Results: Gefitinib at either 50 mg/kg or 100 mg/kg administered i.p. three times weekly was effective in inhibiting EGF induced EGFR tyrosine phosphorylation and downstream signaling. The PGIS overexpressors showed significant decreases in tumor multiplicity consistent with prior studies. Gefitinib had no effect on tumor multiplicity or volume in wildtype mice. Among the PGIS overexpressors, a significant reduction in tumor multiplicity was shown in the 50 mg/kg, but not the 100 mg/kg, gefitinib treatment group vs. vehicle control animals (1.13 +/- 0.29 vs. 2.29 +/- 0.32 tumors/mouse, p = 0.015). We examined the phosphorylation status in selected downstream effectors of EGFR (Erk, Akt, Src, PTEN). The major difference in the 50 mg/kg vs. 100 mg/kg group was an increase in p-Src in the PGIS OE mice receiving the higher dose. Conclusion: We conclude that gefitinib alone has no chemopreventive efficacy in this model; it augmented the effect of PGIS overexpression at 50 mg/kg but not 100 mg/kg. Increased p-Src is correlated with loss of efficacy at the higher dose, suggesting the potential for combined EGFR and Src inhibition strategies in chemoprevention. (C) 2010 Published by Elsevier Ireland Ltd. C1 [Keith, Robert L.; Mozer, Anthony B.; Hudish, Tyler M.; Le, Mysan; Miller, York E.] Vet Adm Med Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80220 USA. [Keith, Robert L.; Karoor, Vijaya; Miller, York E.] Univ Colorado, Dept Med, Denver, CO 80262 USA. RP Miller, YE (reprint author), Denver VA Med Ctr, Dept Med, 1055 Clermont St,Pulm 111A, Denver, CO 80220 USA. EM york.miller@ucdenver.edu FU Department of Veterans Affairs; NCI [P50 CA58187] FX Supported by Department of Veterans Affairs Merit Review Grants (YEM and RLK) and NCI P50 CA58187 (SPORE in Lung Cancer, YEM and RLK). NR 26 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2010 VL 70 IS 1 BP 37 EP 42 DI 10.1016/j.lungcan.2010.01.004 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 658QE UT WOS:000282503700006 PM 20116128 ER PT J AU Chaudhry, S Arena, RA Hansen, JE Lewis, GD Myers, JN Sperling, LS LaBudde, BD Wasserman, K AF Chaudhry, Sundeep Arena, Ross A. Hansen, James E. Lewis, Gregory D. Myers, Jonathan N. Sperling, Laurence S. LaBudde, Brian D. Wasserman, Karlman TI The Utility of Cardiopulmonary Exercise Testing to Detect and Track Early-Stage Ischemic Heart Disease SO MAYO CLINIC PROCEEDINGS LA English DT Article ID CORONARY-ARTERY-DISEASE; CARDIAC REHABILITATION; MORTALITY; WOMEN; MEN; METAANALYSIS; PREDICTOR; NIACIN; TRIAL AB Evidence demonstrating the potential value of noninvasive cardiopulmonary exercise testing (CPET) to accurately detect exercise-induced myocardial ischemia is emerging. This case-based concept report describes CPET abnormalities in an asymptomatic at-risk man with suspected early-stage ischemic heart disease. When CPET was repeated 1 year after baseline assessment, his cardiovascular function had worsened, and an anti-atherosclerotic regimen was initiated. When the patient was retested after 3.3 years, the diminished left ventricular function had reversed with pharmacotherapy directed at decreasing cardiovascular events in patients with coronary artery disease. Thus, in addition to identifying appropriate patients in need of escalating therapy for atherosclerosis, CPET was useful in monitoring progression and reversal of abnormalities of the coronary circulation in a safe and cost-effective manner without the use of radiation. Serial CPET parameters may be useful to track changes marking the progression and/or regression of the underlying global ischemic burden. Mayo Clin Proc. 2010;85(10):928-932 C1 [Chaudhry, Sundeep; LaBudde, Brian D.] MET TEST, Dept Dev, Atlanta, GA USA. [Arena, Ross A.] Virginia Commonwealth Univ, Dept Phys Therapy, Richmond, VA 23284 USA. [Hansen, James E.; Wasserman, Karlman] Harbor UCLA Med Ctr, Div Resp & Crit Care Physiol & Med, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Lewis, Gregory D.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Myers, Jonathan N.] Stanford Univ, VA Palo Alto Hlth Care Syst, Div Cardiol, Palo Alto, CA 94304 USA. [Sperling, Laurence S.] Emory Univ, Div Prevent Cardiol, Atlanta, GA 30322 USA. RP Chaudhry, S (reprint author), 1117 Perimeter Ctr W,Ste W-211, Atlanta, GA 30338 USA. EM schaudhry@mettest.net RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 NR 21 TC 4 Z9 5 U1 0 U2 1 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2010 VL 85 IS 10 BP 928 EP 932 DI 10.4065/mcp.2010.0183 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 670VF UT WOS:000283454700008 PM 20884826 ER PT J AU Cedfeldt, AS Bower, EA English, C Grady-Weliky, TA Girard, DE Choi, D AF Cedfeldt, Andrea S. Bower, Elizabeth A. English, Clea Grady-Weliky, Tana A. Girard, Donald E. Choi, Dongseok TI Personal time off and residents' career satisfaction, attitudes and emotions SO MEDICAL EDUCATION LA English DT Article ID INTERNAL-MEDICINE RESIDENTS; HEALTH-CARE; BURNOUT; PHYSICIANS; PROGRAMS; STRESS; PREDICTORS; STUDENTS AB OBJECTIVES Doctors who are satisfied with their careers have less stress and burnout and are less likely to make medical errors and more likely to provide a higher quality of patient care. In response to reports that residents experienced barriers to taking time off, Oregon Health and Science University designed a survey to evaluate residents' awareness of their programmes' policies for time off, their ability to find time for personal needs, and associations of both with career satisfaction, emotions and training experience. METHODS All 675 residents in a large, urban, tertiary care academic medical centre located in the USA were invited to participate in a confidential, web-based, cross-sectional survey in 2008; 66% completed the survey. The survey instrument consisted of a variety of items including yes/no, multiple choice, Likert scale and narrative response types. RESULTS Only 41% of respondents were aware of their programmes' policies regarding time off. Residents who reported awareness of a policy were more able to find time to take care of personal needs (odds ratio = 1.553, p = 0.026). These respondents reported more positive experiences and emotions, fewer negative experiences and emotions, higher levels of career satisfaction and relatively less perceived stress than those who were unaware of a time-off policy. In addition, these respondents reported, on average, fewer work and more sleep hours. CONCLUSIONS Our results highlight the importance of ensuring mechanisms for residents to find time to fulfil personal needs in order to enhance resident well-being and career satisfaction. Ensuring resident awareness of time-off policies is one way to do this. Our study demonstrates that ensuring residents are able to find time for personal needs has significant consequences with respect to resident perceptions of well-being and may be an effective strategy to promote career satisfaction and prevent burnout. C1 [Cedfeldt, Andrea S.; Girard, Donald E.] Oregon Hlth & Sci Univ, Div Grad Med Educ, Portland, OR 97239 USA. [Cedfeldt, Andrea S.] Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR USA. [Bower, Elizabeth A.; Girard, Donald E.] Oregon Hlth & Sci Univ, Div Continuing Med Educ, Portland, OR 97239 USA. [Bower, Elizabeth A.; Girard, Donald E.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [English, Clea] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97239 USA. [Grady-Weliky, Tana A.] Oregon Hlth & Sci Univ, Off Educ & Student Affairs, Portland, OR 97239 USA. [Grady-Weliky, Tana A.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. RP Choi, D (reprint author), Oregon Hlth & Sci Univ, Div Grad Med Educ, 3181 SW Sam Jackson Pk Rd,CB669, Portland, OR 97239 USA. EM choid@ohsu.edu OI Bower, Elizabeth/0000-0001-5331-4378 NR 32 TC 8 Z9 8 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0308-0110 J9 MED EDUC JI Med. Educ. PD OCT PY 2010 VL 44 IS 10 BP 977 EP 984 DI 10.1111/j.1365-2923.2010.03773.x PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 659BC UT WOS:000282541000007 PM 20880367 ER PT J AU Makredes, M Hui, SK Kimball, AB AF Makredes, Maryanne Hui, Shiu Kee Kimball, Alexa B. TI Melanoma in Hong Kong between 1983 and 2002: a decreasing trend in incidence observed in a complex socio-political and economic setting SO MELANOMA RESEARCH LA English DT Article DE epidemiology; Hong Kong; melanoma incidence; melanoma mortality ID MALIGNANT-MELANOMA AB The aim of this study was to examine the incidence and mortality of cutaneous melanoma (CM) in Hong Kong. The epidemiology, clinical, and pathological features of melanoma in Asians are different from those in the European population, yet there is little in the literature that describes about melanoma in Asians. Data from the Hong Kong Cancer Registry from 1983 to 2002 were collected and reviewed. Population-based data were analyzed, focusing on the mortality and incidence rates over this 20-year period. The mean Hong Kong CM incidence rate between 1983 and 2002 was 0.8/100 000 for men and 0.6/100 000 for women. There was an overall decrease in the incidence of CM in Hong Kong between 1983 and 2002 (P < 0.001). The crude mortality rate of melanoma varied from year-to-year in Hong Kong between 1983 and 2002, showing an overall increase within this period (P < 0.001). Unlike most parts of the world, the overall incidence in Hong Kong is shown to trend downward between 1983 and 2002. Various factors including ethnic shifts within the Hong Kong population and the organization of the health care system may play a role in this observation. In addition, the mortality of melanoma increased between 1940 and 1990 in most parts of the world, but in Hong Kong, the mortality rate in the past 20 years reveals a modest upward trend. Its significance requires further investigation. Melanoma Res 20: 427-430 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Makredes, Maryanne] Univ Massachusetts, Med Ctr, Dept Dermatol, Worcester, MA USA. [Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Hui, Shiu Kee] St Teresas Hosp, Skin Laser & Plast Surg Ctr, Kowloon, Hong Kong, Peoples R China. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials & Outcomes Skin CURTIS, Clin Res Support Off, Worcester, MA USA. EM harvardskinstudies@partners.org NR 12 TC 1 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD OCT PY 2010 VL 20 IS 5 BP 427 EP 430 DI 10.1097/CMR.0b013e3283281072 PG 4 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 647JO UT WOS:000281615000009 PM 20729764 ER PT J AU Mantzoros, CS AF Mantzoros, Christos S. TI Accepting the torch SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material C1 [Mantzoros, Christos S.] VA Boston Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston, MA USA. [Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Human Nutr Unit, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Mantzoros, CS (reprint author), VA Boston Healthcare Syst, Endocrinol Sect, Boston, MA USA. EM metabolismjournal@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 2010 VL 59 IS 10 BP 1394 EP 1395 DI 10.1016/j.metabol.2010.08.001 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 656YG UT WOS:000282376400002 PM 20855035 ER PT J AU Weinrauch, LA Sun, J Gleason, RE Boden, GH Creech, RH Dailey, G Kennedy, FP Weir, MR D'Elia, JA AF Weinrauch, Larry A. Sun, Jennifer Gleason, Ray E. Boden, Guenther H. Creech, R. H. Dailey, George Kennedy, Frank P. Weir, Matthew R. D'Elia, John A. TI Pulsatile intermittent intravenous insulin therapy for attenuation of retinopathy and nephropathy in type 1 diabetes mellitus SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID IMPROVED GLYCEMIC CONTROL; HEART-RATE-VARIABILITY; ABNORMALITIES; COMPLICATIONS; MANAGEMENT; INFUSION; GLUCAGON; DELIVERY; TRIAL AB Many hormones are secreted in a pulsatile fashion that is more efficient than continuous secretion when tested in vivo. A trial of multiple daily insulin doses with or without the addition of weekly pulsatile insulin infusion therapy was designed to determine if deterioration of renal and retinal function could be blunted. Sixty-five study subjects were evaluated prospectively in 7 centers. Thirty-six patients were randomly allocated to the infusion group and 29 to the standard therapy group. Mean serum creatinine was 1.6 mg/dL in both groups. Subjects were excluded if clearance was less than 30 mL/min. There were no significant differences between the groups with respect to age, duration of diabetes, sex distribution, glycohemoglobin, blood pressure, angiotensin-converting enzyme inhibitor use, proteinuria, or baseline diabetic retinopathy (DR) severity level (all eyes exhibited DR; 8 were deemed technically not amenable to evaluation). Progression of DR was noted in 31.6% of 57 patients (32.3% treated, 30.8% control; P = 1.0) with both eyes evaluable. For patients with 12 or more months of follow-up, 27.9% of 43 patients demonstrated progression of DR (32.0% treated, 22.2% control; P =.57). There were no significant differences between study groups with respect to progression or marked progression, nor was there any influence of duration of follow-up. Progression of DR was noted in 18.8% of 122 eyes that could be adequately evaluated (17.9% of 67 treated, 20% of 55 controls; P = .39). Serum crcatinine increased to 1.7 mg/dL in the treatment group and to 1.9 mg/dL in the control group (P = .03). Statistically significant preservation of renal function by pulsatile insulin infusion was not matched by a statistically significant prevention of DR progression compared with standard diabetes care. Inadequate statistical power or duration of the study, or lack of further benefit of pulsatile insulin infusion on the retina in the presence of angiotensin-converting enzyme inhibition may be responsible. (C) 2010 Elsevier Inc. All rights reserved. C1 [Weinrauch, Larry A.; Sun, Jennifer; Gleason, Ray E.; D'Elia, John A.] Joslin Diabet Ctr, William P Beetham Eye Unit, Boston, MA 02215 USA. [Weinrauch, Larry A.; Sun, Jennifer; Gleason, Ray E.; D'Elia, John A.] Joslin Diabet Ctr, John Cook Renal Unit, Boston, MA 02215 USA. [Weir, Matthew R.] Univ Maryland, Baltimore, MD 21201 USA. [Kennedy, Frank P.] Mayo Med Ctr, Rochester, MN USA. [Dailey, George] Scripps Med Ctr, San Diego, CA USA. [Creech, R. H.] Summit Med Ctr, Nashville, TN USA. [Boden, Guenther H.] Temple Univ, Ctr Hlth, Philadelphia, PA 19122 USA. RP Weinrauch, LA (reprint author), Joslin Diabet Ctr, William P Beetham Eye Unit, Boston, MA 02215 USA. OI D'Elia, John/0000-0001-9482-581X; Weinrauch, Larry/0000-0003-1357-9528 NR 30 TC 4 Z9 4 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 2010 VL 59 IS 10 BP 1429 EP 1434 DI 10.1016/j.metabol.2010.01.004 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 656YG UT WOS:000282376400007 PM 20189608 ER PT J AU Frutuoso, MS Hori, JI Pereira, MSF Junior, DSL Sonego, F Kobayashi, KS Flavell, RA Cunha, FQ Zamboni, DS AF Frutuoso, Mariana S. Hori, Juliana I. Pereira, Marcelo S. F. Junior, Djalma S. L. Sonego, Fabiane Kobayashi, Koichi S. Flavell, Richard A. Cunha, Fernando Q. Zamboni, Dario S. TI The pattern recognition receptors Nod1 and Nod2 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila SO MICROBES AND INFECTION LA English DT Article DE Nod1; Nod2; Legionella pneumophila; Neutrophils ID LEGIONNAIRES-DISEASE; HOST-DEFENSE; INTRACELLULAR GROWTH; PHAGOSOME TRAFFICKING; IMMUNE-RESPONSES; MURINE MODEL; IN-VIVO; PROTEIN; CELLS; PNEUMONIA AB The intracellular bacterium Legionella pneumophila induces a severe form of pneumonia called Legionnaires diseases, which is characterized by a strong neutrophil (NE) infiltrate to the lungs of infected individuals. Although the participation of pattern recognition receptors, such as Toll-like receptors, was recently demonstrated, there is no information on the role of nod-like receptors (NLRs) for bacterial recognition in vivo and for NE recruitment to the lungs. Here, we employed a murine model of Legionnaires disease to evaluate host and bacterial factors involved in NE recruitment to the mice lungs. We found that L. pneumophila type four secretion system, known as Dot/Icm, was required for NE recruitment as dot/icm mutants fail to trigger NE recruitment in a process independent of bacterial multiplication. By using mice deficient for Nod1, Nod2, and Rip2, we found that these receptors accounted for NE recruitment to the lungs of infected mice. In addition, Rip2-dependent responses were important for cytokine production and bacterial clearance. Collectively, these studies show that Nod1, Nod2, and Rip2 account for generation of innate immune responses in vivo, which are important for NE recruitment and bacterial clearance in a murine model of Legionnaires diseases. (C) 2010 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. C1 [Frutuoso, Mariana S.; Hori, Juliana I.; Pereira, Marcelo S. F.; Junior, Djalma S. L.; Zamboni, Dario S.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Cell Biol, FMRP USP, BR-14049900 Ribeirao Preto, SP, Brazil. [Sonego, Fabiane; Cunha, Fernando Q.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, FMRP USP, BR-14049900 Ribeirao Preto, SP, Brazil. [Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06510 USA. [Flavell, Richard A.] Howard Hughes Med Inst, New Haven, CT 06510 USA. RP Zamboni, DS (reprint author), Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Cell Biol, FMRP USP, BR-14049900 Ribeirao Preto, SP, Brazil. EM dszamboni@fmrp.usp.br RI Vacinas, Inct/J-9431-2013; Zamboni, Dario/D-3024-2012; Issa Hori, Juliana/D-3486-2014; Lima-Junior, Djalma/H-4833-2013; Cunha, Fernando/M-3090-2014; OI Zamboni, Dario/0000-0002-7856-7512; Issa Hori, Juliana/0000-0002-5421-3728; Lima-Junior, Djalma/0000-0002-2092-8047; Cunha, Fernando Queiroz/0000-0003-4755-1670 FU PEW Latin America Program in Biomedical Sciences; INCTV/CNPq; FAPESP [06/52867-4] FX We are grateful to Catarina Horta and Giuliana Bertozi for the technical assistance. We are much indebted to Dr. Niels Olsen Saraiva Camara for help in the Multiplex experiments. This work was supported by PEW Latin America Program in Biomedical Sciences, INCTV/CNPq and FAPESP grant number 06/52867-4 (to D.S.Z). J.I.H, M.S.F.P, D.S.L.J and F.S. are recipient of doctoral fellowships from FAPESP. R.A.F. is an Investigator of the Howard Hughes Medical Institute. D.S.Z and F.Q.C are research fellows from CNPq. NR 51 TC 42 Z9 43 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD OCT PY 2010 VL 12 IS 11 BP 819 EP 827 DI 10.1016/j.micinf.2010.05.006 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 676IU UT WOS:000283905200004 PM 20685341 ER PT J AU Jeffreys, MD Leibowitz, RQ Finley, E Arar, N AF Jeffreys, Matthew D. Leibowitz, Ruth Q. Finley, Erin Arar, Nedal TI Trauma Disclosure to Health Care Professionals by Veterans: Clinical Implications SO MILITARY MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ADMINISTERED PTSD SCALE; HELP-SEEKING; SEXUAL-ABUSE; DOMESTIC VIOLENCE; EMOTIONAL DISCLOSURE; CHILDHOOD RAPE; PANDORA BOX; EXPERIENCES; WOMENS AB Trauma disclosure is the initial step toward healing trauma-related distress. This study used qualitative methods to better understand factors facilitating and inhibiting change in the disclosure process. Fifty-six veterans were interviewed about their disclosure experiences between August 2004 and 2005. Emerging themes and barriers to disclosure from 23 of these interviews are reported in this article. Barriers to trauma disclosure included lack of trust in the provider, fears about the potential negative consequences of disclosure, and trauma avoidance. Providers perceived as caring and communicating at the same level as the participants facilitated disclosure, whereas providers perceived as uncaring or disinterested inhibited disclosure. Veterans reported both positive and negative reactions to initial disclosure, but nearly all agreed that disclosure was worthwhile over the long term. Improving patient provider communications and creating settings that facilitate trauma disclosure may improve healing after trauma. C1 [Jeffreys, Matthew D.; Finley, Erin; Arar, Nedal] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX 78229 USA. [Leibowitz, Ruth Q.] Salem Hosp Reg Rehabil Ctr, Salem, OR 97301 USA. RP Jeffreys, MD (reprint author), S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, 7400 Merton Minter, San Antonio, TX 78229 USA. OI Finley, Erin/0000-0003-4497-7721 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX Dr. Leibowitz acknowledges Dr. Polly Hitchcock Noel for her mentorship. The authors also acknowledge Drs. Dianne Dunn and John Casada for their work in interviewing study participants. This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (PI: Ruth Leibowitz, PhD). NR 57 TC 5 Z9 5 U1 1 U2 4 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD OCT PY 2010 VL 175 IS 10 BP 719 EP 724 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 658CX UT WOS:000282468500005 PM 20968260 ER PT J AU Freedy, JR Magruder, KM Mainous, AG Frueh, BC Geesey, ME Camemolla, M AF Freedy, John R. Magruder, Kathryn M. Mainous, Arch G. Frueh, B. Chris Geesey, Mark E. Camemolla, Mark TI Gender Differences in Traumatic Event Exposure and Mental Health Among Veteran Primary Care Patients SO MILITARY MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; AFFAIRS PRIMARY-CARE; NEUROPSYCHIATRIC INTERVIEW MINI; ADMINISTERED PTSD SCALE; COLLABORATIVE CARE; PSYCHOMETRIC PROPERTIES; PHYSICAL SYMPTOMS; MILITARY TRAUMA; WOMEN VETERANS; WAR VETERANS AB Objective: This study evaluated gender differences in lifetime traumatic events. PTSD, and depression among VA primary care patients. Method: Participants were 865 adults attending primary care at one of four VA health centers (n = 681 males, 184 females). Results: Mental health findings included: male PTSD 12.3% vs. female PTSD 9.2% (p > 0.05); male depression 15.9% vs. female depression 29.3% (p < 0.001). Men reported more war zone exposure (p < 0.001). Women reported more physical and sexual victimization (p < 0.001). Male logistic regression equations determined PTSD was associated with disability (OR = 3.42; 1.74-6.72, 95% CI) and war zone exposure (OR = 7.14; 3.82-13.30, 95% CI); depression was associated with war zone exposure (OR = 2.27; 1.40-3.68, 95% CI) and interpersonal violence (OR = 1.75; 1.10-2.79, 95% CI). Female PTSD was associated with sexual victimization (OR = 4.50; 1.20-16.80, 95% CI); depression was not predicted. Conclusions: We discuss findings in terms of the crucial need to improve identification and management of PTSD within VA primary care settings. C1 [Freedy, John R.; Mainous, Arch G.; Geesey, Mark E.; Camemolla, Mark] Med Univ S Carolina, Dept Family Med, Charleston, SC 29425 USA. [Magruder, Kathryn M.; Frueh, B. Chris] Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. [Magruder, Kathryn M.; Frueh, B. Chris] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Freedy, JR (reprint author), Med Univ S Carolina, Dept Family Med, 295 Calhoun St, Charleston, SC 29425 USA. OI Mainous, Arch/0000-0002-2535-7685 FU Veterans Affairs Health Services Research and Development FX This research was partially supported by a grant from the Veterans Affairs Health Services Research and Development Program to Dr. Magruder. NR 78 TC 14 Z9 14 U1 1 U2 7 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 OCT PY 2010 VL 175 IS 10 BP 750 EP 758 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 658CX UT WOS:000282468500010 PM 20968265 ER PT J AU Berra, L Sampson, J Wiener-Kronish, J AF Berra, L. Sampson, J. Wiener-Kronish, J. TI Pseudomonas aeruginosa: acute lung injury or ventilator-associated pneumonia? SO MINERVA ANESTESIOLOGICA LA English DT Review DE Pseudomonas aeruginosa, microbiology; Pseudomonas aeruginosa, diagnosis; Pseudomonas aeruginosa, epidemiology ID INFLAMMATORY MEDIATOR RELEASE; NONHEMOLYTIC PHOSPHOLIPASE-C; III SECRETION SYSTEM; BIOFILM DEVELOPMENT; TWITCHING MOTILITY; GENOME SEQUENCE; RISK-FACTORS; EXOTOXIN-A; INFECTIONS; VIRULENCE AB Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative, aerobic, rod-shaped and polar-flagella bacterium with unipolar motility. Furthermore, it is an opportunistic pathogen responsible for ventilator-acquired pneumonia (VAP). VAP due to P. aeruginosa is usually multidrug-resistant and associated with severe infection and increased mortality. The goals of this review are as follows: (I) to present selected recent epidemiological literature characterizing the population at risk of I? aeruginosa pneumonia, (II) to describe some of the virulence factors of P. aeruginosa that are related to infection, and (III) to illustrate clinical outcomes of ventilated patients with large burdens of P. aeruginosa as well as the mechanism by which this bacterium may evade the host immune response. (Minerva Anestesiol 2010;76.824-32) C1 [Berra, L.; Wiener-Kronish, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Sampson, J.] St Johns Univ, New York, NY USA. RP Berra, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM lberra@partners.org NR 44 TC 9 Z9 9 U1 2 U2 6 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD OCT PY 2010 VL 76 IS 10 BP 824 EP 832 PG 9 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA 665AS UT WOS:000283006900011 PM 20935618 ER PT J AU Dominici, L Golshan, M AF Dominici, L. Golshan, M. TI Can axillary lymph node dissection be omitted in patients with breast cancer and positive sentinel nodes? SO MINERVA CHIRURGICA LA English DT Review DE Breast neoplasms; Sentinel lymph node biopsy; Lymphatic metastasis ID FOLLOW-UP; PREOPERATIVE CHEMOTHERAPY; RADICAL-MASTECTOMY; MSKCC NOMOGRAM; SCORING SYSTEM; BIOPSY; METASTASES; INVOLVEMENT; COMPLETION; PREDICTION AB Sentinel lymph node biopsy has evolved as the surgical procedure of choice for women with clinically negative axillae, as part of an effort to move toward the less invasive surgical management of breast cancer. Axillary lymph node dissection remains the standard of care for patients with a positive axillary node and was previously performed on all patients with breast cancer prior to the implementation of the sentinel lymph node biopsy. There is, however, controversy regarding whether or not all patients with a positive sentinel lymph node need to undergo completion axillary dissection for either prognostic or therapeutic purposes. This article reviews the literature related to this controversial and evolving topic. C1 [Dominici, L.; Golshan, M.] Harvard Univ, Brigham & Womens Hosp, Dept Surg, Sch Med,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Golshan, M (reprint author), Dana Farber Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 62 TC 0 Z9 0 U1 0 U2 1 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0026-4733 J9 MINERVA CHIR JI Minerva Chir. PD OCT PY 2010 VL 65 IS 5 BP 547 EP 554 PG 8 WC Surgery SC Surgery GA 691XO UT WOS:000285114300006 PM 21081866 ER PT J AU Roh, MH Yassin, Y Miron, A Mehra, KK Mehrad, M Monte, NM Mutter, GL Nucci, MR Ning, G Mckeon, FD Hirsch, MS Wa, XA Crum, CP AF Roh, Michael H. Yassin, Yosuf Miron, Alexander Mehra, Karishma K. Mehrad, Mitra Monte, Nicolas M. Mutter, George L. Nucci, Marisa R. Ning, Geng Mckeon, Frank D. Hirsch, Michelle S. Wa, Xian Crum, Christopher P. TI High-grade fimbrial-ovarian carcinomas are unified by altered p53, PTEN and PAX2 expression SO MODERN PATHOLOGY LA English DT Article DE ovarian cancer; p16(ink4); p53; PTEN; PAX2; tubal intraepithelial carcinoma ID TUBAL INTRAEPITHELIAL CARCINOMA; PELVIC SEROUS CARCINOMA; MUTATIONS; CANCER; PATHWAYS; TUMORS; WOMEN AB High-grade endometrioid and serous carcinomas of the ovary and fallopian tube are responsible for the majority of cancer deaths and comprise a spectrum that includes early or localized (tubal intraepithelial carcinoma) and advanced (invasive or metastatic) disease. We subdivided a series of these tumors into three groups, (1) classic serous, (2) mixed serous and endometrioid and (3) endometrioid carcinomas and determined: (1) the frequencies of coexisting tubal intraepithelial carcinoma, (2) frequency of a dominant ovarian mass suggesting an ovarian origin and (3) immuno-localization of WT-1, p53, PTEN, PAX2 and p16(ink4). All tumors were analyzed for p53 mutations. Thirty six, 25 and 8% of groups 1-3 were associated with tubal intraepithelial carcinoma (P = 0.09) and 34, 45 and 62% predominated in one ovary (P = 0.028), respectively. Differences in frequencies of diffuse p53 immunostaining (85-93%), WT-1 (70-98%) and p16(ink4) positivity (69-75%) were not significant for all groups. Greater than 95% reduction in PAX2 and PTEN occurred in 67-75 and 5-12%, respectively; however, PAX2 and PTEN staining intensity, when present, was often heterogeneous, highlighting different tumor populations. PAX2 and PTEN expression were markedly reduced or absent in 12 of 12 and 4 of 12 tubal intraepithelial carcinomas. In summary, high-grade mullerian carcinomas share identical frequencies of altered or reduced expression of p53, PTEN and PAX2, all of which can be appreciated in tubal intraepithelial carcinomas. Because only a subset of these tumors appears to arise in the fallopian tube, attention to expression of these biomarkers in the ovary and other mullerian sites might facilitate the identification of other carcinogenic pathways. PAX2 and PTEN, in addition to p53 and p16(ink4), comprise a potentially important gene combination in high-grade pelvic carcinogenesis. Modern Pathology (2010) 23, 1316-1324; doi:10.1038/modpathol.2010.119; published online 18 June 2010 C1 [Mehra, Karishma K.; Mehrad, Mitra; Monte, Nicolas M.; Mutter, George L.; Nucci, Marisa R.; Ning, Geng; Hirsch, Michelle S.; Wa, Xian; Crum, Christopher P.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Roh, Michael H.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. [Yassin, Yosuf; Miron, Alexander] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Mehra, Karishma K.; Mehrad, Mitra; Monte, Nicolas M.; Mutter, George L.; Nucci, Marisa R.; Ning, Geng; Hirsch, Michelle S.; Wa, Xian; Crum, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Mckeon, Frank D.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Wa, Xian] ASTAR, Inst Med Biol, Singapore, Singapore. RP Crum, CP (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Amory 3-127,75 Francis St, Boston, MA 02115 USA. EM ccrum@partners.org FU NCI [P50CA10500, 1R21CA124688-01A1]; Columbia Hospital For Women Research Foundation; Charlotte Geyer Foundation; Division of Women's and Perinatal Pathology, Brigham and Women's Hospital; Dana Farber Cancer Institute FX We thank Mei Zheng, Tatiana Zolotarev and Terri Woo for technical assistance in immunohistochemistry. This work was supported by grants from the NCI (P50CA10500 [SPORE]: D. Cramer, PI), NCI 1R21CA124688-01A1 (CP Crum, PI), The Columbia Hospital For Women Research Foundation (CP Crum, PI), the Charlotte Geyer Foundation (CPC), the Francis Ward Paine and TSA Pemberton Funds from the Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, the Women's Cancer Program at the Dana Farber Cancer Institute, and a gift in memory of Elizabeth Ford Smith. NR 28 TC 58 Z9 60 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2010 VL 23 IS 10 BP 1316 EP 1324 DI 10.1038/modpathol.2010.119 PG 9 WC Pathology SC Pathology GA 657LA UT WOS:000282413000003 PM 20562848 ER PT J AU Duarte, VM Han, E Veena, MS Salvado, A Suh, JD Liang, LJ Faull, KF Srivatsan, ES Wang, MB AF Duarte, Victor M. Han, Eugene Veena, Mysore S. Salvado, Amanda Suh, Jeffrey D. Liang, Li-Jung Faull, Kym F. Srivatsan, Eri S. Wang, Marilene B. TI Curcumin Enhances the Effect of Cisplatin in Suppression of Head and Neck Squamous Cell Carcinoma via Inhibition of IKK beta Protein of the NF kappa B Pathway SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID LIPOSOME-ENCAPSULATED CURCUMIN; CANCER-CELLS; IN-VITRO; COLORECTAL-CANCER; GENE-EXPRESSION; GROWTH; APOPTOSIS; KINASE; ANGIOGENESIS; CETUXIMAB AB Previous experiments have shown that curcumin or cisplatin treatment suppresses growth of head and neck squamous cell carcinoma (HNSCC). To study the potential cooperative effect of both agents, two HNSCC cell lines were treated with curcumin or cisplatin alone or in combination. In vivo studies consisted of intravenous tail vein injection of liposomal curcumin, with intraperitoneal cisplatin, into nude mice growing xenograft HNSCC tumors. Introduction of curcumin and suboptimal concentrations of cisplatin showed a significant suppressive effect compared with treatment with either agent alone. Reduced expression of cyclin D1, I kappa B alpha, phospho-I kappa B alpha, and IKK beta occurred in cisplatin- and curcumin-treated cell lines. Confocal microscopy showed expression of IKK beta in the nucleus of the cell lines. Chromatin immunoprecipitation assay on DNA isolated from IKK beta immunoprecipitated samples showed PCR amplification of interleukin-8 promoter sequences, a binding site of NF kappa B, indicating an interaction between IKK beta and NF kappa B. Curcumin inhibited IKK beta in the cytoplasm and nucleus, leading to reduced NF kappa B activity, with no effect on phospho-AKT. In vivo studies showed significant growth inhibition of xenograft tumors treated with a combination of liposomal curcumin and cisplatin. The suppressive effect of curcumin was mediated through inhibition of cytoplasmic and nuclear IKK beta, resulting in inhibition of NF kappa B activity. Cisplatin treatment led to cellular senescence, indicating an effect mediated by p53 activation. The mechanisms of the two agents through different growth signaling pathways suggest potential for the clinical use of subtherapeutic doses of cisplatin in combination with curcumin, which will allow effective suppression of tumor growth while minimizing the toxic side effects of cisplatin. Mol Cancer Ther; 9(10); 2665-75. (C) 2010 AACR. C1 [Duarte, Victor M.; Han, Eugene; Veena, Mysore S.; Salvado, Amanda; Suh, Jeffrey D.; Srivatsan, Eri S.; Wang, Marilene B.] VA Greater Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Duarte, Victor M.; Salvado, Amanda; Wang, Marilene B.] UCLA David Geffen Sch Med, Div Head & Neck Surg, Neuropsychiat Semel Inst, Los Angeles, CA 90095 USA. [Liang, Li-Jung] UCLA David Geffen Sch Med, Dept Med, Neuropsychiat Semel Inst, Los Angeles, CA 90095 USA. UCLA David Geffen Sch Med, Pasarow Mass Spectrometry Lab, Neuropsychiat Semel Inst, Los Angeles, CA 90095 USA. RP Wang, MB (reprint author), UCLA David Geffen Sch Med, Div Head & Neck Surg, Neuropsychiat Semel Inst, 200 UCLA Med Plaza Suite 550, Los Angeles, CA 90095 USA. EM mbwang@ucla.edu FU VA Greater Los Angeles Healthcare; NIH [R21 CA116826-01]; Veterans Administration (Washington, DC); West Los Angeles Surgical Education Research Center; UCLA Academic Senate FX VA Greater Los Angeles Healthcare, West Los Angeles Surgical Education Research Center, and UCLA Academic Senate (M. B. Wang); NIH grant R21 CA116826-01 (M. B. Wang); and Veterans Administration (Washington, DC) Merit grant (E. S. Srivatsan). NR 31 TC 63 Z9 68 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2010 VL 9 IS 10 BP 2665 EP 2675 DI 10.1158/1535-7163.MCT-10-0064 PG 11 WC Oncology SC Oncology GA 661JS UT WOS:000282724600003 PM 20937593 ER PT J AU Okamoto, W Okamoto, I Tanaka, K Hatashita, E Yamada, Y Kuwata, K Yamaguchi, H Arao, T Nishio, K Fukuoka, M Janne, PA Nakagawa, K AF Okamoto, Wataru Okamoto, Isamu Tanaka, Kaoru Hatashita, Erina Yamada, Yuki Kuwata, Kiyoko Yamaguchi, Haruka Arao, Tokuzo Nishio, Kazuto Fukuoka, Masahiro Jaenne, Pasi A. Nakagawa, Kazuhiko TI TAK-701, a Humanized Monoclonal Antibody to Hepatocyte Growth Factor, Reverses Gefitinib Resistance Induced by Tumor-Derived HGF in Non-Small Cell Lung Cancer with an EGFR Mutation SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID FACTOR SCATTER FACTOR; TYROSINE KINASE-ACTIVITY; FACTOR RECEPTOR; MET AMPLIFICATION; C-MET; ACTIVATING MUTATIONS; ACQUIRED-RESISTANCE; CARCINOMA-CELLS; GASTRIC-CANCER; IDENTIFICATION AB Most non-small cell lung cancer (NSCLC) tumors with an activating mutation of the epidermal growth factor receptor (EGFR) are initially responsive to EGFR tyrosine kinase inhibitors (TKI) such as gefitinib but ultimately develop resistance to these drugs. Hepatocyte growth factor (HGF) induces EGFR-TKI resistance in NSCLC cells with such a mutation. We investigated strategies to overcome gefitinib resistance induced by HGF. Human NSCLC cells with an activating EGFR mutation (HCC827 cells) were engineered to stably express HGF (HCC827-HGF cells). HCC827-HGF cells secreted large amounts of HGF and exhibited resistance to gefitinib in vitro to an extent similar to that of HCC827 GR cells, in which the gene for the HGF receptor MET is amplified. A MET-TKI reversed gefitinib resistance in HCC827-HGF cells as well as in HCC827 GR cells, suggesting that MET activation induces gefitinib resistance in both cell lines. TAK-701, a humanized monoclonal antibody to HGF, in combination with gefitinib inhibited the phosphorylation of MET, EGFR, extracellular signal-regulated kinase, and AKT in HCC827-HGF cells, resulting in suppression of cell growth and indicating that autocrine HGF-MET signaling contributes to gefitinib resistance in these cells. Combination therapy with TAK-701 and gefitinib also markedly inhibited the growth of HCC827-HGF tumors in vivo. The addition of TAK-701 to gefitinib is a promising strategy to overcome EGFR-TKI resistance induced by HGF in NSCLC with an activating EGFR mutation. Mol Cancer Ther; 9(10); 2785-92. (C) 2010 AACR. C1 [Okamoto, Wataru; Okamoto, Isamu; Tanaka, Kaoru; Hatashita, Erina; Yamada, Yuki; Kuwata, Kiyoko; Yamaguchi, Haruka; Nakagawa, Kazuhiko] Kinki Univ, Sch Med, Dept Med Oncol, Osaka 5898511, Japan. [Arao, Tokuzo; Nishio, Kazuto] Kinki Univ, Sch Med, Dept Genome Biol, Osaka 5898511, Japan. [Fukuoka, Masahiro] Izumi City Hosp, Ctr Canc, Osaka, Japan. [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Okamoto, I (reprint author), Kinki Univ, Sch Med, Dept Med Oncol, 377-2 Ohno Higashi, Osaka 5898511, Japan. EM chi-okamoto@dotd.med.kindai.ac.jp FU National Institute of Health [R01CA135257]; National Cancer Institute [P50CA090578] FX National Institute of Health R01CA135257 (P. A. Janne) and National Cancer Institute Lung SPORE P50CA090578 (P. A. Janne). NR 29 TC 39 Z9 42 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2010 VL 9 IS 10 BP 2785 EP 2792 DI 10.1158/1535-7163.MCT-10-0481 PG 8 WC Oncology SC Oncology GA 661JS UT WOS:000282724600013 PM 20716641 ER PT J AU Bhatt, RS Wang, XE Zhang, LA Collins, MP Signoretti, S Alsop, DC Goldberg, SN Atkins, MB Mier, JW AF Bhatt, Rupal S. Wang, Xiaoen Zhang, Liang Collins, Michael P. Signoretti, Sabina Alsop, David C. Goldberg, S. Nahum Atkins, Michael B. Mier, James W. TI Renal Cancer Resistance to Antiangiogenic Therapy Is Delayed by Restoration of Angiostatic Signaling SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID VASCULAR ENDOTHELIAL GROWTH; CELL CARCINOMA; TUMOR ANGIOGENESIS; PROGNOSTIC-FACTOR; SUNITINIB; RECEPTOR; SUPPRESSION; METASTASIS; INHIBITION; EXPRESSION AB Treatment of metastatic renal cell cancer (RCC) with antiangiogenic agents that block vascular endothelial growth factor (VEGF) receptor 2 signaling produces tumor regression in a substantial fraction of patients; however, resistance typically develops within 6 to 12 months. The purpose of this study was to identify molecular pathways involved in resistance. Treatment of mice bearing either 786-0 or A498 human RCC xenografts with sorafenib or sunitinib produced tumor growth stabilization followed by regrowth despite continued drug administration analogous to the clinical experience. Tumors and plasma were harvested at day 3 of therapy and at the time of resistance to assess pathways that may be involved in resistance. Serial perfusion imaging, and plasma and tumor collections were obtained in mice treated with either placebo or sunitinib alone or in combination with intratumoral injections of the angiostatic chemokine CXCL9. Sunitinib administration led to an early downmodulation of IFN gamma levels as well as reduction of IFN gamma receptor and downstream angiostatic chemokines CXCL9 to 11 within the tumor. Intratumoral injection of CXCL9, although producing minimal effects by itself, when combined with sunitinib resulted in delayed resistance in vivo accompanied by a prolonged reduction of microvascular density and tumor perfusion as measured by perfusion imaging relative to sunitinib alone. These results provide evidence that resistance to VEGF receptor therapy is due at least in part to resumption of angiogenesis in association with reduction of IFN gamma-related angiostatic chemokines, and that this resistance can be delayed by concomitant administration of CXCL9. Mol Cancer Ther; 9(10); 2793-802. (C) 2010 AACR. C1 [Bhatt, Rupal S.; Zhang, Liang; Atkins, Michael B.; Mier, James W.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol & Canc Biol, Boston, MA 02215 USA. [Wang, Xiaoen; Alsop, David C.; Goldberg, S. Nahum] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Collins, Michael P.; Signoretti, Sabina] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Signoretti, Sabina] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02215 USA. RP Bhatt, RS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol & Canc Biol, Boston, MA 02215 USA. EM rbhatt@bidmc.harvard.edu RI Bell, Tiffany/F-4403-2010; Alsop, David/J-5764-2013 OI Alsop, David/0000-0002-8206-1995 FU DF/HCC Kidney Cancer SPORE [2 P50 CA101942]; Beth Israel Deaconess Medical Center - Harvard/MIT Health Sciences and Technology; Pfizer Inc.; Merck Co; National Comprehensive Cancer Network, Jenkintown PA FX DF/HCC Kidney Cancer SPORE: 2 P50 CA101942 VHL Family Alliance Grant, Clinical Investigator Training Program: Beth Israel Deaconess Medical Center - Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Co (R. S. Bhatt), and a grant from the National Comprehensive Cancer Network, Jenkintown PA. NR 30 TC 30 Z9 31 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2010 VL 9 IS 10 BP 2793 EP 2802 DI 10.1158/1535-7163.MCT-10-0477 PG 10 WC Oncology SC Oncology GA 661JS UT WOS:000282724600014 PM 20699227 ER PT J AU Afkarian, M Bhasin, M Dillon, ST Guerrero, MC Nelson, RG Knowler, WC Thadhani, R Libermann, TA AF Afkarian, Maryam Bhasin, Manoj Dillon, Simon T. Guerrero, Manuel C. Nelson, Robert G. Knowler, William C. Thadhani, Ravi Libermann, Towia A. TI Optimizing a Proteomics Platform for Urine Biomarker Discovery SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID SAMPLE PREPARATION; DIABETIC-NEPHROPATHY; 2-DIMENSIONAL ELECTROPHORESIS; GEL-ELECTROPHORESIS; PROTEINS; QUANTITATION; COLLECTION; PREDICT AB Biomarker discovery approaches in urine have been hindered by concerns for reproducibility and inadequate standardization of proteomics protocols. In this study, we describe an optimized quantitative proteomics strategy for urine biomarker discovery, which is applicable to fresh or long frozen samples. We used urine from healthy controls to standardize iTRAQ (isobaric tags for relative and absolute quantitation) for variation induced by protease inhibitors, starting protein and iTRAQ label quantities, protein extraction methods, and depletion of albumin and immunoglobulin G (IgG). We observed the following: (a) Absence of protease inhibitors did not affect the number or identity of the high confidence proteins. (b) Use of less than 20 mu g of protein per sample led to a significant drop in the number of identified proteins. (c) Use of as little as a quarter unit of an iTRAQ label did not affect the number or identity of the identified proteins. (d) Protein extraction by methanol precipitation led to the highest protein yields and the most reproducible spectra. (e) Depletion of albumin and IgG did not increase the number of identified proteins or deepen the proteome coverage. Applying this optimized protocol to four pairs of long frozen urine samples from diabetic Pima Indians with or without nephropathy, we observed patterns suggesting segregation of cases and controls by iTRAQ spectra. We also identified several previously reported candidate biomarkers that showed trends toward differential expression, albeit not reaching statistical significance in this small sample set. Molecular & Cellular Proteomics 9:2195-2204, 2010. C1 [Bhasin, Manoj; Dillon, Simon T.; Guerrero, Manuel C.; Libermann, Towia A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Genom & Prote Ctr, Sch Med, Boston, MA 02215 USA. [Bhasin, Manoj; Dillon, Simon T.; Guerrero, Manuel C.; Libermann, Towia A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dana Farber Harvard Canc Ctr Canc Prote Core, Sch Med, Boston, MA 02215 USA. [Afkarian, Maryam; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Nelson, Robert G.; Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA. RP Libermann, TA (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Genom & Prote Ctr, Sch Med, Res N Bldg,Rm 380C,99 Brookline Ave, Boston, MA 02215 USA. EM tliberma@bidmc.harvard.edu RI Libermann, Towia/F-9866-2010; Nelson, Robert/B-1470-2012; OI Libermann, Towia/0000-0002-4006-8179 FU National Institutes of Health through NIDDK; Juvenile Diabetes Research Foundation FX This work was supported, in whole or in part, by the National Institutes of Health through the Intramural Research Program of the NIDDK. This work was also supported by a research grant from the Juvenile Diabetes Research Foundation (to R. T.). NR 25 TC 39 Z9 41 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2010 VL 9 IS 10 BP 2195 EP 2204 DI 10.1074/mcp.M110.000992 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 656VJ UT WOS:000282368900010 PM 20511394 ER PT J AU Latif, R Michalek, K Davies, TF AF Latif, Rauf Michalek, Krzysztof Davies, Terry F. TI Subunit Interactions Influence TSHR Multimerization SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN THYROTROPIN RECEPTOR; EXTRACELLULAR DOMAIN; OLIGOMERIZATION; ECTODOMAIN; CLEAVAGE; ACTIVATION; REVEALS; BINDING; SITES AB The TSH receptor (TSHR) is the key molecule influencing thyroid growth and development and is an antigenic target in autoimmune thyroid disease. The TSHR exists in monomeric and multimeric forms, and it has been shown previously that multimeric complexes of the TSHR preferentially localize in lipid rafts. However, unlike other glycoprotein hormone receptors, the TSHR exists in several forms on the cell membrane due to intramolecular cleavage of its ectodomain, which causes the production of alpha- and beta-subunits of various lengths. After cleavage and reduction of disulfide bonds, alpha-subunits consisting of the receptor ectodomain may be lost from the cell surface by receptor shedding, leading to accumulation of excess beta-subunits within the membrane. Because cell surface expression of these various forms of the TSHR is critical to receptor signaling and autoimmune responses, we set out to model the influence of beta-subunits on full-length TSHRs. To study this interaction, we generated three truncated ectodomain beta-subunits linked to green fluorescent protein (named beta-316, -366, and -409) as examples of native cleaved forms of the TSHR. These constructs were transfected into human embryonic kidney 293 cells in the presence and absence of the full-length receptor. Whereas the beta-316 and beta-366 forms showed cell surface expression, the expression of beta-409 was primarily intracellular. Cotransfection of the beta-subunits with a full-length hemagglutinin-tagged wild-type (WT) receptor (HT-WT-TSHR) in both transient and stable systems caused a significant decrease in surface expression of the full-length WT receptors. This decrease was not seen with control plasmid consisting of a plasma membrane-targeted protein tagged to red fluorescent protein. To ascertain if this response was due to homointeraction of the truncated beta-constructs with the WT-TSHRs, we immunoprecipitated membranes prepared from the cotransfected cells using antihemagglutinin and then probed with anti-green fluorescent protein. These studies confirmed dimerization of the beta-subunits with the WT full-length receptor, and this interaction was further observed in vivo by fluorescence resonance energy transfer. We then studied the functional consequences of this interaction on TSHR signaling by examining G alpha s-mediated signals. The well-expressed truncated constructs, when coexpressed with full-length TSHR, did not alter constitutive cAMP levels, but there was a significant decrease in TSH-induced cAMP generation. Furthermore, we observed that truncated beta-316 and beta-366 had faster internalization rate, which may lead to a significant decrease in the expression of the full-length receptor on the cell surface, thus contributing to the decreased signaling response. However, the decrease in surface receptors may also be due to inhibition of newly formed receptors reaching the surface as result of receptor-receptor interaction. It is well known that under normal physiological conditions both cleaved and uncleaved TSHR forms coexist on the cell surface of normal thyrocytes. Our studies allow us to conclude, therefore, that multimerization of cleaved/truncated forms of the beta-subunits with the full-length TSHR has a profound influence on TSHR internalization and signaling. Hence, the degree of intramolecular cleavage must also modulate TSHR signaling. (Molecular Endocrinology 24: 2009-2018, 2010) C1 [Latif, Rauf; Michalek, Krzysztof; Davies, Terry F.] James J Peters Vet Affairs Med Ctr, Mt Sinai Sch Med, Thyroid Res Unit, New York, NY 10468 USA. [Michalek, Krzysztof] Univ Med Sci, Dept Endocrinol, PL-60355 Poznan, Poland. RP Latif, R (reprint author), James J Peters Vet Affairs Med Ctr, Room 2F-30,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rauf.latif@mssm.edu OI latif, rauf/0000-0002-4226-3728 FU Department of Endocrinology, University of Medical Sciences, Poznan, Poland; National Institute of Diabetes and Kidney and Digestive Diseases [DK069713]; Veterans Affairs [4535-05-074]; David Owen Segal Endowment FX We thank Zhong Yao (VAMC) for technical assistance and Professor Jerzy Sowinski (Department of Endocrinology, University of Medical Sciences, Poznan, Poland) for advice and support.; This work was supported by: National Institutes of Health Grant DK069713 from National Institute of Diabetes and Kidney and Digestive Diseases, the Veterans Affairs Merit Award program 4535-05-074 (to T. F. D.), and the David Owen Segal Endowment (to K.M.). NR 21 TC 7 Z9 7 U1 0 U2 0 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 OCT 1 PY 2010 VL 24 IS 10 BP 2009 EP 2018 DI 10.1210/me.2010-0001 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 655AY UT WOS:000282214700010 PM 20719860 ER PT J AU Seepersaud, R Bensing, BA Yen, YFT Sullam, PM AF Seepersaud, Ravin Bensing, Barbara A. Yen, Yihfen T. Sullam, Paul M. TI Asp3 mediates multiple protein-protein interactions within the accessory Sec system of Streptococcus gordonii SO MOLECULAR MICROBIOLOGY LA English DT Article ID SURFACE GLYCOPROTEINS GSPB; MOLECULAR CHAPERONE SECB; TRANSLOCATION CHANNEL; III SECRETION; IB-ALPHA; BINDING; EXPORT; MEMBRANE; HSA; GLYCOSYLATION AB P>Bacterial binding to human platelets is an important step in the pathogenesis of infective endocarditis. Streptococcus gordonii can mediate its platelet attachment through a cell wall glycoprotein termed GspB ('gordonii surface protein B'). GspB export is mediated by a seven-component accessory Sec system, containing two homologues of the general secretory pathway (SecA2 and SecY2) and five accessory Sec proteins (Asps1-5). Here we show that the Asps are required for optimal export of GspB independent of the glycosylation process. Furthermore, yeast two-hybrid screening of the accessory Sec system revealed interactions occurring between Asp3 and the other components of the system. Asp3 was shown to bind SecA2, Asp1, Asp2 and itself. Mutagenesis of Asp3 identified N- and C-terminal regions that are essential for GspB transport, and conserved residues within the C-terminal domain mediated Asp3 binding to other accessory Sec components. The loss of binding by Asp3 also resulted in an impaired ability of S. gordonii to secrete GspB. These studies indicate that Asp3 is a central element mediating multiple interactions among accessory Sec components that are essential for GspB transport to the cell surface. C1 [Seepersaud, Ravin; Bensing, Barbara A.; Yen, Yihfen T.; Sullam, Paul M.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Sullam, PM (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. EM paul.sullam@ucsf.edu FU Department of Veterans Affairs, National Institutes of Health [R01 AI41513, R01 AI057433] FX This study was supported by the Department of Veterans Affairs, the VA Merit Review programme, and grants R01 AI41513 and R01 AI057433 from the National Institutes of Health. We thank Jason McGovern for his help with the YTH assay. NR 42 TC 20 Z9 20 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 2010 VL 78 IS 2 BP 490 EP 505 DI 10.1111/j.1365-2958.2010.07346.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 663IN UT WOS:000282876900017 PM 20807195 ER PT J AU Gaudet, S AF Gaudet, Suzanne TI Connecting cell fate decision networks in hematopoeisis from the outside in SO MOLECULAR SYSTEMS BIOLOGY LA English DT Editorial Material C1 [Gaudet, Suzanne] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gaudet, Suzanne] Harvard Univ, Sch Med, Ctr Canc Syst Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gaudet, Suzanne] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Gaudet, S (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, 44 Binney St,Smith 836B, Boston, MA 02115 USA. EM Suzanne_Gaudet@dfci.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD OCT PY 2010 VL 6 AR 418 DI 10.1038/msb.2010.75 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 676RJ UT WOS:000283934000003 PM 20924353 ER PT J AU Yagi, H Soto-Gutierrez, A Navarro-Alvarez, N Nahmias, Y Goldwasser, Y Kitagawa, Y Tilles, AW Tompkins, RG Parekkadan, B Yarmush, ML AF Yagi, Hiroshi Soto-Gutierrez, Alejandro Navarro-Alvarez, Nalu Nahmias, Yaakov Goldwasser, Yoni Kitagawa, Yuko Tilles, Arno W. Tompkins, Ronald G. Parekkadan, Biju Yarmush, Martin L. TI Reactive Bone Marrow Stromal Cells Attenuate Systemic Inflammation via sTNFR1 SO MOLECULAR THERAPY LA English DT Article ID MESENCHYMAL STEM-CELLS; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; MULTIPLE ORGAN FAILURE; SEPTIC SHOCK; RESPONSE SYNDROME; POSTTRANSCRIPTIONAL CONTROL; INTERFERON-GAMMA; DOUBLE-BLIND; TNF-ALPHA AB Excessive systemic inflammation following trauma, sepsis, or burn could lead to distant organ damage. The transplantation of bone marrow stromal cells or mesenchymal stem cells (MSCs) has been reported to be an effective treatment for several immune disorders by modulating the inflammatory response to injury. We hypothesized that MSCs can dynamically secrete systemic factors that can neutralize the activity of inflammatory cytokines. In this study, we showed that cocultured MSCs are able to decrease nuclear factor kappa-B (NF kappa B) activation in target epithelial cells incubated in inflammatory serum conditions. Proteomic screening revealed a responsive secretion of soluble tumor necrosis factor (TNF) receptor 1 (sTNFR1) when MSCs were exposed to lipopolysaccharide (LPS)-stimulated rat serum. The responsive effect was eliminated when NF kappa B activation was blocked in MSCs. Intramuscular transplantation of MSCs in LPS-endotoxic rats decreased a panel of inflammatory cytokines and inflammatory infiltration of macrophages and neutrophils in lung, kidney, and liver when compared to controls. These results suggest that improvements of inflammatory responses in animal models after local transplantation of MSCs are at least, in part, explained by the NF kappa B-dependent secretion of sTNFR1 by MSCs. C1 [Yagi, Hiroshi; Soto-Gutierrez, Alejandro; Nahmias, Yaakov; Goldwasser, Yoni; Tilles, Arno W.; Tompkins, Ronald G.; Parekkadan, Biju; Yarmush, Martin L.] Harvard Univ, Sch Med, Dept Surg, Ctr Engn Med & Surg Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Yagi, Hiroshi; Soto-Gutierrez, Alejandro; Nahmias, Yaakov; Goldwasser, Yoni; Tilles, Arno W.; Tompkins, Ronald G.; Parekkadan, Biju; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA. [Yagi, Hiroshi; Kitagawa, Yuko] Keio Univ, Sch Med, Dept Surg, Tokyo 160, Japan. [Soto-Gutierrez, Alejandro] Childrens Hosp Pittsburgh, Ctr Innovat Regenerat Therapies, Dept Surg, Transplantat Sect,McGowan Inst Regenerat Med, Pittsburgh, PA 15201 USA. [Soto-Gutierrez, Alejandro] Univ Pittsburgh, Pittsburgh, PA USA. [Navarro-Alvarez, Nalu] Harvard Univ, Sch Med, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Massachusetts Gen Hosp, Boston, MA USA. [Nahmias, Yaakov] Hebrew Univ Jerusalem, Selim & Rachel Benin Sch Comp Sci & Engn, Jerusalem, Israel. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Yarmush, ML (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM alejandro.sotogutierrez@chp.edu; ireis@sbi.org RI Nahmias, Yaakov/H-4725-2013; OI Nahmias, Yaakov/0000-0002-6051-616X FU National Institutes of Health [1K99DK083556-01, 5R01DK059766-06]; Broad Medical Research Foundation [BMRP498382]; Shriners Hospitals for Children; American Liver Foundation FX We acknowledge the technical assistance of Bob Crowther for preparing histological samples. This work was supported by grants from the National Institutes of Health (1K99DK083556-01 to A.S.-G., 5R01DK059766-06 to M.L.Y.), the Broad Medical Research Foundation (BMRP498382 to B.P.), the Shriners Hospitals for Children and the American Liver Foundation support to A.S.-G. All authors have no conflict of interest. NR 50 TC 53 Z9 64 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD OCT PY 2010 VL 18 IS 10 BP 1857 EP 1864 DI 10.1038/mt.2010.155 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 659BE UT WOS:000282541200017 PM 20664529 ER PT J AU Gultepe, E Reynoso, FJ Jhaveri, A Kulkarni, P Nagesha, D Ferris, C Harisinghani, M Campbell, RB Sridhar, S AF Gultepe, Evin Reynoso, Francisco J. Jhaveri, Aditi Kulkarni, Praveen Nagesha, Dattatri Ferris, Craig Harisinghani, Mukesh Campbell, Robert B. Sridhar, Srinivas TI Monitoring of magnetic targeting to tumor vasculature through MRI and biodistribution SO NANOMEDICINE LA English DT Article DE biodistribution; magnetic targeting; magnetoliposomes; melanoma/skin cancer; MRI; novel drug-delivery systems; toxicology ID DRUG-DELIVERY; CONTRAST AGENTS; CANCER; LIPOSOMES; NANOPARTICLES; THERAPY; THERAPEUTICS AB Aims: The development of noninvasive imaging techniques for the assessment of cancer treatment is rapidly becoming highly important. The aim of the present study is to show that magnetic cationic liposomes (MCLs), incorporating superparamagnetic iron oxide nanoparticles (SPIONs), are a versatile theranostic nanoplatform for enhanced drug delivery and monitoring of cancer treatment. Materials & methods: MCLs (with incorporated high SPION cargo) were administered to a severe combined immunodeficiency mouse with metastatic (B16-F10) melanoma grown in the right flank. Pre- and post-injection magnetic resonance (MR) images were used to assess response to magnetic targeting effects. Biodistribution studies were conducted by (111)In-labeled MCLs and the amount of radioactivity recovered was used to confirm the effect of targeting for intratumoral administrations. Results: We have shown that tumor signal intensities in T(2)-fweighted MR images decreased by an average of 20 +/- 5% and T(2)star relaxation times decreased by 14 +/- 7 ms 24 h after intravenous administration of our MCL formulation. This compares to an average decrease in tumor signal intensity of 57 +/- 12% and a T(2)star relaxation time decrease of 27 +/- 8 ms after the same time period with the aid of magnetic guidance. Conclusion: MR and biodistribution analysis clearly show the efficacy of MCLs as MRI contrast agents, prove the use of magnetic guidance, and demonstrate the potential of MCLs as agents for imaging, guidance and therapeutic delivery. C1 [Gultepe, Evin; Reynoso, Francisco J.; Jhaveri, Aditi; Kulkarni, Praveen; Nagesha, Dattatri; Ferris, Craig; Campbell, Robert B.; Sridhar, Srinivas] Northeastern Univ, Elect Mat Res Inst, Boston, MA 02115 USA. [Harisinghani, Mukesh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Sridhar, S (reprint author), Northeastern Univ, Elect Mat Res Inst, Boston, MA 02115 USA. EM s.sridhar@neu.edu RI Sridhar, Srinivas/A-3688-2012 FU NHLBI NIH HHS [HHSN268201000044C] NR 33 TC 24 Z9 26 U1 2 U2 19 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD OCT PY 2010 VL 5 IS 8 BP 1173 EP 1182 DI 10.2217/NNM.10.84 PG 10 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 679YM UT WOS:000284196700009 PM 21039195 ER PT J AU Bernstein, BE Stamatoyannopoulos, JA Costello, JF Ren, B Milosavljevic, A Meissner, A Kellis, M Marra, MA Beaudet, AL Ecker, JR Farnham, PJ Hirst, M Lander, ES Mikkelsen, TS Thomson, JA AF Bernstein, Bradley E. Stamatoyannopoulos, John A. Costello, Joseph F. Ren, Bing Milosavljevic, Aleksandar Meissner, Alexander Kellis, Manolis Marra, Marco A. Beaudet, Arthur L. Ecker, Joseph R. Farnham, Peggy J. Hirst, Martin Lander, Eric S. Mikkelsen, Tarjei S. Thomson, James A. TI The NIH Roadmap Epigenomics Mapping Consortium SO NATURE BIOTECHNOLOGY LA English DT Article ID GENE-EXPRESSION; EPIGENETIC REGULATION; HUMAN-DISEASE; HUMAN GENOME; PLURIPOTENT; MECHANISMS; CELLS; MAPS C1 [Bernstein, Bradley E.; Meissner, Alexander; Kellis, Manolis; Lander, Eric S.; Mikkelsen, Tarjei S.] Harvard & MIT, Broad Inst, Cambridge, MA USA. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA USA. [Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Stamatoyannopoulos, John A.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. [Stamatoyannopoulos, John A.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Costello, Joseph F.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Ren, Bing] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Milosavljevic, Aleksandar; Beaudet, Arthur L.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Marra, Marco A.; Hirst, Martin] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. [Ecker, Joseph R.] Salk Inst Biol Studies, Genom Anal Lab, La Jolla, CA 92037 USA. [Farnham, Peggy J.] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. [Thomson, James A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. RP Bernstein, BE (reprint author), Harvard & MIT, Broad Inst, Cambridge, MA USA. EM Bernstein.Bradley@mgh.harvard.edu RI Mikkelsen, Tarjei/A-1306-2007; Ecker, Joseph/B-9144-2008; Tang, Macy/B-9798-2014; Waha, Andreas/J-2950-2014; Hirst, Martin/B-7684-2016; Marra, Marco/B-5987-2008; OI Mikkelsen, Tarjei/0000-0002-8133-3135; Ecker, Joseph/0000-0001-5799-5895; Farnham, Peggy/0000-0003-4469-7914 FU NHGRI NIH HHS [R01 HG003523, R01 HG005085, R01 HG004037] NR 30 TC 541 Z9 549 U1 7 U2 46 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2010 VL 28 IS 10 BP 1045 EP 1048 DI 10.1038/nbt1010-1045 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 663GF UT WOS:000282870500025 PM 20944595 ER PT J AU Harris, RA Wang, T Coarfa, C Nagarajan, RP Hong, CB Downey, SL Johnson, BE Fouse, SD Delaney, A Zhao, YJ Olshen, A Ballinger, T Zhou, X Forsberg, KJ Gu, JC Echipare, L O'Geen, H Lister, R Pelizzola, M Xi, YX Epstein, CB Bernstein, BE Hawkins, RD Ren, B Chung, WY Gu, HC Bock, C Gnirke, A Zhang, MQ Haussler, D Ecker, JR Li, W Farnham, PJ Waterland, RA Meissner, A Marra, MA Hirst, M Milosavljevic, A Costello, JF AF Harris, R. Alan Wang, Ting Coarfa, Cristian Nagarajan, Raman P. Hong, Chibo Downey, Sara L. Johnson, Brett E. Fouse, Shaun D. Delaney, Allen Zhao, Yongjun Olshen, Adam Ballinger, Tracy Zhou, Xin Forsberg, Kevin J. Gu, Junchen Echipare, Lorigail O'Geen, Henriette Lister, Ryan Pelizzola, Mattia Xi, Yuanxin Epstein, Charles B. Bernstein, Bradley E. Hawkins, R. David Ren, Bing Chung, Wen-Yu Gu, Hongcang Bock, Christoph Gnirke, Andreas Zhang, Michael Q. Haussler, David Ecker, Joseph R. Li, Wei Farnham, Peggy J. Waterland, Robert A. Meissner, Alexander Marra, Marco A. Hirst, Martin Milosavljevic, Aleksandar Costello, Joseph F. TI Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications SO NATURE BIOTECHNOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; TRANSPOSABLE ELEMENTS; HUMAN GENOME; IMMUNOPRECIPITATION; GENES; 5-HYDROXYMETHYLCYTOSINE; ARABIDOPSIS; EXPRESSION; CONVERSION; RESOLUTION AB Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant ( their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression. C1 [Nagarajan, Raman P.; Hong, Chibo; Downey, Sara L.; Johnson, Brett E.; Fouse, Shaun D.; Olshen, Adam; Costello, Joseph F.] Univ Calif San Francisco, Dept Neurosurg, Brain Tumor Res Ctr, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Harris, R. Alan; Coarfa, Cristian; Waterland, Robert A.; Milosavljevic, Aleksandar] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Wang, Ting; Zhou, Xin; Forsberg, Kevin J.; Gu, Junchen] Washington Univ, Sch Med, Dept Genet, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA. [Delaney, Allen; Zhao, Yongjun; Marra, Marco A.; Hirst, Martin] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada. [Ballinger, Tracy; Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. [Echipare, Lorigail; O'Geen, Henriette; Farnham, Peggy J.] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA. [Echipare, Lorigail; O'Geen, Henriette; Farnham, Peggy J.] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. [Lister, Ryan; Pelizzola, Mattia; Ecker, Joseph R.] Salk Inst Biol Studies, Genom Anal Lab, La Jolla, CA 92037 USA. [Xi, Yuanxin; Li, Wei] Baylor Coll Med, Dept Mol & Cellular Biol, Dan L Duncan Canc Ctr, Div Biostat, Houston, TX 77030 USA. [Epstein, Charles B.; Bernstein, Bradley E.; Gu, Hongcang; Bock, Christoph; Gnirke, Andreas; Meissner, Alexander] Harvard & MIT, Broad Inst, Cambridge, MA USA. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA USA. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Hawkins, R. David; Ren, Bing] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Ren, Bing] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Chung, Wen-Yu; Zhang, Michael Q.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Chung, Wen-Yu; Zhang, Michael Q.] Univ Texas Dallas, Dept Mol & Cell Biol, Ctr Syst Biol, Dallas, TX 75230 USA. [Bock, Christoph; Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Bock, Christoph; Meissner, Alexander] Harvard Stem Cell Inst, Cambridge, MA USA. [Bock, Christoph] Max Planck Inst Informat, Saarbrucken, Germany. [Waterland, Robert A.] Baylor Coll Med, Dept Pediat, USDA ARS Childrens Nutr Res Ctr, Houston, TX 77030 USA. RP Costello, JF (reprint author), Univ Calif San Francisco, Dept Neurosurg, Brain Tumor Res Ctr, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. EM jcostello@cc.ucsf.edu RI Bock, Christoph/B-6723-2008; Lister, Ryan/B-5168-2012; Ecker, Joseph/B-9144-2008; Tang, Macy/B-9798-2014; Hirst, Martin/B-7684-2016; Marra, Marco/B-5987-2008; OI Bock, Christoph/0000-0001-6091-3088; Lister, Ryan/0000-0001-6637-7239; Ecker, Joseph/0000-0001-5799-5895; Pelizzola, Mattia/0000-0001-6672-9636; Gu, Junchen/0000-0002-0928-7453; Farnham, Peggy/0000-0003-4469-7914 FU National Institute on Drug Abuse (NIDA); NIH [5U01ES017154-02, 5U01DA025956-02, 6U01ES017155-02, 5U01ES017166-02, T32 CA108462-04, F32CA141799, T32 CA108462-06, T32 GM008568]; CIRM [TB1-01190] FX We would like to thank the US National Institutes of Health (NIH) Roadmap Epigenomics Program; sponsored by the National Institute on Drug Abuse (NIDA) and the National Institute of Environmental Health Sciences (NIEHS). J.F.C. and M. H. are supported by NIH grant 5U01ES017154-02. A. Milosavljevic is supported by NIH grant 5U01DA025956-02. A. Meissner and B. E. B. are supported by NIH grant 6U01ES017155-02. J.R.E. and B. R. are supported by NIH grant 5U01ES017166-02. R.P.N. was supported by NIH T32 CA108462-04 and F32CA141799. S. L. D. was supported by CIRM TB1-01190. S. D. F. was supported by NIH T32 CA108462-06. B.E.J. was supported by NIH T32 GM008568. M. A. M. is a Terry Fox Young Investigator and a Michael Smith Senior Research Scholar. We thank Z. Zhang and H. Li for modifying the ZOOM algorithm for bisulfite alignments. NR 44 TC 314 Z9 320 U1 5 U2 76 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2010 VL 28 IS 10 BP 1097 EP U194 DI 10.1038/nbt.1682 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 663GF UT WOS:000282870500032 PM 20852635 ER PT J AU Ghaffari, R Aranyosi, AJ Richardson, GP Freeman, DM AF Ghaffari, Roozbeh Aranyosi, Alexander J. Richardson, Guy P. Freeman, Dennis M. TI Tectorial membrane travelling waves underlie abnormal hearing in Tectb mutant mice SO NATURE COMMUNICATIONS LA English DT Article ID OUTER-HAIR-CELL; MAMMALIAN COCHLEA; BASILAR-MEMBRANE; MOTIONS; AMPLIFICATION; MECHANICS; AMPLIFIER; BUNDLES; MOUSE; MODEL AB Remarkable sensitivity and exquisite frequency selectivity are hallmarks of mammalian hearing, but their underlying mechanisms remain unclear. Cochlear insults and hearing disorders that decrease sensitivity also tend to broaden tuning, suggesting that these properties are linked. However, a recently developed mouse model of genetically altered hearing (Tectb(-/-)) shows decreased sensitivity and sharper frequency selectivity. In this paper, we show that the Tectb mutation reduces the spatial extent and propagation velocity of tectorial membrane (TM) travelling waves and that these changes in wave propagation are likely to account for all of the hearing abnormalities associated with the mutation. By reducing the spatial extent of TM waves, the Tectb mutation decreases the spread of excitation and thereby increases frequency selectivity. Furthermore, the change in TM wave velocity reduces the number of hair cells that effectively couple energy to the basilar membrane, which reduces sensitivity. These results highlight the importance of TM waves in hearing. C1 [Ghaffari, Roozbeh; Freeman, Dennis M.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Ghaffari, Roozbeh; Aranyosi, Alexander J.; Freeman, Dennis M.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Richardson, Guy P.] Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England. [Freeman, Dennis M.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Freeman, Dennis M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Freeman, DM (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. EM freeman@mit.edu OI Aranyosi, Alexander/0000-0002-8133-5026 FU National Institutes of Health [R01-DC000238]; Wellcome Trust [071394/Z/03/Z, 087737] FX We thank J.J. Guinan, C.A. Shera, A.J. Grodzinsky, S.C. Page and S. Farrahi for helpful discussions and comments on the manuscript. This research was supported by the National Institutes of Health Grant R01-DC000238. R.G. was supported in part by a training grant from the National Institutes of Health to the Speech and Hearing Bioscience and Technology Program in the Harvard-MIT Division of Health Sciences and Technology. G.P.R. was supported by Wellcome Trust Grants 071394/Z/03/Z and 087737. NR 30 TC 30 Z9 30 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2010 VL 1 AR 96 DI 10.1038/ncomms1094 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673GJ UT WOS:000283647100015 PM 20981024 ER PT J AU Calvo, SE Tucker, EJ Compton, AG Kirby, DM Crawford, G Burtt, NP Rivas, M Guiducci, C Bruno, DL Goldberger, OA Redman, MC Wiltshire, E Wilson, CJ Altshuler, D Gabriel, SB Daly, MJ Thorburn, DR Mootha, VK AF Calvo, Sarah E. Tucker, Elena J. Compton, Alison G. Kirby, Denise M. Crawford, Gabriel Burtt, Noel P. Rivas, Manuel Guiducci, Candace Bruno, Damien L. Goldberger, Olga A. Redman, Michelle C. Wiltshire, Esko Wilson, Callum J. Altshuler, David Gabriel, Stacey B. Daly, Mark J. Thorburn, David R. Mootha, Vamsi K. TI High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency SO NATURE GENETICS LA English DT Article ID RESPIRATORY-CHAIN DISORDERS; MITOCHONDRIAL DISEASE; NONSENSE MUTATION; LEIGH-SYNDROME; NDUFS4 GENE; CHILDREN; DNA; ENCEPHALOPATHY; CRITERIA; DATABASE AB Discovering the molecular basis of mitochondrial respiratory chain disease is challenging given the large number of both mitochondrial and nuclear genes that are involved. We report a strategy of focused candidate gene prediction, high-throughput sequencing and experimental validation to uncover the molecular basis of mitochondrial complex I disorders. We created seven pools of DNA from a cohort of 103 cases and 42 healthy controls and then performed deep sequencing of 103 candidate genes to identify 151 rare variants that were predicted to affect protein function. We established genetic diagnoses in 13 of 60 previously unsolved cases using confirmatory experiments, including cDNA complementation to show that mutations in NUBPL and FOXRED1 can cause complex I deficiency. Our study illustrates how large-scale sequencing, coupled with functional prediction and experimental validation, can be used to identify causal mutations in individual cases. C1 [Calvo, Sarah E.; Rivas, Manuel; Goldberger, Olga A.; Altshuler, David; Daly, Mark J.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Calvo, Sarah E.; Goldberger, Olga A.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Calvo, Sarah E.; Crawford, Gabriel; Burtt, Noel P.; Rivas, Manuel; Guiducci, Candace; Redman, Michelle C.; Altshuler, David; Gabriel, Stacey B.; Daly, Mark J.; Mootha, Vamsi K.] Harvard & MIT, Broad Inst, Cambridge, MA USA. [Tucker, Elena J.; Compton, Alison G.; Kirby, Denise M.; Bruno, Damien L.; Thorburn, David R.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Tucker, Elena J.; Compton, Alison G.; Kirby, Denise M.; Bruno, Damien L.; Thorburn, David R.] Royal Childrens Hosp, Victorian Clin Genet Serv, Melbourne, Vic, Australia. [Tucker, Elena J.; Thorburn, David R.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Wiltshire, Esko] Univ Otago Wellington, Dept Paediat & Child Hlth, Wellington, New Zealand. [Wiltshire, Esko] Capital & Coast Dist Hlth Board, Cent Reg Genet Serv, Wellington, New Zealand. [Wilson, Callum J.] Starship Childrens Hosp, Natl Metab Serv, Auckland, New Zealand. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM david.thorburn@mcri.edu.au; vamsi@hms.harvard.edu RI Altshuler, David/A-4476-2009; Tucker, Elena/B-3487-2012; Thorburn, David/G-6266-2013; Bruno, Damien/C-3665-2013; OI Altshuler, David/0000-0002-7250-4107; thorburn, david/0000-0002-7725-9470; Compton, Alison/0000-0002-2725-7055 FU Australian National Health & Medical Research Council [436901]; Australian Postgraduate Award; US National Institutes of Health [GM077465] FX We thank S. Tregoning, A. Laskowski and S. Smith for assistance with enzyme assays and DNA preparation, M. McKenzie and M. Ryan for the NDUFAF2 antibody, J. Boehm for the lentiviral expression vector, S. Flynn for assistance with human subjects protocols, R. Onofrio for designing PCR primers, K. Ardlie and S. Mahan for assistance in DNA sample preparation, J. Wilkinson and L. Ambrogio for Illumina sequence project management, T. Fennel for sequence alignment, L. Ziaugra for genotyping assistance, M. Cabili for tool evaluation, J. Flannick for assistance with pooled sequence analysis, I. Adzhubei and S. Sunyaev for PolyPhen-2.0 predictions, M. DePristo, E. Banks and A. Sivachenko for advice on sequence data analysis, M. Garber for assistance with evolutionary conservation analyses, J. Pirruccello, R. Do and S. Kathiresan for data and analysis of control data, and the many physicians who referred subjects and assisted with these studies. This work was supported by a grant (436901) and Principal Research Fellowship from the Australian National Health & Medical Research Council awarded to D. R. T., an Australian Postgraduate Award to E. J. T. and a grant from the US National Institutes of Health (GM077465) to V. K. M. The authors wish to dedicate this article to the memory of our co-author Denise Kirby, an outstanding scientist and dear colleague who died during the preparation of this manuscript. NR 51 TC 171 Z9 187 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2010 VL 42 IS 10 BP 851 EP + DI 10.1038/ng.659 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 655UO UT WOS:000282276600014 PM 20818383 ER PT J AU Goode, LL Chenevix-Trench, G Song, H Ramus, SJ Notaridou, M Lawrenson, K Widschwendter, M Vierkant, RA Larson, MC Kjaer, SK Birrer, MJ Berchuck, A Schildkraut, J Tomlinson, I Kiemeney, LA Cook, LS Gronwald, J Garcia-Closas, M Gore, ME Campbell, I Whittemore, AS Sutphen, R Phelan, C Anton-Culver, H Pearce, CL Lambrechts, D Rossing, MA Chang-Claude, J Moysich, KB Goodman, MT Dork, T Nevanlinna, H Ness, RB Rafnar, T Hogdall, C Hogdall, E Fridley, BL Cunningham, JM Sieh, W McGuire, V Godwin, AK Cramer, DW Hernandez, D Levine, D Lu, K Iversen, ES Palmieri, RT Houlston, R van Altena, AM Aben, KKH Massuger, LFAG Brooks-Wilson, A Kelemen, LE Le, ND Jakubowska, A Lubinski, J Medrek, K Stafford, A Easton, DF Tyrer, J Bolton, KL Harrington, P Eccles, D Chen, A Molina, AN Davila, BN Arango, H Tsai, Y Chen, ZH Risch, HA McLaughlin, J Narod, SA Ziogas, A Brewster, W Gentry-Maharaj, A Menon, U Wu, AH Stram, DO Pike, MC Beesley, J Webb, PM Chen, XQ Ekici, AB Thiel, FC Beckmann, MW Yang, H Wentzensen, N Lissowska, J Fasching, PA Despierre, E Amant, F Vergote, I Doherty, J Hein, R Wang-Gohrke, S Lurie, G Carney, ME Thompson, PJ Runnebaum, I Hillemanns, P Durst, M Antonenkova, N Bogdanova, N Leminen, A Butzow, R Heikkinen, T Stefansson, K Sulem, P Besenbacher, S Sellers, TA Gayther, SA Pharoah, PDP AF Goode, Llen L. Chenevix-Trench, Georgia Song, Honglin Ramus, Susan J. Notaridou, Maria Lawrenson, Kate Widschwendter, Martin Vierkant, Robert A. Larson, Melissa C. Kjaer, Susanne K. Birrer, Michael J. Berchuck, Andrew Schildkraut, Joellen Tomlinson, Ian Kiemeney, Lambertus A. Cook, Linda S. Gronwald, Jacek Garcia-Closas, Montserrat Gore, Martin E. Campbell, Ian Whittemore, Alice S. Sutphen, Rebecca Phelan, Catherine Anton-Culver, Hoda Pearce, Celeste Leigh Lambrechts, Diether Rossing, Mary Anne Chang-Claude, Jenny Moysich, Kirsten B. Goodman, Marc T. Doerk, Thilo Nevanlinna, Heli Ness, Roberta B. Rafnar, Thorunn Hogdall, Claus Hogdall, Estrid Fridley, Brooke L. Cunningham, Julie M. Sieh, Weiva McGuire, Valerie Godwin, Andrew K. Cramer, Daniel W. Hernandez, Dena Levine, Douglas Lu, Karen Iversen, Edwin S. Palmieri, Rachel T. Houlston, Richard van Altena, Anne M. Aben, Katja K. H. Massuger, Leon F. A. G. Brooks-Wilson, Angela Kelemen, Linda E. Le, Nhu D. Jakubowska, Anna Lubinski, Jan Medrek, Krzysztof Stafford, Anne Easton, Douglas F. Tyrer, Jonathan Bolton, Kelly L. Harrington, Patricia Eccles, Diana Chen, Ann Molina, Ashley N. Davila, Barbara N. Arango, Hector Tsai, Yu Chen, Zhihua Risch, Harvey A. McLaughlin, John Narod, Steven A. Ziogas, Argyrios Brewster, Wendy Gentry-Maharaj, Aleksandra Menon, Usha Wu, Anna H. Stram, Daniel O. Pike, Malcolm C. Beesley, Jonathan Webb, Penelope M. Chen, Xiaoqing Ekici, Arif B. Thiel, Falk C. Beckmann, Matthias W. Yang, Hannah Wentzensen, Nicolas Lissowska, Jolanta Fasching, Peter A. Despierre, Evelyn Amant, Frederic Vergote, Ignace Doherty, Jennifer Hein, Rebecca Wang-Gohrke, Shan Lurie, Galina Carney, Michael E. Thompson, Pamela J. Runnebaum, Ingo Hillemanns, Peter Duerst, Matthias Antonenkova, Natalia Bogdanova, Natalia Leminen, Arto Butzow, Ralf Heikkinen, Tuomas Stefansson, Kari Sulem, Patrick Besenbacher, Soeren Sellers, Thomas A. Gayther, Simon A. Pharoah, Paul D. P. CA Wellcome Trust Case-Control Conso Australian Canc Study Ovarian Canc Australian Ovarian Canc Study Grp OCAC TI A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24 SO NATURE GENETICS LA English DT Article ID COLORECTAL-CANCER; POLY(ADP-RIBOSE) POLYMERASE; EPITHELIAL-CELLS; MULTIPLE LOCI; IN-VITRO; GENE; METAANALYSIS; VARIANTS; CARRIERS AB Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2)(1). Here, we report on nine additional candidate loci (defined as having P <= 10(-4)) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P <= 5 x 10(-8) (8q24, P = 8.0 x 10(-15) and 2q31, P = 3.8 x 10(-14)) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 x 10(-8) and 17q21, P = 1.4 x 10(-7)). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development. C1 [Goode, Llen L.; Vierkant, Robert A.; Larson, Melissa C.; Fridley, Brooke L.] Mayo Clin Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Chenevix-Trench, Georgia; Beesley, Jonathan; Webb, Penelope M.; Chen, Xiaoqing; Australian Canc Study Ovarian Canc] Post Off Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld, Australia. [Song, Honglin; Stafford, Anne; Tyrer, Jonathan; Harrington, Patricia] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cancer Res United Kingdom, Cambridge, England. [Notaridou, Maria; Lawrenson, Kate; Widschwendter, Martin; Menon, Usha; Gayther, Simon A.] UCL, Dept Gynecol Oncol, Elizabeth Garrett Anderson EGA Inst Womens Hlt, London, England. [Kjaer, Susanne K.; Runnebaum, Ingo] Juliane Marie Ctr, Dept Gynecol & Obstet, Copenhagen, Denmark. [Kjaer, Susanne K.; Runnebaum, Ingo] Inst Canc Epidemiol, Dept Virus, Hormones & Canc, Danish Canc Soc, Copenhagen, Denmark. [Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Berchuck, Andrew; Schildkraut, Joellen] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC USA. [Tomlinson, Ian] London Sch Med & Dent, Inst Canc, Ctr Mol Oncol & Imaging, London, England. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol, Biostatist & Hlth Technol Assessment HTA, NL-6525 ED Nijmegen, Netherlands. [Lubinski, Jan] Univ New Mexico, Div Epidemiol & Biostatist, Albuquerque, NM 87131 USA. [Cook, Linda S.] Alberta Hlth Services Canc Care, Calgary, AB, Canada. [Gronwald, Jacek; Medrek, Krzysztof] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland. [Garcia-Closas, Montserrat; Wentzensen, Nicolas] Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Rockville, MD USA. [Gore, Martin E.] Royal Marsden Hosp, Gynecol Oncol Unit, London, England. [Campbell, Ian] Peter MacCallum Canc Inst, Ctr Canc Genom & Predict Med, Melbourne, Australia. [Campbell, Ian] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Whittemore, Alice S.; Molina, Ashley N.; Davila, Barbara N.] Stanford Univ, Sch Med, Div Epidemiol & Biostatist, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Sutphen, Rebecca; Sieh, Weiva; McGuire, Valerie] Univ S Florida, Coll Med, Pediat Epidemiol Ctr, Tampa, FL USA. [Phelan, Catherine] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA. [Pearce, Celeste Leigh; Wu, Anna H.; Stram, Daniel O.; Pike, Malcolm C.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [Lambrechts, Diether] VIB, Vesalius Res Ctr, Brussels, Belgium. [Lambrechts, Diether] LU Leuven, Louvain, Belgium. [Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Chang-Claude, Jenny; Hein, Rebecca] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. [Goodman, Marc T.; Carney, Michael E.; Thompson, Pamela J.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Doerk, Thilo] Hannover Med Sch, Clin Obstet & Gynaecol, Hannover, Germany. [Nevanlinna, Heli; Leminen, Arto; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki, Finland. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Rafnar, Thorunn; Stefansson, Kari; Sulem, Patrick; Besenbacher, Soeren] DeCODE Genet, Reykjavik, Iceland. [Hogdall, Claus] Juliane Marie Ctr, Dept Gynecol & Obstet, Copenhagen, Denmark. [Hogdall, Estrid] Hormones & Canc Inst Canc Epidemiol, Danish Canc Soc, Dept Virus, Copenhagen, Denmark. [Cunningham, Julie M.] Mayo Clin Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Godwin, Andrew K.] Fox Chase Canc Ctr, Dept Med Oncol, Womens Canc Program, Philadelphia, PA 19111 USA. [Cramer, Daniel W.] Brigham & Womens Hosp, Obstetr & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Hernandez, Dena] Natl Inst Hlth, NIA, Bethesda, MD USA. [Levine, Douglas] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lu, Karen] MD Anderson Canc Ctr, Houston, TX USA. [Iversen, Edwin S.] Duke Univ, Dept Stat, Durham, NC USA. [Palmieri, Rachel T.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Houlston, Richard] Inst Canc Res, Royal Canc Hosp, Mol & Populat Genet Team, London, England. [van Altena, Anne M.; Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Dept Gynaecol, NL-6525 ED Nijmegen, Netherlands. [Aben, Katja K. H.] Comprehens Canc Ctr E, Nijmegen, Netherlands. [Brooks-Wilson, Angela] Genome Sci Ctr, British Columbia Canc Agcy, Vancouver, BC, Canada. [Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC, Canada. [Kelemen, Linda E.] Alberta Hlth Serv Canc Care, Calgary, AB, Canada. [Le, Nhu D.] British Columbia Canc Agcy, Cancer Control Res, Vancouver, BC V5Z 4E6, Canada. [Easton, Douglas F.] Univ Cambridge, Strangeways Res Lab, Canc Res United Kingdom Genet Epidemiol Unit, Cambridge, England. [Bolton, Kelly L.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England. [Eccles, Diana] Univ Southampton, Sch Med, Wessex Clin Genet Serv Princess Anne Hosp, Southampton, Hants, England. [Arango, Hector] W Coast Gynecol Oncol, Clearwater, FL USA. [Risch, Harvey A.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. [McLaughlin, John] Canc Care Ontario, Toronto, ON, Canada. [Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada. [Brewster, Wendy] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Australian Ovarian Canc Study Grp] Peter MacCallum Canc Inst, Melbourne, Australia. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, D-8520 Erlangen, Germany. [Thiel, Falk C.] Univ Breast Ctr Franconia, Univ Hosp Erlangen, Dept Gynecol & Obstet, Erlangen, Germany. [Beckmann, Matthias W.; Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Beckmann, Matthias W.; Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Fasching, Peter A.] Univ Calif Los Angeles, Dept Med, Div Hematol & Oncol, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Despierre, Evelyn; Amant, Frederic; Vergote, Ignace] Univ Hosp Leuven, Dept Gynecol Oncol, Leuven, Belgium. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Duerst, Matthias] Friedrich Schiller Univ, Clin Obstet & Gynaecol, Jena, Germany. [Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandro N, Minsk, Byelarus. [Bogdanova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandro N, Minsk, Byelarus. [Bogdanova, Natalia] Hannover Med Sch, Clin Obstet & Gynaecol, D-3000 Hannover, Germany. [Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki, Finland. [Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland. [Pharoah, Paul D. P.] Univ Cambridge, Strangeways Res Lab, Canc Res United Kingdom Dept Oncol, Cambridge, England. [Pharoah, Paul D. P.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England. RP Gayther, SA (reprint author), Mayo Clin Coll Med, Dept Hlth Sci Res, Rochester, MN USA. EM gayther@usc.edu RI Menon, Usha/C-4716-2008; Verdrengh, Evelien/H-4571-2012; Webb, Penelope/D-5736-2013; Ekici, Arif/C-3971-2013; Fridley, Brooke/D-8315-2015; Garcia-Closas, Montserrat /F-3871-2015; van Altena, Anne/B-9824-2016; McLaughlin, John/E-4577-2013; Kiemeney, Lambertus/D-3357-2009; Tang, Macy/B-9798-2014; Brooks-Wilson, Angela/E-9399-2012; Massuger, Leon/H-8072-2014; Jakubowska, Anna/O-8050-2014; Dork, Thilo/J-8620-2012; Aben, Katja/G-9686-2016; Gronwald, Jacek/A-4576-2017; OI Webb, Penelope/0000-0003-0733-5930; Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat /0000-0003-1033-2650; Kiemeney, Lambertus/0000-0002-2368-1326; Brooks-Wilson, Angela/0000-0003-1009-6408; Aben, Katja/0000-0002-0214-2147; Gronwald, Jacek/0000-0002-3643-2871; Vierkant, Robert/0000-0001-6242-5221; Kjaer, Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798; Lissowska, Jolanta/0000-0003-2695-5799; Nevanlinna, Heli/0000-0002-0916-2976; Besenbacher, Soren/0000-0003-1455-1738; Houlston, Richard/0000-0002-5268-0242 FU Ovarian Cancer Research Fund; Mermaid 1; Danish Cancer Society; National Cancer Institute, Bethesda, Maryland, USA [R01-CA61107]; US National Institutes of Health; National Cancer Institute [R01CA- 122443, CA-58860, CA-92044, R01-CA58598, N01-CN-55424, N01-PC-67001, N01-PC-35137]; Mayo Foundation; US National Cancer Institute; Department of Health and Human Services; Ovarian Cancer Specialized Program of Research Excellence (SPORE) [P50 CA083638]; Cancer Research UK; Eastern Cancer Registration and Information Centre for subject recruitment; US National Institutes of Health [R01-CA106414, R01-CA-63682, R01CA- 63678, R01-CA112523, R01-CA-87538]; American Cancer Society [CRTG-00-196-01-CCE]; Advanced Cancer Detection Center; Department of Defense [DAMD17-98-1-8659]; Canadian Institutes for Health Research; Canadian Cancer Society; University of California, Irvine [R01-CA-114343]; Lon V Smith Foundation [LVS-39420]; OAK Foundation; National Health and Medical Research Council of Australia [199600]; US Army Medical Research and Materiel Command [DAMD17-01-1-0729, W81XWH-06-1-0220]; Cancer Council Tasmania; Cancer Foundation of Western Australia; ELAN Foundation; Erlangen University Hospital; German Federal Ministry of Education and Research of Germany; Programme of Clinical Biomedical Research [01 GB 9401]; University of Ulm; German Cancer Research Center; California Cancer Research Program [00-01389V-20170, 2110200]; Helsinki University Central Hospital; Academy of Finland; Finnish Cancer Society FX This study made use of data generated by the Wellcome Trust Case Control consortium. A full list of the investigators who contributed to the generation of the data is available from http://www. wtccc. org. uk/.Funding for the project was provided by the Wellcome Trust under award 076113. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith.; The MAL study is supported by grants from Mermaid 1, the Danish Cancer Society and the National Cancer Institute, Bethesda, Maryland, USA (R01-CA61107). The MAY study and the phase 3 and combined analyses were supported by the US National Institutes of Health, National Cancer Institute grants R01CA- 122443 and funding from the Mayo Foundation. The PBCS was funded by Intramural Research Funds of the US National Cancer Institute, Department of Health and Human Services. The Fox Chase Cancer Center ovarian cancer study, part of the National Cancer Institute collaboration, is supported by an Ovarian Cancer Specialized Program of Research Excellence (SPORE) (P50 CA083638). The NCO study is supported by the US National Institutes of Health, National Cancer Institute grant R01-CA-76016. The SEA study is funded by a programme grant from Cancer Research UK. We thank the SEARCH team and the Eastern Cancer Registration and Information Centre for subject recruitment. The TBO study was supported by the US National Institutes of Health (R01-CA106414); the American Cancer Society (CRTG-00-196-01-CCE); and the Advanced Cancer Detection Center Grant, Department of Defense (DAMD17-98-1-8659). The TOR study was supported by grants from the Canadian Institutes for Health Research, the National Cancer Institute of Canada with funds provided by the Canadian Cancer Society and the US National Institutes of Health (R01-CA-63682 and R01CA- 63678). Additional support for the TOR, NCO, MAY, TBO and NCI studies was provided by the University of California, Irvine grant R01-CA-114343. The UCI study is supported by the US National Institutes of Health, National Cancer Institute grants CA-58860, CA-92044 and the Lon V Smith Foundation grant LVS-39420. The UKO study is supported by funding from Cancer Research UK, the Eve Appeal and the OAK Foundation. Some of this work was undertaken at University College London Hospital/University College London, who received a proportion of funding from the Department of Health's National Institutes for Health Research Biomedical Research Centre funding scheme. We particularly thank I. Jacobs, E. Wozniak, A. Ryan, J. Ford and N. Balogun for their contribution to the study. The AUS study is supported by the National Health and Medical Research Council of Australia (199600), US Army Medical Research and Materiel Command under DAMD17-01-1-0729 (award no. W81XWH-06-1-0220) and the Cancer Council Tasmania and Cancer Foundation of Western Australia. G. C.-M. T. and P. M. W. are Research Fellows of the National Health and Medical Research Council. The Australian Ovarian Cancer Study (AOCS) Management Group (D. Bowtell, A. deFazio, G. C.-T., D. G., A. K. G. and P. M. W.) gratefully acknowledges the contribution of all the clinical and scientific collaborators (see http://www. aocstudy. org/). The Australian Cancer Study (ACS) Management Group comprises P. D. P. P., P. M. W., A. Green, N. Hayward and D. Whiteman. The BAV study is supported by the ELAN Foundation and Erlangen University Hospital. The BEL study is supported by the National Cancer Plan-Action 29 for the support of Translational Research. The DOV study (Seattle Diseases of the Ovary) was supported by the US National Institutes of Health grants R01-CA112523 and R01-CA-87538. The GER study was supported by the German Federal Ministry of Education and Research of Germany, the Programme of Clinical Biomedical Research (01 GB 9401), and the genotyping was supported in part by the state of Baden-Wrttemberg through the Medical Faculty, University of Ulm (P. 685).; Data management wassupported by the German Cancer Research Center. The HAW study was supported by the US Public Health Service grant R01-CA58598 and contracts N01-CN-55424, N01-PC-67001 and N01-PC-35137 from the National Cancer Institute, US National Institutes of Health, Department of Health and Human Services. Funding for the USC study was received from the California Cancer Research Program grants 00-01389V-20170 and 2110200, US Public Health Service grants CA14089, CA17054, CA61132, CA63464, N01-PC-67010 and R03CA113148 and the California Department of Health Services sub-contract 050E8709 as part of its statewide cancer reporting program (University of Southern California). The HJO study gratefully acknowledges the contribution of F. Kramer and W. Zheng to the recruitment of subjects at Hannover Medical School. The HMO study gratefully acknowledges the help of L. Gacucova in sample preparation. The HOC study was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland and the Finnish Cancer Society. NR 30 TC 131 Z9 132 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2010 VL 42 IS 10 BP 874 EP + DI 10.1038/ng.668 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 655UO UT WOS:000282276600018 ER PT J AU Bolton, KL Tyrer, J Song, H Ramus, SJ Notaridou, M Jones, C Sher, T Gentry-Maharaj, A Wozniak, E Tsai, YY Weidhaas, J Paik, D Van den Berg, DJ Stram, DO Pearce, CL Wu, AH Brewster, W Anton-Culver, H Ziogas, A Narod, SA Levine, DA Kaye, SB Brown, R Paul, J Flanagan, J Sieh, W McGuire, V Whittemore, AS Campbell, I Gore, ME Lissowska, J Yang, HP Medrek, K Gronwald, J Lubinski, J Jakubowska, A Le, ND Cook, LS Kelemen, LE Brook-Wilson, A Massuger, LFAG Kiemeney, LA Aben, KKH van Altena, AM Houlston, R Tomlinson, I Palmieri, RT Moorman, PG Schildkraut, J Iversen, ES Phelan, C Vierkant, RA Cunningham, JM Goode, EL Fridley, BL Kruger-Kjaer, S Blaeker, J Hogdall, E Hogdall, C Gross, J Karlan, BY Ness, RB Edwards, RP Odunsi, K Moyisch, KB Baker, JA Modugno, F Heikkinenen, T Butzow, R Nevanlinna, H Leminen, A Bogdanova, N Antonenkova, N Doerk, T Hillemanns, P Duurst, M Runnebaum, I Thompson, PJ Carney, ME Goodman, MT Lurie, G Wang-Gohrke, S Hein, R Chang-Claude, J Rossing, MA Cushing-Haugen, KL Doherty, J Chen, C Rafnar, T Besenbacher, S Sulem, P Stefansson, K Birrer, MJ Terry, KL Hernandez, D Cramer, DW Vergote, I Amant, F Lambrechts, D Despierre, E Fasching, PA Beckmann, MW Thiel, FC Ekici, AB Chen, XQ Johnatty, SE Webb, PM Beesley, J Chanock, S Garcia-Closas, M Sellers, T Easton, DF Berchuck, A Chenevix-Trench, G Pharoah, PDP Gayther, SA AF Bolton, Kelly L. Tyrer, Jonathan Song, Honglin Ramus, Susan J. Notaridou, Maria Jones, Chris Sher, Tanya 3 Gentry-Maharaj, Aleksandra Wozniak, Eva Tsai, Ya-Yu Weidhaas, Joanne Paik, Daniel Van den Berg, David J. Stram, Daniel O. Pearce, Celeste Leigh Wu, Anna H. Brewster, Wendy Anton-Culver, Hoda Ziogas, Argyrios Narod, Steven A. Levine, Douglas A. Kaye, Stanley B. Brown, Robert Paul, Jim Flanagan, James Sieh, Weiva McGuire, Valerie Whittemore, Alice S. Campbell, Ian Gore, Martin E. Lissowska, Jolanta Yang, Hanna P. Medrek, Krzysztof Gronwald, Jacek Lubinski, Jan Jakubowska, Anna Le, Nhu D. Cook, Linda S. Kelemen, Linda E. Brook-Wilson, Angela Massuger, Leon F. A. G. Kiemeney, Lambertus A. Aben, Katja K. H. van Altena, Anne M. Houlston, Richard Tomlinson, Ian Palmieri, Rachel T. Moorman, Patricia G. Schildkraut, Joellen Iversen, Edwin S. Phelan, Catherine Vierkant, Robert A. Cunningham, Julie M. Goode, Ellen L. Fridley, Brooke L. Kruger-Kjaer, Susan Blaeker, Jan Hogdall, Estrid Hogdall, Claus Gross, Jenny Karlan, Beth Y. Ness, Roberta B. Edwards, Robert P. Odunsi, Kunle Moyisch, Kirsten B. Baker, Julie A. Modugno, Francesmary Heikkinenen, Tuomas Butzow, Ralf Nevanlinna, Heli Leminen, Arto Bogdanova, Natalia Antonenkova, Natalia Doerk, Thilo Hillemanns, Peter Duerst, Matthias Runnebaum, Ingo Thompson, Pamela J. Carney, Michael E. Goodman, Marc T. Lurie, Galina Wang-Gohrke, Shan Hein, Rebecca Chang-Claude, Jenny Rossing, Mary Anne Cushing-Haugen, Kara L. Doherty, Jennifer Chen, Chu Rafnar, Thorunn Besenbacher, Soren Sulem, Patrick Stefansson, Kari Birrer, Michael J. Terry, Kathryn L. Hernandez, Dena Cramer, Daniel W. Vergote, Ignace Amant, Frederic Lambrechts, Diether Despierre, Evelyn Fasching, Peter A. Beckmann, Matthias W. Thiel, Falk C. Ekici, Arif B. Chen, Xiaoqing Johnatty, Sharon E. Webb, Penelope M. Beesley, Jonathan Chanock, Stephen Garcia-Closas, Montserrat Sellers, Tom Easton, Douglas F. Berchuck, Andrew Chenevix-Trench, Georgia Pharoah, Paul D. P. Gayther, Simon A. CA Australian Ovarian Canc Study Grp Australian Canc Study Ovarian Canc Ovarian Canc Assoc Consortium TI Common variants at 19p13 are associated with susceptibility to ovarian cancer SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BRCA1; GENOTYPES; COMPLEX; BREAST; CELLS AB Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women(1). We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5 x 10(-4) and P = 6 x 10(-4), respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3 x 10(-9) and P = 4 x 10(-11), respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development. C1 [Bolton, Kelly L.; Tyrer, Jonathan; Song, Honglin; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge, England. [Bolton, Kelly L.; Yang, Hanna P.; Kiemeney, Lambertus A.; Chanock, Stephen; Garcia-Closas, Montserrat] Natl Canc Inst, Natl Inst Hlth, Div Canc Epidemiol & Genet, Rockville, MD USA. [Ramus, Susan J.; Notaridou, Maria; Jones, Chris; Sher, Tanya 3; Gentry-Maharaj, Aleksandra; Gayther, Simon A.] UCL, Inst Womens Hlth, Dept Gynecol Oncol, EGA, London, England. [Tsai, Ya-Yu] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Weidhaas, Joanne] Yale Univ, Dept Therapeut Radiol, New Haven, CT 06510 USA. [Paik, Daniel] Yale Univ, Dept Obstet & Gynecol, New Haven, CT USA. [Van den Berg, David J.; Stram, Daniel O.; Pearce, Celeste Leigh; Wu, Anna H.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Brewster, Wendy; Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA. [Narod, Steven A.] Ctr Res Womens Hlth, Toronto, ON, Canada. [Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA. [Kaye, Stanley B.] Inst Canc Res, Med Sect, Sutton, Surrey, England. [Brown, Robert; Flanagan, James] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London, England. [Paul, Jim] Univ Glasgow, Canc Res UK Clin Trials Unit, Glasgow, Lanark, Scotland. [Sieh, Weiva; McGuire, Valerie; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Australian Ovarian Canc Study Grp] Peter MacCallum Canc Inst, Melbourne, Australia. [Campbell, Ian; Gore, Martin E.] Royal Marsden Hosp, Gynecol Oncol Unit, London SW3 6JJ, England. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Medrek, Krzysztof; Gronwald, Jacek; Lubinski, Jan; Jakubowska, Anna] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland. [Le, Nhu D.] British Columbia Canc Agcy, Canc Control Res, Vancouver, BC V5Z 4E6, Canada. [Cook, Linda S.] Univ New Mexico, Div Epidemiol & Biostatist, Albuquerque, NM 87131 USA. [Cook, Linda S.; Kelemen, Linda E.] Alberta Hlth Serv Canc Care, Calgary, AB, Canada. [Brook-Wilson, Angela] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. [Brook-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada. [Massuger, Leon F. A. G.; van Altena, Anne M.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Gynaecol, Nijmegen, Netherlands. [Aben, Katja K. H.] Comprehens Canc Ctr E, Nijmegen, Netherlands. [Houlston, Richard] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England. [Tomlinson, Ian] Wellcome Trust Ctr Human Genet, Populat & Funct Genet Lab, Oxford, England. [Palmieri, Rachel T.; Moorman, Patricia G.; Schildkraut, Joellen; Berchuck, Andrew] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC USA. [Iversen, Edwin S.] Duke Univ, Dept Stat, Durham, NC USA. [Vierkant, Robert A.; Goode, Ellen L.; Fridley, Brooke L.] Mayo Clin Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Cunningham, Julie M.] Mayo Clin Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Kruger-Kjaer, Susan; Hogdall, Estrid] Danish Canc Soc, Dept Virus, Copenhagen, Denmark. [Kruger-Kjaer, Susan; Hogdall, Estrid] Danish Canc Soc, Canc Inst Canc Epidemiol, Canc Inst Canc Epidemiol, Copenhagen, Denmark. [Blaeker, Jan] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Hogdall, Claus] Juliane Marie Ctr, Gynaecol Clin, Copenhagen, Denmark. [Gross, Jenny; Karlan, Beth Y.] Cedars Sinai Med Ctr, Womens Canc Res Inst, Samuel Oschin Comprehens Canc Ctr, Los Angeles, CA 90048 USA. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Edwards, Robert P.] Magee Womens Hosp, Pittsburgh, PA USA. [Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Moyisch, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. [Baker, Julie A.] Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA. [Modugno, Francesmary] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Heikkinenen, Tuomas; Butzow, Ralf; Nevanlinna, Heli; Leminen, Arto] Univ Helsinki, Cent Hosp, Dept Obstet & Gynaecol, Helsinki, Finland. [Bogdanova, Natalia; Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandro, Minsk, Byelarus. [Doerk, Thilo; Hillemanns, Peter] Hannover Med Sch, Clin Obstet & Gynaecol, D-3000 Hannover, Germany. [Duerst, Matthias; Runnebaum, Ingo] Friedrich Schiller Univ, Clin Obstet & Gynaecol, Jena, Germany. [Thompson, Pamela J.; Carney, Michael E.; Goodman, Marc T.; Lurie, Galina] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany. [Hein, Rebecca; Chang-Claude, Jenny] Deutsch Krebsforschungszentrum, Div Canc Epidemiol, Unit Genet Epidemiol, D-6900 Heidelberg, Germany. [Rossing, Mary Anne; Cushing-Haugen, Kara L.; Doherty, Jennifer; Chen, Chu] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Rafnar, Thorunn; Besenbacher, Soren; Sulem, Patrick; Stefansson, Kari] DeCODE Genet, Reykjavik, Iceland. [Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Terry, Kathryn L.; Cramer, Daniel W.] Brigham & Womens Hosp, Obstetr & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Hernandez, Dena] Natl Inst Hlth, NIA, Bethesda, MD USA. [Vergote, Ignace; Amant, Frederic; Despierre, Evelyn] Univ Hosp Leuven, Dept Gynecol Oncol, Louvain, Belgium. [Lambrechts, Diether] Vesalius Res Ctr VIB & KU Leuven, Louvain, Belgium. [Fasching, Peter A.] David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA USA. [Beckmann, Matthias W.] Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Beckmann, Matthias W.] Inst Oncol, M Sklodowska Curie Canc Ctr, Warsaw, Poland. [Thiel, Falk C.] Univ Hosp Erlangen, Dept Obstet & Gynaecol, Erlangen, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Chen, Xiaoqing; Johnatty, Sharon E.; Webb, Penelope M.; Beesley, Jonathan; Chenevix-Trench, Georgia; Australian Canc Study Ovarian Canc] Post Off Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld, Australia. RP Pharoah, PDP (reprint author), Univ Cambridge, Dept Oncol, Cambridge, England. EM paul1@srl.cam.ac.uk RI Bowtell, David/H-1007-2016; Johnatty, Sharon/R-8890-2016; Gronwald, Jacek/A-4576-2017; Brooks-Wilson, Angela/E-9399-2012; Verdrengh, Evelien/H-4571-2012; Lester, Jenny/B-5933-2012; Webb, Penelope/D-5736-2013; Ekici, Arif/C-3971-2013; Kiemeney, Lambertus/D-3357-2009; Tang, Macy/B-9798-2014; Massuger, Leon/H-8072-2014; Jakubowska, Anna/O-8050-2014; Fridley, Brooke/D-8315-2015; Garcia-Closas, Montserrat /F-3871-2015; campbell, Ian/F-6006-2011; van Altena, Anne/B-9824-2016; Aben, Katja/G-9686-2016 OI Bowtell, David/0000-0001-9089-7525; Johnatty, Sharon/0000-0002-7888-1966; Gronwald, Jacek/0000-0002-3643-2871; Brooks-Wilson, Angela/0000-0003-1009-6408; Vierkant, Robert/0000-0001-6242-5221; Weidhaas, Joanne/0000-0002-5096-3281; Ramus, Susan/0000-0003-0005-7798; Lissowska, Jolanta/0000-0003-2695-5799; Nevanlinna, Heli/0000-0002-0916-2976; Besenbacher, Soren/0000-0003-1455-1738; Houlston, Richard/0000-0002-5268-0242; Webb, Penelope/0000-0003-0733-5930; Kiemeney, Lambertus/0000-0002-2368-1326; Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat /0000-0003-1033-2650; Aben, Katja/0000-0002-0214-2147 FU Cancer Research UK; Wellcome Trust [076113]; Ovarian Cancer Research Fund; Mermaid/Eve Appeal; National Health and Medical Research Council; Deutsche Krebshilfe; National Health Service; Danish Cancer Society; Ovarian Cancer Research Fund [PPD/RPCI.07]; Roswell Park Cancer Institute Alliance Foundation; US National Cancer Institute [CA58860, CA92044, P50CA105009, R01CA122443, R01CA126841-01, R01CA16056, R01CA61107, R01CA71766, R01CA054419, R01CA114343, R01CA87538, R01CA112523, R01CA58598, N01CN55424, N01PC35137]; US Army Medical Research and Material Command [DAMD17-01-1-0729]; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; National Health and Medical Research Council of Australia [199600, 400281]; German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research [01 GB 9401]; University of Ulm [P. 685]; Mayo Foundation; Lon V. Smith Foundation [LVS-39420]; Oak Foundation; University College Hospital National Institute for Health Research Biomedical Research Centre; Royal Marsden Hospital Biomedical Research Centre FX The genotyping and data analysis for this study was supported by a project grant from Cancer Research UK. We acknowledge the computational resources provided by the University of Cambridge (CamGrid). This study makes use of data generated by the Wellcome Trust Case-Control consortium. A full list of the investigators who contributed to the generation of the data is available from http://www. wtccc. org. uk/. Funding for the project was provided by the Wellcome Trust under award 076113. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of K. Sladek Smith. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute. Information about TCGA and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome. nih. gov/. S.J.R. is supported by the Mermaid/Eve Appeal. G. C.-T. and P. M. W. are supported by the National Health and Medical Research Council. P. A. F. is supported by the Deutsche Krebshilfe. M. E. G. acknowledges National Health Service funding to the National Institutes of Health Research Centre at the Royal Marsden Hospital, and D. F. E. is a Principal Research Fellow of Cancer Research UK. Funding of the constituent studies was provided by the Danish Cancer Society, the Ovarian Cancer Research Fund (PPD/RPCI.07), the Roswell Park Cancer Institute Alliance Foundation, the US National Cancer Institute (CA58860, CA92044, P50CA105009, R01CA122443, R01CA126841-01, R01CA16056, R01CA61107, R01CA71766, R01CA054419, R01CA114343, R01CA87538, R01CA112523, R01CA58598, N01CN55424, N01PC35137 and Intramural research funds), the US Army Medical Research and Material Command (DAMD17-01-1-0729), Cancer Council Victoria, Cancer Council Queensland, Cancer Council New South Wales, Cancer Council South Australia, Cancer Council Tasmania and Cancer Foundation of Western Australia, the National Health and Medical Research Council of Australia (199600 and 400281), the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401), the state of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P. 685), the Mayo Foundation, the Lon V. Smith Foundation (LVS-39420), the Oak Foundation, the University College Hospital National Institute for Health Research Biomedical Research Centre and the Royal Marsden Hospital Biomedical Research Centre. NR 24 TC 144 Z9 148 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2010 VL 42 IS 10 BP 880 EP + DI 10.1038/ng.666 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 655UO UT WOS:000282276600019 PM 20852633 ER PT J AU Antoniou, AC Wang, XS Fredericksen, ZS McGuffog, L Tarrell, R Sinilnikova, OM Healey, S Morrison, J Kartsonaki, C Lesnick, T Ghoussaini, M Barrowdale, D Peock, S Cook, M Oliver, C Frost, D Eccles, D Evans, DG Eeles, R Izatt, L Chu, C Douglas, F Paterson, J Stoppa-Lyonnet, D Houdayer, C Mazoyer, S Giraud, S Lasset, C Remenieras, A Caron, O Hardouin, A Berthet, P Hogervorst, FBL Rookus, MA Jager, A van den Ouweland, A Hoogerbrugge, N van der Luijt, RB Meijers-Heijboer, H Garcia, EBG Devilee, P Vreeswijk, MPG Lubinski, J Jakubowska, A Gronwald, J Huzarski, T Byrski, T Gorski, B Cybulski, C Spurdle, AB Holland, H Goldgar, DE John, EM Hopper, JL Southey, M Buys, SS Daly, MB Terry, MB Schmutzler, RK Wappenschmidt, B Engel, C Meindl, A Preisler-Adams, S Arnold, N Niederacher, D Sutter, C Domchek, SM Nathanson, KL Rebbeck, T Blum, JL Piedmonte, M Rodriguez, GC Wakeley, K Boggess, JF Basil, J Blank, SV Friedman, E Kaufman, B Laitman, Y Milgrom, R Andrulis, IL Glendon, G Ozcelik, H Kirchhoff, T Vijai, J Gaudet, MM Altshuler, D Guiducci, C Loman, N Harbst, K Rantala, J Ehrencrona, H Gerdes, AM Thomassen, M Sunde, L Peterlongo, P Manoukian, S Bonanni, B Viel, A Radice, P Caldes, T de la Hoya, M Singer, CF Fink-Retter, A Greene, MH Mai, PL Loud, JT Guidugli, L Lindor, NM Hansen, TVO Nielsen, FC Blanco, I Lazaro, C Garber, J Ramus, SJ Gayther, SA Phelan, C Narod, S Szabo, CI Benitez, J Osorio, A Nevanlinna, H Heikkinen, T Caligo, MA Beattie, MS Hamann, U Godwin, AK Montagna, M Casella, C Neuhausen, SL Karlan, BY Tung, N Toland, AE Weitzel, J Olopade, O Simard, J Soucy, P Rubinstein, WS Arason, A Rennert, G Martin, NG Montgomery, GW Chang-Claude, J Flesch-Janys, D Brauch, H Severi, G Baglietto, L Cox, A Cross, SS Miron, P Gerty, SM Tapper, W Yannoukakos, D Fountzilas, G Fasching, PA Beckmann, MW Silva, IDS Peto, J Lambrechts, D Paridaens, R Rudiger, T Forsti, A Winqvist, R Pylkaas, K Diasio, RB Lee, AM Eckel-Passow, J Vachon, C Blows, F Driver, K Dunning, A Pharoah, PPD Offit, K Pankratz, VS Hakonarson, H Chenevix-Trench, G Easton, DF Couch, FJ AF Antoniou, Antonis C. Wang, Xianshu Fredericksen, Zachary S. McGuffog, Lesley Tarrell, Robert Sinilnikova, Olga M. Healey, Sue Morrison, Jonathan Kartsonaki, Christiana Lesnick, Timothy Ghoussaini, Maya Barrowdale, Daniel Peock, Susan Cook, Margaret Oliver, Clare Frost, Debra Eccles, Diana Evans, D. Gareth Eeles, Ros Izatt, Louise Chu, Carol Douglas, Fiona Paterson, Joan Stoppa-Lyonnet, Dominique Houdayer, Claude Mazoyer, Sylvie Giraud, Sophie Lasset, Christine Remenieras, Audrey Caron, Olivier Hardouin, Agnes Berthet, Pascaline Hogervorst, Frans B. L. Rookus, Matti A. Jager, Agnes van den Ouweland, Ans Hoogerbrugge, Nicoline van der Luijt, Rob B. Meijers-Heijboer, Hanne Garcia, Encarna B. Gomez Devilee, Peter Vreeswijk, Maaike P. G. Lubinski, Jan Jakubowska, Anna Gronwald, Jacek Huzarski, Tomasz Byrski, Tomasz Gorski, Bohdan Cybulski, Cezary Spurdle, Amanda B. Holland, Helene Goldgar, David E. John, Esther M. Hopper, John L. Southey, Melissa Buys, Saundra S. Daly, Mary B. Terry, Mary-Beth Schmutzler, Rita K. Wappenschmidt, Barbara Engel, Christoph Meindl, Alfons Preisler-Adams, Sabine Arnold, Norbert Niederacher, Dieter Sutter, Christian Domchek, Susan M. Nathanson, Katherine L. Rebbeck, Timothy Blum, Joanne L. Piedmonte, Marion Rodriguez, Gustavo C. Wakeley, Katie Boggess, John F. Basil, Jack Blank, Stephanie V. Friedman, Eitan Kaufman, Bella Laitman, Yael Milgrom, Roni Andrulis, Irene L. Glendon, Gord Ozcelik, Hilmi Kirchhoff, Tomas Vijai, Joseph Gaudet, Mia M. Altshuler, David Guiducci, Candace Loman, Niklas Harbst, Katja Rantala, Johanna Ehrencrona, Hans Gerdes, Anne-Marie Thomassen, Mads Sunde, Lone Peterlongo, Paolo Manoukian, Siranoush Bonanni, Bernardo Viel, Alessandra Radice, Paolo Caldes, Trinidad de la Hoya, Miguel Singer, Christian F. Fink-Retter, Anneliese Greene, Mark H. Mai, Phuong L. Loud, Jennifer T. Guidugli, Lucia Lindor, Noralane M. Hansen, Thomas V. O. Nielsen, Finn C. Blanco, Ignacio Lazaro, Conxi Garber, Judy Ramus, Susan J. Gayther, Simon A. Phelan, Catherine Narod, Stephen Szabo, Csilla I. Benitez, Javier Osorio, Ana Nevanlinna, Heli Heikkinen, Tuomas Caligo, Maria A. Beattie, Mary S. Hamann, Ute Godwin, Andrew K. Montagna, Marco Casella, Cinzia Neuhausen, Susan L. Karlan, Beth Y. Tung, Nadine Toland, Amanda E. Weitzel, Jeffrey Olopade, Olofunmilayo Simard, Jacques Soucy, Penny Rubinstein, Wendy S. Arason, Adalgeir Rennert, Gad Martin, Nicholas G. Montgomery, Grant W. Chang-Claude, Jenny Flesch-Janys, Dieter Brauch, Hiltrud Severi, Gianluca Baglietto, Laura Cox, Angela Cross, Simon S. Miron, Penelope Gerty, Sue M. Tapper, William Yannoukakos, Drakoulis Fountzilas, George Fasching, Peter A. Beckmann, Matthias W. Silva, Isabel dos Santos Peto, Julian Lambrechts, Diether Paridaens, Robert Ruediger, Thomas Foersti, Asta Winqvist, Robert Pylkaes, Katri Diasio, Robert B. Lee, Adam M. Eckel-Passow, Jeanette Vachon, Celine Blows, Fiona Driver, Kristy Dunning, Alison Pharoah, Paul P. D. Offit, Kenneth Pankratz, V. Shane Hakonarson, Hakon Chenevix-Trench, Georgia Easton, Douglas F. Couch, Fergus J. CA EMBRACE GEMO Study Collaborators HEBON KConFab SWE-BRCA MOD SQUAD GENICA TI A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR; COMMON VARIANTS; CONFER SUSCEPTIBILITY; OVARIAN-CANCER; NONSENSE; ALLELES; COMPLEX; 2Q35 AB Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P(trend) = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P(trend) = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P(trend) = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P(trend) = 1.1 x 10(-7)). C1 [Antoniou, Antonis C.; McGuffog, Lesley; Morrison, Jonathan; Kartsonaki, Christiana; Barrowdale, Daniel; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Tung, Nadine; Blows, Fiona; Driver, Kristy; Dunning, Alison; Pharoah, Paul P. D.; Easton, Douglas F.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Wang, Xianshu; Guidugli, Lucia; Szabo, Csilla I.; Toland, Amanda E.; Couch, Fergus J.] Dept Lab Med & Pathol, Mayo Clin, Rochester, MN USA. [Fredericksen, Zachary S.; Tarrell, Robert; Lesnick, Timothy; Weitzel, Jeffrey; Eckel-Passow, Jeanette; Vachon, Celine; Pankratz, V. Shane] Dept Hlth Sci Res, Mayo Clin, Rochester, MN USA. [Sinilnikova, Olga M.; Giraud, Sophie; Olopade, Olofunmilayo] Univ Lyon Ctr Leon Berard, Ctr Hosp, Unit Mixte Genet Constitutionnelle Canc Frequents, Lyon, France. [Sinilnikova, Olga M.; Mazoyer, Sylvie; Simard, Jacques] Univ Lyon, Ctr Leon Berard, CNRS, Equipe Labellisee LIGUE 2008, Lyon, France. [Healey, Sue; Ghoussaini, Maya; Spurdle, Amanda B.; Holland, Helene; Simard, Jacques; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Eccles, Diana; Gerty, Sue M.; Tapper, William] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Evans, D. Gareth] Cent Manchester Univ Hosp, Manchester Acad Hlth Sci Ctr, NHSFT, Manchester, Lancs, England. [Eeles, Ros] Inst Canc Res & Royal Marsden NHS Fdn, Oncogenet Team, Sutton, Surrey, England. [Izatt, Louise; Soucy, Penny] Guys & St Thomas NHS Fdn Trust, Clin Genet, London, England. [Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Douglas, Fiona] Newcastle Tyne Hosp NHS Trust, Ctr Life, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England. Addenbrookes Hosp, Dept Clin Genet, E Anglian Reg Genet Serv, Cambridge, England. [Stoppa-Lyonnet, Dominique; Houdayer, Claude] Univ Paris 05, Inst Curie, INSERM U509, Serv Genet Oncolog, Paris, France. [Lasset, Christine] Univ Lyon 1, CNRS, UMR5558, F-69365 Lyon, France. [Lasset, Christine] Ctr Leon Berard, Unit Prevent & Epidemiol Genet, Lyon, France. [Remenieras, Audrey] Inst Cancerol Gustave Roussy, Dept Genet, Villejuif, France. [Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Consultat Genet, Villejuif, France. [Hardouin, Agnes; Berthet, Pascaline; Miron, Penelope] Ctr Francois Baclesse, F-14021 Caen, France. [GEMO Study Collaborators] Federat Natl Ctr Lutte Contre Canc, Grp Genet & Canc, Canc Genet Network, GEMO Study, Paris, France. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Jager, Agnes] Erasmus Univ, Med Ctr, Rotterdam Family Canc Clin, Dept Clin Genet, Rotterdam, Netherlands. [van den Ouweland, Ans] Rotterdam Family Canc Clin, Erasmus Univ Med Ctr, Dept Clin Genet, Rotterdam, Netherlands. Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [van der Luijt, Rob B.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Meijers-Heijboer, Hanne] Vrije Univ Amsterdam, Dept Clin Genet, Amsterdam, Netherlands. [Garcia, Encarna B. Gomez] Maastricht Univ, Med Ctr, Dept Clin Genet, Sch Oncol & Dev Biol, Maastricht, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands. [Vreeswijk, Maaike P. G.] Leiden Univ, Med Ctr, Dept Toxicogenet, Leiden, Netherlands. [Lubinski, Jan; Jakubowska, Anna; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Gorski, Bohdan; Cybulski, Cezary] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland. [KConFab] Peter MacCallum Canc Inst, Kathleen Cuningham Fdn Consortium Res Familial Br, kConFab, Melbourne, Vic 3000, Australia. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. [John, Esther M.] Stanford Univ, Sch Med, Canc Prevent Inst Calif, Stanford, CA USA. [Hopper, John L.; Southey, Melissa] Univ Melbourne, Melbourne, Vic, Australia. [Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA. [Daly, Mary B.; Godwin, Andrew K.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Terry, Mary-Beth] Columbia Univ, New York, NY USA. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Cologne, CIO, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Div Tumor Genet, Klinikum Rechts Isar, Munich, Germany. [Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, Munster, Germany. [Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Kiel, Germany. [Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Div Mol Genet, Dept Obstet & Gynaecol, Dusseldorf, Germany. [Sutter, Christian] Univ Heidelberg, Div Mol Diagnost, Inst Human Genet, Heidelberg, Germany. [Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy] Univ Penn, Philadelphia, PA 19104 USA. [Blum, Joanne L.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Piedmonte, Marion] Roswell Pk Canc Inst, Gynecol Oncol Grp Stat & Data Ctr, Buffalo, NY 14263 USA. [Rodriguez, Gustavo C.] Northshore Univ Hlth Syst, Evanston NW Healthcare, Evanston, IL USA. [Wakeley, Katie] Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. [Boggess, John F.] Univ N Carolina, Chapel Hill, NC USA. [Basil, Jack] St Elizabeth Hosp, Edgewood, KY USA. [Blank, Stephanie V.] NYU, Sch Med, New York, NY USA. [Friedman, Eitan; Laitman, Yael; Milgrom, Roni] Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, Tel Hashomer, Israel. [Kaufman, Bella] Inst Oncol, Sheba Med Ctr, Tel Hashomer, Israel. [Andrulis, Irene L.; Glendon, Gord] Ontario Canc Inst, Ontario Canc Genet Network, Toronto, ON M4X 1K9, Canada. [Ozcelik, Hilmi] Samuel Lunenfeld Res Inst, Fred Litwin Ctr Canc Genet, Toronto, ON, Canada. [Andrulis, Irene L.; Offit, Kenneth] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Kirchhoff, Tomas; Vijai, Joseph] Mem Hosp, Clin Genet Serv, New York, NY USA. [Kirchhoff, Tomas; Vijai, Joseph] Sloan Kettering Inst, Canc Biol & Genet Program, Mem Sloan Kettering Canc Ctr, New York, NY USA. [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, New York, NY USA. [Altshuler, David; Guiducci, Candace] Broad Inst Harvard, Cambridge, MA USA. [Altshuler, David; Guiducci, Candace] MIT, Cambridge, MA 02139 USA. [Loman, Niklas; Harbst, Katja] Lund Univ, Dept Oncol, Lund, Sweden. [Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Ehrencrona, Hans] Uppsala Univ, Dept Genet & Pathol Rudbeck Lab, Uppsala, Sweden. [Gerdes, Anne-Marie] Dept Clin Genet, Copenhagen, Denmark. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Sunde, Lone] Aalborg & Aarhus Univ, Dept Clin Genet, Aalborg, Denmark. [Peterlongo, Paolo; Radice, Paolo] Fdn Inst Ricovero Cura Carattere Sci, Unit Genet Susceptibil Canc, Dept Expt Oncol & Mol Med, Ist Nazl Tumori, Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist Fdn Italiana Ricera Cancro FIRC Oncol Mol, IFOM, Milan, Italy. [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predict Med, Milan, Italy. [Bonanni, Bernardo; de la Hoya, Miguel] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy. [Viel, Alessandra] Ctr Riferimento Oncol, Div Expt Oncol, IRCCS, I-33081 Aviano, PN, Italy. [Caldes, Trinidad] Hosp Clin San Carlos, Madrid, Spain. [Singer, Christian F.; Fink-Retter, Anneliese] Med Univ Vienna, Dept Obstet Gynecol, Vienna, Austria. [Greene, Mark H.; Mai, Phuong L.; Loud, Jennifer T.] Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Bethesda, MD USA. [Lindor, Noralane M.] Mayo Clin Rochester, Rochester, MN USA. [Hansen, Thomas V. O.; Nielsen, Finn C.] Copenhagen Univ Hosp, Dept Clin Biochem, Copenhagen, Denmark. [Blanco, Ignacio; Lazaro, Conxi] Gran Via Hosp, Catalan Inst Oncol, Hereditary Canc Program, Barcelona, Spain. [Garber, Judy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ramus, Susan J.; Gayther, Simon A.] UCL, Dept Gynecol Oncol, EGA, London, England. [Phelan, Catherine] Res Inst, Womens Coll, Toronto, ON, Canada. [Narod, Stephen] H Lee Moffitt Canc Ctr & Res Inst, Dept Epidemiol & Genet, Tampa, FL USA. [Benitez, Javier; Osorio, Ana] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Madrid, Spain. [Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Ctr Hosp, Dept Obstet & Gynecol, Helsinki, Finland. [Caligo, Maria A.] Univ Pisa, Dept Oncol, Div Surg Mol & Ultrastructural Pathol, Pisa, Italy. [Beattie, Mary S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Beattie, Mary S.] Univ Calif San Francisco, Canc Risk Program, Helen Diller Family Canc Ctr, San Francisco, CA 94143 USA. [Hamann, Ute; Foersti, Asta] German Canc Res Ctr, Heidelberg, Germany. [Montagna, Marco; Casella, Cinzia] Ist Oncol Veneto IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Neuhausen, Susan L.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA. [Karlan, Beth Y.] Canc Res Inst, Samuel Oschin Canc Inst, Div Gynecol Oncol, Cedars Sinai Med Ctr, Los Angeles, CA USA. [Karlan, Beth Y.] Univ Calif Los Angeles, Dept Obstet & Gynecol, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Toland, Amanda E.] Ohio State Univ, Coll Med, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Weitzel, Jeffrey] City Hope Canc Ctr, Div Clin Canc Genet, Duarte, CA USA. [Olopade, Olofunmilayo] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Simard, Jacques] Univ Quebec, Ctr Hosp, Canc Genom Lab, Quebec City, PQ, Canada. [Simard, Jacques] Univ Laval, Ctr Rech Ctr Hosp Univ Quebec CHUQ, Quebec City, PQ G1K 7P4, Canada. [Rubinstein, Wendy S.] Northshore Univ Hlth Syst, Evanston, IL USA. [Arason, Adalgeir] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Rennert, Gad] Queensland Inst Med Res, QIMR GWAS Collect, Brisbane, Qld 4006, Australia. [Martin, Nicholas G.; Montgomery, Grant W.] B Rappaport Fac Med Techn, Haifa, Israel. [Martin, Nicholas G.; Montgomery, Grant W.] Carmel Hosp, Dept Commun Med & Epidemiol, Clalit Hlth Serv Natl Canc Control Ctr, Haifa, Israel. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany. [Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany. [Severi, Gianluca; Baglietto, Laura] Canc Epidemiol Ctr, MCCS, Melbourne, Australia. [Cox, Angela] Univ Sheffield, Dept Oncol, Fac Med Dent & Hlth, Inst Canc Studies, Sheffield, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Fac Med Dent & Hlth, Sheffield, S Yorkshire, England. [Miron, Penelope] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab Inst Radioisotopes & Radiodiagno, Athens, Greece. [Fountzilas, George] Aristotle Univ Thessaloniki, Papageorgiou Hosp, Dept Med Oncol, Thessaloniki, Greece. [Fountzilas, George] Aristotle Univ Thessaloniki, Papageorgiou Hosp, Dept Med Oncol, Thessaloniki, Greece. [Fasching, Peter A.] Calif State Univ Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90032 USA. [Beckmann, Matthias W.] Univers Hosp Erlangen, Dept Gynecol & Obstet, Erlangen, Germany. [Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, Cancer Res UK Epidemiol & Genet Grp, London WC1, England. [Lambrechts, Diether] VRC, VIB, Leuven, Belgium. [Paridaens, Robert] Univ Hosp Leuven, Multidisciplinary Breast Ctr, Leuven, Belgium. [Ruediger, Thomas] Inst Pathol, Stadt Klinikum Karlsruhe, Karlsruhe, Germany. [Foersti, Asta] Lund Univ, Ctr Primary Hlth Care Res, Lund, Sweden. [Winqvist, Robert; Pylkaes, Katri] Univ Oulu, Dept Clin Genet & Biocenter Oulu, Canc Genet Lab, Oulu Univ Hosp, Oulu, Finland. [Diasio, Robert B.; Lee, Adam M.] Mayo Clin, Dept Pharmacol, Rochester, MN USA. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Gen, Philadelphia, PA 19104 USA. RP Couch, FJ (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. EM couch.fergus@mayo.edu RI Spurdle, Amanda/A-4978-2011; BYRSKI, Tomasz/I-2844-2014; Ehrencrona, Hans/M-5619-2014; Jakubowska, Anna/O-8050-2014; Montgomery, Grant/B-7148-2008; Gronwald, Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Osorio, Ana/I-4324-2014; Altshuler, David/A-4476-2009; Arnold, Norbert/E-3012-2010; Toland, Amanda/E-4202-2011; montagna, marco/E-2225-2012; Verdrengh, Evelien/H-4571-2012; Fink, Rainer/C-5333-2008; Andrulis, Irene/E-7267-2013; Sunde, Lone/H-7402-2013; Joseph, Vijai/J-9158-2013; Hoogerbrugge, Nicoline/O-1016-2013; Radice, Paolo/O-3119-2013; Blanco, Ignacio/D-2565-2013 OI Kirchhoff, Tomas/0000-0002-9055-2364; Yannoukakos, Drakoulis/0000-0001-7509-3510; Dunning, Alison Margaret/0000-0001-6651-7166; Martin, Nicholas/0000-0003-4069-8020; Evans, Gareth/0000-0002-8482-5784; Ramus, Susan/0000-0003-0005-7798; Spurdle, Amanda/0000-0003-1337-7897; Barrowdale, Daniel/0000-0003-1661-3939; Cross, Simon/0000-0003-2044-1754; Sunde, Lone/0000-0002-8479-165X; Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Ehrencrona, Hans/0000-0002-5589-3622; Montgomery, Grant/0000-0002-4140-8139; Gronwald, Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562; Eeles, Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901; Osorio, Ana/0000-0001-8124-3984; Altshuler, David/0000-0002-7250-4107; Arnold, Norbert/0000-0003-4523-8808; montagna, marco/0000-0002-4929-2150; Fink, Rainer/0000-0002-6896-4266; Joseph, Vijai/0000-0002-7933-151X; Blanco, Ignacio/0000-0002-7414-7481 FU Breast Cancer Research Foundation (BCRF); US National Institutes of Health [CA128978]; Cancer Research UK FX Financial support for this study was provided by the Breast Cancer Research Foundation (BCRF), Susan G. Komen for the Cure and US National Institutes of Health grant CA128978 to F. J. C. and by Cancer Research UK to D. F. E. and A. C. A. A. C. A. is a Cancer Research UK Senior Cancer Research Fellow and D. F. E. is a Cancer Research UK Principal Research Fellow. The authors thank Cancer Genetic Markers of Susceptability (CGEMS) and Wellcome Trust Case Control Consortium (WTCCC) for provision of genotype data from controls. Study specific acknowledgments listed in Supplementary Note. NR 32 TC 180 Z9 185 U1 5 U2 35 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2010 VL 42 IS 10 BP 885 EP + DI 10.1038/ng.669 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 655UO UT WOS:000282276600020 PM 20852631 ER PT J AU Masters, SL Dunne, A Subramanian, SL Hull, RL Tannahill, GM Sharp, FA Becker, C Franchi, L Yoshihara, E Chen, Z Mullooly, N Mielke, LA Harris, J Coll, RC Mills, KHG Mok, KH Newsholme, P Nunez, G Yodoi, J Kahn, SE Lavelle, EC O'Neill, LAJ AF Masters, Seth L. Dunne, Aisling Subramanian, Shoba L. Hull, Rebecca L. Tannahill, Gillian M. Sharp, Fiona A. Becker, Christine Franchi, Luigi Yoshihara, Eiji Chen, Zhe Mullooly, Niamh Mielke, Lisa A. Harris, James Coll, Rebecca C. Mills, Kingston H. G. Mok, K. Hun Newsholme, Philip Nunez, Gabriel Yodoi, Junji Kahn, Steven E. Lavelle, Ed C. O'Neill, Luke A. J. TI Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1 beta in type 2 diabetes SO NATURE IMMUNOLOGY LA English DT Article ID HUMAN PANCREATIC-ISLETS; LOW-DENSITY-LIPOPROTEIN; BETA-CELL MASS; NALP3 INFLAMMASOME; INSULIN-RESISTANCE; TRANSGENIC MICE; MOUSE MODEL; IN-VITRO; AMYLIN; MELLITUS AB Interleukin 1 beta (IL-1 beta) is an important inflammatory mediator of type 2 diabetes. Here we show that oligomers of islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas during type 2 diabetes, triggered the NLRP3 inflammasome and generated mature IL-1 beta. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1 beta production in vitro. Processing of IL-1 beta initiated by IAPP first required priming, a process that involved glucose metabolism and was facilitated by minimally oxidized low-density lipoprotein. Finally, mice transgenic for human IAPP had more IL-1 beta in pancreatic islets, which localized together with amyloid and macrophages. Our findings identify previously unknown mechanisms in the pathogenesis of type 2 diabetes and treatment of pathology caused by IAPP. C1 [Masters, Seth L.; Dunne, Aisling; Mielke, Lisa A.; Harris, James; Mills, Kingston H. G.; Lavelle, Ed C.; O'Neill, Luke A. J.] Trinity Coll Dublin, Sch Biochem & Immunol, Immunol Res Ctr, Dublin, Ireland. [Masters, Seth L.; Tannahill, Gillian M.; Becker, Christine; Coll, Rebecca C.; O'Neill, Luke A. J.] Trinity Coll Dublin, Sch Biochem & Immunol, Inflammat Res Grp, Dublin, Ireland. [Dunne, Aisling; Mielke, Lisa A.; Mills, Kingston H. G.] Trinity Coll Dublin, Sch Biochem & Immunol, Immune Regulat Res Grp, Dublin, Ireland. [Subramanian, Shoba L.; Hull, Rebecca L.; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Subramanian, Shoba L.; Hull, Rebecca L.; Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Sharp, Fiona A.; Harris, James; Lavelle, Ed C.] Trinity Coll Dublin, Adjuvant Res Grp, Sch Biochem & Immunol, Dublin, Ireland. [Franchi, Luigi; Nunez, Gabriel] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Franchi, Luigi; Nunez, Gabriel] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Yoshihara, Eiji; Chen, Zhe; Yodoi, Junji] Kyoto Univ, Dept Biol Responses, Inst Virus Res, Kyoto 6068501, Japan. [Mullooly, Niamh; Newsholme, Philip] Univ Coll Dublin, Sch Biomol & Biomed Sci, Conway Inst, Dublin 2, Ireland. [Mok, K. Hun] Trinity Coll Dublin, Sch Biochem & Immunol, Prot Folding & Biomol NMR Spect Grp, Dublin, Ireland. RP Masters, SL (reprint author), Trinity Coll Dublin, Sch Biochem & Immunol, Immunol Res Ctr, Dublin, Ireland. EM smasters@tcd.ie RI Chen, Zhe/F-6273-2010; Mok, K. Hun/C-2607-2009; Masters, Seth/N-2886-2013; Coll, Rebecca/J-2124-2014; OI Chen, Zhe/0000-0003-3626-9848; Masters, Seth/0000-0003-4763-576X; Coll, Rebecca/0000-0002-7359-6023; Newsholme, Philip/0000-0002-0500-6984; Harris, James/0000-0002-5634-9637; Hull, Rebecca/0000-0001-9690-4087 FU National Health and Medical Research Council [516783]; Science Foundation Ireland; United States Department of Veterans Affairs; US National Institutes of Health [DK-75998, AI063331]; Crohn's and Colitis Foundation FX We thank A. Mori for assistance with Nlrp3-/- mice; J. Tschopp (University of Lausanne) for Nlrp3-/- mice; and E. Latz (University of Bonn) for YFP-ASC BMDMs. Supported by the National Health and Medical Research Council (516783 to S.L.M.), Science Foundation Ireland (for work at Trinity College Dublin), the United States Department of Veterans Affairs (for work at the VA Puget Sound Health Care System), the US National Institutes of Health (DK-75998 to S.E.K. for work at VA Puget Sound Health Care System, and AI063331 for work at the University of Michigan) and the Crohn's and Colitis Foundation (L.F.). NR 53 TC 473 Z9 487 U1 8 U2 72 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 OCT PY 2010 VL 11 IS 10 BP 897 EP U1501 DI 10.1038/ni.1935 PG 9 WC Immunology SC Immunology GA 651KP UT WOS:000281926900008 PM 20835230 ER PT J AU Berger, SB Romero, X Ma, CY Wang, GX Faubion, WA Liao, GX Compeer, E Keszei, M Rameh, L Wang, NH Boes, M Regueiro, JR Reinecker, HC Terhorst, C AF Berger, Scott B. Romero, Xavier Ma, Chunyan Wang, Guoxing Faubion, William A. Liao, Gongxian Compeer, Ewoud Keszei, Marton Rameh, Lucia Wang, Ninghai Boes, Marianne Regueiro, Jose R. Reinecker, Hans-Christian Terhorst, Cox TI SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages SO NATURE IMMUNOLOGY LA English DT Article ID DENDRITIC CELLS; IMMUNE-RESPONSES; APOPTOTIC CELLS; NADPH OXIDASE; T-CELL; AUTOPHAGY; MATURATION; PHAGOCYTOSIS; RECEPTOR; INNATE AB Phagocytosis is a pivotal process by which macrophages eliminate microorganisms after recognition by pathogen sensors. Here we unexpectedly found that the self ligand and cell surface receptor SLAM functioned not only as a costimulatory molecule but also as a microbial sensor that controlled the killing of Gram-negative bacteria by macrophages. SLAM regulated activity of the NADPH oxidase NOX2 complex and phagolysosomal maturation after entering the phagosome, following interaction with the bacterial outer membrane proteins OmpC and OmpF. SLAM recruited a complex containing the intracellular class III phosphatidylinositol kinase Vps34, its regulatory protein kinase Vps15 and the autophagy-associated molecule beclin-1 to the phagosome, which was responsible for inducing the accumulation of phosphatidylinositol-3-phosphate, a regulator of both NOX2 function and phagosomal or endosomal fusion. Thus, SLAM connects the Gram-negative bacterial phagosome to ubiquitous cellular machinery responsible for the control of bacterial killing. C1 [Berger, Scott B.; Romero, Xavier; Ma, Chunyan; Wang, Guoxing; Faubion, William A.; Liao, Gongxian; Compeer, Ewoud; Keszei, Marton; Wang, Ninghai; Regueiro, Jose R.; Terhorst, Cox] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Immunol, Boston, MA 02215 USA. [Faubion, William A.] Mayo Clin, Dept Internal Med, Rochester, MN USA. [Rameh, Lucia] Boston Biomed Res Inst, Watertown, MA USA. [Boes, Marianne] Harvard Univ, Dept Dermatol, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA. [Regueiro, Jose R.] Univ Complutense, Fac Med, E-28040 Madrid, Spain. [Reinecker, Hans-Christian] Harvard Univ, Dept Med, Gastrointestinal Unit, Sch Med, Boston, MA 02215 USA. [Reinecker, Hans-Christian] Harvard Univ, Ctr Study Inflammatory Bowel Dis, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA. RP Berger, SB (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Immunol, Boston, MA 02215 USA. EM sberger@bidmc.harvard.edu; terhorst@bidmc.harvard.edu RI Wang, Guoxing/G-6586-2013; Keszei, Marton/F-3295-2014; Regueiro, Jose/B-5499-2014; compeer, ewoud/E-8553-2015; OI Keszei, Marton/0000-0002-1158-2179; Regueiro, Jose/0000-0001-8442-7762; Compeer, Ewoud/0000-0002-3050-7633 FU US National Institutes of Health [AI-15066, DK-068181, DK-003506-20]; Crohn's and Colitis Foundation of America FX We thank H. Remold, P. Klebba and members of the Terhorst lab for critical review of the manuscript; S. Laroux for help with initial oxidative burst experiments; A. Nohturft, M. Yaffe, P. Klebba and G. Pier for discussions; B. McCormick (University of Massachusetts) for E. coli F18; C. Nagler (University of Chicago) and P. Klemm (Technical University of Denmark) for eGFP-expressing bacteria; H. Nikaido (University of California Berkeley), P. Klebba (University of Oklahoma) and G. Pier (Harvard Medical School) for mutant strains of E. coli and S. aureus; M. Yaffe (Massachusetts Institute of Technology) for the p40-eGFP construct; L. Cantley (Harvard Medical School) for Vps34-Myc; R. Tsien (University of California San Diego) for the mCherry construct; J. Backer (Albert Einstein College of Medicine) for the Vps34-Vps15-V5 construct; P. Hawkins (Babraham Institute) for p40phox-deficient mice; and S. Targan (Cedars-Sinai) for the highly purified OmpC preparation. Supported by the US National Institutes of Health (AI-15066 to C. T., and DK-068181 and DK-003506-20 to H. C. R.) and the Crohn's and Colitis Foundation of America (S.B. and X.R.). NR 43 TC 75 Z9 80 U1 4 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2010 VL 11 IS 10 BP 920 EP U70 DI 10.1038/ni.1931 PG 9 WC Immunology SC Immunology GA 651KP UT WOS:000281926900011 PM 20818396 ER PT J AU Ng, CT Jaworski, JP Jayaraman, P Sutton, WF Delio, P Kuller, L Anderson, D Landucci, G Richardson, BA Burton, DR Forthal, DN Haigwood, NL AF Ng, Cherie T. Jaworski, J. Pablo Jayaraman, Pushpa Sutton, William F. Delio, Patrick Kuller, LaRene Anderson, David Landucci, Gary Richardson, Barbra A. Burton, Dennis R. Forthal, Donald N. Haigwood, Nancy L. TI Passive neutralizing antibody controls SHIV viremia and enhances B cell responses in infant macaques SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1/SIV CHIMERIC VIRUS; MONOCLONAL-ANTIBODIES; PROTECTION; INFECTION; HIV; TRANSMISSION; BROAD AB Maternal HIV-1-specific antibodies are efficiently transferred to newborns, but their role in disease control is unknown. We administered neutralizing IgG, including the human neutralizing monoclonal IgG1b12, at levels insufficient to block infection, to six newborn macaques before oral challenge with simian-HIV strain SF162P3 (SHIV(SF162P3)). All of the macaques rapidly developed neutralizing antibodies and had significantly reduced plasma viremia for six months. These studies support the use of neutralizing antibodies in enhancing B cell responses and viral control in perinatal settings. C1 [Ng, Cherie T.; Jayaraman, Pushpa; Haigwood, Nancy L.] Univ Washington, Dept Global Hlth, Pathobiol Program, Seattle, WA 98195 USA. [Ng, Cherie T.; Jayaraman, Pushpa] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Jaworski, J. Pablo; Sutton, William F.; Haigwood, Nancy L.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Jaworski, J. Pablo; Sutton, William F.; Haigwood, Nancy L.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA. [Delio, Patrick; Kuller, LaRene; Anderson, David] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. [Landucci, Gary; Forthal, Donald N.] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA. [Richardson, Barbra A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Burton, Dennis R.] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA. [Burton, Dennis R.] Harvard Univ, Boston, MA 02115 USA. RP Haigwood, NL (reprint author), Univ Washington, Dept Global Hlth, Pathobiol Program, Seattle, WA 98195 USA. EM haigwoon@ohsu.edu OI Jaworski, Juan Pablo/0000-0002-1311-060X FU US National Institutes of Health [R01HD038653, R01AI33292, R01AI052039]; Elizabeth Glaser Pediatric AIDS Foundation FX We would like to thank Z. Brower for technical support, D. Morris and K. Filer for manuscript preparation, M. L. Marthas and K. K. A. Van Rompay for advice on subcutaneous dosing of IgG and oral inoculation of infants, J. Overbaugh (Fred Hutchinson Cancer Research Center) for the Env-deleted viral backbone plasmid Q23 Delta Env, S. Barnett and I. Srinivasan (Novartis) for recombinant gp120-SF162 and V. Planelles (University of Utah) for the plasmid pEMC*. M. Piatak and J. D. Lifson (Science Applications International Corporation) kindly provided RNA standards and advice on real-time PCR. SHIVSF162P3 was supplied by N. Miller (US National Institutes of Health Division of AIDS) and R. Pal (Advanced Bioscience Labs). TZM-bl were supplied by the US National Institutes of Health AIDS Research Reference Reagent Program. This study was supported by grants from the US National Institutes of Health R01HD038653 (N. L. H.), R01AI33292 (D. R. B.) and R01AI052039 (D. N. F.) and from the Elizabeth Glaser Pediatric AIDS Foundation (N. L. H.). NR 19 TC 77 Z9 78 U1 1 U2 6 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 OCT PY 2010 VL 16 IS 10 BP 1117 EP 1119 DI 10.1038/nm.2233 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 660LR UT WOS:000282644800041 PM 20890292 ER PT J AU Ray, NB Durairaj, L Chen, BB McVerry, BJ Ryan, AJ Donahoe, M Waltenbaugh, AK O'Donnell, CP Henderson, FC Etscheidt, CA Mccoy, DM Agassandian, M Hayes-Rowan, EC Coon, TA Butler, PL Gakhar, L Mathur, SN Sieren, JC Tyurina, YY Kagan, VE McLennan, G Mallampalli, RK AF Ray, Nancy B. Durairaj, Lakshmi Chen, Bill B. McVerry, Bryan J. Ryan, Alan J. Donahoe, Michael Waltenbaugh, Alisa K. O'Donnell, Christopher P. Henderson, Florita C. Etscheidt, Christopher A. Mccoy, Diann M. Agassandian, Marianna Hayes-Rowan, Emily C. Coon, Tiffany A. Butler, Phillip L. Gakhar, Lokesh Mathur, Satya N. Sieren, Jessica C. Tyurina, Yulia Y. Kagan, Valerian E. McLennan, Geoffrey Mallampalli, Rama K. TI Dynamic regulation of cardiolipin by the lipid pump Atp8b1 determines the severity of lung injury in experimental pneumonia SO NATURE MEDICINE LA English DT Article ID CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; FAMILIAL INTRAHEPATIC CHOLESTASIS; PULMONARY-EDEMA; PROTEIN-A; IN-VIVO; SURFACTANT; DISEASE; GENE; PHOSPHOLIPIDS; PURIFICATION AB Pneumonia remains the leading cause of death from infection in the US, yet fundamentally new conceptual models underlying its pathogenesis have not emerged. We show that humans and mice with bacterial pneumonia have markedly elevated amounts of cardiolipin, a rare, mitochondrial-specific phospholipid, in lung fluid and find that it potently disrupts surfactant function. Intratracheal cardiolipin administration in mice recapitulates the clinical phenotype of pneumonia, including impaired lung mechanics, modulation of cell survival and cytokine networks and lung consolidation. We have identified and characterized the activity of a unique cardiolipin transporter, the P-type ATPase transmembrane lipid pump Atp8b1, a mutant version of which is associated with severe pneumonia in humans and mice. Atp8b1 bound and internalized cardiolipin from extracellular fluid via a basic residue-enriched motif. Administration of a peptide encompassing the cardiolipin binding motif or Atp8b1 gene transfer in mice lessened bacteria-induced lung injury and improved survival. The results unveil a new paradigm whereby Atp8b1 is a cardiolipin importer whose capacity to remove cardiolipin from lung fluid is exceeded during inflammation or when Atp8b1 is defective. This discovery opens the door for new therapeutic strategies directed at modulating the abundance or molecular interactions of cardiolipin in pneumonia. C1 [Chen, Bill B.; McVerry, Bryan J.; Donahoe, Michael; Waltenbaugh, Alisa K.; O'Donnell, Christopher P.; Hayes-Rowan, Emily C.; Coon, Tiffany A.; Mallampalli, Rama K.] Univ Pittsburgh, Dept Internal Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15260 USA. [Ray, Nancy B.; Durairaj, Lakshmi; Ryan, Alan J.; Henderson, Florita C.; Etscheidt, Christopher A.; Mccoy, Diann M.; Agassandian, Marianna; Mathur, Satya N.; Sieren, Jessica C.; McLennan, Geoffrey] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Butler, Phillip L.; Gakhar, Lokesh] Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA. [Tyurina, Yulia Y.; Kagan, Valerian E.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Ctr Free Radl & Antioxidant Hlth, Pittsburgh, PA USA. [McLennan, Geoffrey] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. [McLennan, Geoffrey] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Dept Internal Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15260 USA. EM mallampallirk@upmc.edu RI Gakhar, Lokesh/F-2113-2010 FU US Department of Veterans Affairs; US National Institutes of Health [R01 HL068135, HL080229, HL081784, HL096376, HL097376, HL098174, HL70755, HL094488, NIOSH OH008282, K23 HL075402, U01 HL102288] FX We thank M. E. Anderson, M.J. Welsh, J. Zabner and M. Gladwin for critical review of the manuscript and helpful suggestions. The Atp8b1G308V/G308V 129S1/SvlmJ mutant mice14 were a generous gift from L. Bull (University of California-San Francisco). Nontypable H. influenza strain 12 bacteria were kindly provided by D. Look (University of Iowa) 29. Antibodies to ATP8b1 were generous gifts from D. Ortiz (Tufts University) 30 and M. Ananthanarayanan (Mount Sinai School of Medicine) 31. This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs and US National Institutes of Health R01 grants HL068135, HL080229, HL081784, HL096376, HL097376 and HL098174 (to R. K. M.), HL70755, HL094488 and NIOSH OH008282 (to V. E. K.) and K23 HL075402 and U01 HL102288 (to L. D.). The contents do not represent the views of the Department of Veterans Affairs or the US government. NR 38 TC 67 Z9 69 U1 1 U2 12 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 OCT PY 2010 VL 16 IS 10 BP 1120 EP U1 DI 10.1038/nm.2213 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 660LR UT WOS:000282644800042 PM 20852622 ER PT J AU Quigley, M Pereyra, F Nilsson, B Porichis, F Fonseca, C Eichbaum, Q Julg, B Jesneck, JL Brosnahan, K Imam, S Russell, K Toth, I Piechocka-Trocha, A Dolfi, D Angelosanto, J Crawford, A Shin, H Kwon, DS Zupkosky, J Francisco, L Freeman, GJ Wherry, EJ Kaufmann, DE Walker, BD Ebert, B Haining, WN AF Quigley, Michael Pereyra, Florencia Nilsson, Bjoern Porichis, Filippos Fonseca, Catia Eichbaum, Quentin Julg, Boris Jesneck, Jonathan L. Brosnahan, Kathleen Imam, Sabrina Russell, Kate Toth, Ildiko Piechocka-Trocha, Alicja Dolfi, Douglas Angelosanto, Jill Crawford, Alison Shin, Haina Kwon, Douglas S. Zupkosky, Jennifer Francisco, Loise Freeman, Gordon J. Wherry, E. John Kaufmann, Daniel E. Walker, Bruce D. Ebert, Benjamin Haining, W. Nicholas TI Transcriptional analysis of HIV-specific CD8(+) T cells shows that PD-1 inhibits T cell function by upregulating BATF SO NATURE MEDICINE LA English DT Article ID CHRONIC VIRAL-INFECTION; MEMORY DIFFERENTIATION; NEGATIVE REGULATOR; GENE-EXPRESSION; ACTIVATION; EXHAUSTION; AP-1; NONPROGRESSORS; PERSISTENCE; RECEPTORS AB CD8(+) T cells in chronic viral infections such as HIV develop functional defects including loss of interleukin-2 (IL-2) secretion and decreased proliferative potential that are collectively termed 'exhaustion' 1. Exhausted T cells express increased amounts of multiple inhibitory receptors, such as programmed death-1 (PD-1)(2,3), that contribute to impaired virus-specific T cell function. Although reversing PD-1 inhibition is therefore an attractive therapeutic strategy, the cellular mechanisms by which PD-1 ligation results in T cell inhibition are not fully understood. PD-1 is thought to limit T cell activation by attenuating T cell receptor (TCR) signaling(4,5). It is not known whether PD-1 also acts by upregulating genes in exhausted T cells that impair their function. Here we analyzed gene expression profiles from HIV-specific CD8(+) T cells in individuals with HIV and show that PD-1 coordinately upregulates a program of genes in exhausted CD8(+) T cells from humans and mice. This program includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family. Enforced expression of BATF was sufficient to impair T cell proliferation and cytokine secretion, whereas BATF knockdown reduced PD-1 inhibition. Silencing BATF in T cells from individuals with chronic viremia rescued HIV-specific T cell function. Thus, inhibitory receptors can cause T cell exhaustion by upregulating genes-such as BATF-that inhibit T cell function. Such genes may provide new therapeutic opportunities to improve T cell immunity to HIV. C1 [Pereyra, Florencia; Porichis, Filippos; Eichbaum, Quentin; Julg, Boris; Toth, Ildiko; Piechocka-Trocha, Alicja; Kwon, Douglas S.; Zupkosky, Jennifer; Kaufmann, Daniel E.; Walker, Bruce D.] Massachusetts Gen Hosp, Ragon Inst, MIT, Charlestown, MA USA. [Pereyra, Florencia; Porichis, Filippos; Eichbaum, Quentin; Julg, Boris; Toth, Ildiko; Piechocka-Trocha, Alicja; Kwon, Douglas S.; Zupkosky, Jennifer; Kaufmann, Daniel E.; Walker, Bruce D.] Harvard Univ, Charlestown, MA USA. [Quigley, Michael; Fonseca, Catia; Jesneck, Jonathan L.; Brosnahan, Kathleen; Imam, Sabrina; Russell, Kate; Haining, W. Nicholas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Jesneck, Jonathan L.; Ebert, Benjamin] Broad Inst, Canc Program, Cambridge, MA USA. [Dolfi, Douglas; Angelosanto, Jill; Crawford, Alison; Shin, Haina; Wherry, E. John] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Dolfi, Douglas; Angelosanto, Jill; Crawford, Alison; Shin, Haina; Wherry, E. John] Univ Penn, Inst Immunol, Philadelphia, PA 19104 USA. [Francisco, Loise] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA. [Kaufmann, Daniel E.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ebert, Benjamin] Harvard Univ, Sch Med, Div Hematol, Brigham & Womens Hosp, Boston, MA USA. [Haining, W. Nicholas] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Ragon Inst, MIT, Charlestown, MA USA. EM bwalker@partners.org; nicholas_haining@dfci.harvard.edu OI Russell, Kate/0000-0001-9343-3355 FU US National Institutes of Health [AI082630, AI56299, HHSN26620050030C, HL092565]; International HIV Controllers Study; Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative FX We would like to thank the subjects for taking part in the study; E. Cutrell, B. Baker, K. Moss, A. Rathod and C. Brume for coordinating sample management; and A. Sharpe, T. Golub, G. Lauer, M. Altfeld and H. Joffe for valuable discussions. This work was supported by US National Institutes of Health grants AI082630, AI56299, HHSN26620050030C and HL092565, the International HIV Controllers Study and the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative. NR 30 TC 150 Z9 156 U1 1 U2 14 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 OCT PY 2010 VL 16 IS 10 BP 1147 EP U127 DI 10.1038/nm.2232 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 660LR UT WOS:000282644800046 PM 20890291 ER PT J AU Song, CM Koren, T Wang, P Barabasi, AL AF Song, Chaoming Koren, Tal Wang, Pu Barabasi, Albert-Laszlo TI Modelling the scaling properties of human mobility SO NATURE PHYSICS LA English DT Article ID RANDOM SEARCHES; LEVY FLIGHTS; RANDOM-WALKS; PATTERNS; DIFFUSION; NETWORKS; PREDICTABILITY; EPIDEMICS; OUTBREAKS; DYNAMICS AB Individual human trajectories are characterized by fat-tailed distributions of jump sizes and waiting times, suggesting the relevance of continuous-time random-walk (CTRW) models for human mobility. However, human traces are barely random. Given the importance of human mobility, from epidemic modelling to traffic prediction and urban planning, we need quantitative models that can account for the statistical characteristics of individual human trajectories. Here we use empirical data on human mobility, captured by mobile-phone traces, to show that the predictions of the CTRW models are in systematic conflict with the empirical results. We introduce two principles that govern human trajectories, allowing us to build a statistically self-consistent microscopic model for individual human mobility. The model accounts for the empirically observed scaling laws, but also allows us to analytically predict most of the pertinent scaling exponents. C1 [Song, Chaoming; Koren, Tal; Wang, Pu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys Biol & Comp Sci, Ctr Complex Network Res, Boston, MA 02115 USA. [Song, Chaoming; Koren, Tal; Wang, Pu; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Song, CM (reprint author), Northeastern Univ, Dept Phys Biol & Comp Sci, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu FU James S. McDonnell Foundation; NSF [DMR-0426737, IIS-0513650]; Defense Threat Reduction Agency Award [HDTRA1-08-1-0027]; US Army Research Laboratory [W911NF-09-2-0053] FX We thank M. Gonzales, D. Wang, J. Bagrow and Z. Qu for discussions and continents on the manuscript. This work was supported by the James S. McDonnell Foundation 21st Century Initiatite in Studying Complex Systems; NSF within the Information Technology Research (DMR-0426737), and IIS-0513650 programmes; the Defense Threat Reduction Agency Award HDTRA1-08-1-0027 and the Network Science Collaborative Technology Alliance sponsored by the US Army Research Laboratory under Agreement Number W911NF-09-2-0053. NR 40 TC 262 Z9 273 U1 8 U2 62 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1745-2473 EI 1745-2481 J9 NAT PHYS JI Nat. Phys. PD OCT PY 2010 VL 6 IS 10 BP 818 EP 823 DI 10.1038/NPHYS1760 PG 6 WC Physics, Multidisciplinary SC Physics GA 672GC UT WOS:000283570000027 ER PT J AU Rades, D Abrahm, JL AF Rades, Dirk Abrahm, Janet L. TI The role of radiotherapy for metastatic epidural spinal cord compression SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID PAINFUL BONE METASTASES; HIGH-DOSE DEXAMETHASONE; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; SINGLE FRACTION; PALLIATIVE RADIOTHERAPY; VERTEBRAL METASTASIS; RADIATION-THERAPY; CANCER-PATIENTS; MOTOR DEFICITS AB Radiotherapy alone is the most common treatment for metastatic epidural spinal cord compression (MESCC). Decompressive surgery followed by radiotherapy is generally indicated only in 10-15% of MESCC cases. Chemotherapy has an unclear role and may be considered for selected patients with hematological or germ-cell malignancies. If radiotherapy alone is given, it is important to select the appropriate regimen. Similar functional outcomes can be achieved with short-course radiotherapy regimens and longer-course radiotherapy regimens. Longer-course radiotherapy is associated with better local control of MESCC than short-course radiotherapy. Patients with a more favorable survival prognosis (expected survival of >= 6 months) should receive longer-course radiotherapy, as they may live long enough to develop a recurrence of MESCC. Patients with an expected survival of <6 months should be considered for short-course radiotherapy. A recurrence of MESCC in the previously irradiated region after short-course radiotherapy may be treated with another short-course of radiotherapy. After primary administration of longer-course radiotherapy, decompressive surgery should be performed if indicated. Alternatively, re-irradiation can be performed using high-precision techniques to reduce the cumulative dose received by the spinal cord. Larger prospective trials are required to better define the appropriate treatment for the individual patient. C1 [Rades, Dirk] Univ Lubeck, Dept Radiat Oncol, D-23538 Lubeck, Germany. [Abrahm, Janet L.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Rades, D (reprint author), Univ Lubeck, Dept Radiat Oncol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM rades.dirk@gmx.net NR 77 TC 54 Z9 54 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD OCT PY 2010 VL 7 IS 10 BP 590 EP 598 DI 10.1038/nrclinonc.2010.137 PG 9 WC Oncology SC Oncology GA 655WW UT WOS:000282287300010 PM 20808299 ER PT J AU Meyerson, M Gabriel, S Getz, G AF Meyerson, Matthew Gabriel, Stacey Getz, Gad TI Advances in understanding cancer genomes through second-generation sequencing SO NATURE REVIEWS GENETICS LA English DT Review ID CELL LUNG-CANCER; BURROWS-WHEELER TRANSFORM; MYELOID-LEUKEMIA GENOME; TYROSINE KINASE JAK2; SHORT READ ALIGNMENT; COPY-NUMBER; ACTIVATING MUTATIONS; MISSENSE MUTATIONS; POLYCYTHEMIA-VERA; SOMATIC MUTATIONS AB Cancers are caused by the accumulation of genomic alterations. Therefore, analyses of cancer genome sequences and structures provide insights for understanding cancer biology, diagnosis and therapy. The application of second-generation DNA sequencing technologies (also known as next-generation sequencing) - through whole-genome, whole-exome and whole-transcriptome approaches - is allowing substantial advances in cancer genomics. These methods are facilitating an increase in the efficiency and resolution of detection of each of the principal types of somatic cancer genome alterations, including nucleotide substitutions, small insertions and deletions, copy number alterations, chromosomal rearrangements and microbial infections. This Review focuses on the methodological considerations for characterizing somatic genome alterations in cancer and the future prospects for these approaches. C1 [Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU National Cancer Institute [U24CA143867, U24CA143845]; National Human Genome Research Institute [U54HG003067] FX We thank M. Lawrence and G. Saksena for careful review of the manuscript. We acknowledge support from The Cancer Genome Atlas programme of the National Cancer Institute, U24CA143867 and U24CA143845, and from the National Human Genome Research Institute, U54HG003067. NR 119 TC 515 Z9 527 U1 11 U2 132 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 EI 1471-0064 J9 NAT REV GENET JI Nat. Rev. Genet. PD OCT PY 2010 VL 11 IS 10 BP 685 EP 696 DI 10.1038/nrg2841 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 651FL UT WOS:000281911300009 PM 20847746 ER PT J AU Heard, E Tishkoff, S Todd, JA Vidal, M Wagner, GP Wang, J Weigel, D Young, R AF Heard, Edith Tishkoff, Sarah Todd, John A. Vidal, Marc Wagner, Guenter P. Wang, Jun Weigel, Detlef Young, Richard TI Ten years of genetics and genomics: what have we achieved and where are we heading? SO NATURE REVIEWS GENETICS LA English DT Article ID RECENT POSITIVE SELECTION; SACCHAROMYCES-CEREVISIAE GENOME; EMBRYONIC STEM-CELLS; TRANSPOSABLE ELEMENTS; HUMAN-POPULATIONS; MESSENGER-RNAS; DRAFT SEQUENCE; COMPLEX TRAITS; DISEASE; BIOLOGY AB To celebrate the first 10 years of Nature Reviews Genetics, we asked eight leading researchers for their views on the key developments in genetics and genomics in the past decade and the prospects for the future. Their responses highlight the incredible changes that the field has seen, from the explosion of genomic data and the many possibilities it has opened up to the ability to reprogramme adult cells to pluripotency. The way ahead looks similarly exciting as we address questions such as how cells function as systems and how complex interactions among genetics, epigenetics and the environment combine to shape phenotypes. C1 [Heard, Edith] Inst Curie, Mammalian Dev Epigenet Grp, INSERM, Unite Genet & Biol Dev,CNRS,UMR3215,U934, F-75248 Paris 05, France. [Tishkoff, Sarah] Univ Penn, Dept Genet, Sch Med, Philadelphia, PA 19104 USA. [Tishkoff, Sarah] Univ Penn, Dept Biol, Sch Med, Philadelphia, PA 19104 USA. [Todd, John A.] Univ Cambridge, Addenbrookes Hosp, Juvenile Diabet Res Fdn,Cambridge Inst Med Res, Wellcome Trust Diabet & Inflammat Lab, Cambridge CB2 0XY, England. [Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Wagner, Guenter P.] Yale Univ, Yale Syst Biol Inst, New Haven, CT 06520 USA. [Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark. [Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Weigel, Detlef] Max Planck Inst Dev Biol, Dept Mol Biol, D-72076 Tubingen, Germany. [Young, Richard] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Heard, E (reprint author), Inst Curie, Mammalian Dev Epigenet Grp, INSERM, Unite Genet & Biol Dev,CNRS,UMR3215,U934, 26 Rue Ulm, F-75248 Paris 05, France. EM Edith.Heard@curie.fr; tishkoff@mail.med.upenn.edu; john.todd@cimr.cam.ac.uk; marc_vidal@dfci.harvard.edu; gunter.wagner@yale.edu; wangj@genomics.org.cn; weigel@weigelworld.org; young@wi.mit.edu RI Weigel, Detlef/C-1418-2008; Young, Richard/F-6495-2012; Heard, Edith/D-7197-2017; OI Weigel, Detlef/0000-0002-2114-7963; Young, Richard/0000-0001-8855-8647; Heard, Edith/0000-0001-8052-7117; Wagner, Gunter/0000-0002-3097-002X FU NHGRI NIH HHS [R01 HG002668-07, R01 HG002668]; Wellcome Trust [079895, 091157] NR 104 TC 37 Z9 39 U1 0 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 EI 1471-0064 J9 NAT REV GENET JI Nat. Rev. Genet. PD OCT PY 2010 VL 11 IS 10 BP 723 EP 733 DI 10.1038/nrg2878 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 651FL UT WOS:000281911300012 PM 20820184 ER PT J AU Tamietto, M de Gelder, B AF Tamietto, Marco de Gelder, Beatrice TI Neural bases of the non-conscious perception of emotional signals SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID TRANSCRANIAL MAGNETIC STIMULATION; LATERAL GENICULATE-NUCLEUS; HAPPY FACIAL EXPRESSIONS; PRIMARY VISUAL-CORTEX; EVENT-RELATED FMRI; HUMAN AMYGDALA; FEARFUL FACES; AFFECTIVE BLINDSIGHT; SUPERIOR COLLICULUS; BINOCULAR-RIVALRY AB Many emotional stimuli are processed without being consciously perceived. Recent evidence indicates that subcortical structures have a substantial role in this processing. These structures are part of a phylogenetically ancient pathway that has specific functional properties and that interacts with cortical processes. There is now increasing evidence that non-consciously perceived emotional stimuli induce distinct neurophysiological changes and influence behaviour towards the consciously perceived world. Understanding the neural bases of the non-conscious perception of emotional signals will clarify the phylogenetic continuity of emotion systems across species and the integration of cortical and subcortical activity in the human brain. C1 [Tamietto, Marco; de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. [Tamietto, Marco; de Gelder, Beatrice] Inst Sci Interchange Fdn, I-10133 Turin, Italy. [Tamietto, Marco] Univ Turin, Dept Psychol, I-10123 Turin, Italy. [de Gelder, Beatrice] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP de Gelder, B (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, POB 90153, NL-5000 LE Tilburg, Netherlands. EM M.Tamietto@uvt.nl; degelder@nmr.mgh.harvard.edu OI Tamietto, Marco/0000-0002-8815-8499 FU Veni [451-07-032]; Netherlands Organization for Scientific Research (NWO); Fondazione Carlo Molo, Turin, Italy; Regione Piemonte, Italy; Grammatica Invisibile delle Relazioni Sociali (GIRS); Future and Emerging Technologies (FET); European Union [ICT-2009-C, 249858]; Cassa di Risparmio di Torino (CRT) Foundation FX We gratefully acknowledge valuable comments from P. Whalen and two anonymous referees. M. T. was supported by a Veni grant (451-07-032) from the Netherlands Organization for Scientific Research (NWO) and also partly supported by the Fondazione Carlo Molo, Turin, Italy and by a Bando Scienze Umane e Sociali 2008 grant from the Regione Piemonte, Italy, for the project Grammatica Invisibile delle Relazioni Sociali (GIRS) (grant number 4). B.d.G. was supported by an Future and Emerging Technologies (FET) Open Scheme grant (ICT-2009-C) from the European Union for the Emotional Interaction Grounded in Realistic Context (also known as TANGO) Project (249858) and by a Lagrange Fellow visiting professorship to the University of Torino, Turin, Italy funded by the Cassa di Risparmio di Torino (CRT) Foundation. NR 163 TC 311 Z9 325 U1 23 U2 123 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD OCT PY 2010 VL 11 IS 10 BP 697 EP 709 DI 10.1038/nrn2889 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 651LF UT WOS:000281928500003 PM 20811475 ER PT J AU Thomas, M Lieberman, J Lal, A AF Thomas, Marshall Lieberman, Judy Lal, Ashish TI Desperately seeking microRNA targets SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID MAMMALIAN MESSENGER-RNAS; 3' UNTRANSLATED REGIONS; POSTTRANSCRIPTIONAL REGULATION; SYSTEMATIC IDENTIFICATION; CELL-PROLIFERATION; BINDING-SITES; C-ELEGANS; PROTEIN; RECOGNITION; EXPRESSION AB MicroRNAs ( miRNAs) suppress gene expression by inhibiting translation, promoting mRNA decay or both. Each miRNA may regulate hundreds of genes to control the cell's response to developmental and other environmental cues. The best way to understand the function of a miRNA is to identify the genes that it regulates. Target gene identification is challenging because miRNAs bind to their target mRNAs by partial complementarity over a short sequence, suppression of an individual target gene is often small, and the rules of targeting are not completely understood. Here we review computational and experimental approaches to the identification of miRNA-regulated genes. The examination of changes in gene expression that occur when miRNA expression is altered and biochemical isolation of miRNA-associated transcripts complement target prediction algorithms. Bioinformatic analysis of over-represented pathways and nodes in protein-DNA interactomes formed from experimental candidate miRNA gene target lists can focus attention on biologically significant target genes. C1 [Thomas, Marshall; Lieberman, Judy; Lal, Ashish] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. [Thomas, Marshall; Lieberman, Judy; Lal, Ashish] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. EM lieberman@idi.harvard.edu; lalas@mail.nih.gov RI Lieberman, Judy/A-2717-2015 NR 74 TC 270 Z9 282 U1 2 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD OCT PY 2010 VL 17 IS 10 BP 1169 EP 1174 DI 10.1038/nsmb.1921 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 659JU UT WOS:000282563600004 PM 20924405 ER PT J AU Choi, WS Jeong, BC Joo, YJ Lee, MR Kim, J Eck, MJ Song, HK AF Choi, Woo Suk Jeong, Byung-Cheon Joo, Yoo Jin Lee, Myeong-Ryeol Kim, Joon Eck, Michael J. Song, Hyun Kyu TI Structural basis for the recognition of N-end rule substrates by the UBR box of ubiquitin ligases SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID ADAPTER PROTEIN CLPS; SACCHAROMYCES-CEREVISIAE; TERMINAL AMIDASE; MOLECULAR-BASIS; MICE LACKING; PATHWAY; DEGRADATION; COMPONENT; BINDING; ARABIDOPSIS AB The N-end rule pathway is a regulated proteolytic system that targets proteins containing destabilizing N-terminal residues (N-degrons) for ubiquitination and proteasomal degradation in eukaryotes. The N-degrons of type 1 substrates contain an N-terminal basic residue that is recognized by the UBR box domain of the E3 ubiquitin ligase UBR1. We describe structures of the UBR box of Saccharomyces cerevisiae UBR1 alone and in complex with N-degron peptides, including that of the cohesin subunit Scc1, which is cleaved and targeted for degradation at the metaphase-anaphase transition. The structures reveal a previously unknown protein fold that is stabilized by a novel binuclear zinc center. N-terminal arginine, lysine or histidine side chains of the N-degron are coordinated in a multispecific binding pocket. Unexpectedly, the structures together with our in vitro biochemical and in vivo pulse-chase analyses reveal a previously unknown modulation of binding specificity by the residue at position 2 of the N-degron. C1 [Choi, Woo Suk; Jeong, Byung-Cheon; Joo, Yoo Jin; Lee, Myeong-Ryeol; Kim, Joon; Song, Hyun Kyu] Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea. [Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Song, HK (reprint author), Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea. EM hksong@korea.ac.kr RI Song, Hyun Kyu/D-6763-2016 OI Song, Hyun Kyu/0000-0001-5684-4059 FU Basic Science Research Program through the National Research Foundation of Korea [NRF 2007-0055395]; 21C Frontier Functional Proteomics Project [FPR08B2-270]; World-Class University [R33-10108]; Plant Signaling Network Research Center; Ministry for Health, Welfare & Family Affairs, Republic of Korea [A092006] FX We thank the staff at the 4A and 6B beamlines, Pohang Accelerator Laboratory, Korea, and the NW12 beamline, Photon Factory, Japan, for help with the data collection. We also thank Y.T. Kwon (University of Pittsburgh) for providing us with unpublished data of UBR fragments and A. Varshavsky ( California Institute of Technology) for yeast strains and plasmids used for the in vivo study. This work was supported by a Basic Science Research Program through the National Research Foundation of Korea (NRF 2007-0055395), the 21C Frontier Functional Proteomics Project (FPR08B2-270), World-Class University Project (R33-10108), the Plant Signaling Network Research Center and the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092006). NR 42 TC 40 Z9 40 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD OCT PY 2010 VL 17 IS 10 BP 1175 EP + DI 10.1038/nsmb.1907 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 659JU UT WOS:000282563600005 PM 20835240 ER PT J AU Menon, V Katz, R Mukamal, K Kestenbaum, B de Boer, IH Siscovick, DS Sarnak, MJ Shlipak, MG AF Menon, Vandana Katz, Ronit Mukamal, Kenneth Kestenbaum, Bryan de Boer, Ian H. Siscovick, David S. Sarnak, Mark J. Shlipak, Michael G. TI Alcohol consumption and kidney function decline in the elderly Alcohol and Kidney Disease SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE alcohol; kidney disease; outcomes; progression ID STAGE RENAL-DISEASE; GLOMERULAR-FILTRATION-RATE; CORONARY-HEART-DISEASE; CARDIOVASCULAR HEALTH; OLDER-ADULTS; SERUM CREATININE; RISK-FACTORS; METAANALYSIS; ASSOCIATION; DAMAGE AB Methods. This prospective cohort study included 4343 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged >= 65 from four US communities. We used previously defined categories based on weekly alcohol consumption: none, former, < 1 drink, 1-6 drinks, 7-13 drinks and >= 14 drinks. Cystatin C was measured at baseline, year 3 and year 7; eligible subjects had at least two measures. Estimated GFR(cys) was calculated from cystatin C. The primary outcome was rapid kidney function as an annual estimated GFR (eGFR(cys)) loss > 3 mL/min/1.73 m(2)/year. Results. Eight percent of the cohort reported former alcohol use and 52% reported current alcohol consumption. During a mean follow-up of 5.6 years, 1075 (25%) participants had rapid kidney function decline. In adjusted logistic regression models, there was no association between alcohol use and kidney function decline (odds ratio, 95% confidence interval: none = reference; former = 1.18, 0.89-1.56; < 1 drink = 1.20, 0.99-1.47; 1-6 = 1.18, 0.95-1.45; 7-13 = 1.10, 0.80-1.53; > 14 = 0.89, 0.61-1.13). Results were similar with kidney function decline as a continuous outcome. Conclusions. Our results suggest that moderate alcohol consumption has neither adverse nor beneficial effects on kidney function. Although clinicians will need to consider the potential deleterious effects associated with alcohol consumption, there does not appear to be a basis for recommending that older adults discontinue or initiate light to moderate alcohol consumption to protect against kidney disease. C1 [Menon, Vandana; Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Katz, Ronit] Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Mukamal, Kenneth] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Kestenbaum, Bryan; de Boer, Ian H.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Menon, V (reprint author), Tufts Med Ctr, Div Nephrol, Boston, MA USA. EM vmenon@tuftsmedicalcenter.org FU NIDDK [K23 DK067303, RO1 AG 027002]; American Heart Association; National Heart, Lung and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295]; National Institute of Neurological Disorders and Stroke FX This study was supported by grants NIDDK K23 DK067303 and RO1 AG 027002. Dr Shlipak's work on this project was supported by RO1 DK066488-01 and the American Heart Association Established Investigator Award. This research was supported by N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and U01 HL080295 from the National Heart, Lung and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. NR 25 TC 16 Z9 16 U1 4 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD OCT PY 2010 VL 25 IS 10 BP 3301 EP 3307 DI 10.1093/ndt/gfq188 PG 7 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 654ML UT WOS:000282172300028 PM 20400446 ER PT J AU Haslinger, R Pipa, G Brown, E AF Haslinger, Robert Pipa, Gordon Brown, Emery TI Discrete Time Rescaling Theorem: Determining Goodness of Fit for Discrete Time Statistical Models of Neural Spiking SO NEURAL COMPUTATION LA English DT Article ID MAXIMUM-LIKELIHOOD-ESTIMATION; CORTEX AB One approach for understanding the encoding of information by spike trains is to fit statistical models and then test their goodness of fit. The time-rescaling theorem provides a goodness-of-fit test consistent with the point process nature of spike trains. The interspike intervals (ISIs) are rescaled (as a function of the model's spike probability) to be independent and exponentially distributed if the model is accurate. A Kolmogorov-Smirnov (KS) test between the rescaled ISIs and the exponential distribution is then used to check goodness of fit. This rescaling relies on assumptions of continuously defined time and instantaneous events. However, spikes have finite width, and statistical models of spike trains almost always discretize time into bins. Here we demonstrate that finite temporal resolution of discrete timemodels prevents their rescaled ISIs from being exponentially distributed. Poor goodness of fit may be erroneously indicated even if the model is exactly correct. We present two adaptations of the time-rescaling theorem to discrete time models. In the first we propose that instead of assuming the rescaled times to be exponential, the reference distribution be estimated through direct simulation by the fitted model. In the second, we prove a discrete time version of the time-rescaling theorem that analytically corrects for the effects of finite resolution. This allows us to define a rescaled time that is exponentially distributed, even at arbitrary temporal discretizations. We demonstrate the efficacy of both techniques by fitting generalized linear models to both simulated spike trains and spike trains recorded experimentally in monkey V1 cortex. Both techniques give nearly identical results, reducing the false-positive rate of the KS test and greatly increasing the reliability of model evaluation based on the time-rescaling theorem. C1 [Haslinger, Robert] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Haslinger, Robert; Pipa, Gordon; Brown, Emery] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Pipa, Gordon] Max Planck Inst Brain Res, Dept Neurophysiol, D-60528 Frankfurt, Germany. [Pipa, Gordon] Frankfurt Inst Adv Studies, D-60438 Frankfurt, Germany. [Brown, Emery] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Haslinger, R (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM robhh@nmr.mgh.harvard.edu; mail@g-pipa.com; enb@neurostat.mit.edu RI Pipa, Gordon/M-1813-2014 OI Pipa, Gordon/0000-0002-3416-2652 FU NIH [K25 NS052422-02, DP1 OD003646-01, MH59733-07]; Hertie Foundation; Max Planck Society; EU [FP6-2005-NEST-Path-043309] FX We thank Sergio Neuenschwander and Bruss Lima for the generous use of their data. This work was supported by NIH grants K25 NS052422-02, DP1 OD003646-01, MH59733-07, the Hertie Foundation, the Max Planck Society, and EU grant FP6-2005-NEST-Path-043309. NR 19 TC 17 Z9 17 U1 0 U2 2 PU M I T PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0899-7667 J9 NEURAL COMPUT JI Neural Comput. PD OCT PY 2010 VL 22 IS 10 BP 2477 EP 2506 DI 10.1162/NECO_a_00015 PG 30 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA 645ID UT WOS:000281445100001 PM 20608868 ER PT J AU Rosenfeld, MR Chamberlain, MC Grossman, SA Peereboom, DM Lesser, GJ Batchelor, TT Desideri, S Salazar, AM Ye, XB AF Rosenfeld, Myrna R. Chamberlain, Marc C. Grossman, Stuart A. Peereboom, David M. Lesser, Glenn J. Batchelor, Tracy T. Desideri, Serena Salazar, Andres M. Ye, Xiaobu TI A multi-institution phase II study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma(dagger) SO NEURO-ONCOLOGY LA English DT Article DE glioblastoma; glioma; Hiltonol; phase II; poly-ICLC ID TOLL-LIKE RECEPTOR-3; PSEUDO-PROGRESSION; GENE-EXPRESSION; TRIAL; CONCOMITANT; INDUCTION; RADIATION; RESPONSES; SURVIVAL; CELLS AB The objectives of this study were to determine the safety and efficacy of polyinosinic-polycytidylic acid stabilized with poly-l-lysine and carboxymethylcellulose (poly-ICLC) when added to radiation and temozolomide (TMZ) in adults with newly diagnosed glioblastoma (GB). Patients received external beam radiation with concurrent TMZ (75 mg/m(2)/day) followed by adjuvant TMZ (150-200 mg/m(2)/day for 5 consecutive days once every 9 weeks) and intramuscular poly-ICLC (20 mg/kg/dose given 3x per week for weeks 2-8). An adjuvant cycle was operationally defined as 9 weeks and patients continued adjuvant therapy until toxicity or disease progression. Ninety-seven patients were enrolled (60 men) with a median age of 56 years (range 21-85) and Karnofsky performance status of 90% (range 60%-100%). Fourteen patients did not start adjuvant treatment. Common treatment-related Grade 3-4 toxicities included neutropenia (20.6%), leukopenia (16.5%), thrombocytopenia (9%), and rash (1%). The entire cohort had a median survival of 17.2 months (95% CI: 15.5-19.3 months) with survival at 12, 18, and 24 months of 73.2%, 47.4%, and 29.9%. For subjects 18-70 years old, median overall survival was 18.3 months (95% CI: 15.9-19.8 months), as compared with 14.6 (95% CI: 13.2-16.8) reported by the EORTC 26981/22981 trial. These results demonstrate that poly-ICLC can be added to standard radiation and TMZ in patients with newly diagnosed GB without additional significant toxicities. Survival data at 12 and 18 months suggest that this may improve the efficacy of chemoradiation and adjuvant TMZ in this patient population. C1 [Rosenfeld, Myrna R.] Univ Penn, Dept Neurol, New Approaches Brain Tumor Therapy Consortium, Philadelphia, PA 19104 USA. [Chamberlain, Marc C.] Univ Washington, Seattle, WA 98195 USA. [Grossman, Stuart A.; Desideri, Serena; Ye, Xiaobu] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Peereboom, David M.] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. [Lesser, Glenn J.] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Salazar, Andres M.] Oncovir, Washington, DC USA. RP Rosenfeld, MR (reprint author), Univ Penn, Dept Neurol, New Approaches Brain Tumor Therapy Consortium, 3 W Gates,3400 Spruce St, Philadelphia, PA 19104 USA. EM myrna.rosenfeld@uphs.upenn.edu OI Rosenfeld, Myrna/0000-0001-5095-2534 FU National Cancer Institute [UO1CA137443] FX This study was supported in part by National Cancer Institute grant UO1CA137443. NR 24 TC 40 Z9 41 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2010 VL 12 IS 10 BP 1071 EP 1077 DI 10.1093/neuonc/noq071 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 654LW UT WOS:000282170800008 PM 20615924 ER PT J AU Zhang, JH Fung, SJ Xi, MC Sampogna, S Chase, MH AF Zhang, Jian-Hua Fung, Simon J. Xi, Mingchu Sampogna, Sharon Chase, Michael H. TI Apnea produces neuronal degeneration in the pons and medulla of guinea pigs SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Apnea; Single-stranded DNA; lmmunohistochemistry; Guinea pig; Brainstem ID OBSTRUCTIVE SLEEP-APNEA; CHRONIC INTERMITTENT HYPOXIA; VENTRAL RESPIRATORY GROUP; DEMONSTRATING CELL-DEATH; LATERAL TEGMENTAL FIELD; RAT-BRAIN; DNA-DAMAGE; IN-VIVO; SUBNUCLEAR ORGANIZATION; CATECHOLAMINE NEURONS AB Obstructive sleep apnea and other sleep-related breathing disorders result in recurrent periods of oxygen deprivation (hypoxia), hypercapnia and an increase in the cellular production of reactive oxygen species (oxidative stress-related injury). Individuals with these disorders suffer from a variety of cellular abnormalities that result in cardiopulmonary dysfunctions, disturbances in sleep and other pathologies. In the present experiment, using an animal model of sleep apnea, we determined that the degeneration of neurons and glia, due to apoptosis, occurs in specific regions of the pons and medulla. Adult guinea pigs, which were divided into control (normoxic) and experimental (hypoxic) groups, were anesthetized with alpha-chloralose and immobilized with Flaxedil. Apnea (hypoxia) was induced by ventilatory arrest in order to desaturate the oxyhemoglobin to 75% SpO(2). A sequence of apnea, followed by ventilation with recovery to > 95% SpO(2), was repeated for a period of 3 h. At the end of the period of recurrent apnea, the animals were perfused and brain sections were immunostained with a mouse monoclonal antibody raised against single-stranded DNA (ssDNA). Apoptotic neurons and glia, which were not found in the control group of animals, were present in brainstem regions in hypoxic group of animals; these regions involved in the control of respiration (e.g., the parafacial respiratory group and the ventral respiratory group), cardiovascular functions (e.g., the nucleus ambiguus, the nucleus tractus solitarius and the dorsal motor nucleus of the vagus) as well as REM sleep (the nucleus pontis oralis) and wakefulness (e.g., the dorsal raphe and locus ceruleus). We suggest apoptotic neurons and glia in critical areas of the pons and medulla results in many of the comorbidities experienced by patients with sleep-disordered breathing pathologies. (c) 2010 Elsevier Inc. All rights reserved. C1 [Zhang, Jian-Hua; Fung, Simon J.; Xi, Mingchu; Sampogna, Sharon; Chase, Michael H.] WebSci Int, Los Angeles, CA 90024 USA. [Zhang, Jian-Hua; Fung, Simon J.; Xi, Mingchu; Chase, Michael H.] VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Chase, Michael H.] Univ Calif Los Angeles, Dept Physiol, Sch Med, Los Angeles, CA 90025 USA. RP Zhang, JH (reprint author), WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90024 USA. EM jzhang@websciences.org NR 69 TC 15 Z9 16 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 2010 VL 40 IS 1 SI SI BP 251 EP 264 DI 10.1016/j.nbd.2010.05.032 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 645OY UT WOS:000281473400030 PM 20554036 ER PT J AU Reinsberger, C Tanaka, N Cole, AJ Lee, JW Dworetzky, BA Bromfield, EB Hamiwka, L Bourgeois, BF Golby, AJ Madsen, JR Stufflebeam, SM AF Reinsberger, Claus Tanaka, Naoaki Cole, Andrew J. Lee, Jong Woo Dworetzky, Barbara A. Bromfield, Edward B. Hamiwka, Lorie Bourgeois, Blaise F. Golby, Alexandra J. Madsen, Joseph R. Stufflebeam, Steven M. TI Current dipole orientation and distribution of epileptiform activity correlates with cortical thinning in left mesiotemporal epilepsy SO NEUROIMAGE LA English DT Article ID TEMPORAL-LOBE EPILEPSY; SURFACE-BASED ANALYSIS; HIPPOCAMPAL ATROPHY; COORDINATE SYSTEM; WHITE-MATTER; ABNORMALITIES; SCLEROSIS; SEIZURES; GRAY AB To evaluate cortical architecture in mesial temporal lobe epilepsy (MTLE) with respect to electrophysiology, we analyze both magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 19 patients with left MTLE. We divide the patients into two groups: 9 patients (Group A) have vertically oriented antero-medial equivalent current dipoles (ECDs). 10 patients (Group B) have ECDs that are diversely oriented and widely distributed. Group analysis of MRI data shows widespread cortical thinning in Group B compared with Group A. in the left hemisphere involving the cingulate, supramarginal, occipitotemporal and parahippocampal gyri, precuneus and parietal lobule, and in the right hemisphere involving the fronto-medial, -central and -basal gyri and the precuneus. These results suggest that regardless of the presence of hippocampal sclerosis, in a subgroup of patients with MTLE a large cortical network is affected. This finding may, in part, explain the unfavorable outcome in some MTLE patients after epilepsy surgery. (C) 2010 Elsevier Inc. All rights reserved. C1 [Reinsberger, Claus; Tanaka, Naoaki; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Reinsberger, Claus] Univ Munich, Dept Neurol, D-97078 Wurzburg, Germany. [Reinsberger, Claus; Lee, Jong Woo; Dworetzky, Barbara A.; Bromfield, Edward B.; Stufflebeam, Steven M.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Cole, Andrew J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. [Hamiwka, Lorie] Ohio State Univ, Coll Med, Div Child Neurol, Columbus, OH 43210 USA. [Bourgeois, Blaise F.] Childrens Hosp Boston, Dept Neurol, Boston, MA 02115 USA. [Golby, Alexandra J.] Brigham & Womens Hosp, Dept Neurosurg & Radiol, Boston, MA 02115 USA. [Madsen, Joseph R.] Childrens Hosp Boston, Dept Neurosurg, Boston, MA 02115 USA. [Stufflebeam, Steven M.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Stufflebeam, SM (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. EM sms@nmr.mgh.harvard.edu RI Hamiwka, Lorie/C-5585-2008; OI Hamiwka, Lorie/0000-0002-6946-4028; Dworetzky, Barbara/0000-0002-3364-2347 FU Felgenhauer Stiftung of the German Neurological Society; National Institutes of Health [P41RR14075, RO1NS037462-07, 5K08MH067966, U41-RR019703, P01CA067165]; Mental Illness and Neuroscience Discovery Institute; NARSAD; Japan Epilepsy Research Foundation; Brain Science Foundation; Klarman Family Foundation FX This work was supported by an educational grant of the Felgenhauer Stiftung of the German Neurological Society, National Institutes of Health (P41RR14075, RO1NS037462-07, 5K08MH067966, U41-RR019703, and P01CA067165), Mental Illness and Neuroscience Discovery Institute, NARSAD Young Investigators Award, Japan Epilepsy Research Foundation, Brain Science Foundation, and Klarman Family Foundation. NR 18 TC 5 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2010 VL 52 IS 4 BP 1238 EP 1242 DI 10.1016/j.neuroimage.2010.04.264 PG 5 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 635YY UT WOS:000280695200012 PM 20472073 ER PT J AU Polimeni, JR Fischl, B Greve, DN Wald, LL AF Polimeni, Jonathan R. Fischl, Bruce Greve, Douglas N. Wald, Lawrence L. TI Laminar analysis of 7 T BOLD using an imposed spatial activation pattern in human V1 SO NEUROIMAGE LA English DT Article ID OCULAR DOMINANCE COLUMNS; HUMAN CEREBRAL-CORTEX; HUMAN VISUAL-CORTEX; HUMAN BRAIN ACTIVATION; SURFACE-BASED ANALYSIS; POINT-SPREAD FUNCTION; SPIN-ECHO FMRI; FUNCTIONAL MRI; STRIATE CORTEX; BLOOD OXYGENATION AB With sufficient image encoding, high-resolution fMRI studies are limited by the biological point-spread of the hemodynamic signal. The extent of this spread is determined by the local vascular distribution and by the spatial specificity of blood flow regulation, as well as by measurement parameters that (i) alter the relative sensitivity of the acquisition to activation-induced hemodynamic changes and (ii) determine the image contrast as a function of vessel size. In particular, large draining vessels on the cortical surface are a major contributor to both the BOLD signal change and to the spatial bias of the BOLD activation away from the site of neuronal activity. In this work, we introduce a laminar surface-based analysis method and study the relationship between spatial localization and activation strength as a function of laminar depth by acquiring 1 mm isotropic, single-shot EPI at 7 T and sampling the BOLD signal exclusively from the superficial, middle, or deep cortical laminae. We show that highly-accelerated EPI can limit image distortions to the point where a boundary-based registration algorithm accurately aligns the EPI data to the surface reconstruction. The spatial spread of the BOLD response tangential to the cortical surface was analyzed as a function of cortical depth using our surface-based analysis. Although sampling near the pial surface provided the highest signal strength, it also introduced the most spatial error. Thus, avoiding surface laminae improved spatial localization by about 40% at a cost of 36% in z-statistic, implying that optimal spatial resolution in functional imaging of the cortex can be achieved using anatomically-informed spatial sampling to avoid large pial vessels. (C) 2010 Elsevier Inc. All rights reserved. C1 [Polimeni, Jonathan R.; Fischl, Bruce; Greve, Douglas N.; Wald, Lawrence L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Fischl, Bruce] MIT, CSAIL, Cambridge, MA 02139 USA. [Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Polimeni, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Bldg 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM jonp@nmr.mgh.harvard.edu RI Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; FU Athinoula A. Martinos Center for Biomedical Imaging; NIH NCRR [P41 RR14075]; National Institute for Biomedical Imaging and Bioengineering [R01 EB006758, R01 EB006847]; National Institute on Aging [AG02238]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; Ellison Medical Foundation FX We would like to thank Dr. Thomas Benner for his assistance with the EPI protocol, Ms. Kyoko Fujimoto for her help in conducting the experiments, Dr. Graham Wiggins for the 32-channel array coil, and Mr. Thomas Witzel and Drs. Oliver Hinds, Mukund Balasubramanian, and Eric Schwartz for their useful discussions. This work was supported by the Athinoula A. Martinos Center for Biomedical Imaging, the NIH NCRR grant P41 RR14075. Further support was provided by the National Institute for Biomedical Imaging and Bioengineering (R01 EB006758, and R01 EB006847), the National Institute on Aging (AG02238), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01) and by the Autism & Dyslexia Project funded by the Ellison Medical Foundation. NR 75 TC 107 Z9 107 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2010 VL 52 IS 4 BP 1334 EP 1346 DI 10.1016/j.neuroimage.2010.05.005 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 635YY UT WOS:000280695200022 PM 20460157 ER PT J AU Sampat, MP Healy, BC Meier, DS Dell'Oglio, E Liguori, M Guttmann, CRG AF Sampat, Mehul P. Healy, Brian C. Meier, Dominik S. Dell'Oglio, Elisa Liguori, Maria Guttmann, Charles R. G. TI Disease modeling in multiple sclerosis: Assessment and quantification of sources of variability in brain parenchymal fraction measurements SO NEUROIMAGE LA English DT Article ID FOLLOW-UP; QUANTITATIVE-ANALYSIS; CORTICAL THICKNESS; MR-IMAGES; ATROPHY; RELIABILITY; DISABILITY; REPRODUCIBILITY; MATTER; VOLUME AB The measurement of brain atrophy from magnetic resonance imaging (MRI) has become an established method of estimating disease severity and progression in multiple sclerosis (MS). Most commonly reported in the form of brain parenchymal fraction (BPF), it is more sensitive to the degenerative component of the disease and shows progression more reliably than lesion burden. Typically, the reliability of BPF and other morphometric measurements is assessed by evaluating scan-rescan experiments. While these experiments provide good estimates of real-life error related to imperfect patient repositioning in the MRI scanner, measurement variance due to physiological and reversible pathological fluctuations in brain volume are not taken into account. In this work, we propose a new model for estimating variability in serial morphometry, particularly the BPF measurement. Specifically, we attempt to detect and explicitly model the remaining sources of error to more accurately describe the overall variability in BPF measurements. Our results show that sources of variability beyond subject repositioning error are important and cannot be ignored. We demonstrate that scan-rescan experiments only provide a lower bound on the true error in repeated measurements of patients' BPF. We have estimated the variance due to patient repositioning during scan-rescan (sigma(2)(sr) = 3.0e-06), variance assigned to physiological fluctuations (sigma(2)(p) = 5.74e-06) and the variance associated with lesion activity (sigma(2)(les) = 1.09e-05). These variance components can be used to determine the relative impact of their sources on sample size estimates for studies investigating change over time in MS patients. Our results demonstrate that sample size calculations based exclusively on scan-rescan variability (sigma(sr)) are likely to underestimate the number of patients required. If the physiological variability (sigma(p)) is incorporated in sample size calculations, the required sample size would increase by a factor of 5.69 based on standard t-test sample size calculation. (C) 2010 Elsevier Inc. All rights reserved. C1 [Meier, Dominik S.; Liguori, Maria; Guttmann, Charles R. G.] Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Imaging, Sch Med, Boston, MA 02115 USA. [Sampat, Mehul P.] Univ Calif San Francisco, Dept Neurol, Adv Imaging Multiple Sclerosis Lab, San Francisco, CA 94143 USA. [Healy, Brian C.] Harvard Univ, Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Sch Med, Boston, MA 02115 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Dept Neurol, Ctr Biostat, Boston, MA 02114 USA. [Dell'Oglio, Elisa] Harvard Univ, Brigham & Womens Hosp, Lab Neuroimaging Res, Sch Med, Boston, MA 02115 USA. [Liguori, Maria] CNR, Inst Neurol Sci, Mangone, Italy. RP Guttmann, CRG (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Imaging, Sch Med, 221 Longwood Ave,RF 394, Boston, MA 02115 USA. EM guttmann@bwh.harvard.edu RI Liguori, Maria/D-4390-2016 OI Liguori, Maria/0000-0003-4338-0392 NR 35 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2010 VL 52 IS 4 BP 1367 EP 1373 DI 10.1016/j.neuroimage.2010.03.075 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 635YY UT WOS:000280695200025 PM 20362675 ER PT J AU Foley, AR Hu, Y Zou, Y Yang, M Medne, L Leach, M Conlin, L Spinner, N Shaikh, T Neumeyer, AM Bliss, L Winder, T Bonnemann, CG AF Foley, A. R. Hu, Y. Zou, Y. Yang, M. Medne, L. Leach, M. Conlin, L. Spinner, N. Shaikh, T. Neumeyer, A. M. Bliss, L. Winder, T. Bonnemann, C. G. TI Large genomic deletions as a novel type of mutation in Ullrich CMD SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 15th International Congress of the World-Muscle-Society CY OCT 12-16, 2010 CL Kumamoto, JAPAN SP World Muscle Soc C1 [Yang, M.] Univ Colorado, Dept Neurol, Childrens Hosp, Denver, CO 80202 USA. [Medne, L.] Univ Penn, Childrens Hosp Philadelphia, Div Neurol, Div Clin Genet, Philadelphia, PA 19104 USA. [Shaikh, T.] Univ Penn, Childrens Hosp Philadelphia, Div Genet, Dept Pediat, Philadelphia, PA 19104 USA. [Winder, T.] Prevent Genet, Marshfield, WI USA. [Neumeyer, A. M.; Bliss, L.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2010 VL 20 IS 9-10 BP 602 EP 603 DI 10.1016/j.nmd.2010.07.026 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 659JO UT WOS:000282563000022 ER PT J AU Bindoff, LA Fiskerstrand, T H'mida-Ben Brahim, D Johansson, S M'zahem, A Haukanes, BI Drouot, N Zimmermann, J Cole, AJ Vedeler, C Bredrup, C Assoum, M Tazir, M Klockgether, T Hamri, A Steen, VM Boman, H Koenig, M Knappskog, PM AF Bindoff, L. A. Fiskerstrand, T. H'mida-Ben Brahim, D. Johansson, S. M'zahem, A. Haukanes, B. I. Drouot, N. Zimmermann, J. Cole, A. J. Vedeler, C. Bredrup, C. Assoum, M. Tazir, M. Klockgether, T. Hamri, A. Steen, V. M. Boman, H. Koenig, M. Knappskog, P. M. TI Genetic characterisation of PHARC - a novel syndrome resembling Refsum's disease SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 15th International Congress of the World-Muscle-Society CY OCT 12-16, 2010 CL Kumamoto, JAPAN SP World Muscle Soc C1 [Bindoff, L. A.; Vedeler, C.] Univ Bergen, Dept Neurol, N-5014 Bergen, Norway. [Fiskerstrand, T.; Johansson, S.; Haukanes, B. I.; Steen, V. M.; Boman, H.; Knappskog, P. M.] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. [H'mida-Ben Brahim, D.; Drouot, N.; Assoum, M.; Koenig, M.] Univ Strasbourg, INSERM, CNRS, IGBMC, Strasbourg, France. [Zimmermann, J.] Univ Klinikum, Klin & Poliklin Neurol, Bonn, Germany. [M'zahem, A.; Hamri, A.] Ctr Hosp Univ Ben Badis, Constantine, Algeria. [Cole, A. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cole, A. J.] Harvard Univ, Sch Med, MGH Epilepsy Serv, Boston, MA USA. [Bredrup, C.] Haukeland Hosp, Dept Ophthalmol, N-5021 Bergen, Norway. [Tazir, M.] Ctr Hosp Univ Mustapha, Serv Neurol, Algiers, Algeria. [Klockgether, T.] DZNE, Bonn, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2010 VL 20 IS 9-10 BP 680 EP 680 DI 10.1016/j.nmd.2010.07.266 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 659JO UT WOS:000282563000262 ER PT J AU Ciesielski, KT Ahlfors, SP Bedrick, EJ Kerwin, AA Hamalainen, MS AF Ciesielski, Kristina T. Ahlfors, Seppo P. Bedrick, Edward J. Kerwin, Andra A. Hamalainen, Matti S. TI Top-down control of MEG alpha-band activity in children performing Categorical N-Back Task SO NEUROPSYCHOLOGIA LA English DT Article DE Top down control of alpha band activity; Cognitive development; Dorsal visual cortical network; Visual Categorical N Back Task; Magnetoencephalography ID SELECTIVE VISUAL-ATTENTION; REACTION TIME TASKS; HIGH-RESOLUTION EEG; WORKING-MEMORY; PARIETAL CORTEX; BASAL GANGLIA; BRAIN; RHYTHMS; DESYNCHRONIZATION; MODULATION AB Top-down cognitive control has been associated in adults with the prefrontal-parietal network In children the brain mechanisms of top-down control have rarely been studied We examined developmental differences in top-down cognitive control by monitoring event-related desynchronization (ERD) and event-related synchronization (ERS) of alpha-band oscillatory activity (8-13 Hz) during anticipation target detection and post-response stages of a visual working memory task Magnetoencephalography (MEG) was used to record brain oscillatory activity from healthy 10-year-old children and young adults performing the Categorical N-Back Task (CNBT) Neuropsychological measures assessing frontal lobe networks were also acquired Whereas adults showed a modulation of the ERD at the anticipatory stages of CNBT and ERS at the post-response stage children displayed only some anticipatory modulation of ERD but no ERS at the post-response stage with alpha-band remaining at a desynchronized state Since neuropsychological and prior neuroimaging findings indicate that the prefrontal-parietal networks are not fully developed in 10-year olds and since the children performed as well as the adults on CNBT and yet displayed different patterns of ERD/ERS we suggest that children may be using different top-down cognitive strategies and hence different developmentally apt neuronal networks (C) 2010 Elsevier Ltd All rights reserved C1 [Ciesielski, Kristina T.; Ahlfors, Seppo P.; Kerwin, Andra A.; Hamalainen, Matti S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Ciesielski, Kristina T.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Ahlfors, Seppo P.; Hamalainen, Matti S.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02135 USA. [Bedrick, Edward J.] Univ New Mexico, Hlth Sci Ctr, Dept Epidemiol, Albuquerque, NM 87131 USA. RP Ciesielski, KT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Hamalainen, Matti/C-8507-2013; Ahlfors, Seppo/P-3644-2016 FU National Center for Research Resources [P41RR14075] FX We thank Drs Bruce Rosen for his continuous support and Mark Vangel for helpful comments Study was supported in part by the National Center for Research Resources (P41RR14075) Authorship KTC and MSH are both senior authors NR 71 TC 7 Z9 7 U1 3 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD OCT PY 2010 VL 48 IS 12 BP 3573 EP 3579 DI 10.1016/j.neuropsychologia.2010.08.006 PG 7 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 677UM UT WOS:000284017300022 PM 20713071 ER PT J AU Spreng, RN Rosen, HJ Strother, S Chow, TW Diehl-Schmid, J Freedman, M Graff-Radford, NR Hodges, JR Lipton, AM Mendez, MF Morelli, SA Black, SE Miller, BL Levine, B AF Spreng, R. Nathan Rosen, Howard J. Strother, Stephen Chow, Tiffany W. Diehl-Schmid, Janine Freedman, Morris Graff-Radford, Neill R. Hodges, John R. Lipton, Anne M. Mendez, Mario F. Morelli, Sylvia A. Black, Sandra E. Miller, Bruce L. Levine, Brian TI Occupation attributes relate to location of atrophy in frontotemporal lobar degeneration SO NEUROPSYCHOLOGIA LA English DT Article DE Frontotemporal dementia; Laterality; Reserve ID ALZHEIMERS-DISEASE; DEVELOPMENTAL DYSLEXIA; LIFETIME OCCUPATION; PROGRESSIVE APHASIA; RESERVE HYPOTHESIS; COGNITIVE RESERVE; SEMANTIC DEMENTIA; WORK GROUP; BRAIN; EDUCATION AB Frontotemporal lobar degeneration (FTLD) often presents with asymmetric atrophy We assessed whether premorbid occupations in FTLD patients were associated with these hemispheric asymmetries In a multi-center chart review of 588 patients occupation information was related to location of tissue loss or dysfunction Patients with atrophy lateralized to the right had professions more dependent on verbal abilities than patients with left-lateralized or symmetrical atrophy In a subgroup of 96 well-characterized patients with quantified neuroimaging data the lateralization effect was localized to the temporal lobes and Included verbal and mathematical ability Patients whose professions placed high demands on language and mathematics had relatively preserved left temporal relative to right temporal volumes Thus occupation selection occurring in early adulthood is related to lateralized brain asymmetry in patients who develop FTLD decades later in the relatively deficient hemisphere The finding suggests that verbal and mathematical occupations may have been pursued due to developmental right-lateralized functional impairment that precedes the neurodegeneranve process Alternatively long-term engagement of activities associated with these occupations contributed to left-lateralized reserve right-lateralized dysfunction or both (C) 2010 Elsevier Ltd All rights reserved C1 [Spreng, R. Nathan; Strother, Stephen; Chow, Tiffany W.; Levine, Brian] Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON, Canada. [Spreng, R. Nathan; Freedman, Morris; Black, Sandra E.; Levine, Brian] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. [Rosen, Howard J.; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Rosen, Howard J.; Miller, Bruce L.] UCSF Memory & Aging Ctr, San Francisco, CA USA. [Chow, Tiffany W.; Freedman, Morris; Black, Sandra E.; Levine, Brian] Univ Toronto, Dept Med Neurol, Toronto, ON M5S 1A1, Canada. [Chow, Tiffany W.] Univ Toronto, Dept Psychiat Geriatr Psychiat, Toronto, ON M5S 1A1, Canada. [Diehl-Schmid, Janine] Tech Univ Munich, Dept Psychiat, Munich, Germany. [Diehl-Schmid, Janine] Tech Univ Munich, Dept Psychotherapy, Munich, Germany. [Freedman, Morris] Baycrest Ctr Geriatr Care, Div Neurol, Behav Neurol Program, Toronto, ON, Canada. [Freedman, Morris] Mt Sinai Hosp, Dept Med, Div Neurol, Univ Hlth Network, Toronto, ON M5G 1X5, Canada. [Graff-Radford, Neill R.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Hodges, John R.] MRC, Cognit & Brain Sci Unit, Cambridge, England. [Lipton, Anne M.] Presbyterian Med Ctr, Dept Neurol, Dallas, TX USA. [Mendez, Mario F.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. [Mendez, Mario F.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Mendez, Mario F.] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Morelli, Sylvia A.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Spreng, RN (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. RI Levine, Brian/G-4328-2010; OI Levine, Brian/0000-0003-4343-811X; Morelli, Sylvia/0000-0002-3353-678X; Black, Sandra/0000-0001-7093-8289; Strother, Stephen/0000-0002-3198-217X; Spreng, R. Nathan/0000-0003-1530-8916 FU Canadian Institutes of Health Research [MGP-62963]; National Institute of Child Health and Human Development [HD42385-01] FX This study was supported by Canadian Institutes of Health Research (MGP-62963) and the National Institute of Child Health and Human Development (HD42385-01) grants to B Levine The authors declare no actual or potential conflicts of interest All appropriate approval and procedures were followed concerning human subjects We thank Morris Moscovitch for his involvement Pheth Sengdy Irina Nica and Namita Kumar for their assistance and Karen Spreng for her contributions during the course of this project NR 54 TC 9 Z9 9 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD OCT PY 2010 VL 48 IS 12 BP 3634 EP 3641 DI 10.1016/j.neuropsychologia.2010.08.020 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 677UM UT WOS:000284017300030 PM 20800604 ER PT J AU Hauck, EF Ogilvy, CS Siddiqui, AH Hopkins, LN Levy, EI AF Hauck, Erik F. Ogilvy, Christopher S. Siddiqui, Adnan H. Hopkins, L. Nelson Levy, Elad I. TI Direct Endovascular Recanalization of Chronic Carotid Occlusion: Should We Do It? Case Report SO NEUROSURGERY LA English DT Article DE Carotid occlusion; Carotid stent; Endovascular; Intracranial stent AB BACKGROUND AND IMPORTANCE: Patients with chronic carotid artery occlusion face a significant risk of stroke. It is believed that treatment is indicated if medical therapy fails or even as prophylaxis in high-risk patients. Direct surgical repair with carotid endarterectomy has a considerable failure rate and significant associated risks. Indirect repair with an extracranial-to-intracranial bypass has become the mainstay of surgical treatment. In this case study, the authors assess the feasibility of direct endovascular recanalization in the setting of chronic carotid occlusion, and discuss technical nuances and indications in comparison with the world literature and alternative options. CLINICAL PRESENTATION: Two patients presented with symptomatic, chronic, complete occlusion of the proximal carotid artery. The duration of documented occlusion exceeded 3 years in one patient and 6 months in the other. METHODS: Endovascular recanalization was attempted using extracranial and intracranial stenting with proximal protection (flow arrest/reversal). Both patients had an excellent radiographic result, improving from Thrombolysis in Cerebral Infarction (TICI) grade 0 (no perfusion) to grade 3 (complete perfusion). The first patient's clinical symptoms resolved. The second patient remained unchanged with a mild facial droop. CONCLUSION: These preliminary results show potential for the endovascular management of this complicated disease. Long-term results and more data will determine the ultimate place of endovascular recanalization for symptomatic chronic carotid occlusion among other therapies. C1 [Hauck, Erik F.; Ogilvy, Christopher S.; Siddiqui, Adnan H.; Hopkins, L. Nelson; Levy, Elad I.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Neurosurg & Radiol, Buffalo, NY 14260 USA. [Hauck, Erik F.; Ogilvy, Christopher S.; Siddiqui, Adnan H.; Hopkins, L. Nelson; Levy, Elad I.] SUNY Buffalo, Sch Med & Biomed Sci, Toshiba Stroke Res Ctr, Buffalo, NY 14260 USA. Millard Fillmore Gates Hosp, Dept Neurosurg, Buffalo, NY USA. [Ogilvy, Christopher S.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Hauck, EF (reprint author), SUNY Buffalo, Sch Med & Biomed Sci, Dept Neurosurg & Radiol, Buffalo, NY 14260 USA. NR 0 TC 8 Z9 9 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 OCT PY 2010 VL 67 IS 4 BP 1148 EP 1152 DI 10.1227/NEU.0b013e3181edaf99 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 654VA UT WOS:000282197900072 PM 20881534 ER PT J AU Larson, PS AF Larson, Paul S. TI Minimally Invasive Surgery for Movement Disorders SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Deep brain stimulation; Stereotactic surgery; Frameless deep brain stimulation; Interventional MRI; Gene transfer ID PHASE-I TRIAL; SUBTHALAMIC NUCLEUS; PARKINSONS-DISEASE; OPEN-LABEL; BRAIN; TOLERABILITY; SAFETY AB Movement disorders surgery, particularly deep brain stimulation (DBS), is already a minimally invasive procedure However new innovations in the delivery devices for DBS electrodes, new methods for target localization, and alternatives to implanted hardware are all strategies that can make movement disorders surgery less invasive Frameless DBS techniques can increase patient comfort and shorten operative time Interventional magnetic resonance imaging can further reduce operative time, and allows DBS placement to be done with a patient asleep and usually with a single brain penetration Finally, gene transfer eliminates the need for implanted hardware or batteries and simplifies postoperative care C1 [Larson, Paul S.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Larson, Paul S.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Larson, PS (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,Box 0112, San Francisco, CA 94143 USA. FU Medtronic Inc; Surgivision Inc; Ceregene Inc; Genzyme Inc FX This article describes work that was supported by research grants and support to the author from Medtronic Inc Surgivision Inc Ceregene Inc and Genzyme Inc NR 11 TC 4 Z9 4 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 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD OCT PY 2010 VL 21 IS 4 BP 691 EP + DI 10.1016/j.nec.2010.07.012 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 681DO UT WOS:000284291800011 PM 20947036 ER PT J AU Burkhardt, JK Zinn, PO Bozinov, O Colen, RR Bertalanffy, H Kasper, EM AF Burkhardt, Jan-Karl Zinn, Pascal O. Bozinov, Oliver Colen, Rivka R. Bertalanffy, Helmut Kasper, Ekkehard M. TI Neurosurgical education in Europe and the United States of America SO NEUROSURGICAL REVIEW LA English DT Review DE Neurosurgery; Education; Residency; Curriculum; United States; Europe ID RESIDENT DUTY HOURS; TRAINING-PROGRAMS AB Training in neurological surgery is one of the most competitive and demanding specializations in medicine. It therefore demands careful planning in both the scientific and clinical neurosurgery arena to finally turn out physicians that can be clinically sound and scientifically competitive. National and international training and career options are pointed out, based on the available relevant literature, with the objective of comparing the neurosurgical training in Europe and the USA. Despite clear European Association of Neurosurgical Societies guidelines, every country in Europe maintains its own board requirements, which is reflected in an institutional curriculum that is specific to the professional society of that particular country. In contrast, the residency program in the USA is required to comply with the Accreditation Council for Graduate Medical Education guidelines. Rather similar guidelines exist for the education of neurosurgical residents in the USA and Europe; their translation into the practical hospital setting and the resulting clinical lifestyle of a resident diverges enormously. Since neurosurgical education remains heterogeneous worldwide, we argue that a more standardized curriculum across different nations would greatly facilitate the interaction of different centers, allow a direct comparison of available services, and support the exchange of vital information for quality control and future improvements. Furthermore, the exchange of residents between different training centers may improve education by increasing their knowledge base, both technically as well as intellectually. C1 [Burkhardt, Jan-Karl; Bozinov, Oliver; Bertalanffy, Helmut] Univ Zurich, Univ Hosp, Dept Neurosurg, CH-8091 Zurich, Switzerland. [Burkhardt, Jan-Karl] Univ Zurich Hosp, Dept Surg Res, Regenerat Med Program, CH-8091 Zurich, Switzerland. [Zinn, Pascal O.; Kasper, Ekkehard M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurosurg, Boston, MA 02215 USA. [Colen, Rivka R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Zinn, Pascal O.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02115 USA. RP Burkhardt, JK (reprint author), Univ Zurich, Univ Hosp, Dept Neurosurg, Frauenklin Str 10,Nord 1, CH-8091 Zurich, Switzerland. EM JanKarl.Burkhardt@gmail.com RI lyp, maggie/G-1471-2011; OI Bozinov, Oliver/0000-0002-4620-3992 FU Swiss National Science Foundation FX Dr. Pascal O. Zinn is recipient of a scholarship by the Swiss National Science Foundation. NR 19 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5607 J9 NEUROSURG REV JI Neurosurg. Rev. PD OCT PY 2010 VL 33 IS 4 BP 409 EP 414 DI 10.1007/s10143-010-0257-6 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 662VY UT WOS:000282843600007 PM 20429023 ER PT J AU Yenari, MA Kauppinen, TM Swanson, RA AF Yenari, Midori A. Kauppinen, Tiina M. Swanson, Raymond A. TI Microglial Activation in Stroke: Therapeutic Targets SO NEUROTHERAPEUTICS LA English DT Review DE NF-kappa B; AP-1; PARP-1; minocycline; inflammation; ischemia; TREM2 ID FOCAL CEREBRAL-ISCHEMIA; NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; METABOTROPIC GLUTAMATE RECEPTORS; TRANSIENT FOREBRAIN ISCHEMIA; TUMOR-NECROSIS-FACTOR; BLOOD-BRAIN-BARRIER; HEAT-SHOCK-PROTEIN; POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; INDUCED NEURONAL DEATH AB Microglial activation is an early response to brain ischemia and many other stressors. Microglia continuously monitor and respond to changes in brain homeostasis and to specific signaling molecules expressed or released by neighboring cells. These signaling molecules, including ATP, glutamate, cytokines, prostaglandins, zinc, reactive oxygen species, and HSP60, may induce microglial proliferation and migration to the sites of injury. They also induce a nonspecific innate immune response that may exacerbate acute ischemic injury. This innate immune response includes release of reactive oxygen species, cytokines, and proteases. Microglial activation requires hours to days to fully develop, and thus presents a target for therapeutic intervention with a much longer window of opportunity than acute neuroprotection. Effective agents are now available for blocking both microglial receptor activation and the microglia effector responses that drive the inflammatory response after stroke. Effective agents are also available for targeting the signal transduction mechanisms linking these events. However, the innate immune response can have beneficial as well deleterious effects on outcome after stoke, and a challenge will be to find ways to selectively suppress the deleterious effects of microglial activation after stroke without compromising neurovascular repair and remodeling. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. RP Swanson, RA (reprint author), VAMC, 4150 Clement St, San Francisco, CA 94121 USA. EM raymond.swanson@ucsf.edu OI Kauppinen, Tiina/0000-0001-7219-9862; Swanson, Raymond/0000-0002-3664-5359 FU Department of Veterans Affairs; Department of Defense [W81XH-05-2-0094, DAMD17-03-1-0532]; National Institutes of Health [NS14543, NS40516]; American Heart Association [0835222N] FX This work was supported by the Department of Veterans Affairs (R.A.S., M.A.Y.), the Department of Defense (W81XH-05-2-0094, R.A.S.; DAMD17-03-1-0532, M.A.Y.), the National Institutes of Health (NS14543, R.A.S.; NS40516, M.A.Y.), and the American Heart Association (0835222N, T.M.K.). NR 232 TC 123 Z9 127 U1 3 U2 40 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD OCT PY 2010 VL 7 IS 4 BP 378 EP 391 PG 14 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 654VG UT WOS:000282198500005 PM 20880502 ER PT J AU Cavallari, JM Fang, SC Mittleman, MA Christiani, DC AF Cavallari, Jennifer M. Fang, Shona C. Mittleman, Murray A. Christiani, David C. TI Circadian variation of heart rate variability among welders SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CARDIOVASCULAR-DISEASE; RHYTHM; EXPOSURES; CLOCK; TIME AB Objective To compare the circadian variation of hourly heart rate variability (HRV) on work and non-workdays among boilermaker construction workers. Method A panel study of 18 males monitored by 24-h ambulatory ECG over 44 observation-days on paired work and non-workdays was conducted. ECGs were analysed and the SD of normal-to-normal beats index (SDNNi) was calculated from 5-min data and summarised hourly. SDNN(i)s over work and non-workdays were compared using linear mixed-effects models to account for repeated measures and harmonic regression to account for circadian variation. Results Both work and non-work hourly HRV exhibited circadian variation with an increase in the evening and a decrease in the afternoon. SDNNi was lower on workdays as compared with non-workdays with the largest, statistically significant differences observed between 10:00 and 16:00, during active working. Lower SDNNi, albeit smaller yet statistically significant differences, was also observed in the evening hours following work (17:00-21:00) and early morning (4:00). In regression models using all time periods, an average workday SDNNi was 8.1 ms (95% CI -9.8 to -6.3) lower than non-workday SDNNi. The circadian pattern of HRV exhibited two peaks which differed on work and non-workdays. Conclusion While workday and non-workday HRV followed a circadian pattern, decreased HRV and variation of the circadian pattern were observed on workdays. Declines and changes in the circadian pattern of HRV is a concern among this exposed population. C1 [Cavallari, Jennifer M.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Mittleman, Murray A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mittleman, Murray A.] Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Cavallari, JM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave,FXB-103, Boston, MA 02115 USA. EM jcavalla@hsph.harvard.edu FU NIEHS [ES009860, ES00002]; Flight Attendants Medical Research Institute [T32 ES 07069, T42 OH008416]; NIH FX This research was supported by NIEHS grants ES009860 and ES00002. JMC was supported by T32 ES 07069, T42 OH008416, The Flight Attendants Medical Research Institute. The authors thank R Hauser, R Herrick, JY Kim, S Magari, J Schwartz, and the International Brotherhood of Boilermakers, Local 29, Quincy, MA, USA.; Other funders: NIH; Flight Attendants Medical Research Institute. NR 13 TC 8 Z9 8 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD OCT PY 2010 VL 67 IS 10 BP 717 EP 719 DI 10.1136/oem.2010.055210 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 827ZJ UT WOS:000295469100011 PM 20798005 ER PT J AU Chintakuntlawar, AV Chodosh, J AF Chintakuntlawar, Ashish V. Chodosh, James TI Cellular and Tissue Architecture of Conjunctival Membranes in Epidemic Keratoconjunctivitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE adenovirus; conjunctiva; epidemic keratoconjunctivitis; membrane; pseudomembrane ID ADENOVIRUS TYPE-19; KERATITIS; RECEPTOR; BETA AB Purpose: Conjunctival membranes are differentiated from pseudomembranes by bleeding on removal. The authors sought to study the cellular constituents and extracellular structure of formed conjunctival exudates in epidemic keratoconjunctivitis (EKC), and to determine whether these represent true conjunctival membranes. Methods: Formed conjunctival exudates harvested from 2 patients with EKC were studied by immunohistochemistry. Adenoviral infection was evaluated by PCR. Results: Each patient's tears were PCR positive for adenovirus, but not HSV-I. Both conjunctival specimens contained a fibrinous stroma richly populated with cells positive for CD4, CD8, CD20, CD68, myeloperoxidase, and fascin. Both specimens also contained cells positive for CD31 and Tie-2, and demonstrated expression of transforming growth factor-beta and vascular endothelial growth factor. Conclusions: Conjunctival exudates in EKC contain a range of leukocytes representing both innate and acquired immune responses, along with angiogenic factors and proliferating endothelial cells. Therefore, true conjunctival membranes can and do form in EKC. C1 [Chintakuntlawar, Ashish V.; Chodosh, James] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA. RP Chodosh, J (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu FU U.S. Public Health Service [R01 EY13124]; Research to Prevent Blindness, New York, NY FX This work was supported by U.S. Public Health Service grant R01 EY13124 and Research to Prevent Blindness, New York, NY. The authors wish to thank Roger Astley for technical assistance. NR 26 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD OCT PY 2010 VL 18 IS 5 BP 341 EP 345 DI 10.3109/09273948.2010.498658 PG 5 WC Ophthalmology SC Ophthalmology GA 671EH UT WOS:000283482600003 PM 20735288 ER PT J AU Elhalis, H Azizi, B Jurkunas, UV AF Elhalis, Hussain Azizi, Behrooz Jurkunas, Ula V. TI Fuchs Endothelial Corneal Dystrophy SO OCULAR SURFACE LA English DT Article DE antioxidants; apoptosis; collagen VIII; corneal endothelium; Fuchs endothelial corneal dystrophy; genetics; oxidative stress; proteomics ID GROWTH-FACTOR-BETA; THIOL-SPECIFIC ANTIOXIDANT; INDUCED PROTEIN TGFBIP; DESCEMETS-MEMBRANE; OXIDATIVE STRESS; INTERSTITIAL KERATITIS; PEROXIREDOXIN SUBTYPES; CLUSTERIN EXPRESSION; ALZHEIMERS-DISEASE; EPITHELIAL-CELLS AB Fuchs endothelial corneal dystrophy (FECD) Is characterized by progressive loss of corneal endothelial cells, thickening of Descement's membrane and deposition of extracellular matrix in the form of guttae. When the number of endothelial cells becomes critically low, the cornea swells and causes loss of vision. The clinical course of FECD usually spans 10-20 years. Corneal transplantation is currently the only modality used to restore vision. Over the last several decades genetic studies have detected several genes, as well as areas of chromosomal loci associated with the disease. Proteomic studies have given rise to several hypotheses regarding the pathogenesis of FECD. This review expands upon the recent findings from proteomic and genetic studies and builds upon recent advances in understanding the causes of this common corneal disorder. C1 [Elhalis, Hussain; Azizi, Behrooz; Jurkunas, Ula V.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Jurkunas, Ula V.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Elhalis, Hussain; Azizi, Behrooz; Jurkunas, Ula V.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Jurkunas, UV (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Stamford St, Boston, MA 02114 USA. FU [R01 EY020581]; [K12 EY016335] FX Supported in part by R01 EY020581 (UVJ), K12 EY016335 (UVJ) NR 111 TC 46 Z9 51 U1 3 U2 14 PU ETHIS COMMUNICATINS, INC PI NEW YORK PA 75 MAIDEN LANE, STE 408, NEW YORK, NY 10038 USA SN 1542-0124 J9 OCUL SURF JI Ocul. Surf. PD OCT PY 2010 VL 8 IS 4 BP 173 EP 184 PG 12 WC Ophthalmology SC Ophthalmology GA 673DR UT WOS:000283639700003 PM 20964980 ER PT J AU Kufe, D AF Kufe, D. TI Oncogenic function of the MUC1 receptor subunit in gene regulation SO ONCOGENE LA English DT Editorial Material DE MUC1; MUC1-C subunit; nuclear localization; transcriptional regulation; Wnt/beta-catenin; p53 ID BETA-CATENIN; BREAST; TUMORIGENICITY; CARCINOMA; CANCER AB The mucin 1 (MUC1) oncoprotein is overexpressed by diverse human cancers; however, it has remained largely unclear how MUC1 contributes to tumorigenesis. In this issue of Oncogene and in concert with published work, Behrens et al. report that the MUC1 receptor subunit activates genes involved in invasion, angiogenesis and metastasis. Oncogene (2010) 29, 5663-5666; doi:10.1038/onc.2010.334; published online 16 August 2010 C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Room D830, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [R01 CA042802, R01 CA042802-13, R01 CA097098, R01 CA097098-01] NR 10 TC 12 Z9 12 U1 3 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 2010 VL 29 IS 42 BP 5663 EP 5666 DI 10.1038/onc.2010.334 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 668IT UT WOS:000283262500002 PM 20711235 ER PT J AU Monahan, KB Rozenberg, GI Krishnamurthy, J Johnson, SM Liu, W Bradford, MK Horner, J DePinho, RA Sharpless, NE AF Monahan, K. B. Rozenberg, G. I. Krishnamurthy, J. Johnson, S. M. Liu, W. Bradford, M. K. Horner, J. DePinho, R. A. Sharpless, N. E. TI Somatic p16(INK4a) loss accelerates melanomagenesis SO ONCOGENE LA English DT Article DE melanoma; RAS; p16(INK4a) ID TUMOR-SUPPRESSOR PTEN; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; CELL-MIGRATION; P53 GENE; GERMLINE MUTATIONS; MELANOCYTIC NEVI; ONCOGENIC RAS; SUN EXPOSURE; IN-VIVO AB Loss of p16(INK4a)-RB and ARF-p53 tumor suppressor pathways, as well as activation of RAS-RAF signaling, is seen in a majority of human melanomas. Although heterozygous germline mutations of p16(INK4a) are associated with familial melanoma, most melanomas result from somatic genetic events: often p16(INK4a) loss and N-RAS or B-RAF mutational activation, with a minority possessing alternative genetic alterations such as activating mutations in K-RAS and/or p53 inactivation. To generate a murine model of melanoma featuring some of these somatic genetic events, we engineered a novel conditional p16(INK4a)-null allele and combined this allele with a melanocyte-specific, inducible CRE recombinase strain, a conditional p53-null allele and a loxP-stop-loxP activatable oncogenic K-Ras allele. We found potent synergy between melanocyte-specific activation of K-Ras and loss of p16(INK4a) and/or p53 in melanomagenesis. Mice harboring melanocyte-specific activated K-Ras and loss of p16(INK4a) and/or p53 developed invasive, unpigmented and nonmetastatic melanomas with short latency and high penetrance. In addition, the capacity of these somatic genetic events to rapidly induce melanomas in adult mice suggests that melanocytes remain susceptible to transformation throughout adulthood. Oncogene (2010) 29, 5809-5817; doi: 10.1038/onc.2010.314; published online 9 August 2010 C1 [Monahan, K. B.; Rozenberg, G. I.; Krishnamurthy, J.; Johnson, S. M.; Liu, W.; Bradford, M. K.; Sharpless, N. E.] Univ N Carolina, Sch Med, Ctr Environm Hlth & Susceptibil, Dept Med,Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Monahan, K. B.; Rozenberg, G. I.; Krishnamurthy, J.; Johnson, S. M.; Liu, W.; Bradford, M. K.; Sharpless, N. E.] Univ N Carolina, Sch Med, Ctr Environm Hlth & Susceptibil, Dept Genet,Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Horner, J.; DePinho, R. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci,Dept Med Oncol, Boston, MA 02115 USA. [Horner, J.; DePinho, R. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci,Dept Med, Boston, MA 02115 USA. [Horner, J.; DePinho, R. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci,Dept Genet, Boston, MA 02115 USA. RP Sharpless, NE (reprint author), Univ N Carolina, Sch Med, Lineberger Canc Ctr, Dept Med, CB 7295,Mason Farm Rd, Chapel Hill, NC 27599 USA. EM nes@med.unc.edu FU NIH [AG024379, ES14635]; American Federation of Aging; Golfers Against Cancer Foundation; Sidney Kimmel Foundation; National Cancer Center FX We thank Eric Brown, Marcus Bosenberg, Vincent Hearing for advice and reagents. This work was supported by Grants from NIH (AG024379 and ES14635), as well as from the American Federation of Aging (to KJ), the Golfers Against Cancer Foundation, the Sidney Kimmel Foundation and the National Cancer Center (to KBM). NR 55 TC 24 Z9 26 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 2010 VL 29 IS 43 BP 5809 EP 5817 DI 10.1038/onc.2010.314 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 672LY UT WOS:000283586200006 PM 20697345 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI New Results Will Change the Paradigm for Phase I Trials and Drug Approval SO ONCOLOGIST LA English DT Editorial Material ID METASTATIC BREAST-CANCER; CHEMOTHERAPY; MELANOMA C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 10 N Grove St, Boston, MA 02114 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD OCT PY 2010 VL 15 IS 10 BP 1023 EP 1025 DI 10.1634/theoncologist.2010-0267 PG 3 WC Oncology SC Oncology GA 678ZF UT WOS:000284123900001 PM 20930096 ER PT J AU Buhl, AM James, DF Jain, S Neuberg, D Rassenti, LZ Maroc, N Kipps, TJ AF Buhl, A. M. James, D. F. Jain, S. Neuberg, D. Rassenti, L. Z. Maroc, N. Kipps, T. J. TI Measurement of CLLU1 can monitor for minimal residual disease in patients with chronic lymphocytic leukemia after therapy SO ONKOLOGIE LA English DT Meeting Abstract C1 [Buhl, A. M.] Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark. [Buhl, A. M.; James, D. F.; Rassenti, L. Z.; Kipps, T. J.] Moores UCSD Canc Ctr, La Jolla, CA USA. [Buhl, A. M.; James, D. F.; Rassenti, L. Z.; Kipps, T. J.] CLL Res Consortium, La Jolla, CA USA. [Jain, S.] UCSD, Div Biostat & Bioinformat, La Jolla, CA USA. [Neuberg, D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Maroc, N.] Ipsogen, Marseille, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PD OCT PY 2010 VL 33 SU 6 BP 22 EP 22 PG 1 GA 664UN UT WOS:000282988400060 ER PT J AU Diering, N Aung, T Chapuy, B Koch, R Becker, S Krause, D Truemper, L Wulf, GG AF Diering, N. Aung, T. Chapuy, B. Koch, R. Becker, S. Krause, D. Truemper, L. Wulf, G. G. TI Putative tumor stem cells of SP phenotype in aggressive B-cell lymphoma SO ONKOLOGIE LA English DT Meeting Abstract C1 [Diering, N.; Aung, T.; Koch, R.; Becker, S.; Krause, D.; Truemper, L.; Wulf, G. G.] Univ Gottingen, Gottingen, Germany. [Chapuy, B.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PD OCT PY 2010 VL 33 SU 6 BP 188 EP 188 PG 1 GA 664UN UT WOS:000282988401085 ER PT J AU Ghosh, S Koralov, SB Stevanovic, I Sundrud, MS Sasaki, Y Rajewsky, K Rao, A Muller, MR AF Ghosh, S. Koralov, S. B. Stevanovic, I Sundrud, M. S. Sasaki, Y. Rajewsky, K. Rao, A. Mueller, M. R. TI Hyperactivable NFAT1 ameliorates autoimmune encephalitis in vivo SO ONKOLOGIE LA English DT Meeting Abstract C1 [Ghosh, S.; Koralov, S. B.; Stevanovic, I; Sundrud, M. S.; Rajewsky, K.; Rao, A.; Mueller, M. R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ghosh, S.; Koralov, S. B.; Stevanovic, I; Sundrud, M. S.; Rajewsky, K.; Rao, A.; Mueller, M. R.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Sasaki, Y.] RIKEN, Ctr Dev Biol, Lab Stem Cell Biol, Kobe, Hyogo, Japan. [Mueller, M. R.] Univ Klinikum Tubingen, Abt Hamatol Onkol Immunol Rheumatol & Pulmonol, Tubingen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PD OCT PY 2010 VL 33 SU 6 BP 272 EP 272 PG 1 GA 664UN UT WOS:000282988401325 ER PT J AU Hamrah, P Cruzat, A Dastjerdi, MH Zheng, LX Shahatit, BM Bayhan, HA Dana, R Pavan-Langston, D AF Hamrah, Pedram Cruzat, Andrea Dastjerdi, Mohammad H. Zheng, Lixin Shahatit, Bashar M. Bayhan, Hasan A. Dana, Reza Pavan-Langston, Deborah TI Corneal Sensation and Subbasal Nerve Alterations in Patients with Herpes Simplex Keratitis An In Vivo Confocal Microscopy Study SO OPHTHALMOLOGY LA English DT Article ID PRIMARY SJOGRENS-SYNDROME; DRY EYE; SENSITIVITY; INNERVATION; MORPHOLOGY; PLEXUS; VIRUS; LASIK; EPIDEMIOLOGY; KERATOCONUS AB Purpose: To study and correlate corneal sensation in patients with herpes simplex keratitis (HSK) with density and morphologic features of subbasal corneal nerves by in vivo confocal microscopy (IVCM). Design: Prospective, cross-sectional, controlled, single-center study. Participants: Thirty-one eyes with the diagnosis of acute (n = 7) or chronic (n = 24) HSK and their contralateral clinically unaffected eyes were studied and compared with normal controls (n = 15). Methods: In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmlogie, Chartres, France) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5-5.5 cm), and severe (<= 2.5 cm) loss of sensation. Main Outcome Measures: Changes in corneal nerve density, total nerve number, main nerve trunks, branching, and tortuosity were evaluated after IVCM and were correlated to corneal sensation, disease duration, and number of recurrences. Results: Herpes simplex keratitis eyes, as compared with controls, demonstrated significant (P<0.001) decrease in mean nerve density (448.9 +/- 409.3 vs. 2258.4 +/- 989.0 mu m/frame), total nerve number (5.2 +/- 4.5 vs. 13.1 +/- 3.8), main nerve trunks (2.3 +/- 1.6 vs. 4.7 +/- 1.2), and nerve branches (3.2 +/- 4.3 vs. 9.8 +/- 3.3). In contralateral unaffected eyes, mean nerve density (992.7 +/- 465.0 mu m/frame), total nerve number (7.8 +/- 3.3), and branches (4.5 +/- 2.3) were decreased significantly as compared with controls (P<0.002). Reduced nerve density, total nerve count, and main trunks in HSK eyes were correlated significantly with corneal sensation across all subgroups (P<0.001). Nerve density decreased within days of infection and was correlated to frequency of episodes in patients with HSK (P<0.02). Conclusions: In vivo confocal microscopy revealed that the loss of corneal sensation in HSK correlates strongly with profound diminishment of the subbasal nerve plexus after herpes simplex virus infection. Surprisingly, the contralateral, clinically unaffected eyes also demonstrated a diminishment of the subbasal nerve plexus as compared with normal subjects, revealing bilateral nerve alteration in an apparently unilateral disease. C1 [Hamrah, Pedram; Cruzat, Andrea; Dastjerdi, Mohammad H.; Zheng, Lixin; Shahatit, Bashar M.; Bayhan, Hasan A.; Dana, Reza; Pavan-Langston, Deborah] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Cornea Serv & Ocular Surface Imaging Ctr, Boston, MA 02114 USA. RP Hamrah, P (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu OI Cruzat, Andrea/0000-0002-3724-7037 FU National Institutes of Health, Bethesda, Maryland [NIH K12-EY016335, NIH K24-EY019098]; New England Corneal Transplant Research Fund, Boston, Massachusetts; Falk Medical Research Foundation, Chicago, IIlinois FX Supported by the National Institutes of Health (grant nos.: NIH K12-EY016335 and NIH K24-EY019098), Bethesda, Maryland; the New England Corneal Transplant Research Fund, Boston, Massachusetts; and the Falk Medical Research Foundation, Chicago, IIlinois. The funding organizations had no role in the design or conduct of this research. The author(s) have no proprietary or commercial interest in any materials discussed in this article. NR 34 TC 82 Z9 85 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2010 VL 117 IS 10 BP 1930 EP 1936 DI 10.1016/j.ophtha.2010.07.010 PG 7 WC Ophthalmology SC Ophthalmology GA 656VV UT WOS:000282370100011 PM 20810171 ER PT J AU Hoepf, M Laby, DM AF Hoepf, Marcia Laby, Daniel M. TI Optic Neuropathy in a Child with Alopecia SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE optic neuritis; alopecia; autoimmune disease; strabismus surgery; lymphocytes; pediatric ID OCULAR ALTERATIONS; AREATA; NEURITIS; ABNORMALITIES AB A 4-year-old boy develops an insidious optic neuropathy, of unknown etiology, followed shortly thereafter by a focal patch of hair loss (biopsy proven-alopecia areata) on the back of his head. The temporal aspects of these findings suggest a common, likely inflammatory, etiology. (Optom Vis Sci 2010;87:E787-E789) C1 [Hoepf, Marcia] New England Coll Optometry, Boston, MA USA. [Laby, Daniel M.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Laby, DM (reprint author), Eye Care Kids LLC, 95 Washington St,Suite 592, Canton, MA 02021 USA. EM drlaby@eyecareforkidsllc.com NR 14 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD OCT PY 2010 VL 87 IS 10 BP E787 EP E789 DI 10.1097/OPX.0b013e3181f362fc PG 3 WC Ophthalmology SC Ophthalmology GA 656WL UT WOS:000282371700011 PM 20729770 ER PT J AU Sonis, ST AF Sonis, S. T. TI New thoughts on the initiation of mucositis SO ORAL DISEASES LA English DT Review DE mucositis; PAMP; DAMP; pathobiology ID CYCLOOXYGENASE-2 COX-2 EXPRESSION; MOLECULAR-PATTERN MOLECULES; INDUCED ORAL MUCOSITIS; FACTOR-KAPPA-B; CANCER PATIENTS; THYMIDYLATE SYNTHASE; GENE POLYMORPHISM; CHEMOTHERAPY; DAMAGE; CELLS AB It has been slightly more than a decade since the classic mechanistic paradigm that defined the pathogenesis of mucositis was revised. A five-stage sequence of linked biological events forms the basis for our current understanding of how regimen-related mucosal injury occurs. The first stage is the initiation phase, although the gateway to toxicity has been the least studied. This essay proposes new thoughts on the phase's components, how they might interact, and how they present new opportunities for treatment interventions and mucositis risk prediction. C1 Brigham & Womens Hosp, Harvard Farber Canc Ctr, Boston, MA 02115 USA. RP Sonis, ST (reprint author), Brigham & Womens Hosp, Harvard Farber Canc Ctr, 75 Francis St, Boston, MA 02115 USA. EM ssonis@partners.org NR 41 TC 52 Z9 59 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD OCT PY 2010 VL 16 IS 7 BP 597 EP 600 DI 10.1111/j.1601-0825.2010.01681.x PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 650EI UT WOS:000281831600004 PM 20846150 ER PT J AU Watkins, B Pouliot, K Fey, E Tuthill, C Sonis, S AF Watkins, B. Pouliot, K. Fey, E. Tuthill, C. Sonis, S. TI Attenuation of radiation- and chemoradiation-induced mucositis using gamma-d-glutamyl-l-tryptophan (SCV-07) SO ORAL DISEASES LA English DT Article DE SCV-07; gamma-d-glutamyl-l-tryptophan; radiation; mucositis; animal models ID INDUCED ORAL MUCOSITIS; INDUCED APOPTOSIS; PATHOBIOLOGY; CYTOKINES; CELLS; STAT3 AB Objective: To evaluate the efficacy of a novel immunomodulating peptide (SCV-07) in attenuating the course of radiation-induced mucositis in an established animal model of oral mucositis (OM). Material and Methods: In three separate experiments, golden Syrian hamsters received either an acute radiation challenge to the buccal mucosa of eight fractionated doses of 7.5 Gy of radiation over a 2-week-period, or a combination of acute radiation and cisplatin. In each experiment, animals were treated with varying doses or schedules of SCV-07 or placebo. OM was scored in a blinded fashion using digital images obtained during the experimental period. Results: We found that SCV-07 reduced the severity and duration of both acute and fractionated radiation-induced OM. Similarly, when radiation and chemotherapy were used to induce OM, treatment with SCV-07 significantly reduced the duration of ulcerative OM. The therapeutic benefit was dependent on both dose and schedule of administration. Conclusion: Taken together, we found SCV-07 was able to modify the duration and severity of oral mucositis and was dependent on schedule and dose. C1 [Watkins, B.; Pouliot, K.; Fey, E.] Biomodels LLC, Watertown, MA USA. [Tuthill, C.] SciClone Pharmaceut Inc, Foster City, CA USA. [Sonis, S.] Harvard Farber Canc Ctr, Div Oral Med, Boston, MA USA. RP Sonis, S (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM ssonis@partners.org FU SciClone Pharmaceuticals FX This study was funded by SciClone Pharmaceuticals. NR 15 TC 7 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1354-523X EI 1601-0825 J9 ORAL DIS JI Oral Dis. PD OCT PY 2010 VL 16 IS 7 BP 655 EP 660 DI 10.1111/j.1601-0825.2010.01671.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 650EI UT WOS:000281831600012 PM 20412446 ER PT J AU Thompson, LR Boudreau, R Newman, AB Hannon, MJ Chu, CR Nevitt, MC Kwoh, CK AF Thompson, L. R. Boudreau, R. Newman, A. B. Hannon, M. J. Chu, C. R. Nevitt, M. C. Kwoh, C. Kent CA OAI Investigators TI The association of osteoarthritis risk factors with localized, regional and diffuse knee pain SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Knee osteoarthritis; Pain localization; Risk factors; Knee pain ID NUTRITION EXAMINATION SURVEY; NATIONAL-HEALTH; PERCEPTION; EPIDEMIOLOGY; LOCATION; GENDER AB Objective: To identify determinants of different patterns of knee pain with a focus on risk factors for knee osteoarthritis (OA). Design: The Knee Pain Map is an interviewer-administered assessment that asks subjects to characterize their knee pain as localized, regional, or diffuse. A total of 2677 participants from the Osteoarthritis Initiative were studied. We used multinomial logistic regression to examine the relationship between risk factors for OA and knee pain patterns. We examined the bivariate and multivariate relationships of knee pain pattern with age, body mass index (BMI), sex, race, family history of total joint replacement, knee injury, knee surgery, and hand OA. Results: We compared 2462 knees with pain to 1805 knees without pain. In the bivariate analysis, age, sex, BMI, injury, surgery, and hand OR were associated with at least one pain pattern. In the multivariate model, all of these variables remained significantly associated with at least one pattern. When compared to knees without pain, higher BMI, injury, and surgery were associated with all patterns. BMI had its strongest association with diffuse pain. Older age was less likely to be associated with localized pain while female sex was associated with regional pain. Conclusions: We have shown that specific OA risk factors are associated with different knee pain patterns. Better understanding of the relationship between OA risk factors and knee pain patterns may help to characterize the heterogeneous subsets of knee OA. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. C1 [Thompson, L. R.; Newman, A. B.; Hannon, M. J.; Chu, C. R.; Kwoh, C. Kent] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Boudreau, R.; Newman, A. B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Nevitt, M. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Kwoh, CK (reprint author), S702 BSTWR,200 Lothrop St, Pittsburgh, PA 15261 USA. EM kwoh@pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187 FU National Institutes of Health [N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260, N01AR-2-2261, N01-AR-2-2262]; Department of Health and Human Services; Merck Research Laboratories; Novartis Pharmaceuticals Corporation, GlaxoSmithKline; Pfizer, Inc.; Foundation for the National Institutes of Health; National Institute of Aging (NIA) [AG 021885]; University of Pittsburgh FX The OAI is a public private partnership which comprised five contracts (N01-AR-2-2258; N01-AR-2-2259; N01-AR-2-2260; N01AR-2-2261; N01-AR-2-2262) funded by the National Institutes of Health, a branch of the Department of Health and Human Services, and conducted by the OAI Study Investigators. Private funding partners include Merck Research Laboratories; Novartis Pharmaceuticals Corporation, GlaxoSmithKline; and Pfizer, Inc. Private sector funding for the OAI is managed by the Foundation for the National Institutes of Health. This manuscript has received the approval of the OAI Publications Committee based on a review of its scientific content and data interpretation.; This study was also supported by the National Institute of Aging (NIA) Ruth L Kirschstein National Research Service Award Institutional Research Training Grant AG 021885, and the University of Pittsburgh, School of Medicine Clinical Scientist Training Program. NR 24 TC 14 Z9 14 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD OCT PY 2010 VL 18 IS 10 BP 1244 EP 1249 DI 10.1016/j.joca.2010.05.014 PG 6 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 670UK UT WOS:000283452600002 PM 20633678 ER PT J AU Rauch, SD AF Rauch, Steven D. TI Clinical Hints and Precipitating Factors in Patients Suffering from Meniere's Disease SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Meniere's disease; Vertigo; Migraine ID MIGRAINE; INNERVATION; HEARING AB Meniere's disease is one of the most fascinating and most vexing of all clinical conditions encountered by the otolaryngologist Operationally speaking, a Meniere's ear is a fragile ear. In fact, Meniere's disease can and should be redefined as a degenerating inner ear that has impairment of one or more homeostatic systems, resulting in instability of hearing and balance function This updated definition is a valuable guide to the clinical epidemiology and presentation of Meniere's disease and to understanding the effects of conservative treatments In the absence of a definitive test for Meniere's disease, the greatest challenge for the clinician may be differentiating this condition from migraine. Ultimately, Meniere's vertigo attacks are controllable in more than 99% of cases, but hearing loss and other auditory symptoms tend to be unresponsive to treatment. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Rauch, SD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 23 Z9 24 U1 3 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 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 2010 VL 43 IS 5 BP 1011 EP + DI 10.1016/j.otc.2010.05.003 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 646UX UT WOS:000281569700006 PM 20713240 ER PT J AU Fuzaylov, G Ying, BY Tang, YF Sethna, NF AF Fuzaylov, Gennadiy Ying, Binyu Tang, Yanfeng Sethna, Navil F. TI Successful resuscitation after inadvertent intravenous injection of bupivacaine in an adolescent SO PEDIATRIC ANESTHESIA LA English DT Letter C1 [Fuzaylov, Gennadiy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Ying, Binyu] Second Affiliated Hosp, Wenzhou Med Coll, Wenzhou, Peoples R China. [Ying, Binyu; Tang, Yanfeng] Yu Ying Children Hosp, Wenzhou, Peoples R China. [Tang, Yanfeng] Second Affiliated Hosp, Intens Care Unit, Wenzhou, Peoples R China. [Sethna, Navil F.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. RP Fuzaylov, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM gfuzaylov@partners.org NR 4 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD OCT PY 2010 VL 20 IS 10 BP 958 EP 959 DI 10.1111/j.1460-9592.2010.03404.x PG 2 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 651TK UT WOS:000281949800009 PM 20849502 ER PT J AU George, RE Lahti, JM Adamson, PC Zhu, KJ Finkelstein, D Ingle, AM Reid, JM Krailo, M Neuberg, D Blaney, SM Diller, L AF George, Rani E. Lahti, Jill M. Adamson, Peter C. Zhu, Kejin Finkelstein, David Ingle, A. Mark Reid, Joel M. Krailo, Mark Neuberg, Donna Blaney, Susan M. Diller, Lisa TI Phase I Study of Decitabine With Doxorubicin and Cyclophosphamide in Children With Neuroblastoma and Other Solid Tumors: A Children's Oncology Group Study SO PEDIATRIC BLOOD & CANCER LA English DT Article DE decitabine; demethylation; neuroblastoma; pediatric solid tumor ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; LOW-DOSE DECITABINE; SICKLE-CELL-ANEMIA; DNA METHYLATION; GENE-EXPRESSION; MYELODYSPLASTIC SYNDROME; CASPASE-8 EXPRESSION; INDUCED APOPTOSIS; 5-AZA-2'-DEOXYCYTIDINE DECITABINE AB Background. Demethylating agents may alter the expression of genes involved in chemotherapy resistance We conducted a phase I trial to determine the toxicity and molecular effects of the demethylating agent, decitabine, followed by doxorubicin and cyclophosphamide in children with refractory solid tumors Procedure. Stratum A included children with any solid tumor, Stratum B included neuroblastoma patients only Patients received a 1-hr decitabine infusion for 7 days, followed by doxorubicin (45 mg/m(2)) and cyclophosphamide (1 g/m(2)) on day 7 Pharmacokinetic studies were performed after the first dose of decitabine Biological studies included methylation and gene expression analyses of caspase-8, MAGE-1 and fetal hemoglobin (HbF), and expression profiling of pre- and post-treatment peripheral blood and bone marrow cells Results, the maximum-tolerated dose of decitabine was 5 mg/m(2)/clay for 7 days Dose-limiting toxicities at 10 mg/m(2)/clay were neutropenia and thrombocytopenia Decitabine exhibited rapid clearance from plasma Three of 9 patients in Stratum A and 4/12 patients in Stratum B had stable disease for >= 4 months Sustained MAGE-1 demethylation and increased HbF expression were observed in the majority of patients post-treatment (12/20 and 14/16, respectively) Caspase-8 promoter demethylation and gene expression were seen in 2/7 bone marrow samples Differentially expressed genes were identified by microarray analysis Conclusion. Low-dose decitabine when combined with doxorubicin/cyclophosphamide has tolerable toxicity in children However, doses of decitabine capable of producing clinically relevant biologic effects were not well tolerated with this combination Alternative strategies of combining demethylating agents with non-cytotoxic, biologically targeted agents such as histone deactelyase inhibitors should be explored Pediatr Blood Cancer 2010,55 629-638 (C) 2010 Wiley-Liss, Inc C1 [George, Rani E.; Diller, Lisa] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [George, Rani E.; Diller, Lisa] Childrens Hosp, Boston, MA 02115 USA. [Lahti, Jill M.; Zhu, Kejin; Finkelstein, David] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Ingle, A. Mark] Childrens Oncol Grp, Arcadia, CA USA. [Reid, Joel M.] Mayo Clin, Coll Med, Rochester, MN USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Blaney, Susan M.] Texas Childrens Canc Ctr, Houston, TX USA. RP George, RE (reprint author), Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Dana 322-44 Binney St, Boston, MA 02115 USA. FU NIH/NINDS [K08NS047983]; ASCO and COG Y1A; National Cancer Institute [U01 CA97452]; NCRR [M01 RR00188] FX Grant sponsor NIH/NINDS, Grant number K08NS047983, Grant sponsor ASCO and COG Y1A (REG), Grant sponsor National Cancer Institute, Grant number U01 CA97452, Grant sponsor NCRR, Grant number M01 RR00188 NR 50 TC 28 Z9 32 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT PY 2010 VL 55 IS 4 BP 629 EP 638 DI 10.1002/pbc.22607 PG 10 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 646LU UT WOS:000281542900010 PM 20589651 ER PT J AU Huang, JT Liang, MG AF Huang, Jennifer T. Liang, Marilyn G. TI Vascular Malformations SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Vascular malformation; Capillary malformation; Venous malformation; Lymphatic malformation; Arteriovenous malformation; Glomuvenous malformations ID PORT-WINE STAINS; PULSED DYE-LASER; OCCULT SPINAL DYSRAPHISM; PSEUDO-KAPOSI SARCOMA; ND-YAG LASERS; VENOUS MALFORMATIONS; ARTERIOVENOUS-MALFORMATION; LYMPHANGIOMA CIRCUMSCRIPTUM; LYMPHATIC MALFORMATIONS; CLINICAL CLASSIFICATION AB Vascular malformations are rare but important skin disorders in children, which often require multidisciplinary care. The goal of this article is to orient pediatricians to the various types of vascular malformations. We discuss the clinical characteristics, diagnostic criteria, and management of capillary, venous, arteriovenous, and lymphatic malformations. Associated findings and syndromes are also discussed briefly. C1 [Huang, Jennifer T.; Liang, Marilyn G.] Childrens Hosp, Dermatol Program, Boston, MA 02115 USA. [Huang, Jennifer T.; Liang, Marilyn G.] Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Sch Med, Boston, MA 02114 USA. RP Liang, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Sch Med, 55 Fruit St,Bartlett 616, Boston, MA 02114 USA. NR 96 TC 6 Z9 6 U1 3 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD OCT PY 2010 VL 57 IS 5 BP 1091 EP + DI 10.1016/j.pcl.2010.08.003 PG 21 WC Pediatrics SC Pediatrics GA 676BR UT WOS:000283885600004 PM 20888460 ER PT J AU Damore, D Mansbach, JM Clark, S Ramundo, M Camargo, CA AF Damore, Dorothy Mansbach, Jonathan M. Clark, Sunday Ramundo, Maria Camargo, Carlos A., Jr. TI Insurance Status and the Variable Management of Children Presenting to the Emergency Department With Bronchiolitis SO PEDIATRIC EMERGENCY CARE LA English DT Article DE insurance; socioeconomic status; bronchiolitis ID RESPIRATORY SYNCYTIAL VIRUS; SERIOUS BACTERIAL-INFECTION; HEALTH-INSURANCE; UNITED-STATES; US CHILDREN; CARE; INFANTS; HOSPITALIZATIONS; ASTHMA; COVERAGE AB Objective: To determine if insurance type is associated with differences in the management of children presenting to the emergency department (ED) with bronchiolitis Methods: We analyzed data from a 30-center, prospective cohort study of children younger than 2 years with bronchiolitis presenting to the ED. Insurance status was defined as private, public, and no insurance. Results: Of 1450 patients, 473 (33%) had private, 928 (64%) had public, and 49 (3%) had no insurance. Multivariable analysis found that children with public insurance were less likely to receive inhaled beta-agonists (odds ratio [ OR], 0.68; 95% confidence interval [CI], 0.50-0.92) or antibiotics (OR, 0.61; 95% CI, 0.42-0.89) the week before the ED visit. Children without insurance were less likely to have a primary care provider (OR, 0.15; 95% CI, 0.04-0.57) or receive laboratory testing in the ED (OR, 0.41; 95% CI, 0.19-0.88). The children's clinical presentation (eg, respiratory rate, oxygen saturation, and retractions) and ED treatments (eg, inhaled beta-agonists, inhaled racemic epinephrine, systemic corticosteroids, and antibiotics) were similar. Likewise, hospital admission (multivariable OR 1.04; 95% CI, 0.45-2.42) was similar between insurance groups. Conclusions: We noted some pre-ED and ED management differences across insurance types for children presenting to the ED with bronchiolitis. Although these variations may reflect treatments with unproven benefits, all children regardless of insurance should receive similar care. Despite these management variations, there were no differences in medications delivered in the ED or admission rate. C1 [Damore, Dorothy] New York Presbyterian Hosp, Div Pediat Emergency Med, Weill Cornell Med Ctr, Cornell Med Coll, New York, NY USA. [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Dept Med, Childrens Hosp Boston, Boston, MA USA. [Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Ramundo, Maria] Northeastern Ohio Univ Coll Med & Pharm, Coll Med, Dept Emergency Med, Akron Childrens Hosp, Akron, OH 90034 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Damore, D (reprint author), Albany Med Ctr, 43 New Scotland Ave,MC 139, Albany, NY 12208 USA. EM damored@mail.amc.edu FU Thrasher Research Fund (Salt Lake City, UT); Merck (Rahway, NJ); AstraZeneca; GSK; MedImmune; Merck; Novartis FX Dr Camargo has received financial support from a variety of groups for participation in conferences, consulting, and medical research.; Over the past year, industry sponsors with a potential interest in bronchiolitis were AstraZeneca, GSK, MedImmune, Merck, and Novartis.; Funding for this study was received from Thrasher Research Fund (Salt Lake City, UT) and an unrestricted data analysis grant from Merck (Rahway, NJ). NR 39 TC 1 Z9 1 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD OCT PY 2010 VL 26 IS 10 BP 716 EP 721 DI 10.1097/PEC.0b013e3181f39861 PG 6 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 664EQ UT WOS:000282943400002 PM 20881909 ER PT J AU Duro, D Fitzgibbons, S Valim, C Yang, CFJ Zurakowski, D Dolan, M Bechard, L Yu, YM Duggan, C Jaksic, T AF Duro, Debora Fitzgibbons, Shimae Valim, Clarissa Yang, Chi-Fu Jeffrey Zurakowski, David Dolan, Melanie Bechard, Lori Yu, Yong Ming Duggan, Christopher Jaksic, Tom TI [(13)C]Methionine Breath Test to Assess Intestinal Failure-Associated Liver Disease SO PEDIATRIC RESEARCH LA English DT Article ID TOTAL PARENTERAL-NUTRITION; SHORT-BOWEL SYNDROME; HEPATIC MITOCHONDRIAL-FUNCTION; METHIONINE METABOLISM; TRANSPLANTATION; CHILDREN; INJURY; CHOLESTASIS; EMULSION; OUTCOMES AB Oxidation of L[1-(13)C]methionine ([(13)C]-Met) in liver mitochondria can be quantified by measuring exhaled (13)CO(2). We hypothesized that (13)CO(2) recovery after i.v. administered [(13)C]-Met would provide a noninvasive measure of liver function in pediatric intestinal failure-associated liver disease (IFALD). After Institutional Review Board (IRB) approval, 27 patients underwent L[1-(13)C]-Met breath tests ([(13)C]-MBTs), five of whom underwent repeat testing after clinical changes in liver function. Sterile, pyrogen-free [(13)C]-Met was given i.v. Six breath samples collected during 120 min were analyzed for (13)CO(2) enrichment using isotope ratio mass spectrometry. Pediatric end-stage liver disease (PELD) scores were recorded, and total carbon dioxide (CO(2)) production was measured by indirect calorimetry. Twenty-seven patients (median age = 5.3 mu) underwent a total of 34 [(13)C]-MBTs without adverse events. Fourteen patients had documented liver biopsies (five with cirrhosis and nine with cholestasis or fibrosis). The [(13)C]-MBT differentiated patients with and without cirrhosis (medians 210 and 350, respectively, p = 0.04). Serial [(13)C]-MBTs in five patients reflected changing PELD scores. i.v. administering the stable isotope [(13)C]-Met with serial breath sampling provides a useful, safe, and potentially clinically relevant evaluation of hepatic function in pediatric IFALD. The [(13)C]-MBT may also help quantify progression or improvement of IFALD. (Pediatr Res 68: 349-354, 2010) C1 [Duro, Debora; Dolan, Melanie; Bechard, Lori; Duggan, Christopher] Harvard Univ, Sch Med, Children Hosp Boston, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [Fitzgibbons, Shimae; Yang, Chi-Fu Jeffrey; Zurakowski, David; Jaksic, Tom] Harvard Univ, Sch Med, Children Hosp Boston, Dept Surg, Boston, MA 02115 USA. [Valim, Clarissa] Harvard Univ, Sch Med, Children Hosp Boston, Clin Res Program, Boston, MA 02115 USA. [Yu, Yong Ming] Shriners Burns Hosp Children, Boston, MA 02114 USA. [Yu, Yong Ming] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Duro, D (reprint author), Univ Miami, Div Pediat Gastroenterol & Nutr, 1601 NW 12th Ave,MCCD Room 3005A, Miami, FL 33136 USA. EM dduro@med.miaimi.edu FU NIH [T32-HD43034-05A1, P30DK040561]; Clinical Nutrition Research Center, NIH [P30 DK40561-13]; Children's Hospital, Boston; Howard Hughes Medical Institute FX Supported by the Institutional Grant from NIH T32-HD43034-05A1, Pilot Feasibility Grant from the Clinical Nutrition Research Center, NIH #P30 DK40561-13, and by a Junior Faculty Career Development Award from Children's Hospital, Boston [D.D.] and by the Howard Hughes Medical Institute Medical Student Fellowship [to C.-F.J.Y.]. The study isotopic analyses were supported by NIH #P30DK040561 [D.D.. Y.M.Y., C.D., T.J.]. NR 40 TC 9 Z9 9 U1 1 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 2010 VL 68 IS 4 BP 349 EP 354 PG 6 WC Pediatrics SC Pediatrics GA 653FO UT WOS:000282074100015 PM 20581744 ER PT J AU Royal, JD Kurtz, JL AF Royal, Justin D. Kurtz, Jaime L. TI I ate what?! The effect of stress and dispositional eating style on food intake and behavioral awareness SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Stress; Eating; Dietary restraint; Emotion; Awareness ID RESTRAINED EATERS; NEGATIVE AFFECT; QUESTIONNAIRE; SCALES; VALIDATION; MOOD AB Many studies have found that individual differences such as emotional eating and dietary restraint affect the relationship between stress and eating. However, little research examines whether people are differentially aware of how much they cat during a stressful situation. The current study placed 52 female undergraduate students in either a low-stress (solving easy anagrams) or high-stress (working on unsolvable anagrams) situation while having the opportunity to eat. Participants then guessed how much food they ate. Results showed that emotional eating and stress were related to overestimation of total food consumption, whereas dietary restraint partially mediated the relationship between stress condition and actual food intake. Published by Elsevier Ltd. C1 [Kurtz, Jaime L.] James Madison Univ, Dept Psychol, Harrisonburg, VA 22807 USA. [Royal, Justin D.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Kurtz, JL (reprint author), James Madison Univ, Dept Psychol, MSC 7704, Harrisonburg, VA 22807 USA. EM kurtzjl@jmu.edu NR 25 TC 8 Z9 8 U1 5 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD OCT PY 2010 VL 49 IS 6 BP 565 EP 569 DI 10.1016/j.paid.2010.04.022 PG 5 WC Psychology, Social SC Psychology GA 640XL UT WOS:000281087400002 ER PT J AU Jimenez, SS Niles, BL Park, CL AF Jimenez, Sherlyn S. Niles, Barbara L. Park, Crystal L. TI A mindfulness model of affect regulation and depressive symptoms: Positive emotions, mood regulation expectancies, and self-acceptance as regulatory mechanisms SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Mindfulness; Depressive symptoms; Self-acceptance; Affect regulation; Positive emotions ID GENERALIZED EXPECTANCIES; STRESS REDUCTION; ANXIETY; INTERVENTION; MEDITATION; INVENTORY; RESPONSES; FEELINGS; THERAPY; ISSUES AB Mindfulness is increasingly conceptualized in terms of its regulatory function with research suggesting that mindfulness may have a salutary effect on psychological well-being. The present cross-sectional study of 514 college students (84% Caucasian and 62% females), using self-report questionnaires, tested a proposed model for understanding the relationship between dispositional mindfulness and depressive symptoms through three types of affect regulation: emotion regulation, mood regulation and self-regulation, as measured by positive emotions, mood regulation expectancies (i.e., perceived mood repair ability), and self-acceptance, respectively. Structural equation modeling revealed that the model fit the data well, with the relationship between mindfulness, as measured by the Freiburg Mindfulness Inventory, and depressive symptoms, as measured by the Center for Epidemiological Studies-Depression Scale, fully mediated by the proposed regulatory processes. Higher levels of dispositional mindfulness were associated with higher levels of positive emotions, mood regulation expectancies, and self-acceptance, which in turn, were all inversely related to depressive symptoms. Self-acceptance emerged as the strongest mediator of mindfulness and depressive symptoms. Our findings suggest that mindfulness might serve a regulatory function by targeting low positive emotionality, poor mood regulation, and negative self-concept, risk factors implicated in the onset, development, and maintenance of depressive symptoms. Published by Elsevier Ltd. C1 [Jimenez, Sherlyn S.; Niles, Barbara L.] VA Boston Healthcare Syst, Natl Ctr PTSD 116B 4, Boston, MA 02130 USA. [Jimenez, Sherlyn S.; Park, Crystal L.] Univ Connecticut, Dept Psychol, Unit 1020, Storrs, CT 06269 USA. RP Jimenez, SS (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 4, 150 S Huntington Ave, Boston, MA 02130 USA. EM sherlyn.jimenez@gmail.com NR 44 TC 39 Z9 40 U1 4 U2 49 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD OCT PY 2010 VL 49 IS 6 BP 645 EP 650 DI 10.1016/j.paid.2010.05.041 PG 6 WC Psychology, Social SC Psychology GA 640XL UT WOS:000281087400016 ER PT J AU Bethel-Brown, CS Zhang, HY Fowler, SC Chertoff, ME Watson, GS Stanford, JA AF Bethel-Brown, Crystal S. Zhang, Hongyu Fowler, Stephen C. Chertoff, Mark E. Watson, G. Stennis Stanford, John A. TI Within-session analysis of amphetamine-elicited rotation behavior reveals differences between young adult and middle-aged F344/BN rats with partial unilateral striatal dopamine depletion SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Parkinson's disease; Animal models; Behavioral assay; Basal ganglia; Rotation; Striatum; Amphetamine ID PARKINSONS-DISEASE; BASAL GANGLIA; PROGRESSIVE DEGENERATION; NIGROSTRIATAL PATHWAY; MOVEMENT INITIATION; FISCHER-344 RATS; PARTIAL LESIONS; 6-OHDA LESIONS; ANIMAL-MODEL; TIME-COURSE AB Preclinical modeling of Parkinson's disease using 6-hydroxydopamine (6-OHDA) has been valuable in developing and testing therapeutic strategies. Recent efforts have focused on modeling early stages of disease by infusing 6-OHDA into the striatum. The partial DA depletion that follows intrastriatal 6-OHDA is more variable than the near-complete depletion following medial forebrain bundle infusion, and behavioral screening assays are not as well characterized in the partial lesion model. We compared relationships between amphetamine-elicited rotation behavior and DA depletion following intrastriatal 6-OHDA (12.5 mu g) in 6 month vs. 18 month F344/BN rats, at 2-weeks and 6-weeks post-lesion. We compared the total number of rotations with within-session (bin-by-bin) parameters of rotation behavior as indicators of DA depletion. Striatal DA depletion was greater in the young adult than in the middle-aged rats at 2 weeks but not at 6 weeks post-lesion. The total number of rotations for the whole session and striatal DA depletion did not differ between the two age groups. Regression analysis revealed a greater relationship between within-session parameters of rotation behavior and DA depletion in the middle-aged group than in the young adult group. These results have implications for estimating DA depletion in preclinical studies using rats of different ages. (C) 2010 Elsevier Inc. All rights reserved. C1 [Stanford, John A.] Univ Kansas, Med Ctr, Dept Physiol, Landon Ctr Aging, Kansas City, KS 66160 USA. [Bethel-Brown, Crystal S.; Zhang, Hongyu] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA. [Chertoff, Mark E.] Univ Kansas, Med Ctr, Dept Speech & Hearing, Kansas City, KS 66160 USA. [Fowler, Stephen C.; Chertoff, Mark E.; Stanford, John A.] Univ Kansas, Med Ctr, Kansas Intellectual & Dev Disabil Res Ctr, Kansas City, KS 66160 USA. [Fowler, Stephen C.] Univ Kansas, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA. [Fowler, Stephen C.] Univ Kansas, Schiefelbusch Inst Life Span Studies, Lawrence, KS 66045 USA. [Watson, G. Stennis] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. [Watson, G. Stennis] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr GRECC, Seattle, WA 98108 USA. RP Stanford, JA (reprint author), Univ Kansas, Med Ctr, Dept Physiol, Landon Ctr Aging, Mailstop 3051,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM jstanford@kumc.edu FU NIH [AG023549, AG026491, MH43429, AG23640]; Smith Intellectual and Developmental Disabilities Research Center [HD02528]; Lied Endowed Basic Science Research Grant FX This study was supported by NIH grants AG023549 (JAS), AG026491 (JAS), MH43429 (SCF), AG23640 (GSW), the Smith Intellectual and Developmental Disabilities Research Center (HD02528), and a Lied Endowed Basic Science Research Grant (JAS). NR 42 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD OCT PY 2010 VL 96 IS 4 BP 423 EP 428 DI 10.1016/j.pbb.2010.06.014 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 653TT UT WOS:000282120500007 PM 20600242 ER PT J AU Xia, Y Xu, S Liu, X Chen, ACH AF Xia, Yumin Xu, Shizheng Liu, Xiaoming Chen, Aaron C. -H. TI Photodynamic Therapy as Consolidation Treatment for Primary Cutaneous Adenoid Cystic Carcinoma: A Case Report SO PHOTOMEDICINE AND LASER SURGERY LA English DT Article ID ACID; SKIN AB Objective: The purpose of this case report was to evaluate the efficacy of photodynamic therapy (PDT) for a patient with primary cutaneous adenoid cystic carcinoma (PCACC). Materials and Methods: A 53-year-old female patient presented with a lesion at the pre-auricular area. After performing a local resection along a margin of 0.5 cm beyond the surrounding tissue, PCACC was clearly revealed based on the histological features and the exclusion of differentiation of other metastasis in the skin. The patient was then treated repetitively with 5-aminolevulinic acid (ALA)-PDT. After the final PDT treatment, the control pathological biopsy at the same location demonstrated no tumor cell in the specimen. Results: The 40-month follow-up diagnosis showed no evidence of recurrence or metastasis observed on the treated area. Conclusion: ALA-PDT was a safe and effective therapy for obtaining good cosmetic results and reducing recurrence in this case report. C1 [Xia, Yumin; Xu, Shizheng; Liu, Xiaoming] Wuhan Univ, Renmin Hosp, Dept Dermatol, Wuhan 430060, Peoples R China. [Chen, Aaron C. -H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Chen, Aaron C. -H.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Xia, Y (reprint author), Wuhan Univ, Renmin Hosp, Dept Dermatol, 238 Jiefang Rd, Wuhan 430060, Peoples R China. EM ymxia@whu.edu.cn NR 15 TC 1 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-5418 J9 PHOTOMED LASER SURG JI Photomed. Laser Surg. PD OCT PY 2010 VL 28 IS 5 BP 707 EP 710 DI 10.1089/pho.2009.2663 PG 4 WC Surgery SC Surgery GA 668FA UT WOS:000283252800022 PM 20929386 ER PT J AU Craft, D AF Craft, David TI Calculating and controlling the error of discrete representations of Pareto surfaces in convex multi-criteria optimization SO PHYSICA MEDICA LA English DT Article DE IMRT; Multi objective; Pareto; Optimization; Discrete approximation ID FLUENCE MAP OPTIMIZATION; IMRT AB A discrete set of points and their convex combinations can serve as a sparse representation of the Pareto surface in multiple objective convex optimization. We develop a method to evaluate the quality of such a representation, and show by example that in multiple objective radiotherapy planning, the number of Pareto optimal solutions needed to represent Pareto surfaces of up to five dimensions grows at most linearly with the number of objectives. The method described is also applicable to the representation of convex sets. (C) 2009 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. C1 [Craft, David] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Craft, David] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Craft, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM dcraft@partners.org FU NCI [1 R01 CA103904-01A1] FX This work was supported by NCI Grant 1 R01 CA103904-01A1: Multi-criteria IMRT Optimization. NR 15 TC 3 Z9 3 U1 0 U2 2 PU IST EDITORIALI POLGRAFICI INT PI PISA PA CASELLA POSTALE N 1, SUCCURSALE N 8, 56123 PISA, ITALY SN 1120-1797 J9 PHYS MEDICA JI Phys. Medica PD OCT PY 2010 VL 26 IS 4 BP 184 EP 191 DI 10.1016/j.ejmp.2009.11.005 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 737TQ UT WOS:000288591500002 PM 20022275 ER PT J AU Osawa, M Nishimura, EK Fisher, DE AF Osawa, Masatake Nishimura, Emi K. Fisher, David E. TI Shin-Ichi Nishikawa MD, PhD SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Biographical-Item C1 [Osawa, Masatake; Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Mass Gen Hosp, Boston, MA 02129 USA. [Nishimura, Emi K.] Tokyo Med & Dent Univ, Dept Stem Cell Biol, Med Res Inst, Chiyoda Ku, Tokyo 1010062, Japan. RP Osawa, M (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Mass Gen Hosp, Boston, MA 02129 USA. EM mosawa@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD OCT PY 2010 VL 23 IS 5 BP 683 EP 683 DI 10.1111/j.1755-148X.2010.00743.x PG 1 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 646OO UT WOS:000281552100015 ER PT J AU Wang, YX Suo, HC Zheng, Y Liu, KD Zhuang, CX Kahle, KT Ma, H Yan, XL AF Wang, Yingxiang Suo, Haicui Zheng, Yan Liu, Kaidong Zhuang, Chuxiong Kahle, Kristopher T. Ma, Hong Yan, Xiaolong TI The soybean root-specific protein kinase GmWNK1 regulates stress-responsive ABA signaling on the root system architecture SO PLANT JOURNAL LA English DT Article DE GmWNK1; ABA; root system architecture; GmCYP707A; soybean; osmotic stress ID BIMOLECULAR FLUORESCENCE COMPLEMENTATION; ABSCISIC-ACID; CL-COTRANSPORTERS; FLOWERING TIME; WNK KINASES; ARABIDOPSIS; GENE; PLANTS; FAMILY; IDENTIFICATION AB P>In humans, members of the WNK protein kinase family are osmosensitive regulators of cell volume homeostasis and epithelial ion transport, and mutation of these proteins causes a rare inherited form of hypertension due to increased renal NaCl re-absorption. A related class of kinases was recently discovered in plants, but their functions are largely unknown. We have identified a root-specific WNK kinase homolog, GmWNK1, in soybean (Glycine max). GmWNK1 expression was detected in the root, specifically in root cells associated with lateral root formation, and was down-regulated by abscisic acid (ABA), as well as by mannitol, sucrose, polyethylene glycol and NaCl. In vitro and in vivo experiments showed that GmWNK1 interacts with another soybean protein, GmCYP707A1, which is a key ABA 8'-hydroxylase that functions in ABA catabolism. Furthermore, 35S-GmWNK1 transgenic soybean plants had reduced lateral root number and length compared with wild-type, suggesting a role of GmWNK1 in the regulation of root system architecture. We propose that GmWNK1 functions to fine-tune ABA-dependent ABA homeostasis, thereby mediating the regulation of the root system architecture by ABA and osmotic signals. The study has revealed a new function of a plant WNK1 gene from the important staple crop soybean, and has identified a new component of a regulatory pathway that is involved not only in ABA signaling, but also in the repression of lateral root formation by an ABA-dependent mechanism distinct from known ABA signaling pathways. C1 [Wang, Yingxiang; Suo, Haicui; Zheng, Yan; Liu, Kaidong; Zhuang, Chuxiong; Yan, Xiaolong] S China Agr Univ, Root Biol Ctr, Guangzhou 510642, Guangdong, Peoples R China. [Wang, Yingxiang; Ma, Hong] Fudan Univ, Sch Life Sci, Inst Plant Biol, Shanghai 200433, Peoples R China. [Kahle, Kristopher T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Ma, Hong] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Ma, Hong] Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA. RP Wang, YX (reprint author), S China Agr Univ, Root Biol Ctr, Guangzhou 510642, Guangdong, Peoples R China. EM yxwang@scau.edu.cn RI Wang, Yingxiang/E-2139-2016 OI Wang, Yingxiang/0000-0001-6085-5615 FU National Natural Science Foundation of China [30900918]; National Key Basic Research Special Funds of China [2005CB120902]; McKnight Foundation [05-780] FX This work was supported by grants from the National Natural Science Foundation of China (Grant No. 30900918) to Y. W., the National Key Basic Research Special Funds of China (2005CB120902) and the McKnight Foundation's Collaborative Crop Research Program (05-780) to X. Y. We are grateful to Dr. Chengbin Xiang (School of Life Sciences, University of Science and Technology of China) for providing the pDOR207 and p308R vectors and valuable comments on this manuscript, Dr. Tom Kerppola (Department of Biological Chemistry Investigator Howard Hughes Medical Institute) for the YFP vector. We are also grateful to Dr. Yongchao Liang (Chinese Academy of Agriculture Science at Beijing), Dr. Tom Beeckman (Plant Systems Biology, Ghent University of Belgium), Dr. Leon Kochian (Department of Agriculture-Agricultural Research Service at Cornell University) for the critical review of this manuscript. NR 59 TC 16 Z9 20 U1 2 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0960-7412 J9 PLANT J JI Plant J. PD OCT PY 2010 VL 64 IS 2 BP 230 EP 242 DI 10.1111/j.1365-313X.2010.04320.x PG 13 WC Plant Sciences SC Plant Sciences GA 663IH UT WOS:000282876100005 PM 20735771 ER PT J AU Sheen, J AF Sheen, Jen TI Discover and Connect Cellular Signaling SO PLANT PHYSIOLOGY LA English DT Article ID ARABIDOPSIS-THALIANA; TRANSCRIPTION FACTOR; SNF1-RELATED KINASES; PHOSPHATE STARVATION; SEEDLING GROWTH; GENE-EXPRESSION; PLANT BIOLOGY; ABSCISIC-ACID; SUGAR; PROTEIN C1 [Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu FU National Science Foundation [IOS-0843244]; National Institutes of Health [R01 GM060493, R01 GM070567]; Center for Computational and Integrative Biology at Massachusetts General Hospital FX This work was supported by the National Science Foundation (grant no. IOS-0843244), by the National Institutes of Health (grant nos. R01 GM060493 and R01 GM070567), and by the Center for Computational and Integrative Biology at Massachusetts General Hospital. NR 42 TC 12 Z9 12 U1 0 U2 5 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD OCT PY 2010 VL 154 IS 2 BP 562 EP 566 DI 10.1104/pp.110.161364 PG 5 WC Plant Sciences SC Plant Sciences GA 658TM UT WOS:000282512300029 PM 20921185 ER PT J AU Talbot, SG Parrett, BM Yaremchuk, MJ AF Talbot, Simon G. Parrett, Brian M. Yaremchuk, Michael J. TI Sepsis after Autologous Fat Grafting SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID BREAST; INJECTION C1 [Talbot, Simon G.; Parrett, Brian M.; Yaremchuk, Michael J.] Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast Surg, 15 Parkman St,WAC 435, Boston, MA 02114 USA. EM myaremchuk@partners.org NR 8 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 2010 VL 126 IS 4 BP 162E EP 164E DI 10.1097/PRS.0b013e3181ca4541 PG 3 WC Surgery SC Surgery GA 659IB UT WOS:000282559100045 PM 20885205 ER PT J AU Lindsay, RW Smitson, C Edwards, C Cheney, ML Hadlock, TA AF Lindsay, Robin W. Smitson, Christopher Edwards, Colin Cheney, Mack L. Hadlock, Tessa A. TI Correction of the Nasal Base in the Flaccidly Paralyzed Face: An Orphaned Problem in Facial Paralysis SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter ID GRAFTS C1 [Lindsay, Robin W.] Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Lindsay, Robin W.; Smitson, Christopher; Edwards, Colin; Cheney, Mack L.; Hadlock, Tessa A.] Harvard Univ, Sch Med, Boston, MA USA. [Lindsay, Robin W.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. RP Lindsay, RW (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Dept Otolaryngol Head & Neck Surg, 243 Charles Street, Boston, MA 02114 USA. EM robin_lindsay@meei.harvard.edu NR 5 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 2010 VL 126 IS 4 BP 185E EP 186E DI 10.1097/PRS.0b013e3181ea923c PG 2 WC Surgery SC Surgery GA 659IB UT WOS:000282559100053 PM 20885213 ER PT J AU Dimitriadi, M Sleigh, JN Walker, A Chang, HC Sen, A Kalloo, G Harris, J Barsby, T Walsh, MB Satterlee, JS Li, C Van Vactor, D Artavanis-Tsakonas, S Hart, AC AF Dimitriadi, Maria Sleigh, James N. Walker, Amy Chang, Howard C. Sen, Anindya Kalloo, Geetika Harris, Jevede Barsby, Tom Walsh, Melissa B. Satterlee, John S. Li, Chris Van Vactor, David Artavanis-Tsakonas, Spyros Hart, Anne C. TI Conserved Genes Act as Modifiers of Invertebrate SMN Loss of Function Defects SO PLOS GENETICS LA English DT Article ID SPINAL MUSCULAR-ATROPHY; MENTAL-RETARDATION PROTEIN; NEMATODE CAENORHABDITIS-ELEGANS; MOTOR-NEURON PROTEIN; NUCLEOSIDE-DIPHOSPHATE KINASE; AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID PRECURSOR PROTEIN; EGF RECEPTOR TRAFFICKING; DROSOPHILA ALPHA-ACTININ; GROWTH-FACTOR RECEPTOR AB Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species. C1 [Dimitriadi, Maria; Kalloo, Geetika; Hart, Anne C.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Sleigh, James N.; Walker, Amy; Harris, Jevede; Barsby, Tom; Satterlee, John S.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp,Ctr Canc Res, Boston, MA 02115 USA. [Sleigh, James N.; Barsby, Tom] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. [Chang, Howard C.; Sen, Anindya; Van Vactor, David; Artavanis-Tsakonas, Spyros] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Walsh, Melissa B.] Brown Univ, Dept Mol & Cellular Biol, Providence, RI 02912 USA. [Li, Chris] CUNY City Coll, Dept Biol, New York, NY 10031 USA. [Artavanis-Tsakonas, Spyros] Coll France, F-75231 Paris, France. RP Dimitriadi, M (reprint author), Brown Univ, Dept Neurosci, Providence, RI 02912 USA. EM anne_hart@brown.edu OI Sleigh, James/0000-0002-3782-9045 FU Spinal Muscular Atrophy Foundation; National Institutes of Health (NIH) [R01 NS42459, R01 NS26084]; NIH/NCRR/RCMI [G12-RR03060]; City College of New York; Families of SMA Postdoctoral Fellowship; NIH National Center for Research Resources FX This work was supported by the Spinal Muscular Atrophy Foundation (DVV, SA-T, ACH), by National Institutes of Health (NIH R01 NS42459) and NIH/NCRR/RCMI Grant G12-RR03060 (CL), and by the City College of New York, respectively. Also by NIH R01 NS26084 (SA-T) and a Families of SMA Postdoctoral Fellowship (AS). Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 155 TC 37 Z9 53 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2010 VL 6 IS 10 AR e1001172 DI 10.1371/journal.pgen.1001172 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 673GP UT WOS:000283647800004 PM 21124729 ER PT J AU Gaudet, MM Kirchhoff, T Green, T Vijai, J Korn, JM Guiducci, C Segre, AV McGee, K McGuffog, L Kartsonaki, C Morrison, J Healey, S Sinilnikova, OM Stoppa-Lyonnet, D Mazoyer, S Gauthier-Villars, M Sobol, H Longy, M Frenay, M Hogervorst, FBL Rookus, MA Collee, JM Hoogerbrugge, N van Roozendaal, KEP Piedmonte, M Rubinstein, W Nerenstone, S Van Le, L Blank, SV Caldes, T de la Hoya, M Nevanlinna, H Aittomaki, K Lazaro, C Blanco, I Arason, A Johannsson, OT Barkardottir, RB Devilee, P Olopade, OI Neuhausen, SL Wang, XS Fredericksen, ZS Peterlongo, P Manoukian, S Barile, M Viel, A Radice, P Phelan, CM Narod, S Rennert, G Lejbkowicz, F Flugelman, A Andrulis, IL Glendon, G Ozcelik, H Toland, AE Montagna, M D'Andrea, E Friedman, E Laitman, Y Borg, A Beattie, M Ramus, SJ Domchek, SM Nathanson, KL Rebbeck, T Spurdle, AB Chen, XQ Holland, H John, EM Hopper, JL Buys, SS Daly, MB Southey, MC Terry, MB Tung, N Hansen, TVO Nielsen, FC Greene, MI Mai, PL Osorio, A Duran, M Andres, R Benitez, J Weitzel, JN Garber, J Hamann, U Peock, S Cook, M Oliver, C Frost, D Platte, R Evans, DG Lalloo, F Eeles, R Izatt, L Walker, L Eason, J Barwell, J Godwin, AK Schmutzler, RK Wappenschmidt, B Engert, S Arnold, N Gadzicki, D Dean, M Gold, B Klein, RJ Couch, FJ Chenevix-Trench, G Easton, DF Daly, MJ Antoniou, AC Altshuler, DM Offit, K AF Gaudet, Mia M. Kirchhoff, Tomas Green, Todd Vijai, Joseph Korn, Joshua M. Guiducci, Candace Segre, Ayellet V. McGee, Kate McGuffog, Lesley Kartsonaki, Christiana Morrison, Jonathan Healey, Sue Sinilnikova, Olga M. Stoppa-Lyonnet, Dominique Mazoyer, Sylvie Gauthier-Villars, Marion Sobol, Hagay Longy, Michel Frenay, Marc Hogervorst, Frans B. L. Rookus, Matti A. Collee, J. Margriet Hoogerbrugge, Nicoline van Roozendaal, Kees E. P. Piedmonte, Marion Rubinstein, Wendy Nerenstone, Stacy Van Le, Linda Blank, Stephanie V. Caldes, Trinidad de la Hoya, Miguel Nevanlinna, Heli Aittomaki, Kristiina Lazaro, Conxi Blanco, Ignacio Arason, Adalgeir Johannsson, Oskar T. Barkardottir, Rosa B. Devilee, Peter Olopade, Olofunmilayo I. Neuhausen, Susan L. Wang, Xianshu Fredericksen, Zachary S. Peterlongo, Paolo Manoukian, Siranoush Barile, Monica Viel, Alessandra Radice, Paolo Phelan, Catherine M. Narod, Steven Rennert, Gad Lejbkowicz, Flavio Flugelman, Anath Andrulis, Irene L. Glendon, Gord Ozcelik, Hilmi Toland, Amanda E. Montagna, Marco D'Andrea, Emma Friedman, Eitan Laitman, Yael Borg, Ake Beattie, Mary Ramus, Susan J. Domchek, Susan M. Nathanson, Katherine L. Rebbeck, Tim Spurdle, Amanda B. Chen, Xiaoqing Holland, Helene John, Esther M. Hopper, John L. Buys, Saundra S. Daly, Mary B. Southey, Melissa C. Terry, Mary Beth Tung, Nadine Hansen, Thomas V. Overeem Nielsen, Finn C. Greene, Mark I. Mai, Phuong L. Osorio, Ana Duran, Mercedes Andres, Raquel Benitez, Javier Weitzel, Jeffrey N. Garber, Judy Hamann, Ute Peock, Susan Cook, Margaret Oliver, Clare Frost, Debra Platte, Radka Evans, D. Gareth Lalloo, Fiona Eeles, Ros Izatt, Louise Walker, Lisa Eason, Jacqueline Barwell, Julian Godwin, Andrew K. Schmutzler, Rita K. Wappenschmidt, Barbara Engert, Stefanie Arnold, Norbert Gadzicki, Dorothea Dean, Michael Gold, Bert Klein, Robert J. Couch, Fergus J. Chenevix-Trench, Georgia Easton, Douglas F. Daly, Mark J. Antoniou, Antonis C. Altshuler, David M. Offit, Kenneth CA GEMO Study Collaborators HEBON Study Collaborators OCGN kConFab TI Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer SO PLOS GENETICS LA English DT Article ID BRCA2 MUTATION CARRIERS; SUSCEPTIBILITY GENES; RECURRENT BRCA1; RISK; POPULATION; MODEL; PREDISPOSITION; ASSOCIATION; PHENOTYPE; FREQUENCY AB The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer. C1 [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, New York, NY USA. [Kirchhoff, Tomas; Vijai, Joseph; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Sloan Kettering Inst, Clin Genet Serv, New York, NY 10021 USA. [Kirchhoff, Tomas] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY 10021 USA. [Green, Todd; Korn, Joshua M.; Guiducci, Candace; Daly, Mark J.; Altshuler, David M.] Harvard Univ, Sch Med, Broad Inst Harvard, Boston, MA USA. [Green, Todd; Korn, Joshua M.; Guiducci, Candace; Daly, Mark J.; Altshuler, David M.] Harvard Univ, Sch Med, MIT, Boston, MA USA. [Segre, Ayellet V.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Segre, Ayellet V.] MIT, Cambridge, MA 02139 USA. [Segre, Ayellet V.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Segre, Ayellet V.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [McGee, Kate; Dean, Michael; Gold, Bert] NCI, Ctr Canc Res, Canc Inflammat Program, Human Genet Sect, Frederick, MD 21701 USA. [McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Platte, Radka; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Sinilnikova, Olga M.] CHU Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Sinilnikova, Olga M.; Mazoyer, Sylvie] Univ Lyon, Ctr Leon Berard, CNRS UMR5201, Equipe Labellisee LIGUE 2008, Lyon, France. [Stoppa-Lyonnet, Dominique] Univ Paris 05, INSERM U830, Serv Genet, Inst Curie, F-75248 Paris, France. [Stoppa-Lyonnet, Dominique; Gauthier-Villars, Marion] Inst Curie, Serv Genet Oncol, Paris, France. [Sobol, Hagay] Univ Aix Marseille 2, Inst J Paoli I Calmettes, INSERM CIC P9502, Dept Oncol Genet Prevent & Depistage, F-13284 Marseille 07, France. [Longy, Michel] Inst Bergonie, Bordeaux, France. [Frenay, Marc] Ctr Antoine Lacassagne, F-06054 Nice, France. [GEMO Study Collaborators] Fed Natl Ctr Lutte Contre Canc, GEMO Study Canc Genet Network Grp Genet & Canc, Paris, France. [Hogervorst, Frans B. L.; HEBON Study Collaborators] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Collee, J. Margriet] Erasmus Univ, Med Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [Hoogerbrugge, Nicoline] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [van Roozendaal, Kees E. P.] Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands. [Piedmonte, Marion] Roswell Pk Canc Inst, Gynecol Oncol Grp Stat, Buffalo, NY 14263 USA. [Piedmonte, Marion] Roswell Pk Canc Inst, Ctr Data, Buffalo, NY 14263 USA. [Rubinstein, Wendy] NorthShore Univ Hlth Syst, Evanston, IL USA. [Nerenstone, Stacy] Hartford Hosp, Cent Connecticut Canc Consortium, Hartford, CT 06115 USA. [Van Le, Linda] Univ N Carolina, Chapel Hill, NC USA. [Blank, Stephanie V.] NYU, Sch Med, New York, NY USA. [Caldes, Trinidad; de la Hoya, Miguel] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain. [Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. [Lazaro, Conxi; Blanco, Ignacio] Catalan Inst Oncol, Hereditary Canc Program, Barcelona, Spain. [Arason, Adalgeir; Johannsson, Oskar T.; Barkardottir, Rosa B.] Landspitali LSH, Dept Oncol, Reykjavik, Iceland. [Arason, Adalgeir; Barkardottir, Rosa B.] Landspitali LSH, Dept Pathol, Reykjavik, Iceland. [Arason, Adalgeir; Johannsson, Oskar T.; Barkardottir, Rosa B.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands. [Olopade, Olofunmilayo I.] Univ Chicago, Med Ctr, Dept Med, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. [Neuhausen, Susan L.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA. [Wang, Xianshu; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Fredericksen, Zachary S.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Expt Oncol & Mol Med, Unit Genet Susceptibil Canc, Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy. [Barile, Monica] IEO, Div Canc Prevent & Genet, Milan, Italy. [Viel, Alessandra] IRCCS, CRO, Div Expt Oncol 1, Aviano, PN, Italy. [Phelan, Catherine M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Narod, Steven] Womens Coll Res Inst, Toronto, ON, Canada. [Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath] CHS Natl Canc Control Ctr, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Andrulis, Irene L.; Ozcelik, Hilmi] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; OCGN] Univ Toronto, Ontario Canc Genet Network, Toronto, ON, Canada. [Toland, Amanda E.] Ohio State Univ, Dept Mol Virol, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Dept Immunol, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Dept Med Genet & Internal Med, Columbus, OH 43210 USA. [Montagna, Marco; D'Andrea, Emma] IRCCS, Ist Oncol Veneto, Immunol & Mol Oncol Unit, Padua, Italy. [D'Andrea, Emma] Univ Padua, Dept Oncol & Surg Sci, Padua, Italy. [Friedman, Eitan; Laitman, Yael] Sheba Med Ctr, Inst Genet, Susan Levy Gertner Oncogenet Unit, Tel Hashomer, Israel. [Borg, Ake] Lund Univ, Dept Oncol, Lund, Sweden. [Beattie, Mary] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. [Ramus, Susan J.] UCL, UCL EGA Inst Womens Hlth, Gynaecol Oncol Unit, London WC1E 6BT, England. [Domchek, Susan M.] Hosp Univ Penn, Dept Oncol, Philadelphia, PA 19104 USA. [Nathanson, Katherine L.] Univ Penn, Sch Med, Dept Cell & Mol Biol, Philadelphia, PA 19104 USA. [Rebbeck, Tim] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Spurdle, Amanda B.; Chen, Xiaoqing; Holland, Helene] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia. [Chenevix-Trench, Georgia; kConFab] Peter MacCallum Canc Ctr, Melbourne, Australia. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [Hopper, John L.] Univ Melbourne, Ctr Genet Epidemiol, Melbourne, Vic, Australia. [Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Southey, Melissa C.] Univ Melbourne, Ctr Genet Epidemiol, Melbourne, Vic, Australia. [Terry, Mary Beth] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Hansen, Thomas V. Overeem; Nielsen, Finn C.] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark. [Greene, Mark I.; Mai, Phuong L.] NCI, Clin Genet Branch, Rockville, MD USA. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Duran, Mercedes] Univ Valladolid IBGM UVA, Inst Biol & Mol Genet, Valladolid, Spain. [Andres, Raquel] Hosp Clin Univ Lozano Blesa, Oncol Serv, Zaragoza, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Genotyping Unit, Madrid, Spain. [Weitzel, Jeffrey N.] City Hope Canc Ctr, Duarte, CA USA. [Garber, Judy] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hamann, Ute] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, Ros] Inst Canc Res, Oncogenet Team, London SW3 6JB, England. [Eeles, Ros] Royal Marsden NHS Fdn Trust, London, England. [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, London, England. [Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England. [Eason, Jacqueline] Nottingham Univ Hosp NHS Trust, Nottingham Clin Genet Serv, Nottingham, England. [Barwell, Julian] Univ Hosp Leicester NHS Trust, Leicestershire Clin Genet Serv, Leicester, Leics, England. [Godwin, Andrew K.] Fox Chase Canc Ctr, Dept Med Oncol, Womens Canc Program, Philadelphia, PA 19111 USA. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Obstet & Gynaecol, Cologne, Germany. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, CIO, Cologne, Germany. [Engert, Stefanie] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Dept Obstet & Gynaecol, D-8000 Munich, Germany. [Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Kiel, Germany. [Gadzicki, Dorothea] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany. RP Gaudet, MM (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. EM offitk@mskcc.org RI Spurdle, Amanda/A-4978-2011; Radice, Paolo/O-3119-2013; Blanco, Ignacio/D-2565-2013; Osorio, Ana/I-4324-2014; GLADIEFF, Laurence/O-5129-2014; Ligtenberg, Marjolijn/N-9666-2013; manoukian, siranoush/E-7132-2017; Altshuler, David/A-4476-2009; Klein, Robert/K-1888-2013; Hoogerbrugge, Nicoline/O-1016-2013; Segre, Ayellet/E-9800-2010; Arnold, Norbert/E-3012-2010; Toland, Amanda/E-4202-2011; montagna, marco/E-2225-2012; Dean, Michael/G-8172-2012; D'Andrea, Emma/B-4374-2013; Andrulis, Irene/E-7267-2013; Joseph, Vijai/J-9158-2013 OI Evans, Gareth/0000-0002-8482-5784; Ramus, Susan/0000-0003-0005-7798; Spurdle, Amanda/0000-0003-1337-7897; Nevanlinna, Heli/0000-0002-0916-2976; Kirchhoff, Tomas/0000-0002-9055-2364; Blanco, Ignacio/0000-0002-7414-7481; Osorio, Ana/0000-0001-8124-3984; GLADIEFF, Laurence/0000-0002-6980-9719; Ligtenberg, Marjolijn/0000-0003-1290-1474; manoukian, siranoush/0000-0002-6034-7562; Eeles, Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901; Altshuler, David/0000-0002-7250-4107; Klein, Robert/0000-0003-3539-5391; Arnold, Norbert/0000-0003-4523-8808; montagna, marco/0000-0002-4929-2150; Dean, Michael/0000-0003-2234-0631; Joseph, Vijai/0000-0002-7933-151X FU Starr Cancer Research Consortium; Breast Cancer Research Foundation; NIH NCI [P20CA103694-3]; Lymphoma Foundation; Robert and Kate Niehaus Clinical Cancer Genetics Initiative at MSKCC FX This study was supported by the Starr Cancer Research Consortium and the Breast Cancer Research Foundation, as well as by NIH NCI: P20CA103694-3 and the Lymphoma Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The LUMC study would like to thank Hans Vasen, Inge van Leeuwen, and Hanne Meijers for patient accrual. For the CNIO study, the authors would like to thank R. M. Alonso, G. Pita and R. M. Milne for their assistance. We thank IBGM, Universidad de Valladolid and Consejeria de Sanidad Junta de Castilla y Leon. For the SWE-BRCA, the authors would like to also acknowledge the contribution of Per Karlsson, Margareta Nordling, Annika Bergman and Zakaria Einbeigi, Gothenburg, Sahlgrenska University Hospital; Marie Stenmark-Askmalm and Sigrun Liedgren Linkoping University Hospital; Ake Borg, Niklas Loman, Hakan Olsson, Ulf Kristoffersson, Helena Jernstrom, Katja Harbst and Karin Henriksson, Lund University Hospital; Annika Lindblom, Brita Arver, Anna von Wachenfeldt, Annelie Liljegren, Gisela Barbany-Bustinza and Johanna Rantala, Stockholm, Karolinska University Hospital; Beatrice Melin, Henrik Gronberg, Eva-Lena Stattin and Monica Emanuelsson, Umea University Hospital; Hans Ehrencrona, Richard Rosenquist Brandell and Niklas Dahl, Uppsala University Hospital. Douglas F. Easton is the PI of the EMBRACE study. EMBRACE Collaborating Centers are: Coordinating Centre, Cambridge: Susan Peock, Margaret Cook, Clare Oliver, Debra Frost. North of Scotland Regional Genetics Service, Aberdeen: Helen Gregory, Zosia Miedzybrodzka. Northern Ireland Regional Genetics Service, Belfast: Patrick J. Morrison, Lisa Jeffers. West Midlands Regional Clinical Genetics Service, Birmingham: Trevor Cole, Carole McKeown, Kai-Ren Ong, Laura Boyes. South Western Regional Genetics Service, Bristol: Alan Donaldson. East Anglian Regional Genetics Service, Cambridge: Joan Paterson. All Wales Medical Genetics Services, Cardiff: Alexandra Murray, Mark T. Rogers, Emma McCann. St James's Hospital, Dublin & National Centre for Medical Genetics, Dublin: M. John Kennedy, David Barton. South East of Scotland Regional Genetics Service, Edinburgh: Mary Porteous. Peninsula Clinical Genetics Service. Exeter: Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman. West of Scotland Regional Genetics Service, Glasgow: Rosemarie Davidson, Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt, Sarah Gibson. South East Thames Regional Genetics Service, Guys Hospital London: Louise Izatt, Gabriella Pichert, Chris Jacobs, Caroline Langman. North West Thames Regional Genetics Service, Kennedy-Galton Centre, Harrow: Huw Dorkins. Leicestershire Clinical Genetics Service, Leicester: Julian Barwell. Yorkshire Regional Genetics Service, Leeds: Carol Chu, Tim Bishop, Julie Miller. Merseyside & Cheshire Clinical Genetics Service. Liverpool: Ian Ellis, Catherine Houghton. Manchester Regional Genetics Service, Manchester: D Gareth Evans, Fiona Lalloo, Felicity Holt. North East Thames Regional Genetics Service, North East Thames: Lucy Side, Alison Male, Cheryl Berlin. Nottingham Centre for Medical Genetics, Nottingham: Carol Gardiner. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, Oonagh Claber. Oxford Regional Genetics Service, Oxford: Lisa Walker, Diane McLeod, Dorothy Halliday, Sarah Durrell, Barbara Stayner. The Institute of Cancer Research and Royal Marsden NHS Foundation Trust: Ros Eeles, Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Lucia D'Mello, Elizabeth Page, Audrey Ardern-Jones, Kelly Kohut, Jennifer Wiggins. Elena Castro, Anita Mitra, Lisa Robertson. North Trent Clinical Genetics Service, Sheffield: Jackie Cook, Oliver Quarrell, Cathryn Bardsley. South Essex Cancer Research Network, Southend: Anne Robinson.; South West Thames Regionl Genetics Service, London: Shirley Hodgson, Sheila Goff, Glen Brice, Lizzie Winchester. Wessex Clinical Genetics Service. Princess Anne Hospital, Southampton: Diana Eccles, Anneke Lucassen, Gillian Crawford, Emma Tyler, Donna McBride. HEBCS thanks Dr. Carl Blomqvist and Tuomas Heikkinen for their help with the patient data and samples. Fox Chase Cancer Center (FCCC) thanks Ms. JoEllen Weaver and Mr. John Malick for expert technical assistance. The UCSF study would like to acknowledge Ms. Salina Chan for her database management assistance. CONsorzio Studi Italiani Tumori Ereditari Alla Mammella, CONSIT TEAM acknowledges Marco Pierotti, Bernard Peissel, Daniela Zaffaroni and Carla B. Ripamonti of the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Bernardo Bonanni of the Istituto Europeo di Oncologia, Milan, Italy and Loris Bernard of the Cogentech, Consortium for Genomic Technologies, Milan, Italy. CBCS would like to thank Bent Ejlerten, Mette K. Andersen, Susanne Kjaergaard and Anne-Marie Gerdes for clinical data. The authors wish to thank Nichole Hansen for help in manuscript preparation. The authors also acknowledge support of the Robert and Kate Niehaus Clinical Cancer Genetics Initiative at MSKCC. NR 43 TC 56 Z9 58 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2010 VL 6 IS 10 AR e1001183 DI 10.1371/journal.pgen.1001183 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 673GP UT WOS:000283647800014 PM 21060860 ER PT J AU Padmanabhan, S Melander, O Johnson, T Di Blasio, AM Lee, WK Gentilini, D Hastie, CE Menni, C Monti, MC Delles, C Laing, S Corso, B Navis, G Kwakernaak, AJ van der Harst, P Bochud, M Maillard, M Burnier, M Hedner, T Kjeldsen, S Wahlstrand, B Sjogren, M Fava, C Montagnana, M Danese, E Torffvit, O Hedblad, B Snieder, H Connell, JMC Brown, M Samani, NJ Farrall, M Cesana, G Mancia, G Signorini, S Grassi, G Eyheramendy, S Wichmann, HE Laan, M Strachan, DP Sever, P Shields, DC Stanton, A Vollenweider, P Teumer, A Volzke, H Rettig, R Newton-Cheh, C Arora, P Zhang, F Soranzo, N Spector, TD Lucas, G Kathiresan, S Siscovick, DS Luan, JA Loos, RJF Wareham, NJ Penninx, BW Nolte, IM McBride, M Miller, WH Nicklin, SA Baker, AH Graham, D McDonald, RA Pell, JP Sattar, N Welsh, P Munroe, P Caulfield, MJ Zanchetti, A Dominiczak, AF AF Padmanabhan, Sandosh Melander, Olle Johnson, Toby Di Blasio, Anna Maria Lee, Wai K. Gentilini, Davide Hastie, Claire E. Menni, Cristina Monti, Maria Cristina Delles, Christian Laing, Stewart Corso, Barbara Navis, Gerjan Kwakernaak, Arjan J. van der Harst, Pim Bochud, Murielle Maillard, Marc Burnier, Michel Hedner, Thomas Kjeldsen, Sverre Wahlstrand, Bjorn Sjogren, Marketa Fava, Cristiano Montagnana, Martina Danese, Elisa Torffvit, Ole Hedblad, Bo Snieder, Harold Connell, John M. C. Brown, Morris Samani, Nilesh J. Farrall, Martin Cesana, Giancarlo Mancia, Giuseppe Signorini, Stefano Grassi, Guido Eyheramendy, Susana Wichmann, H. Erich Laan, Maris Strachan, David P. Sever, Peter Shields, Denis Colm Stanton, Alice Vollenweider, Peter Teumer, Alexander Voelzke, Henry Rettig, Rainer Newton-Cheh, Christopher Arora, Pankaj Zhang, Feng Soranzo, Nicole Spector, Timothy D. Lucas, Gavin Kathiresan, Sekar Siscovick, David S. Luan, Jian'an Loos, Ruth J. F. Wareham, Nicholas J. Penninx, Brenda W. Nolte, Ilja M. McBride, Martin Miller, William H. Nicklin, Stuart A. Baker, Andrew H. Graham, Delyth McDonald, Robert A. Pell, Jill P. Sattar, Naveed Welsh, Paul Munroe, Patricia Caulfield, Mark J. Zanchetti, Alberto Dominiczak, Anna F. CA Global BPgen Consortium TI Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension SO PLOS GENETICS LA English DT Article ID TAMM-HORSFALL PROTEIN; CHRONIC KIDNEY-DISEASE; URINARY-EXCRETION; RISK-FACTORS; LOCI; NEPHROPATHY; FEASIBILITY; MUTATIONS; MORTALITY; BURDEN AB Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk. C1 [Padmanabhan, Sandosh; Lee, Wai K.; Hastie, Claire E.; Menni, Cristina; Delles, Christian; Laing, Stewart; McBride, Martin; Miller, William H.; Nicklin, Stuart A.; Baker, Andrew H.; Graham, Delyth; McDonald, Robert A.; Sattar, Naveed; Welsh, Paul; Dominiczak, Anna F.] Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Melander, Olle; Sjogren, Marketa; Fava, Cristiano; Montagnana, Martina; Danese, Elisa; Hedblad, Bo] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden. [Johnson, Toby; Munroe, Patricia; Caulfield, Mark J.] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Clin Pharmacol & Barts & London Genome Ctr, London, England. [Di Blasio, Anna Maria; Gentilini, Davide; Monti, Maria Cristina; Corso, Barbara; Zanchetti, Alberto] Ist Auxolog Italiano, Milan, Italy. [Menni, Cristina; Cesana, Giancarlo; Mancia, Giuseppe; Grassi, Guido] Univ Milano Bicocca, Osped San Gerardo, Dipartimento Med Clin & Prevenz, Milan, Italy. [Monti, Maria Cristina; Corso, Barbara] Univ Pavia, Dept Hlth Sci, I-27100 Pavia, Italy. [Navis, Gerjan; Kwakernaak, Arjan J.] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands. [van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Bochud, Murielle; Maillard, Marc; Burnier, Michel; Vollenweider, Peter] Univ Lausanne, Lausanne, Switzerland. [Bochud, Murielle] CHU Vaudois, Univ Inst Social & Prevent Med, CH-1011 Lausanne, Switzerland. [Maillard, Marc; Burnier, Michel] CHU Vaudois, Serv Nephrol, CH-1011 Lausanne, Switzerland. [Hedner, Thomas; Wahlstrand, Bjorn] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden. [Kjeldsen, Sverre] Univ Oslo, Ullevaal Hosp, Dept Cardiol, N-0407 Oslo, Norway. [Fava, Cristiano] Univ Verona, Sect Internal Med C, Dept Med, I-37100 Verona, Italy. [Montagnana, Martina; Danese, Elisa] Univ Verona, Sect Clin Chem, Dept Life & Reprod Sci, I-37100 Verona, Italy. [Torffvit, Ole] Univ Lund Hosp, Dept Nephrol, Inst Clin Sci, S-22185 Lund, Sweden. [Snieder, Harold; Nolte, Ilja M.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Unit Genet Epidemiol & Bioinformat, Groningen, Netherlands. [Connell, John M. C.] Univ Dundee, Ninewells Hosp, Coll Med Dent & Nursing, Dundee, Scotland. [Brown, Morris] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England. [Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England. [Farrall, Martin] Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford, England. [Signorini, Stefano] Azienda Osped Desio & Vimercate, Milan, Italy. [Eyheramendy, Susana] Pontificia Univ Catolica Chile, Dept Stat, Santiago, Chile. [Wichmann, H. Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. [Wichmann, H. Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Laan, Maris] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Strachan, David P.] Univ London, Div Community Hlth Sci, London, England. [Sever, Peter] Univ London Imperial Coll Sci Technol & Med, Int Ctr Circulatory Hlth Natl Heart & Lung Inst, London, England. [Shields, Denis Colm] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 2, Ireland. [Stanton, Alice] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [Vollenweider, Peter] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland. [Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany. [Newton-Cheh, Christopher; Arora, Pankaj; Kathiresan, Sekar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA. [Newton-Cheh, Christopher; Arora, Pankaj; Kathiresan, Sekar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. [Newton-Cheh, Christopher; Arora, Pankaj; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Zhang, Feng; Soranzo, Nicole; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Soranzo, Nicole] Wellcome Trust Sanger Inst, Hinxton, England. [Lucas, Gavin] Inst Municipal Invest Med, Cardiovasc Epidemiol & Genet Grp, E-08003 Barcelona, Spain. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Luan, Jian'an; Loos, Ruth J. F.; Wareham, Nicholas J.] Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, EMGO Inst, Amsterdam, Netherlands. [Penninx, Brenda W.] Leiden Univ Med Ctr, Dept Psychiat, Leiden, Netherlands. [Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Pell, Jill P.] Univ Glasgow, Publ Hlth & Hlth Policy Sect, Glasgow, Lanark, Scotland. [Zanchetti, Alberto] Univ Milan, Milan, Italy. RP Padmanabhan, S (reprint author), Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. EM anna.dominiczak@glasgow.ac.uk RI Laan, Maris/A-4100-2011; Bochud, Murielle/A-3981-2010; Arora, Pankaj/F-3437-2011; Lucas, Gavin/D-4346-2012; Colaus, PsyColaus/K-6607-2013; danese, elisa/K-6992-2013; Stanton, Alice/F-4697-2012; Danese, Elisa/N-2848-2016; Padmanabhan, Sandosh/S-3963-2016; OI Johnson, Toby/0000-0002-5998-3270; Welsh, Paul/0000-0002-7970-3643; Laan, Maris/0000-0002-8519-243X; Bochud, Murielle/0000-0002-5727-0218; Arora, Pankaj/0000-0003-2420-3550; Danese, Elisa/0000-0002-2454-0410; Padmanabhan, Sandosh/0000-0003-3869-5808; Menni, Cristina/0000-0001-9790-0571; Soranzo, Nicole/0000-0003-1095-3852; Monti, Maria Cristina/0000-0003-1586-527X FU British Heart Foundation (BHF) Chair [CH/98001]; BHF [RG/07/005/23633, SP/08/005/25115, FS/05/095/19937]; European Community; Fondazione Istituto Auxologico Italiano; Regione Lombardia FX This research was supported by the following grants: British Heart Foundation (BHF) Chair CH/98001 to AFD; BHF Programme RG/07/005/23633 to AFD, SP, CD; BHF Special Project Grant SP/08/005/25115 to AFD, SP, CD; SP was supported by an intermediate research fellowship from the BHF (FS/05/095/19937). We thank the British Heart Foundation, European Community Framework 6 Network of Excellence InGenious HyperCare, Fondazione Istituto Auxologico Italiano, and Regione Lombardia for funding the discovery study and validation in the MONICA/PAMELA populations. The discovery study and validations in the MONICA/PAMELA populations are part of the activities of the EC Network of Excellence InGenious HyperCare (LSMH-CT-2006-037093) coordinated by Prof. A Zanchetti. Further financial support has been provided by Fondazione Istituto Auxologico Italiano, Milan, and Regione Lombardia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 121 Z9 128 U1 1 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2010 VL 6 IS 10 AR e1001177 DI 10.1371/journal.pgen.1001177 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 673GP UT WOS:000283647800009 PM 21082022 ER PT J AU Yazdanpanah, Y Sloan, CE Charlois-Ou, C Le Vu, S Semaille, C Costagliola, D Pillonel, J Poullie, AI Scemama, O Deuffic-Burban, S Losina, E Walensky, RP Freedberg, KA Paltiel, AD AF Yazdanpanah, Yazdan Sloan, Caroline E. Charlois-Ou, Cecile Le Vu, Stephane Semaille, Caroline Costagliola, Dominique Pillonel, Josiane Poullie, Anne-Isabelle Scemama, Olivier Deuffic-Burban, Sylvie Losina, Elena Walensky, Rochelle P. Freedberg, Kenneth A. Paltiel, A. David TI Routine HIV Screening in France: Clinical Impact and Cost-Effectiveness SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; OPPORTUNISTIC INFECTIONS; LATE DIAGNOSIS; LIFETIME COST; CONSEQUENCES; TRANSMISSION; CARE; ERA AB Background: In France, roughly 40,000 HIV-infected persons are unaware of their HIV infection. Although previous studies have evaluated the cost-effectiveness of routine HIV screening in the United States, differences in both the epidemiology of infection and HIV testing behaviors warrant a setting-specific analysis for France. Methods/Principal Findings: We estimated the life expectancy (LE), cost and cost-effectiveness of alternative HIV screening strategies in the French general population and high-risk sub-populations using a computer model of HIV detection and treatment, coupled with French national clinical and economic data. We compared risk-factor-based HIV testing ("current practice'') to universal routine, voluntary HIV screening in adults aged 18-69. Screening frequencies ranged from once to annually. Input data included mean age (42 years), undiagnosed HIV prevalence (0.10%), annual HIV incidence (0.01%), test acceptance (79%), linkage to care (75%) and cost/test ((sic)43). We performed sensitivity analyses on HIV prevalence and incidence, cost estimates, and the transmission benefits of ART. "Current practice'' produced LEs of 242.82 quality-adjusted life months (QALM) among HIV-infected persons and 268.77 QALM in the general population. Adding a one-time HIV screen increased LE by 0.01 QALM in the general population and increased costs by (sic)50/person, for a cost-effectiveness ratio (CER) of (sic)57,400 per quality-adjusted life year (QALY). More frequent screening in the general population increased survival, costs and CERs. Among injection drug users (prevalence 6.17%; incidence 0.17%/year) and in French Guyana (prevalence 0.41%; incidence 0.35%/year), annual screening compared to every five years produced CERs of (sic)51,200 and (sic)46,500/QALY. Conclusions/Significance: One-time routine HIV screening in France improves survival compared to "current practice'' and compares favorably to other screening interventions recommended in Western Europe. In higher-risk groups, more frequent screening is economically justifiable. C1 [Yazdanpanah, Yazdan] Ctr Hosp Tourcoing, Serv Univ Malad Infect & Voyageur, Tourcoing, France. [Yazdanpanah, Yazdan] INSERM, U995, Avenir Act Themat & Incitat Programme, F-59045 Lille, France. [Yazdanpanah, Yazdan; Semaille, Caroline] Fac Med Lille, EA 2694, F-59045 Lille, France. [Sloan, Caroline E.; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Charlois-Ou, Cecile] Ctr Natl Rech Sci, CRESGE LEM, UMR8179, Lille, France. [Le Vu, Stephane; Semaille, Caroline; Pillonel, Josiane] Inst Veille Sanitaire, Dept Infect Dis, HIV AIDS STI HCV Unit, St Maurice, France. [Costagliola, Dominique] INSERM, U943, Paris, France. [Costagliola, Dominique] INSERM, UMR S 943, Paris, France. [Costagliola, Dominique] Univ Paris 06, Paris, France. [Costagliola, Dominique] Grp Hosp Pitie Salpetriere, AP HP, Serv Malad Infect & Trop, F-75634 Paris, France. [Poullie, Anne-Isabelle; Scemama, Olivier] Haute Autorite Sante, Econ & Publ Hlth Assessment Dept, St Denis, France. [Deuffic-Burban, Sylvie] INSERM, U995, Fac Med Lille, F-59045 Lille, France. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Paltiel, A. David] Yale Univ, Sch Med, New Haven, CT USA. RP Yazdanpanah, Y (reprint author), Ctr Hosp Tourcoing, Serv Univ Malad Infect & Voyageur, Tourcoing, France. EM yyazdan@yahoo.com RI Costagliola, Dominique/H-5849-2011 OI Walensky, Rochelle P./0000-0002-8795-379X; Costagliola, Dominique/0000-0003-0765-0869 FU Haute Autorite de Sante; Institut de Veille Sanitaire, Sidaction; Agence Nationale de Recherches sur le SIDA et les hepatites virales; National Institute of Allergy and Infectious Diseases [R01 AI042006, K24 AI062476, P30 AI42851]; National Institute of Mental Health [R01 MH65869]; National Institute on Drug Abuse [R01 DA015612]; Boehringer-Ingelheim; Bristol-Myers Squibb; Gilead Sciences; GlaxoSmithKline; Merck-Sharp Dohme-Chibret; Pfizer; Roche; Schering Plough; Tibotec; Abbott; Janssen-Cilag FX Supported by the Haute Autorite de Sante, the Institut de Veille Sanitaire, Sidaction, the Agence Nationale de Recherches sur le SIDA et les hepatites virales, the National Institute of Allergy and Infectious Diseases (R01 AI042006, K24 AI062476, P30 AI42851), the National Institute of Mental Health (R01 MH65869), and the National Institute on Drug Abuse (R01 DA015612). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; With the exception of Yazdan Yazdanpanah and Dominique Costagliola, none of the authors report any association that might pose a conflict of interest (e. g. pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding). Dr. Yazdanpanah has received travel grants, consultancy fees and honoraria for presentation at workshops from Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck-Sharp & Dohme-Chibret, Pfizer, Roche, Schering Plough and Tibotec. Dominique Costagliola has received travel grants, consultancy fees, honoraria and study grants from various pharmaceutical companies including Abbott, Boehringer-Ingelheim, Bristol-Myers-Squibb, Gilead Sciences, Glaxo-SmithKline, Janssen-Cilag, Merck-Sharp & Dohme-Chibret and Roche. NR 62 TC 47 Z9 49 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 1 PY 2010 VL 5 IS 10 AR e13132 DI 10.1371/journal.pone.0013132 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 656TI UT WOS:000282359300023 PM 20976112 ER PT J AU Jain, NB Higgins, LD Katz, JN Garshick, E AF Jain, Nitin B. Higgins, Laurence D. Katz, Jeffrey N. Garshick, Eric TI Association of Shoulder Pain With the Use of Mobility Devices in Persons With Chronic Spinal Cord Injury SO PM&R LA English DT Article AB Objective: To assess the prevalence of shoulder pain and its association with the use of assistive devices for mobility in persons with chronic spinal cord injury (SCI). Design: Cross-sectional analysis conducted within a cohort study. Setting: SCI service in a hospital and the community. Participants: Between August 2005 and January 2008, 93 participants with chronic SCI completed a standardized health questionnaire and pain questionnaire. Main Outcome Measures: Shoulder pain in last 6 months elicited by use of the McGill Pain Questionnaire pain diagram. Results: Of the 93 participants, 65 (69.9%) reported pain at any site in the 6 months before testing. Shoulder pain, reported by 39.8% of participants, was the third most common site of pain after the legs and back. When stratified by the use of assistive mobility devices, shoulder pain was reported by 46.7% of motorized wheelchair users, 35.4% of manual wheelchair users, 47.6% of participants using aids such as crutch(es) or canes, and 33.3% of participants walking without assistance (P = .7 for comparison of 4 groups). Conclusions: Shoulder pain is highly prevalent in SCI. The authors of previous studies have largely attributed shoulder pain in SCI to manual wheelchair use. However, our results provide evidence for similarly elevated prevalence of shoulder pain among motorized wheelchair users and those patients using crutches or canes. This finding suggests that in addition to overuse injury from cyclic wheelchair propulsion, the assessment of other mechanical and nonmechanical factors that lead to shoulder pain in SCI is an unmet research need that may have treatment implications. PM R 2010;2:896-900 C1 [Jain, Nitin B.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Jain, Nitin B.; Katz, Jeffrey N.] Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, Boston, MA 02115 USA. [Garshick, Eric] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. [Higgins, Laurence D.; Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Jain, Nitin B.; Higgins, Laurence D.; Katz, Jeffrey N.] Harvard Univ, Sch Med, Boston, MA USA. RP Jain, NB (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. EM njain1@partners.org FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service [B6618R]; National Institute of Child Health and Human Development [RO1 HD042141] FX Research associated with this article was completed with resources provided within the VA Boston Healthcare System. Supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service (Merit Review Grant B6618R), and National Institute of Child Health and Human Development (RO1 HD042141). NR 28 TC 23 Z9 23 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD OCT PY 2010 VL 2 IS 10 BP 896 EP 900 DI 10.1016/j.pmrj.2010.05.004 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V23SE UT WOS:000208361700004 PM 20970758 ER PT J AU Collinger, JL Impink, BG Ozawa, H Boninger, ML AF Collinger, Jennifer L. Impink, Bradley G. Ozawa, Haishin Boninger, Michael L. TI Effect of an Intense Wheelchair Propulsion Task on Quantitative Ultrasound of Shoulder Tendons SO PM&R LA English DT Article AB Objective: To investigate acute ultrasound changes of biceps and supraspinatus tendon appearance after an intense wheelchair propulsion task, and how these changes relate to demographic and biomechanical risk factors. Design: A survey. Setting: Research laboratory and research space at the National Veterans Wheelchair Games. Participants: A convenience sample of 60 manual wheelchair users were recruited through research registries and rehabilitation clinics as well as from participants at the 2007 and 2008 National Veterans Wheelchair Games. The subjects were between 18 and 65 years of age at least 1 year after injury and did not have progressive disabilities. Main Outcome Measures: Quantitative ultrasound (QUS) measures of biceps and supraspinatus tendon appearance, stroke frequency, resultant force, tendinopathy score, and duration of wheelchair use. Results: Biceps tendon appearance after an intense propulsion task was significantly related to chronic biceps tendinopathy, duration of wheelchair use, stroke frequency, and resultant force. The subjects with a higher stroke frequency or resultant force tended to have a brighter, more organized tendon appearance compared with the prepropulsion imaging session (baseline). The subjects with tendinopathy or a longer duration of wheelchair use were more likely to have a darker, diffuse tendon appearance immediately after the propulsion task. Supraspinatus tendon appearance after propulsion was only significantly predicted by baseline QUS measures. Conclusions: QUS has proven to be sensitive to risk factors for tendon pathology. Future studies can apply grayscale-based QUS to study the development and prevention of repetitive strain injuries, particularly on an individual basis. PM R 2010;2:920-925 C1 [Collinger, Jennifer L.; Impink, Bradley G.; Ozawa, Haishin; Boninger, Michael L.] Dept Vet Affairs, Human Engn Res Labs, Pittsburgh, PA USA. [Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. [Collinger, Jennifer L.; Ozawa, Haishin; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Collinger, Jennifer L.; Impink, Bradley G.; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Boninger, ML (reprint author), Dept Vet Affairs, Human Engn Res Labs, Pittsburgh, PA USA. EM boninger@pitt.edu OI Boninger, Michael/0000-0001-6966-919X FU Office of Research and Development, Rehabilitation Research & Development Service, Department of Veterans Affairs [B3142C]; National Institute of Health [R21HD054529]; National Institute on Disability and Rehabilitation Research Rehabilitation Engineering Research Center on Spinal Cord Injury [H133E070024]; National Science Foundation Graduate Research Fellowship FX This material is the result of work supported with resources and the use of facilities at the Human Engineering Research Laboratories, VA Pittsburgh Healthcare System. This study was supported by the Office of Research and Development, Rehabilitation Research & Development Service, Department of Veterans Affairs, Grant B3142C, the National Institute of Health, Grant R21HD054529, the National Institute on Disability and Rehabilitation Research Rehabilitation Engineering Research Center on Spinal Cord Injury, Grant H133E070024, and a National Science Foundation Graduate Research Fellowship. The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. NR 18 TC 10 Z9 10 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD OCT PY 2010 VL 2 IS 10 BP 920 EP 925 DI 10.1016/j.pmrj.2010.06.007 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V23SE UT WOS:000208361700007 PM 20970761 ER PT J AU Harris, AHS Bradley, KA Bowe, T Henderson, P Moos, R AF Harris, Alex H. S. Bradley, Katharine A. Bowe, Thomas Henderson, Patricia Moos, Rudolf TI Associations Between AUDIT-C and Mortality Vary by Age and Sex SO POPULATION HEALTH MANAGEMENT LA English DT Article ID ALCOHOL SCREENING SCORES; IDENTIFICATION TEST AUDIT; ALL-CAUSE MORTALITY; USE DISORDERS; GENERAL-POPULATION; RISK DRINKING; CONSUMPTION; QUESTIONNAIRES; WOMEN; COMORBIDITY AB We sought to determine the sex-and age-specific risk of mortality associated with scores on the 3-item Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) questionnaire using data from a national sample of Veterans Health Administration (VHA) patients. Men (N = 215,924) and women (N = 9168) who completed the AUDIT-C in a patient survey were followed for 24 months. AUDIT-C categories (0, 1-4, 5-8, 9-12) were evaluated as predictors of mortality in logistic regression models, adjusted for age, race, education, marital status, smoking, depression, and comorbidities. For women, AUDIT-C scores of 9-12 were associated with a significantly increased risk of death compared to the AUDIT-C 1-4 group (odds ratio [OR] 7.09; 95% confidence interval [CI] = 2.67, 18.82). For men overall, AUDIT-C scores of 5-8 and 9-12 were associated with increased risk of death compared to the AUDIT-C 1-4 group (OR 1.13, 95% CI = 1.05, 1.21, and OR 1.63, 95% CI = 1.45, 1.84, respectively) but these associations varied by age. These results provide sex-and age-tailored risk information that clinicians can use in evidence-based conversations with patients about the health-related risks of their alcohol consumption. This study adds to the growing literature establishing the AUDIT-C as a scaled marker of alcohol-related risk or "vital sign" that might facilitate the detection and management of alcohol-related risks and problems. (Population Health Management 2010;13:263-268) C1 [Harris, Alex H. S.; Bowe, Thomas; Henderson, Patricia; Moos, Rudolf] Stanford Univ, Sch Med, VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Bradley, Katharine A.] Univ Washington, Sch Med, Seattle, WA USA. [Bradley, Katharine A.] Puget Sound HC Syst, Seattle, WA USA. RP Harris, AHS (reprint author), Stanford Univ, Sch Med, VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM Alexander.Harris2@va.gov FU National Institute of Alcohol and Alcoholism [R03 AA016793-01]; VA Office of Quality and Performance FX This work was made possible through a grant from the National Institute of Alcohol and Alcoholism (R03 AA016793-01) and support from the VA Office of Quality and Performance. The views presented in this paper do not necessarily represent the views of the Department of Veterans Affairs. NR 33 TC 19 Z9 19 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1942-7891 J9 POPUL HEALTH MANAG JI Popul. Health Manag. PD OCT PY 2010 VL 13 IS 5 BP 263 EP 268 DI 10.1089/pop.2009.0060 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 658BJ UT WOS:000282463400005 PM 20879907 ER PT J AU Stetler, RA Gan, Y Zhang, WT Liou, AK Gao, YQ Cao, GD Chen, J AF Stetler, R. Anne Gan, Yu Zhang, Wenting Liou, Anthony K. Gao, Yanqin Cao, Guodong Chen, Jun TI Heat shock proteins: Cellular and molecular mechanisms in the central nervous system SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Heat shock protein; Synaptic transmission; Protein degradation; Cell death; Cerebral ischemia; Parkinson's disease; Huntington's disease; Alzheimer's disease; Prion; Charcot-Marie-Tooth ID CHAPERONE-MEDIATED AUTOPHAGY; FOCAL CEREBRAL-ISCHEMIA; ENDOPLASMIC-RETICULUM STRESS; CYSTEINE-STRING PROTEIN; ALPHA-SYNUCLEIN AGGREGATION; CLATHRIN-COATED VESICLES; N-TERMINAL KINASE; INHIBITS HUNTINGTIN AGGREGATION; HUMAN NEUROMUSCULAR DISORDERS; UBIQUITIN-PROTEASOME PATHWAY AB Emerging evidence indicates that heat shock proteins (HSPs) are critical regulators in normal neural physiological function as well as in cell stress responses. The functions of HSPs represent an enormous and diverse range of cellular activities, far beyond the originally identified roles in protein folding and chaperoning. HSPs are now understood to be involved in processes such as synaptic transmission, autophagy, ER stress response, protein kinase and cell death signaling. In addition, manipulation of HSPs has robust effects on the fate of cells in neurological injury and disease states. The ongoing exploration of multiple HSP superfamilies has underscored the pluripotent nature of HSPs in the cellular context, and has demanded the recent revamping of the nomenclature referring to these families to reflect a re-organization based on structure and function. In keeping with this re-organization, we first discuss the HSP superfamilies in terms of protein structure, regulation, expression and distribution in the brain. We then explore major cellular functions of HSPs that are relevant to neural physiological states, and from there we discuss known and proposed HSP impacts on major neurological disease states. This review article presents a three-part discussion on the array of HSP families relevant to neuronal tissue, their cellular functions, and the exploration of therapeutic targets of these proteins in the context of neurological diseases. Published by Elsevier Ltd. C1 [Stetler, R. Anne] Univ Pittsburgh, Sch Med, Dept Neurol, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Stetler, R. Anne; Cao, Guodong; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15261 USA. [Stetler, R. Anne; Gan, Yu; Zhang, Wenting; Gao, Yanqin; Cao, Guodong; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China. RP Stetler, RA (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. EM stetlerra@upmc.edu; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU American Heart Association [09POST22006065]; National Institutes of Health [NS36736, NS43802, NS45048]; VA Merit Review Grant; Chinese National Science Foundation [30870794, 30670642] FX We thank Armando Signore for the artwork, Carol Culver and Sulaiman Hassan for editorial assistance, and Pat Strickler for secretarial support. This work was supported by funds from the American Heart Association (09POST22006065 to R.A.S.), the National Institutes of Health (NS36736, NS43802 and NS45048 to J.C.), the VA Merit Review Grant (to J.C.) and the Chinese National Science Foundation (30870794, 30670642 to Y.G.). NR 322 TC 85 Z9 89 U1 2 U2 39 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD OCT PY 2010 VL 92 IS 2 BP 184 EP 211 DI 10.1016/j.pneurobio.2010.05.002 PG 28 WC Neurosciences SC Neurosciences & Neurology GA 661LG UT WOS:000282729200005 PM 20685377 ER PT J AU Merkulova, M McKee, M Dip, PV Gruber, G Marshansky, V AF Merkulova, Maria McKee, Mary Dip, Phat Vinh Grueber, Gerhard Marshansky, Vladimir TI N-terminal domain of the V-ATPase a2-subunit displays integral membrane protein properties SO PROTEIN SCIENCE LA English DT Article DE V-ATPase; a2-subunit; integral monotopic domain; solubility; detergent; refolding ID CIRCULAR-DICHROISM SPECTRA; SIZE-EXCLUSION CHROMATOGRAPHY; RENAL TUBULAR-ACIDOSIS; YEAST VACUOLAR ATPASE; HUMAN H+-ATPASE; SECONDARY STRUCTURE; INCLUSION-BODIES; SUBUNIT INTERACTIONS; ESCHERICHIA-COLI; PROTON PUMP AB V-ATPase is a multisubunit membrane complex that functions as nanomotor coupling ATP hydrolysis with proton translocation across biological membranes. Recently, we uncovered details of the mechanism of interaction between the N-terminal tail of the V-ATPase a2-subunit isoform (a2N(1-402)) and ARNO, a GTP/GDP exchange factor for Art-family small GTPases. Here, we describe the development of two methods for preparation of the a2N(1-402) recombinant protein in milligram quantities sufficient for further biochemical, biophysical, and structural studies. We found two alternative amphiphilic chemicals that were required for protein stability and solubility during purification: (i) non-detergent sulfobetaine NDSB-256 and (ii) zwitterionic detergent FOS-CHOLINE (R) 12 (FC-12). Moreover, the other factors including mild alkaline pH, the presence of reducing agents and the absence of salt were beneficial for stabilization and solubilization of the protein. A preparation of a2N(1-402) in NDSB-256 was successfully used in pull-down and BlAcore (TM) protein-protein interaction experiments with ARNO, whereas the purity and quality of the second preparation in FC-12 was validated by size-exclusion chromatography and CD spectroscopy. Surprisingly, the detergent requirement for stabilization and solubilization of a2N(1-402) and its cosedimentation with liposomes were different from peripheral domains of other transmembrane proteins. Thus, our data suggest that in contrast to current models, so called "cytosolic" tail of the a2-subunit might actually be embedded into and/or closely associated with membrane phospholipids even in the absence of any obvious predicted transmembrane segments. We propose that a2N(1-402) should be categorized as an integral monotopic domain of the a2-subunit isoform of the V-ATPase. C1 [Merkulova, Maria; McKee, Mary; Marshansky, Vladimir] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Merkulova, Maria; McKee, Mary; Marshansky, Vladimir] Massachusetts Gen Hosp, Div Nephrol, Simches Res Ctr, Boston, MA 02114 USA. [Merkulova, Maria; McKee, Mary; Marshansky, Vladimir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Dip, Phat Vinh; Grueber, Gerhard] Nanyang Technol Univ, Sch Biol Sci, Div Struct & Computat Biol, Singapore 637551, Singapore. RP Marshansky, V (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, 185 Cambridge St,CPZN,Suite 8212, Boston, MA 02114 USA. EM vladimir_marshansky@hms.harvard.edu OI Dip, Phat Vinh/0000-0002-1535-9644 FU National Institutes of Health (NIH) [DK038452]; Boston Area Diabetes Endocrinology Research Center (BADERC) [DK057521-08]; A*STAR BMRC [09/1/22/19/609] FX Grant sponsor: National Institutes of Health (NIH); Grant number: DK038452; Grant sponsor: Boston Area Diabetes Endocrinology Research Center (BADERC); Grant number: DK057521-08; Grant sponsor: A*STAR BMRC; Grant number: 09/1/22/19/609. NR 47 TC 10 Z9 10 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD OCT PY 2010 VL 19 IS 10 BP 1850 EP 1862 DI 10.1002/pro.470 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 661HO UT WOS:000282716900005 PM 20669186 ER PT J AU McCarthy, JF Valenstein, M Zivin, K Zeber, JE Kilbourne, AM AF McCarthy, John F. Valenstein, Marcia Zivin, Kara Zeber, John E. Kilbourne, Amy M. TI Access-Related Measures and Out-of-System Utilization Among Veterans With Bipolar Disorder SO PSYCHIATRIC SERVICES LA English DT Article ID SERIOUS MENTAL-ILLNESS; HEALTH-CARE; MEDICAL-CARE; VA; SATISFACTION; SERVICES; BARRIERS AB Objective: This study examined associations between access-related measures and out-of-system health services utilization (general medicine and mental health services) among patients with bipolar disorder at a U.S. Department of Veterans Affairs (VA) medical center. Methods: VA patients (N=391) with bipolar disorder answered questions about health services access (non-VA insurance coverage, travel distance to their VA facility, service-connected disability status, and difficulty receiving needed mental health care) and out-of-system services utilization. Multivariable Tobit regression was used to evaluate associations between access measures and propensity to receive out-of-system services. Results: More than half the veterans (56%) reported some non-VA utilization. Out-of-system utilization was more likely among patients who were married, younger, homeless, with private insurance, without service-connected disabilities, and who reported access difficulties. Conclusions: Out-of-system utilization was associated with multiple measures of access and indicators specific to VA and non-VA providers. Enhancing health system access for patients with bipolar disorder may reduce out-of-system utilization, potentially enhancing continuity of care. (Psychiatric Services 61: 1035-1038, 2010) C1 [McCarthy, John F.] US Dept Vet Affairs, Natl Serious Mental Illness Treatment Resource &, Ann Arbor, MI 48113 USA. Ctr Clin Management Res, Ann Arbor, MI 48113 USA. RP McCarthy, JF (reprint author), US Dept Vet Affairs, Natl Serious Mental Illness Treatment Resource &, POB 130170, Ann Arbor, MI 48113 USA. EM john.mccarthy2@va.gov FU VA [IIR 02-283] FX This study was supported by VA grant IIR 02-283. NR 14 TC 3 Z9 3 U1 0 U2 4 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 OCT PY 2010 VL 61 IS 10 BP 1035 EP 1038 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 657WB UT WOS:000282448500018 PM 20889645 ER PT J AU Eddy, KT Swanson, SA Crosby, RD Franko, DL Engel, S Herzog, DB AF Eddy, K. T. Swanson, S. A. Crosby, R. D. Franko, D. L. Engel, S. Herzog, D. B. TI How should DSM-V classify eating disorder not otherwise specified (EDNOS) presentations in women with lifetime anorexia or bulimia nervosa? SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Anorexia nervosa; bulimia nervosa; classification; eating disorder not otherwise specified; longitudinal ID DIAGNOSTIC CROSSOVER; PURGING DISORDER; VALIDITY; RELAPSE AB Objective. Anorexia nervosa (AN) and bulimia nervosa (BN) are marked by longitudinal symptom fluctuations. DSM-IV-TR does not address how to classify eating disorder (ED) presentations in individuals who no longer meet full criteria for these disorders. To consider this issue, we examined subthreshold presentations in women with initial diagnoses of AN and BN. Method. A total of 246 women with AN or BN were followed for a median of 9 years; weekly symptom data were collected at frequent intervals using the Longitudinal Interval Follow-up Evaluation of Eating Disorders (LIFE-EAT-II). Outcomes were ED presentations that were subthreshold for >= 3 months, including those narrowly missing full criteria for AN or BN, along with binge eating disorder (BED) and purging disorder. Results. During follow-up, most women (77.6%) experienced a subthreshold presentation. Subthreshold presentation was related to intake diagnosis (Wald chi(2)=8.065, df=2, p=0.018). Individuals with AN most often developed subthreshold presentations resembling AN; those with BN were more likely to develop subthreshold BN. Purging disorder was experienced by half of those with BN and one-quarter of those with AN binge/purge type (ANBP); BED occurred in 20% with BN. Transition from AN or BN to most subthreshold types was associated with improved psychosocial functioning (p<0.001). Conclusions. Subthreshold presentations in women with lifetime AN and BN were common, resembled the initial diagnosis, and were associated with modest improvements in psychosocial functioning. For most with lifetime AN and BN, subthreshold presentations seem to represent part of the course of illness and to fit within the original AN or BN diagnosis. C1 [Eddy, K. T.; Franko, D. L.; Herzog, D. B.] Massachusetts Gen Hosp, Dept Psychiat, Harris Ctr, Boston, MA 02214 USA. [Swanson, S. A.] NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. [Crosby, R. D.; Engel, S.] Neuropsychiat Res Inst, Fargo, ND USA. [Crosby, R. D.; Engel, S.] Univ N Dakota, Sch Med & Hlth Sci, Dept Clin Neurosci, Fargo, ND USA. [Franko, D. L.] Northwestern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA USA. RP Eddy, KT (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Harris Ctr, 2 Longfellow Pl,Ste 200, Boston, MA 02214 USA. EM keddy@partners.org OI Crosby, Ross/0000-0001-9131-1629 FU [RO1 MH038333]; [F32 MH084396] FX Support for this research was provided by RO1 MH038333 (PI D.B.H.) and F32 MH084396 (PI K.T.E.). NR 17 TC 10 Z9 10 U1 1 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD OCT PY 2010 VL 40 IS 10 BP 1735 EP 1744 DI 10.1017/S0033291709992200 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 644VF UT WOS:000281408700015 PM 20047706 ER PT J AU Zhang, XY Xiu, MH Chen, DC Yang, FD Wu, GY Lu, L Kosten, TA Kosten, TR AF Zhang, Xiang Yang Xiu, Mei Hong Chen, Da Chun Yang, Fu De Wu, Gui Ying Lu, Lin Kosten, Therese A. Kosten, Thomas R. TI Nicotine dependence and serum BDNF levels in male patients with schizophrenia SO PSYCHOPHARMACOLOGY LA English DT Article DE Schizophrenia; Smoking; Nicotine; Brain-derived neurotrophic factor; Neurotrophin ID NEUROTROPHIC FACTOR BDNF; FACTOR MESSENGER-RNA; LONG-TERM TREATMENT; RAT-BRAIN; EXPERIMENTAL PARKINSONISM; STRIATAL INCREASE; BIPOLAR DISORDER; DECREASED LEVELS; KNOCKOUT MICE; SMOKING AB Schizophrenia is associated with a significantly high prevalence of smoking. Upregulation of neurotrophins by nicotine is well established. Accumulating evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. The purposes of this study were to compare BDNF levels in smokers to nonsmokers with schizophrenia and examine the association between BDNF levels and psychopathological symptoms. Serum BDNF levels were measured in 139 male inpatients with DSM-IV schizophrenia: 102 smokers and 37 nonsmokers. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). The positive PANSS symptoms were lower in smokers than in nonsmokers, while the negative symptoms were lower in those who smoked more cigarettes. BDNF levels were significantly higher in smokers than in nonsmokers (p < 0.05). Higher BDNF levels correlated with fewer negative symptoms and with smoking more cigarettes. The fewer positive symptoms in smokers and fewer negative symptoms in those who smoked more cigarettes may be associated with nicotine-induced upregulation of BDNF. C1 [Zhang, Xiang Yang; Kosten, Thomas R.] VA Med Ctr, Houston, TX 77030 USA. [Zhang, Xiang Yang; Xiu, Mei Hong; Chen, Da Chun; Yang, Fu De] Beijing HuiLongGuan Hosp, Ctr Biol Psychiat, Beijing 100096, Peoples R China. [Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. [Zhang, Xiang Yang; Wu, Gui Ying; 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; US National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639]; VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC) 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), US National Institute of Health K05-DA0454, P50-DA18827, and U01-MH79639. NR 63 TC 14 Z9 16 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2010 VL 212 IS 3 BP 301 EP 307 DI 10.1007/s00213-010-1956-y PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 662RD UT WOS:000282828100002 PM 20661552 ER PT J AU Yehuda, R Flory, JD Pratchett, LC Buxbaum, J Ising, M Holsboer, F AF Yehuda, Rachel Flory, Janine D. Pratchett, Laura C. Buxbaum, Joseph Ising, Marcus Holsboer, Florian TI Putative biological mechanisms for the association between early life adversity and the subsequent development of PTSD SO PSYCHOPHARMACOLOGY LA English DT Article DE PTSD; Early life stress; Cortisol; Gene x environment interaction; Gene expression; Epigenetics; Glucocorticoid receptor ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; PERIPHERAL MONONUCLEAR LEUKOCYTES; PITUITARY-ADRENAL RESPONSES; NATIONAL COMORBIDITY SURVEY; DEXAMETHASONE-SUPPRESSION; GLUCOCORTICOID-RECEPTOR; DNA METHYLATION; HOLOCAUST SURVIVORS; MATERNAL-BEHAVIOR AB Early Life Stress (ELS) increases risk for both adult traumatization and posttraumatic stress disorder (PTSD). Adult PTSD may also reflect a continuation of a response to an earlier exposure to adversity. Given similarities between neuroendocrine aspects of PTSD and ELS, such as in reduced cortisol signaling and glucocorticoid receptor (GR) responsiveness, some aspects of the biology of PTSD may reflect biological correlates of risk. This paper will examine how empirical findings regarding the biological basis of ELS can inform our understanding of the neuroendocrinology of PTSD. This paper will also propose a hypothetical model to guide future research that integrates genetic, epigenetic, neuroendocrine, and psychological observations to understand the contribution of ELS neurobiology to PTSD. Recent genetic findings demonstrate heritable aspects of at least some of these cortisol-related disturbances. Furthermore, ELS may produce at least some of the PTSD-associated changes in glucocorticoid responsiveness through epigenetic mechanisms such as developmental programming. These, then, may contribute to enduring changes in stress responsiveness as well as enhanced risk for adult exposure and PTSD. Molecular mechanisms associated with gene x environment interactions or GR programming are essential in explaining current observations in the neuroendocrinology of PTSD that have been difficult to understand through the lens of contemporary stress theory. C1 [Yehuda, Rachel; Flory, Janine D.; Pratchett, Laura C.] James J Peters Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. [Yehuda, Rachel; Buxbaum, Joseph] Mt Sinai Sch Med, Dept Psychiat & Neurobiol, New York, NY USA. [Flory, Janine D.] CUNY, Queens Coll, Dept Psychol, New York, NY USA. [Flory, Janine D.] CUNY, Grad Ctr, New York, NY USA. [Ising, Marcus; Holsboer, Florian] Max Planck Inst Psychiat, D-80804 Munich, Germany. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, Dept Psychiat, 526 OOMH,130 W Kingsbridge Rd, Bronx, NY USA. EM rachel.yehuda@va.gov OI Buxbaum, Joseph/0000-0001-8898-8313 FU NIMH [MH088101, DOD PT073577, 10164894] FX This work was supported by the following funding: NIMH MH088101, DOD PT073577 and 10164894, and VA Merit Review to RY. We thank Dr. Linda M. Bierer for her careful reading of this manuscript and thoughtful suggestions. NR 130 TC 80 Z9 83 U1 8 U2 38 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2010 VL 212 IS 3 BP 405 EP 417 DI 10.1007/s00213-010-1969-6 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 662RD UT WOS:000282828100011 PM 20706708 ER PT J AU Bruner, DW Hanisch, LJ Reeve, BB Minasian, LM Rowland, JH O'Mara, AM Sit, L Sloan, JA Cleeland, CS Denicoff, AM Trimble, EL Clauser, SB Geoghegan, C Paul, DB Abernethy, AP Schrag, D Basch, EM AF Bruner, Deborah Watkins Hanisch, Laura J. Reeve, Bryce B. Minasian, Lori M. Rowland, Julia H. O'Mara, Ann M. Sit, Laura Sloan, Jeff A. Cleeland, Charles S. Denicoff, Andrea M. Trimble, Edward L. Clauser, Steven B. Geoghegan, Cindy Paul, Diane B. Abernethy, Amy P. Schrag, Deborah Basch, Ethan M. TI Perceived Barriers to Implementing the Patient-Reported Outcomes-Common Toxicity Criteria Adverse Event (PRO-CTCAE) System in Cancer Clinical Trials SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 [Bruner, Deborah Watkins] Univ Penn, Sch Nursing, Biobehav Hlth Sci Div, Philadlephia, PA USA. [Hanisch, Laura J.] Univ Penn, Psychiat, Philadelphia, PA 19104 USA. [Reeve, Bryce B.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Minasian, Lori M.; O'Mara, Ann M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Rowland, Julia H.; Clauser, Steven B.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Sit, Laura; Basch, Ethan M.] Mem Sloan Kettering Canc Ctr, Epidemiol & Biostat, New York, NY 10021 USA. [Sloan, Jeff A.] Mayo Clin, Hlth Sci Res, Rochester, MN USA. [Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Symptom Res, Houston, TX 77030 USA. [Denicoff, Andrea M.; Trimble, Edward L.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Geoghegan, Cindy] Patient & Partners LLC, Madison, CT USA. [Paul, Diane B.] Patient Advocate, Brooklyn, NY USA. [Abernethy, Amy P.] Duke Univ, Sch Med, Med, Durham, NC USA. [Schrag, Deborah] Dana Farber Canc Inst, Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT PY 2010 VL 19 SU 1 MA 1006 BP 31 EP 32 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V38QU UT WOS:000209358700096 ER PT J AU Basch, E Reeve, B Cleeland, CS Sloan, JA Schrag, D Atkinson, TM Mendoza, TR Hay, JL Abernethy, AP Minasian, L Kwitkowski, V Trentacosti, AM Burke, L Sit, L Bruner, DW AF Basch, Ethan Reeve, Bryce Cleeland, Charles S. Sloan, Jeff A. Schrag, Deborah Atkinson, Thomas M. Mendoza, Tito R. Hay, Jennifer L. Abernethy, Amy P. Minasian, Lori Kwitkowski, Virginia Trentacosti, Ann Marie Burke, Laurie Sit, Laura Bruner, Deborah W. TI Development of the Patient-Reported Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 [Basch, Ethan; Sit, Laura] Mem Sloan Kettering Canc Ctr, Epidemiol & Biostat, New York, NY 10021 USA. [Reeve, Bryce] NCI, Outcomes Res, Bethesda, MD 20892 USA. [Cleeland, Charles S.; Mendoza, Tito R.] Univ Texas MD Anderson Canc Ctr, Symptom Res, Houston, TX 77030 USA. [Sloan, Jeff A.] Mayo Clin, Biomed Stat & Informat, Rochester, MN USA. [Schrag, Deborah] Dana Farber Canc Inst, Med, Boston, MA 02115 USA. [Atkinson, Thomas M.; Hay, Jennifer L.] Mem Sloan Kettering Canc Ctr, Psychiat & Behav Sci, New York, NY 10021 USA. [Abernethy, Amy P.] Duke Univ, Sch Med, Med, Durham, NC USA. [Minasian, Lori] NCI, Canc Prevent, Rockville, MD USA. [Kwitkowski, Virginia] US FDA, Drug Oncol Prod, Silver Spring, MD USA. [Burke, Laurie] US FDA, Study Endpoints & Labeling Dev, Silver Spring, MD USA. [Bruner, Deborah W.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT PY 2010 VL 19 SU 1 MA 161439 BP 50 EP 51 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA V38QU UT WOS:000209358700153 ER PT J AU Kaafarani, HMA Rosen, AK Nebeker, JR Shimada, S Mull, HJ Rivard, PE Savitz, L Helwig, A Shin, MH Itani, KMF AF Kaafarani, Haytham M. A. Rosen, Amy K. Nebeker, Jonathan R. Shimada, Stephanie Mull, Hillary J. Rivard, Peter E. Savitz, Lucy Helwig, Amy Shin, Marlena H. Itani, Kamal M. F. TI Development of trigger tools for surveillance of adverse events in ambulatory surgery SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID RETURN HOSPITAL VISITS; POSTDISCHARGE SYMPTOMS; ANALGESIA; DISCHARGE; QUALITY; PROGRAM AB Background The trigger tool methodology uses clinical algorithms applied electronically to 'flag' medical records where adverse events (AEs) have most likely occurred. The authors sought to create surgical triggers to detect AEs in the ambulatory care setting. Methods Four consecutive steps were used to develop ambulatory surgery triggers. First, the authors conducted a comprehensive literature review for surgical triggers. Second, a series of multidisciplinary focus groups (physicians, nurses, pharmacists and information technology specialists) provided user input on trigger selection. Third, a clinical advisory panel designed an initial set of 10 triggers. Finally, a three-phase Delphi process (surgical and trigger tool experts) evaluated and rated the suggested triggers. Results The authors designed an initial set of 10 surgical triggers including five global triggers (flagging medical records for the suspicion of any AE) and five AE-specific triggers (flagging medical records for the suspicion of specific AEs). Based on the Delphi rating of the trigger's utility for system-level interventions, the final triggers were: (1) emergency room visit(s) within 21 days from surgery; (2) unscheduled readmission within 30 days from surgery; (3) unscheduled procedure (interventional radiological, urological, dental, cardiac or gastroenterological) or reoperation within 30 days from surgery; (4) unplanned initial hospital length of stay more than 24 h; and (5) lower-extremity Doppler ultrasound order entry and ICD code for deep vein thrombosis or pulmonary embolus within 30 days from surgery. Conclusion The authors therefore propose a systematic methodology to develop trigger tools that takes into consideration previously published work, end-user preferences and expert opinion. C1 [Kaafarani, Haytham M. A.; Itani, Kamal M. F.] VA Boston Healthcare Syst, Dept Surg, W Roxbury, MA USA. [Kaafarani, Haytham M. A.; Rosen, Amy K.; Shimada, Stephanie; Mull, Hillary J.; Rivard, Peter E.; Shin, Marlena H.] CHQOER, Bedford, MA USA. [Kaafarani, Haytham M. A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Rosen, Amy K.; Shimada, Stephanie; Mull, Hillary J.; Shin, Marlena H.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Nebeker, Jonathan R.] VA Salt Lake City Geriatr Res Educ & Clin Ctr, Salt Lake City, UT USA. [Nebeker, Jonathan R.] Univ Utah, Salt Lake City, UT USA. [Rivard, Peter E.] Suffolk Univ, Boston, MA 02114 USA. [Savitz, Lucy] Intermt Healthcare, Salt Lake City, UT USA. [Helwig, Amy] Agcy Healthcare Res & Qual, Rockville, MD USA. [Itani, Kamal M. F.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Itani, KMF (reprint author), VABHCS 112, Dept Surg, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM kitani@va.gov FU Agency for Healthcare Research and Quality (AHRQ) [HHSA290200600012540] FX Funding was provided by the Agency for Healthcare Research and Quality (AHRQ), contract no HHSA290200600012540. NR 17 TC 13 Z9 13 U1 1 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD OCT PY 2010 VL 19 IS 5 BP 425 EP 429 DI 10.1136/qshc.2008.031591 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 690UB UT WOS:000285032700013 PM 20513790 ER PT J AU Boockvar, KS Livote, EE Goldstein, N Nebeker, JR Siu, A Fried, T AF Boockvar, K. S. Livote, E. E. Goldstein, N. Nebeker, J. R. Siu, A. Fried, T. TI Electronic health records and adverse drug events after patient transfer SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID MEDICATION RECONCILIATION; SYSTEM; CARE; DISCREPANCIES; SAFETY AB Background Our objective was to examine the frequencies of medication error and adverse drug events (ADEs) at the time of patient transfer in a system with an electronic health record (EHR) as compared with a system without an ERR. It was hypothesised that the frequencies of these events would be lower in the EHR system because of better information exchange across sites of care. Methods 469 patients transferred between seven nursing homes and three hospitals in New York and Connecticut between 1999 and 2005 were followed retrospectively. Two groups of patients were compared: OS Veterans Affairs (VA) patients, with an EHR, and non-VA patients, without an EHR, on the following measures: (1) medication prescribing discrepancies at nursing home/hospital transfer, (2) high-risk medication discrepancies and (3) ADEs caused by medication discrepancies according to structured medical record review by pairs of physician and pharmacist raters. Results The overall incidence of ADEs caused by medication discrepancies was 0.20 per hospitalisation episode. After controlling for demographic and clinical covariates, there were no significant differences between VA and non-VA groups in medication discrepancies (mean difference 0.02; 95% CI -0.81 to 0.85), high-risk medication discrepancies ( 0.18; 95%CI -0.22 to 0.58) or occurrence of an ADEs caused by a medication discrepancy (OR 0.96; 95% CI 0.18 to 5.01). Conclusions There was no difference, with and without an EHR, in the occurrence of medication discrepancies or ADEs caused by medication discrepancies at the time of transfer between sites of care. Reducing such problems may require specialised computer tools to facilitate medication review. C1 [Boockvar, K. S.; Livote, E. E.; Goldstein, N.; Siu, A.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Boockvar, K. S.; Goldstein, N.; Siu, A.] Mt Sinai Sch Med, Dept Geriatr, New York, NY USA. [Boockvar, K. S.; Goldstein, N.; Siu, A.] Mt Sinai Sch Med, Dept Palliat Med, New York, NY USA. [Boockvar, K. S.] Jewish Home Lifecare, New York, NY USA. [Nebeker, J. R.] VA Geriatr Res Educ & Clin Ctr, Salt Lake City, UT USA. [Fried, T.] Yale Univ, Sch Med, New Haven, CT USA. [Fried, T.] VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, West Haven, CT USA. RP Boockvar, KS (reprint author), James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU VA Health Services Research and Development Service; Now York State Department of Health; Mount Sinai Practice Improvement Cluster; NIH [5K23AG025933-04] FX Financial support was provided by the VA Health Services Research and Development Service, the Now York State Department of Health and the Mount Sinai Practice Improvement Cluster. Dr. Goldstein was supported by 5K23AG025933-04 from NIH. NR 24 TC 8 Z9 10 U1 2 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD OCT PY 2010 VL 19 IS 5 AR e16 DI 10.1136/qshc.2009.033050 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 690UB UT WOS:000285032700036 PM 20724395 ER PT J AU Singh, H Petersen, LA Daci, K Collins, C Khan, M El-Serag, HB AF Singh, Hardeep Petersen, Laura A. Daci, Kuang Collins, Clyde Khan, Myrna El-Serag, Hashem B. TI Reducing referral delays in colorectal cancer diagnosis: is it about how you ask? SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID OCCULT BLOOD-TEST; SCREENING COLONOSCOPY; MALPRACTICE CLAIMS; FOLLOW-UP; COMMUNICATION; QUALITY; CONSULTATIONS; DETERMINANTS; SURVIVAL; IMPROVE AB Objectives Delays in colorectal cancer (CRC) diagnosis related to colonoscopy referrals are not well studied. The authors tested whether certain details of information transmitted through computerised provider order entry (CPOE)-based referrals affected timeliness of diagnostic colonoscopy for patients with newly diagnosed CRC. Methods The authors studied a 6-year cohort of all newly diagnosed patients with CRC at a large tertiary care Veterans Affairs hospital and its affiliated multispecialty clinics. Referring providers included primary care clinicians, resident trainees and other specialists. From the colonoscopy referral preceding CRC diagnosis, the authors determined request date, type and frequency of diagnostic clues provided (symptoms, signs, test results), notation of in and documented evidence of verbal contact between referring provider and consultant to expedite referral. The authors compared distributions of proportions of diagnostic clues between patients with a lag of >60 and <= 60 day, and examined predictors of lag time. Results Of 367 electronic referrals identified with a median lag of 57 days, 178 (48.5%) had a lag of >60 days. Referrals associated with longer lag times included those with 'positive faecal occult blood test' (92 days, p<0.0001), 'haematochesia' (75 days, p=0.02), 'history of polyps' (221 days, p=0.0006) and when 'screening' (vs specific symptoms) was given as the reason for diagnostic colonoscopy (203 days, p=0.002). Independent predictors of shorter wait times included three diagnostic clues, notation of urgency and documentation of verbal contact. Conclusions Attention to certain details of diagnostic information provided to consultants through CPOE-based referrals may help reduce delays in CRC diagnosis. C1 [Singh, Hardeep; Petersen, Laura A.; Khan, Myrna] Michael E DeBakey VA Med Ctr, Houston VA HSR&D Ctr Excellence, Houston, TX USA. [Singh, Hardeep; Petersen, Laura A.; Khan, Myrna] Michael E DeBakey VA Med Ctr, Ctr Inquiry Improve Outpatient Safety Effect Elec, Houston, TX USA. [Singh, Hardeep; Petersen, Laura A.; Khan, Myrna] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [El-Serag, Hashem B.] Michael E DeBakey VA Med Ctr, Sect Gastroenterol & Hepatol, Houston, TX USA. [El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.tmc.edu FU NIH [K23, K23CA125585]; VA National Center of Patient Safely; Houston VA HSR&D Center of Excellence [HFP90-020] FX The study was supported by an NIH K23 career development award (K23CA125585) to HS. the VA National Center of Patient Safely, and in part the Houston VA HSR&D Center of Excellence (HFP90-020). NR 30 TC 17 Z9 17 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD OCT PY 2010 VL 19 IS 5 AR e27 DI 10.1136/qshc.2009.033712 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 690UB UT WOS:000285032700047 PM 20584706 ER PT J AU Palmer, WE AF Palmer, William E. TI Femoroacetabular Impingement: Caution Is Warranted in Making Imaging-based Assumptions and Diagnoses SO RADIOLOGY LA English DT Editorial Material ID TOTAL HIP-ARTHROPLASTY; ACETABULAR LABRUM; OSTEOARTHRITIS; ARTHROSCOPY; DYSPLASIA; TEARS C1 Massachusetts Gen Hosp, Dept Musculoskeletal Imaging, Boston, MA 02114 USA. RP Palmer, WE (reprint author), Massachusetts Gen Hosp, Dept Musculoskeletal Imaging, 55 Fruit St,YAW 6030, Boston, MA 02114 USA. EM wpalmer@partners.org NR 27 TC 31 Z9 32 U1 1 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 OCT PY 2010 VL 257 IS 1 BP 4 EP 7 DI 10.1148/radiol.10091298 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 658XH UT WOS:000282527200002 PM 20851933 ER PT J AU Walsh, CJ Phan, CM Misra, M Bredella, MA Miller, KK Fazeli, PK Bayraktar, HH Klibanski, A Gupta, R AF Walsh, Conor J. Phan, Catherine M. Misra, Madhusmita Bredella, Miriam A. Miller, Karen K. Fazeli, Pouneh K. Bayraktar, Harun H. Klibanski, Anne Gupta, Rajiv TI Women with Anorexia Nervosa: Finite Element and Trabecular Structure Analysis by Using Flat-Panel Volume CT SO RADIOLOGY LA English DT Article ID QUANTITATIVE COMPUTED-TOMOGRAPHY; DISTAL RADIUS; BONE; IMAGES; MICROARCHITECTURE; OSTEOPOROSIS; PREVALENCE; STRENGTH; FRACTURE; DENSITY AB Purpose: To use finite element modeling based on flat-panel volume computed tomography (CT) and bone mineral density (BMD) provided by dual-energy x-ray absorptiometry (DXA) to compare bone failure load, stiffness, and trabecular structure in women with anorexia nervosa (AN) and age-matched normal-weight control subjects. Materials and Methods: The study was approved by the institutional review board and complied with HIPAA guidelines. Informed consent was obtained. Fourteen women, eight with AN (mean age, 26.6 years) and six control subjects (mean age, 26.3 years), underwent flat-panel volume CT of the distal radius to determine apparent trabecular bone volume fraction (BV/TV), apparent trabecular number (TbN), apparent trabecular thickness (TbTh), and apparent trabecular separation (TbSp). Bone strength and stiffness were calculated from uniaxial compression tests by using finite element models created from flat-panel volume CT. DXA was used to determine BMD of the radius, lumbar spine, and hip. Means +/- standard deviations of all variables were calculated for both groups and compared (Student t test). Univariate regression analysis and stepwise regression modeling were performed. Results: Patients with AN had lower values for stiffness (284.77 kN/mm +/- 76.14 vs 389.97 kN/mm +/- 84.90, P=.04), failure load (4.98 kN +/- 1.23 vs 7.01 kN +/- 1.52, P=.02), BV/TV (0.32% +/- 0.09 vs 0.44% +/- 0.02, P=.007), and TbN (1.15 mm(-3) +/- 0.20 vs 1.43 mm(-3) +/- 0.13, P=.008) and higher values for TbSp (0.62 mm +/- 0.20 vs 0.40 mm +/- 0.04, P =.02) compared with normal-weight control subjects. TbTh was lower in women with AN (P=.1). BMD measurements were significantly lower for the AN group. BMD measurements and trabecular parameters (except TbTh) correlated with stiffness and failure load (r = 0.58 to 0.83). Conclusion: Failure load and stiffness are abnormal in women with AN compared with those in normal-weight control subjects and correlate with BMD and trabecular parameters. (C) RSNA, 2010 C1 [Walsh, Conor J.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Phan, Catherine M.; Bredella, Miriam A.; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Misra, Madhusmita; Miller, Karen K.; Fazeli, Pouneh K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. [Bayraktar, Harun H.] Dassault Syst Simulia, Providence, RI USA. RP Walsh, CJ (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave,Room 3-470, Cambridge, MA 02139 USA. EM walshcj@alm.mit.edu FU NCRR NIH HHS [M01 RR001066]; NHLBI NIH HHS [K24 HL092902]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-14, R01 DK052625] NR 27 TC 27 Z9 28 U1 0 U2 1 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 OCT PY 2010 VL 257 IS 1 BP 167 EP 174 DI 10.1148/radiol.10100222 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 658XH UT WOS:000282527200023 PM 20713613 ER PT J AU Gupta, R Phan, CM Leidecker, C Brady, TJ Hirsch, JA Nogueira, RG Yoo, AJ AF Gupta, Rajiv Phan, Catherine M. Leidecker, Christianne Brady, Thomas J. Hirsch, Joshua A. Nogueira, Raul G. Yoo, Albert J. TI Evaluation of Dual-Energy CT for Differentiating Intracerebral Hemorrhage from Iodinated Contrast Material Staining SO RADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; CEREBRAL-ARTERY OCCLUSION; INTRAARTERIAL THROMBOLYSIS; COMPUTED-TOMOGRAPHY; INITIAL-EXPERIENCE; THERAPY; TRIAL; RECANALIZATION; TRANSFORMATION; EXTRAVASATION AB Purpose: To evaluate the efficacy of dual-energy computed tomography (CT) in the differentiation of intracerebral hemorrhage (ICH) from iodinated contrast material in patients who received contrast material via intraarterial or intravenous delivery. Materials and Methods: This retrospective study was approved by the local institutional review board, which waived the informed consent requirement for the analysis. Sixteen patients with acute stroke and two with head trauma who had undergone intraarterial or intravenous administration of iodinated contrast material were evaluated by using dual-energy CT to differentiate areas of hyperattenuation secondary to contrast material staining from those representing ICH. A dual-energy CT scanner was used for imaging at 80 and 140 kV, and a three-material decomposition algorithm was used to obtain virtual unenhanced images and iodine overlay images. The sensitivity, specificity, and accuracy of dual-energy CT in the prospective differentiation of intraparenchymal contrast material from hemorrhage were obtained. Follow-up images were used as the standard of reference. Results: There were 28 intraparenchymal areas of hyperattenuation classified at dual-energy CT as iodinated contrast material staining (n = 20, 71%), hemorrhage (n = 5, 18%), or both (n = 3, 11 %). Two of the three areas of hyperattenuation seen on both virtual unenhanced and iodine overlay images were related to mineralization. The sensitivity, specificity, and accuracy of dual-energy CT in the identification of hemorrhage were 100% (six of six areas), 91% (20 of 22 areas), and 93% (26 of 28 areas), respectively. Conclusion: Dual-energy CT can help differentiate ICH from iodinated contrast material staining with high sensitivity and specificity in patients who have recently received intraarterial or intravenous iodinated contrast material. (C) RSNA, 2010 C1 [Gupta, Rajiv; Phan, Catherine M.; Brady, Thomas J.; Hirsch, Joshua A.; Nogueira, Raul G.; Yoo, Albert J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Leidecker, Christianne] Siemens Med Solut, Malvern, PA USA. RP Phan, CM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Neuroradiol GRB 273A, Boston, MA 02114 USA. EM cmphan@partners.org NR 31 TC 56 Z9 64 U1 0 U2 3 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 OCT PY 2010 VL 257 IS 1 BP 205 EP 211 DI 10.1148/radiol.10091806 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 658XH UT WOS:000282527200027 PM 20679449 ER PT J AU Hendee, WR Becker, GJ Borgstede, JP Bosma, J Casarella, WJ Erickson, BA Maynard, CD Thrall, JH Wallner, PE AF Hendee, William R. Becker, Gary J. Borgstede, James P. Bosma, Jennifer Casarella, William J. Erickson, Beth A. Maynard, C. Douglas Thrall, James H. Wallner, Paul E. TI Addressing Overutilization in Medical Imaging SO RADIOLOGY LA English DT Article ID RADIATION; EXPOSURE; CANCER AB The growth in medical imaging over the past 2 decades has yielded unarguable benefits to patients in terms of longer lives of higher quality. This growth reflects new technologies and applications, including high-tech services such as multisection computed tomography (CT), magnetic resonance (MR) imaging, and positron emission tomography (PET). Some part of the growth, however, can be attributed to the overutilization of imaging services. This report examines the causes of the overutilization of imaging and identifies ways of addressing the causes so that overutilization can be reduced. In August 2009, the American Board of Radiology Foundation hosted a 2-day summit to discuss the causes and effects of the overutilization of imaging. More than 60 organizations were represented at the meeting, including health care accreditation and certification entities, foundations, government agencies, hospital and health systems, insurers, medical societies, health care quality consortia, and standards and regulatory agencies. Key forces influencing overutilization were identified. These include the payment mechanisms and financial incentives in the U. S. health care system; the practice behavior of referring physicians; self-referral, including referral for additional radiologic examinations; defensive medicine; missed educational opportunities when inappropriate procedures are requested; patient expectations; and duplicate imaging studies. Summit participants suggested several areas for improvement to reduce overutilization, including a national collaborative effort to develop evidence-based appropriateness criteria for imaging; greater use of practice guidelines in requesting and conducting imaging studies; decision support at point of care; education of referring physicians, patients, and the public; accreditation of imaging facilities; management of self-referral and defensive medicine; and payment reform. (C) RSNA, 2010 C1 [Hendee, William R.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. [Hendee, William R.; Erickson, Beth A.] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Hendee, William R.] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. [Hendee, William R.] Med Coll Wisconsin, Dept Populat Hlth, Milwaukee, WI 53226 USA. [Borgstede, James P.] Univ Colorado, Dept Radiol, Denver, CO 80202 USA. [Becker, Gary J.] Amer Board Radiol, Tucson, AZ USA. [Bosma, Jennifer] Amer Board Radiol Fdn, Tucson, AZ USA. [Casarella, William J.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. [Maynard, C. Douglas] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC USA. [Thrall, James H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wallner, Paul E.] 21st Century Oncol, Ft Myers, FL USA. RP Hendee, WR (reprint author), Med Coll Wisconsin, Dept Radiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM whendee@mcw.edu NR 28 TC 142 Z9 144 U1 0 U2 16 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 OCT PY 2010 VL 257 IS 1 BP 240 EP 245 DI 10.1148/radiol.10100063 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 658XH UT WOS:000282527200032 PM 20736333 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI The U.S. Preventive Services Task Force Guidelines Are Not Supported by the Scientific Evidence SO RADIOLOGY LA English DT Letter ID BREAST-CANCER; WOMEN C1 Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Dept Radiol, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Dept Radiol, 15 Parkman St,ACC240, Boston, MA 02114 USA. EM dkopans@partners.org NR 9 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 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2010 VL 257 IS 1 BP 294 EP 295 DI 10.1148/radiol.100920 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 658XH UT WOS:000282527200038 PM 20851947 ER PT J AU Caglar, HB Othus, M Allen, AM AF Caglar, Hale B. Othus, Megan Allen, Aaron M. TI Esophagus in-field: A new predictor for esophagitis SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Non-small cell lung cancer; Esophageal toxicity; Radiation ID CELL LUNG-CANCER; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; MODULATED RADIATION-THERAPY; GROUP RTOG TRIALS; CONCURRENT CHEMOTHERAPY; PHASE-II; CARCINOMA; TOXICITY; IRRADIATION; AMIFOSTINE AB Purpose: To define optimization parameters for limiting esophageal toxicity with concurrent chemoradiation (CRT) for non-small cell lung cancer (NSCLC). Materials and methods: A retrospective analysis of patients treated with concurrent chemoradiation at the Dana-Farber/Brigham and Women's Hospital Cancer Center was done with IRB approval. All patients were treated with concurrent CRT. All patients underwent 3-D conformal radiotherapy planned with ECLIPSE (Varian, Palo Alto, CA) treatment planning system. Patients had their esophagus contoured in two ways: the entire esophagus (Esoph) and esophagus in-field (Esoph(in)). Together with clinical variables, dose volume metrics including mean dose, V5-V60 of both structures (Esoph and Esoph(in),) were analyzed for correlation with acute esophagitis (>= grade 3) and late esophageal stricture. The analyses and graphics were completed using R (R Development Core Team, 2006). Logistic regression analysis was used to assess the relationships between dosimetric factors and swallowing complications while controlling for non-dosimetric variables. Results: 109 patients were studied between 2000 and 2006. 25% of patients had grade 3 or greater acute esophagitis. 5/109 (5.5%) had late esophageal stricture with a six-month actuarial risk of stricture of 6.5% (95% CI = 1-11%). Mean dose and V45-V60 for both Esoph and Esoph(in) significantly correlated with development of acute esophagitis. V55 and V60 for both Esoph and Esoph(in) significantly correlated with development of stricture. On Multivariate analysis V55 of the Esoph and Esoph(in) was most predictive of toxicity. Limiting the V55 Esoph(in) to 50% was the best cut-point for acute esophagitis. Conclusions: In the setting of concurrent CRT, V55 of the Esoph or Esoph(in) is the best predictor of acute esophagitis. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 97 (2010) 48-53 C1 [Caglar, Hale B.; Allen, Aaron M.] Dana Farber Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. [Othus, Megan] Harvard Univ, Sch Med, Biostat Core Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Allen, AM (reprint author), Rabin Med Ctr, Davidoff Ctr, Dept Radiat Oncol, Petah Tiqwa, Israel. EM Aallen@lroc.harvard.edu NR 22 TC 16 Z9 16 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2010 VL 97 IS 1 SI SI BP 48 EP 53 DI 10.1016/j.radonc.2010.07.024 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 673TH UT WOS:000283685400009 PM 20832884 ER PT J AU Anzueto, A Miravitlles, M AF Anzueto, Antonio Miravitlles, Marc TI Short-course fluoroquinolone therapy in exacerbations of chronic bronchitis and COPD SO RESPIRATORY MEDICINE LA English DT Review DE Chronic bronchitis; COPD; AECB; Fluoroquinolones; Duration of therapy; Short-course therapy ID OBSTRUCTIVE PULMONARY-DISEASE; ACUTE BACTERIAL EXACERBATION; LONG-TERM OUTCOMES; ANTIBIOTIC-TREATMENT; 5-DAY MOXIFLOXACIN; DOUBLE-BLIND; ANTIMICROBIAL TREATMENT; PSEUDOMONAS-AERUGINOSA; ORAL LEVOFLOXACIN; LUNG-FUNCTION AB Acute exacerbations of chronic bronchitis (AECB) and chronic obstructive pulmonary disease (COPD) are associated with significant healthcare costs and contribute to the progress of the disease. Although a number of factors may trigger these episodes, between 40% and 60% are bacterial in nature. Antimicrobial therapy can be effective in treating exacerbations, leading to improved peak expiratory flow rates, fewer hospitalizations, lower relapse rates, and greater clinical success. Evidence suggests that short-course antimicrobial therapy can be as effective as standard duration therapy (>7 days) in treating exacerbations. Randomized trials have shown that clinical and bacteriological success rates are comparable with both 5-day and standard antibiotic courses. Furthermore, 5-day fluoroquinolone therapy is associated with faster recovery, fewer relapses, prolonged duration between episodes, and less hospitalization when compared with standard therapy. Both moxifloxacin and gemifloxacin have received FDA-approval for 5-day therapy in AECB. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78229 USA. [Miravitlles, Marc] Hosp Clin Barcelona, IDIBAPS, Fudacio Clin, Barcelona 08036, Catalonia, Spain. RP Anzueto, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Dept Med, 111E,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu OI Miravitlles, Marc/0000-0002-9850-9520 FU Schering-Plough Corporation FX The authors would like to acknowledge the editorial assistance of Dr. Ching-Ling Chen in the preparation of this manuscript. Support for this assistance was provided by Schering-Plough Corporation. The authors accept full responsibility for the contents of this manuscript. NR 49 TC 7 Z9 9 U1 0 U2 4 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 OCT PY 2010 VL 104 IS 10 BP 1396 EP 1403 DI 10.1016/j.rmed.2010.05.018 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 655JW UT WOS:000282247300002 PM 20580215 ER PT J AU Huang, PM Syrkina, O Yu, LY Dedaj, R Zhao, H Shiedlin, A Liu, YY Garg, H Quinn, DA Hales, CA AF Huang, Pei-ming Syrkina, Olga Yu, Lunyin Dedaj, Rejmon Zhao, Hang Shiedlin, Aviva Liu, Yung-yang Garg, Hari Quinn, Deborah A. Hales, Charles A. TI High MW hyaluronan inhibits smoke inhalation-induced lung injury and improves survival SO RESPIROLOGY LA English DT Article DE hyaluronan; lung injury; smoke inhalation ID NITRIC-OXIDE; BURN INJURY; SHEEP; FRAGMENTS; REMOVAL; HEPARIN; REPAIR; ALPHA; ACID; MICE AB Background and objective: High MW hyaluronan (HMW HA) as opposed to low MW hyaluronan (LMW HA) has been shown to have anti-inflammatory and anti-apoptotic effects. We hypothesized that treatment with HMW HA would block smoke inhalation lung injury by inhibiting smoke-induced lung inflammation and airway epithelial cell apoptosis. Methods: Anesthetized, intubated male rats were randomly allocated to either control or smoke inhalation injury groups. Rats were treated with 3-mL subcutaneous normal saline solution (sham) or LMW HA (35 kDa) or HMW HA (1600 kDa) 18 h before exposure to 15 min of cotton smoke (n = 5 each). Rats were also treated post smoke inhalation with 1600 kDa HA by intra-peritoneal injection (3 mL) or intra-tracheal nebulization (200 mL). Lung neutrophil infiltration, airway apoptosis, airway mucous plugging and lung injury were assessed 4 h after smoke inhalation injury. Results: Rats pretreated with 1600 kDa HA had significantly less smoke-induced neutrophil infiltration, lung oedema, airway apoptosis and mucous plugging. Pretreatment with 35 kDa HA, in contrast, increased smoke-induced neutrophil infiltration and lung injury score. Intra-tracheal administration of a single dose 1600 kDa HA, but not intra-peritoneal injection, significantly improved survival post smoke inhalation. Conclusions: High MW hyaluronan (1600 kDa) may prove to be a beneficial therapy for smoke inhalation through inhibition of smoke-induced inflammation, lung oedema, airway epithelial cell apoptosis and airway mucous plugging. C1 [Huang, Pei-ming; Syrkina, Olga; Yu, Lunyin; Dedaj, Rejmon; Zhao, Hang; Liu, Yung-yang; Garg, Hari; Quinn, Deborah A.; Hales, Charles A.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Boston, MA 02114 USA. [Huang, Pei-ming; Syrkina, Olga; Yu, Lunyin; Dedaj, Rejmon; Zhao, Hang; Liu, Yung-yang; Garg, Hari; Quinn, Deborah A.; Hales, Charles A.] Harvard Univ, Sch Med, Boston, MA USA. [Syrkina, Olga; Hales, Charles A.] Shriners Burn Hosp, Boston, MA USA. [Shiedlin, Aviva] Genzyme Corp, Cambridge, MA USA. [Huang, Pei-ming] Natl Taiwan Univ Hosp, Dept Surg, Taipei 100, Taiwan. [Huang, Pei-ming] Natl Taiwan Univ, Coll Med, Taipei, Taiwan. [Liu, Yung-yang] Taipei Vet Gen Hosp, Dept Chest Med, Taipei, Taiwan. RP Hales, CA (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM chales@partners.org OI HUANG, PEI-MING/0000-0001-5493-7673 FU Shriners Burn Hospital [8620] FX This study was supported by a Grant from the Shriners Burn Hospital No. 8620. NR 37 TC 15 Z9 17 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1323-7799 J9 RESPIROLOGY JI Respirology PD OCT PY 2010 VL 15 IS 7 BP 1131 EP 1139 DI 10.1111/j.1440-1843.2010.01829.x PG 9 WC Respiratory System SC Respiratory System GA 655DZ UT WOS:000282225400017 PM 20874749 ER PT J AU Gomez, M Church, LWP Judson, MA AF Gomez, Mario Church, L. W. Preston Judson, Marc A. TI Tuberculous mediastinal lymphadenitis that evolved into pulmonary tuberculosis following transbronchial needle aspiration SO RESPIROLOGY LA English DT Article DE bronchoscopy; lymphadenitis; transbronchial needle aspiration; tuberculosis ID LYMPHADENOPATHY; ADULTS AB This case report describes a patient with multi-drug-resistant mediastinal lymph node tuberculosis that evolved to smear-positive pulmonary tuberculosis following transbronchial needle aspiration. This is the first report of this complication, and bronchoscopists should be vigilant for its occurrence. C1 [Gomez, Mario; Judson, Marc A.] Med Univ S Carolina, Div Pulm Crit Care Allergy & Sleep Med, Charleston, SC 29425 USA. [Church, L. W. Preston] Ralph H Johnson VA Med Ctr, Div Infect Dis, Charleston, SC USA. RP Gomez, M (reprint author), Med Univ S Carolina, Div Pulm Crit Care Allergy & Sleep Med, 96 Jonathan Lucas St,Suite 812 CSB,POB 250630, Charleston, SC 29425 USA. EM mariogomezdel@gmail.com OI Judson, Marc/0000-0002-4663-7985 FU Centocor; Gilead; Celegene; Merck FX Drs Gomez and Church do not have any conflict of interest to declare. Dr Judson is a consultant to Lilly and Centocor. He is on the speaker's bureau for Bohringer-Ingelheim. He has received grants from Centocor, Gilead, Celegene and Merck. NR 10 TC 1 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1323-7799 J9 RESPIROLOGY JI Respirology PD OCT PY 2010 VL 15 IS 7 BP 1140 EP 1141 PG 2 WC Respiratory System SC Respiratory System GA 655DZ UT WOS:000282225400018 PM 20573061 ER PT J AU Flaxel, CJ Edwards, AR Aiello, LP Arrigg, PG Beck, RW Bressler, NM Bressler, SB Ferris, FL Gupta, SK Haller, JA Lazarus, HS Qin, HJ AF Flaxel, Christina J. Edwards, Allison R. Aiello, Lloyd Paul Arrigg, Paul G. Beck, Roy W. Bressler, Neil M. Bressler, Susan B. Ferris, Frederick L., III Gupta, Shailesh K. Haller, Julia A. Lazarus, Howard S. Qin, Haijing TI FACTORS ASSOCIATED WITH VISUAL ACUITY OUTCOMES AFTER VITRECTOMY FOR DIABETIC MACULAR EDEMA Diabetic Retinopathy Clinical Research Network SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE diabetic macular edema; retinal thickness; visual acuity; vitrectomy ID VITREOMACULAR TRACTION AB Purpose: To evaluate factors associated with favorable outcomes after vitrectomy for diabetic macular edema. Methods: Data were collected prospectively on 241 eyes undergoing vitrectomy for diabetic macular edema. Multivariate models were used to evaluate associations of 20 preoperative and intraoperative factors with 6-month outcomes of visual acuity and retinal thickness. Results: Median central subfield thickness decreased from 412 mu m to 278 mu m at 6 months, butmedian visual acuity remained unchanged (20/80, Snellen equivalent). Greater visual acuity improvement occurred in eyes with worse baseline acuity (P < 0.001) and in eyes in which an epiretinal membrane was removed (P = 0.006). Greater reduction in central subfield thickness occurred with worse baseline visual acuity (P < 0.001), greater preoperative retinal thickness (P = 0.001), removal of internal limiting membrane (P = 0.003), and optical coherence tomography evidence of vitreoretinal abnormalities (P = 0.006). No associations with clinician's preoperative assessments of the posterior vitreous were identified. Conclusion: These results suggest that the removal of epiretinal membranes may favorably affect visual outcome after vitrectomy. Preoperative presence of vitreoretinal abnormalities appeared to be associated with somewhat greater reductions in retinal thickness but not with visual acuity outcome. These results may be useful for future studies evaluating vitrectomy for diabetic macular edema. RETINA 30: 1488-1495, 2010 C1 [Edwards, Allison R.; Beck, Roy W.; Qin, Haijing] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Flaxel, Christina J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. [Bressler, Neil M.; Bressler, Susan B.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Ferris, Frederick L., III] NEI, Bethesda, MD 20892 USA. [Ferris, Frederick L., III] NIH, Bethesda, MD 20892 USA. [Gupta, Shailesh K.] Univ Florida, Coll Med, Dept Ophthalmol, Jacksonville, FL USA. [Haller, Julia A.] Wills Eye Inst, Philadelphia, PA USA. [Lazarus, Howard S.] Amer Eye Inst, Los Angeles, CA USA. RP Edwards, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrstat1@jaeb.org FU National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and Department of Health and Human Services [EY14231, EY018817, EY14229] FX Supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and Department of Health and Human Services (EY14231, EY018817, and EY14229). NR 11 TC 35 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2010 VL 30 IS 9 BP 1488 EP 1495 DI 10.1097/IAE.0b013e3181e7974f PG 8 WC Ophthalmology SC Ophthalmology GA 659JC UT WOS:000282561800018 PM 20924264 ER PT J AU Lee, JE Kim, KH Kim, IK Jea, SY Kim, WS AF Lee, Joo Eun Kim, Kyeong Hwan Kim, Ivana K. Jea, Seung Youn Kim, Wan Soo TI COMPARISON OF 20-GAUGE TRANSCONJUNCTIVAL SUTURELESS VITRECTOMY WITH CONVENTIONAL VITRECTOMY SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article; Proceedings Paper CT Retina Congress CY SEP 30-OCT 04, 2009 CL New York, NY DE conventional instruments; self-sealing sclerotomies; sutureless vitrectomy; transconjunctival; TSV; vitrectomy; 20-gauge pars plana vitrectomy ID SURGERY; SYSTEM AB Purpose: The purpose of the study was to compare the efficacy and safety of a transconjunctival sutureless technique for pars plana vitrectomy using conventional 20-gauge instruments versus the conventional technique. Methods: Clinical data were reviewed retrospectively for a consecutive series of patients who underwent transconjunctival sutureless vitrectomy (TSV; 38 eyes of 37 patients) and a control group who underwent vitrectomy using the conventional technique (38 eyes of 38 patients). Results: Eighty-nine of 107 sclerotomies (83.2%) in the TSV group self-sealed without the need for sutures. The TSV group showed earlier visual improvement from baseline, as early as 7 postoperative days, compared with 60 days in the conventional group. This was attributed to less surgically induced astigmatism in the TSV group; mean astigmatism at baseline and postoperative days 7, 30, and 90 was -1.05 diopter (D), -2.53 D, -1.32 D, and -1.09 D, respectively, in the TSV group and -1.09 D, -3.91 D (P = 0.0285), -2.57 D (P = 0.0203), and -1.18 D, respectively, in the conventional group. No serious complications were observed in either group, including postoperative hypotony, wound leakage, or endophthalmitis. Conclusion: The 20-gauge TSV technique is as effective as the conventional technique and offers earlier postoperative recovery. RETINA 30: 1496-1504, 2010 C1 [Lee, Joo Eun; Kim, Wan Soo] Inje Univ Coll Med, Haeundae Paik Hosp, Dept Ophthalmol, Pusan 612030, South Korea. [Kim, Kyeong Hwan] Maryknoll Med Ctr, Dept Ophthalmol, Pusan, South Korea. [Lee, Joo Eun; Kim, Ivana K.; Jea, Seung Youn] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Lee, JE (reprint author), Inje Univ Coll Med, Haeundae Paik Hosp, Dept Ophthalmol, 1435 Jwa Dong, Pusan 612030, South Korea. EM jooeun2@korea.com RI Kim, Kyeong Hwan/C-5036-2012 OI Kim, Kyeong Hwan/0000-0002-7359-663X NR 10 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2010 VL 30 IS 9 BP 1496 EP 1504 DI 10.1097/IAE.0b013e3181d427d3 PG 9 WC Ophthalmology SC Ophthalmology GA 659JC UT WOS:000282561800019 PM 20588205 ER PT J AU Bayes-Genis, A Pascual-Figal, D Januzzi, JL Maisel, A Casas, T Chavarri, MV Ordonez-Llanos, J AF Bayes-Genis, Antoni Pascual-Figal, Domingo Januzzi, James L. Maisel, Alan Casas, Teresa Valdes Chavarri, Mariano Ordonez-Llanos, Jordi TI Soluble ST2 Monitoring Provides Additional Risk Stratification for Outpatients With Decompensated Heart Failure SO REVISTA ESPANOLA DE CARDIOLOGIA LA Spanish DT Article DE Heart failure; Prognosis; NT-proBNP; ST2 ID NATRIURETIC PEPTIDE; MYOCARDIAL-INFARCTION; FAMILY-MEMBER; PROTEIN; RECEPTOR; IL-33; COMPRISE; DYSPNEA; SYSTEM; SERUM AB Introduction and objectives. The novel biomarker ST2 provides diagnostic information in a variety of clinical settings. The objective was to determine whether measurement of the soluble ST2 (sST2) concentration improves risk stratification in outpatients with decompensated heart failure (HF). Methods. The concentrations of sST2 and N-terminal probrain natriuretic peptide (NT-proBNP) and a heart failure severity score (HFSS), based on Framingham criteria, were determined at baseline and 2 weeks later in 48 outpatients with decompensated hf. The ratio of the value of each variable at week 2 relative to baseline was determined. Patients were followed for 1 year and cardiac events (i.e. death, HF admission and heart transplantation) were recorded. Results. By 1 year, 56% of patients had experienced a cardiac event. The sST2 ratio was significantly lower in patients who did not have a cardiac event (0.6 +/- 0.39 vs. 1.39 +/- 0.92; P<.001). After multivariable adjustment, the sST2 ratio remained an independent predictor of risk (odds ratio=1.054; 95% confidence interval, 1.01-1.09; P=.017). The optimum cut-point for the sST2 ratio determined by receiver operating curve [ROC] analysis was 0.75; this accounted for 25% of the change in sST2 by week 2. Among patients with an sST2 ratio >0.75 and a baseline NT-proBNP level >1000 ng/L, 72% had a cardiac event (P=.018), while no events occurred in patients with marker values below these reference levels. Conclusions. Determination of the sST2 concentration in serial samples provided additional risk stratification in outpatients with decompensated HF. Repeated measurement of sST2 may aid clinical decision-making. C1 [Bayes-Genis, Antoni] Hosp Badalona Germans Trias & Pujol, Dept Cardiol, Serv Cardiol, Barcelona 08916, Spain. [Bayes-Genis, Antoni] Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain. [Pascual-Figal, Domingo; Casas, Teresa; Valdes Chavarri, Mariano] Hosp Virgen Arrixaca, Dept Cardiol, Murcia, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Maisel, Alan] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Ordonez-Llanos, Jordi] Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, E-08193 Barcelona, Spain. [Ordonez-Llanos, Jordi] Hosp Santa Creu & Sant Pau, Serv Bioquim, Barcelona, Spain. RP Bayes-Genis, A (reprint author), Hosp Badalona Germans Trias & Pujol, Dept Cardiol, Serv Cardiol, Ctra Canyet S-N, Barcelona 08916, Spain. EM abayesgenis@gmail.com RI Ordonez-Llanos, Jordi/B-4961-2011; Pascual Figal, Domingo /B-3794-2008; Bayes-Genis, Antoni/C-4002-2015 OI Ordonez-Llanos, Jordi/0000-0003-4896-5832; Pascual Figal, Domingo /0000-0002-4993-9540; Bayes-Genis, Antoni/0000-0002-3044-197X NR 18 TC 35 Z9 38 U1 1 U2 5 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 OCT PY 2010 VL 63 IS 10 BP 1171 EP 1178 DI 10.1016/S0300-8932(10)70249-9 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 659BN UT WOS:000282542100009 PM 20875357 ER PT J AU Chakraborty, BH Steinhauer, SR AF Chakraborty, Beatrice H. Steinhauer, Stuart R. TI Reporting of minority participation rates and racial differences in schizophrenia and psychophysiological research: Improving but still not adequate SO SCHIZOPHRENIA RESEARCH LA English DT Letter C1 [Chakraborty, Beatrice H.] VA Pittsburgh Healthcare Syst, Biometr Res Program, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Sch Med, Pittsburgh, PA 15213 USA. RP Chakraborty, BH (reprint author), VA Pittsburgh Healthcare Syst, Biometr Res Program, 7180 Highland Dr,151R, Pittsburgh, PA 15206 USA. EM Bec27@pitt.edu; Sthauer@pitt.edu FU NCRR NIH HHS [RR024153]; NIMH NIH HHS [MH55762, R01 MH055762] NR 4 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2010 VL 123 IS 1 BP 90 EP 91 DI 10.1016/j.schres.2010.06.006 PG 2 WC Psychiatry SC Psychiatry GA 665IR UT WOS:000283029100015 PM 20837319 ER PT J AU Snelgrove, RJ Jackson, PL Hardison, MT Noerager, BD Kinloch, A Gaggar, A Shastry, S Rowe, SM Shim, YM Hussell, T Blalock, JE AF Snelgrove, Robert J. Jackson, Patricia L. Hardison, Matthew T. Noerager, Brett D. Kinloch, Andrew Gaggar, Amit Shastry, Suresh Rowe, Steven M. Shim, Yun M. Hussell, Tracy Blalock, J. Edwin TI A Critical Role for LTA(4)H in Limiting Chronic Pulmonary Neutrophilic Inflammation SO SCIENCE LA English DT Article ID LEUKOTRIENE A(4) HYDROLASE; CYSTIC-FIBROSIS; ENZYME; CHEMOATTRACTANT; PEPTIDASE; AMINOPEPTIDASE; ARGININE; DISEASE; CELLS; COPD AB Leukotriene A(4) hydrolase (LTA(4)H) is a proinflammatory enzyme that generates the inflammatory mediator leukotriene B-4 (LTB4). LTA(4)H also possesses aminopeptidase activity with unknown substrate and physiological importance; we identified the neutrophil chemoattractant proline-glycine-proline (PGP) as this physiological substrate. PGP is a biomarker for chronic obstructive pulmonary disease (COPD) and is implicated in neutrophil persistence in the lung. In acute neutrophil-driven inflammation, PGP was degraded by LTA(4)H, which facilitated the resolution of inflammation. In contrast, cigarette smoke, a major risk factor for the development of COPD, selectively inhibited LTA(4)H aminopeptidase activity, which led to the accumulation of PGP and neutrophils. These studies imply that therapeutic strategies inhibiting LTA(4)H to prevent LTB4 generation may not reduce neutrophil recruitment because of elevated levels of PGP. C1 [Snelgrove, Robert J.; Jackson, Patricia L.; Hardison, Matthew T.; Gaggar, Amit; Shastry, Suresh; Rowe, Steven M.; Blalock, J. Edwin] Univ Alabama, Dept Med, Lung Hlth Ctr, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Snelgrove, Robert J.; Hussell, Tracy] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Leukocyte Biol Sect, London SW7 2AZ, England. [Noerager, Brett D.] Univ Montevallo, Dept Biol Chem & Math, Montevallo, AL 35115 USA. [Kinloch, Andrew] Univ London Imperial Coll Sci Technol & Med, Kennedy Inst Rheumatol, London W6 8LH, England. [Gaggar, Amit; Rowe, Steven M.; Blalock, J. Edwin] Univ Alabama, Gregory Fleming James Cyst Fibrosis Ctr, Birmingham, AL 35294 USA. [Gaggar, Amit] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Rowe, Steven M.] Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. [Shim, Yun M.] Univ Virginia, Dept Med, Div Pulm & Crit Care Med, Charlottesville, VA 22908 USA. RP Snelgrove, RJ (reprint author), Univ Alabama, Dept Med, Lung Hlth Ctr, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. EM rjs198@imperial.ac.uk RI Hussell, Tracy/O-4630-2014; Kinloch, Anthony/F-6042-2011 OI Hussell, Tracy/0000-0001-7186-6141; Kinloch, Anthony/0000-0002-8752-7184 FU Wellcome Trust [082727/Z/07/Z]; National Heart, Lung, and Blood Institute [HL07783, HL090999, HL087824, HL102371-A1, K08HL091127]; Cystic Fibrosis Foundation [GAGGAR07]; National Institute of Diabetes and Digestive and Kidney Diseases [1K23DK075788, 1R03DK084110-01]; Flight Attendant Medical Research Institute; Medical Research Council [P171/03/C1/048]; NIH [RR19231, P30CA13148, P50 AT00477, U54CA100949, P30AR050948, P30 DK079337] FX This project was supported by grants from the Wellcome Trust (082727/Z/07/Z to R.J.S.), the National Heart, Lung, and Blood Institute (HL07783, HL090999, and HL087824 to J.E.B. and HL102371-A1 to A. G.), the Cystic Fibrosis Foundation (GAGGAR07 to A. G.), the National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK075788 and 1R03DK084110-01 to S. M. R.), the Flight Attendant Medical Research Institute (Young Clinical Scientist Award to Y.M.S.) and the National Heart, Lung, and Blood Institute (K08HL091127 to Y.M.S.), and the Medical Research Council (P171/03/C1/048 to T. H.). The Univ. of Alabama Birmingham (UAB) Lung Health Center Pulmonary Proteomics Laboratory is funded through the NIH (by grants RR19231, P30CA13148, P50 AT00477, U54CA100949, P30AR050948, and P30 DK079337). We thank R. Moore and L. Wilson of the UAB Targeted Metabolomics and Proteomics Laboratory for their technical assistance with mass spectrometry, D. Muccio of the UAB Chemistry Department for the use of his fast protein liquid chromatography system, G. Xia for technical assistance, and D. Saliba of the Kennedy Institute of Rheumatology, Imperial College London, for his technical assistance in the generation of murine LTA4H. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the NIH. NR 30 TC 105 Z9 109 U1 1 U2 15 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 OCT 1 PY 2010 VL 330 IS 6000 BP 90 EP 94 DI 10.1126/science.1190594 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 656KW UT WOS:000282334500042 PM 20813919 ER PT J AU Cash, SS Halgren, E Dehghani, N Rossetti, AO Thesen, T Wang, CM Devinsky, O Kuzniecky, R Doyle, W Madsen, JR Eross, L Halasz, P Karmos, G Csercsa, R Wittner, L Ulbert, I AF Cash, Sydney S. Halgren, Eric Dehghani, Nima Rossetti, Andrea O. Thesen, Thomas Wang, ChunMao Devinsky, Orrin Kuzniecky, Ruben Doyle, Werner Madsen, Joseph R. Eross, Lorand Halasz, Peter Karmos, George Csercsa, Richard Wittner, Lucia Ulbert, Istvan TI Response to Comment on "The Human K-Complex Represents an Isolated Cortical Down-State" SO SCIENCE LA English DT Editorial Material ID DELTA WAVES; SLEEP C1 [Cash, Sydney S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Epilepsy Div, Boston, MA 02114 USA. [Halgren, Eric; Dehghani, Nima] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Halgren, Eric; Dehghani, Nima] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Halgren, Eric; Dehghani, Nima] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Thesen, Thomas; Wang, ChunMao; Devinsky, Orrin; Kuzniecky, Ruben; Doyle, Werner] NYU, Sch Med, Comprehens Epilepsy Ctr, New York, NY 10016 USA. [Madsen, Joseph R.] Childrens Hosp, Boston, MA 02115 USA. [Rossetti, Andrea O.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Eross, Lorand; Wittner, Lucia; Ulbert, Istvan] Natl Inst Neurosci, H-1145 Budapest, Hungary. [Halasz, Peter] Natl Inst Psychiat & Neurol, Epilepsy Ctr, H-1145 Budapest, Hungary. [Karmos, George; Csercsa, Richard; Wittner, Lucia; Ulbert, Istvan] Hungarian Acad Sci, Inst Psychol, H-1394 Budapest, Hungary. [Halasz, Peter; Karmos, George; Ulbert, Istvan] Peter Pazmany Catholic Univ, Dept Informat Technol, H-1083 Budapest, Hungary. RP Cash, SS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Epilepsy Div, Boston, MA 02114 USA. EM scash@partners.org RI Ulbert, Istvan/F-2213-2010; Wittner, Lucia/C-9386-2013; OI Wittner, Lucia/0000-0001-6800-0953; Eross, Lorand/0000-0002-5796-5546; Dehghani, Nima/0000-0003-2032-8903 NR 13 TC 1 Z9 1 U1 0 U2 2 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 OCT 1 PY 2010 VL 330 IS 6000 DI 10.1126/science.1182204 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 656KW UT WOS:000282334500018 ER PT J AU Kaimal, AJ Kuppermann, M AF Kaimal, Anjali J. Kuppermann, Miriam TI Understanding Risk, Patient and Provider Preferences, and Obstetrical Decision Making: Approach to Delivery After Cesarean SO SEMINARS IN PERINATOLOGY LA English DT Review DE vaginal birth after cesarean; shared decision making; risk communication; patient-provider communication ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE DECISIONS; VAGINAL BIRTH; MATERNAL REQUEST; SECTION; MODE; PERCEPTION; EXPERIENCE; AIDS; GYNECOLOGISTS AB Decision making regarding approach to delivery after cesarean is complex and requires consideration of the probabilities of clinical outcomes and the preferences of pregnant women. Depending on the clinical situation, a range of management options may be appropriate, and understanding women's beliefs and values regarding the process and outcomes of obstetrical interventions, as well as providing them with clear information regarding risk, is a necessary part of providing evidence-based, patient-centered care. We conducted a review of the literature on risk communication, patient and provider preferences, and obstetrical decision-making and offer recommendations on how to incorporate patient preferences in the context of delivery after cesarean. Semin Perinatol 34:331-336 (C) 2010 Elsevier Inc. All rights reserved. C1 [Kuppermann, Miriam] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Kuppermann, Miriam] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kaimal, Anjali J.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Kuppermann, M (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, 3333 Calif St,Suite 335, San Francisco, CA 94143 USA. EM kuppermannm@obgyn.ucsf.edu NR 51 TC 24 Z9 24 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD OCT PY 2010 VL 34 IS 5 BP 331 EP 336 DI 10.1053/j.semperi.2010.05.006 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 662TI UT WOS:000282835100006 PM 20869549 ER PT J AU Cuschieri, J Bulger, E Schaeffer, V Sakr, S Nathens, AB Hennessy, L Minei, J Moore, EE O'Keefe, G Sperry, J Remick, D Tompkins, R Maier, RV AF Cuschieri, Joseph Bulger, Eileen Schaeffer, Valerie Sakr, Sana Nathens, Avery B. Hennessy, Laura Minei, Joseph Moore, Ernest E. O'Keefe, Grant Sperry, Jason Remick, Daniel Tompkins, Ronald Maier, Ronald V. CA Inflammation Host Response Injury TI EARLY ELEVATION IN RANDOM PLASMA IL-6 AFTER SEVERE INJURY IS ASSOCIATED WITH DEVELOPMENT OF ORGAN FAILURE SO SHOCK LA English DT Article DE IL-6; multiple organ dysfunction syndrome; prognosis ID SCALE COLLABORATIVE PROJECT; ORIENTED RESEARCH CORE; STANDARD OPERATING PROCEDURES; CLINICAL CARE; HOST RESPONSE; TRAUMA PATIENT; MECHANICAL VENTILATION; SEPTIC PATIENTS; INFLAMMATION; INTERLEUKIN-6 AB Excessive proinflammatory activation after trauma plays a role in late morbidity and mortality, including the development of multiple organ dysfunction syndrome (MODS). To date, identification of patients at risk has been challenging. Results from animal and human studies suggest that circulating interleukin 6 (IL-6) may serve as a biomarker for excessive inflammation. The purpose of this analysis was to determine the association of IL-6 with outcome in a multicenter developmental cohort and in a single-center validation cohort. Severely injured patients with shock caused by hemorrhage were evaluated within a multicenter developmental cohort (n = 79). All had blood drawn within 12 h of injury. Plasma IL-6 was determined by multiplex proteomic analysis. Clinical and outcome data were prospectively obtained. Within this developmental cohort, a plasma IL-6 level was determined for the subsequent development of MODS by developing a receiver operating curve and defining the optimal IL-6 level using the Youden Index. This IL-6 level was then evaluated within a separate validation cohort (n = 56). A receiver operating curve was generated for IL-6 and MODS development, with an IL-6 level of 350 pg/mL having the highest sensitivity and specificity within the developmental cohort. IL-6 was associated with MODS after adjusting for Acute Physiology and Chronic Health Evaluation, Injury Severity Score, male sex, and blood transfusions with an odds ratio of 3.9 (95% confidence interval, 1.33 - 11.19). An IL-6 level greater than 350 pg/mL within the validation cohort was associated with an increase in MODS score, MODS development, ventilator days, intensive care unit length of stay, and hospital length of stay. However, this IL-6 level was not associated with either the development of nosocomial infection or mortality. Elevation in plasma IL-6 seems to correlate with a poor prognosis. This measurement may be useful as a biomarker for prognosis and serve to identify patients at higher risk of adverse outcome that would benefit from novel therapeutic interventions. C1 [Cuschieri, Joseph; Bulger, Eileen; Schaeffer, Valerie; Sakr, Sana; Hennessy, Laura; O'Keefe, Grant; Maier, Ronald V.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. [Nathens, Avery B.] Univ Toronto, St Michaels Hosp, Dept Surg, Toronto, ON M5B 1W8, Canada. [Minei, Joseph] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA. [Moore, Ernest E.] Univ Colorado, Denver Hlth Med Ctr, Dept Surg, Denver, CO 80202 USA. [Sperry, Jason] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Remick, Daniel] Boston Univ, Dept Pathol, Boston, MA 02215 USA. [Tompkins, Ronald] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. RP Cuschieri, J (reprint author), Univ Washington, Harborview Med Ctr, Dept Surg, 325 9th Ave,Box 359796, Seattle, WA 98104 USA. EM jcuschie@u.washington.edu OI Remick, Daniel/0000-0002-2615-3713 FU National Institutes of Health [RO1 GM 078054-02, U54 GM62119-01A1, T32 GM007037] FX This study was supported by the National Institutes of Health (grant no. RO1 GM 078054-02 to J.C., grant no. U54 GM62119-01A1 to R. T., and grant no. T32 GM007037 to G.O'K.). NR 41 TC 31 Z9 37 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD OCT PY 2010 VL 34 IS 4 BP 346 EP 351 DI 10.1097/SHK.0b013e3181d8e687 PG 6 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 651EN UT WOS:000281907800005 PM 20844410 ER PT J AU Martini, WZ Wolf, SE Chinkes, DL Chung, KK Dubick, MA Blackbourne, L Yu, YM AF Martini, Wenjun Z. Wolf, Steven E. Chinkes, David L. Chung, Kevin K. Dubick, Michael A. Blackbourne, Lorne Yu, Yong-Ming TI ENHANCED ALBUMIN SYNTHESIS IN SEVERELY BURNED ADULTS SO SHOCK LA English DT Article DE Burn injury; stable isotopes; gas chromatography and mass spectrometry ID TRANSCAPILLARY ESCAPE RATE; PROTEIN-SYNTHESIS; HEPATIC PROTEINS; THERMAL-INJURY; AMINO-ACID; PERMEABILITY; FIBRINOGEN; METABOLISM; MORBIDITY; DISEASE AB Albumin plays an important role in maintaining physiological homeostasis. Although decreased albumin concentration has been well described as an acute-phase response following injury, it is unclear whether the decrease is due to compromised synthesis of albumin, dilution, or imbalance between synthesis and breakdown rates, particularly after injury. We investigated changes in albumin synthesis in severely burned patients using stable isotope infusion techniques. Five patients (29 +/- 3 years; 80 +/- 7 kg) with burn of 48% +/- 4% total body surface area (TBSA) were enrolled and studied in the ICU at the Burn Unit of the US Army Institute of Surgical Research. Five age-and sex-matched healthy volunteers (33 +/- 5 years; 81 +/- 6 kg) were included as controls. On the study day (13 +/- 3 days after burn), a primed constant infusion (4 h) of stable isotope d(5)-phenlylalanine and d(3)-ketoisocaproic acid was given. Hourly arterial blood samples were drawn during the infusion to determine albumin synthesis rates, using gas chromatography-mass spectrometry analysis. Burned patients had higher heart and respiration rates. Plasma total protein in burn patients (4.5 +/- 0.3 g . dL(-1)) was lower compared with controls (6.8 +/- 0.2 g . dL(-1)). Plasma albumin concentration in burn patients (1.1 +/- 0.1 g . dL(-1)) was also lower compared with controls (3.8 +/- 0.1 g . dL(-1); both P < 0.05). Albumin synthesis rate in burn patients (4.6 +/- 0.2 mg . kg(-1) . h(-1)) was enhanced compared with controls (2.2 +/- 0.2 mg . kg(-1) . h(-1); P < 0.05). Despite the decrease in albumin concentration, albumin synthesis was enhanced in severely burned patients during the flow phase. C1 [Martini, Wenjun Z.; Wolf, Steven E.; Chung, Kevin K.; Dubick, Michael A.; Blackbourne, Lorne] USA, Inst Surg Res, Houston, TX 78234 USA. [Chinkes, David L.] Univ Texas Med Branch, Galveston, TX USA. [Yu, Yong-Ming] Harvard Univ, Sch Med, Boston, MA USA. [Yu, Yong-Ming] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Martini, WZ (reprint author), USA, Inst Surg Res, 3400 Rawley E Chambers Ave, Houston, TX 78234 USA. EM wenjun.martini@amedd.army.mil OI Wolf, Steven/0000-0003-2972-3440 FU US Army Medical Research and Materiel Command; US Army Institute of Surgical Research; Pharmacy Department at Brooke Army Medical Center FX This study was supported by the US Army Medical Research and Materiel Command.; The authors thank Annette McClinton for her regulatory assistance throughout the study. The authors appreciate the support received from the research nurses at the US Army Institute of Surgical Research and the Pharmacy Department at Brooke Army Medical Center. NR 38 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD OCT PY 2010 VL 34 IS 4 BP 364 EP 368 DI 10.1097/SHK.0b013e3181d8844b PG 5 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 651EN UT WOS:000281907800008 PM 20160662 ER PT J AU Torriani, M Gupta, R Donahue, DM AF Torriani, Martin Gupta, Rajiv Donahue, Dean M. TI Botulinum toxin injection in neurogenic thoracic outlet syndrome: results and experience using a ultrasound-guided approach SO SKELETAL RADIOLOGY LA English DT Article DE Neurogenic thoracic outlet syndrome; Botulinum toxin; Injection; Ultrasound ID CERVICAL DYSTONIA; DOUBLE-BLIND AB The purpose of this study was to describe the technique, complications, and rate of symptom relief after ultrasound-guided botulinum toxin injection in subjects with suspected neurogenic thoracic outlet syndrome (NTOS). This study was IRB-approved and followed HIPPA guidelines. Subjects investigated for NTOS were identified via retrospective review of medical records. Procedures included botulinum toxin injections of the anterior scalene, pectoralis minor, and subclavius muscles performed under real-time ultrasound guidance. Technical success was defined as satisfactory muscle identification, intramuscular needle placement, and intramuscular delivery of medication. Follow-up was performed to determine procedure-related complications and therapy response using a binary assessment and modified visual analogue scale (VAS). Forty-one subjects with suspected NTOS underwent a total of 92 injections (58 anterior scalene, 33 pectoralis minor, and 1 subclavius muscle). Technical success was achieved in all procedures. No complications occurred. Symptom improvement occurred after 69% of procedures. The VAS before and after the procedure changed from 7.1 to 2.8 (P < 0.0001) respectively. The mean time to symptom improvement and duration of symptom improvement were 12 and 31 days respectively. Botulinum toxin injection under ultrasound guidance is a safe and well-tolerated procedure with a satisfactory rate of temporary symptom relief in subjects with suspected NTOS. C1 [Torriani, Martin; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Torriani, Martin] Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. [Torriani, Martin; Gupta, Rajiv; Donahue, Dean M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Donahue, Dean M.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,YAW 6048, Boston, MA 02114 USA. EM mtorriani@hms.harvard.edu NR 13 TC 21 Z9 22 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD OCT PY 2010 VL 39 IS 10 BP 973 EP 980 DI 10.1007/s00256-010-0897-1 PG 8 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 637VI UT WOS:000280846400004 PM 20186413 ER PT J AU Ovbiagele, B Schwamm, LH Smith, EE Hernandez, AF Olson, DM Pan, WQ Fonarow, GC Saver, JL AF Ovbiagele, Bruce Schwamm, Lee H. Smith, Eric E. Hernandez, Adrian F. Olson, DaiWai M. Pan, Wenqin Fonarow, Gregg C. Saver, Jeffrey L. TI Patterns and Predictors of Discharge Statin Prescription Among Hospitalized Patients With Intracerebral Hemorrhage SO STROKE LA English DT Article DE clinical trials; health services; hemorrhagic stroke; intracerebral hemorrhage; practice patterns; prevention; statins; utilization ID TRANSIENT ISCHEMIC ATTACK; QUALITY-OF-CARE; STATEWIDE STROKE REGISTRY; GUIDELINES PROGRAM; THERAPY; CHOLESTEROL AB Background and Purpose-Many patients hospitalized with intracerebral hemorrhage are at high future risk for ischemic events and may benefit from stain therapy. However, little is known about patterns of statin prescription among patients with intracerebral hemorrhage, especially after the finding of higher hemorrhagic stroke risk in the statin treatment arm of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. We evaluated recent nationwide trends in discharge statin treatment after intracerebral hemorrhage hospitalization. Methods-Using data from 25 673 patients with hemorrhagic stroke admitted to Get With Guidelines-Stroke participating hospitals between January 1, 2005, and December 31, 2007, we assessed factors associated with discharge statin prescription, including treatment over time and in relation to dissemination of the SPARCL results. Piecewise logistic multivariable regression models were fit to track statin use in various periods. Results-Mean age was 67.9 +/- 15 years, 48.1% female, and discharge statin treatment in 39.5%. Variables independently associated with lower discharge statin use included female sex (OR 0.87, 95% CI, 0.82 to 0.93), prior stroke/transient ischemic attack (OR 0.85, 95% CI, 0.78 to 0.92), academic center (OR 0.87, 95% CI, 0.82 to 0.93), and Midwest region (OR 0.65, 95% CI, 0.56 to 0.80). Statin prescription climbed over the study period from 66.9% to 74.5% (P<0.001) among eligible patients with a decrease during SPARCL reporting (P=0.03) and then a return to prior levels thereafter. Conclusions-Discharge statin prescription among hospitalized patients with intracerebral hemorrhage has modestly risen over time. The clinical implications of this care pattern among patients with intracerebral hemorrhage require further study. (Stroke. 2010;41:2271-2277.) C1 [Ovbiagele, Bruce; Saver, Jeffrey L.] Univ Calif Los Angeles, Med Ctr, Dept Neurol, Los Angeles, CA 90095 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. [Hernandez, Adrian F.; Olson, DaiWai M.; Pan, Wenqin] Duke Clin Res Inst, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Div Cardiol, Los Angeles, CA 90095 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Dept Med, Los Angeles, CA 90095 USA. RP Ovbiagele, B (reprint author), Univ Calif Los Angeles, Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA. EM Ovibes@mednet.ucla.edu RI Smith, Eric/C-5443-2012; Hernandez, Adrian F./A-7818-2016; OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Saver, Jeffrey/0000-0001-9141-2251 FU American Heart Association (AHA); American Stroke Association; Pfizer, Inc, New York, NY; Merck-Schering Plough Partnership (North Wales, Pa); National Institutes of Health (NIH) (National Institute of Neurological Disorders and Stroke [NINDS] [R01 NS062028]; Canadian Institutes for Health Research; Canadian Stroke Network; Hotchkiss Brain Institute; Johnson Johnson; Medtronic; Merck FX Get With The Guidelines Program (GWTG) is funded by the American Heart Association (AHA) and the American Stroke Association. GWTG is also supported in part by unrestricted educational grants to the AHA by Pfizer, Inc, New York, NY, and the Merck-Schering Plough Partnership (North Wales, Pa). E.E.S. receives research support from the National Institutes of Health (NIH) (National Institute of Neurological Disorders and Stroke [NINDS] R01 NS062028), the Canadian Institutes for Health Research, the Canadian Stroke Network and the Hotchkiss Brain Institute. G.C.F. receives research support from the NIH (significant).; L.H.S. serves as chair of the American Heart Association (AHA) Get With the Guidelines (GWTG) Steering Committee; serves as a consultant to the Research Triangle Institute, CryoCath, and to the Massachusetts Department of Public Health; and has provided expert medical opinions in malpractice lawsuits regarding stroke treatment and prevention. E.E.S. serves as a member of the GWTG Science Subcommittee and receives salary support from the Canadian Institutes for Health Research. A.F.H. is a member of the AHA GWTG analytical center at the Duke Clinical Research Institute and reports receiving research support from Johnson & Johnson, Medtronic, and Merck; honoraria from AstraZeneca; and serving on the speakers' bureau for Novartis. A.F.H. has made available online a detailed listing of financial disclosures (http://www. dcri. duke. edu/research/ coi. jsp). W.P. and D.M.O. are members of the Duke Clinical Research Institute that serves as the AHA GWTG data- coordinating center. G.C.F. serves as a consultant to Pfizer (modest), Merck (modest), and Schering Plough (modest); receives speaker honoraria from AstraZeneca (significant), Pfizer (significant), Merck (significant), Schering Plough (significant), Bristol Myers Squibb (significant), and Sanofi- Aventis (significant). There are no other disclosures to report. NR 19 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2010 VL 41 IS 10 BP 2271 EP 2277 DI 10.1161/STROKEAHA.110.593228 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 655CY UT WOS:000282221700037 PM 20724709 ER PT J AU Lima, FO Furie, KL Silva, GS Lev, MH Camargo, ECS Singhal, AB Harris, GJ Halpern, EF Koroshetz, WJ Smith, WS Yoo, AJ Nogueira, RG AF Lima, Fabricio O. Furie, Karen L. Silva, Gisele S. Lev, Michael H. Camargo, Erica C. S. Singhal, Aneesh B. Harris, Gordon J. Halpern, Elkan F. Koroshetz, Walter J. Smith, Wade S. Yoo, Albert J. Nogueira, Raul G. TI The Pattern of Leptomeningeal Collaterals on CT Angiography Is a Strong Predictor of Long-Term Functional Outcome in Stroke Patients With Large Vessel Intracranial Occlusion SO STROKE LA English DT Article DE acute stroke; brain imaging; brain ischemia; leptomeningeal collaterals; outcome ID ACUTE ISCHEMIC-STROKE; INTRAARTERIAL THROMBOLYSIS; PROACT-II; RECANALIZATION; CIRCULATION; PERFUSION; INFARCT; EXTENT; TRIAL; SCORE AB Background and Purpose-The role of noninvasive methods in the evaluation of collateral circulation has yet to be defined. We hypothesized that a favorable pattern of leptomeningeal collaterals, as identified by CT angiography, correlates with improved outcomes. Methods-Data from a prospective cohort study at 2 university-based hospitals where CT angiography was systematically performed in the acute phase of ischemic stroke were analyzed. Patients with complete occlusion of the intracranial internal carotid artery and/or the middle cerebral artery (M1 or M2 segments) were selected. The leptomeningeal collateral pattern was graded as a 3-category ordinal variable (less, equal, or greater than the unaffected contralateral hemisphere). Univariate and multivariate analyses were performed to define the independent predictors of good outcome at 6 months (modified Rankin Scale score <= 2). Results-One hundred ninety-six patients were selected. The mean age was 69 +/- 17 years and the median National Institute of Health Stroke Scale score was 13 (interquartile range, 6 to 17). In the univariate analysis, age, baseline National Institute of Health Stroke Scale score, prestroke modified Rankin Scale score, Alberta Stroke Programme Early CT score, admission blood glucose, history of hypertension, coronary artery disease, congestive heart failure, atrial fibrillation, site of occlusion, and collateral pattern were predictors of outcome. In the multivariate analysis, age (OR, 0.95; 95% CI, 0.93 to 0.98; P=0.001), baseline National Institute of Health Stroke Scale (OR, 0.75; 0.69 to 0.83; P<0.001), prestroke modified Rankin Scale score (OR, 0.41; 0.22 to 0.76; P=0.01), intravenous recombinant tissue plasminogen activator (OR, 4.92; 1.83 to 13.25; P=0.01), diabetes (OR, 0.31; 0.01 to 0.98; P=0.046), and leptomeningeal collaterals (OR, 1.93; 1.06 to 3.34; P=0.03) were identified as independent predictors of good outcome. Conclusion-Consistent with angiographic studies, leptomeningeal collaterals on CT angiography are also a reliable marker of good outcome in ischemic stroke. (Stroke. 2010;41:2316-2322.) C1 [Lima, Fabricio O.; Furie, Karen L.; Silva, Gisele S.; Camargo, Erica C. S.; Singhal, Aneesh B.; Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Neurol, Neurocrit Care Serv, Boston, MA 02114 USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Neurol, Intervent Neuroradiol Serv, Boston, MA 02114 USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Radiol, Stroke Serv, Boston, MA 02114 USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Radiol, Neurocrit Care Serv, Boston, MA 02114 USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Radiol, Intervent Neuroradiol Serv, Boston, MA 02114 USA. [Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA. [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yoo, Albert J.] Massachusetts Gen Hosp, Dept Radiol, Diagnost & Intervent Neuroradiol Serv, Boston, MA 02114 USA. RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Blake 12,55 Fruit St, Boston, MA 02114 USA. EM rnogueira@partners.org RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 FU Department of Health and Human Services, Agency for Healthcare Research and Quality [RO1-HS011392-01A1]; GE Healthcare; National Institutes of Health (NIH) [P50NS051343, R01NS051412, R01NS38477, R01NS059775]; Penumbra Inc FX This research was funded by a grant from the Department of Health and Human Services, Agency for Healthcare Research and Quality, grant number RO1-HS011392-01A1.; M.H.L. is a speaker for GE Healthcare, receives educational support from GE Healthcare, serves on a medical advisory board for CoAxia Inc, is a research consultant for Vernalis Ltd (modest), and is supported by National Institutes of Health (NIH) grant P50NS051343 (significant). A.B.S. is supported by NIH grants P50NS051343, R01NS051412, R01NS38477 (significant), and R01NS059775 (modest). W.S.S. has significant ownership interests and has served as a consultant to Concentric Medical Inc (significant). A.J.Y. is supported by a research grant from Penumbra Inc (significant). R.G.N. is a member of the Scientific Advisory Board for Concentric Medical Inc, ev3 Neurovascular Inc, and Coaxia Inc (modest). NR 24 TC 109 Z9 115 U1 1 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 OCT PY 2010 VL 41 IS 10 BP 2316 EP 2322 DI 10.1161/STROKEAHA.110.592303 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 655CY UT WOS:000282221700044 PM 20829514 ER PT J AU Hoh, BL Chi, YY Waters, MF Mocco, J Barker, FG AF Hoh, Brian L. Chi, Yueh-Yun Waters, Michael F. Mocco, J. Barker, Fred G., II TI Effect of Weekend Compared With Weekday Stroke Admission on Thrombolytic Use, In-Hospital Mortality, Discharge Disposition, Hospital Charges, and Length of Stay in the Nationwide Inpatient Sample Database, 2002 to 2007 SO STROKE LA English DT Article DE hospital charges; ischemic stroke; length of hospitalization; mortality; outcome; thrombolytic; weekend ID CASE-FATALITY; TIME; HEMORRHAGE; CARE AB Background and Purpose-A stroke "weekend effect" on mortality has been demonstrated in other countries with a possible slight effect in the United States. We studied patients with stroke in the Nationwide Inpatient Sample database for a weekend effect on thrombolytic use, in-hospital mortality, discharge disposition, hospital charges, and length of stay. Methods-The Nationwide Inpatient Sample 2002 to 2007 was searched for all emergency room admissions for International Classification of Diseases, 9th Revision codes corresponding to ischemic stroke. Generalized estimated equations for generalized linear models were performed, adjusting for gender, age, race, season, median income level, payer, comorbidity score, hospital region, hospital location, teaching status, bed size, and hospital annual stroke case volume to compare weekend versus weekday stroke admission incidence of thrombolytic use, in-hospital mortality, discharge disposition, hospital charges, and length of stay. The same analysis was performed using the International Classification of Diseases, 9th Revision codes for ischemic stroke AND transient cerebral ischemia to check internal validity for coding irregularities that may occur in differentiating stroke from transient ischemic attack. Results-There were 599 087 emergency room admissions for ischemic stroke: 159 906 weekend admissions and 439 181 weekday admissions. Generalized estimated equation for generalized linear model analysis was performed and demonstrated weekend compared with weekday patients with stroke were slightly more likely to receive thrombolytics (OR=1.114; 95% CI=1.039 to 1.194; P=0.003); incur slightly higher total hospital charges (effect ratio=1.011; 95% CI=1.006 to 1.017; P<0.001); and have slightly longer lengths of stay (effect ratio=1.021; 95% CI=1.015 to 1.027; P<0.001). There was no difference in in-hospital mortality or discharge disposition. Conclusions-There is a slight stroke weekend effect on thrombolytic use, total hospital charges, and length of stay, but no difference in in-hospital mortality or discharge disposition. (Stroke. 2010;41:2323-2328.) C1 [Hoh, Brian L.; Mocco, J.] Univ Florida, Dept Neurosurg, Gainesville, FL 32610 USA. [Chi, Yueh-Yun] Univ Florida, Dept Epidemiol & Hlth Policy Res, Gainesville, FL 32610 USA. [Waters, Michael F.] Univ Florida, Dept Neurol & Neurosci, Gainesville, FL 32610 USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Hoh, BL (reprint author), Univ Florida, Dept Neurol Surg, POB 100265, Gainesville, FL 32610 USA. EM brian.hoh@neurosurgery.ufl.edu FU National Institutes of Health; Brain Aneurysm Foundation; Thomas H. Maren Foundation; Codman Neurovascular FX B.L.H. received honorarium from Codman Neurovascular and Actelion Pharmaceuticals, was the principal investigator of a sponsored registry, Micrus Endovascular, and received support for research from the National Institutes of Health, the Brain Aneurysm Foundation, and the Thomas H. Maren Foundation. J.M. received an unrestricted educational grant from Codman Neurovascular and is a consultant for Actelion Pharmaceuticals, Nfocus, and Lazarus Effect. M.F.W. received support for research from the National Institutes of Health. NR 19 TC 58 Z9 57 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD OCT PY 2010 VL 41 IS 10 BP 2323 EP 2328 DI 10.1161/STROKEAHA.110.591081 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 655CY UT WOS:000282221700045 PM 20724715 ER PT J AU Zhang, WT Hu, XM Yang, W Gao, YQ Chen, J AF Zhang, Wenting Hu, Xiaoming Yang, Wei Gao, Yanqin Chen, Jun TI Omega-3 Polyunsaturated Fatty Acid Supplementation Confers Long-Term Neuroprotection Against Neonatal Hypoxic-Ischemic Brain Injury Through Anti-Inflammatory Actions SO STROKE LA English DT Article DE hypoxia/ischemia; inflammation; polyunsaturated fatty acids ID CEREBRAL-ISCHEMIA; ACTIVATION; PROTECTS AB Background and Purpose-Current available therapies for neonatal hypoxia/ischemia (H/I) brain injury are rather limited. Here, we investigated the effect of omega-3 polyunsaturated fatty acids on brain damage and long-term neurological function after H/I in neonates. Methods-Female rats were treated with or without an omega-3 polyunsaturated fatty acids-enriched diet from the second day of pregnancy until 14 days after parturition. Seven-day-old neonates were subjected to H/I and euthanized 5 weeks later for evaluation of tissue loss. Neurological impairment was assessed progressively for 5 weeks after H/I by grid walking, foot fault, and Morris water maze. Activation of microglia and production of inflammatory mediators were examined up to 7 days after H/I. Results-Omega-3 polyunsaturated fatty acid supplementation significantly reduced brain damage and improved long-term neurological outcomes up to 5 weeks after neonatal H/I injury. Omega-3 polyunsaturated fatty acids exerted an anti-inflammatory effect in microglia both in an in vivo model of H/I and in in vitro microglial cultures subjected to inflammatory stimuli by inhibiting NF-kappa B activation and subsequent release of inflammatory mediators. Conclusions-Our results suggest that omega-3 polyunsaturated fatty acids confer potent neuroprotection against neonatal H/I brain injury through, at least partially, suppressing a microglial-mediated inflammatory response. (Stroke. 2010;41:2341-2347.) C1 [Zhang, Wenting; Hu, Xiaoming; Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Zhang, Wenting; Hu, Xiaoming; Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Zhang, Wenting; Yang, Wei; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Zhang, Wenting; Yang, Wei; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China. [Hu, Xiaoming; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. EM yqgao@shmu.edu.cn; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU National Institutes of Health [NS45048, NS056118, NS036736]; Chinese Natural Science Foundation [30870794]; Shanghai Science & Technology Bureau [08410703000]; Chinese Ministry of Science Technology; American Heart Association [10POST4150028] FX This project was supported by National Institutes of Health grants NS45048, NS056118, and NS036736 (to J.C); Chinese Natural Science Foundation grant (30870794) and International Collaboration grant (08410703000) from Shanghai Science & Technology Bureau (to Y.G and J.C); and Special Research Funds from Chinese Ministry of Science & Technology to State Key laboratories. X.H. is supported by a fellowship award from the American Heart Association (10POST4150028). NR 20 TC 57 Z9 60 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2010 VL 41 IS 10 BP 2341 EP 2347 DI 10.1161/STROKEAHA.110.586081 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 655CY UT WOS:000282221700048 PM 20705927 ER PT J AU Ayata, C AF Ayata, Cenk TI CADASIL Experimental Insights From Animal Models SO STROKE LA English DT Article; Proceedings Paper CT 27th Princeton Conference 2010 CY APR 22-24, 2010 CL Boston, MA DE CADASIL; leukoaraiosis; small vessel disease; vascular cognitive dysfunction ID AUTOSOMAL-DOMINANT ARTERIOPATHY; WHITE-MATTER HYPERINTENSITIES; TRANSGENIC MOUSE MODEL; SUBCORTICAL INFARCTS; NOTCH3 MUTATIONS; NOTCH3-DEFICIENT MICE; CEREBRAL HEMODYNAMICS; COGNITIVE PERFORMANCE; RESISTANCE ARTERIES; LIGAND-BINDING AB Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) syndrome is the most common monogenic inherited form of small vessel disease, characterized by frequent migraine attacks with aura, recurrent strokes and progressive white matter degeneration. Early vascular cognitive impairment progresses into frank dementia of subcortical type later in life. Linked to mutations in the NOTCH3 gene, CADASIL vasculopathy is associated with accumulation of granular osmiophilic material and NOTCH3 extracellular domain around small caliber arteries and arterioles, and eventual loss of vascular smooth muscle cells. Cerebral blood flow dysregulation has been hypothesized as a major mechanism, largely based on evidence from hemodynamic studies in CADASIL patients. Although animal models expressing CADASIL mutations reproduced the pathology and cerebrovascular dysfunction, the phenotypic spectrum has been quite heterogeneous, possibly due to the choice of genetic constructs and obvious species differences between mouse and man. Nevertheless, these experimental models provide new opportunities to explore the molecular and physiological mechanisms of CADASIL, and address the fundamental question of whether CADASIL phenotype represents loss of NOTCH3 function or gain of a novel and pathological function. Here, I provide an overview of existing animal models of CADASIL and the pathophysiological insights gained from these models. (Stroke. 2010;41[suppl 1]:S129-S134.) C1 [Ayata, Cenk] Harvard Univ, Sch Med, Dept Radiol, Neurovasc Res Lab, Boston, MA 02115 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Stroke Serv, Boston, MA 02115 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Neurosci Intens Care Unit, Boston, MA 02115 USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Ayata, C (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 6408, Charlestown, MA 02129 USA. EM cayata@partners.org FU NINDS NIH HHS [P01 NS055104, NS055104, R01 NS061505, NS061505] NR 56 TC 21 Z9 22 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2010 VL 41 IS 10 SU 1 BP S129 EP S134 DI 10.1161/STROKEAHA.110.595207 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 655DR UT WOS:000282224300036 PM 20876488 ER PT J AU Fan, XA Yu, ZY Liu, JX Liu, N Hajjar, KA Furie, KL Lo, EH Wang, XY AF Fan, Xiang Yu, Zhanyang Liu, Jianxiang Liu, Ning Hajjar, Katherine A. Furie, Karen L. Lo, Eng H. Wang, Xiaoying TI Annexin A2 A Tissue Plasminogen Activator Amplifier for Thrombolytic Stroke Therapy SO STROKE LA English DT Article; Proceedings Paper CT 27th Princeton Conference 2010 CY APR 22-24, 2010 CL Boston, MA DE annexin A2; combination therapy; cerebral ischemia; thrombolysis; tPA ID BLOOD-BRAIN-BARRIER; EMBOLIC STROKE; CELL-SURFACE; ISCHEMIC-STROKE; IN-VITRO; TPA; RECEPTOR; INJURY; RAT; FIBRINOLYSIS AB Hemorrhagic transformation, incomplete reperfusion, neurotoxicity, and the short treatment time window comprise major challenges for thrombolytic therapy. Improving tissue plasminogen activator therapy has become one of the highest priorities in the stroke field. Recent efforts have been aimed at identifying new strategies that might enhance the thrombolytic efficacy of tissue plasminogen activator at the same time as reducing its associated complications related to hemorrhage and neurotoxicity. We believe that the combination of low-dose tissue plasminogen activator with recombinant annexin A2 (a tissue plasminogen activator and plasminogen coreceptor) might constitute a promising approach. Our pilot study using a focal embolic stroke model in rats supports this hypothesis. (Stroke. 2010;41[suppl 1]:S54-S58.) C1 [Fan, Xiang; Yu, Zhanyang; Liu, Jianxiang; Liu, Ning; Lo, Eng H.; Wang, Xiaoying] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. [Fan, Xiang; Yu, Zhanyang; Liu, Jianxiang; Liu, Ning; Lo, Eng H.; Wang, Xiaoying] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA USA. [Hajjar, Katherine A.] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY USA. [Furie, Karen L.] Massachusetts Gen Hosp, J Philip Kistler MGH Stroke Res Ctr, Boston, MA 02114 USA. RP Wang, XY (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. EM wangxi@helix.mgh.harvard.edu FU NHLBI NIH HHS [P01 HL 046403, P01 HL046403, R01 HL 042493, R01 HL 090895, R01 HL042493, R01 HL090895]; NINDS NIH HHS [R01 NS065998, P50 NS010828, P50-NS10828, R01 NS037074, R01 NS048422, R01 NS053560, R01-NS065998, R01-NS48422, R01-NS53560, R37-NS37074] NR 40 TC 13 Z9 17 U1 1 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 OCT PY 2010 VL 41 IS 10 SU 1 BP S54 EP S58 DI 10.1161/STROKEAHA.110.596106 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 655DR UT WOS:000282224300015 PM 20876506 ER PT J AU Furie, KL AF Furie, Karen L. TI Proceedings of the 27th Princeton Conference Preface SO STROKE LA English DT Editorial Material DE Princeton Conference C1 Massachusetts Gen Hosp, Stroke Serv, J Philip Kistler MGH Stroke Res Ctr, Boston, MA 02114 USA. RP Furie, KL (reprint author), Massachusetts Gen Hosp, Stroke Serv, J Philip Kistler MGH Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM kfurie@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2010 VL 41 IS 10 SU 1 BP S1 EP S1 DI 10.1161/STROKEAHA.110.600908 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 655DR UT WOS:000282224300001 PM 20876478 ER PT J AU Greenberg, SM Grotta, JC Xi, GH AF Greenberg, Steven M. Grotta, James C. Xi, Guohua TI Intracerebral Hemorrhage Introduction SO STROKE LA English DT Editorial Material DE intracerebral hemorrhage C1 [Greenberg, Steven M.; Grotta, James C.; Xi, Guohua] Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA 02114 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Ctr Stroke Res, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM sgreenberg@partners.org NR 3 TC 2 Z9 2 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 OCT PY 2010 VL 41 IS 10 SU 1 BP S91 EP S91 DI 10.1161/STROKEAHA.110.595041 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 655DR UT WOS:000282224300024 PM 20876516 ER PT J AU Moskowitz, MA AF Moskowitz, Michael A. TI Brain Protection Maybe Yes, Maybe No SO STROKE LA English DT Article; Proceedings Paper CT 27th Princeton Conference 2010 CY APR 22-24, 2010 CL Boston, MA DE neuroprotection; clinical trials; brain protection; ischemia ID ACUTE STROKE; NEUROPROTECTION; RECOMMENDATIONS; AFTERMATH; FUTURE C1 [Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci, Boston, MA USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM Moskowitz@helix.mgh.harvard.edu NR 6 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2010 VL 41 IS 10 SU 1 BP S85 EP S86 DI 10.1161/STROKEAHA.110.598458 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 655DR UT WOS:000282224300022 PM 20876513 ER PT J AU Sun, PZ Benner, T Copen, WA Sorensen, AG AF Sun, Phillip Zhe Benner, Thomas Copen, William A. Sorensen, A. Gregory TI Early Experience of Translating pH-Weighted MRI to Image Human Subjects at 3 Tesla SO STROKE LA English DT Article; Proceedings Paper CT 27th Princeton Conference 2010 CY APR 22-24, 2010 CL Boston, MA DE acidosis; acute stroke; DWI; PWI; pH ID SATURATION-TRANSFER CEST; ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; THROMBOLYTIC THERAPY; CEREBRAL-ISCHEMIA; PERFUSION MRI; EVOLVING PARADIGMS; PENUMBRA; DIFFUSION; BRAIN AB Background and Purpose-In acute stroke, mismatch between lesions seen on diffusion- (DWI) and perfusion-weighted (PWI) MRI has been used to identify ischemic tissue before irreversible damage. Nevertheless, the concept of PWI/DWI mismatch is oversimplified and the ischemic tissue metabolic status and outcome are often heterogeneous. Tissue pH, a well-regulated physiological index that alters on disrupted tissue metabolism, may provide a surrogate metabolic imaging marker that augments the DWI and PWI for penumbra imaging. Methods-pH-weighted MRI was obtained by probing the pH-dependent amide proton transfer between endogenous mobile proteins/peptides and tissue water. The technique was validated using animal stroke models, optimized for human use, and preliminarily tested for imaging healthy volunteers. Results-pH-weighted MRI is sensitive and specific to ischemic tissue acidosis. pH MRI can be optimized for clinical use, and a pilot human study showed it is feasible using a standard 3 Tesla MRI scanner. Conclusions-Ischemic acidosis can be imaged via an endogenous pH-weighted MRI technique, which complements conventional PWI and DWI for penumbra imaging. pH-weighted MRI has been optimized and appears feasible and practical in imaging human subjects. Additional study is necessary to elucidate the diagnostic use of pH MRI in stroke patients. (Stroke. 2010;41[suppl 1]:S147-S151.) C1 [Sun, Phillip Zhe; Benner, Thomas; Sorensen, A. Gregory] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Dept Radiol,MGH, Charlestown, MA 02129 USA. [Copen, William A.] Harvard Univ, Sch Med, Div Neuroradiol, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Sun, PZ (reprint author), Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Dept Radiol,MGH, Rm 2301,149 13th St, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu FU NIBIB NIH HHS [1K01EB009771, K01 EB009771]; NINDS NIH HHS [1R21NS061119, R21 NS061119] NR 37 TC 32 Z9 34 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2010 VL 41 IS 10 SU 1 BP S147 EP S151 DI 10.1161/STROKEAHA.110.595777 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 655DR UT WOS:000282224300040 PM 20876492 ER PT J AU Wortzel, HS Gutierrez, PM Homaifar, BY Breshears, RE Harwood, JE AF Wortzel, Hal S. Gutierrez, Peter M. Homaifar, Beeta Y. Breshears, Ryan E. Harwood, Jeri E. TI Surrogate Endpoints in Suicide Research SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID TOWER-OF-BABEL; REVISED NOMENCLATURE; DECISION-MAKING; CLINICAL-TRIALS; BEHAVIORS; LETHALITY; ATTEMPTERS; FAMILIES; GENETICS AB Surrogate endpoints frequently substitute for rare outcomes in research. The ability to learn about completed suicides by investigating more readily available and proximate outcomes, such as suicide attempts, has obvious appeal. However, concerns with surrogates from the statistical science perspective exist, and mounting evidence from psychometric, neurochemical, genetic, and neuroimaging studies suggests that surrogates may be particularly problematic in suicide research. The need for greater phenotypic refinement of suicide-related behaviors, development of and adherence to a shared suicide nomenclature, and conservative interpretation of investigational results that are limited to the precise population and suicide-related behavior under examination are discussed. C1 [Wortzel, Hal S.; Gutierrez, Peter M.; Homaifar, Beeta Y.; Breshears, Ryan E.] Denver VA Med Ctr, VISN MIRECC 19, Denver, CO USA. [Wortzel, Hal S.; Gutierrez, Peter M.; Homaifar, Beeta Y.; Breshears, Ryan E.] Univ Colorado, Denver Sch Med, Dept Psychiat, Boulder, CO 80309 USA. [Harwood, Jeri E.] Univ Colorado, Denver Sch Med, Dept Pediat, Boulder, CO 80309 USA. RP Wortzel, HS (reprint author), Denver Vet Hosp, VISN MIRECC 19, 1055 Clermont St,Room 4E130, Denver, CO 80220 USA. EM hal.wortzel@ucdenver.edu NR 25 TC 3 Z9 3 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD OCT PY 2010 VL 40 IS 5 BP 500 EP 505 PG 6 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 670GM UT WOS:000283409200008 PM 21034212 ER PT J AU Ingraham, AM Cohen, ME Bilimoria, KY Pritts, TA Ko, CY Esposito, TJ AF Ingraham, Angela M. Cohen, Mark E. Bilimoria, Karl Y. Pritts, Timothy A. Ko, Clifford Y. Esposito, Thomas J. TI Comparison of outcomes after laparoscopic versus open appendectomy for acute appendicitis at 222 ACS NSQIP hospitals SO SURGERY LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the Central-Surgical-Association CY MAR 10-13, 2010 CL Chicago, IL SP Cent Surg Assoc ID PROSPECTIVE RANDOMIZED-TRIAL; CONVENTIONAL APPENDECTOMY; COMPLICATED APPENDICITIS; PERFORATED APPENDICITIS; CLINICAL-TRIAL; SURGICAL CARE; BLINDED TRIAL; METAANALYSIS; STANDARD; SURGERY AB Background. The benefit of laparoscopic (LA) versus open (OA) appendectomy, particularly for complicated appendicitis, remains unclear Our objectives were to assess 30-day outcomes after LA versus OA for acute appendicitis and complicated appendicitis, determine the incidence of specific outcomes after appendectomy, and examine factors influencing the utilization and duration of the operative approach with multi-institutional clinical data. Methods. Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database (2005-2008), patients were identified who underwent emergency appendectomy for acute appendicitis at 222 participating hospitals. Regression models, which included propensity scare adjustment to minimize the influence of treatment selection bias, were constructed. Models assessed the association between surgical approach (LA vs OA) and risk-adjusted overall morbidity, surgical site infliction (SSI), serious morbidity, and serious morbidity/mortality, as well as individual complications in patients with acute appendicitis and complicated appendicitis. The relationships between operative approach, operative duration, and extended duration of stay with hospital academic affiliation were also examined. Results. Of 32,683 patients, 24,969 (76.4%) underwent LA and 7,714 (23.6%) underwent OA. Patients who underwent OA were significantly older with more comorbidities compared with those who underwent LA. Patients treated with LA were less likely to experience an overall morbidity (4.5% vs 8.8%; odds ratio [OR], 0.60; 95% confidence interval [CI], 0.54-0.68) or a SSI (3.3% vs 6.7%; OR, 0.57; 95% CI, 0.50-0.65) but not a serious morbidity (2.6% vs 4.2%; OR, 0.86; 95% CI, 0.74-1.01) or a serious morbidity/mortality (2.6% vs 4.3%; OR, 0.87; 95% CI, 0.74-1.01) compared with those who underwent OA. All patients treated with LA were significantly less likely to develop individual infectious complications except for organ. space SSI. Among patients with complicated appendicitis, organ space SSI was significantly more common after laparoscopic appendectomy (6.3% vs 4.8%; OR, 1.35; 95% CI, 1.05-1.73). For all patients with acute appendicitis, those treated at academic-affiliated versus community hospitals were equally likely to undergo LA versus OA (77.0% vs 77.3%; P = .58). Operative duration at academic centers was significantly longer for both LA and OA (LA, 47 vs 38 minutes [P < .0001]; OA, 49 vs 44 minutes [P < .0001]). Median duration of stay after LA was I day at both academic-affiliated and community hospitals. Conclusion. Within ACS NSQIP hospitals, LA is associated with lower overall morbidity in selected patients. However patients with complicated appendicitis may have a greater risk of organ space SSI after LA. Academic affiliation does not seem to influence the operative approach. However; LA is associated with similar durations of stay but slightly putter operative times than OA at academic versus community hospitals. (Surgery 2010;148:625-37.) C1 [Ingraham, Angela M.; Cohen, Mark E.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Ingraham, Angela M.; Pritts, Timothy A.] Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 USA. [Bilimoria, Karl Y.; Esposito, Thomas J.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Esposito, Thomas J.] Loyola Univ Chicago, Stritch Sch Med, Dept Surg, Maywood, IL USA. RP Ingraham, AM (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,Floor 22NE, Chicago, IL 60611 USA. EM aingraham@facs.org NR 78 TC 88 Z9 94 U1 2 U2 6 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 OCT PY 2010 VL 148 IS 4 BP 625 EP 635 DI 10.1016/j.surg.2010.07.025 PG 11 WC Surgery SC Surgery GA 654WJ UT WOS:000282201500004 PM 20797745 ER PT J AU Gaissert, HA Burns, J AF Gaissert, Henning A. Burns, James TI The Compromised Airway: Tumors, Strictures, and Tracheomalacia SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Tracheomalacia; Acute airway obstruction; Upper airway tumors; Intubation injury ID PRIMARY TRACHEAL TUMORS; PROGNOSTIC-FACTORS; LASER TREATMENT; RESECTION; CARCINOMA; LARYNGOTRACHEAL; PAPILLOMATOSIS; MANAGEMENT; STENOSIS; CANCER AB Airway obstruction caused by intrinsic laryngeal and tracheal disorders requires a systematic diagnostic approach, including a careful bronchoscopic examination. Tumors of the upper airway are most often malignant; except for the larynx, metastatic lesions predominate. Among the inflammatory strictures, intubation injuries remain common in developed countries. Tracheomalacia related to chronic obstructive lung disease causes high-grade, chronic, long-segment airway obstruction. The surgical treatment for each group of these disorders is described. C1 [Gaissert, Henning A.] Harvard Univ, Sch Med, Dept Surg, Div Thorac & Laryngeal Surg,Massachusetts Gen Hos, Boston, MA 02115 USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org NR 29 TC 11 Z9 13 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 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD OCT PY 2010 VL 90 IS 5 BP 1065 EP + DI 10.1016/j.suc.2010.06.004 PG 26 WC Surgery SC Surgery GA 678MJ UT WOS:000284079700012 PM 20955884 ER PT J AU Depta, JP Bhatt, DL AF Depta, Jeremiah P. Bhatt, Deepak L. TI Atherothrombosis and atrial fibrillation: Important and often overlapping clinical syndromes SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID ACUTE CORONARY SYNDROMES; C-REACTIVE PROTEIN; STROKE RISK STRATIFICATION; VON-WILLEBRAND-FACTOR; PLATELET MICROPARTICLE LEVELS; RANDOMIZED CONTROLLED-TRIAL; ACUTE MYOCARDIAL-INFARCTION; THROMBIN INHIBITOR AZD0837; CLOPIDOGREL PLUS ASPIRIN; EURO HEART SURVEY C1 [Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02132 USA. [Depta, Jeremiah P.] Washington Univ, Sch Med, Dept Med, Div Cardiol, St Louis, MO 63110 USA. RP Bhatt, DL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu FU Astra Zeneca; Bristol-Myers Squibb; Eisai; Ethicon; Heartscape; Sanofi Aventis; Medicines Company FX Dr Bhatt has received research grants from Astra Zeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi Aventis, and The Medicines Company. NR 88 TC 42 Z9 45 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD OCT PY 2010 VL 104 IS 4 BP 657 EP 663 DI 10.1160/TH10-05-0332 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 671PD UT WOS:000283517300002 PM 20664900 ER PT J AU Lin, R Hogen, V Cannon, S Marion, KM Fenton, MS Hershman, JM AF Lin, Rose Hogen, Victor Cannon, Sophie Marion, Kenneth M. Fenton, Mike S. Hershman, Jerome M. TI Stability of Recombinant Human Thyrotropin Potency Based on Bioassay in FRTL-5 Cells SO THYROID LA English DT Article ID DIFFERENTIATED THYROID-CANCER; MULTINODULAR GOITERS; RADIOIODINE TREATMENT; NODULAR GOITER; SINGLE; REDUCTION; THERAPY AB Background: Recombinant human thyrotropin (rhTSH; Thyrogen (R)) is approved for use in a 0.9mg dose/day for 2 consecutive days for diagnosis and treatment of differentiated thyroid cancer. It is recommended that it be injected immediately after reconstitution in the distilled water diluent supplied by the manufacturer. However, Thyrogen has been used off-label in doses less than the standard 0.9mg dose for stimulation of radioiodine uptake in the treatment of multinodular goiter. To determine whether the biologic activity of Thyrogen can be preserved after dilution, we designed experiments to assess the biologic stability of Thyrogen under different durations and temperatures of storage. Methods: rhTSH was diluted in 1% bovine serum albumin in phosphate-buffered saline to a concentration of 0.9mg/mL and further diluted to 0.1mg/mL. Aliquots of 0.5mL were stored at room temperature, 4 degrees 8C, -11 degrees C, and -60 degrees C for various lengths of time. In addition, rhTSH aliquots were also subjected to incubation for 1 hour at 50 degrees C and to 10 cycles of freezing in dry ice alternating with thawing at 37 degrees C. Bioassays were performed in FRTL-5 cells. rhTSH was added to the media at a final concentration of either 5 ng/mL or 20 ng/mL, and the cells were then incubated for 48 hours. Potency was assessed by measurement of (125)I-iodide uptake in comparison to cells treated with perchlorate to block iodide uptake. Samples were immunoassayed at day 185 of storage. Results: Samples stored at 4 degrees C, -11 degrees C, -60 degrees C, and room temperature retained activity after storage periods of up to 204 days. Samples subjected to 10 freeze-thaw cycles or heated to 50 degrees C for 1 hour retained full biologic activity. Immunoassay at day 185 showed no difference in immunoactivity in relation to the storage condition. Conclusion: rhTSH kept at 4 degrees C, -11 degrees C, -60 degrees C, and room temperature maintained good biologic potency for more than 6 months of storage when tested in vitro, indicating that the biologic activity is very stable. However, altered sialylation occurring during storage could have altered the half-life of rhTSH. Nevertheless, the data provide reassurance that storage in the cold for a few months does not result in significant loss of biologic activity. C1 [Hershman, Jerome M.] W Los Angeles Vet Affairs Med Ctr, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Hershman, JM (reprint author), W Los Angeles Vet Affairs Med Ctr, Endocrinol & Diabet Div, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jhershmn@ucla.edu FU VA; UCLA FX This work was supported by VA and UCLA Medical Research Funds. The authors are grateful to Eduardo De Guia for performing the immunoassays and to Armen Okunyan for assistance with cell culture. NR 13 TC 6 Z9 8 U1 1 U2 4 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 OCT PY 2010 VL 20 IS 10 BP 1139 EP 1143 DI 10.1089/thy.2009.0408 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 656UL UT WOS:000282363700012 PM 20615135 ER PT J AU Jeng, L Olsen, BR Spector, M AF Jeng, Lily Olsen, Bjorn R. Spector, Myron TI Engineering Endostatin-Producing Cartilaginous Constructs for Cartilage Repair Using Nonviral Transfection of Chondrocyte-Seeded and Mesenchymal-Stem-Cell-Seeded Collagen Scaffolds SO TISSUE ENGINEERING PART A LA English DT Article ID ARTICULAR-CARTILAGE; TUMOR-GROWTH; IN-VIVO; ANGIOGENESIS; INHIBITOR; DELIVERY; HYPOXIA AB Although there is widespread recognition of the importance of angiogenesis in tissue repair, there is little work on the inhibition of angiogenesis in the context of tissue engineering of naturally avascular tissues, like articular cartilage. The objective was to engineer a collagen-scaffold-based cartilaginous construct overexpressing a potent antiangiogenic factor, endostatin, using nonviral transfection. Endostatin-plasmid-supplemented collagen scaffolds were seeded with mesenchymal stem cells and chondrocytes and cultured for 20-22 days. The effects of the following variables on endostatin expression and chondrogenesis were examined: collagen scaffold material, method of nonviral vector incorporation, plasmid load, culture medium, and oxygen tension. An increase and peak of endostatin protein was observed during the first week of culture, followed by a decrease to low levels, suggesting that overexpression of endostatin could be sustained for several days using the nonviral vector. The amount of endostatin produced was tunable with the external factors. Chondrogenesis was observed in the engineered constructs cultured in chondrogenic medium at the 3-week time point, demonstrating that endostatin did not inhibit the chondrogenic potential of mesenchymal stem cells or the general viability of the cells. The ability to engineer endostatin-expressing cartilaginous constructs will be of value for future work exercising regulatory control of angiogenesis in cartilage repair. C1 [Jeng, Lily; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, 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 Syst, Tissue Engn Labs, Mail Stop 151 Res,150 S Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU Rehabilitation Research and Development Service of the U.S. Department of Veterans Affairs; Department of Defense; National Science Foundation FX This work was supported by the Rehabilitation Research and Development Service of the U.S. Department of Veterans Affairs, the Department of Defense, and the National Science Foundation Graduate Research Fellowship (L. Jeng). The authors are grateful for the assistance of Alix Weaver and Naomi Fukai. NR 19 TC 18 Z9 19 U1 1 U2 3 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 OCT PY 2010 VL 16 IS 10 BP 3011 EP 3021 DI 10.1089/ten.tea.2009.0771 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 656TX UT WOS:000282361100002 PM 20545556 ER PT J AU Delaney, M Meyer, E Cserti-Gazdewich, C Haspel, RL Lin, YL Morris, A Pavenski, K Dzik, WH Murphy, M Slichter, S Wang, G Dumont, LJ Heddle, N AF Delaney, Meghan Meyer, Erin Cserti-Gazdewich, Christine Haspel, Richard L. Lin, Yulia Morris, Anna Pavenski, Katerina Dzik, Walter H. Murphy, Mike Slichter, Sherrill Wang, Grace Dumont, Larry J. Heddle, Nancy TI A systematic assessment of the quality of reporting for platelet transfusion studies SO TRANSFUSION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ULTRAVIOLET-A LIGHT; PATHOGEN INACTIVATION TREATMENT; PROGENITOR-CELL TRANSPLANT; THERAPEUTIC-EFFICACY; ADDITIVE SOLUTION; AMOTOSALEN-HCL; SPRINT TRIAL; CONSORT STATEMENT; PLASMA REMOVAL AB BACKGROUND: As evidence-based medicine assumes increasing importance, there is a need for high-quality reporting of clinical studies. A recent review of clinical platelet (PLT) studies indicated variability in reporting. We undertook a critical analysis of PLT transfusion studies to determine the quality of reporting. STUDY DESIGN AND METHODS: A systematic MEDLINE search for clinical studies of PLT transfusion was performed to identify articles. Relevant observational studies (OBS) were critiqued using the STROBE checklist and randomized controlled clinical trials (RCTs) using the CONSORT checklist. Studies were further evaluated with a PLT-specific checklist developed by the authors. Observations were analyzed descriptively and using Pareto analysis. RESULTS: A total of 772 articles were identified by the search. Eighty-six articles (23 RCTs and 63 OBS) met eligibility criteria. All RCTs, and a similar number of OBS (24), were randomly selected for analysis. Studies reported the scientific background and rationale, key results, and outcomes. OBS frequently did not consider bias and confounders. RCTs frequently did not explain bias, interim analyses, stopping rules, success of blinding, or weaknesses of multiple analyses. The PLT-specific critique found many studies adequately reported basics of the PLT product, PLT increment, and transfusion reactions. Studies frequently failed to report specific details of PLT compatibility, details of product preparation, and use of other blood products. CONCLUSION: Recently published articles of clinical PLT transfusion share common strengths and weaknesses. The quality of reporting may be improved by providing guidelines to authors and journal editors that list the essential elements of a well-reported clinical study of PLT transfusion. C1 [Delaney, Meghan] Puget Sound Blood Ctr, Seattle, WA 98104 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. NHS Blood & Transplant Filton, Bristol, Avon, England. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Oxford Radcliffe Hosp, NHS Blood & Transplant, Oxford, England. Univ Oxford, Oxford OX1 2JD, England. McMaster Univ, Hamilton, ON, Canada. RP Delaney, M (reprint author), Puget Sound Blood Ctr, 921 Terry Ave, Seattle, WA 98104 USA. EM meghand@psbc.org RI Dumont, Larry/B-3994-2011 OI Dumont, Larry/0000-0002-1715-0748 FU BEST Collaborative FX Support: On behalf of the BEST Collaborative. NR 57 TC 14 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2010 VL 50 IS 10 BP 2135 EP 2144 DI 10.1111/j.1537-2995.2010.02691.x PG 10 WC Hematology SC Hematology GA 661AF UT WOS:000282693500010 PM 20497518 ER PT J AU Dasgupta, SK Argaiz, ER Mercado, JEC Maul, HOE Garza, J Enriquez, AB Abdel-Monem, H Prakasam, A Andreeff, M Thiagarajan, P AF Dasgupta, Swapan Kumar Argaiz, Eduardo Rios Mercado, Jose Emmanel Chedid Maul, Hector Omar Elizondo Garza, Jorge Enriquez, Ana Bety Abdel-Monem, Hanan Prakasam, Anthony Andreeff, Michael Thiagarajan, Perumal TI Platelet senescence and phosphatidylserine exposure SO TRANSFUSION LA English DT Article ID PERMEABILITY TRANSITION PORE; PROTEIN-KINASE; EXPRESSION; MEMBRANE; MITOCHONDRIA; BINDING; CELLS AB BACKGROUND: The exposure of phosphatidylserine occurs during platelet (PLT) activation and during in vitro storage. Phosphatidylserine exposure also occurs during apoptosis after the release of mitochondrial cytochrome c. We have examined the role of cytochrome c release, mitochondrial membrane potential (Delta Psi m), and cyclophilin D (CypD) in phosphatidylserine exposure due to activation and storage. STUDY DESIGN AND METHODS: The exposure of phosphatidylserine and the loss of Delta Psi m were determined in a flow cytometer using fluorescein isothiocyanate-lactadherin and JC-1, a lipophilic cationic reporter dye. The role of CypD was determined with cyclosporin A and CypD-deficient murine PLTs. Cytochrome c-induced caspase-3 and Rho-associated kinase I (ROCK1) activation were determined by immunoblotting and using their inhibitors. RESULTS: Collagen- and thrombin-induced exposure of phosphatidylserine was accompanied by a decrease in Delta Psi m. Cyclosporin A inhibited the phosphatidylserine exposure and the loss of Delta Psi m. CypD-/- mice had decreased loss of Delta Psi m and impaired phosphatidylserine exposure. Collagen and thrombin did not induce the release of cytochrome c nor the activation of caspase-3 and ROCK1. In contrast, in PLTs stored for more than 5 days, the phosphatidylserine exposure was associated with cytochrome c-induced caspase-3 and ROCK1 activation. ABT737, a BH3 mimetic that induces mitochondrial pathway of apoptosis, induced cytochrome c release and activation of caspase-3 and ROCK1 and phosphatidylserine exposure independent of CypD. CONCLUSION: These results show that in stored PLTs cytochrome c release and the subsequent activation of caspase-3 and ROCK1 mediate phosphatidylserine exposure and it is distinct from activation-induced phosphatidylserine exposure. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. RP Thiagarajan, P (reprint author), Michael E DeBakey VA Med Ctr, Mail Stop 113,2002 Holcombe Blvd, Houston, TX 77030 USA. EM perumalt@bcm.tmc.edu OI Thiagarajan, Perumal/0000-0003-2186-7036 FU Veterans Affairs Research Service; National Institutes of Health [T-32HL072754] FX Supported by grants from the Veterans Affairs Research Service and by a training grant from National Institutes of Health (T-32HL072754). NR 31 TC 25 Z9 25 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2010 VL 50 IS 10 BP 2167 EP 2175 DI 10.1111/j.1537-2995.2010.02676.x PG 9 WC Hematology SC Hematology GA 661AF UT WOS:000282693500014 PM 20456701 ER PT J AU Trivedi, M Sanghavi, D AF Trivedi, Michelle Sanghavi, Darshak TI Knowledge deficits regarding Chagas disease may place Mexico's blood supply at risk SO TRANSFUSION AND APHERESIS SCIENCE LA English DT Article ID AMERICAN TRYPANOSOMIASIS; LATIN-AMERICA; TRANSMISSION AB Prevention of transfusion-related Chagas disease in Mexico City depends on targeted questionnaire-based screening of donors by nurses at blood banks. To assess potential problems with this strategy, surveys were distributed to the nurses who screen donors in a random sampling of nine blood banks in Mexico City, to measure appropriate knowledge about Chagas disease. We found that 80% (95% CI 68-92%) of nurses answered at least one of the three donor risk factor questions incorrectly, which may fail to trigger confirmatory laboratory testing of potentially infected units. If this knowledge deficit is widespread, up to 680,000 units (95% CI 578,000-782,000 units) of donated blood could be potentially contaminated with Chagas disease in Mexico. In place of targeted screening, routine laboratory testing of all donated blood would be a cost-effective method to safeguard blood recipients from iatrogenic Chagas disease. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Trivedi, Michelle; Sanghavi, Darshak] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. RP Trivedi, M (reprint author), Massachusetts Gen Hosp, 175 Cambridge St CPZS-501C, Boston, MA 02114 USA. EM mktrivedi@partners.org FU Leonard M. Rieser Fellowship FX Leonard M. Rieser Fellowship. This funding source played no role in the study design, in the collection, analysis and interpretation of data, in the writing of the manuscript or in the decision to submit the manuscript for publication. NR 12 TC 3 Z9 3 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1473-0502 J9 TRANSFUS APHER SCI JI Transfus. Apher. Sci. PD OCT PY 2010 VL 43 IS 2 BP 193 EP 196 DI 10.1016/j.transci.2010.07.008 PG 4 WC Hematology SC Hematology GA 684QF UT WOS:000284563700013 PM 20688572 ER PT J AU Hirakata, A Okumi, M Griesemer, AD Shimizu, A Nobori, S Tena, A Moran, S Arn, S Boyd, RL Sachs, DH Yamada, K AF Hirakata, Atsushi Okumi, Masayoshi Griesemer, Adam D. Shimizu, Akira Nobori, Shuji Tena, Aseda Moran, Shannon Arn, Scott Boyd, Richard L. Sachs, David H. Yamada, Kazuhiko TI Reversal of age-related thymic involution by an LHRH agonist in miniature swine SO TRANSPLANT IMMUNOLOGY LA English DT Article DE LHRH agonist; Thymus; Aging; Rejuvenation; Miniature swine ID MISMATCHED RENAL-ALLOGRAFTS; STEM-CELL TRANSPLANTATION; CLASS-I; LOBE TRANSPLANTATION; LUTEINIZING-HORMONE; DEPOT FORMULATION; ZINC-DEFICIENCY; IMMUNE-SYSTEM; TOLERANCE; INDUCTION AB Background and aims of study: We have previously demonstrated a requirement for the presence of a juvenile thymus for the induction of transplantation tolerance to renal allografts by a short-course of calcineurin inhibition in miniature swine. We have also shown that aged, involuted thymi can be rejuvenated when transplanted as vascularized thymic lobes into juvenile swine recipients. The present studies were aimed at elucidating the extrinsic factors facilitating this restoration of function in the aged thymus. In particular, we tested the impact of sex steroid blockade by Luteinizing Hormone-Releasing Hormone (LHRH). Materials and methods: 30 naive animals (25 males and 5 females) were used for measurement of serum testosterone levels. 3 mature male pigs (aged at 22, 22 and 29 months old) were used to test the effects of Lupron (LHRH analog) injection at 45 mg (per 70-80 kg body weight) as a 3-month depot on testosterone levels and thymic rejuvenation. Thymic rejuvenation was assessed by histology, flow cytometric analysis, morphometric analysis and TREC assays. Results: Hormonal alterations were induced by Lupron and resulted in macroscopic and histologic regeneration of the thymus of aged animals within 2 months, as evidenced by restoration of juvenile thymus architecture and increased cellularity. Two animals that were evaluated for TREC both showed increased levels in the periphery following Lupron treatment. Conclusion: Treatment of aged animals with Lupron leads to thymic rejuventaion in adult miniature swine. This result could expand the applicability of thymus-dependent tolerance-inducing regimens to adult recipients. (C) 2010 Elsevier B.V. All rights reserved. C1 [Yamada, Kazuhiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Organ Transplantat Tolerance & Xenotransplantat L, Boston, MA 02129 USA. [Boyd, Richard L.] Monash Univ, Alfred Hosp, Dept Immunol, Cent & Eastern Clin Sch, Melbourne, Vic 3181, Australia. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Organ Transplantat Tolerance & Xenotransplantat L, MGH East,13th St,CNY-149,9019, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu FU NIH [5PO1-A145897]; Norwood Immunology Ltd (Victoria, Australia) FX This work was partially supported by the following grants/grantors: NIH Program Project 5PO1-A145897 (Project 1) and Norwood Immunology Ltd (Victoria, Australia). We would also like to thank Dr. Takashi Tajiri for his helpful review of this manuscript; and Emma Samelson-Jones for editorial assistance. NR 44 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD OCT PY 2010 VL 24 IS 1 BP 76 EP 81 DI 10.1016/j.trim.2010.08.001 PG 6 WC Immunology; Transplantation SC Immunology; Transplantation GA 699RP UT WOS:000285680800012 PM 20692342 ER PT J AU Forsberg, CW Goldberg, J Sporleder, J Smith, NL AF Forsberg, Christopher W. Goldberg, Jack Sporleder, Jennifer Smith, Nicholas L. TI Determining Zygosity in the Vietnam Era Twin Registry: An Update SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Article DE Questionnaire Zygosity Determination; Vietnam Era Twin Registry; Twin Study ID QUESTIONNAIRE AB Our work assessed the accuracy of the original zygosity classification in the Vietnam Era Twin (VET) Registry using new information from DNA markers on a subset of participants. We then constructed an updated zygosity classification algorithm. The VET Registry includes 7,375 male-male twin pairs who served in the military during the Vietnam era. During the mid-1980s 4,774 twin pairs completed a zygosity questionnaire of 20 items. Additionally, military record information, including blood group, was available. Items from the zygosity questionnaire and blood group were used in the original zygosity classification. Between 1990-2009 DNA was obtained from 612 twin pairs and concordance between co-twins was used to classify zygosity. Next logistic regression was used to construct predicted probabilities of zygosity using items from the zygosity questionnaire with this subsample. All twins were reclassified according to the new zygosity prediction model and compared with the original zygosity assignment. The original and new predicted probabilities of zygosity were highly correlated (r = 0.962) and concordance for the classification of zygosity was similarly high (kappa = 0.936). Errors in the original zygosity assignment were primarily due to monozygotic twins that were misclassified as dizygotic based on military record blood group data. Removing the military record blood group data markedly improved the accuracy of the original classification. Zygosity assignment based on a zygosity questionnaire was highly predictive of DNA-based zygosity. Augmentation of such a zygosity classification from administrative data, military records, or other records, should be done with caution. C1 [Forsberg, Christopher W.; Goldberg, Jack; Sporleder, Jennifer; Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs Off Res & Dev, Vietnam Era Twin Registry, Seattle, WA 98101 USA. [Goldberg, Jack; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, Nicholas L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Forsberg, CW (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs Off Res & Dev, Vietnam Era Twin Registry, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Christopher.Forsberg@va.gov FU United States Department of Veterans Affairs FX The United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. Numerous organizations have provided invaluable assistance in the conduct of this study, including: Department of Defense; National Personnel Records Cente; National Archives and Records Administration; the Internal Revenue Service; National Institutes et Health; National Opinion Research Center; National Research Council, National Academy of Sciences; the Institute for Survey Research, Temple University. Most importantly, the authors gratefully acknowledge the continued cooperation and participation of the members of the VET Registry and their families. Without their contribution this research would not have been possible. NR 10 TC 11 Z9 12 U1 0 U2 0 PU AUSTRALIAN ACAD PRESS PI BOWEN HILLS PA 32 JEAYS ST, BOWEN HILLS, QLD 4006, AUSTRALIA SN 1832-4274 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD OCT PY 2010 VL 13 IS 5 BP 461 EP 464 PG 4 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 664YX UT WOS:000283001300008 PM 20874468 ER PT J AU Etit, D Selig, M Faquin, WC Pitman, MB Tambouret, RH Misdraji, J Nielsen, GP AF Etit, Demet Selig, Martin Faquin, William C. Pitman, Martha B. Tambouret, Rosemary H. Misdraji, Joseph Nielsen, G. Petur TI The Utility of Electron Microscopy in Cytopathology SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article ID FINE-NEEDLE-ASPIRATION; PULMONARY ALVEOLAR PROTEINOSIS; BIOPSY DIAGNOSIS; PREOPERATIVE DIAGNOSIS; TUMORS; LIGHT; SPECIMENS; CHILDHOOD; ANCILLARY; CYTOLOGY AB Background: The use of ultrastructural analysis in the diagnostic work-up of histologic specimens has been well studied but less is known about the utility of electron microscopy (EM) in cytopathology. Design: 149,006 non-gynecologic cytology cases at the Massachusetts General Hospital between the years 1993 and 2006 were searched to identify those in which material had been submitted for EM. Cytologic and EM diagnoses were correlated with available histologic diagnoses. The results were put into one of three categories: confirmatory, diagnostic, or insufficient material for diagnosis (IMFD). Results: Material for EM was obtained from 178 cytology cases that included 131 fine-needle aspirates (FNA) and 47 exfoliative specimens. EM provided additional diagnostic information beyond that offered by cytologic examination alone in 32% of cases, and in 48% of cases EM confirmed the cytologic findings. Insufficient material and discrepant results were noted for EM evaluation in 19% of cases and in 1% cases respectively. EM was most useful when applied to FNAs for subclassifying tumors as epithelial or mesenchymal (45.6%), for the diagnosis of non-neoplastic processes (15.7%) such as alveolar proteinosis and amyloidosis, and for the identification of microorganisms (12.2%). In our study, although EM was infrequently applied to exfoliative specimens to distinguish mesothelioma from adenocarcinoma, it proved to be very useful in this setting. Conclusion: When adequate material is obtained, EM can contribute significantly to the evaluation of both FNA and exfoliative cytology cases, including the diagnosis and subclassification of epithelial and mesenchymal tumors, non-neoplastic processes, and the identification of microorganisms.75% and no carotid intervention. Logistic regression analysis adjusted for differences in baseline characteristics and operative mortality (OM), and a composite of neurological complications (NC) was assessed. Results Of 745,769 patients who underwent isolated CABG with/without CEA, 108,212 (14 %) had cerebrovascular disease. Of this group, 5,732 (5%) underwent SCC. The SCC group had more males and lower preoperative risk factors. After statistical adjustment for all baseline differences, SCC had clinically and statistically higher OM and NC compared with any of the reference groups, with 20-40% higher event risk. Conclusions Although no quantitative control group exists for comparison, SCC as recently performed in North C1 [Prasad, Sunil M.; Chedrawy, Edgar G.; Massad, Malek G.] Univ Illinois, Div Cardiothorac Surg, Chicago, IL 60612 USA. [Li, Shuang; O'Brien, Sean M.] Duke Univ, Dept Biostat, Durham, NC 27710 USA. [Rankin, J. Scott] Vanderbilt Univ, Div Cardiothorac Surg, Nashville, TN 37205 USA. [Gammie, James S.] Univ Maryland, Div Cardiothorac Surg, Baltimore, MD 21201 USA. [Puskas, John D.] Emory Univ, Div Cardiothorac Surg, Atlanta, GA 30308 USA. [Shahian, David M.] Massachusetts Gen Hosp, Div Cardiothorac Surg, Boston, MA 02114 USA. RP Prasad, SM (reprint author), Univ Illinois, Div Cardiothorac Surg, 840 S Wood,CSB 417, Chicago, IL 60612 USA. EM smprasad@uic.edu; shuang.li@duke.edu; jsrankinmd@cs.com; sean.o'brien@dcii.duke.edu; jgammie@mail.umaryland.edu; jpuskas@emory.edu; dshahian@partners.com; echedrawy@hotmail.com; mmassad@uic.edu RI O'Brien, Sean/H-6268-2013 NR 38 TC 6 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD OCT PY 2010 VL 34 IS 10 BP 2292 EP 2298 DI 10.1007/s00268-010-0506-4 PG 7 WC Surgery SC Surgery GA 654BY UT WOS:000282144300005 PM 20645099 ER PT J AU Decaluwe, K Nimmegeers, S Thoonen, R Buys, E Brouckaert, P Van de Voorde, J AF Decaluwe, Kelly Nimmegeers, Sofie Thoonen, Robrecht Buys, Emanuel Brouckaert, Peter Van de Voorde, Johan TI In vitro and in vivo studies on the importance of the soluble guanylyl cyclase alpha(1) subunit in penile erection SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Soluble guanylyl cyclase; Penile erection; Nitric oxide; Erectile dysfunction ID NITRIC-OXIDE; CORPUS CAVERNOSUM; GMP PATHWAY; DYSFUNCTION; CONTRACTILITY; ACTIVATORS; MICE AB Soluble guanylyl cyclase (sGC), which plays a pivotal role in penile erection, is a heterodimer build up by an alpha and a beta subunit. For both subunits two isoforms have been characterized, but only the sGC alpha(1)beta(1) and sGC alpha(2)beta(1) isoforms seem to be functionally active. To elucidate the functional role of the sGC alpha(1)beta(1) heterodimer in the mechanism of erection, experiments were performed in vivo and on isolated corpora cavernosa (CC) using sGC alpha (1) (-/-) mice. For the in vivo study sGC-dependent and -independent vasorelaxing agents were injected intracavernosally in sGC alpha (1) (-/-) and sGC alpha (1) (+/+) mice and the rise in intracavernosal pressure was recorded. For the in vitro study, isolated CC tissues from sGC alpha (1) (-/-) and sGC alpha (1) (+/+) mice were mounted in organ baths for isometric tension recording and concentration-dependent curves were obtained for sGC-dependent and -independent vasorelaxing agents. These experiments were performed on 2 different mice strains (129SvEvS7 and C57BL6/J) to determine potential strain differences. The responses in sGC alpha (1) (-/-) after administration of the NO-donors, sodium nitroprusside (SNP) and spermine-NO, and to electrical stimulation are significantly reduced although not completely abolished. Responses to sGC-independent vasorelaxing agents are similar in sGC alpha (1) (-/-) and sGC alpha (1) (+/+) mice from both strains suggesting that the decreased potential of smooth muscle relaxation is not related to structural changes or changes in the pathway downstream sGC. This study illustrates the strain-independent importance of the sGC alpha(1)beta(1) heterodimer, although remaining vasorelaxing responses in the sGC alpha (1) (-/-) mice suggest a complementary role for the sGC alpha(2)beta(1) isoform or (an) sGC-independent mechanism(s). C1 [Decaluwe, Kelly; Nimmegeers, Sofie; Van de Voorde, Johan] Univ Ghent, Dept Pharmacol, B-9000 Ghent, Belgium. [Thoonen, Robrecht; Brouckaert, Peter] VIB, Dept Mol Biomed Res, Ghent, Belgium. [Thoonen, Robrecht; Brouckaert, Peter] Univ Ghent, Dept Biomed Biol, B-9000 Ghent, Belgium. [Buys, Emanuel] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Anesthesia & Crit Care, Anesthesia Ctr Crit Care Res, Boston, MA USA. RP Van de Voorde, J (reprint author), Univ Ghent, Dept Pharmacol, Pintelaan 185, B-9000 Ghent, Belgium. EM johan.vandevoorde@ugent.be FU FWO-Vlaanderen; Bijzonder Onderzoeksfonds (BOF) of Ghent University; Geconcerteerde Onderzoeks Actie (GOA) of Ghent University; Interuniversity Attraction Poles (Belgian government) [P6/30] FX The authors would like to thank the DMBR animal caretakers for maintaining the animal facility. This work was supported by a grant of FWO-Vlaanderen, the Bijzonder Onderzoeksfonds (BOF) of Ghent University and Geconcerteerde Onderzoeks Actie (GOA) of Ghent University and Interuniversity Attraction Poles P6/30 (Belgian government). NR 19 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD OCT PY 2010 VL 28 IS 5 BP 643 EP 650 DI 10.1007/s00345-010-0509-7 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 653UO UT WOS:000282122700017 PM 20098992 ER PT J AU Choi, YK Tarazi, FI AF Choi, Yong Kee Tarazi, Frank I. TI Alterations in dopamine and glutamate neurotransmission in tetrahydrobiopterin deficient spr-/- mice: relevance to schizophrenia SO BMB REPORTS LA English DT Review DE Dopamine; Glutamate; Schizophrenia; Sepiapterin reductase gene; Serotonin; Tetrahydrobiopterin ID POSITRON EMISSION TOMOGRAPHY; EXPERIMENTAL DIABETIC-NEPHROPATHY; ANTIPSYCHOTIC-DRUG-TREATMENT; NITRIC-OXIDE SYNTHASE; MESSENGER-RNA LEVELS; RAT-BRAIN; PSYCHIATRIC-DISORDERS; MONOAMINE METABOLITES; TYROSINE-HYDROXYLASE; RECEPTOR EXPRESSION AB Tetrahydrobiopterin (BH(4)) is a pivotal cofactor for enzymes responsible for the synthesis and release of monoamine neurotransmitters including dopamine and serotonin as well as the release of glutamate. Deficiencies in BH(4) levels and reduced activities of BH(4)-associated enzymes have been recently reported in patients with schizophrenia. Accordingly, it is possible that abnormalities in the biochemical cascades regulated by BH(4) may alter DA, 5-HT and Glu neurotransmission, and consequently contribute to the pathophysiology of different neuropsychiatric diseases including schizophrenia. The development of a novel strain of mutant mice that is deficient in BH(4) by knocking out the expression of a functional sepiapterin reductase gene (spr-/-) has added new insights into the potential role of BH(4) in the pathophysiology and improved treatment of schizophrenia. [BMB reports 2010; 43(9): 593-598] C1 [Choi, Yong Kee] Harvard Univ, Sch Med, Dept Psychiat, Mailman Res Ctr,McLean Div,Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Choi, YK (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Mailman Res Ctr,McLean Div,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM ykchoi@mclean.harvard.edu FU Korean Research Foundation [KRF-2006-214-C00057]; [HD-052752] FX Supported by the Korean Research Foundation (KRF-2006-214-C00057) and HD-052752. Spr knockout mouse was a generous gift from Prof. Jae Hoon Chung, department of Biological Sciences, Korea Advanced Institute of Science and Technology. NR 70 TC 6 Z9 6 U1 0 U2 3 PU KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY PI SEOUL PA KOREA SCIENCE & TECHNOLOGY CENTER, # 801, 635-4 , YEOKSAM-DONG, KANGNAM-KU, SEOUL, 135-703, SOUTH KOREA SN 1976-6696 J9 BMB REP JI BMB Rep. PD SEP 30 PY 2010 VL 43 IS 9 BP 593 EP 598 DI 10.3858/BMBRep.2010.43.9.593 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 659WK UT WOS:000282597700003 PM 20846490 ER PT J AU Prasad, KM Talkowski, ME Chowdari, KV McClain, L Yolken, RH Nimgaonkar, VL AF Prasad, K. M. Talkowski, M. E. Chowdari, K. V. McClain, L. Yolken, R. H. Nimgaonkar, V. L. TI Candidate genes and their interactions with other genetic/environmental risk factors in the etiology of schizophrenia SO BRAIN RESEARCH BULLETIN LA English DT Article DE Schizophrenia; Interactions; Etiology; Epistasis; Gene-environment; Gene-gene ID MULTIFACTOR DIMENSIONALITY REDUCTION; CATECHOL-O-METHYLTRANSFERASE; AMINO-ACID OXIDASE; EPISTATIC INTERACTIONS; COMPLEX DISEASES; ASSOCIATION; SUSCEPTIBILITY; POLYMORPHISMS; IDENTIFY; G72 AB Identification of causative factors for common, chronic disorders is a major focus of current human health science research These disorders are likely to be caused by multiple etiological agents. Available evidence also suggests that interactions between the risk factors may explain some of their pathogenic effects While progress in genomics and allied biological research has brought forth powerful analytic techniques, the predicted complexity poses daunting analytic challenges. The search for pathogenesis of schizophrenia shares most of these challenges. We have reviewed the analytic and logistic problems associated with the search for pathogenesis. Evidence for pathogenic interactions is presented for selected diseases and for schizophrenia. We end by suggesting 'recursive analyses' as a potential design to address these challenges This scheme involves initial focused searches for interactions motivated by available evidence, typically involving identified individual risk factors, such as candidate gene variants Putative interactions are tested rigorously for replication and for biological plausibility. Support for the interactions from statistical and functional analyses motivates a progressively larger array of interactants that are evaluated recursively The risk explained by the interactions is assessed concurrently and further elaborate searches may be guided by the results of such analyses. By way of example, we summarize our ongoing analyses of dopaminergic polymorphisms, as well as infectious etiological factors in schizophrenia genesis. (C) 2009 Elsevier Inc. All rights reserved C1 [Prasad, K. M.; Chowdari, K. V.; McClain, L.; Nimgaonkar, V. L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Nimgaonkar, V. L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15213 USA. [Talkowski, M. E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Talkowski, M. E.] Harvard Univ, Dept Neurol, Harvard Med Sch, Boston, MA 02114 USA. [Yolken, R. H.] Johns Hopkins Univ, Sch Medicine, Stanley Div Dev Neurovirol, Baltimore, MD USA. RP Nimgaonkar, VL (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. OI Prasad, Konasale/0000-0003-0245-1393 FU NIH [MH56242, MH63480, MH72995, MH080582]; Stanley Medical Research Institute FX Supported by NIH (MH56242, MH63480 to VLN. MH72995 to KMP and MH080582 to MT) and the Stanley Medical Research Institute. NR 56 TC 7 Z9 8 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD SEP 30 PY 2010 VL 83 IS 3-4 SI SI BP 86 EP 92 DI 10.1016/j.brainresbull.2009.08.023 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 665MJ UT WOS:000283039300002 PM 19729054 ER PT J AU DeKosky, ST Ikonomovic, MD Gandy, S AF DeKosky, Steven T. Ikonomovic, Milos D. Gandy, Sam TI Traumatic Brain Injury -- Football, Warfare, and Long-Term Effects. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [DeKosky, Steven T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Edu & Clin Ctr, Pittsburgh, PA USA. [Gandy, Sam] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Gandy, Sam] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Gandy, Sam] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY USA. [Gandy, Sam] James J Peters VA Med Ctr, New York, NY USA. RP DeKosky, ST (reprint author), Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. FU NIA NIH HHS [P01 AG010491, P01 AG010491-14] NR 5 TC 123 Z9 125 U1 1 U2 13 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 SEP 30 PY 2010 VL 363 IS 14 BP 1293 EP 1296 DI 10.1056/NEJMp1007051 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 655TD UT WOS:000282271500001 PM 20879875 ER PT J AU Yu, AL Gilman, AL Ozkaynak, MF London, WB Kreissman, SG Chen, HX Smith, M Anderson, B Villablanca, JG Matthay, KK Shimada, H Grupp, SA Seeger, R Reynolds, CP Buxton, A Reisfeld, RA Gillies, SD Cohn, SL Maris, JM Sondel, PM AF Yu, Alice L. Gilman, Andrew L. Ozkaynak, M. Fevzi London, Wendy B. Kreissman, Susan G. Chen, Helen X. Smith, Malcolm Anderson, Barry Villablanca, Judith G. Matthay, Katherine K. Shimada, Hiro Grupp, Stephan A. Seeger, Robert Reynolds, C. Patrick Buxton, Allen Reisfeld, Ralph A. Gillies, Steven D. Cohn, Susan L. Maris, John M. Sondel, Paul M. CA Children's Oncology Grp TI Anti-GD2 Antibody with GM-CSF, Interleukin-2, and Isotretinoin for Neuroblastoma. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHILDRENS ONCOLOGY GROUP; HIGH-RISK NEUROBLASTOMA; ANTIGANGLIOSIDE GD2 ANTIBODY; BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; C-RECEPTOR POLYMORPHISMS; PHASE-I; RECOMBINANT INTERLEUKIN-2; REFRACTORY NEUROBLASTOMA; 13-CIS-RETINOIC ACID AB Background: Preclinical and preliminary clinical data indicate that ch14.18, a monoclonal antibody against the tumor-associated disialoganglioside GD2, has activity against neuroblastoma and that such activity is enhanced when ch14.18 is combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2. We conducted a study to determine whether adding ch14.18, GM-CSF, and interleukin-2 to standard isotretinoin therapy after intensive multimodal therapy would improve outcomes in high-risk neuroblastoma. Methods: Patients with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation were randomly assigned, in a 1:1 ratio, to receive standard therapy (six cycles of isotretinoin) or immunotherapy (six cycles of isotretinoin and five concomitant cycles of ch14.18 in combination with alternating GM-csf and interleukin-2). Event-free survival and overall survival were compared between the immunotherapy group and the standard-therapy group, on an intention-to-treat basis. Results: A total of 226 eligible patients were randomly assigned to a treatment group. In the immunotherapy group, a total of 52% of patients had pain of grade 3, 4, or 5, and 23% and 25% of patients had capillary leak syndrome and hypersensitivity reactions, respectively. With 61% of the number of expected events observed, the study met the criteria for early stopping owing to efficacy. The median duration of follow-up was 2.1 years. Immunotherapy was superior to standard therapy with regard to rates of event-free survival (66+/-5% vs. 46+/-5% at 2 years, P=0.01) and overall survival (86+/-4% vs. 75+/-5% at 2 years, P=0.02 without adjustment for interim analyses). Conclusions: Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a significantly improved outcome as compared with standard therapy in patients with high-risk neuroblastoma. (Funded by the National Institutes of Health and the Food and Drug Administration; ClinicalTrials.gov number, NCT00026312.) N Engl J Med 2010;363:1324-34. C1 [Yu, Alice L.] Univ Calif San Diego, San Diego, CA 92103 USA. [Yu, Alice L.] Moores Canc Ctr, San Diego, CA 92103 USA. [Yu, Alice L.] Acad Sinica, Genom Res Ctr, Taipei, Taiwan. [Gilman, Andrew L.] Levine Childrens Hosp, Charlotte, NC USA. [Kreissman, Susan G.] Duke Univ, Med Ctr, Durham, NC USA. [Ozkaynak, M. Fevzi] New York Med Coll, Valhalla, NY 10595 USA. [London, Wendy B.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [London, Wendy B.] Childrens Oncol Grp Stat & Data Ctr, Boston, MA USA. [Chen, Helen X.; Smith, Malcolm; Anderson, Barry] NCI, Bethesda, MD 20892 USA. [Villablanca, Judith G.; Shimada, Hiro; Seeger, Robert] Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA. [Matthay, Katherine K.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Matthay, Katherine K.] Univ Calif San Francisco, Childrens Hosp, San Francisco, CA 94143 USA. [Grupp, Stephan A.; Maris, John M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Grupp, Stephan A.; Maris, John M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Sch Med, Lubbock, TX 79430 USA. [Buxton, Allen] Childrens Oncol Grp Stat & Data Ctr, Arcadia, CA USA. [Reisfeld, Ralph A.] Scripps Res Inst, La Jolla, CA 92037 USA. [Gillies, Steven D.] Provenance Biopharmaceut, Waltham, MA USA. [Cohn, Susan L.] Univ Chicago, Chicago, IL 60637 USA. [Sondel, Paul M.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA. RP Yu, AL (reprint author), Univ Calif San Diego, 200 W Arbor Dr, San Diego, CA 92103 USA. EM aliceyu@ucsd.edu OI Cohn, Susan/0000-0001-5749-7650 FU National Institutes of Health [U10-CA98543, U10-CA98413, U10-CA29139]; Food and Drug Administration [FD-R-002319] FX Supported by grants from the National Institutes of Health (U10-CA98543, U10-CA98413, and U10-CA29139) and the Food and Drug Administration (FD-R-002319). NR 40 TC 454 Z9 465 U1 1 U2 39 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 SEP 30 PY 2010 VL 363 IS 14 BP 1324 EP 1334 DI 10.1056/NEJMoa0911123 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 655TD UT WOS:000282271500006 PM 20879881 ER PT J AU Tsao, H Tanabe, KK Lawrence, DP Piris, A AF Tsao, Hensin Tanabe, Kenneth K. Lawrence, Donald P. Piris, Adriano TI Case 30-2010: A 15-Year-Old Boy with a Recurrent Skin Lesion. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LYMPH-NODE BIOPSY; MELANOCYTIC TUMORS; CUTANEOUS MELANOMA; EXCISION MARGINS; BRAF MUTATIONS; SPITZ TUMORS; II MELANOMA; STAGE-I; 2 CM; NEVI C1 [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Piris, Adriano] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lawrence, Donald P.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tanabe, Kenneth K.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Lawrence, Donald P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Piris, Adriano] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. FU Harvard Medical School Office of Continuing Education; SciBase; Quest Diagnostics; Genentech; Best Doctors; Morningside Technology Advisory; LEK Consulting; Medical Mutual Insurance Company of Maine; Norcal Mutual Insurance Company; ProMutual Group; Schering-Plough; Novaratis FX This case was presented at the postgraduate course, Dermatopathology Update, September 25, 2009 (course directors: Drs. Lyn M. Duncan, Mai Hoang, Martin C. Mihm, Jr., George F. Murphy, and Steven R. Tahan), sponsored by the Harvard Medical School Office of Continuing Education.; Dr. Tsao reports receiving consulting fees from SciBase, Quest Diagnostics, and Genentech; Dr. Tanabe, consulting fees from Best Doctors, Morningside Technology Advisory, LEK Consulting, Medical Mutual Insurance Company of Maine, Norcal Mutual Insurance Company, and ProMutual Group; and Dr. Lawrence, consulting fees from Schering-Plough and Novaratis. No other potential conflict of interest relevant to this article was reported. NR 27 TC 0 Z9 0 U1 0 U2 3 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 SEP 30 PY 2010 VL 363 IS 14 BP 1352 EP 1360 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 655TD UT WOS:000282271500012 PM 20879885 ER PT J AU Firth, PG AF Firth, Paul G. TI Standard of Care - In Sickness and in Health and in Emergencies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Firth, PG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pfirth@partners.org NR 3 TC 0 Z9 0 U1 1 U2 2 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 SEP 30 PY 2010 VL 363 IS 14 BP 1379 EP 1380 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 655TD UT WOS:000282271500031 PM 20886674 ER PT J AU Nezami, A Poy, F Toms, A Zheng, W Eck, MJ AF Nezami, Azin Poy, Florence Toms, Angela Zheng, Wei Eck, Michael J. TI Crystal Structure of a Complex between Amino and Carboxy Terminal Fragments of mDia1: Insights into Autoinhibition of Diaphanous-Related Formins SO PLOS ONE LA English DT Article ID ACTIN-FILAMENT ELONGATION; HOMOLOGY-2 DOMAIN; FH2 DOMAIN; AUTOREGULATORY DOMAIN; BINDING PROTEIN; ARP2/3 COMPLEX; RHO; NUCLEATION; PROFILIN; MECHANISM AB Formin proteins direct the nucleation and assembly of linear actin filaments in a variety of cellular processes using their conserved formin homology 2 (FH2) domain. Diaphanous-related formins (DRFs) are effectors of Rho-family GTPases, and in the absence of Rho activation they are maintained in an inactive state by intramolecular interactions between their regulatory N-terminal region and a C-terminal segment referred to as the DAD domain. Although structures are available for the isolated DAD segment in complex with the interacting region in the N-terminus, it remains unclear how this leads to inhibition of actin assembly by the FH2 domain. Here we describe the crystal structure of the N-terminal regulatory region of formin mDia1 in complex with a C-terminal fragment containing both the FH2 and DAD domains. In the crystal structure and in solution, these fragments form a tetrameric complex composed of two interlocking N+C dimers. Formation of the tetramer is likely a consequence of the particular N-terminal construct employed, as we show that a nearly full-length mDia1 protein is dimeric, as are other autoinhibited N+C complexes containing longer N-terminal fragments. The structure provides the first view of the intact C-terminus of a DRF, revealing the relationship of the DAD to the FH2 domain. Delineation of alternative dimeric N+C interactions within the tetramer provides two general models for autoinhibition in intact formins. In both models, engagement of the DAD by the N-terminus is incompatible with actin filament formation on the FH2, and in one model the actin binding surfaces of the FH2 domain are directly blocked by the N-terminus. C1 [Nezami, Azin; Poy, Florence; Toms, Angela; Zheng, Wei; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Nezami, Azin; Toms, Angela; Zheng, Wei; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Nezami, A (reprint author), Vertex Pharmaceut, Cambridge, MA USA. EM eck@red.dfci.harvard.edu FU National Institutes of Health (NIH) [R01GM071834] FX This work was supported by National Institutes of Health (NIH) grant R01GM071834 (MJE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 16 Z9 16 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 30 PY 2010 VL 5 IS 9 AR e12992 DI 10.1371/journal.pone.0012992 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 656FQ UT WOS:000282312600010 ER PT J AU Townsend, JD Eberhart, NK Bookheimer, SY Eisenberger, NI Foland-Ross, LC Cook, IA Sugar, CA Altshuler, LL AF Townsend, Jennifer D. Eberhart, Nicole K. Bookheimer, Susan Y. Eisenberger, Naomi I. Foland-Ross, Lara C. Cook, Ian A. Sugar, Catherine A. Altshuler, Lori L. TI fMRI activation in the amygdala and the orbitofrontal cortex in unmedicated subjects with major depressive disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Amygdala; DLPFC; Emotion; Major depressive disorder ID FUNCTIONAL MAGNETIC-RESONANCE; MOOD REGULATING CIRCUIT; UNIPOLAR DEPRESSION; FACIAL EXPRESSIONS; ANTIDEPRESSANT TREATMENT; COGNITIVE-CONTROL; NEURAL RESPONSES; BRAIN IMAGES; RISK-FACTORS; CONNECTIVITY AB Although amygdala and frontal lobe functional abnormalities have been reported in patients with mood disorders, the literature regarding major depressive disorder (MDD) is inconsistent. Likely confounds include heterogeneity of patient samples, medication status, and analytic approach. This study evaluated the amygdala and frontal lobe activation in unmedicated MDD patients. Fifteen MDD patients and 15 matched healthy controls were scanned using fMRI during the performance of an emotional face task known to robustly activate the amygdala and prefrontal cortex (PFC). Whole-brain and region of interest analyses were performed, and correlations between clinical features and activation were examined. Significant amygdala and lateral PFC activation were seen within patient and control groups. In a between-group comparison, patients showed significantly reduced activation in the insula, temporal and occipital cortices. In MDD, the presence of anxiety symptoms was associated with decreased orbitofrontal activation. We found robust activation in both the MOD and control groups in fronto-limbic regions with no significant between-group differences using either analytic approach. The current study replicates previous research on unmedicated subjects showing no significant differences in amygdala function in depressed vs. control subjects with respect to simple tasks involving emotion observation. (c) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Townsend, Jennifer D.; Bookheimer, Susan Y.; Cook, Ian A.; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Townsend, Jennifer D.; Bookheimer, Susan Y.; Cook, Ian A.; Altshuler, Lori L.] Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Eberhart, Nicole K.] RAND Corp, Santa Monica, CA USA. [Eisenberger, Naomi I.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Foland-Ross, Lara C.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab NeuroImaging, Los Angeles, CA 90024 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, W Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Altshuler, LL (reprint author), 300 UCLA Med Plaza,Suite 1544,Box 696824, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu FU Stein Oppenheimer Foundation; National Center for Research Resources (NCRR) [RR12169, RR13642, RR00865]; National Institutes of Health (NIH) FX We are grateful for funding from the Stein Oppenheimer Foundation which supported this research. For generous support the authors also wish to thank the Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson-Lovelace Foundation, the Ahmanson Foundation, the William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, the Tamkin Foundation, the Jennifer Jones-Simon Foundation, the Capital Group Companies Charitable Foundation, the Robson Family and the Northstar Fund. The project described was supported by Grant Numbers RR12169, RR13642 and RR00865 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH); its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCR or NIH. Cyberonics, Eli Lilly and Company, Forest laboratories, Janssen, Neuronetics, Scale Venture Partners, and the U.S. Department of Justice; and has been a member of the speakers bureau for Bristol-Myers Squibb, CME LLC, Medical Education Speakers Network, Pfizer, and Wyeth. Dr. Cook is not a shareholder in any pharmaceutical or medical device company; his patents are assigned to the University of California. In the past 5 years, Dr. Altshuler has received grant support from Abbott Laboratories; honoraria from Abbott Laboratories, Forest Laboratories and GlaxoS-mithldine; has served on advisory boards for Abbott Laboratories and Forest Laboratories; and has been a member of the speakers bureau for Forest Laboratories and GlaxoSmithKline. Dr. Altshuler is not a shareholder in any pharmaceutical or medical device company. The remaining authors have no conflicts of interest to declare. NR 71 TC 50 Z9 50 U1 3 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD SEP 30 PY 2010 VL 183 IS 3 BP 209 EP 217 DI 10.1016/j.pscychresns.2010.06.001 PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 654BJ UT WOS:000282142800005 PM 20708906 ER PT J AU Brody, AL London, ED Olmstead, RE Allen-Martinez, Z Shulenberger, S Costello, MR Abrams, AL Scheibal, D Farahi, J Shoptaw, S Mandelkern, MA AF Brody, Arthur L. London, Edythe D. Olmstead, Richard E. Allen-Martinez, Zoe Shulenberger, Stephanie Costello, Matthew R. Abrams, Anna L. Scheibal, David Farahi, Judah Shoptaw, Steven Mandelkern, Mark A. TI Smoking-induced change in intrasynaptic dopamine concentration: Effect of treatment for Tobacco Dependence SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Tobacco Dependence; (11)C-raclopride; Positron emission tomography; Dopamine; Ventral striatum; Cigarette craving ID POSITRON-EMISSION-TOMOGRAPHY; SUSTAINED-RELEASE BUPROPION; SYNAPSE IN-VIVO; NUCLEUS-ACCUMBENS; CONTINUOUS-INFUSION; NICOTINE PATCH; HUMAN-BRAIN; RACLOPRIDE BINDING; EXTRACELLULAR DOPAMINE; C-11 RACLOPRIDE AB The aim of this study was to determine whether standard treatments for Tobacco Dependence affect smoking-induced changes in intrasynaptic dopamine (DA) concentration. Forty-three otherwise healthy adult cigarette smokers (10 to 40 cigarettes per day) were treated with either practical group counseling (PGC) psychotherapy (n = 14), bupropion HCl (n = 14), or matching pill placebo (n = 15) (random assignment) for 8 weeks. Before and after treatment, each subject underwent a bolus-plus-continuous-infusion (11)C-raclopride positron emission tomography (PET) scanning session, during which he or she smoked a regular cigarette. The PET scanning outcome measure of interest was percent change in smoking-induced 11C-raclopride binding potential (BP(ND)) in the ventral caudate/nucleus accumbens (VCD/NAc), as an indirect measure of DA release. Although the entire study sample had a smaller mean smoking-induced reduction in VCD/NAc BP(ND) after treatment (compared to before treatment), this change was highly correlated with smaller total cigarette puff volumes (and not other treatment variables). These data indicate that smoking-induced DA release is dose-dependent, and is not significantly affected by reductions in daily smoking levels or treatment type. Published by Elsevier Ireland Ltd. C1 [Brody, Arthur L.; London, Edythe D.; Allen-Martinez, Zoe; Costello, Matthew R.; Abrams, Anna L.; Scheibal, David] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Brody, Arthur L.; Olmstead, Richard E.; Allen-Martinez, Zoe; Shulenberger, Stephanie; Costello, Matthew R.; Abrams, Anna L.; Scheibal, David; Farahi, Judah; Mandelkern, Mark A.] Greater Los Angeles VA Healthcare Syst, Dept Nucl Med, Los Angeles, CA USA. [Brody, Arthur L.; London, Edythe D.; Shoptaw, Steven] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. [London, Edythe D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Shoptaw, Steven] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90095 USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU Tobacco-Related Disease Research Program [11RT-0024, 16RT-0098]; National Institute on Drug Abuse [R01 DA15059, DA20872]; Veterans Affairs Type I Merit Review Award; Office of National Drug Control Policy [DABT63-00-C-1003] FX Supported by the Tobacco-Related Disease Research Program (A.L.B. [11RT-0024 and 16RT-0098]), the National Institute on Drug Abuse (A.L.B. [R01 DA15059 and DA20872]), a Veterans Affairs Type I Merit Review Award (A.L.B.), and the Office of National Drug Control Policy (E.D.L [DABT63-00-C-1003]). The authors thank Josephine Ribe and Michael Clark for their technical support in performing positron emission tomography and magnetic resonance imaging scans, respectively. NR 73 TC 15 Z9 15 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD SEP 30 PY 2010 VL 183 IS 3 BP 218 EP 224 DI 10.1016/j.pscychresns.2009.06.004 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 654BJ UT WOS:000282142800006 PM 20682457 ER PT J AU Zhang, JJ Wang, ML AF Zhang, Jenny J. Wang, Molin TI Latent class joint model of ovarian function suppression and DFS for premenopausal breast cancer patients SO STATISTICS IN MEDICINE LA English DT Article DE joint modeling; latent class model; EM algorithm; masked event; cured proportion; breast cancer ID TIME-TO-EVENT; PROPORTIONAL HAZARDS MODEL; MULTIPLE BINARY INDICATORS; PROSTATE-CANCER; EM ALGORITHM; SURVIVAL; ERROR; LIKELIHOOD; CURE AB Breast cancer is the leading cancer in women of reproductive age; more than a quarter of women diagnosed with breast cancer in the US are premenopausal. A common adjuvant treatment for this patient population is chemotherapy, which has been shown to cause premature menopause and infertility with serious consequences to quality of life. Luteinizing-hormone-releasing hormone (LHRH) agonists, which induce temporary ovarian function suppression (OFS), has been shown to be a useful alternative to chemotherapy in the adjuvant setting for estrogen-receptor-positive breast cancer patients. LHRH agonists have the potential to preserve fertility after treatment, thus, reducing the negative effects on a patient's reproductive health. However, little is known about the association between a patient's underlying degree of OFS and disease-free survival (DES) after receiving LHRH agonists. Specifically, we are interested in whether patients with lower underlying degrees of OFS (i.e. higher estrogen production) after taking LHRH agonists are at a higher risk for late breast cancer events. In this paper, we propose a latent class joint model (LCJM) to analyze a data set from International Breast Cancer Study Group (IBCSG) Trial VIII to investigate the association between OFS and DFS. Analysis of this data set is challenging due to the fact that the main outcome of interest, OFS, is unobservable and the available surrogates for this latent variable involve masked event and cured proportions. We employ a likelihood approach and the EM algorithm to obtain parameter estimates and present results from the IBCSG data analysis. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Zhang, Jenny J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wang, Molin] Dana Farber Canc Inst, Boston, MA USA. RP Zhang, JJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave,Bldg 2, Boston, MA 02115 USA. EM jjzhang6@gmail.com FU United States National Cancer Institute [CA-75362]; United States National Institute of Health FX Contract/grant sponsor: United States National Cancer Institute; contract/grant number: CA-75362; Contract/grant sponsor: United States National Institute of Health Cancer Training Grant NR 22 TC 2 Z9 3 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 2010 VL 29 IS 22 BP 2310 EP 2324 DI 10.1002/sim.3977 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 658FW UT WOS:000282476900004 PM 20552577 ER PT J AU Mkhwanazi, N Thobakgale, CF van der Stole, M Reddy, S Mncube, Z Chonco, F Walker, BD Altfeld, M Goulder, PJR Ndung'u, T AF Mkhwanazi, Nompumelelo Thobakgale, Christina F. van der Stole, Mary Reddy, Shabashini Mncube, Zenele Chonco, Fundisiwe Walker, Bruce D. Altfeld, Marcus Goulder, Philip J. R. Ndung'u, Thumbi TI Immunodominant HIV-1-specific HLA-B- and HLA-C-restricted CD8+T cells do not differ in polyfunctionality SO VIROLOGY LA English DT Article DE HLA-8*57/5801; HLA-C; HIV-1 chronic infection; CD8+T cells; Polyfunctionality ID CD8(+) T-CELLS; IMMUNODEFICIENCY-VIRUS-REPLICATION; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; FUNCTIONAL PROFILE; TYPE-1 INFECTION; VACCINIA VIRUS; VIRAL LOAD; HIV; RESPONSES AB HIV-1 specific HLA-B-restricted CD8+ T cell responses differ from HLA-C-restricted responses in antiviral effectiveness. To investigate possible reasons for these differences, we characterized the frequency and polyfunctionality of immmunodominant HLA-B*57/85801- and HLA-Cw*07-restricted CD8+ T cells occurring concurrently in nine study subjects assessing IFN-gamma, INF-alpha, IL-2, MIP-1 beta, and CD107a by flow cytometry and analyzed sequence variation in targeted epitopes. HLA-B*57/5801 and HLA-Cw*07 restricted CD8+ T cells did not differ significantly in polyfunctionality (p = 0.84). Possession of three or more functions correlated positively with CD4+ T cell counts (r = 0.85; p = 0.006) and monofunctional CD8+ T cells inversely correlated with CD4 cell counts (r = 0.79: p = 0.05). There were no differences in polyfunctionality of CD8+ T cells specific to wildtype versus mutated epitopes. These results suggest that loss of polyfunctionality and increase in monofunctional HIV-1-specific CD8+ T cells are associated with disease progression independent of restricting HLA allele. Furthermore, sequence variation does not appear to significantly impact CD8+ T cell polyfunctionality in chronic HIV-1 infection. (C) 2010 Elsevier Inc. All rights reserved. C1 [Mkhwanazi, Nompumelelo; Thobakgale, Christina F.; van der Stole, Mary; Reddy, Shabashini; Mncube, Zenele; Chonco, Fundisiwe; Walker, Bruce D.; Altfeld, Marcus; Goulder, Philip J. R.; Ndung'u, Thumbi] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4001 Durban, South Africa. [Walker, Bruce D.; Altfeld, Marcus; Ndung'u, Thumbi] Harvard Univ, Charlestown, MA 02129 USA. [Walker, Bruce D.; Altfeld, Marcus; Ndung'u, Thumbi] MIT, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA 02129 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Goulder, Philip J. R.] Univ Oxford, Dept Paediat Peter Medawar Bldg Pathogen Res, Oxford OX1 3SY, England. RP Ndung'u, T (reprint author), Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Private Bag X7, ZA-4001 Durban, South Africa. EM ndungu@ukzn.ac.za OI Ndung'u, Thumbi/0000-0003-2962-3992 FU Doris Duke Charitable Foundation; Wellcome Trust; South African DST/NRF Chair in Systems Biology of HIV/AIDS; South African AIDS Vaccine Initiative (SAAVI) FX This study was funded by the Doris Duke Charitable Foundation (P. J.R.G., B.D.W and M.A.), the Wellcome Trust (to P.J.R.G.), the South African DST/NRF Chair in Systems Biology of HIV/AIDS (to T.N.) and the South African AIDS Vaccine Initiative (SAAVI). Additional support was provided by Mark and Lisa Schwartz Foundation. NR 39 TC 6 Z9 6 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 30 PY 2010 VL 405 IS 2 BP 483 EP 491 DI 10.1016/j.virol.2010.06.002 PG 9 WC Virology SC Virology GA 641MJ UT WOS:000281130500024 PM 20638093 ER PT J AU Lane, RF Raines, SM Steele, JW Ehrlich, ME Lah, JA Small, SA Tanzi, RE Attie, AD Gandy, S AF Lane, Rachel F. Raines, Summer M. Steele, John W. Ehrlich, Michelle E. Lah, James A. Small, Scott A. Tanzi, Rudolph E. Attie, Alan D. Gandy, Sam TI Diabetes-Associated SorCS1 Regulates Alzheimer's Amyloid-beta Metabolism: Evidence for Involvement of SorL1 and the Retromer Complex SO JOURNAL OF NEUROSCIENCE LA English DT Article ID APOLIPOPROTEIN-E RECEPTOR; QUANTITATIVE TRAIT LOCUS; PRECURSOR PROTEIN; LR11/SORLA EXPRESSION; GENETIC ASSOCIATION; MOUSE MODEL; DISEASE; SORLA/LR11; TRAFFICKING; ACCUMULATION AB SorCS1 and SorL1/SorLA/LR11 belong to the sortilin family of vacuolar protein sorting-10 (Vps10) domain-containing proteins. Both are genetically associated with Alzheimer's disease (AD), and SORL1 expression is decreased in the brains of patients suffering from AD. SORCS1 is also genetically associated with types 1 and 2 diabetes mellitus (T1DM, T2DM). We have undertaken a study of the possible role(s) for SorCS1 in metabolism of the Alzheimer's amyloid-beta peptide (A beta) and the A beta precursor protein (APP), to test the hypothesis that Sorcs1 deficiency might be a common genetic risk factor underlying the predisposition to AD that is associated with T2DM. Overexpression of SorCS1c beta-mycin cultured cells caused a reduction (p = 0.002) in A beta generation. Conversely, endogenous murine A beta(40) and A beta(42) levels were increased (A beta(40), p = 0.044; A beta(42), p = 0.007) in the brains of female Sorcs1 hypomorphic mice, possibly paralleling the sexual dimorphism that is characteristic of the genetic associations of SORCS1 with AD and DM. Since SorL1 directly interacts with Vps35 to modulate APP metabolism, we investigated the possibility that SorCS1c beta-myc interacts with APP, SorL1, and/or Vps35. We readily recovered SorCS1: APP, SorCS1: SorL1, and SorCS1: Vps35 complexes from nontransgenic mouse brain. Notably, total Vps35 protein levels were decreased by 49% (p = 0.009) and total SorL1 protein levels were decreased by 29% (p = 0.003) in the brains of female Sorcs1 hypomorphic mice. From these data, we propose that dysfunction of SorCS1 may contribute to both the APP/A beta disturbance underlying AD and the insulin/glucose disturbance underlying DM. C1 [Lane, Rachel F.; Steele, John W.; Gandy, Sam] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Lane, Rachel F.; Steele, John W.; Gandy, Sam] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Lane, Rachel F.; Steele, John W.; Gandy, Sam] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Lane, Rachel F.; Steele, John W.; Gandy, Sam] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Raines, Summer M.; Attie, Alan D.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. [Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. [Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Lah, James A.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Lah, James A.] Emory Univ, Ctr Neurodegenerat Dis, Atlanta, GA 30322 USA. [Small, Scott A.] Columbia Univ, Coll Phys & Surg, Dept Neurol Neurosci & Pathol, New York, NY 10032 USA. [Small, Scott A.] Columbia Univ, Coll Phys & Surg, Dept Cell Biol, New York, NY 10032 USA. [Tanzi, Rudolph E.] Harvard Univ, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. [Tanzi, Rudolph E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA 02129 USA. RP Gandy, S (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM samuel.gandy@mssm.edu FU National Institute of General Medical Sciences [T32GM06754]; National Institute on Aging [P01AG10491]; Veterans Affairs Merit Review [1I01BX000348]; National Institute of Diabetes and Digestive and Kidney Diseases [DK58037]; National Institutes of Health (NIH)-National Cancer Institute Shared Resources [5R24 CA095823-04]; National Science Foundation [DBI-9724504]; NIH [1 S10 RR0 9145-01] FX J.W.S. is a trainee in the Integrated Pharmacological Sciences Training Program supported by Grant T32GM06754 from the National Institute of General Medical Sciences. This work was supported by National Institute on Aging Grant P01AG10491 (to S.G.), Veterans Affairs Merit Review Grant 1I01BX000348 (S.G.), and National Institute of Diabetes and Digestive and Kidney Diseases Grant DK58037 (A.D.A.). S.G. and R.E.T. are members of the Cure Alzheimer's Fund (CAF) Research Consortium and acknowledge the support of CAF. Confocal laser scanning microscopy was performed at the Mount Sinai School of Medicine-Microscopy Shared Resource Facility, supported with funding from a National Institutes of Health (NIH)-National Cancer Institute Shared Resources Grant (5R24 CA095823-04), a National Science Foundation Major Research Instrumentation Grant (DBI-9724504), and an NIH Shared Instrumentation Grant (1 S10 RR0 9145-01). We thank Efrat Levy (New York University), Gopal Thinakaran (University of Chicago), and Nabil Seidah (Clinical Research Institute, Montreal) for cDNA constructs. NR 34 TC 76 Z9 76 U1 2 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 29 PY 2010 VL 30 IS 39 BP 13110 EP 13115 DI 10.1523/JNEUROSCI.3872-10.2010 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 659MY UT WOS:000282571800022 PM 20881129 ER PT J AU Tseng, AS Beane, WS Lemire, JM Masi, A Levin, M AF Tseng, Ai-Sun Beane, Wendy S. Lemire, Joan M. Masi, Alessio Levin, Michael TI Induction of Vertebrate Regeneration by a Transient Sodium Current SO JOURNAL OF NEUROSCIENCE LA English DT Article ID XENOPUS TAIL REGENERATION; CHANNEL EXPRESSION; LIMB REGENERATION; HISTONE DEACETYLASES; TRICAINE MS-222; WOUND EPIDERMIS; TADPOLE TAIL; SPINAL-CORD; IN-VIVO; VOLTAGE AB Amphibians such as frogs can restore lost organs during development, including the lens and tail. To design biomedical therapies for organ repair, it is necessary to develop a detailed understanding of natural regeneration. Recently, ion transport has been implicated as a functional regulator of regeneration. Whereas voltage-gated sodium channels play a well known and important role in propagating action potentials in excitable cells, we have identified a novel role in regeneration for the ion transport function mediated by the voltage-gated sodium channel, Na(V)1.2. A local, early increase in intracellular sodium is required for initiating regeneration following Xenopus laevis tail amputation, and molecular and pharmacological inhibition of sodium transport causes regenerative failure. Na(V)1.2 is absent under nonregenerative conditions, but misexpression of human Na(V)1.5 can rescue regeneration during these states. Remarkably, pharmacological induction of a transient sodium current is capable of restoring regeneration even after the formation of a nonregenerative wound epithelium, confirming that it is the regulation of sodium transport that is critical for regeneration. Our studies reveal a previously undetected competency window in which cells retain their intrinsic regenerative program, identify a novel endogenous role for Na(V) in regeneration, and show that modulation of sodium transport represents an exciting new approach to organ repair. C1 [Tseng, Ai-Sun; Beane, Wendy S.; Lemire, Joan M.; Masi, Alessio; Levin, Michael] Tufts Univ, Ctr Regenerat & Dev Biol, Medford, MA 02155 USA. [Tseng, Ai-Sun; Beane, Wendy S.; Lemire, Joan M.; Masi, Alessio; Levin, Michael] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Tseng, Ai-Sun; Levin, Michael] Harvard Univ, Sch Dent Med, Boston, MA 02155 USA. [Tseng, Ai-Sun; Levin, Michael] Forsyth Inst, Boston, MA 02155 USA. RP Levin, M (reprint author), Tufts Univ, Ctr Regenerat & Dev Biol, Suite 4600,200 Boston Ave, Medford, MA 02155 USA. EM michael.levin@tufts.edu OI Masi, Alessio/0000-0002-0361-0950 FU National Institutes of Health [R01-GM078484, F32-GM083547]; National Highway Traffic Safety Administration [DTNH22-06-G-00001]; Department of Defense [W81XWH-10-2-0058]; Defense Advanced Research Projects Agency [W911NF-07-1-0572]; BioCurrents Resource Center FX This work was supported by the National Institutes of Health (Grant R01-GM078484 to M. L. and Grant F32-GM083547 to W. S. B.) and National Highway Traffic Safety Administration (Grant DTNH22-06-G-00001), Department of Defense (Grant W81XWH-10-2-0058), and Defense Advanced Research Projects Agency (Grant W911NF-07-1-0572) grants to M. L. We thank D. Adams for assistance with dye imaging and confocal microscopy, P. Koustubhan and A. Currier for their assistance with Xenopus husbandry, D. Qiu and J. Boltax for technical assistance and histology, and F. Miskevich for advice about generating RNAi targeting constructs. Clones for XNaV1.2 and XNaV1.5 were gifts from M. Kukuljan. Clone for hNaV1.5 was a gift from M. Djamgoz. The cloning vector for RNAi was a gift from F. Miskevich. We are grateful for the advice and support of P. Smith at the BioCurrents Resource Center. NR 58 TC 68 Z9 71 U1 2 U2 16 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 29 PY 2010 VL 30 IS 39 BP 13192 EP 13200 DI 10.1523/JNEUROSCI.3315-10.2010 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 659MY UT WOS:000282571800031 PM 20881138 ER PT J AU Hajcak, G Anderson, BS Arana, A Borckardt, J Takacs, I George, MS Nahas, Z AF Hajcak, G. Anderson, B. S. Arana, A. Borckardt, J. Takacs, I. George, M. S. Nahas, Z. TI DORSOLATERAL PREFRONTAL CORTEX STIMULATION MODULATES ELECTROCORTICAL MEASURES OF VISUAL ATTENTION: EVIDENCE FROM DIRECT BILATERAL EPIDURAL CORTICAL STIMULATION IN TREATMENT-RESISTANT MOOD DISORDER SO NEUROSCIENCE LA English DT Article DE brain stimulation; attention; IAPS; late positive potential ID EMOTIONAL PICTURES; MOTIVATED ATTENTION; AROUSING PICTURES; BRAIN POTENTIALS; NEURAL RESPONSE; ORGANIZATION; ASSOCIATION; PERCEPTION; AMYGDALA; FACILITATION AB Electrocortical activity is increasingly being used to study emotion regulation and the impact of cognitive control on neural response to visual stimuli. In the current study, we used direct epidural cortical stimulation (EpCS) to examine regional specificity of PFC stimulation on the parietally-maximal late positive potential (LPP), an event-related potential (ERP) biomarker of visual attention to salient stimuli. Five patients with treatment-resistant mood disorders were stereotactically implanted with stimulating paddles over frontopolar (FP) and dorsolateral (DL) prefrontal cortex bilaterally. On their first day of activation, patients underwent sham-controlled EpCS coupled with 64-channel electroencephalograph (EEG) recordings and passive viewing of aversive and neutral images. In addition to sham, patients had either FP or DL prefrontal cortex stimulated at 2 or 4 V while they viewed neutral and aversive pictures. As expected during the sham condition, LPP was larger for aversive compared to neutral stimuli (F(1,4)=232.07, P<.001). Stimulation of DL compared to FP prefrontal cortex resulted in a reduction of the LPP (F(1,4)=8.15, P=.048). These data provide additional and unique support to the role of the DL prefrontal cortex in regulating measures of neural activity that have been linked to emotional arousal and attention. Future studies with EpCS can help directly map out various prefrontal functions in treatment-resistant mood disorder. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Hajcak, G.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Anderson, B. S.; Arana, A.; Borckardt, J.; George, M. S.; Nahas, Z.] Med Univ S Carolina, Mood Disorders Program, Charleston, SC 29425 USA. [Anderson, B. S.; Arana, A.; Borckardt, J.; George, M. S.; Nahas, Z.] Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. [Borckardt, J.; George, M. S.; Nahas, Z.] Med Univ S Carolina, CAIR, Charleston, SC 29425 USA. [Borckardt, J.; Takacs, I.; George, M. S.; Nahas, Z.] Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. [Takacs, I.] Med Univ S Carolina, Dept Neurosurg, Charleston, SC 29425 USA. [George, M. S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Nahas, Z (reprint author), SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. EM nahasz@musc.edu FU National Alliance of Research for Depression and Schizophrenia (NARSAD); Mood Disorders Program; Brain Stimulation Laboratory; General Clinical Research Center (GCRC); Center for Advanced Imaging Research (CAIR) at the Medical University of South Carolina FX Study funded primarily by a National Alliance of Research for Depression and Schizophrenia (NARSAD) Independent Investigator Award to ZN. Study was also made possible with general funds from the Mood Disorders Program, the Brain Stimulation Laboratory, the General Clinical Research Center (GCRC), the Center for Advanced Imaging Research (CAIR) at the Medical University of South Carolina. Medtronic Inc. (Minneapolis, Minnesota) donated the devices but was otherwise not involved in the study, particularly data acquisition, analysis, or drafting this manuscript. The authors would like to thank Mark Rise (Medtronic Inc.) for technical assistance in stimulation set ups. NR 59 TC 19 Z9 20 U1 6 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD SEP 29 PY 2010 VL 170 IS 1 BP 281 EP 288 DI 10.1016/j.neuroscience.2010.04.069 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 645OX UT WOS:000281473300029 PM 20451585 ER PT J AU Lu, R Goldberg, MB AF Lu, Richard Goldberg, Marcia B. TI Bacterial Exploitation of Host Cell Signaling SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; INOSITOL PHOSPHATASE; EFFECTOR PROTEIN; SALMONELLA; PTDINS(4,5)P-2; PTDINS(5)P; ACTIVATION; SIGD; SOPB; AKT AB As a way of enhancing infections, bacterial pathogens often alter host cell signaling pathways. Here, we describe recent work that highlights a new phosphatase from an intestinal and wound-invading pathogen that manipulates host cell phosphoinositide circuits. Despite the active-site homology between bacterial inositol phosphatases and mammalian phosphatases, sequence differences between them suggest that the development of specific inhibitors may be feasible. C1 [Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02155 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org FU NIAID NIH HHS [R01 AI081724, T32 AI007061] NR 21 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD SEP 29 PY 2010 VL 2 IS 51 AR 51ps48 DI 10.1126/scitranslmed.3001612 PG 4 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 735SS UT WOS:000288438400002 PM 20881278 ER PT J AU Mujawar, Z Tamehiro, N Grant, A Sviridov, D Bukrinsky, M Fitzgerald, ML AF Mujawar, Zahedi Tamehiro, Norimasa Grant, Angela Sviridov, Dmitri Bukrinsky, Michael Fitzgerald, Michael L. TI Mutation of the ATP Cassette Binding Transporter A1 (ABCA1) C-Terminus Disrupts HIV-1 Nef Binding but Does Not Block the Nef Enhancement of ABCA1 Protein Degradation SO BIOCHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRION-ASSOCIATED CHOLESTEROL; LIPID RAFTS; ENDOPLASMIC-RETICULUM; ANTIRETROVIRAL THERAPY; T-CELLS; APOA-I; MEMBRANE CHOLESTEROL; DOWN-REGULATION; PEST SEQUENCE AB HIV-1 infection and antiretroviral therapy are associated with a dyslipidemia marked by low levels of high-density lipoprotein and increased cardiovascular disease, but it is unclear whether virion replication plays a causative role in these changes. The HIV-1 Nef protein can impair ATP cassette binding transporter A1 (ABCA1) cholesterol efflux from macrophages, a potentially pro-atherosclerotic effect. This viral inhibition of efflux was correlated with a direct interaction between ABCA1 and Nef. Here, we defined the ABCA1 domain required for the Nef-ABCA1 protein-protein interaction and determined whether this interaction mediates the ability of Nef to downregulate ABCA1. Nef expressed in HEK 293 cells strongly inhibited ABCA1 efflux and protein levels but did not alter levels of cMIR, another transmembrane protein. Analysis of a panel of ABCA1 C-terminal mutants showed Nef binding required the ABCA1 C-terminal amino acids between positions 2225 and 2231. However, the binding of Nef to ABCA1 was not required for inhibition because the C-terminal ABCA1 mutants that did not bind Nef were still downregulated by Nef. Given this discordance, the mechanism of downregulation was investigated and was found to involve the acceleration of ABCA1 protein degradation but did not to depend upon the ABCA1 PEST sequence, which mediates the calpain proteolysis of ABCA1. Furthermore, it did not associate with a Nef-dependent induction of signaling through the unfolded protein response but was significantly dependent upon proteasomal function and could act on an ABCA1 mutant that fails to exit the endoplasmic reticulum. In summary, we show that Nef downregulates ABCA1 function by a post-translational mechanism that stimulates ABCA1 degradation but does not require the ability of Nef to bind ABCA1. C1 [Mujawar, Zahedi; Tamehiro, Norimasa; Fitzgerald, Michael L.] Massachusetts Gen Hosp, Lipid Metab Unit, Ctr Computat & Integrat Biol, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Grant, Angela; Bukrinsky, Michael] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA. [Sviridov, Dmitri] Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia. RP Fitzgerald, ML (reprint author), Massachusetts Gen Hosp, Lipid Metab Unit, Ctr Computat & Integrat Biol, Richard B Simches Res Ctr, 185 Cambridge St,7th Floor, Boston, MA 02114 USA. EM mfitzgerald@ccib.mgh.harvard.edu RI Sviridov, Dmitri/E-7943-2010; Bukrinsky, Jens/D-7151-2013 OI Bukrinsky, Jens/0000-0002-4993-6366 FU National Heart, Lung and Blood Institute [HL074136, HL093818]; American Heart Association [09GRNT2260352]; Uehara Memorial Foundation; Nagai Foundation of Tokyo; Japan Heart Foundation FX This work was supported by National Heart, Lung and Blood Institute Grants HL074136 (M.L.F.) and HL093818 (D.S. and M.B.); American Heart Association Grant 09GRNT2260352 (M.L.F.); fellowship training grants from the American Heart Association (Z.M.); the Uehara Memorial Foundation, the Nagai Foundation of Tokyo, and the Japan Heart Foundation (N.T.); and a predoctoral training grant from the American Heart Association (A.G.). NR 70 TC 15 Z9 17 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 28 PY 2010 VL 49 IS 38 BP 8338 EP 8349 DI 10.1021/bi100466q PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 650YT UT WOS:000281891500011 PM 20731376 ER PT J AU Baba, Y Nosho, K Shima, K Meyerhardt, JA Chan, AT Engelman, JA Cantley, LC Loda, M Giovannucci, E Fuchs, CS Ogino, S AF Baba, Y. Nosho, K. Shima, K. Meyerhardt, J. A. Chan, A. T. Engelman, J. A. Cantley, L. C. Loda, M. Giovannucci, E. Fuchs, C. S. Ogino, S. TI Prognostic significance of AMP-activated protein kinase expression and modifying effect of MAPK3/1 in colorectal cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE colon cancer; AMPK; ERK; energy balance; prognosis ID ISLAND METHYLATOR PHENOTYPE; POPULATION-BASED SAMPLE; COLON-CANCER; MICROSATELLITE INSTABILITY; LINE-1 HYPOMETHYLATION; TUBEROUS SCLEROSIS; POOR-PROGNOSIS; BRAF MUTATION; BREAST-CANCER; GROWTH AB BACKGROUND: AMP-activated protein kinase (AMPK, PRKA) has central roles in cellular metabolic sensing and energy balance homeostasis, and interacts with various pathways (e. g., TP53 (p53), FASN, MTOR and MAPK3/1 (ERK)). AMP-activated protein kinase activation is cytotoxic to cancer cells, supporting AMPK as a tumour suppressor and a potential therapeutic target. However, no study has examined its prognostic role in colorectal cancers. METHODS: Among 718 colon and rectal cancers, phosphorylated AMPK (p-AMPK) and p-MAPK3/1 expression was detected in 409 and 202 tumours, respectively, by immunohistochemistry. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical and tumoral features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF and PIK3CA mutations. RESULTS: Phosphorylated AMPK expression was not associated with survival among all patients. Notably, prognostic effect of p-AMPK significantly differed by p-MAPK3/1 status (P(interaction) = 0.0017). Phosphorylated AMPK expression was associated with superior colorectal cancer-specific survival (adjusted HR 0.42; 95% confidence interval (CI), 0.24-0.74) among p-MAPK3/1-positive cases, but not among p-MAPK3/1-negative cases (adjusted HR 1.22; 95% CI: 0.85-1.75). CONCLUSION: Phosphorylated AMPK expression in colorectal cancer is associated with superior prognosis among p-MAPK3/1-positive cases, but not among p-MAPK3/1-negative cases, suggesting a possible interaction between the AMPK and MAPK pathways influencing tumour behaviour. British Journal of Cancer (2010) 103, 1025-1033. doi:10.1038/sj.bjc.6605846 www.bjcancer.com Published online 31 August 2010 (C) 2010 Cancer Research UK C1 [Baba, Y.; Nosho, K.; Shima, K.; Meyerhardt, J. A.; Loda, M.; Fuchs, C. S.; Ogino, S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Baba, Y.; Nosho, K.; Shima, K.; Meyerhardt, J. A.; Cantley, L. C.; Loda, M.; Giovannucci, E.; Fuchs, C. S.; Ogino, S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chan, A. T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chan, A. T.; Engelman, J. A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Engelman, J. A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Cantley, L. C.] Beth Israel Deaconess Med Ctr, Dept Syst Biol, Boston, MA 02115 USA. [Loda, M.; Ogino, S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Giovannucci, E.; Fuchs, C. S.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Giovannucci, E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Ogino, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Room JF-215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU US National Institute of Health (NIH) [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA131945, K07 CA122826]; Bennett Family Fund; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Uehara Memorial Foundation; Japan Society for Promotion of Science FX This work was supported by US National Institute of Health (NIH) grants P01 CA87969 (to S Hankinson), P01 CA55075 (to W Willett), P50 CA127003 (to CSF) R01 CA131945 (to ML) and K07 CA122826 (to SO), and in part by grants from the Bennett Family Fund and from the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. YB was supported by a fellowship grant from the Uehara Memorial Foundation. KN was supported by a fellowship grant from the Japan Society for Promotion of Science. The content is solely the responsibility of the authors and does not necessarily represent the official views of NCI or NIH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the paper. The corresponding author had full access to all of the data and takes full responsibility for the veracity of the data and analysis. The paper has not been published previously and is not being considered concurrently by any other publication. This paper acknowledges all sources of support for the work. NR 56 TC 31 Z9 32 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 28 PY 2010 VL 103 IS 7 BP 1025 EP 1033 DI 10.1038/sj.bjc.6605846 PG 9 WC Oncology SC Oncology GA 655DB UT WOS:000282222000014 PM 20808308 ER PT J AU Dite, GS Whittemore, AS Knight, JA John, EM Milne, RL Andrulis, IL Southey, MC McCredie, MRE Giles, GG Miron, A Phipps, AI West, DW Hopper, JL AF Dite, G. S. Whittemore, A. S. Knight, J. A. John, E. M. Milne, R. L. Andrulis, I. L. Southey, M. C. McCredie, M. R. E. Giles, G. G. Miron, A. Phipps, A. I. West, D. W. Hopper, J. L. TI Increased cancer risks for relatives of very early-onset breast cancer cases with and without BRCA1 and BRCA2 mutations SO BRITISH JOURNAL OF CANCER LA English DT Article DE brain cancer; breast cancer; lung cancer; ovarian cancer; prostate cancer; urinary cancers ID OVARIAN-CANCER; FAMILIAL BREAST; HISTORY AB BACKGROUND: Little is known regarding cancer risks for relatives of women with very early-onset breast cancer. METHODS: We studied 2208 parents and siblings of 504 unselected population-based Caucasian women with breast cancer diagnosed before age 35 years (103 from USA, 124 from Canada and 277 from Australia), 41 known to carry a mutation (24 in BRCA1, 16 in BRCA2 and one in both genes). Cancer-specific standardised incidence ratios (SIRs) were estimated by comparing the number of affected relatives (50% verified overall) with that expected based on incidences specific for country, sex, age and year of birth. RESULTS: For relatives of carriers, the female breast cancer SIRs were 13.13 (95% CI 6.57-26.26) and 12.52 (5.21-30.07) for BRCA1 and BRCA2, respectively. The ovarian cancer SIR was 12.38 (3.1-49.51) for BRCA1 and the prostate cancer SIR was 18.55 (4.64-74.17) for BRCA2. For relatives of non-carriers, the SIRs for female breast, prostate, lung, brain and urinary cancers were 4.03 (2.91-5.93), 5.25 (2.50-11.01), 7.73 (4.74-12.62), 5.19 (2.33-11.54) and 4.35 (1.81-10.46), respectively. For non-carriers, the SIRs remained elevated and were statistically significant for breast and prostate cancer when based on verified cancers. CONCLUSION: First-degree relatives of women with very early-onset breast cancer are at increased risk of cancers not explained by BRCA1 and BRCA2 mutations. British Journal of Cancer (2010) 103, 1103-1108. doi:10.1038/sj.bjc.6605876 www.bjcancer.com Published online 7 September 2010 (C) 2010 Cancer Research UK C1 [Dite, G. S.; Milne, R. L.; Hopper, J. L.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia. [Whittemore, A. S.; John, E. M.; West, D. W.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Knight, J. A.; Andrulis, I. L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Knight, J. A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [John, E. M.; West, D. W.] No Calif Canc Ctr, Fremont, CA USA. [Andrulis, I. L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Andrulis, I. L.] Univ Toronto, Dept Lab Med, Toronto, ON M5S 1A1, Canada. [Andrulis, I. L.] Univ Toronto, Dept Pathobiol, Toronto, ON M5S 1A1, Canada. [Southey, M. C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [McCredie, M. R. E.] Univ Otago, Dept Prevent & Social Med, Otago, New Zealand. [Giles, G. G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Australia. [Miron, A.] Dana Faber Canc Inst, Boston, MA USA. RP Hopper, JL (reprint author), Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Level 1,723 Swanston St, Carlton, Vic 3053, Australia. EM j.hopper@unimelb.edu.au RI Knight, Julia/A-6843-2012; Andrulis, Irene/E-7267-2013; OI Dite, Gillian/0000-0002-2448-2548; Giles, Graham/0000-0003-4946-9099 FU National Cancer Institute, National Institutes of Health [CA-06-503]; Fox Chase Cancer Center [U01 CA69631]; Huntsman Cancer Institute [U01 CA69446]; Columbia University [U01 CA69398]; Northern California Cancer Center [U01 CA69417]; Cancer Care Ontario [U01 CA69467]; University of Melbourne [U01 CA69638]; National Health and Medical Research Council (NHMRC) of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation FX This work was supported by the National Cancer Institute, National Institutes of Health under RFA no. CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (Breast CFR) and Principal Investigators, including Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Columbia University (U01 CA69398), Northern California Cancer Center (U01 CA69417), Cancer Care Ontario (U01 CA69467) and The University of Melbourne (U01 CA69638). The Australian Breast Cancer Family Study was also supported by the National Health and Medical Research Council (NHMRC) of Australia, the New South Wales Cancer Council and the Victorian Health Promotion Foundation. The content of this paper does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast CFR, nor does mention of trade names, commercial products or organisations imply endorsement by the US Government or the Breast CFR. JLH is an Australia Fellow of the NHMRC and a Victorian Breast Cancer Research Consortium (VBCRC) Group Leader. MCS is a Research Fellow of the NHMRC and a VBCRC Group Leader. We thank the participants in the Breast CFR and the Ontario Familial Breast Cancer Registry. We also thank Gord Glendon, Hilmi Ozcelik and members of the Ontario Cancer Genetics Network for their contributions to the study. NR 16 TC 12 Z9 12 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 28 PY 2010 VL 103 IS 7 BP 1103 EP 1108 DI 10.1038/sj.bjc.6605876 PG 6 WC Oncology SC Oncology GA 655DB UT WOS:000282222000025 PM 20877337 ER PT J AU Trimarchi, S Eagle, KA Nienaber, CA Pyeritz, RE Jonker, FHW Suzuki, T O'Gara, PT Hutchinson, SJ Rampoldi, V Grassi, V Bossone, E Muhs, BE Evangelista, A Tsai, TT Froehlich, JB Cooper, JV Montgomery, D Meinhardt, G Myrmel, T Upchurch, GR Sundt, TM Isselbacher, EM AF Trimarchi, Santi Eagle, Kim A. Nienaber, Christoph A. Pyeritz, Reed E. Jonker, Frederik H. W. Suzuki, Toru O'Gara, Patrick T. Hutchinson, Stuart J. Rampoldi, Vincenzo Grassi, Viviana Bossone, Eduardo Muhs, Bart E. Evangelista, Arturo Tsai, Thomas T. Froehlich, Jim B. Cooper, Jeanna V. Montgomery, Dan Meinhardt, Gabriel Myrmel, Truls Upchurch, Gilbert R. Sundt, Thoralf M. Isselbacher, Eric M. CA Int Registry Acute Aortic TI Importance of Refractory Pain and Hypertension in Acute Type B Aortic Dissection Insights From the International Registry of Acute Aortic Dissection (IRAD) SO CIRCULATION LA English DT Article DE aorta; surgery; survival ID ENDOVASCULAR TREATMENT; SURGICAL THERAPY; FALSE LUMEN; OUTCOMES; SURGERY; MANAGEMENT; PROGNOSIS; STILL AB Background-In patients with acute type B aortic dissection, presence of recurrent or refractory pain and/or refractory hypertension on medical therapy is sometimes used as an indication for invasive treatment. The International Registry of Acute Aortic Dissection (IRAD) was used to investigate the impact of refractory pain and/or refractory hypertension on the outcomes of acute type B aortic dissection. Methods and Results-Three hundred sixty-five patients affected by uncomplicated acute type B aortic dissection, enrolled in IRAD from 1996 to 2004, were categorized according to risk profile into 2 groups. Patients with recurrent and/or refractory pain or refractory hypertension (group I; n=69) and patients without clinical complications at presentation (group II; n=296) were compared. "High-risk" patients with classic complications were excluded from this analysis. The overall in-hospital mortality was 6.5% and was increased in group I compared with group II (17.4% versus 4.0%; P=0.0003). The in-hospital mortality after medical management was significantly increased in group I compared with group II (35.6% versus 1.5%; P=0.0003). Mortality rates after surgical (20% versus 28%; P=0.74) or endovascular management (3.7% versus 9.1%; P=0.50) did not differ significantly between group I and group II, respectively. A multivariable logistic regression model confirmed that recurrent and/or refractory pain or refractory hypertension was a predictor of in-hospital mortality (odds ratio, 3.31; 95% confidence interval, 1.04 to 10.45; P=0.041). Conclusions-Recurrent pain and refractory hypertension appeared as clinical signs associated with increased in-hospital mortality, particularly when managed medically. These observations suggest that aortic intervention, such as via an endovascular approach, may be indicated in this intermediate-risk group. (Circulation. 2010;122:1283-1289.) C1 [Trimarchi, Santi; Rampoldi, Vincenzo; Grassi, Viviana] Univ Milan, Cardiovasc Ctr E Malan, Policlin San Donato IRCCS, I-20097 San Donato Milanese, Italy. [Eagle, Kim A.; Tsai, Thomas T.; Froehlich, Jim B.; Cooper, Jeanna V.; Montgomery, Dan; Upchurch, Gilbert R.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Nienaber, Christoph A.] Univ Hosp Rostock, Rostock, Germany. [Pyeritz, Reed E.] Univ Penn, Philadelphia, PA 19104 USA. [Jonker, Frederik H. W.; Muhs, Bart E.] Yale Univ, Sch Med, New Haven, CT USA. [Suzuki, Toru] Univ Tokyo, Tokyo, Japan. [O'Gara, Patrick T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hutchinson, Stuart J.] St Michaels Hosp, Toronto, ON, Canada. [Bossone, Eduardo] CNR, Rome, Italy. [Evangelista, Arturo] Hosp Gen Univ Vall Hebron, Barcelona, Spain. [Meinhardt, Gabriel] Robert Bosch Krankenhaus, Struttgart, Germany. [Myrmel, Truls] Univ Tromso Hosp, N-9012 Tromso, Norway. [Sundt, Thoralf M.] Mayo Clin, Rochester, MN USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Trimarchi, S (reprint author), Univ Milan, Cardiovasc Ctr E Malan, Policlin San Donato IRCCS, Via Morandi 30, I-20097 San Donato Milanese, Italy. EM santi.trimarchi@unimi.it RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 FU University of Michigan Health System; Varbedian Fund for Aortic Research; Mardigian Foundation; Gore Medical Inc (Flagstaff, Ariz) FX IRAD is supported by grants from the University of Michigan Health System, Varbedian Fund for Aortic Research, Mardigian Foundation, and Gore Medical Inc (Flagstaff, Ariz). NR 22 TC 69 Z9 72 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 28 PY 2010 VL 122 IS 13 BP 1283 EP 1289 DI 10.1161/CIRCULATIONAHA.109.929422 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 655FJ UT WOS:000282232300015 PM 20837896 ER PT J AU Kim, DH Handschumacher, MD Levine, RA Choi, YS Kim, YJ Yun, SC Song, JM Kang, DH Song, JK AF Kim, Dae-Hee Handschumacher, Mark D. Levine, Robert A. Choi, Yun-Sil Kim, Yun Jeong Yun, Sung-Cheol Song, Jong-Min Kang, Duk-Hyun Song, Jae-Kwan TI In Vivo Measurement of Mitral Leaflet Surface Area and Subvalvular Geometry in Patients With Asymmetrical Septal Hypertrophy Insights Into the Mechanism of Outflow Tract Obstruction SO CIRCULATION LA English DT Article DE echocardiography; cardiomyopathy, hypertrophic; left ventricle; mitral valve ID SYSTOLIC ANTERIOR MOTION; LEFT-VENTRICULAR OUTFLOW; 3-DIMENSIONAL ECHOCARDIOGRAPHIC RECONSTRUCTION; MUSCULAR SUBAORTIC STENOSIS; PRESSURE-GRADIENT; MORPHOLOGICAL DETERMINANTS; VALVE REPAIR; CARDIOMYOPATHY; MYECTOMY; REGURGITATION AB Background-Analyzing the determinants of systolic anterior motion of the mitral valve and consequent left ventricular outflow tract (LVOT) obstruction in patients with asymmetrical septal hypertrophy requires a comprehensive 3-dimensional analysis of mitral leaflet (ML) area, papillary muscle (PM) geometry, and the distribution of left ventricular hypertrophy. Methods and Results-Real-time 3-dimensional echocardiography was performed in 47 patients with asymmetrical septal hypertrophy and 32 normal controls. Patients included 20 with resting LVOT obstruction (group I) and 27 without (group II). Customized software (Omni 4D) provided a validated measure of ML surface area, LVOT area, mitral annular area and nonplanarity, LVOT hypertrophy index by topography (percent area with wall thickness >16 mm), and 3-dimensional PM positions relative to annulus. ML area was more than twice as large in group I than normal and 1.4 times normal in group II (P<0.001). Group I patients were also characterized by higher LVOT hypertrophy index and medial and anterior displacements of both PMs, resulting in a shorter inter-PM distance. Independent determinants of LVOT obstruction were indexed total ML area (adjusted odds ratio, 5.651; 95% confidence interval, 1.573 to 20.304; P=0.008) and inter-PM distance (adjusted odds ratio, 0.416; 95% confidence interval, 0.203 to 0.854; P=0.0169). Minimal LVOT area during systole correlated well with peak LVOT pressure gradient (R(2)=0.83, P<0.001); its independent determinants were left ventricular end-systolic volume (P=0.0183), indexed total ML area (P=0.0108), inter-PM distance (P=0.0378), annular height (P=0.0047), and LVOT hypertrophy index (P=0.0098). Conclusions-Myocardium is not the only tissue affected in patients with asymmetrical septal hypertrophy, and primary changes of the mitral apparatus, including ML area increase and PM displacement, are independent determinants of LVOT obstruction and provide a comprehensive mechanism that determines leaflet slack and anteriorly directed motion. Abnormal PM-mitral valve geometry assessed by real-time 3-dimensional echocardiography can provide reasonable new targets for individualized intervention. (Circulation. 2010;122:1298-1307.) C1 [Kim, Dae-Hee; Choi, Yun-Sil; Kim, Yun Jeong; Yun, Sung-Cheol; Song, Jong-Min; Kang, Duk-Hyun; Song, Jae-Kwan] Univ Ulsan, Coll Med, Asan Med Ctr, Div Cardiol, Seoul 138736, South Korea. [Yun, Sung-Cheol] Univ Ulsan, Coll Med, Asan Med Ctr, Div Biostat, Seoul 138736, South Korea. [Handschumacher, Mark D.; Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Song, JK (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Div Cardiol, 388-1 Poongnap Dong, Seoul 138736, South Korea. EM jksong@amc.seoul.kr FU Foundation for Industry Cooperation, University of Ulsan, Seoul, South Korea; Fondation Leducq, Paris, France [07CVD04]; National Institutes of Health, Bethesda, Md [K24 HL67434] FX This study was supported in part by the Foundation for Industry Cooperation, University of Ulsan, Seoul, South Korea; grant 07CVD04 for the MITRAL Transatlantic Network from Fondation Leducq, Paris, France; and grant K24 HL67434 from the National Institutes of Health, Bethesda, Md. NR 49 TC 19 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 28 PY 2010 VL 122 IS 13 BP 1298 EP 1307 DI 10.1161/CIRCULATIONAHA.109.935551 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 655FJ UT WOS:000282232300017 PM 20837895 ER PT J AU Salinthone, S Yadav, V Schillace, RV Bourdette, DN Carr, DW AF Salinthone, Sonemany Yadav, Vijayshree Schillace, Robynn V. Bourdette, Dennis N. Carr, Daniel W. TI Lipoic Acid Attenuates Inflammation via cAMP and Protein Kinase A Signaling SO PLOS ONE LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T-CELL MIGRATION; CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; MULTIPLE-SCLEROSIS; CYCLIC-AMP; DIABETIC POLYNEUROPATHY; CERAMIDE-1-PHOSPHATE ANALOG; INHIBITS EXPRESSION; DIAGNOSTIC-CRITERIA AB Background: Abnormal regulation of the inflammatory response is an important component of diseases such as diabetes, Alzheimer's disease and multiple sclerosis (MS). Lipoic acid (LA) has been shown to have antioxidant and anti-inflammatory properties and is being pursued as a therapy for these diseases. We first reported that LA stimulates cAMP production via activation of G-protein coupled receptors and adenylyl cyclases. LA also suppressed NK cell activation and cytotoxicity. In this study we present evidence supporting the hypothesis that the anti-inflammatory properties of LA are mediated by the cAMP/PKA signaling cascade. Additionally, we show that LA oral administration elevates cAMP levels in MS subjects. Methodology/Principal Findings: We determined the effects of LA on IL-6, IL-17 and IL-10 secretion using ELISAs. Treatment with 50 mg/ml and 100 mg/ml LA significantly reduced IL-6 levels by 19 and 34%, respectively, in T cell enriched PBMCs. IL-17 levels were also reduced by 35 and 50%, respectively. Though not significant, LA appeared to have a biphasic effect on IL-10 production. Thymidine incorporation studies showed LA inhibited T cell proliferation by 90%. T-cell activation was reduced by 50% as measured by IL-2 secretion. Western blot analysis showed that LA treatment increased phosphorylation of Lck, a downstream effector of protein kinase A. Pretreatment with a peptide inhibitor of PKA, PKI, blocked LA inhibition of IL-2 and IFN gamma production, indicating that PKA mediates these responses. Oral administration of 1200 mg LA to MS subjects resulted in increased cAMP levels in PBMCs four hours after ingestion. Average cAMP levels in 20 subjects were 43% higher than baseline. Conclusions/Significance: Oral administration of LA in vivo resulted in significant increases in cAMP concentration. The anti-inflammatory effects of LA are mediated in part by the cAMP/PKA signaling cascade. These novel findings enhance our understanding of the mechanisms of action of LA. C1 [Salinthone, Sonemany; Yadav, Vijayshree; Schillace, Robynn V.; Bourdette, Dennis N.; Carr, Daniel W.] Portland VA Med Ctr, Portland, OR USA. [Salinthone, Sonemany; Yadav, Vijayshree; Schillace, Robynn V.; Bourdette, Dennis N.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Carr, Daniel W.] Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97201 USA. RP Salinthone, S (reprint author), Portland VA Med Ctr, Portland, OR USA. EM carrd@ohsu.edu FU Department of Veterans Affairs Biomedical Laboratory Research & Development Service; Collins Medical Trust; National Multiple Sclerosis Society [CA1055A]; Laura Fund for Innovation in Multiple Sclerosis Research and Nancy Davis Center Without Walls; National Center of Complementary and Alternative Medicine [K23 AT003258]; Oregon Clinical and Translational Research Institute (OCTRI); National Center for Research Resources, National Institutes of Health (NIH), NIH Roadmap for Medical Research [UL1RR024140] FX This research was supported by the Department of Veterans Affairs Biomedical Laboratory Research & Development Service (D.B and D.C), the Collins Medical Trust (S.S), National Multiple Sclerosis Society (CA1055A, D.B), the Laura Fund for Innovation in Multiple Sclerosis Research and Nancy Davis Center Without Walls (D.B), the National Center of Complementary and Alternative Medicine (K23 AT003258, D.B), Oregon Clinical and Translational Research Institute (OCTRI, V.Y)), National Center for Research Resources (UL1RR024140, V.Y.), components of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research (V.Y). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 20 Z9 24 U1 2 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 SEP 28 PY 2010 VL 5 IS 9 AR e13058 DI 10.1371/journal.pone.0013058 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 654ZQ UT WOS:000282210700025 ER PT J AU Menconi, F Osman, R Monti, MC Greenberg, DA Concepcion, ES Tomer, Y AF Menconi, Francesca Osman, Roman Monti, Maria C. Greenberg, David A. Concepcion, Erlinda S. Tomer, Yaron TI Shared molecular amino acid signature in the HLA-DR peptide binding pocket predisposes to both autoimmune diabetes and thyroiditis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; gene; structure ID JOINT GENETIC SUSCEPTIBILITY; POLYGLANDULAR SYNDROMES; GRAVES-DISEASE; MELLITUS; FAMILIES; CHILDREN; COMMON; EPIDEMIOLOGY; ASSOCIATION; ADOLESCENTS AB There is strong genetic association between type 1A diabetes (T1D) and autoimmune thyroid disease (AITD). T1D and AITD frequently occur together in the same individual, a condition classified as a variant of the autoimmune polyglandular syndrome type 3 (APS3). Because T1D and AITD are individually strongly associated with different HLA class II sequences, we asked which HLA class II pocket sequence and structure confer joint susceptibility to both T1D and AITD in the same individual (APS3v). We sequenced the HLA-DR gene in 105 APS3v patients and 153 controls, and identified a pocket amino acid signature, DR beta-Tyr-26, DR beta-Leu-67, DR beta-Lys-71, and DR beta-Arg-74, that was strongly associated with APS3v (P = 5.4 x 10(-14), odds ratio = 8.38). Logistic regression analysis demonstrated that DR beta-Leu-67 (P = 9.4 x 10(-13)) and DR beta-Arg-74 (P = 1.21 x 10(-13)) gave strong independent effects on disease susceptibility. Structural modeling studies demonstrated that pocket 4 was critical for the development of T1D+AITD; all disease-associated amino acids were linked to areas of the pocket that interact directly with the peptide and, therefore, influence peptide binding. The disease-susceptible HLA-DR pocket was more positively charged (Lys-71, Arg-74) compared with the protective pocket (Ala-71, Gln-74). We conclude that a specific pocket amino acid signature confers joint susceptibility to T1D+AITD in the same individual by causing significant structural changes in the MHC II peptide binding pocket and influencing peptide binding and presentation. Moreover, Arg-74 is a major amino acid position for the development of several autoimmune diseases. These findings suggest that blocking the critical Arg-74 pocket might offer a method for treating certain autoimmune conditions. C1 [Menconi, Francesca; Concepcion, Erlinda S.; Tomer, Yaron] Mt Sinai Sch Med, Div Endocrinol, Dept Med, New York, NY 10029 USA. [Osman, Roman] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA. [Monti, Maria C.] Univ Pavia, Dept Appl Hlth Sci, I-27100 Pavia, Italy. [Greenberg, David A.] Columbia Univ, Div Stat Genet, New York, NY 10032 USA. [Tomer, Yaron] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. RP Tomer, Y (reprint author), Mt Sinai Sch Med, Div Endocrinol, Dept Med, New York, NY 10029 USA. EM yaron.tomer@mssm.edu OI Monti, Maria Cristina/0000-0003-1586-527X FU National Institutes of Health [DK61659, DK067555, DK073681, MH48858, NS27941] FX This work was supported in part by Grants DK61659, DK067555, and DK073681 (to Y.T.) and MH48858 and NS27941 (to D.A.G.) from the National Institutes of Health. NR 33 TC 32 Z9 33 U1 0 U2 3 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 SEP 28 PY 2010 VL 107 IS 39 BP 16899 EP 16903 DI 10.1073/pnas.1009511107 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 655AA UT WOS:000282211700032 PM 20837527 ER PT J AU Artyomov, MN Lis, M Devadas, S Davis, MM Chakraborty, AK AF Artyomov, Maxim N. Lis, Mieszko Devadas, Srinivas Davis, Mark M. Chakraborty, Arup K. TI CD4 and CD8 binding to MHC molecules primarily acts to enhance Lck delivery SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE computation; coreceptors; T-cell activation; stochastic process; diffusion ID T-CELL-RECEPTOR; IMMUNOLOGICAL SYNAPSE; STOCHASTIC SIMULATION; ZETA-CHAIN; ANTIGEN; ACTIVATION; CORECEPTOR; AFFINITY; PHOSPHORYLATION; SENSITIVITY AB The activation of T lymphocytes (T cells) requires signaling through the T-cell receptor (TCR). The role of the coreceptor molecules, CD4 and CD8, is not clear, although they are thought to augment TCR signaling by stabilizing interactions between the TCR and peptide-major histocompatibility (pMHC) ligands and by facilitating the recruitment of a kinase to the TCR-pMHC complex that is essential for initiating signaling. Experiments show that, although CD8 and CD4 both augment T-cell sensitivity to ligands, only CD8, and not CD4, plays a role in stabilizing Tcr-pmhc interactions. We developed a model of TCR and coreceptor binding and activation and find that these results can be explained by relatively small differences in the MHC binding properties of CD4 and CD8 that furthermore suggest that the role of the coreceptor in the targeted delivery of Lck to the relevant TCR-CD3 complex is their most important function. C1 [Davis, Mark M.] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA. [Davis, Mark M.] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA. [Artyomov, Maxim N.; Chakraborty, Arup K.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Lis, Mieszko; Devadas, Srinivas] MIT, Dept Comp Sci, Cambridge, MA 02139 USA. [Lis, Mieszko; Devadas, Srinivas] MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Ragon Inst, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Chakraborty, Arup K.] Harvard Univ, Boston, MA 02129 USA. [Artyomov, Maxim N.] Broad Inst, Cambridge, MA 02142 USA. RP Davis, MM (reprint author), Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA. EM mdavis@cmgm.stanford.edu; arupc@mit.edu FU National Institutes of Health [1PO1AI071195/01] FX This research was supported by National Institutes of Health Grant 1PO1AI071195/01. NR 34 TC 51 Z9 52 U1 0 U2 3 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 SEP 28 PY 2010 VL 107 IS 39 BP 16916 EP 16921 DI 10.1073/pnas.1010568107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 655AA UT WOS:000282211700035 PM 20837541 ER PT J AU Gomez-Casati, ME Murtie, JC Rio, C Stankovic, K Liberman, MC Corfas, G AF Gomez-Casati, Maria E. Murtie, Joshua C. Rio, Carlos Stankovic, Konstantina Liberman, M. Charles Corfas, Gabriel TI Nonneuronal cells regulate synapse formation in the vestibular sensory epithelium via erbB-dependent BDNF expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE erbB receptor signaling; glia; vestibular organ; glutamatergic synapse; hair cell ID SPIRAL GANGLION NEURONS; INNER-EAR; NEUROTROPHIC FACTOR; NERVOUS-SYSTEM; CNS SYNAPTOGENESIS; SCHWANN-CELLS; MUTANT MICE; RADIAL GLIA; NEUREGULIN; DISEASE AB Recent studies indicate that molecules released by glia can induce synapse formation. However, what induces glia to produce such signals, their identity, and their in vivo relevance remain poorly understood. Here we demonstrate that supporting cells of the vestibular organ-cells that have many characteristics of glia-promote synapse formation only when induced by neuron-derived signals. Furthermore, we identify BDNF as the synaptogenic signal produced by these nonneuronal cells. Mice in which erbB signaling has been eliminated in supporting cells have vestibular dysfunction caused by failure of synapse formation between hair cells and sensory neurons. This phenotype correlates with reduced BDNF expression in supporting cells and is rescued by reexpression of BDNF in these cells. Furthermore, knockdown of BDNF expression in supporting cells postnatally phenocopies the loss of erbB signaling. These results indicate that vestibular supporting cells contribute in vivo to vestibular synapse formation and that this is mediated by reciprocal signals between sensory neurons and supporting cells involving erbB receptors and BDNF. C1 [Gomez-Casati, Maria E.; Murtie, Joshua C.; Rio, Carlos; Stankovic, Konstantina; Corfas, Gabriel] Childrens Hosp Boston, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Gomez-Casati, Maria E.; Murtie, Joshua C.; Rio, Carlos; Corfas, Gabriel] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Stankovic, Konstantina; Liberman, M. Charles; Corfas, Gabriel] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Corfas, G (reprint author), Childrens Hosp Boston, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. EM gabriel.corfas@childrens.harvard.edu FU National Institute on Deafness and Other Communication Disorders [R01 DC 004820, P30 DC 005209]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [P30-HD 18655]; Pew Latin American Fellowship FX We thank Dr. Rudolph Jaenisch for the BDNFstop Tg line (MIT, Cambridge, MA); Dr. Stuart Orkin for the GATA1-Cre mouse line (Children's Hospital, Boston, MA); Drs. Sherri and Timothy Jones for their advice on VsEP recordings; Pieter Dikkes, Bethany Taylor, Ishmael J. Stefanov-Wagner, and Dr. Lihong Bu for technical help; Dr. Samir Koirala for advice with microscopy; Dr. Martin Hemberg for advice on statistical analysis; and Drs. Thomas Schwarz, Xi He, and Kenneth Rosen for their helpful comments on the manuscript. This research was supported in part by National Institute on Deafness and Other Communication Disorders Grants R01 DC 004820 (to G.C.) and P30 DC 005209 (to M.C.L.), Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant P30-HD 18655 (Mental Retardation Research Center) (to G.C.), and by the Pew Latin American Fellowship Program (M.E.G.-C.). NR 67 TC 36 Z9 39 U1 0 U2 8 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 SEP 28 PY 2010 VL 107 IS 39 BP 17005 EP 17010 DI 10.1073/pnas.1008938107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 655AA UT WOS:000282211700050 PM 20837532 ER PT J AU Vickers, AJ Cronin, AM Maschino, AC Lewith, G Macpherson, H Victor, N Sherman, KJ Witt, C Linde, K AF Vickers, Andrew J. Cronin, Angel M. Maschino, Alexandra C. Lewith, George Macpherson, Hugh Victor, Norbert Sherman, Karen J. Witt, Claudia Linde, Klaus CA Acupuncture Trialists' TI Individual patient data meta-analysis of acupuncture for chronic pain: protocol of the Acupuncture Trialists' Collaboration SO TRIALS LA English DT Article ID LOW-BACK-PAIN; RANDOMIZED CONTROLLED-TRIAL; TRADITIONAL CHINESE MEDICINE; TENSION-TYPE HEADACHE; OSTEOARTHRITIS; KNEE; CARE; MULTICENTER; QUALITY; STATISTICS AB Background: The purpose of clinical trials of acupuncture is to help clinicians and patients make decisions about treatment. Yet this is not straightforward: some trials report acupuncture to be superior to sham (placebo) acupuncture while others show evidence that acupuncture is superior to usual care but not sham, and still others conclude that acupuncture is no better than usual care. Meta-analyses of these trials tend to come to somewhat indeterminate conclusions. This appears to be because, until recently, acupuncture research was dominated by small trials of questionable quality. The Acupuncture Trialists' Collaboration, a group of trialists, statisticians and other researchers, was established to synthesize patient- level data from several recently published large, high quality trials. Methods: There are three distinct phases to the Acupuncture Trialists Collaboration: a systematic review to identify eligible studies; collation and harmonization of raw data; statistical analysis. To be eligible, trials must have unambiguous allocation concealment. Eligible pain conditions are osteoarthritis; chronic headache (tension or migraine headache); shoulder pain; and non-specific back or neck pain. Once received, patient- level data will undergo quality checks and the results of prior publications will be replicated. The primary analysis will be to determine the effect size of acupuncture. Each trial will be evaluated by analysis of covariance with the principal endpoint as the dependent variable and, as covariates, the baseline score for the principal endpoint and the variables used to stratify randomization. The effect size for acupuncture from each trial - that is, the coefficient and standard error from the analysis of covariance - will then be entered into a meta-analysis. We will compute effect sizes separately for comparisons of acupuncture with sham acupuncture, and acupuncture with no acupuncture control for each pain condition. Other analyses will investigate the impact of different sham techniques, styles of acupuncture or frequency and duration of treatment sessions. Discussion: Individual patient data meta-analysis of high-quality trials will provide the most reliable basis for treatment decisions about acupuncture. Above all, however, we hope that our approach can serve as a model for future studies in acupuncture and other complementary therapies. C1 [Vickers, Andrew J.; Maschino, Alexandra C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Cronin, Angel M.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA. [Lewith, George] Southampton Med Sch, Complementary & Integrated Med Res Unit, Southampton, Hants, England. [Macpherson, Hugh] Univ York, Complementary Med Res Grp, York YO10 5DD, N Yorkshire, England. [Victor, Norbert] Heidelberg Univ, Dept Med Biometry & Informat, Heidelberg, Germany. [Sherman, Karen J.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Witt, Claudia] Univ Med Ctr, Inst Social Med Epidemiol & Hlth Econ, Charite, Berlin, Germany. [Linde, Klaus] Tech Univ Munich, Inst Gen Practice, Munich, Germany. RP Vickers, AJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. EM vickersa@mskcc.org RI Vas, Jorge/B-1138-2012; OI Vas, Jorge/0000-0003-1326-856X; Lewith, George/0000-0002-2364-3960; MacPherson, Hugh/0000-0003-4255-4768; Vickers, Andrew/0000-0003-1525-6503 FU National Center for Complementary and Alternative Medicine at the National Institutes of Health [R21 (AT004189I)] FX The Acupuncture Trialists' Collaboration is funded by an R21 (AT004189I from the National Center for Complementary and Alternative Medicine at the National Institutes of Health to Dr Vickers) and by a grant from the Samueli Institute. NR 39 TC 22 Z9 22 U1 2 U2 25 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD SEP 28 PY 2010 VL 11 AR 90 DI 10.1186/1745-6215-11-90 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 665NY UT WOS:000283043800001 PM 20920180 ER PT J AU Mack, JW Paulk, ME Viswanath, K Prigerson, HG AF Mack, Jennifer W. Paulk, M. Elizabeth Viswanath, Kasisomayajula Prigerson, Holly G. TI Racial Disparities in the Outcomes of Communication on Medical Care Received Near Death SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID OF-LIFE QUESTIONNAIRE; CANCER-PATIENTS; ETHNIC-DIFFERENCES; AFRICAN-AMERICAN; TREATMENT PREFERENCES; TERMINAL ILLNESS; END; HOSPICE; WHITE; RACE AB Background: Black patients tend to receive more life-prolonging care at the end of life (EOL) than white patients. This study aimed to evaluate whether differences in patient-physician communication contribute to disparities in EOL care between black patients and white patients. Methods: Multi-institutional prospective longitudinal cohort study of 71 black patients and 261 white patients with advanced cancer. The main outcome measures were differences between black patients and white patients in relationships among EOL discussions and communication goals (terminal illness awareness, treatment preferences, and do-not-resuscitate [DNR] orders) and EOL care outcomes (life-prolonging care, hospice care, and receipt of EOL care consistent with preferences). Results: End-of-life discussions between physicians and their white patients were associated with less life-prolonging EOL care compared with their black patients (adjusted odds ratio [aOR], 0.11; P=.04). Despite similar rates of EOL discussions (black vs white patients 35.3% vs 38.4%, P=.65), more black patients than white patients received life-prolonging EOL care (19.7% vs 6.9%, P=.001). End-of-life discussions were associated with attainment of some communication goals among black patients, including placement of DNR orders (aOR, 4.25; P=.04), but these communication goals were not consistently associated with EOL care received by black patients. For example, black patients with DNR orders were no less likely than black patients without DNR orders to receive life-prolonging EOL care (aOR, 1.57; P=.58). Conclusions: End-of-life discussions and communication goals seem to assist white patients in receiving less life-prolonging EOL care, but black patients do not experience the same benefits of EOL discussions. Instead, black patients tend to receive life-prolonging measures at the EOL even when they have DNR orders or state a preference for symptom-directed care. C1 [Mack, Jennifer W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mack, Jennifer W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Mack, Jennifer W.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Paulk, M. Elizabeth] Univ Texas Dallas, SW Med Ctr, Palliat Care Serv, Dallas, TX 75230 USA. RP Mack, JW (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM Jennifer_Mack@dfci.harvard.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA106370]; Fetzer Religion at the End-of-Life Grant; Center for Psycho-oncology and Palliative Care Research, Dana-Farber Cancer Institute; American Cancer Society FX This research was supported by grant MH63892 from the National Institute of Mental Health and grant CA106370 from the National Cancer Institute (Dr Prigerson), by a Fetzer Religion at the End-of-Life Grant, and by the Center for Psycho-oncology and Palliative Care Research, Dana-Farber Cancer Institute. Dr Mack was supported by an American Cancer Society Mentored Research Scholar Grant. NR 39 TC 58 Z9 58 U1 2 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 27 PY 2010 VL 170 IS 17 BP 1533 EP 1540 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 655WQ UT WOS:000282286700003 PM 20876403 ER PT J AU Pontari, MA Krieger, JN Litwin, MS White, PC Anderson, RU McNaughton-Collins, M Nickel, JC Shoskes, DA Alexander, RB O'Leary, M Zeitlin, S Chuai, S Landis, JR Cen, LY Propert, KJ Kusek, JW Nyberg, LM Schaeffer, AJ AF Pontari, Michel A. Krieger, John N. Litwin, Mark S. White, Paige C. Anderson, Rodney U. McNaughton-Collins, Mary Nickel, J. Curtis Shoskes, Daniel A. Alexander, Richard B. O'Leary, Michael Zeitlin, Scott Chuai, Shannon Landis, J. Richard Cen, Liyi Propert, Kathleen J. Kusek, John W. Nyberg, Leroy M., Jr. Schaeffer, Anthony J. CA Chronic Prostatitis Collaborative TI Pregabalin for the Treatment of Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome A Randomized Controlled Trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; INTERSTITIAL CYSTITIS; SYMPTOM INDEX; RESPONSIVENESS; DESIGN; SCALES AB Background: Evidence suggests that the urogenital pain of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) may be neuropathic. Methods: This randomized, double-blind, placebo-controlled trial was conducted across 10 tertiary care centers in North America to determine whether pregabalin, which has been proved effective in other chronic pain syndromes, is effective in reducing CP/CPPS symptoms. In 2006-2007, 324 men with pelvic pain for at least 3 of the previous 6 months were enrolled in this study. Men were randomly assigned to receive pregabalin or placebo in a 2:1 ratio and were treated for 6 weeks. Pregabalin dosage was increased from 150 to 600 mg/d during the first 4 weeks. The primary outcome was a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score. Multiple secondary outcomes were assessed. Results: Of 218 men assigned to receive pregabalin, 103 (47.2%) reported at least a 6-point decrease in the NIH-CPSI total score at 6 weeks compared with 35.8% (38 of 106 men) assigned to receive placebo (P = .07, exact Mantel-Haenszel test, adjusting for clinical sites). Compared with the placebo group, men assigned to receive pregabalin experienced reductions in the NIH-CPSI total score and subscores (P < .05), a higher Global Response Assessment response rate (31.2% and 18.9%; P = .02), and improvement in total McGill Pain Questionnaire score (P = .01). Results for the other outcomes did not differ between groups. Conclusion: Pregabalin therapy for 6 weeks was not superior to placebo use in the rate of a 6-point decrease (improvement) in the NIH-CPSI total score in men with CP/CPPS. C1 [Pontari, Michel A.] Temple Univ, Sch Med, Dept Urol, Philadelphia, PA 19140 USA. [Krieger, John N.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Litwin, Mark S.; Zeitlin, Scott] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Litwin, Mark S.; Zeitlin, Scott] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Litwin, Mark S.; Zeitlin, Scott] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. [Litwin, Mark S.; Zeitlin, Scott] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90095 USA. [White, Paige C.] Univ Mississippi, Dept Surg, Gulfport, MS USA. [White, Paige C.] Coast Urol Ctr, Gulfport, MS USA. [Anderson, Rodney U.] Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA. [McNaughton-Collins, Mary] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Nickel, J. Curtis] Queens Univ, Dept Urol, Kingston, ON K7L 3N6, Canada. [Shoskes, Daniel A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA. [Alexander, Richard B.] Univ Maryland, Dept Urol, Baltimore, MD 21201 USA. [O'Leary, Michael] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [O'Leary, Michael] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Chuai, Shannon; Landis, J. Richard; Cen, Liyi; Propert, Kathleen J.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Kusek, John W.] NIDDK, Bethesda, MD USA. [Schaeffer, Anthony J.] Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. RP Pontari, MA (reprint author), Temple Univ, Sch Med, Dept Urol, 3401 N Broad St,Ste 330, Philadelphia, PA 19140 USA. EM Pontarm@tuhs.temple.edu FU Sanofi-Aventis; Pfizer; GlaxoSmithKline; Merck; Allergan; Watson; American Medical Systems; Boehringer Ingelheim; National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases [DK65209, U01 DK65268, U01 DK65297, U01 DK65187, U01 DK65277, U01 DK65189, U01 DK65174, U01 DK65266, U01 DK65257, U01 DK65186, U01 DK65287]; National Institute of Diabetes and Digestive and Kidney Diseases; National Center for Minority Health and Health Disparities FX Dr Pontari received consulting fees from Sanofi-Aventis, Pfizer, and GlaxoSmithKline and reported clinical trial participation with Pfizer; Dr Krieger received consulting and advising fees from Pfizer; Dr Litwin received consulting fees from Sanofi-Aventis; Dr Anderson received consulting fees from Bioness Inc, investigator fees from Boston Scientific and Allergan, and speaker fees from GlaxoSmithKline and Astella; Dr Nickel reports receiving consulting fees from Merck, GlaxoSmithKline, Pfizer, Ortho Women's Health, Fan Labs, Watson, Medtronic, NeurAxon, and Genyous Biomed and research support from Merck, GlaxoSmithKline, Allergan, Watson, Pfizer, and American Medical Systems; Dr Shoskes received consulting fees from Roche, is on the advisory board of Fan Labs, and has a financial interest in Triurol; Dr Alexander received lecture fees from Boehringer Ingelheim; Dr O'Leary received consulting fees from Sanofi-Aventis; Dr Landis received consulting fees from Sanofi-Aventis; Dr Kusek holds stock in Decode Genetics; and Dr Schaeffer was a consultant for Alita Pharmaceuticals, American Medical Systems, NovaBay Pharmaceuticals, Regeneron Pharm Inc, IMS Health, Exoxemis Inc, CombinatoRx Inc, Monitor Company Group LP, and Advanstar Communications and received meeting honorarium from the Scientific Consulting Group.; No author received compensation for the performance of this study except as salary support from a grant from the National Institutes of Health. This study was supported by cooperative agreements U01 DK65209, U01 DK65268, U01 DK65297, U01 DK65187, U01 DK65277, U01 DK65189, U01 DK65174, U01 DK65266, U01 DK65257, U01 DK65186, and U01 DK65287 from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Minority Health and Health Disparities. Pregabalin and matching placebo capsules were provided by Pfizer Inc. Previous Presentation: This study was presented at the meeting of the American Urological Association; April 26, 2009; Chicago, Illinois. NR 28 TC 31 Z9 32 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 27 PY 2010 VL 170 IS 17 BP 1586 EP 1593 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 655WQ UT WOS:000282286700011 PM 20876412 ER PT J AU Dougan, M Dougan, S Slisz, J Firestone, B Vanneman, M Draganov, D Goyal, G Li, WB Neuberg, D Blumberg, R Hacohen, N Porter, D Zawel, L Dranoff, G AF Dougan, Michael Dougan, Stephanie Slisz, Joanna Firestone, Brant Vanneman, Matthew Draganov, Dobrin Goyal, Girija Li, Weibo Neuberg, Donna Blumberg, Richard Hacohen, Nir Porter, Dale Zawel, Leigh Dranoff, Glenn TI IAP inhibitors enhance co-stimulation to promote tumor immunity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NF-KAPPA-B; LINKED LYMPHOPROLIFERATIVE SYNDROME; ALPHA-DEPENDENT APOPTOSIS; UBIQUITIN PROTEIN LIGASE; TNF-ALPHA; ACTIVATION; XIAP; CIAP2; C-IAP1; CELLS AB The inhibitor of apoptosis proteins (IAPs) have recently been shown to modulate nuclear factor kappa B (NF-kappa B) signaling downstream of tumor necrosis factor (TNF) family receptors, positioning them as essential survival factors in several cancer cell lines, as indicated by the cytotoxic activity of several novel small molecule IAP antagonists. In addition to roles in cancer, increasing evidence suggests that IAPs have an important function in immunity; however, the impact of IAP antagonists on antitumor immune responses is unknown. In this study, we examine the consequences of IAP antagonism on T cell function in vitro and in the context of a tumor vaccine in vivo. We find that IAP antagonists can augment human and mouse T cell responses to physiologically relevant stimuli. The activity of IAP antagonists depends on the activation of NF-kappa B2 signaling, a mechanism paralleling that responsible for the cytotoxic activity in cancer cells. We further show that IAP antagonists can augment both prophylactic and therapeutic antitumor vaccines in vivo. These findings indicate an important role for the IAPs in regulating T cell-dependent responses and suggest that targeting IAPs using small molecule antagonists may be a strategy for developing novel immunomodulating therapies against cancer. C1 [Dougan, Michael; Vanneman, Matthew; Draganov, Dobrin; Goyal, Girija; Dranoff, Glenn] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. [Dougan, Michael; Vanneman, Matthew; Draganov, Dobrin; Goyal, Girija; Dranoff, Glenn] Harvard Univ, Brigham & Womens Hosp, Sch Med, Canc Vaccine Ctr,Dana Farber Canc Inst, Boston, MA 02115 USA. [Dougan, Michael; Vanneman, Matthew; Draganov, Dobrin; Goyal, Girija; Dranoff, Glenn] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Dougan, Stephanie; Blumberg, Richard] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Slisz, Joanna; Firestone, Brant; Porter, Dale; Zawel, Leigh] Novartis Inst Biomed Res, Oncol Dis Area, Cambridge, MA 02139 USA. [Slisz, Joanna; Firestone, Brant; Porter, Dale; Zawel, Leigh] Novartis Inst Biomed Res, Dev & Mol Pathways Grp, Cambridge, MA 02139 USA. [Li, Weibo; Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. [Li, Weibo; Hacohen, Nir] Massachusetts Inst Technol & Harvard, Broad Inst, Cambridge, MA 02142 USA. [Neuberg, Donna] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Neuberg, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu FU Dana-Farber Cancer Institute/Novartis; National Institute on Aging [F30AG030298]; Novartis Institute of Biomedical Research FX This work was supported by the Dana-Farber Cancer Institute/Novartis Program in Drug Discovery (grant to G. Dranoff) and grant F30AG030298 from the National Institute on Aging (to M. Dougan).; G. Dranoff is a grantee of and consultant to the Novartis Institute of Biomedical Research. J. Slisz, B. Firestone, D. Porter, and L. Zawel are employees of the Novartis Institute of Biomedical Research. The authors have no additional conflicts of interest. NR 45 TC 42 Z9 43 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 27 PY 2010 VL 207 IS 10 BP 2195 EP 2206 DI 10.1084/jem.20101123 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 660NH UT WOS:000282649800015 PM 20837698 ER PT J AU Ha, W Lee, S Kim, J Jeong, Y Oh, K Kobelke, J Schuster, K Unger, S Schwuchow, A Kim, JK AF Ha, Woosung Lee, Sejin Kim, Jongki Jeong, Yoonseob Oh, Kyunghwan Kobelke, Jens Schuster, Kay Unger, Sonja Schwuchow, Anka Kim, Jun Ki TI A micro-structured aperture made of a hollow triangular-core fiber for novel beam shaping SO OPTICS EXPRESS LA English DT Article ID OPTICAL-FIBERS; LASER-BEAM; GLASS AB We demonstrate a micro-structured aperture made of a unique hollow triangular-core fiber (HTCF) that consists of a central air hole, a high-index hollow triangular core, and silica cladding for all-fiber novel beam shaping. Detailed fabrication processes to embed a hollow triangular structure into a cylindrical optical fiber are described and unique diffraction patterns out of the HTCF for monochromatic light are analyzed both experimentally and theoretically. Fourier-optic analysis combined with guided mode calculation was pursued to interpret experimental patterns in terms of the beam propagation distance. (C) 2010 Optical Society of America C1 [Ha, Woosung; Lee, Sejin; Kim, Jongki; Jeong, Yoonseob; Oh, Kyunghwan] Yonsei Univ, Inst Phys & Appl Phys, Seoul 120749, South Korea. [Kobelke, Jens; Schuster, Kay; Unger, Sonja; Schwuchow, Anka] Inst Photon Technol, D-07745 Jena, Germany. [Kim, Jun Ki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kim, Jun Ki] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Ha, W (reprint author), Yonsei Univ, Inst Phys & Appl Phys, 262 Seongsanno, Seoul 120749, South Korea. EM koh@yonsei.ac.kr FU Brain Korea 21 Project; MEST [2010-0018442, 2009-00479 EC-FP7/2007-2013 219299 GOSPEL, R15-2004-024-00000-0, 2009-352-C00042] FX This work was supported in part by the Brain Korea 21 Project and in part by the NRF grant funded by the MEST (Nos. 2010-0018442, 2009-00479 EC-FP7/2007-2013 219299 GOSPEL, R15-2004-024-00000-0, and 2009-352-C00042). NR 17 TC 3 Z9 3 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD SEP 27 PY 2010 VL 18 IS 20 BP 20918 EP 20925 DI 10.1364/OE.18.020918 PG 8 WC Optics SC Optics GA 673QX UT WOS:000283679200039 PM 20940987 ER PT J AU Sgroi, A Buhler, LH Morel, P Sykes, M Noel, L AF Sgroi, Antonino Buehler, Leo H. Morel, Philippe Sykes, Megan Noel, Luc TI International Human Xenotransplantation Inventory SO TRANSPLANTATION LA English DT Article DE Clinical application; Public health; Regulation; Xenotransplantation; Zoonosis ID PORCINE ENDOGENOUS RETROVIRUS; ACUTE LIVER-FAILURE; BIOARTIFICIAL LIVER; NO EVIDENCE; HEPATIC-FAILURE; PIG KIDNEYS; HUMAN-CELLS; INFECTION; TRANSPLANTATION; RECIPIENTS AB Background. Xenotransplantation carries inherent risks of infectious disease transmission to the recipient and even to society at large, and it should only be carried out with strict regulation and oversight. In collaboration with the International Xenotransplantation Association, the University Hospital Geneva, and the World Health Organization, an international inventory has been established (www.humanxenotransplant.org) aiming to collect basic data on all types of currently ongoing or recently performed xenotransplantation procedures in humans. Methods. We collected information from publications in scientific journals, presentations at international congresses, the internet, and declarations of International Xenotransplantation Association members on xenotransplantation procedures in humans performed during the past 15 years. Results. We identified a total of 29 human applications of xenotransplantation, including 7 that were currently ongoing. Procedures involved transplantation of xenogeneic cells, i.e., islets of Langerhans, kidney cells, chromaffin cells, embryonic stem cells, fetal and adult cells from various organs or extracorporeal perfusion using hepatocytes, liver, spleen, or kidney. The treatments were performed in 12 different countries, 9 of them having no national regulation on xenotransplantation. Conclusion. Several clinical applications of cell xenotransplantation are ongoing around the world, often without any clear governmental regulation. This information should be used to inform national health authorities, healthcare staff, and the public, with the objective of encouraging good practices, with internationally harmonized guidelines and regulation of xenotransplantation. C1 [Noel, Luc] WHO, Clin Procedures, CPR EHT, CH-1211 Geneva 27, Switzerland. [Sgroi, Antonino; Buehler, Leo H.; Morel, Philippe] Univ Hosp Geneva, Dept Surg, Surg Res Unit, Geneva, Switzerland. [Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Noel, L (reprint author), WHO, Clin Procedures, CPR EHT, 20 Ave Appia, CH-1211 Geneva 27, Switzerland. EM noell@who.int FU World Health Organization; Swiss National Science Foundation [3200B0-103935]; National Institutes of Health, MD; National Institute of Immunology, Allergy and Infectious Disease; National Heart, Lung and Blood Institute FX This work was supported by a special fund of the World Health Organization and by the research grant 3200B0-103935 of the Swiss National Science Foundation (L.H.B.); and by grants from the National Institutes of Health, MD, including the National Institute of Immunology, Allergy and Infectious Disease, and the National Heart, Lung and Blood Institute (M.S.). NR 33 TC 14 Z9 14 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 27 PY 2010 VL 90 IS 6 BP 597 EP 603 DI 10.1097/TP.0b013e3181eb2e8c PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 651FG UT WOS:000281910500002 PM 20644502 ER PT J AU Ooi, SKT Wolf, D Hartung, O Agarwal, S Daley, GQ Goff, SP Bestor, TH AF Ooi, Steen K. T. Wolf, Daniel Hartung, Odelya Agarwal, Suneet Daley, George Q. Goff, Stephen P. Bestor, Timothy H. TI Dynamic instability of genomic methylation patterns in pluripotent stem cells SO EPIGENETICS & CHROMATIN LA English DT Article ID DE-NOVO METHYLATION; DNA-METHYLATION; GERM-CELLS; HISTONE H3; DNMT3L; METHYLTRANSFERASES; EXPRESSION; 5-METHYLCYTOSINE; ESTABLISHMENT; MAINTENANCE AB Background: Genomic methylation patterns are established during gametogenesis, and perpetuated in somatic cells by faithful maintenance methylation. There have been previous indications that genomic methylation patterns may be less stable in embryonic stem (ES) cells than in differentiated somatic cells, but it is not known whether different mechanisms of de novo and maintenance methylation operate in pluripotent stem cells compared with differentiating somatic cells. Results: In this paper, we show that ablation of the DNA methyltransferase regulator DNMT3L (DNA methyltransferase 3-like) in mouse ES cells renders them essentially incapable of de novo methylation of newly integrated retroviral DNA. We also show that ES cells lacking DNMT3L lose DNA methylation over time in culture, suggesting that DNA methylation in ES cells is the result of dynamic loss and gain of DNA methylation. We found that wild-type female ES cells lose DNA methylation at a much faster rate than do male ES cells; this defect could not be attributed to sex-specific differences in expression of DNMT3L or of any DNA methyltransferase. We also found that human ES and induced pluripotent stem cell lines showed marked but variable loss of methylation that could not be attributed to sex chromosome constitution or time in culture. Conclusions: These data indicate that DNA methylation in pluripotent stem cells is much more dynamic and error-prone than is maintenance methylation in differentiated cells. DNA methylation requires DNMT3L in stem cells, but DNMT3L is not expressed in differentiating somatic cells. Error-prone maintenance methylation will introduce unpredictable phenotypic variation into clonal populations of pluripotent stem cells, and this variation is likely to be much more pronounced in cultured female cells. This epigenetic variability has obvious negative implications for the clinical applications of stem cells. C1 [Ooi, Steen K. T.; Bestor, Timothy H.] Columbia Univ, Dept Genet & Dev, New York, NY 10027 USA. [Wolf, Daniel; Goff, Stephen P.] Columbia Univ Coll Phys & Surg, HHMI, New York, NY 10032 USA. [Wolf, Daniel; Goff, Stephen P.] Columbia Univ Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Hartung, Odelya; Agarwal, Suneet; Daley, George Q.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Ooi, Steen K. T.] UCL, UCL Canc Inst, London WC1E 6BT, England. RP Bestor, TH (reprint author), Columbia Univ, Dept Genet & Dev, New York, NY 10027 USA. EM thb12@columbia.edu RI Goff, Stephen/K-6337-2014; OI Goff, Stephen/0000-0003-0693-5547; Ooi, Steen/0000-0003-4198-9014 FU NIH; State of New York Dept. of Health FX This article is dedicated to the memory of our friend and colleague Dan Wolf (July 15, 1977-September 24, 2009). We thank E Li for the gift of 7aabb mutant ES cells, CS Lin and Z Wu for XX and XY ES cells, SP Lin for derivation of Dnmt3L-/- ES cells and Z. A. Hilbert for assistance. Supported by grants from the NIH (to S G, G Q D and T H B). S. P G was supported by a grant from the State of New York Dept. of Health NYSTEM program. D W was an associate and S P G and G Q D are Investigators of the Howard Hughes Medical Institute. NR 39 TC 49 Z9 50 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8935 J9 EPIGENET CHROMATIN JI Epigenetics Chromatin PD SEP 24 PY 2010 VL 3 AR 17 DI 10.1186/1756-8935-3-17 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 674VC UT WOS:000283777200001 PM 20868487 ER PT J AU Spinale, FG Mukherjee, R Zavadzkas, JA Koval, CN Bouges, S Stroud, RE Dobrucki, LW Sinusas, AJ AF Spinale, Francis G. Mukherjee, Rupak Zavadzkas, Juozas A. Koval, Christine N. Bouges, Shenikqua Stroud, Robert E. Dobrucki, Lawrence W. Sinusas, Albert J. TI Cardiac Restricted Overexpression of Membrane Type-1 Matrix Metalloproteinase Causes Adverse Myocardial Remodeling following Myocardial Infarction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEFT-VENTRICULAR FUNCTION; TGF-BETA; HEART-FAILURE; 1-MATRIX METALLOPROTEINASE; ACTIVATION; MICE; INHIBITION; MATRIX-METALLOPROTEINASE-9; TRANSCRIPTION; FIBROBLASTS AB The membrane type-1 matrix metalloproteinase (MT1MMP) is a unique member of the MMP family, but induction patterns and consequences of MT1-MMP overexpression (MT1-MMPexp), in a left ventricular (LV) remodeling process such as myocardial infarction (MI), have not been explored. MT1-MMP promoter activity (murine luciferase reporter) increased 20-fold at 3 days and 50-fold at 14 days post-MI. MI was then induced in mice with cardiac restricted MT1-MMPexp (n = 58) and wild type (WT, n = 60). Post-MI survival was reduced (67% versus 46%, p < 0.05), and LV ejection fraction was lower in the post-MI MT1-MMPexp mice compared with WT (41 +/- 2 versus 32 +/- 2%, p < 0.05). In the post-MI MT1-MMPexp mice, LV myocardial MMP activity, as assessed by radiotracer uptake, and MT1-MMP-specific proteolytic activity using a specific fluorogenic assay were both increased by 2-fold. LV collagen content was increased by nearly 2-fold in the post-MI MT1-MMPexp compared with WT. Using a validated fluorogenic construct, it was discovered that MT1-MMP proteolytically processed the pro-fibrotic molecule, latency-associated transforming growth factor-1 binding protein (LTBP-1), and MT1-MMP-specific LTBP-1 proteolytic activity was increased by 4-fold in the post-MIMT1-MMPexp group. Early and persistent MT1-MMP promoter activity occurred post-MI, and increased myocardial MT1-MMP levels resulted in poor survival, worsening of LV function, and significant fibrosis. A molecular mechanism for the adverse LV matrix remodeling with MT1-MMP induction is increased processing of pro-fibrotic signaling molecules. Thus, a proteolytically diverse portfolio exists for MT1-MMP within the myocardium and likely plays a mechanistic role in adverse LV remodeling. C1 [Spinale, Francis G.; Mukherjee, Rupak; Zavadzkas, Juozas A.; Koval, Christine N.; Bouges, Shenikqua; Stroud, Robert E.] Med Univ S Carolina, Charleston, SC 29425 USA. [Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Dobrucki, Lawrence W.; Sinusas, Albert J.] Yale Univ, Sch Med New Haven, New Haven, CT 06510 USA. RP Sinusas, AJ (reprint author), Room 625,770 MUSC Complex,114 Doughty St, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU National Institutes of Health [HL057952, HL059165, HL078825]; Veterans Affairs Health Administration FX This work was supported, in whole or in part, by National Institutes of Health Grants HL057952, HL059165, and HL078825. This work was also supported by a Merit Award from the Veterans Affairs Health Administration. NR 30 TC 34 Z9 34 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 24 PY 2010 VL 285 IS 39 BP 30316 EP 30327 DI 10.1074/jbc.M110.158196 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 652EK UT WOS:000281984300067 PM 20643648 ER PT J AU Klenk, C Vetter, T Zurn, A Vilardaga, JP Friedman, PA Wang, B Lohse, MJ AF Klenk, Christoph Vetter, Thorsten Zuern, Alexander Vilardaga, Jean-Pierre Friedman, Peter A. Wang, Bin Lohse, Martin J. TI Formation of a Ternary Complex among NHERF1, beta-Arrestin, and Parathyroid Hormone Receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED-RECEPTORS; EXCHANGER REGULATORY FACTOR; PROXIMAL TUBULE CELLS; BETA(2)-ADRENERGIC RECEPTOR; (PTH)/PTH-RELATED PEPTIDE; PHOSPHATE-TRANSPORT; ADENOSINE RECEPTOR; PDZ-DOMAIN; KINASE-C; BINDING AB beta-Arrestins are crucial regulators of G-protein coupled receptor (GPCR) signaling, desensitization, and internalization. Despite the long-standing paradigm that agonist-promoted receptor phosphorylation is required for beta-arrestin2 recruitment, emerging evidence suggests that phosphorylation-independent mechanisms play a role in beta-arrestin2 recruitment by GPCRs. Several PDZ proteins are known to interact with GPCRs and serve as cytosolic adaptors to modulate receptor signaling and trafficking. Na(+)/H(+) exchange regulatory factors (NHERFs) exert a major role in GPCR signaling. By combining imaging and biochemical and biophysical methods we investigated the interplay among NHERF1, beta-arrestin2, and the parathyroid hormone receptor type 1 (PTHR). We show that NHERF1 and beta-arrestin2 can independently bind to the PTHR and form a ternary complex in cultured human embryonic kidney cells and Chinese hamster ovary cells. Although NHERF1 interacts constitutively with the PTHR, beta-arrestin2 binding is promoted by receptor activation. NHERF1 interacts directly with beta-arrestin2 without using the PTHR as an interface. Fluorescence resonance energy transfer studies revealed that the kinetics of PTHR and beta-arrestin2 interactions were modulated by NHERF1. These findings suggest a model in which NHERF1 may serve as an adaptor, bringing beta-arrestin2 into close proximity to the PTHR, thereby facilitating beta-arrestin2 recruitment after receptor activation. C1 [Lohse, Martin J.] Univ Wurzburg, Inst Pharmacol & Toxicol, D-97078 Wurzburg, Germany. [Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre; Friedman, Peter A.; Wang, Bin] Univ Pittsburgh, Sch Med, Lab G Coupled Prot Receptor Biol, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA. RP Lohse, MJ (reprint author), Univ Wurzburg, Inst Pharmacol & Toxicol, Versbacher Str 9, D-97078 Wurzburg, Germany. EM lohse@toxi.uni-wuerzburg.de RI Lohse, Martin/A-7160-2012; Klenk, Christoph/E-5158-2014; OI Lohse, Martin/0000-0002-0599-3510; Klenk, Christoph/0000-0001-5199-7144; Wang, Bin/0000-0002-5396-6111 FU Deutsche Forschungsgemeinschaft; European Research Council; National Institutes of Health [DK54171, DK069998, DK087688] FX This work was supported, in whole or in part, by grants of the Deutsche Forschungsgemeinschaft and the European Research Council (to M. J. L.). This work was also supported by National Institutes of Health Grants DK54171 and DK069998 (to P. A. F.) and DK087688 (to J.-P. V.). NR 42 TC 23 Z9 24 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 24 PY 2010 VL 285 IS 39 BP 30355 EP 30362 DI 10.1074/jbc.M110.114900 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 652EK UT WOS:000281984300071 PM 20656684 ER PT J AU Hays, LE Keeble, WW Yates, JE Rathbun, RK Koretsky, T Olson, SB Sun, ZJ Clapp, DW Bagby, GC AF Hays, Laura E. Keeble, Winifred W. Yates, Jane E. Rathbun, R. K. Koretsky, Tara Olson, Susan B. Sun, Zejin Clapp, D. Wade Bagby, Grover C., Jr. TI Human FANCC is hypomorphic in murine Fancc-deficient cells SO BLOOD LA English DT Article ID C GENE; REPOPULATING ABILITY; STEM-CELLS; ANEMIA; EXPRESSION; MICE; INTERFERON; INACTIVATION; INSTABILITY; VECTORS AB Fancc suppresses cross-linker-induced genotoxicity, modulates growth-inhibitory cytokine responses, and modulates endotoxin responses. Although loss of the latter function is known to account for endotoxin-induced marrow failure in murine Fancc (mFancc)-deficient mice, some argue that cytokine and endotoxin hypersensitivities devolve simply from genomic instability. Seeking to resolve this question, we planned to ectopically express instructive human FANCC(hFANCC) mutants in murine Fancc-deficient hematopoietic stem cells. To first assure that hFANCC cDNA was competent in murine cells, we compared hFANCC and mFancc in complementation assays for cross-linking agent hypersensitivity and endotoxin hypersensitivity. We found that mFancc complemented murine Fancc-deficient cells in both assays, but that hFANCC fully suppressed only endotoxin hypersensitivity, not cross-linking agent hypersensitivity. These results support the notions that Fancc is multifunctional and that structural prerequisites for its genoprotective functions differ from those required to constrain endotoxin responses known to lead to marrow failure in Fancc-deficient mice. (Blood. 2010;116(12):2057-2060) C1 [Hays, Laura E.; Keeble, Winifred W.; Yates, Jane E.; Rathbun, R. K.; Koretsky, Tara; Bagby, Grover C., Jr.] Portland VA Med Ctr, Portland, OR 97239 USA. [Hays, Laura E.; Keeble, Winifred W.; Yates, Jane E.; Rathbun, R. K.; Koretsky, Tara; Olson, Susan B.; Bagby, Grover C., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Hays, Laura E.; Bagby, Grover C., Jr.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Olson, Susan B.; Bagby, Grover C., Jr.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Sun, Zejin; Clapp, D. Wade] Indiana Univ Sch Med, Indianapolis, IN USA. RP Hays, LE (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,R&D-2, Portland, OR 97239 USA. EM haysl@ohsu.edu FU Fanconi Anemia Research Fund; Knight Cancer Institute at Oregon Health & Science University; Veterans Association; National Institutes of Health/National Heart, Lung, and Blood Institute [5P01-HL48546]; National Institutes of Health/ National Cancer Institute [1-R01-CA138237-01] FX This work was supported by Fanconi Anemia Research Fund (L.E.H.), the Knight Cancer Institute at Oregon Health & Science University, Veterans Association Merit Review (G.C.B.), National Institutes of Health/National Heart, Lung, and Blood Institute (5P01-HL48546; G.C.B., S.B.O.), and National Institutes of Health/ National Cancer Institute (1-R01-CA138237-01; D.W.C., G.C.B.). NR 20 TC 6 Z9 6 U1 0 U2 0 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 SEP 23 PY 2010 VL 116 IS 12 BP 2057 EP 2060 DI 10.1182/blood-2010-02-266411 PG 4 WC Hematology SC Hematology GA 653ZG UT WOS:000282137300012 PM 20554974 ER PT J AU Mounzer, RH Svendsen, OS Baluk, P Bergman, CM Padera, TP Wiig, H Jain, RK McDonald, DM Ruddle, NH AF Mounzer, Rawad H. Svendsen, Oyvind S. Baluk, Peter Bergman, Cheryl M. Padera, Timothy P. Wiig, Helge Jain, Rakesh K. McDonald, Donald M. Ruddle, Nancy H. TI Lymphotoxin-alpha contributes to lymphangiogenesis SO BLOOD LA English DT Article ID INTERSTITIAL FLUID PRESSURE; LYMPHOID ORGAN DEVELOPMENT; HIGH ENDOTHELIAL VENULES; GROWTH-FACTOR-C; LYMPHATIC VESSELS; TRANSGENIC MICE; LT-ALPHA; CHRONIC INFLAMMATION; SKELETAL-MUSCLE; GENE-EXPRESSION AB Lymphotoxin-alpha (LT alpha), lymphotoxin-beta (LT beta), and tumor necrosis factor-alpha (TNF alpha) are inflammatory mediators that play crucial roles in lymphoid organ development. We demonstrate here that LT alpha also contributes to the function of lymphatic vessels and to lymphangiogenesis during inflammation. LT alpha(-/-) mice exhibited reduced lymph flow velocities and increased interstitial fluid pressure. Airways of LT alpha(-/-) mice infected with Mycoplasma pulmonis had significantly more lymphangiogenesis than wild type (WT) or LT alpha(-/-) mice, as did the skin draining immunization sites of LT beta(-/-) mice. Macrophages, B cells, and T cells, known sources of LT and TNF alpha, were apparent in the skin surrounding the immunization sites as were LT alpha, LT beta, and TNF alpha mRNAs. Ectopic expression of LT alpha led to the development of LYVE-1 and Prox1-positive lymphatic vessels within tertiary lymphoid organs (TLOs). Quantification of pancreatic lymphatic vessel density in RIPLT alpha LT beta(-/-) and WT mice revealed that LT alpha was sufficient for inducing lymphangiogenesis and that LT beta was not required for this process. Kidneys of inducible LT alpha transgenic mice developed lymphatic vessels before the appearance of obvious TLOs. These data indicate that LT alpha plays a significant role in lymphatic vessel function and in inflammation-associated lymphangiogenesis. (Blood. 2010;116(12):2173-2182) C1 [Mounzer, Rawad H.; Bergman, Cheryl M.; Ruddle, Nancy H.] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, New Haven, CT 06520 USA. [Svendsen, Oyvind S.; Wiig, Helge] Univ Bergen, Dept Biomed, Bergen, Norway. [Svendsen, Oyvind S.] Haukeland Hosp, Dept Anesthesia & Intens Care, N-5021 Bergen, Norway. [Baluk, Peter; McDonald, Donald M.] Univ Calif San Francisco, Cardiovasc Res Inst, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Baluk, Peter; McDonald, Donald M.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. [Padera, Timothy P.; Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab, Boston, MA USA. [Ruddle, Nancy H.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. RP Ruddle, NH (reprint author), Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, 10 Amistad St, New Haven, CT 06520 USA. EM nancy.ruddle@yale.edu OI Wiig, Helge/0000-0002-7740-8210; Padera, Timothy/0000-0002-3453-9384 FU National Institutes of Health (NIH) [R01DK 57731, CA 16885, P01 HL24136, R01HL59157, R01CA82923, R01CA085149, K99CA137167, P30 041942]; Lymphatic Research Foundation; Western Norway Regional Health Authority; The Research Council of Norway; Norwegian Cancer Society FX This work was supported by National Institutes of Health (NIH) R01DK 57731 and CA 16885 (N.H.R.); NIH P01 HL24136, R01HL59157, and R01CA82923 (D.M.M.); NIH R01CA085149 (R.K.J.); NIH K99CA137167 (T.P.P.), a pilot grant from NIH P30 041942 (N.H.R.), a Fellowship from the Lymphatic Research Foundation (R.H.M.), Western Norway Regional Health Authority (O.S.S.), and The Research Council of Norway and the Norwegian Cancer Society (H.W.). NR 50 TC 46 Z9 46 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 23 PY 2010 VL 116 IS 12 BP 2173 EP 2182 DI 10.1182/blood-2009-12-256065 PG 10 WC Hematology SC Hematology GA 653ZG UT WOS:000282137300027 PM 20566898 ER PT J AU De Gasperi, R Sosa, MAG Dracheva, S Elder, GA AF De Gasperi, Rita Sosa, Miguel A. Gama Dracheva, Stella Elder, Gregory A. TI Presenilin-1 regulates induction of hypoxia inducible factor-1 alpha: altered activation by a mutation associated with familial Alzheimer's disease SO MOLECULAR NEURODEGENERATION LA English DT Article ID AMYLOID PRECURSOR PROTEIN; GROWTH-FACTOR-I; PROMOTES TAU-PHOSPHORYLATION; GENE-EXPRESSION; SIGNALING PATHWAYS; GAMMA-SECRETASE; INSULIN-RESISTANCE; TYROSINE KINASE; TRANSGENIC MICE; TALKING POINT AB Background: Mutations in presenilin-1 (Psen1) cause familial Alzheimer's disease (FAD). Both hypoxia and ischemia have been implicated in the pathological cascade that leads to amyloid deposition in AD. Here we investigated whether Psen1 might regulate hypoxic responses by modulating induction of the transcription factor hypoxia inducible factor 1-alpha (HIF-1 alpha). Results: In fibroblasts that lack Psen1 induction of HIF-1 alpha was impaired in response to the hypoxia mimetic cobalt chloride, as well as was induction by insulin and calcium chelation. Reintroduction of human Psen1 using a lentiviral vector partially rescued the responsiveness of Psen1(-/-) fibroblasts to cobalt chloride induction. HIF-1 alpha induction did not require Psen1's associated gamma-secretase activity. In addition, the failure of insulin to induce HIF-1 alpha was not explicable on the basis of failed activation of the phosphatidylinositol 3-kinase (PI3K/Akt) pathway which activated normally in Psen1(-/-) fibroblasts. Rather we found that basal levels of HIF-1 alpha were lower in Psen1(-/-) fibroblasts and that the basis for lower constitutive levels of HIF-1 alpha was best explained by accelerated HIF-1 alpha degradation. We further found that Psen1 and HIF-1 alpha physically interact suggesting that Psen1 may protect HIF-1 alpha from degradation through the proteasome. In fibroblasts harboring the M146V Psen1 FAD mutation on a mouse Psen1 null background, metabolic induction of HIF-1 alpha by insulin was impaired but not hypoxic induction by cobalt chloride. Unlike Psen1(-/-) fibroblasts, basal levels of HIF-1 alpha were normal in FAD mutant fibroblasts but activation of the insulin-receptor pathway was impaired. Interestingly, in Psen1(-/-) primary neuronal cultures HIF-1 alpha was induced normally in response to cobalt chloride but insulin induction of HIF-1 alpha was impaired even though activation of the PI3K/Akt pathway by insulin proceeded normally in Psen1(-/-) neuronal cultures. Basal levels of HIF-1 alpha were not significantly different in Psen1(-/-) neurons and HIF-1 alpha levels were normal in Psen1(-/-) embryos. Conclusions: Collectively these studies show that Psen1 regulates induction of HIF-1 alpha although they indicate that cell type specific differences exist in the effect of Psen1 on induction. They also show that the M146V Psen1 FAD mutation impairs metabolic induction of HIF-1 alpha, an observation that may have pathophysiological significance for AD. C1 [Elder, Gregory A.] Vet Adm Med Ctr, James J Peters Dept, Neurol Serv, Bronx, NY 10468 USA. [De Gasperi, Rita; Sosa, Miguel A. Gama; Dracheva, Stella; Elder, Gregory A.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. RP Elder, GA (reprint author), Vet Adm Med Ctr, James J Peters Dept, Neurol Serv, Bronx, NY 10468 USA. EM gregory.elder@mssm.edu FU Department of Veterans Affairs [5I01BX000342-02]; National Institute on Aging [AG20139, AG02219, AG05138, AG029361]; Alzheimer's Association [IIRG-07-57318] FX This work was supported by a Merit Award from the Department of Veterans Affairs (5I01BX000342-02) and grants from the National Institute on Aging (AG20139, AG02219, AG05138, and AG029361), and the Alzheimer's Association (IIRG-07-57318). We thank Drs. Paul Mathews and Nikolaos Robakis for gifts of antibodies, Dr. Nikolaos Robakis for gift of Psen-/- fibroblasts and Ms. Gissel Perez for expert technical assistance. Dr. Vahram Haroutunian is thanked for critical reading of the manuscript. NR 89 TC 13 Z9 13 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PD SEP 23 PY 2010 VL 5 AR 38 DI 10.1186/1750-1326-5-38 PG 20 WC Neurosciences SC Neurosciences & Neurology GA 664QR UT WOS:000282977900001 PM 20863403 ER PT J AU Kerry, VB Auld, S Farmer, P AF Kerry, Vanessa Bradford Auld, Sara Farmer, Paul TI GLOBAL HEALTH An International Service Corps for Health - An Unconventional Prescription for Diplomacy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Kerry, Vanessa Bradford; Farmer, Paul] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02215 USA. [Farmer, Paul] Brigham & Womens Hosp, Dept Global Hlth & Social Equ, Boston, MA 02115 USA. [Kerry, Vanessa Bradford; Auld, Sara] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Kerry, VB (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02215 USA. NR 5 TC 19 Z9 19 U1 0 U2 10 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 SEP 23 PY 2010 VL 363 IS 13 BP 1199 EP 1201 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 652ZA UT WOS:000282050000003 PM 20860500 ER PT J AU Kalager, M Zelen, M Langmark, F Adami, HO AF Kalager, Mette Zelen, Marvin Langmark, Froydis Adami, Hans-Olov TI Effect of Screening Mammography on Breast-Cancer Mortality in Norway SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SWEDISH RANDOMIZED TRIALS; COMPLETENESS; REGISTRY; COHORT AB BACKGROUND A challenge in quantifying the effect of screening mammography on breast-cancer mortality is to provide valid comparison groups. The use of historical control subjects does not take into account chronologic trends associated with advances in breast-cancer awareness and treatment. METHODS The Norwegian breast-cancer screening program was started in 1996 and expanded geographically during the subsequent 9 years. Women between the ages of 50 and 69 years were offered screening mammography every 2 years. We compared the incidence-based rates of death from breast cancer in four groups: two groups of women who from 1996 through 2005 were living in counties with screening (screening group) or without screening (nonscreening group); and two historical-comparison groups that from 1986 through 1995 mirrored the current groups. RESULTS We analyzed data from 40,075 women with breast cancer. The rate of death was reduced by 7.2 deaths per 100,000 person-years in the screening group as compared with the historical screening group (rate ratio, 0.72; 95% confidence interval [CI], 0.63 to 0.81) and by 4.8 deaths per 100,000 person-years in the nonscreening group as compared with the historical nonscreening group (rate ratio, 0.82; 95% CI, 0.71 to 0.93; P<0.001 for both comparisons), for a relative reduction in mortality of 10% in the screening group (P = 0.13). Thus, the difference in the reduction in mortality between the current and historical groups that could be attributed to screening alone was 2.4 deaths per 100,000 person-years, or a third of the total reduction of 7.2 deaths. CONCLUSIONS The availability of screening mammography was associated with a reduction in the rate of death from breast cancer, but the screening itself accounted for only about a third of the total reduction. C1 [Kalager, Mette; Langmark, Froydis; Adami, Hans-Olov] Canc Registry Norway, Oslo, Norway. [Kalager, Mette; Adami, Hans-Olov] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Zelen, Marvin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Zelen, Marvin; Adami, Hans-Olov] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zelen, Marvin; Adami, Hans-Olov] Dana Farber Canc Inst, Boston, MA 02115 USA. [Adami, Hans-Olov] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Kalager, M (reprint author), Oslo Univ Hosp, Dept Surg, N-0310 Oslo, Norway. EM mkalager@hsph.harvard.edu FU Cancer Registry of Norway; Research Council of Norway FX Supported by the Cancer Registry of Norway and the Research Council of Norway. NR 29 TC 247 Z9 250 U1 0 U2 20 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 SEP 23 PY 2010 VL 363 IS 13 BP 1203 EP 1210 DI 10.1056/NEJMoa1000727 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 652ZA UT WOS:000282050000004 PM 20860502 ER PT J AU Hunt, DP Thabet, A Rosenberg, ES AF Hunt, Daniel P. Thabet, Ashraf Rosenberg, Eric S. TI A Woman with Fever and Abdominal Pain Acute Epstein-Barr viral infection (infectious mononucleosis) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SPLENIC INFARCTION; ANTIPHOSPHOLIPID ANTIBODIES; HEREDITARY SPHEROCYTOSIS; VIRUS-INFECTION; PATIENT; COMPLICATIONS C1 [Hunt, Daniel P.; Rosenberg, Eric S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Thabet, Ashraf] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Rosenberg, Eric S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Rosenberg, Eric S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Thabet, Ashraf] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hunt, Daniel P.; Rosenberg, Eric S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Hunt, DP (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 21 TC 8 Z9 8 U1 0 U2 2 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 SEP 23 PY 2010 VL 363 IS 13 BP 1266 EP 1274 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 652ZA UT WOS:000282050000012 PM 20860509 ER PT J AU Anzueto, A AF Anzueto, Antonio TI Endobronchial Valves to Reduce Lung Hyperinflation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COPD; SURGERY C1 [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, Antonio] S Texas Vet Hlth Care Ctr, San Antonio, TX USA. RP Anzueto, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 9 TC 1 Z9 1 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 SEP 23 PY 2010 VL 363 IS 13 BP 1280 EP 1281 DI 10.1056/NEJMe1008256 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 652ZA UT WOS:000282050000015 PM 20860512 ER PT J AU Muss, HB D'Alessandro, HA Brachtel, EF AF Muss, Hyman B. D'Alessandro, Helen Anne Brachtel, Elena F. TI Case 15-2010: Mammography in Elderly Women REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID AGE 80 YEARS; BREAST-CANCER; OLDER C1 [Muss, Hyman B.] Univ N Carolina, Chapel Hill, NC 27514 USA. [D'Alessandro, Helen Anne; Brachtel, Elena F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Muss, HB (reprint author), Univ N Carolina, Chapel Hill, NC 27514 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 23 PY 2010 VL 363 IS 13 BP 1288 EP 1288 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 652ZA UT WOS:000282050000023 ER PT J AU Desikan, RS Sabuncu, MR Schmansky, NJ Reuter, M Cabral, HJ Hess, CP Weiner, MW Biffi, A Anderson, CD Rosand, J Salat, DH Kemper, TL Dale, AM Sperling, RA Fischl, B AF Desikan, Rahul S. Sabuncu, Mert R. Schmansky, Nicholas J. Reuter, Martin Cabral, Howard J. Hess, Christopher P. Weiner, Michael W. Biffi, Alessandro Anderson, Christopher D. Rosand, Jonathan Salat, David H. Kemper, Thomas L. Dale, Anders M. Sperling, Reisa A. Fischl, Bruce CA Alzheimer's Dis Neuroimaging Initi TI Selective Disruption of the Cerebral Neocortex in Alzheimer's Disease SO PLOS ONE LA English DT Article ID MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; DEFAULT-MODE NETWORK; FUNCTIONAL CONNECTIVITY; AMYLOID DEPOSITION; CORTICAL SURFACE; COORDINATE SYSTEM; APOLIPOPROTEIN-E; ELDERLY SUBJECTS; PRODROMAL AD AB Background: Alzheimer's disease (AD) and its transitional state mild cognitive impairment (MCI) are characterized by amyloid plaque and tau neurofibrillary tangle (NFT) deposition within the cerebral neocortex and neuronal loss within the hippocampal formation. However, the precise relationship between pathologic changes in neocortical regions and hippocampal atrophy is largely unknown. Methodology/Principal Findings: In this study, combining structural MRI scans and automated image analysis tools with reduced cerebrospinal fluid (CSF) A beta levels, a surrogate for intra-cranial amyloid plaques and elevated CSF phosphorylated tau (p-tau) levels, a surrogate for neocortical NFTs, we examined the relationship between the presence of Alzheimer's pathology, gray matter thickness of select neocortical regions, and hippocampal volume in cognitively normal older participants and individuals with MCI and AD (n = 724). Amongst all 3 groups, only select heteromodal cortical regions significantly correlated with hippocampal volume. Amongst MCI and AD individuals, gray matter thickness of the entorhinal cortex and inferior temporal gyrus significantly predicted longitudinal hippocampal volume loss in both amyloid positive and p-tau positive individuals. Amongst cognitively normal older adults, thinning only within the medial portion of the orbital frontal cortex significantly differentiated amyloid positive from amyloid negative individuals whereas thinning only within the entorhinal cortex significantly discriminated p-tau positive from p-tau negative individuals. Conclusions/Significance: Cortical Ab and tau pathology affects gray matter thinning within select neocortical regions and potentially contributes to downstream hippocampal degeneration. Neocortical Alzheimer's pathology is evident even amongst older asymptomatic individuals suggesting the existence of a preclinical phase of dementia. C1 [Desikan, Rahul S.; Sabuncu, Mert R.; Schmansky, Nicholas J.; Reuter, Martin; Salat, David H.; Sperling, Reisa A.; Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Desikan, Rahul S.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Cabral, Howard J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hess, Christopher P.; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Weiner, Michael W.] Dept Vet Affairs, San Francisco, CA USA. [Biffi, Alessandro; Anderson, Christopher D.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA. [Biffi, Alessandro; Anderson, Christopher D.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Kemper, Thomas L.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Sabuncu, Mert R.; Fischl, Bruce] Massachusetts Gen Hosp, Comp Sci & Artificial Intelligence Lab, Cambridge, MA USA. [Sabuncu, Mert R.; Fischl, Bruce] Massachusetts Gen Hosp, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. RP Desikan, RS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM rahul@nmr.mgh.harvard.edu RI Reuter, Martin/B-3456-2010; OI Reuter, Martin/0000-0002-2665-9693; Cabral, Howard/0000-0002-1185-8331; Hess, Christopher/0000-0002-5132-5302; Anderson, Christopher/0000-0002-0053-2002 FU National Center for Research Resources [P41-RR14075, R01 RR 16594-01A1, BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01 EB001550, R01EB006758]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; Mental Illness and Neuroscience Discovery (MIND) Institute; National Institute on Aging [P50 AG05681, P01 AG03991, AG02238, AG021910]; Ellison Medical Foundation; NIH [P30 AG010129, K01 AG030514] FX The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work was supported by grants from the National Center for Research Resources (P41-RR14075, R01 RR 16594-01A1 and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01 EB001550, R01EB006758), National Institute for Neurological Disorders and Stroke (R01 NS052585-01), the Mental Illness and Neuroscience Discovery (MIND) Institute, and the National Institute on Aging (P50 AG05681, P01 AG03991, AG02238 and AG021910). Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U. S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. NR 60 TC 40 Z9 42 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 23 PY 2010 VL 5 IS 9 AR e12853 DI 10.1371/journal.pone.0012853 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 653KV UT WOS:000282091100002 PM 20886094 ER PT J AU Bhatt, DL Eagle, KA Ohman, EM Hirsch, AT Goto, S Mahoney, EM Wilson, PWF Alberts, MJ D'Agostino, R Liau, CS Mas, JL Rother, J Smith, SC Salette, G Contant, CF Massaro, JM Steg, PG AF Bhatt, Deepak L. Eagle, Kim A. Ohman, E. Magnus Hirsch, Alan T. Goto, Shinya Mahoney, Elizabeth M. Wilson, Peter W. F. Alberts, Mark J. D'Agostino, Ralph Liau, Chiau-Suong Mas, Jean-Louis Roether, Joachim Smith, Sidney C., Jr. Salette, Genevieve Contant, Charles F. Massaro, Joseph M. Steg, Ph. Gabriel CA REACH Registry Investigators TI Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or With Atherothrombosis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE CORONARY SYNDROME; REGISTRY; DISEASE; CARE; ROSIGLITAZONE; CLOPIDOGREL; PREVENTION; REDUCTION; MORTALITY; CANGRELOR AB Context Clinicians and trialists have difficulty with identifying which patients are highest risk for cardiovascular events. Prior ischemic events, polyvascular disease, and diabetes mellitus have all been identified as predictors of ischemic events, but their comparative contributions to future risk remain unclear. Objective To categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis using simple clinical descriptors. Design, Setting, and Patients Outpatients with coronary artery disease, cerebrovascular disease, or peripheral arterial disease or with multiple risk factors for atherothrombosis were enrolled in the global Reduction of Atherothrombosis for Continued Health (REACH) Registry and were followed up for as long as 4 years. Patients from 3647 centers in 29 countries were enrolled between 2003 and 2004 and followed up until 2008. Final database lock was in April 2009. Main Outcome Measures Rates of cardiovascular death, myocardial infarction, and stroke. Results A total of 45 227 patients with baseline data were included in this 4-year analysis. During the follow-up period, a total of 5481 patients experienced at least 1 event, including 2315 with cardiovascular death, 1228 with myocardial infarction, 1898 with stroke, and 40 with both a myocardial infarction and stroke on the same day. Among patients with atherothrombosis, those with a prior history of ischemic events at baseline (n=21 890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or peripheral artery disease (n=15 264) had a lower risk (12.2%; 95% CI, 11.4%-12.9%); and patients without established atherothrombosis but with risk factors only (n=8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%) (P<.001 for all comparisons). In addition, in multivariable modeling, the presence of diabetes (hazard ratio [HR], 1.44; 95% CI, 1.36-1.53; P<.001), an ischemic event in the previous year (HR, 1.71; 95% CI, 1.57-1.85; P<.001), and polyvascular disease (HR, 1.99; 95% CI, 1.78-2.24; P<.001) each were associated with a significantly higher risk of the primary end point. Conclusion Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis. JAMA. 2010; 304(12): 1350-1357 C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA 02132 USA. [Alberts, Mark J.] Northwestern Univ, Sch Med, Chicago, IL USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [D'Agostino, Ralph] Boston Univ, Boston, MA 02215 USA. [Eagle, Kim A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Goto, Shinya] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Liau, Chiau-Suong] Taiwan Univ Hosp, Taipei, Taiwan. [Liau, Chiau-Suong] Coll Med, Taipei, Taiwan. [Mas, Jean-Louis] Ctr Raymond Garcin, Paris, France. [Ohman, E. Magnus] Duke Univ, Med Ctr, Durham, NC USA. [Roether, Joachim] Asklepios Klin Altona, Dept Neurol, Hamburg, Germany. [Smith, Sidney C., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Steg, Ph. Gabriel] Hop Bichat Claude Bernard, F-75877 Paris 18, France. [Wilson, Peter W. F.] Emory Univ, Sch Med, Atlanta, GA USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu RI Library, Woodruff Health/A-6096-2012 FU AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Heartscape; Sanofi-Aventis; Medicines Company; Blue Cross Blue Shield of Michigan; National Institutes of Health (NIH); Mardigian Foundation; GORE; Hewlett Foundation; CV Therapeutics; Daiichi Sankyo; Datascope; Eli Lilly; Marquet; Schering-Plough; Abbott Vascular; Ono; Otsuka; Sankyo; Daiichi; Takeda; Asteras; Kowa; AGA Medical; Boehringer Ingelheim; EKR; Servier; Waksman Foundation (Tokyo, Japan) FX Dr Bhatt reported having received institutional research support from AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi-Aventis, and The Medicines Company. Dr Eagle reported having received grant/research support from Bristol-Myers Squibb, Blue Cross Blue Shield of Michigan, the National Institutes of Health (NIH), Sanofi-Aventis, the Mardigian Foundation Varbedian Fund, GORE, and the Hewlett Foundation and being a consultant for the NIH National Heart, Lung, and Blood Institute, Sanofi-Aventis, and the Robert Wood Johnson Foundation. Dr Ohman reported receiving research grants from Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo, Datascope, Eli Lilly, Marquet, Sanofi-Aventis, Schering-Plough, and The Medicines Company and providing consulting or other services for Abiomed, AstraZeneca, CV Therapeutics, Datascope, Gilead Sciences, Liposcience, Marquet, Northpoint Domain, Pozen, Response Biomedical, Sanofi-Aventis, The Medicines Company, and WebMD (theheart.org). Dr Hirsch reported having received research grants from Bristol-Myers Squibb, Sanofi-Aventis, and Abbott Vascular and served as a consultant to Roche, Cytokinetics, ev3, and Talecris. Dr Goto reported having received research grants from Pfizer, Sanofi-Aventis, Ono, Eisai, Otsuka, Sankyo, Daiichi, Takeda, Asteras, Kowa, and AstraZeneca and honoraria from Sanofi-Aventis, Eisai, Otsuka, Daiichi-Sankyo, and Schering-Plough. Dr Mahoney reported having received grant support from Sanofi-Aventis, Bristol-Myers Squibb, Daiichi-Sankyo, and Eli Lilly and honoraria from Sanofi-Aventis and Bristol-Myers Squibb. Dr Wilson reported having received research grants from Sanofi-Aventis. Dr Alberts reported having received research support from AGA Medical, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, EKR, Sanofi-Aventis, and Schering-Plough; having participated in speakers' bureaus for Bristol-Myers Squibb, Boehringer Ingelheim, DiaDexus, Genentech, MedScape, and Sanofi-Aventis; having received honoraria from Bristol-Myers Squibb, Boehringer Ingelheim, DiaDexus, Genentech, MedScape, and Sanofi-Aventis; and having acted as a consultant or advisory board member for Bristol-Myers Squibb, Boehringer Ingelheim, EKR, Genentech, Merck, Pfizer, and Sanofi-Aventis. Dr D'Agostino reported having received honoraria from Sanofi-Aventis. Dr Liau reported no disclosures. Dr Mas reported having received research grants, honoraria, and consulting fees from Sanofi-Aventis, Bristol-Myers Squibb, and Servier and honoraria and consulting fees from Boehringer Ingelheim. Dr Rother reported having participated in speakers' bureaus for Boehringer-Ingelheim, Bristol-Myers Squibb, Sanofi-Aventis, and Lundbeck and having acted as a consultant or advisory board member for Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Sanofi-Aventis, and Lundbeck. Dr Smith Jr reported no disclosures. Dr Salette reported being an employee of Sanofi-Aventis. Dr Contant reported no disclosures. Dr Massaro reported having received honoraria from Sanofi-Aventis. Dr Steg reported having received research grants (to his institution) from Servier; participating in consultancy or advisory boards for Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, Daiichi-Sankyo-Lilly, GlaxoSmithKline, Medtronic, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier, and The Medicines Company; and being a stockholder in Aterovax.; The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The REACH Registry is endorsed by the World Heart Federation. NR 24 TC 198 Z9 211 U1 6 U2 22 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 22 PY 2010 VL 304 IS 12 BP 1350 EP 1357 DI 10.1001/jama.2010.1322 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 652LK UT WOS:000282007900018 PM 20805624 ER PT J AU Cedolin, L Delgutte, B AF Cedolin, Leonardo Delgutte, Bertrand TI Spatiotemporal Representation of the Pitch of Harmonic Complex Tones in the Auditory Nerve SO JOURNAL OF NEUROSCIENCE LA English DT Article ID ANTEROVENTRAL COCHLEAR NUCLEUS; ITERATED RIPPLED NOISE; STEADY-STATE VOWELS; TEMPORAL REPRESENTATION; DISCHARGE PATTERNS; GUINEA-PIG; FUNDAMENTAL FREQUENCIES; ELECTRICAL-STIMULATION; PHASE SENSITIVITY; CROSS-CORRELATION AB The pitch of harmonic complex tones plays an important role in speech and music perception and the analysis of auditory scenes, yet traditional rate-place and temporal models for pitch processing provide only an incomplete description of the psychophysical data. To test physiologically a model based on spatiotemporal pitch cues created by the cochlear traveling wave (Shamma, 1985), we recorded from single fibers in the auditory nerve of anesthetized cat in response to harmonic complex tones with missing fundamentals and equal-amplitude harmonics. We used the principle of scaling invariance in cochlear mechanics to infer the spatiotemporal response pattern to a given stimulus from a series of measurements made in a single fiber as a function of fundamental frequency F(0). We found that spatiotemporal cues to resolved harmonics are available for F(0) values between 350 and 1100 Hz and that these cues are more robust than traditional rate-place cues at high stimulus levels. The lower F(0) limit is determined by the limited frequency selectivity of the cochlea, whereas the upper limit is caused by the degradation of phase locking to the stimulus fine structure at high frequencies. The spatiotemporal representation is consistent with the upper F(0) limit to the perception of the pitch of complex tones with a missing fundamental, and its effectiveness does not depend on the relative phase between resolved harmonics. The spatiotemporal representation is thus consistent with key trends in human psychophysics. C1 [Cedolin, Leonardo; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Cedolin, Leonardo] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Delgutte, B (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM bertrand_delgutte@meei.harvard.edu OI , /0000-0003-1349-9608 FU National Institutes of Health [R01 DC002258, P30 DC005209] FX This work was supported by National Institutes of Health Grants R01 DC002258 and P30 DC005209. We thank Connie Miller for surgical assistance and Ken Hancock for software support. Bob Carlyon, Ken Hancock, Andrew Oxenham, Shihab Shamma, Chris Shera, Garrett Stanley, and Grace Wang made valuable comments on this manuscript. NR 73 TC 23 Z9 24 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 22 PY 2010 VL 30 IS 38 BP 12712 EP 12724 DI 10.1523/JNEUROSCI.6365-09.2010 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 653NG UT WOS:000282097600016 PM 20861376 ER PT J AU Goyal, A Bhatt, DL Steg, PG Gersh, BJ Alberts, MJ Ohman, EM Corbalan, R Eagle, KA Gaxiola, E Gao, RL Goto, S D'Agostino, RB Califf, RM Smith, SC Wilson, PWF AF Goyal, Abhinav Bhatt, Deepak L. Steg, P. Gabriel Gersh, Bernard J. Alberts, Mark J. Ohman, E. Magnus Corbalan, Ramon Eagle, Kim A. Gaxiola, Efrain Gao, Runlin Goto, Shinya D'Agostino, Ralph B. Califf, Robert M. Smith, Sidney C., Jr. Wilson, Peter W. F. CA REACH Registry Investigators TI Attained Educational Level and Incident Atherothrombotic Events in Low- and Middle-Income Compared With High-Income Countries SO CIRCULATION LA English DT Article DE cardiovascular diseases; epidemiology; registries; risk factors; smoking ID RISK-FACTORS; MYOCARDIAL-INFARCTION; SOCIOECONOMIC-STATUS; WOMEN; HEALTH; INEQUALITIES; OUTPATIENTS; MORTALITY; OBESITY; DISEASE AB Background-Studies report a protective effect of higher attained educational level (AEL) on cardiovascular outcomes. However, most of these studies have been conducted in high-income countries (HICs) and lack representation from low and middle-income countries (LMICs), which bear >80% of the global burden of cardiovascular disease. Methods and Results-The Reduction of Atherothrombosis for Continued Health (REACH) Registry is a prospective study of 67 888 subjects with either established atherothrombotic (coronary, cerebrovascular, and/or peripheral arterial) disease or multiple atherothrombotic risk factors enrolled from 5587 physician practices in 44 countries. At baseline, AEL (0 to 8 years, 9 to 12 years, trade or technical school, and university) was self-reported for 61 332 subjects. Outcomes included the baseline prevalence of atherothrombotic risk factors and the rate of incident cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) through 23 months across AEL groups, stratified by sex and world region (LMICs or HICs). Educational attainment was inversely associated with age and diabetes mellitus and directly associated with hypercholesterolemia in all subjects. However, for other risk factors such as obesity, smoking, hypertension, and baseline burden of vascular disease, AEL was protective (inversely associated) in HICs but not protective in LMICs. The protective effect of greater AEL on incident cardiovascular events was strongest in men from HICs (P<0.0001), more modest in women from HICs (P=0.0026) and in men from LMICs (P=0.082), and essentially absent in women from LMICs (P=0.32). Conclusion-In contrast to HICs, higher AEL may not be protective against cardiovascular events in LMICs, particularly in women. (Circulation. 2010;122:1167-1175.) C1 [Goyal, Abhinav] Emory Rollins Sch Publ Hlth, Atlanta, GA USA. [Goyal, Abhinav; Wilson, Peter W. F.] Emory Sch Med, Atlanta, GA 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. [Steg, P. Gabriel] Univ Paris 07, INSERM, U698, Paris, France. [Steg, P. Gabriel] Hop Bichat Claude Bernard, AP HP, F-75877 Paris 18, France. [Gersh, Bernard J.] Mayo Clin, Div Cardiovasc Dis & Internal Med, Rochester, MN USA. [Alberts, Mark J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Ohman, E. Magnus; Califf, Robert M.] Duke Clin Res Inst, Durham, NC USA. [Corbalan, Ramon] Pontificia Univ Catolica Chile, Santiago, Chile. [Eagle, Kim A.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Gaxiola, Efrain] Jardines Hosp Especialidades, Ctr Especializado Terapia Endovasc, Guadalajara, Jalisco, Mexico. [Gao, Runlin] Fuwai Hosp, Beijing, Peoples R China. [Goto, Shinya] Tokai Univ, Sch Med, Kanagawa 2591100, Japan. [D'Agostino, Ralph B.] Boston Univ, Boston, MA 02215 USA. [Smith, Sidney C., Jr.] Univ N Carolina, UNC Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. RP Goyal, A (reprint author), 1518 Clifton Rd NE,Room 456, Atlanta, GA 30322 USA. EM agoyal4@emory.edu RI Library, Woodruff Health/A-6096-2012; Goyal, Abhinav/J-5086-2012 OI Goyal, Abhinav/0000-0002-6286-2349 FU Sanofi-aventis (Paris, France); Bristol-Myers Squibb (Princeton, NJ); Waksman Foundation (Tokyo, Japan) FX The REACH Registry is sponsored by sanofi-aventis (Paris, France), Bristol-Myers Squibb (Princeton, NJ), and the Waksman Foundation (Tokyo, Japan). The sponsors had no role in study design, data collection and data interpretation, manuscript writing, and the decision to submit for publication. Statistical support was provided by sanofi-aventis under the direction of the study authors. NR 22 TC 20 Z9 22 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 SEP 21 PY 2010 VL 122 IS 12 BP 1167 EP 1175 DI 10.1161/CIRCULATIONAHA.109.919274 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 652WR UT WOS:000282042100006 PM 20823388 ER PT J AU Cheng, S Cohen, KS Shaw, SY Larson, MG Hwang, SJ McCabe, EL Martin, RP Klein, RJ Hashmi, B Hoffmann, U Fox, CS Vasan, RS O'Donnell, CJ Wang, TJ AF Cheng, Susan Cohen, Kenneth S. Shaw, Stanley Y. Larson, Martin G. Hwang, Shih-Jen McCabe, Elizabeth L. Martin, Roderick P. Klein, Rachael J. Hashmi, Basma Hoffmann, Udo Fox, Caroline S. Vasan, Ramachandran S. O'Donnell, Christopher J. Wang, Thomas J. TI Association of Colony-Forming Units With Coronary Artery and Abdominal Aortic Calcification SO CIRCULATION LA English DT Article DE angiogenesis; atherosclerosis; epidemiology; risk factors; vasculature ID ENDOTHELIAL PROGENITOR CELLS; SOUTH ASIAN MEN; CARDIOVASCULAR RISK; CAROTID ATHEROSCLEROSIS; COMPUTED-TOMOGRAPHY; HEART-DISEASE; DYSFUNCTION; CALCIUM; NUMBER; POPULATION AB Background-Certain bone marrow-derived cell populations, called endothelial progenitor cells, have been reported to possess angiogenic activity. Experimental data suggest that depletion of these angiogenic cell populations may promote atherogenesis, but limited data are available on their relation to subclinical atherosclerotic cardiovascular disease in humans. Methods and Results-We studied 889 participants of the Framingham Heart Study who were free of clinically apparent cardiovascular disease (mean age, 65 years; 55% women). Participants underwent endothelial progenitor cell phenotyping with an early-outgrowth colony-forming unit assay and cell surface markers. Participants also underwent noncontrast multidetector computed tomography to assess the presence of subclinical atherosclerosis, as reflected by the burden of coronary artery calcification and abdominal aortic calcification. Across decreasing tertiles of colony-forming units, there was a progressive increase in median coronary artery calcification and abdominal aortic calcification scores. In multivariable analyses adjusting for traditional cardiovascular risk factors, each 1-SD increase in colony-forming units was associated with a approximate to 16% decrease in coronary artery calcification (P=0.02) and 17% decrease in abdominal aortic calcification (P=0.03). In contrast, neither CD34(+) /KDR(+) nor CD34(+) variation was associated with significant differences in coronary or aortic calcification. Conclusions-In this large, community-based sample of men and women, lower colony-forming unit number was associated with a higher burden of subclinical atherosclerosis in the coronary arteries and aorta. Decreased angiogenic potential could contribute to the development of atherosclerosis in humans. (Circulation. 2010;122:1176-1182.) C1 [Cheng, Susan; Shaw, Stanley Y.; McCabe, Elizabeth L.; O'Donnell, Christopher J.; Wang, Thomas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Cohen, Kenneth S.; Martin, Roderick P.; Klein, Rachael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Shaw, Stanley Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cheng, Susan; Larson, Martin G.; Hwang, Shih-Jen; McCabe, Elizabeth L.; Fox, Caroline S.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Cheng, Susan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02114 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Metab & Diabet,Dept Med, Boston, MA 02114 USA. [Cheng, Susan] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Clin Investigator Training Program, Boston, MA 02114 USA. [Cohen, Kenneth S.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Hwang, Shih-Jen; Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Martin, Roderick P.] Genzyme Corp, Cambridge, MA USA. [Hashmi, Basma] Harvard Univ, Dept Bioengn, Boston, MA 02114 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. RP Wang, TJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Ellison Medical Foundation; Harvard-MIT/BIDMC; [R01-HL083197]; [R01-HL93328] FX This work was supported in part by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract No. N01-HC-25195), grant R01-HL083197 (Dr Wang), grant R01-HL93328 (Dr Vasan), the Ellison Medical Foundation (Dr Cheng), and the Harvard-MIT/BIDMC Clinical Investigator Training Program (Dr Cheng). NR 49 TC 17 Z9 17 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 SEP 21 PY 2010 VL 122 IS 12 BP 1176 EP 1182 DI 10.1161/CIRCULATIONAHA.109.931279 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 652WR UT WOS:000282042100007 PM 20823386 ER PT J AU Yeh, RW Yu, PB Drachman, DE AF Yeh, Robert W. Yu, Paul B. Drachman, Douglas E. TI Takotsubo Cardiomyopathy Complicated by Cardiac Tamponade Classic Hemodynamic Findings With a New Disease SO CIRCULATION LA English DT Editorial Material C1 [Yeh, Robert W.; Yu, Paul B.; Drachman, Douglas E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Yeh, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, GRB 800, Boston, MA 02114 USA. EM ryeh@partners.org OI Yu, Paul/0000-0003-2145-4944 FU NHLBI NIH HHS [K08 HL079943]; NIAMS NIH HHS [R01 AR057374] NR 3 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 21 PY 2010 VL 122 IS 12 BP 1239 EP 1241 DI 10.1161/CIRCULATIONAHA.110.955633 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 652WR UT WOS:000282042100013 PM 20855670 ER PT J AU Azadani, AN Jaussaud, N Ge, L Chitsaz, S Chuter, TAM Tseng, EE AF Azadani, Ali N. Jaussaud, Nicolas Ge, Liang Chitsaz, Sam Chuter, Timothy A. M. Tseng, Elaine E. TI Impact of Orientation and Size Matched Transcatheter Aortic Valves on Valve-in-Valve Hemodynamics SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 22nd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY SEP 21-25, 2010 CL Washington, DC SP Cardiovascular Res Fdn C1 UCSF Med Ctr, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 21 PY 2010 VL 56 IS 13 SU S MA TCT-132 BP B31 EP B31 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V45NV UT WOS:000209824200133 ER PT J AU Cubeddu, RJ Blankenship, JC Dangas, G Lansky, A Palacios, IF Witzenbichler, B Guagliumi, G Kornowski, R Dudek, D Stone, GW Mehran, R AF Cubeddu, Roberto J. Blankenship, James C. Dangas, George Lansky, Alexandra Palacios, Igor F. Witzenbichler, Bernhard Guagliumi, Giulio Kornowski, Ran Dudek, Dariusz Stone, Gregg W. Mehran, Roxana TI STEMI Presentation During Off-Hours Does Not Compromise Response Times or Mortality: A HORIZONS-A MI Substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 22nd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY SEP 21-25, 2010 CL Washington, DC SP Cardiovascular Res Fdn C1 [Cubeddu, Roberto J.] Aventura Hosp & Med Ctr, Miami, FL USA. [Blankenship, James C.] Geisinger Med Ctr, Danville, PA USA. [Dangas, George; Lansky, Alexandra; Stone, Gregg W.; Mehran, Roxana] Columbia Univ, Med Ctr, New York, NY USA. [Dangas, George; Stone, Gregg W.; Mehran, Roxana] Cardiovasc Res Fdn, New York, NY USA. [Palacios, Igor F.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Witzenbichler, Bernhard] Charite, Campus Benjamin Franklin, Berlin, Germany. [Guagliumi, Giulio] Osped Riuniti Di Bergamo, Bergamo, Italy. [Kornowski, Ran] Rabin Med Ctr, Petah Tiqwa, Israel. [Dudek, Dariusz] Jagiellonian Univ, Krakow, Poland. 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 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 21 PY 2010 VL 56 IS 13 SU S MA TCT-87 BP B20 EP B21 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V45NV UT WOS:000209824200088 ER PT J AU Margey, RJ Suh, WM Sahkuja, R Yeh, R Seto, A Witzke, C Palacios, IF AF Margey, Ronan J. Suh, William M. Sahkuja, Rahul Yeh, Robert Seto, Arnold Witzke, Christian Palacios, Igor F. TI Percutaneous Pericardial Biopsy- A Novel Interventional Technique to Aid Diagnosis and Management of Pericardial Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 [Margey, Ronan J.; Suh, William M.; Sahkuja, Rahul; Yeh, Robert; Seto, Arnold; Witzke, Christian; Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 21 PY 2010 VL 56 IS 13 SU S MA TCT-477 BP B109 EP B110 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V45NV UT WOS:000209824200474 ER PT J AU Nadkarni, S AF Nadkarni, Seemantini TI Intracoronary Laser Speckle Imaging: a Novel Optical Technique to Detect Unstable Atherosclerotic Plaque SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 22nd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY SEP 21-25, 2010 CL Washington, DC SP Cardiovascular Res Fdn C1 [Nadkarni, Seemantini] Harvard Med Sch, Mass Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 21 PY 2010 VL 56 IS 13 SU S MA TCT-368 BP B85 EP B85 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V45NV UT WOS:000209824200366 ER PT J AU Yoo, H Kim, JW Shishkov, M Namati, E Morse, T Shubochkin, R McCarthy, JR Bouma, BE Jaffer, FA Tearney, GJ AF Yoo, Hongki Kim, Jin Won Shishkov, Milen Namati, Eman Morse, Theodore Shubochkin, Roman McCarthy, Jason R. Bouma, Brett E. Jaffer, Farouc A. Tearney, Guillermo J. TI Dual-modality Catheter For Simultaneous Microstructurat And Molecular Imaging In Vivo SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 22nd Annual Transcatheter Cardiovascular Therapeutics (TCT) Symposium CY SEP 21-25, 2010 CL Washington, DC SP Cardiovascular Res Fdn C1 [Yoo, Hongki; Kim, Jin Won; Shishkov, Milen; Namati, Eman; McCarthy, Jason R.; Bouma, Brett E.; Jaffer, Farouc A.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yoo, Hongki; Kim, Jin Won; Shishkov, Milen; Namati, Eman; McCarthy, Jason R.; Bouma, Brett E.; Jaffer, Farouc A.; Tearney, Guillermo J.] Harvard Med Sch, Boston, MA USA. [Morse, Theodore; Shubochkin, Roman] Boston Univ, Boston, MA 02215 USA. [Bouma, Brett E.; Tearney, Guillermo J.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 21 PY 2010 VL 56 IS 13 SU S MA TCT-345 BP B80 EP B80 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V45NV UT WOS:000209824200343 ER PT J AU Siderowf, A Xie, SX Hurtig, H Weintraub, D Duda, J Chen-Plotkin, A Shaw, M Van Deerlin, V Trojanowski, JQ Clark, C AF Siderowf, A. Xie, S. X. Hurtig, H. Weintraub, D. Duda, J. Chen-Plotkin, A. Shaw, L. M. Van Deerlin, V. Trojanowski, J. Q. Clark, C. TI CSF amyloid beta 1-42 predicts cognitive decline in Parkinson disease SO NEUROLOGY LA English DT Article ID CEREBROSPINAL-FLUID TAU; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; LEWY BODIES; FOLLOW-UP; DEMENTIA; BIOMARKERS; DIAGNOSIS; GENOTYPE; PLASMA AB Objective: Cognitive decline associated with Parkinson disease (PD) is common and highly disabling. Biomarkers that help identify patients at risk for cognitive decline would be useful additions to the clinical management of the disease. Methods: A total of 45 patients with PD were enrolled in this prospective cohort study and had at least 1 yearly longitudinal follow-up evaluation. CSF was collected at baseline and cognition was assessed at baseline and follow-up visits using the Mattis Dementia Rating Scale (DRS-2). CSF was tested for amyloid beta 1-42 (A beta(1-42)), p-tau(181p), and total tau levels using the Luminex xMAP platform. Mixed linear models were used to test for associations between baseline CSF biomarker levels and change in cognition over time. Results: Lower baseline CSF A beta(1-42) was associated with more rapid cognitive decline. Subjects with CSF A beta(1-42) levels <= 192 pg/mL declined an average of 5.85 (95% confidence interval 2.11-9.58, p = 0.002) points per year more rapidly on the DRS-2 than subjects above that cutoff, after adjustment for age, disease duration, and baseline cognitive status. CSF total tau and p-tau(181p) levels were not significantly associated with cognitive decline. Conclusions: Reduced CSF A beta(1-42) was an independent predictor of cognitive decline in patients with PD. This observation is consistent with previous research showing that Alzheimer disease pathology contributes to cognitive impairment in PD. This biomarker may provide clinically useful prognostic information, particularly if combined with other risk factors for cognitive impairment in PD. Neurology (R) 2010;75:1055-1061 C1 [Siderowf, A.; Hurtig, H.; Weintraub, D.; Chen-Plotkin, A.; Clark, C.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19107 USA. [Siderowf, A.; Xie, S. X.; Hurtig, H.; Weintraub, D.; Duda, J.; Chen-Plotkin, A.; Van Deerlin, V.; Trojanowski, J. Q.] Univ Penn, Sch Med, Morris K Udall Ctr Excellence Parkinsons Dis Res, Philadelphia, PA 19107 USA. [Xie, S. X.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19107 USA. [Weintraub, D.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19107 USA. [Shaw, L. M.; Van Deerlin, V.; Trojanowski, J. Q.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19107 USA. [Siderowf, A.; Shaw, L. M.; Trojanowski, J. Q.] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19107 USA. [Weintraub, D.; Duda, J.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Siderowf, A (reprint author), Univ Penn, Sch Med, Dept Neurol, 330 S 9th St,2nd Floor, Philadelphia, PA 19107 USA. EM andrew.siderowf@uphs.upenn.edu FU NINDS [NS-053488, SAP4100027296]; Department of Health of the Commonwealth of Pennsylvania; NIH (NINDS) [NINDS U10 NS0444451, NINDS P50 NS053488, NINDS R43NS0636071, NINDS R01NS065087, NINDS P50 NS053488-01, NINDS U10 NS044451-023]; US Department of Defense; Department of Health, Commonwealth of Pennsylvania; NIH/NINDS [NS053488]; Michael J. Fox Foundation for Parkinson's Research; Teva Pharmaceutical Industries Ltd.; Boehringer Ingelheim; Bayer Schering Pharma; Kyowa Hakko Kirin Pharma, Inc.; PRA International; Novartis; Glaxo-SmithKline; Avid Radiopharmaceuticals, Inc.; St Jude Medical; Amarin Corporation; Prestwick Pharmaceutical, Inc.; HP Therapeutics Foundation, Inc.; Cephalon, Inc.; NIH [NS053488, K23 MH067894, K08 AG033101, AG024904, 1RC 2AG-036535, NIA P01 AG 09215-20, NIA P30 AG 10124-18, NIA PO1 AG 17586-10, NIA 1PO1 AG-19724-07, NIA 1 UO1 AG 024904-05, NINDS P50 NS053488-02, NIA UO1 AG029213-01, RC2NS069368, RC1AG035427, NIA P30AG036468]; Penn Center for Excellence in Research on Neurodegenerative Diseases (CERND); Department of Veterans Affairs; Department of Veterans Affairs, NIH [RO1 NS41265-01, RO1 NS44266]; Michael J. Fox Foundation; Samueli Foundation; Burroughs Wellcome Fund; Pfizer Inc.; Applied Pharmacokinetics and Pharmacodynamics: Principles of Therapeutic Drug Monitoring; Molecular Pathology in Clinical Practice; Marian S. Ware Alzheimer Program FX Supported by a Morris K. Udall Parkinson's Disease Research Center of Excellence grant from NINDS (NS-053488) and by SAP4100027296, a health research grant awarded by the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 2001-77.; Dr. Siderowf serves on a scientific advisory board for and has received speaker honoraria from Teva Pharmaceutical Industries Ltd.; serves/has served as a consultant to Supernus Pharmaceuticals, Inc., Teva Pharmaceutical Industries Ltd., Merck Serono, and Schering-Plough Corp.; receives research support from the NIH (NINDS U10 NS0444451 [site PI], NINDS P50 NS053488 [Co-I], NINDS R43NS0636071 [Co-I], and NINDS R01NS065087 [Co-I]), the US Department of Defense, and the Department of Health, Commonwealth of Pennsylvania; and has served as a consultant on manganese litigation. Dr. Xie receives research support from the NIH/NINDS (NS053488 [coinvestigator and core director]). Dr. Hurtig served on a grant review panel for the Michael J. Fox Foundation for Parkinson's Research; serves on the editorial board of Parkinsonism and Related Disorders; serves as Movement Disorders Section Editor for UpToDate; has received speaker honoraria from Teva Pharmaceutical Industries Ltd.; receives research support from Teva Pharmaceutical Industries Ltd., Boehringer Ingelheim, Bayer Schering Pharma, Kyowa Hakko Kirin Pharma, Inc., PRA International, Novartis, Glaxo-SmithKline, Avid Radiopharmaceuticals, Inc., St Jude Medical, Amarin Corporation, Prestwick Pharmaceutical, Inc., HP Therapeutics Foundation, Inc., Cephalon, Inc., NIH (NINDS P50 NS053488-01 [core leader and PI] and NINDS U10 NS044451-023 [site PI]); and holds stock in Teva Pharmaceutical Industries Ltd. Dr. Weintraub has served on a scientific advisory board for Boehringer Ingelheim; serves on the editorial board of Movement Disorders; has received honoraria from Boehringer Ingelheim, ACADIA Pharmaceuticals Inc., GE Healthcare, Novartis, Osmotica Pharmaceutical Corp., BrainCells Inc., Merck Serono, Sanofi-Aventis, Johnson & Johnson, Solvay Pharmaceuticals, Inc., and Pfizer Inc.; and receives research support from Boehringer Ingelheim, the NIH (K23 MH067894 [PI]), the Penn Center for Excellence in Research on Neurodegenerative Diseases (CERND), and the Michael J. Fox Foundation for Parkinson's Research. Dr. Duda served on a grant review panel for the Michael J. Fox Foundation for Parkinson's Research; serves/has served on a scientific advisory boards for Boehringer Ingelheim, the Lewy Body Dementia Association, and the Lewy Body Society; has received honoraria for interviews for articles in the PD Monitor and Commentary, a publication supported by an educational grant from Teva Pharmaceutical Industries Ltd.; receives research support from the Department of Veterans Affairs (Biomedical Laboratory Research and Development Service Merit Award [PI], Cooperative Studies Program 468 [site PI]), the NIH (RO1 NS41265-01 [Co-I], RO1 NS44266 [Co-I]), the Michael J. Fox Foundation, the Department of Health, Commonwealth of Pennsylvania, and the Samueli Foundation; and holds stock in C. R. Bard, Inc., Celgene, Clarient, and Johnson & Johnson. Dr. Chen-Plotkin receives research support from the Burroughs Wellcome Fund and the NIH (K08 AG033101 [PI]). Dr. Shaw has served on a scientific advisory board for Bristol-Myers Squibb; has received funding for travel and speaker honoraria from Pfizer Inc.; ; serves on the editorial board of Therapeutic Drug Monitoring; may potentially receive revenue for patent pending re: O-methylated rapamycin derivatives for alleviation and inhibition of lymphoproliferative disorders, licensed by the University of Pennsylvania to Novartis; receives royalties from publication of Applied Pharmacokinetics and Pharmacodynamics: Principles of Therapeutic Drug Monitoring (Wolters Kluwer/ippincott Williams & Wilkins, 2005); receives research support from the NIH (AG024904 [Co-PI Biomarker Core Laboratory] and 1RC 2AG-036535 (ARRA) [PI Biomarker Core Laboratory]); and receives board of directors' compensation and holds stock options in Saladax Biomedical. Dr. Van Deerlin serves on the editorial board of Molecular Diagnosis and Therapy; has a patent pending re: Compositions and methods for the treatment of frontotemporal lobar degeneration with TDP-43 inclusions; receives royalties from the publication of Molecular Pathology in Clinical Practice (Springer, 2007); and receives research support from the NIH (NS053488 [Neuropathology and Genetics Core, Core Co-Leader] and AG010124 [Neuropathology Core, Co-I]). Dr. Trojanowski has received funding for travel and honoraria from Takeda Pharmaceutical Company Ltd.; has received speaker honoraria from Pfizer Inc.; serves as an Associate Editor of Alzheimer's & Dementia; may accrue revenue on patents re: Modified avidin-biotin technique, Method of stabilizing microtubules to treat Alzheimer's disease, Method of detecting abnormally phosphorylated tau, Method of screening for Alzheimer's disease or disease associated with the accumulation of paired helical filaments, Compositions and methods for producing and using homogeneous neuronal cell transplants, Rat comprising straight filaments in its brain, Compositions and methods for producing and using homogeneous neuronal cell transplants to treat neurodegenerative disorders and brain and spinal cord injuries, Diagnostic methods for Alzheimer's disease by detection of multiple MRNAs, Methods and compositions for determining lipid peroxidation levels in oxidant stress syndromes and diseases, Compositions and methods for producing and using homogenous neuronal cell transplants, Method of identifying, diagnosing and treating alpha-synuclein positive neurodegenerative disorders, Mutation-specific functional impairments in distinct tau isoforms of hereditary frontotemporal dementia and parkinsonism linked to chromosome-17: genotype predicts phenotype, Microtubule stabilizing therapies for neurodegenerative disorders, and Treatment of Alzheimer's and related diseases with an antibody; and receives research support from the NIH (NIA P01 AG 09215-20 [PI], NIA P30 AG 10124-18 [PI], NIA PO1 AG 17586-10 [Project 4 Leader], NIA 1PO1 AG-19724-07 [Core C Leader], NIA 1 UO1 AG 024904-05 [Co-PI Biomarker Core Laboratory], NINDS P50 NS053488-02 [PI], NIA UO1 AG029213-01 (Co-I); RC2NS069368 (PI), RC1AG035427 (PI), and NIA P30AG036468 [PI]) and the Marian S. Ware Alzheimer Program. Dr. Clark serves as Medical Director of and holds stock options in Avid Radiopharmaceuticals, Inc.; has served on scientific advisory boards for Elan Corporation and Wyeth; and receives research support from the Department of Health, Commonwealth of Pennsylvania. NR 36 TC 136 Z9 138 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 21 PY 2010 VL 75 IS 12 BP 1055 EP 1061 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 658EZ UT WOS:000282474500006 PM 20720189 ER PT J AU Aarsland, D Bronnick, K Williams-Gray, C Weintraub, D Marder, K Kulisevsky, J Burn, D Barone, P Pagonabarraga, J Allcock, L Santangelo, G Foltynie, T Janvin, C Larsen, JP Barker, RA Emre, M AF Aarsland, D. Bronnick, K. Williams-Gray, C. Weintraub, D. Marder, K. Kulisevsky, J. Burn, D. Barone, P. Pagonabarraga, J. Allcock, L. Santangelo, G. Foltynie, T. Janvin, C. Larsen, J. P. Barker, R. A. Emre, M. TI Mild cognitive impairment in Parkinson disease A multicenter pooled analysis SO NEUROLOGY LA English DT Article ID ORTHOSTATIC HYPOTENSION; DIAGNOSTIC-CRITERIA; NORWEGIAN PARKWEST; CLINICAL-DIAGNOSIS; EXECUTIVE FUNCTION; RATING-SCALE; DEMENTIA; COHORT; RECOMMENDATIONS; INCIDENT AB Background: In studies of mild cognitive impairment (MCI) in Parkinson disease (PD), patients without dementia have reported variable prevalences and profiles of MCI, likely to be due to methodologic differences between the studies. Objective: The objective of this study was to determine frequency and the profile of MCI in a large, multicenter cohort of well-defined patients with PD using a standardized analytic method and a common definition of MCI. Methods: A total of 1,346 patients with PD from 8 different cohorts were included. Standardized analysis of verbal memory, visuospatial, and attentional/executive abilities was performed. Subjects were classified as having MCI if their age-and education-corrected z score on one or more cognitive domains was at least 1.5 standard deviations below the mean of either control subjects or normative data. Results: A total of 25.8% of subjects (95% confidence interval [CI] 23.5-28.2) were classified as having MCI. Memory impairment was most common (13.3%; 11.6-15.3), followed by visuospatial (11.0%; 9.4-13.0) and attention/executive ability impairment (10.1%; 8.6-11.9). Regarding cognitive profiles, 11.3% (9.7-13.1) were classified as nonamnestic single-domain MCI, 8.9% (7.0-9.9) as amnestic single-domain, 4.8% (3.8-6.1) as amnestic multiple-domain, and 1.3% (0.9-2.1) as nonamnestic multiple-domain MCI. Having MCI was associated with older age at assessment and at disease onset, male gender, depression, more severe motor symptoms, and advanced disease stage. Conclusions: MCI is common in patients with PD without dementia, affecting a range of cognitive domains, including memory, visual-spatial, and attention/executive abilities. Future studies of patients with PD with MCI need to determine risk factors for ongoing cognitive decline and assess interventions at a predementia stage. Neurology (R) 2010;75:1062-1069 C1 [Aarsland, D.; Janvin, C.] Stavanger Univ Hosp, Div Psychiat, N-4068 Stavanger, Norway. [Bronnick, K.; Larsen, J. P.] Stavanger Univ Hosp, Norwegian Ctr Movement Disorders, N-4068 Stavanger, Norway. [Aarsland, D.] Akershus Univ Hosp, Div Mental Hlth Serv, Oslo, Norway. Univ Oslo, Oslo, Norway. [Williams-Gray, C.; Barker, R. A.] Univ Cambridge, Dept Clin Neurosci, Ctr Brain Repair, Cambridge, England. [Weintraub, D.] Univ Penn, Dept Psychiat & Neurol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Parkinsons Dis & Mental Illness Res Educ & Clin C, Philadelphia, PA USA. [Marder, K.] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Kulisevsky, J.; Pagonabarraga, J.] Autonomous Univ Barcelona, St Pau Hosp, Dept Neurol, Movement Disorders Unit, Barcelona, Spain. CIBERNED Ctr Invest Biomed Red Enfermedades Neuro, Barcelona, Spain. [Burn, D.; Allcock, L.] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne, Tyne & Wear, England. [Barone, P.; Santangelo, G.] ICD Hermitage Capodimonte, Dept Neurol Sci, Naples, Italy. [Foltynie, T.] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1E 6BT, England. [Emre, M.] Istanbul Univ, Istanbul Fac Med, Dept Neurol, Behav Neurol & Movement Disorders Unit, Istanbul, Turkey. RP Aarsland, D (reprint author), Stavanger Univ Hosp, Div Psychiat, POB 8100, N-4068 Stavanger, Norway. EM daarsland@gmail.com OI Santangelo, Gabriella/0000-0002-7728-852X; Bronnick, Kolbjorn/0000-0002-9156-1633; Aarsland, Dag/0000-0001-6314-216X FU Merck Serono; Lundbeck Inc.; Novartis; GE Healthcare; GlaxoSmithKline; Solvay Pharmaceuticals, Inc; Parkinson's Disease Society; Patrick Berthoud Trust; Boehringer Ingelheim; ACADIA Pharmaceuticals; Osmotica Pharmaceutical Corp.; BrainCells Inc.; Sanofi-Aventis; Johnson Johnson; Solvay Pharmaceuticals, Inc.; NIH [NIMH K23 MH067894, NINDS P50 NS053488-01, NIA RO1AG031348, NINDS R01NS065087, NS36630, 1UL1 RR024156-01, PO412196-G]; Michael J. Fox Foundation for Parkinson's Research; University of Pennsylvania; Amarin Corporation; Boehringer Ingelheim NeuroSearch; Parkinson Disease Foundation; Huntington's Disease Society of America; Parkinson Study Group; Instituto de Salud Carlos III, Spain; Wellcome Trust; NIHR Health Technology Assessment Programme; Michael J Fox Foundation; UCB; MDS Nordion; Orion Corporation; Brain Research Trust; Parkinson's Appeal; Western Norway Health Trust; Norwegian Research Counsel; Norwegian Parkinson's disease Association; Neuroscience at a Glance (Blackwell Publishing); UK Medical Research Council; NIHR; Parkinson Hastalydy (Gunes Tip Kitapevi); Dementia in Parkinson's Disease (Oxford University Press); Eli Lilly and Company FX Supported by an unrestricted grant from Merck Serono.; Dr. Aarsland serves on scientific advisory boards for Lundbeck Inc. and Merck Serono; has received funding for travel and speaker honoraria from Lundbeck Inc., Novartis, GE Healthcare, and GlaxoSmithKline; serves on the editorial boards of International Psychogeriatrics, Movement Disorders, and the Journal of Neurology, Neurosurgery, and Psychiatry; and receives research support from Lundbeck Inc. and Merck Serono. Dr. Bronnick has received funding for travel and speaker honoraria from Solvay Pharmaceuticals, Inc. Dr. Williams-Gray has received research support from the Parkinson's Disease Society and the Patrick Berthoud Trust. Dr. Weintraub has served on scientific advisory boards for Boehringer Ingelheim, ACADIA Pharmaceuticals, Novartis, Osmotica Pharmaceutical Corp., BrainCells Inc., Merck Serono, Sanofi-Aventis, GE Healthcare, Johnson & Johnson, and Solvay Pharmaceuticals, Inc.; serves on the editorial board of Movement Disorders; has received speaker honoraria from Boehringer Ingelheim and Pfizer Inc.; has received/receives research support from Boehringer Ingelheim, the NIH (NIMH K23 MH067894 [PI], NINDS P50 NS053488-01 [coinvestigator], NIA RO1AG031348 [site PI], and NINDS R01NS065087 [coinvestigator]), and the Michael J. Fox Foundation for Parkinson's Research; and receives payments from the University of Pennsylvania for licensing of Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease. Dr. Marder serves on the editorial board of Neurology (R) and receives research support from Amarin Corporation, Boehringer Ingelheim NeuroSearch, the NIH (NS36630 [PI], 1UL1 RR024156-01 [Director PCIR], PO412196-G [coinvestigator], and PO412196-G [coinvestigator]), the Parkinson Disease Foundation, the Huntington's Disease Society of America, and the Parkinson Study Group. Dr. Kulisevsky has served on scientific advisory boards for Merck Serono and Servier; has received honoraria from Merck Serono, Novartis, Lundbeck Inc., and Schwartz Biomedical, LLC.; serves as an Associate Editor for Revista de Neurologia; and receives research support from Lundbeck Inc. and Instituto de Salud Carlos III, Spain. Dr. Burn serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd. and Merck Serono; serves as a consultant for Archimedes, Inc.; serves as an Associate Editor for the Movement Disorder Journal; has received speaker honoraria from Teva Pharmaceutical Industries Ltd./Lundbeck Inc., Orion Corporation, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and UCB; and has received research support from the Wellcome Trust, the NIHR Health Technology Assessment Programme, the Michael J Fox Foundation, and the Parkinson's Disease Society. Dr. Barone serves on scientific advisory boards for and has received funding for travel and speaker honoraria from Boehringer Ingelheim, Merck Serono, Novartis, UCB, and Lundbeck Inc.; serves as an Associate Editor for the Journal of Neurodegenerative Disorders and Parkinson's Europe; and receives research support from Boehringer Ingelheim, Merck Serono, Novartis, UCB, Lundbeck Inc., and Solvay Pharmaceuticals, Inc. Dr. Pagonabarraga has served on a scientific advisory board for Novartis and has received honoraria from Boehringer Ingelheim, Novartis, Janssen, Lundbeck Inc., GlaxoSmithKline, and Schwartz Biomedical, LLC. Dr. Allcock holds stock in the C/N Group, Inc. Dr. Santangelo reports no disclosures. Dr. Foltynie has served on a scientific advisory board for Solvay Pharmaceuticals, Inc.; has received funding for travel or speaker honoraria from Teva Pharmaceutical Industries Ltd.; ,MDS Nordion, GlaxoSmithKline, and Orion Corporation; and has received research support from the Parkinson's Disease Society, Brain Research Trust, and Parkinson's Appeal. Dr. Janvin reports no disclosures. Dr. Larsen has served on scientific advisory boards for Lundbeck Inc. and GlaxoSmithKline; has received speaker honoraria from GlaxoSmithKline; and receives research support from the Western Norway Health Trust, the Norwegian Research Counsel, and the Norwegian Parkinson's disease Association. Dr. Barker serves on scientific advisory boards for and has received speaker honoraria from Teva Pharmaceutical Industries Ltd. and Lundbeck Inc.; serves as co-editor-in-Chief for the Journal of Neurology and ACNR and on the editorial board of Synapse, Cell Transplantation and Regenerative Medicine; receives royalties from the publication of Neuroscience at a Glance (Blackwell Publishing, 1999); and receives research support from the Parkinson's Disease Society, Wellcome Trust, the UK Medical Research Council, and NIHR Biomedical research award to Addenbrooke's University Hospital. Dr. Emre serves on scientific advisory boards for Merck Serono, Novartis, Schering-Plough Corp., Teva Pharmaceutical Industries Ltd./Lundbeck Inc., Orion Corporation, Noscira, and AC Immune SA; has received funding for travel from Lundbeck Inc.; serves on the editorial board of Practical Neurology; receives royalties from the publication of Parkinson Hastalydy (Gunes Tip Kitapevi, 2009) and Dementia in Parkinson's Disease (Oxford University Press, 2010); has received speaker honoraria from Novartis, Lundbeck Inc., Orion Corporation, Pfizer Inc., and Boehringer Ingelheim; and receives/has received research support from Novartis, Lundbeck Inc., and Eli Lilly and Company. NR 32 TC 239 Z9 249 U1 4 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 21 PY 2010 VL 75 IS 12 BP 1062 EP 1069 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 658EZ UT WOS:000282474500007 PM 20855849 ER PT J AU Feruglio, PF Vinegoni, C Gros, J Sbarbati, A Weissleder, R AF Feruglio, P. Fumene Vinegoni, C. Gros, J. Sbarbati, A. Weissleder, R. TI Block matching 3D random noise filtering for absorption optical projection tomography SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RECONSTRUCTION; MICROSCOPY; ALGORITHM; TOOL AB Absorption and emission optical projection tomography (OPT), alternatively referred to as optical computed tomography (optical-CT) and optical-emission computed tomography (optical-ECT), are recently developed three-dimensional imaging techniques with value for developmental biology and ex vivo gene expression studies. The techniques' principles are similar to the ones used for x-ray computed tomography and are based on the approximation of negligible light scattering in optically cleared samples. The optical clearing is achieved by a chemical procedure which aims at substituting the cellular fluids within the sample with a cell membranes' index matching solution. Once cleared the sample presents very low scattering and is then illuminated with a light collimated beam whose intensity is captured in transillumination mode by a CCD camera. Different projection images of the sample are subsequently obtained over a 360 degrees full rotation, and a standard backprojection algorithm can be used in a similar fashion as for x-ray tomography in order to obtain absorption maps. Because not all biological samples present significant absorption contrast, it is not always possible to obtain projections with a good signal-to-noise ratio, a condition necessary to achieve high-quality tomographic reconstructions. Such is the case for example, for early stage's embryos. In this work we demonstrate how, through the use of a random noise removal algorithm, the image quality of the reconstructions can be considerably improved even when the noise is strongly present in the acquired projections. Specifically, we implemented a block matching 3D (BM3D) filter applying it separately on each acquired transillumination projection before performing a complete three-dimensional tomographical reconstruction. To test the efficiency of the adopted filtering scheme, a phantom and a real biological sample were processed. In both cases, the BM3D filter led to a signal-to-noise ratio increment of over 30 dB on severe noise-affected reconstructions revealing original-noise-hidden-image details. These results show the utility of the BM3D approach for OPT under typical conditions of very low light absorption, suggesting its implementation as an efficient alternative to other filtering schemes such as for example the median filter. C1 [Feruglio, P. Fumene; Vinegoni, C.; Weissleder, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Feruglio, P. Fumene; Sbarbati, A.] Univ Verona, Dept Morphol & Biomed Sci, I-37134 Verona, Italy. [Gros, J.] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02115 USA. RP Vinegoni, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu OI Gros, Jerome/0000-0002-2264-2851 FU National Institutes of Health (NIH) [1-RO1-EB006432, UO1-HL080731, PO1-AI054904]; Regione Veneto; CARIVERONA Foundation (Italy) FX We acknowledge support in part from National Institutes of Health (NIH) grants 1-RO1-EB006432, UO1-HL080731, PO1-AI054904. We also acknowledge support from Regione Veneto and CARIVERONA Foundation (Italy). NR 22 TC 5 Z9 5 U1 0 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 21 PY 2010 VL 55 IS 18 BP 5401 EP 5415 DI 10.1088/0031-9155/55/18/009 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 645RG UT WOS:000281481500009 ER PT J AU Rottmann, J Aristophanous, M Chen, A Court, L Berbeco, R AF Rottmann, J. Aristophanous, M. Chen, A. Court, L. Berbeco, R. TI A multi-region algorithm for markerless beam's-eye view lung tumor tracking SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID STEREOTACTIC BODY RADIOTHERAPY; IMPLANTED FIDUCIAL MARKERS; CANCER RADIOTHERAPY; GATED RADIOTHERAPY; RESPIRATORY MOTION; RADIATION-THERAPY; FEASIBILITY; MANAGEMENT; LOCATION; IMAGES AB Methods that allow online lung tumor tracking during radiotherapy are desirable for a variety of applications that have the potential to vastly improve treatment accuracy, dose conformity and sparing of healthy tissue. Several publications have proposed the use of an on-board kV x-ray imager to assess the tumor location during treatment. However, there is some concern that this strategy may expose the patient to a significant amount of additional dose over the course of a typical radiotherapy treatment. In this paper we present an algorithm that utilizes the on-board portal imager of the treatment machine to track lung tumors. This does not expose the patient to additional dose, but is somewhat more challenging as the quality of portal images is inferior when compared to kV x-ray images. To quantify the performance of the proposed algorithm we retrospectively applied it to portal image sequences retrieved from a dynamic chest phantom study and an SBRT treatment performed at our institution. The results were compared to manual tracking by an expert. For the phantom data the tracking error was found to be smaller than 1 mm and for the patient data smaller than 2 mm, which was in the same range as the uncertainty of the gold standard. C1 [Rottmann, J.; Aristophanous, M.; Chen, A.; Court, L.; Berbeco, R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Rottmann, J.; Aristophanous, M.; Chen, A.; Court, L.; Berbeco, R.] Harvard Univ, Sch Med, Boston, MA USA. [Rottmann, J.] German Canc Res Ctr, Heidelberg, Germany. RP Rottmann, J (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM jrottmann@lroc.harvard.edu OI Chen, Aileen/0000-0002-5385-3360 FU Varian Medical Systems, Inc FX We would like to thank Professor Dr Uwe Oelfke at the German Cancer Research Center in Heidelberg for his friendly, continuous support and fruitful discussions. This work was partially supported by a grant from Varian Medical Systems, Inc. NR 36 TC 45 Z9 45 U1 2 U2 8 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 21 PY 2010 VL 55 IS 18 BP 5585 EP 5598 DI 10.1088/0031-9155/55/18/021 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 645RG UT WOS:000281481500021 PM 20808029 ER PT J AU Lee, SH Jung, SY Park, HA Kang, HB Kim, J Choo, DJ Handforth, A Lee, JY AF Lee, So Hyung Jung, Soo Yeon Park, Hang Ah Kang, Han Byul Kim, Jungahn Choo, Dong Joon Handforth, Adrian Lee, Jae Yeol TI Multi-Functional 3,4-Dihydroquinazoline Derivative as T-Type Calcium Channel Blocker: Pharmacokinetics and Anti-Tremor Activity SO BULLETIN OF THE KOREAN CHEMICAL SOCIETY LA English DT Article DE 3,4-Dihydroquinazoline; T-type calcium channel blocker; Pharmacokinetic parameters; Anti-tremor activity ID HUMAN CANCER-CELLS; CA2+ CHANNELS; DISCOVERY; MIBEFRADIL; PHARMACOLOGY; INHIBITION; GROWTH; POTENT C1 [Lee, So Hyung; Jung, Soo Yeon; Park, Hang Ah; Kang, Han Byul; Kim, Jungahn; Choo, Dong Joon; Lee, Jae Yeol] Kyung Hee Univ, Coll Sci, Res Inst Basic Sci, Seoul 130701, South Korea. [Lee, So Hyung; Jung, Soo Yeon; Park, Hang Ah; Kang, Han Byul; Kim, Jungahn; Choo, Dong Joon; Lee, Jae Yeol] Kyung Hee Univ, Coll Sci, Dept Chem, Seoul 130701, South Korea. [Handforth, Adrian] Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA USA. RP Lee, JY (reprint author), Kyung Hee Univ, Coll Sci, Res Inst Basic Sci, Seoul 130701, South Korea. EM ljy@khu.ac.kr OI Lee, Jae Yeol/0000-0001-6622-6692 NR 24 TC 1 Z9 1 U1 0 U2 1 PU KOREAN CHEMICAL SOC PI SEOUL PA 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 0253-2964 J9 B KOREAN CHEM SOC JI Bull. Korean Chem. Soc. PD SEP 20 PY 2010 VL 31 IS 9 BP 2451 EP 2452 DI 10.5012/bkcs.2010.31.9.2451 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 676XV UT WOS:000283953600003 ER PT J AU Punglia, RS Hassett, MJ AF Punglia, Rinaa S. Hassett, Michael J. TI Using Lifetime Risk Estimates to Recommend Magnetic Resonance Imaging Screening for Breast Cancer Survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID SURVEILLANCE MAMMOGRAPHY; CONTRALATERAL BREAST; RANDOMIZED-TRIALS; WOMEN; THERAPY; CHEMOTHERAPY; POPULATION; RECURRENCE; MASTECTOMY; RADIATION C1 [Punglia, Rinaa S.] Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Punglia, RS (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [1K07 CA118629] NR 21 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 SEP 20 PY 2010 VL 28 IS 27 BP 4108 EP 4110 DI 10.1200/JCO.2010.30.0350 PG 3 WC Oncology SC Oncology GA 651FB UT WOS:000281909700004 PM 20697089 ER PT J AU Ayanian, JZ Zaslavsky, AM Arora, NK Kahn, KL Malin, JL Ganz, PA van Ryn, M Hornbrook, MC Kiefe, CI He, YL Urmie, JM Weeks, JC Harrington, DP AF Ayanian, John Z. Zaslavsky, Alan M. Arora, Neeraj K. Kahn, Katherine L. Malin, Jennifer L. Ganz, Patricia A. van Ryn, Michelle Hornbrook, Mark C. Kiefe, Catarina I. He, Yulei Urmie, Julie M. Weeks, Jane C. Harrington, David P. TI Patients' Experiences With Care for Lung Cancer and Colorectal Cancer: Findings From the Cancer Care Outcomes Research and Surveillance Consortium SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-CARE; LANGUAGE CONCORDANCE; ASIAN-AMERICANS; SATISFACTION; BREAST AB Purpose To assess patients' experiences with cancer care, ratings of their quality of care, and correlates of these assessments. Patients and Methods For 4,093 patients with lung cancer and 3,685 patients with colorectal cancer in multiple US regions and health care delivery systems, we conducted telephone surveys of patients or their surrogates in English, Spanish, or Chinese at 4 to 7 months after diagnosis. The surveys assessed ratings of the overall quality of cancer care and experiences with three domains of interpersonal care (physician communication, nursing care, and coordination and responsiveness of care). Results English-speaking Asian/Pacific Islander patients and Chinese-speaking patients and those in worse health reported significantly worse adjusted experiences with all three domains of interpersonal care, whereas white, black, and Hispanic patients reported generally similar experiences with interpersonal care. The overall quality of cancer care was rated as excellent by 44.4% of patients with lung cancer and 53.0% of patients with colorectal cancer, and these ratings were most strongly correlated with positive experiences with coordination and responsiveness of care (Spearman rank coefficients of 0.49 and 0.42 for lung and colorectal cancer, respectively). After multivariate adjustment, excellent ratings were less common for each cancer among black patients, English-speaking Asian/Pacific Islander patients, Chinese-speaking patients, and patients reporting worse health status (all P <= .05). Conclusion Patients' reports and ratings of care differed significantly by race, language, and health status. Efforts to improve patients' experiences with cancer care should focus on problems affecting Asian and Pacific Islander patients and those in worse health. C1 [Ayanian, John Z.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. NCI, Rockville, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. RAND Corp, Santa Monica, CA USA. Univ Minnesota, Minneapolis, MN USA. NW Hawaii SE Kaiser Permanente NW, Portland, OR USA. Univ Iowa, Iowa City, IA USA. RP Ayanian, JZ (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM ayanian@hcp.med.harvard.edu FU National Cancer Institute [U01 CA093344, U01 CA093324, U01 CA093332, U01 CA093348, U01 CA093329, U01 CA093339, U01 CA093326]; Department of Veterans Affairs [U01 CDA093344]; HARQ [03-438MO-03] FX The Cancer Care Outcomes Research and Surveillance Consortium was supported by National Cancer Institute Grants No. U01 CA093344 to the Statistical Coordinating Center at the Dana-Farber Cancer Institute; U01 CA093324 to Harvard Medical School and Northern California Cancer Center; U01 CA093332 to the Dana-Farber Cancer Institute and Cancer Research Network; U01 CA093348 to the RAND Corporation and University of California, Los Angeles; U01 CA093329 to the University of Alabama at Birmingham; U01 CA093339 to the University of Iowa; and U01 CA093326 to the University of North Carolina; also supported by Department of Veterans Affairs Grants No. U01 CDA093344 (MOU) and HARQ 03-438MO-03 to the Durham Veterans Affairs Medical Center. NR 29 TC 50 Z9 50 U1 2 U2 6 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 SEP 20 PY 2010 VL 28 IS 27 BP 4154 EP 4161 DI 10.1200/JCO.2009.27.3268 PG 8 WC Oncology SC Oncology GA 651FB UT WOS:000281909700011 PM 20713876 ER PT J AU Cortes, J Moore, JO Maziarz, RT Wetzler, M Craig, M Matous, J Luger, S Dey, BR Schiller, GJ Pham, D Abboud, CN Krishnamurthy, M Brown, A Laadem, A Seiter, K AF Cortes, Jorge Moore, Joseph O. Maziarz, Richard T. Wetzler, Meir Craig, Michael Matous, Jeffrey Luger, Selina Dey, Bimalangshu R. Schiller, Gary J. Pham, Dat Abboud, Camille N. Krishnamurthy, Muthuswamy Brown, Archie, Jr. Laadem, Abderrahmane Seiter, Karen TI Control of Plasma Uric Acid in Adults at Risk for Tumor Lysis Syndrome: Efficacy and Safety of Rasburicase Alone and Rasburicase Followed by Allopurinol Compared With Allopurinol Alone-Results of a Multicenter Phase III Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol, Sanofi-aventis U.S. ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; CLASSIFICATION; HYPERURICEMIA; CHILDREN AB Purpose Rasburicase is effective in controlling plasma uric acid in pediatric patients with hematologic malignancies. This study in adults evaluated safety of and compared efficacy of rasburicase alone with rasburicase followed by oral allopurinol and with allopurinol alone in controlling plasma uric acid. Patients and Methods Adults with hematologic malignancies at risk for hyperuricemia and tumor lysis syndrome (TLS) were randomly assigned to rasburicase (0.20 mg/kg/d intravenously days 1-5), rasburicase plus allopurinol (rasburicase 0.20 mg/kg/d days 1 to 3 followed by oral allopurinol 300 mg/d days 3 to 5), or allopurinol (300 mg/d orally days 1 to 5). Primary efficacy variable was plasma uric acid response rate defined as percentage of patients achieving or maintaining plasma uric acid <= 7.5 mg/dL during days 3 to 7. Results Ninety-two patients received rasburicase, 92 rasburicase plus allopurinol, and 91 allopurinol. Plasma uric acid response rate was 87% with rasburicase, 78% with rasburicase plus allopurinol, and 66% with allopurinol. It was significantly greater for rasburicase than for allopurinol (P = .001) in the overall study population, in patients at high risk for TLS (89% v 68%; P = .012), and in those with baseline hyperuricemia (90% v 53%; P = .015). Time to plasma uric acid control in hyperuricemic patients was 4 hours for rasburicase, 4 hours for rasburicase plus allopurinol, and 27 hours for allopurinol. Conclusion In adults with hyperuricemia or at high risk for TLS, rasburicase provided control of plasma uric acid more rapidly than allopurinol. Rasburicase was well tolerated as a single agent and in sequential combination with allopurinol. C1 [Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Duke Med Ctr, Durham, NC USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. New York Methodist Hosp, Brooklyn, NY USA. New York Med Coll, Valhalla, NY 10595 USA. W Virginia Univ, Morgantown, WV 26506 USA. Rocky Mt Canc Ctr, Denver, CO USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. UCLA Sch Med, Los Angeles, CA USA. Univ Florida, Shands Jacksonville Med Ctr, Jacksonville, FL USA. Washington Univ, St Louis, MO USA. Ochsner Clin Fdn, New Orleans, LA USA. Sanofi Aventis US, Bridgewater, NJ USA. RP Cortes, J (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd,Unit 428, Houston, TX 77030 USA. EM jcortes@mdanderson.org FU NCI NIH HHS [P30 CA016672] NR 21 TC 43 Z9 43 U1 0 U2 5 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 SEP 20 PY 2010 VL 28 IS 27 BP 4207 EP 4213 DI 10.1200/JCO.2009.26.8896 PG 7 WC Oncology SC Oncology GA 651FB UT WOS:000281909700017 PM 20713865 ER PT J AU Zietman, A Goitein, M Tepper, JE AF Zietman, Anthony Goitein, Michael Tepper, Joel E. TI Technology Evolution: Is It Survival of the Fittest? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROTON; THERAPY AB New technologies are constantly being developed and introduced into medical practice. Their potential or actual use raises questions of efficacy and cost. All too often financial considerations of profit primarily determine whether a technology will be adopted. In an era in which the need to control costs has become clear, this situation is undesirable. The assessment of efficacy can, however, be very difficult, and the control of financial aspects is likewise problematic. In this article, we address these problems and suggest potential solutions, using proton radiotherapy as an example that may be relevant to the development of other medical devices. C1 [Tepper, Joel E.] Univ N Carolina, Sch Med, Dept Radiat Oncol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tepper, JE (reprint author), Univ N Carolina, Sch Med, Dept Radiat Oncol, Lineberger Comprehens Canc Ctr, CB 7512,101 Manning Dr, Chapel Hill, NC 27599 USA. EM tepper@med.unc.edu NR 9 TC 23 Z9 23 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2010 VL 28 IS 27 BP 4275 EP 4279 DI 10.1200/JCO.2010.29.4645 PG 5 WC Oncology SC Oncology GA 651FB UT WOS:000281909700026 PM 20697074 ER PT J AU Canellos, G AF Canellos, George TI Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine Alone in Treatment of Favorable, Limited-Stage Hodgkin's Lymphoma: Do We Really Have Robust Data? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CHEMOTHERAPY C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Canellos, G (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 3 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 SEP 20 PY 2010 VL 28 IS 27 BP E487 EP E487 DI 10.1200/JCO.2010.29.1161 PG 1 WC Oncology SC Oncology GA 651FB UT WOS:000281909700050 ER PT J AU Cotter, SE Devlin, PM Sahni, D Hansen, JL O'Farrell, DA Ng, AK Wang, LC AF Cotter, Shane E. Devlin, Phillip M. Sahni, Debjani Hansen, Jorgen L. O'Farrell, Desmond A. Ng, Andrea K. Wang, Linda C. TI Treatment of Cutaneous Metastases of Merkel Cell Carcinoma With Surface-Mold Computer-Optimized High-Dose-Rate Brachytherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHEMOTHERAPY; RADIATION; SKIN; RADIOTHERAPY; DIAGNOSIS; SURVIVAL; THERAPY; SCALP C1 [Cotter, Shane E.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Devlin, Phillip M.; Sahni, Debjani; Hansen, Jorgen L.; O'Farrell, Desmond A.; Ng, Andrea K.; Wang, Linda C.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RP Cotter, SE (reprint author), Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. NR 22 TC 5 Z9 5 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 SEP 20 PY 2010 VL 28 IS 27 BP E464 EP E466 DI 10.1200/JCO.2010.29.0635 PG 3 WC Oncology SC Oncology GA 651FB UT WOS:000281909700034 PM 20679604 ER PT J AU Gerstner, ER Frosch, MP Batchelor, TT AF Gerstner, Elizabeth R. Frosch, Matthew P. Batchelor, Tracy T. TI Bevacizumab-Induced Diffusion Restriction in Patients With Glioma: Tumor Progression or Surrogate Marker of Hypoxia? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Gerstner, Elizabeth R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 1 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 SEP 20 PY 2010 VL 28 IS 27 BP E478 EP E478 DI 10.1200/JCO.2010.29.2474 PG 1 WC Oncology SC Oncology GA 651FB UT WOS:000281909700044 ER EF