FN Thomson Reuters Web of Science™ VR 1.0 PT J AU McCarthy, JR Korngold, E Weissleder, R Jaffer, FA AF McCarthy, Jason R. Korngold, Ethan Weissleder, Ralph Jaffer, Farouc A. TI A Light-Activated Theranostic Nanoagent for Targeted Macrophage Ablation in Inflammatory Atherosclerosis SO SMALL LA English DT Article ID ULTRASMALL SUPERPARAMAGNETIC PARTICLES; MULTIFUNCTIONAL MAGNETIC NANOPARTICLES; CORONARY-ARTERY-DISEASE; PHOTODYNAMIC THERAPY; IRON-OXIDE; MOTEXAFIN LUTETIUM; HYPERTHERMIA; TEMPERATURE; DRUG; PHOTOANGIOPLASTY AB The synthesis and utility of a multimodal theranostic nanoagent based upon magnetofluorescent nanoparticles for the treatment of inflammatory atherosclerosis is described. These particles are modified with near-infrared fluorophores and light-activated therapeutic moieties, which allow for the optical determination of agent localization and phototoxic activation at spectrally distinct wavelengths. The resulting agent is readily taken up by murine macrophages in vitro and is highly phototoxic, with an LD(50) of 430 pM. Intravenous administration results in the localization of the nanoagent within macrophage-rich atherosclerotic lesions that can be imaged by intravital fluorescence microscopy. Irradiation of the atheroma with 650 nm light activates the therapeutic component and results in eradication of inflammatory macrophages, which may induce lesion stabilization. Importantly, these agents display limited skin photosensitivity, are highly efficacious, and provide an integrated imaging and therapeutic nanoplatform for atherosclerosis. C1 [McCarthy, Jason R.; Weissleder, Ralph] Harvard Univ, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [McCarthy, Jason R.; Korngold, Ethan; Weissleder, Ralph; Jaffer, Farouc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Korngold, Ethan; Jaffer, Farouc A.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. RP McCarthy, JR (reprint author), Harvard Univ, Sch Med, Ctr Syst Biol, 185 Cambridge St,Suite 5-210, Boston, MA 02114 USA. EM jason_mccarthy@hms.harvard.edu; fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU NIH [R21HL093607, U01-HL080731]; American Heart Association Scientist Development Grant; Howard Hughes Medical Institute Career Development Award FX J. R. M. and E. K. contributed equally to this work. We would like to thank Drs. Rainer Kohler and Jose-Luiz Figueiredo for their assistance with surgery and IVFM imaging and Dr. Elena Aikawa and Yoshiko Iwamoto for histopathology. Special thanks to Dr. Martha Morton for expertise and assistance with the acquisition of NMR spectra. This work was supported in part by NIH grants R21HL093607 (J. M.), U01-HL080731 (J. M., F. J., R. W.), the American Heart Association Scientist Development Grant (F. J.), and the Howard Hughes Medical Institute Career Development Award (F. J.). NR 36 TC 59 Z9 60 U1 1 U2 28 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-6810 J9 SMALL JI Small PD SEP 20 PY 2010 VL 6 IS 18 BP 2041 EP 2049 DI 10.1002/smll.201000596 PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 660SR UT WOS:000282664800013 PM 20721949 ER PT J AU Pekoz, EA Shwartz, M Christiansen, CL Berlowitz, D AF Pekoz, Erol A. Shwartz, Michael Christiansen, Cindy L. Berlowitz, Dan TI Approximate models for aggregate data when individual-level data sets are very large or unavailable SO STATISTICS IN MEDICINE LA English DT Article DE approximate Bayesian models; confidential data; Poisson binomial ID NURSING-HOME QUALITY; LONG-TERM-CARE; RISK ADJUSTMENT; OF-CARE; OUTCOMES AB In this article, we study a Bayesian hierarchical model for profiling health-care facilities using approximately sufficient statistics for aggregate facility-level data when the patient-level data sets are very large or unavailable. Starting with a desired patient-level model, we give several approximate models and the corresponding summary statistics necessary to implement the approximations. The key idea is to use sufficient statistics from an approximate model fitted by matching up derivatives of the models' log-likelihood functions. This derivative matching approach leads to an approximation that performs better than the commonly used approximation given in the literature. The performance of several approximation approaches is compared using data on 5 quality indicators from 32 Veterans Administration nursing homes. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Pekoz, Erol A.; Shwartz, Michael] Boston Univ, Sch Management, Boston, MA 02215 USA. [Shwartz, Michael] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Christiansen, Cindy L.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Berlowitz, Dan] Bedford VA Hosp, Ctr Hlth Qual Outcomes & Econ, Bedford, MA 01730 USA. RP Pekoz, EA (reprint author), Boston Univ, Sch Management, 595 Commonwealth Ave, Boston, MA 02215 USA. EM pekoz@bu.edu OI Christiansen, Cindy/0000-0001-9951-480X FU Department of Veterans Affairs Health Services Research and Development Service [IIR 06-260] FX This research was supported in part by a grant from the Department of Veterans Affairs Health Services Research and Development Service, IIR 06-260. The authors thank the referees for many detailed suggestions that have improved the presentation of this article. NR 18 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 20 PY 2010 VL 29 IS 21 BP 2180 EP 2193 DI 10.1002/sim.3979 PG 14 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 646AC UT WOS:000281506300002 PM 20564302 ER PT J AU Wylie, BJ Hashmi, AH Singh, N Singh, MP Tuchman, J Hussain, M Sabin, L Yeboah-Antwi, K Banerjee, C Brooks, MI Desai, M Udhayakumar, V MacLeod, WB Dash, AP Hamer, DH AF Wylie, Blair J. Hashmi, Ahmar H. Singh, Neeru Singh, Mrigendra P. Tuchman, Jordan Hussain, Mobassir Sabin, Lora Yeboah-Antwi, Kojo Banerjee, Camellia Brooks, Mohamad I. Desai, Meghna Udhayakumar, Venkatachalam MacLeod, William B. Dash, Aditya P. Hamer, Davidson H. TI Availability and utilization of malaria prevention strategies in pregnancy in eastern India SO BMC PUBLIC HEALTH LA English DT Article ID CHLOROQUINE CHEMOPROPHYLAXIS; BURDEN; EPIDEMIOLOGY; TRANSMISSION; EFFICACY; DISTRICT; FAILURE; AREA AB Background: Malaria in pregnancy in India, as elsewhere, is responsible for maternal anemia and adverse pregnancy outcomes such as low birth weight and preterm birth. It is not known whether prevention and treatment strategies for malaria in pregnancy (case management, insecticide-treated bednets, intermittent preventive therapy) are widely utilized in India. Methods: This cross-sectional study was conducted during 2006-2008 in two states of India, Jharkhand and Chhattisgarh, at 7 facilities representing a range of rural and urban populations and areas of more versus less stable malaria transmission. 280 antenatal visits (40/site) were observed by study personnel coupled with exit interviews of pregnant women to assess emphasis upon, availability and utilization of malaria prevention practices by health workers and pregnant women. The facilities were assessed for the availability of antimalarials, lab supplies and bednets. Results: All participating facilities were equipped to perform malaria blood smears; none used rapid diagnostic tests. Chloroquine, endorsed for chemoprophylaxis during pregnancy by the government at the time of the study, was stocked regularly at all facilities although the quantity stocked varied. Availability of alternative antimalarials for use in pregnancy was less consistent. In Jharkhand, no health worker recommended bednet use during the antenatal visit yet over 90% of pregnant women had bednets in their household. In Chhattisgarh, bednets were available at all facilities but only 14.4% of health workers recommended their use. 40% of the pregnant women interviewed had bednets in their household. Only 1.4% of all households owned an insecticide-treated bednet; yet 40% of all women reported their households had been sprayed with insecticide. Antimalarial chemoprophylaxis with chloroquine was prescribed in only 2 (0.7%) and intermittent preventive therapy prescribed in only one (0.4%) of the 280 observed visits. Conclusions: A disconnect remains between routine antenatal practices in India and known strategies to prevent and treat malaria in pregnancy. Prevention strategies, in particular the use of insecticide-treated bednets, are underutilized. Gaps highlighted by this study combined with recent estimates of the prevalence of malaria during pregnancy in these areas should be used to revise governmental policy and target increased educational efforts among health care workers and pregnant women. C1 [Wylie, Blair J.; Hashmi, Ahmar H.; Tuchman, Jordan; Sabin, Lora; Yeboah-Antwi, Kojo; Banerjee, Camellia; Brooks, Mohamad I.; MacLeod, William B.; Hamer, Davidson H.] Boston Univ, Sch Publ Hlth, Ctr Global Hlth & Dev, Boston, MA 02215 USA. [Wylie, Blair J.; Sabin, Lora; Yeboah-Antwi, Kojo; MacLeod, William B.; Hamer, Davidson H.] Boston Univ, Sch Publ Hlth, Dept Int Hlth, Boston, MA USA. [Wylie, Blair J.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA. [Singh, Neeru; Singh, Mrigendra P.; Hussain, Mobassir] Natl Inst Malaria Res Field Stn, Jabalpur, India. [Singh, Neeru] Indian Council Med Res, Reg Med Res Ctr Tribals, Jabalpur, India. [Tuchman, Jordan] Ctr Leadership & Management, Cambridge, MA USA. [Desai, Meghna; Udhayakumar, Venkatachalam] Ctr Dis Control & Prevent, Malaria Branch, Div Parasit Dis, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA USA. [Dash, Aditya P.] Natl Inst Malaria Res, Delhi, India. [Hamer, Davidson H.] Boston Univ, Sch Med, Dept Med, Infect Dis Sect, Boston, MA 02118 USA. RP Wylie, BJ (reprint author), Boston Univ, Sch Publ Hlth, Ctr Global Hlth & Dev, Boston, MA 02215 USA. EM bwylie@partners.org OI MacLeod, William/0000-0001-8003-8874; Hamer, Davidson/0000-0002-4700-1495 FU USAID [GHS-A-00-03-00020-00]; National Institute of Allergy and Infectious Disease [R03 HD52167-01]; Indian National Institute of Malaria Research FX We would like to thank Dr. MK Das, the study nurses, and Amrit Alok for their efforts on behalf of the study. We would like to acknowledge the kind administrative and logistical support of the Chief Medical Officers at each of the participating facilities, the Jharkhand and Chhattisgarh State health officials, and the Indian Council for Medical Research. We acknowledge the contributions made by Chris Gill, a former colleague at the Center for Global Health and Development, in study design and rationale. Financial support For the work in Jharkhand state, the United States Agency for International Development (USAID)/India mission provided funding for this study to the Child and Family Applied Research project at Boston University, Boston, by means of the USAID cooperative agreement (GHS-A-00-03-00020-00).; For the work in Chhattisgarh state, funding was provided by the National Institute of Allergy and Infectious Disease through an R03 grant (R03 HD52167-01) and in collaboration with the Indian National Institute of Malaria Research through the Indo-US Program for Contraception and Reproductive Health Research (CRHR). The opinions expressed herein are those of the authors and do not necessarily reflect the views of the study sponsors. NR 29 TC 5 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD SEP 17 PY 2010 VL 10 AR 557 DI 10.1186/1471-2458-10-557 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 663MC UT WOS:000282891000002 PM 20849590 ER PT J AU Duce, JA Tsatsanis, A Cater, MA James, SA Robb, E Wikhe, K Leong, SL Perez, K Johanssen, T Greenough, MA Cho, HH Galatis, D Moir, RD Masters, CL McLean, C Tanzi, RE Cappai, R Barnham, KJ Ciccotosto, GD Rogers, JT Bush, AI AF Duce, James A. Tsatsanis, Andrew Cater, Michael A. James, Simon A. Robb, Elysia Wikhe, Krutika Leong, Su Ling Perez, Keyla Johanssen, Timothy Greenough, Mark A. Cho, Hyun-Hee Galatis, Denise Moir, Robert D. Masters, Colin L. McLean, Catriona Tanzi, Rudolph E. Cappai, Roberto Barnham, Kevin J. Ciccotosto, Giuseppe D. Rogers, Jack T. Bush, Ashley I. TI Iron-Export Ferroxidase Activity of beta-Amyloid Precursor Protein Is Inhibited by Zinc in Alzheimer's Disease SO CELL LA English DT Article ID ISOFORM MESSENGER-RNAS; CENTRAL-NERVOUS-SYSTEM; TARGETING A-BETA; TRANSGENIC MICE; SENILE PLAQUE; METAL-BINDING; BRAIN IRON; CERULOPLASMIN; EXPRESSION; ACCUMULATION AB Alzheimer's Disease (AD) is complicated by pro-oxidant intraneuronal Fe(2+) elevation as well as extracellular Zn(2+) accumulation within amyloid plaque. We found that the AD beta-amyloid protein precursor (APP) possesses ferroxidase activity mediated by a conserved H-ferritin-like active site, which is inhibited specifically by Zn(2+). Like ceruloplasmin, APP catalytically oxidizes Fe(2+), loads Fe(3+) into transferrin, and has a major interaction with ferroportin in HEK293T cells (that lack ceruloplasmin) and in human cortical tissue. Ablation of APP in HEK293T cells and primary neurons induces marked iron retention, whereas increasing APP695 promotes iron export. Unlike normal mice, APP(-/-) mice are vulnerable to dietary iron exposure, which causes Fe(2+) accumulation and oxidative stress in cortical neurons. Paralleling iron accumulation, APP ferroxidase activity in AD postmortem neocortex is inhibited by endogenous Zn(2+), which we demonstrate can originate from Zn(2+)-laden amyloid aggregates and correlates with A beta burden. Abnormal exchange of cortical zinc may link amyloid pathology with neuronal iron accumulation in AD. C1 [Leong, Su Ling; Perez, Keyla; Johanssen, Timothy; Cappai, Roberto; Barnham, Kevin J.; Ciccotosto, Giuseppe D.; Rogers, Jack T.] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic 3010, Australia. [Greenough, Mark A.] Univ Melbourne, Dept Genet, Melbourne, Vic 3010, Australia. [Leong, Su Ling; Perez, Keyla; Galatis, Denise; Cappai, Roberto; Barnham, Kevin J.; Ciccotosto, Giuseppe D.; Bush, Ashley I.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Duce, James A.; Tsatsanis, Andrew; Cater, Michael A.; James, Simon A.; Robb, Elysia; Wikhe, Krutika; Perez, Keyla; Greenough, Mark A.; Masters, Colin L.; Barnham, Kevin J.; Ciccotosto, Giuseppe D.; Bush, Ashley I.] Univ Melbourne, Mental Hlth Res Inst, Parkville, Vic 3052, Australia. [Cho, Hyun-Hee; Rogers, Jack T.] Harvard Univ, Sch Med, Dept Psychiat, Neurochem Lab, Boston, MA 02129 USA. [Moir, Robert D.; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Genet & Aging Res Unit, Boston, MA 02129 USA. [McLean, Catriona] Alfred Hosp, Dept Anat Pathol, Melbourne, Vic 3004, Australia. RP Rogers, JT (reprint author), Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic 3010, Australia. EM jrogers@partners.org; abush@mhri.edu.au RI Bush, Ashley/A-1186-2007; James, Simon/J-5320-2012; Johanssen, Tim/G-6106-2014 OI Bush, Ashley/0000-0001-8259-9069; James, Simon/0000-0001-9369-3288; Johanssen, Tim/0000-0001-6757-586X FU National Institute on Aging [1RO1AG12686]; Australian Research Council; Australian National Health & Medical Research Council (NHMRC) FX This work was supported by funds from the National Institute on Aging (1RO1AG12686), the Australian Research Council, the Australian National Health & Medical Research Council (NHMRC), Operational Infrastructure Support Victorian State Government, and the Alzheimer's Association. The Victorian Brain Bank Network is supported by The University of Melbourne, The Mental Health Research Institute, The Alfred Hospital, and the Victorian Forensic Institute of Medicine and funded by Neurosciences Australia and the NHMRC. We thank Gerd Multhaup for helpful comments and for providing APP reagents for pilot studies, Paul Adlard for human tissue samples, and Wilma Wasco for the APLP2 construct. C. L. M., R. E. T., K.J.B., and A. I. B. are shareholders, paid consultants, and advisory board members of Prana Biotechnology Ltd. A.I.B. is a shareholder of Cogstate Ltd and Eucalyptus Biosciences Pty Ltd. M. A. C. is a shareholder in Prana Biotechnology Ltd. NR 64 TC 262 Z9 267 U1 10 U2 54 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 17 PY 2010 VL 142 IS 6 BP 857 EP 867 DI 10.1016/j.cell.2010.08.014 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 650NA UT WOS:000281855000009 PM 20817278 ER PT J AU Mao, ZH Sun, W Xu, RJ Novgorodov, S Szulc, ZM Bielawski, J Obeid, LM Mao, CG AF Mao, Zhehao Sun, Wei Xu, Ruijuan Novgorodov, Sergei Szulc, Zdzislaw M. Bielawski, Jacek Obeid, Lina M. Mao, Cungui TI Alkaline Ceramidase 2 (ACER2) and Its Product Dihydrosphingosine Mediate the Cytotoxicity of N-(4-Hydroxyphenyl)retinamide in Tumor Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FENRETINIDE-INDUCED APOPTOSIS; HUMAN NEUROBLASTOMA-CELLS; LONG-CHAIN CERAMIDES; COLON-CANCER CELLS; DIHYDROCERAMIDE DESATURASE; PROSTATE-CANCER; INDUCTION; SPHINGOSINE; CARCINOMA AB Increased generation of dihydrosphingosine (DHS), a bioactive sphingolipid, has been implicated in the cytotoxicity of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) in tumor cells. However, how 4-HPR increases DHS remains unclear. Here we demonstrate that 4-HPR increases the expression of ACER2, which catalyzes the hydrolysis of dihydroceramides to generate DHS, and that ACER2 up-regulation plays a key role in mediating the 4-HPR-induced generation of DHS as well as the cytotoxicity of 4-HPR in tumor cells. Treatment with 4-HPR induced the accumulation of dihydroceramides (DHCs) in tumor cells by inhibiting dihydroceramide desaturase (DES) activity, which catalyzes the conversion of DHCs to ceramides. Treatment with 4-HPR also increased ACER2 expression through a retinoic acid receptor-independent and caspase-dependent manner. Overexpression of ACER2 augmented the 4-HPR-induced generation of DHS as well as 4-HPR cytotoxicity, and 4-HPR-induced death in tumor cells, whereas knocking down ACER2 had the opposite effects. ACER2 overexpression, along with treatment with GT11, another DES inhibitor, markedly increased cellular DHS, leading to tumor cell death, whereas ACER2 overexpression or GT11 treatment alone failed to do so, suggesting that both ACER2 up-regulation and DES inhibition are necessary and sufficient to mediate 4-HPR-induced DHS accumulation, cytotoxicity, and death in tumor cells. Taken together, these results suggest that up-regulation of the ACER2/DHS pathway mediates the cytotoxicity of 4-HPR in tumor cells and that up-regulating or activating ACER2 may improve the anti-cancer activity of 4-HRR and other DHC-inducing agents. C1 [Obeid, Lina M.] Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. [Szulc, Zdzislaw M.; Bielawski, Jacek; Obeid, Lina M.; Mao, Cungui] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, Lina M.; Mao, Cungui] Ralph H Johnson Vet Adm Hosp, Charleston, SC 29425 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. EM maoc@musc.edu FU National Institutes of Health [R01CA104834, P20RR017677]; Veterans Affairs FX This work was supported, in whole or in part, by National Institutes of Health Grants R01CA104834 (to C. M.) and P20RR017677 (to L. M. O.). This work was also supported by a Veterans Affairs merit award (to L. M. O.). NR 48 TC 23 Z9 24 U1 0 U2 4 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 17 PY 2010 VL 285 IS 38 BP 29078 EP 29090 DI 10.1074/jbc.M110.105296 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649BC UT WOS:000281740100009 PM 20628055 ER PT J AU Riemer, AB Keskin, DB Zhang, GL Handley, M Anderson, KS Brusic, V Reinhold, B Reinherz, EL AF Riemer, Angelika B. Keskin, Derin B. Zhang, Guanglan Handley, Maris Anderson, Karen S. Brusic, Vladimir Reinhold, Bruce Reinherz, Ellis L. TI A Conserved E7-derived Cytotoxic T Lymphocyte Epitope Expressed on Human Papillomavirus 16-transformed HLA-A2(+) Epithelial Cancers SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HLA CLASS-I; CERVICAL INTRAEPITHELIAL NEOPLASIA; MAJOR HISTOCOMPATIBILITY COMPLEX; TYPE-16 E6; HIGH-GRADE; IMMUNE-RESPONSES; CTL EPITOPES; E5 PROTEIN; ANTIGEN PRESENTATION; BINDING PREDICTION AB Human Papillomavirus 16 (HPV-16) has been identified as the causative agent of 50% of cervical cancers and many other HPV-associated tumors. The transforming potential/tumor maintenance capacity of this high risk HPV is mediated by two viral oncoproteins, E6 and E7, making them attractive targets for therapeutic vaccines. Of 21 E6 and E7 peptides computed to bind HLA-A*0201, 10 were confirmed through TAP-deficient T2 cell HLA stabilization assay. Those scoring positive were investigated to ascertain which were naturally processed and presented by surface HLA molecules for CTL recognition. Because IFN gamma ELISpot frequencies from healthy HPV-exposed blood donors against HLA-A*0201-binding peptides were unable to identify specificities for tumor targeting, their physical presence among peptides eluted from HPV-16-transformed epithelial tumor HLA-A*0201 immunoprecipitates was analyzed by MS3 Poisson detection mass spectrometry. Only one epitope (E7(11-19)) highly conserved among HPV-16 strains was detected. This 9-mer serves to direct cytolysis by T cell lines, whereas a related 10-mer (E7(11-20)), previously used as a vaccine candidate, was neither detected by MS3 on HPV-transformed tumor cells nor effectively recognized by 9-mer specific CTL. These data underscore the importance of precisely defining CTL epitopes on tumor cells and offer a paradigm for T cell-based vaccine design. C1 [Riemer, Angelika B.; Keskin, Derin B.; Handley, Maris; Reinhold, Bruce; Reinherz, Ellis L.] Harvard Univ, Sch Med, Immunobiol Lab, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. [Riemer, Angelika B.; Zhang, Guanglan; Handley, Maris; Anderson, Karen S.; Brusic, Vladimir; Reinhold, Bruce; Reinherz, Ellis L.] Harvard Univ, Sch Med, Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Immunobiol Lab, Dana Farber Canc Inst,Dept Med Oncol, HIM 419,4 Blackfan Circle, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU Erwin Schrodinger Fellowship FX Supported by an Erwin Schrodinger Fellowship of the Austrian Science Fund. Present address: Dept. of Dermatology, Medical University of Vienna, 1090 Vienna, Austria. NR 94 TC 24 Z9 24 U1 1 U2 6 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 17 PY 2010 VL 285 IS 38 BP 29608 EP 29622 DI 10.1074/jbc.M110.126722 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649BC UT WOS:000281740100062 PM 20615877 ER PT J AU Urgaonkar, S Cortese, JF Barker, RH Cromwell, M Serrano, AE Wirth, DF Clardy, J Mazitschek, R AF Urgaonkar, Sameer Cortese, Joseph F. Barker, Robert H. Cromwell, Mandy Serrano, Adelfa E. Wirth, Dyann F. Clardy, Jon Mazitschek, Ralph TI A Concise Silylamine Approach to 2-Amino-3-hydroxy-indoles with Potent in vivo Antimalaria Activity SO ORGANIC LETTERS LA English DT Article ID PLASMODIUM-FALCIPARUM; 2-AMINOINDOLES; ISATINS; AMIDES; ACIDS AB The development of a concise strategy to access 2-amino-3-hydroxy-indoles, which are disclosed as novel antimalarials with potent in vivo activity, is reported. Starting from isatins the target compounds are synthesized in 2 steps and in good yields via oxoindole intermediates by employing tert-butyldimethylsilyl amine (TBDMSNH(2)) as previously unexplored ammonia equivalent. C1 [Urgaonkar, Sameer; Cortese, Joseph F.; Wirth, Dyann F.; Clardy, Jon; Mazitschek, Ralph] Broad Inst Harvard & MIT, Infect Dis Initiat Program, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Barker, Robert H.; Cromwell, Mandy] Genzyme Corp, Drug Discovery & Dev, Waltham, MA 02451 USA. [Serrano, Adelfa E.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Wirth, Dyann F.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Mazitschek, R (reprint author), Broad Inst Harvard & MIT, Infect Dis Initiat Program, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM ralph@broad.harvard.edu RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X FU Medicines for Malaria Venture (MMV); Broad Institute (SPARC) FX We are grateful to Roger Wiegand (Broad Institute), Ted Sybertz (Genzyme Corporation), Ian Bathurst (MMV), and all members of the Broad Institute-Genzyme-MMV Malaria Drug Development Initiative for thoughtful discussions; Stuart Schreiber (Broad Institute) and the Broad Chemical Biology Program for access to key instrumentation and reagents; Erin Tyndall and Justin Dick for assistance with the P. falciparum viability assay; Chris Johnson, Galina Beletsky, Kachicholu Agu and Stephen Jonston (all Broad Institute) for analytical support; Miryam Garcia Rosa (UPR) for assistance with the animal efficacy studies; Peter Muller for generating the X-ray crystallography data and Li Li for acquisition of HRMS data (both MIT Chemistry Department). This work was supported by grants from Medicines for Malaria Venture (MMV) and The Broad Institute (SPARC). NR 22 TC 17 Z9 17 U1 2 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD SEP 17 PY 2010 VL 12 IS 18 BP 3998 EP 4001 DI 10.1021/ol101566h PG 4 WC Chemistry, Organic SC Chemistry GA 647DP UT WOS:000281596800010 PM 20718474 ER PT J AU Heiden, MGV Locasale, JW Swanson, KD Sharfi, H Heffron, GJ Amador-Noguez, D Christofk, HR Wagner, G Rabinowitz, JD Asara, JM Cantley, LC AF Heiden, Matthew G. Vander Locasale, Jason W. Swanson, Kenneth D. Sharfi, Hadar Heffron, Greg J. Amador-Noguez, Daniel Christofk, Heather R. Wagner, Gerhard Rabinowitz, Joshua D. Asara, John M. Cantley, Lewis C. TI Evidence for an Alternative Glycolytic Pathway in Rapidly Proliferating Cells SO SCIENCE LA English DT Article ID PYRUVATE-KINASE M2; TUMOR-GROWTH; HISTIDINE PHOSPHORYLATION; PHOSPHOTRANSFERASE SYSTEM; RABBIT MUSCLE; PROTEIN; METABOLISM; DEPHOSPHORYLATION; IDENTIFICATION; PEPTIDES AB Proliferating cells, including cancer cells, require altered metabolism to efficiently incorporate nutrients such as glucose into biomass. The M2 isoform of pyruvate kinase (PKM2) promotes the metabolism of glucose by aerobic glycolysis and contributes to anabolic metabolism. Paradoxically, decreased pyruvate kinase enzyme activity accompanies the expression of PKM2 in rapidly dividing cancer cells and tissues. We demonstrate that phosphoenolpyruvate (PEP), the substrate for pyruvate kinase in cells, can act as a phosphate donor in mammalian cells because PEP participates in the phosphorylation of the glycolytic enzyme phosphoglycerate mutase (PGAM1) in PKM2-expressing cells. We used mass spectrometry to show that the phosphate from PEP is transferred to the catalytic histidine (His11) on human PGAM1. This reaction occurred at physiological concentrations of PEP and produced pyruvate in the absence of PKM2 activity. The presence of histidine-phosphorylated PGAM1 correlated with the expression of PKM2 in cancer cell lines and tumor tissues. Thus, decreased pyruvate kinase activity in PKM2-expressing cells allows PEP-dependent histidine phosphorylation of PGAM1 and may provide an alternate glycolytic pathway that decouples adenosine triphosphate production from PEP-mediated phosphotransfer, allowing for the high rate of glycolysis to support the anabolic metabolism observed in many proliferating cells. C1 [Heiden, Matthew G. Vander; Locasale, Jason W.; Swanson, Kenneth D.; Sharfi, Hadar; Christofk, Heather R.; Asara, John M.; Cantley, Lewis C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. [Heiden, Matthew G. Vander; Locasale, Jason W.; Swanson, Kenneth D.; Sharfi, Hadar; Christofk, Heather R.; Asara, John M.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Heiden, Matthew G. Vander] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Heiden, Matthew G. Vander; Locasale, Jason W.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Heffron, Greg J.; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Amador-Noguez, Daniel; Rabinowitz, Joshua D.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA. [Amador-Noguez, Daniel; Rabinowitz, Joshua D.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA. RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Locasale, Jason/0000-0002-7766-3502 FU Damon Runyon Cancer Research Foundation; Burroughs Wellcome Fund; American Cancer Society; Dana-Farber/Harvard Cancer Center; NIH [1K08CA136983, 5P30CA006516-43, 5 T32 CA009361-28, R21/R33 DK070299, P01GM047467, R01 AI078063, R21 CA128620, R01-GM56302, P01CA089021, 1P01CA120964-01A] FX We thank A. Carrecedo and P. P. Pandolfi for normal and neoplastic prostate tissue; L. Burga and G. Wulf for normal breast and breast tumor; G. Bellinger for assistance with mouse dissection; M. Sasaki for help generating constructs; V. Vyas, A. Subtelny, L. Freimark, X. Yang, L. Schmidt, and M. Balastik for technical assistance; M. Bayro and S. Hyberts for help with processing the NMR spectra; and A. Shaywitz, J. Hutti, C. Benes, D. Anastasiou, A. Couvillion, and A. Saci for helpful discussions. This work was partially supported by the Damon Runyon Cancer Research Foundation (M. V. H.), the Burroughs Wellcome Fund (M. V. H.), the American Cancer Society (J. W. L.), Dana-Farber/Harvard Cancer Center (J. M. A. and J. W. L.), and by grants from the NIH (1K08CA136983 to M. V. H., 5P30CA006516-43 to J. M. A., 5 T32 CA009361-28 to J. W. L., R21/R33 DK070299 and P01GM047467 to G. W., R01 AI078063 and R21 CA128620 to J. D. R., R01-GM56302 and P01CA089021 to L. C. C., and 1P01CA120964-01A to J. M. A. and L.C.C.). NR 35 TC 19 Z9 19 U1 5 U2 29 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 SEP 17 PY 2010 VL 329 IS 5998 BP 1492 EP 1499 DI 10.1126/science.1188015 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 650RK UT WOS:000281869000033 ER PT J AU Gupta, V Tallman, MS He, WS Logan, BR Copelan, E Gale, RP Khoury, HJ Klumpp, T Koreth, J Lazarus, HM Marks, DI Martino, R Rizzieri, DA Rowe, JM Sabloff, M Waller, EK DiPersio, JF Bunjes, DW Weisdorf, DJ AF Gupta, Vikas Tallman, Martin S. He, Wensheng Logan, Brent R. Copelan, Edward Gale, Robert Peter Khoury, Hanna J. Klumpp, Thomas Koreth, John Lazarus, Hillard M. Marks, David I. Martino, Rodrigo Rizzieri, David A. Rowe, Jacob M. Sabloff, Mitchell Waller, Edmund K. DiPersio, John F. Bunjes, Donald W. Weisdorf, Daniel J. TI Comparable survival after HLA-well-matched unrelated or matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; IDENTICAL SIBLINGS; CLASS-I; RISK; METAANALYSIS; ADULTS; MANAGEMENT AB We compared the outcomes of unrelated donor (URD, n = 358) with human leukocyte antigen (HLA)-matched sibling donor (MSD, n = 226) transplantations in patients with acute myeloid leukemia (AML) in first complete remission (CR1) having unfavorable cytogenetics at diagnosis. Unfavorable cytogenetic abnormalities were: complex (>= 3 abnormalities), 32%; and noncomplex involving chromosome 7, 25%; chromosome 5, 9%; 11q or MLL rearrangements, 18%; t(6; 9), 5%; and other noncomplex, 10%. URDs were HLA-well-matched (n = 254; 71%) or partially-matched (n = 104; 29%). Three-year leukemia-free survival (LFS) for MSD was 42% (95% confidence interval [CI], 35%-48%) compared with 34% (95% CI, 28%-41%) for HLA-well-matched URD and 29%(95% CI, 20%-39%) for partially-matched URD (P=.08). In multivariate analysis, HLA-well-matched URD and MSD yielded similar LFS (relative risk [RR] = 1.1, 95% CI, 0.86-1.40, P=.44) and overall survival (OS; RR = 1.06, 95% CI, 0.83-1.37, P=.63). LFS and OS were significantly inferior for HLA-partially-matched URD recipients, those with prior myelodysplastic syndrome, and those older than 50 years. All cytogenetic cohorts had similar outcomes. Patients with chronic graft-versus-host disease had a significantly lower risk of relapse (RR = 0.68, 95% CI, 0.47-0.99, P=.05). Hematopoietic cell transplantation (HCT) using HLA-well-matched URD and MSD resulted in similar LFS and OS in AML patients in CR1 with unfavorable cytogenetics. Outcomes of HCT from HLA-partially-matched URD were inferior. (Blood. 2010; 116(11): 1839-1848) C1 [Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Bunjes, Donald W.] Univ Ulm Klinikum, Ulm, Germany. [DiPersio, John F.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Sabloff, Mitchell] Ottawa Hosp Blood & Marrow Transplant Program, Ottawa, ON, Canada. [Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel. [Rizzieri, David A.] Duke Univ, Med Ctr, Durham, NC USA. [Martino, Rodrigo] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Koreth, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Klumpp, Thomas] Fox Chase Temple BMT Program, Philadelphia, PA USA. [Khoury, Hanna J.; Waller, Edmund K.] Emory Univ Hosp, Atlanta, GA 30322 USA. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Copelan, Edward] Cleveland Clin Fdn, Cleveland, OH USA. [He, Wensheng; Logan, Brent R.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Tallman, Martin S.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY USA. [Gupta, Vikas] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. RP Weisdorf, DJ (reprint author), Univ Minnesota, Med Ctr, 420 Delaware St SE,MMC 480, Minneapolis, MN 55455 USA. EM weisd001@umn.edu FU National Cancer Institute [U24-CA76518]; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute and National Cancer Institute [5U01HL069294]; Health Resources and Services Administration (DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen Inc FX The CIBMTR is supported by the National Cancer Institute (Public Health Service Grant/Cooperative Agreement U24-CA76518), the National Institute of Allergy and Infectious Diseases, the National Heart, Lung, and Blood Institute and National Cancer Institute (Grant/Cooperative Agreement 5U01HL069294), the Health Resources and Services Administration (DHHS contract HHSH234200637015C), the Office of Naval Research (grants N00014-06-1-0704 and N00014-08-1-0058), and grants from the following: AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen Inc; anonymous donation to the Medical College of Wisconsin; Astellas Pharma US Inc; Baxter International Inc; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical Inc; Bio-vitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; Canadian Blood and Marrow Transplant Group; Caridian-BCT; Celgene Corporation; CellGenix GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc; CytoTherm; DOR BioPharma Inc; Dynal Biotech, an Invitrogen Company; Eisai Inc; Enzon Pharmaceuticals Inc; European Group for Blood and Marrow Transplantation; Gamida Cell Ltd; GE Healthcare; Genentech Inc; Genzyme Corporation; Histogenetics Inc; HKS Medical Information Systems; Hospira Inc; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co Ltd; Leukemia & Lymphoma Society; Merck & Company; Medical College of Wisconsin; MGI Pharma Inc; Michigan Community Blood Centers; Millennium Pharmaceuticals Inc; Miller Pharmacal Group; Milliman USA Inc; Miltenyi Biotec Inc; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics Inc; Otsuka America Pharmaceutical Inc; Pall Life Sciences; Pfizer Inc; Saladax Biomedical Inc; Schering Corporation; Society for Healthcare Epidemiology of America; Soligenix Inc; StemCyte Inc; StemSoft Software Inc; Sysmex America Inc; THERAKOS Inc; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals Inc; ViraCor Laboratories; ViroPharma Inc; and Wellpoint Inc. NR 34 TC 76 Z9 80 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 16 PY 2010 VL 116 IS 11 BP 1839 EP 1848 DI 10.1182/blood-2010-04-278317 PG 10 WC Hematology SC Hematology GA 654ET UT WOS:000282152000008 PM 20538804 ER PT J AU Badalian-Very, G Vergilio, JA Degar, BA MacConaill, LE Brandner, B Calicchio, ML Kuo, FC Ligon, AH Stevenson, KE Kehoe, SM Garraway, LA Hahn, WC Meyerson, M Fleming, MD Rollins, BJ AF Badalian-Very, Gayane Vergilio, Jo-Anne Degar, Barbara A. MacConaill, Laura E. Brandner, Barbara Calicchio, Monica L. Kuo, Frank C. Ligon, Azra H. Stevenson, Kristen E. Kehoe, Sarah M. Garraway, Levi A. Hahn, William C. Meyerson, Matthew Fleming, Mark D. Rollins, Barrett J. TI Recurrent BRAF mutations in Langerhans cell histiocytosis SO BLOOD LA English DT Article ID HUMAN CANCER; GENE; PATHWAY; ASTROCYTOMAS; SUPPRESSION; FUSION; NEVI AB Langerhans cell histiocytosis (LCH) has a broad spectrum of clinical behaviors; some cases are self-limited, whereas others involve multiple organs and cause significant mortality. Although Langerhans cells in LCH are clonal, their benign morphology and their lack (to date) of reported recurrent genomic abnormalities have suggested that LCH may not be a neoplasm. Here, using 2 orthogonal technologies for detecting cancer-associated mutations in formalin-fixed, paraffin-embedded material, we identified the oncogenic BRAF V600E mutation in 35 of 61 archived specimens (57%). TP53 and MET mutations were also observed in one sample each. BRAF V600E tended to appear in younger patients but was not associated with disease site or stage. Langerhans cells stained for phosphomitogen-activated protein kinase kinase (phospho-MEK) and phospho-extracellular signal-regulated kinase (phospho-ERK) regardless of mutation status. High prevalence, recurrent BRAF mutations in LCH indicate that it is a neoplastic disease that may respond to RAF pathway inhibitors. (Blood. 2010; 116(11): 1919-1923) C1 [Badalian-Very, Gayane; Brandner, Barbara; Garraway, Levi A.; Hahn, William C.; Meyerson, Matthew; Rollins, Barrett J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Badalian-Very, Gayane; Brandner, Barbara; Garraway, Levi A.; Hahn, William C.; Meyerson, Matthew; Rollins, Barrett J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Badalian-Very, Gayane; Brandner, Barbara; Garraway, Levi A.; Hahn, William C.; Rollins, Barrett J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Vergilio, Jo-Anne; Calicchio, Monica L.; Fleming, Mark D.] Childrens Hosp Boston, Dept Pathol, Boston, MA USA. [Vergilio, Jo-Anne; Kuo, Frank C.; Ligon, Azra H.; Fleming, Mark D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Degar, Barbara A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Degar, Barbara A.] Childrens Hosp Boston, Dept Med, Boston, MA USA. [Degar, Barbara A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [MacConaill, Laura E.; Kehoe, Sarah M.; Garraway, Levi A.; Hahn, William C.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Kuo, Frank C.; Ligon, Azra H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ligon, Azra H.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Stevenson, Kristen E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Garraway, Levi A.; Hahn, William C.; Meyerson, Matthew] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA 02139 USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM barrett_rollins@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU Histiocytosis Association of America; Team Ippolittle/Deloitte of the Boston Marathon Jimmy Fund Walk; Mufson family; US Public Health Service [AI050225]; National Cancer Institute Cancer [P30 CA06516] FX This work was supported in part by the Histiocytosis Association of America, Team Ippolittle/Deloitte of the Boston Marathon Jimmy Fund Walk, the Mufson family, and a US Public Health Service grant (AI050225). The Pathology Specimen Locator Core is supported by a National Cancer Institute Cancer Center Support Grant (P30 CA06516) to the Dana-Farber/Harvard Cancer Center. NR 20 TC 282 Z9 290 U1 1 U2 8 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 16 PY 2010 VL 116 IS 11 BP 1919 EP 1923 DI 10.1182/blood-2010-04-279083 PG 5 WC Hematology SC Hematology GA 654ET UT WOS:000282152000017 PM 20519626 ER PT J AU Tsai, AG Yoda, A Weinstock, DM Lieber, MR AF Tsai, Albert G. Yoda, Akinori Weinstock, David M. Lieber, Michael R. TI t(X;14)(p22;q32)/t(Y;14)(p11;q32) CRLF2-IGH translocations from human B-lineage ALLs involve CpG-type breaks at CRLF2, but CRLF2/P2RY8 intrachromosomal deletions do not SO BLOOD LA English DT Letter ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EXPRESSION C1 [Yoda, Akinori; Weinstock, David M.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Tsai, Albert G.; Lieber, Michael R.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Tsai, Albert G.; Lieber, Michael R.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Tsai, Albert G.; Lieber, Michael R.] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. [Tsai, Albert G.; Lieber, Michael R.] Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA. [Tsai, Albert G.; Lieber, Michael R.] Univ So Calif, Keck Sch Med, Dept Biol Sci, Sect Mol & Computat Biol, Los Angeles, CA 90033 USA. RP Weinstock, DM (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St,Dana 510B, Boston, MA 02115 USA. EM dweinstock@partners.org FU NCI NIH HHS [R01 CA100504, R37 CA051105, R01 CA151898] NR 7 TC 9 Z9 9 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 16 PY 2010 VL 116 IS 11 BP 1993 EP 1994 PG 2 WC Hematology SC Hematology GA 654ET UT WOS:000282152000028 PM 20847213 ER PT J AU Kim, K Doi, A Wen, B Ng, K Zhao, R Cahan, P Kim, J Aryee, MJ Ji, H Ehrlich, LIR Yabuuchi, A Takeuchi, A Cunniff, KC Hongguang, H Mckinney-Freeman, S Naveiras, O Yoon, TJ Irizarry, RA Jung, N Seita, J Hanna, J Murakami, P Jaenisch, R Weissleder, R Orkin, SH Weissman, IL Feinberg, AP Daley, GQ AF Kim, K. Doi, A. Wen, B. Ng, K. Zhao, R. Cahan, P. Kim, J. Aryee, M. J. Ji, H. Ehrlich, L. I. R. Yabuuchi, A. Takeuchi, A. Cunniff, K. C. Hongguang, H. Mckinney-Freeman, S. Naveiras, O. Yoon, T. J. Irizarry, R. A. Jung, N. Seita, J. Hanna, J. Murakami, P. Jaenisch, R. Weissleder, R. Orkin, S. H. Weissman, I. L. Feinberg, A. P. Daley, G. Q. TI Epigenetic memory in induced pluripotent stem cells SO NATURE LA English DT Article ID CPG ISLAND SHORES; DNA METHYLATION; REPROGRAMMING FACTORS; MAMMALIAN-CELLS; IPS CELLS; DIFFERENTIATION; TISSUE; GENERATION; MICE; COMPLEMENTATION AB Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer more readily establishes the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment. C1 [Doi, A.; Wen, B.; Ji, H.; Irizarry, R. A.; Jung, N.; Murakami, P.; Feinberg, A. P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. [Doi, A.; Wen, B.; Ji, H.; Irizarry, R. A.; Jung, N.; Murakami, P.; Feinberg, A. P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Kim, K.; Ng, K.; Zhao, R.; Cahan, P.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K. C.; Hongguang, H.; Mckinney-Freeman, S.; Naveiras, O.; Daley, G. Q.] Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA. [Kim, K.; Ng, K.; Zhao, R.; Cahan, P.; Kim, J.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K. C.; Hongguang, H.; Mckinney-Freeman, S.; Naveiras, O.; Orkin, S. H.; Daley, G. Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, K.; Ng, K.; Zhao, R.; Cahan, P.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K. C.; Hongguang, H.; Mckinney-Freeman, S.; Naveiras, O.; Daley, G. Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Kim, K.; Ng, K.; Zhao, R.; Cahan, P.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K. C.; Hongguang, H.; Mckinney-Freeman, S.; Naveiras, O.; Daley, G. Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Kim, K.; Ng, K.; Zhao, R.; Cahan, P.; Yabuuchi, A.; Takeuchi, A.; Cunniff, K. C.; Hongguang, H.; Mckinney-Freeman, S.; Naveiras, O.; Daley, G. Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Kim, J.; Orkin, S. H.] Childrens Hosp, Howard Hughes Med Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Aryee, M. J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Ehrlich, L. I. R.; Seita, J.; Weissman, I. L.] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Yoon, T. J.; Weissleder, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Hanna, J.; Jaenisch, R.] MIT, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Feinberg, AP (reprint author), Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. EM afeinberg@jhu.edu; george.daley@childrens.harvard.edu RI jia, xu/A-8386-2016; HANNA, JACOB/K-1339-2012; OI HANNA, JACOB/0000-0003-2042-9974; Seita, Jun/0000-0002-3008-3615; Wen, Bo/0000-0003-0394-7366; Cahan, Patrick/0000-0003-3652-2540 FU NIH [RO1-DK70055, RO1-DK59279, K99HL093212-01, R37CA054358, P50HG003233, R01AI047457, R01AI047458, CA86065, HL099999]; American Recovery and Reinvestment Act [RC2-HL102815]; LLS [3567-07]; Cooley's Anemia Foundation; Thomas and Stacey Siebel Foundation; Leukemia and Lymphoma Society; California Institute for Regenerative Medicine [T1-00001] FX G.Q.D is an investigator of the Howard Hughes Medical Institute and was supported by NIH grants RO1-DK70055 and RO1-DK59279, and special funds received under the American Recovery and Reinvestment Act (RC2-HL102815). K. K. was supported by NIH (K99HL093212-01), LLS (3567-07) and Cooley's Anemia Foundation. A.P.F was funded by NIH grants R37CA054358 and P50HG003233. I.L.W. was funded by NIH grants R01AI047457, R01AI047458, CA86065 and HL099999, and the Thomas and Stacey Siebel Foundation. L.I.R.E. was supported by a Special Fellow Career Development award from the Leukemia and Lymphoma Society. J.S. is supported by a fellowship from the California Institute for Regenerative Medicine (T1-00001). We acknowledge K. Hochedlinger for sharing his manuscript before publication. NR 54 TC 978 Z9 1013 U1 20 U2 334 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 16 PY 2010 VL 467 IS 7313 BP 285 EP U60 DI 10.1038/nature09342 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 650CF UT WOS:000281824900030 PM 20644535 ER PT J AU Perocchi, F Gohil, VM Girgis, HS Bao, XR McCombs, JE Palmer, AE Mootha, VK AF Perocchi, Fabiana Gohil, Vishal M. Girgis, Hany S. Bao, X. Robert McCombs, Janet E. Palmer, Amy E. Mootha, Vamsi K. TI MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake SO NATURE LA English DT Article ID RAT KIDNEY MITOCHONDRIA; CALCIUM-UPTAKE; YEAST MITOCHONDRIA; INNER MEMBRANE; UNIPORTER; TRANSPORT; CELL; PHOSPHORYLATION; GLYCOPROTEIN; OSCILLATIONS AB Mitochondrial calcium uptake has a central role in cell physiology by stimulating ATP production, shaping cytosolic calcium transients and regulating cell death. The biophysical properties of mitochondrial calcium uptake have been studied in detail, but the underlying proteins remain elusive. Here we use an integrative strategy to predict human genes involved in mitochondrial calcium entry based on clues from comparative physiology, evolutionary genomics and organelle proteomics. RNA interference against 13 top candidates highlighted one gene, CBARA1, that we call hereafter mitochondrial calcium uptake 1 (MICU1). Silencing MICU1 does not disrupt mitochondrial respiration or membrane potential but abolishes mitochondrial calcium entry in intact and permeabilized cells, and attenuates the metabolic coupling between cytosolic calcium transients and activation of matrix dehydrogenases. MICU1 is associated with the mitochondrial inner membrane and has two canonical EF hands that are essential for its activity, indicating a role in calcium sensing. MICU1 represents the founding member of a set of proteins required for high-capacity mitochondrial calcium uptake. Its discovery may lead to the complete molecular characterization of mitochondrial calcium uptake pathways, and offers genetic strategies for understanding their contribution to normal physiology and disease. C1 [Perocchi, Fabiana; Gohil, Vishal M.; Girgis, Hany S.; Bao, X. Robert; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Perocchi, Fabiana; Gohil, Vishal M.; Girgis, Hany S.; Bao, X. Robert; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA. [Perocchi, Fabiana; Gohil, Vishal M.; Girgis, Hany S.; Bao, X. Robert; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [McCombs, Janet E.; Palmer, Amy E.] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu OI Bao, Xiaoyan/0000-0001-7931-2944 FU National Institutes of Health [GM084027, TR2 GM08759, GM0077465, DK080261]; HHMI FX We thank Z. Grabarek, S. Silver and D. Root for advice; S. Calvo and A. Wolf for assistance with bioinformatics; P. Federico for technical assistance; and members of the Mootha Laboratory for valuable feedback. This work was supported by grants from the National Institutes of Health (GM084027) to A.E.P, TR2 GM08759 to J.E.M. and GM0077465, DK080261 awarded to V.K.M., and by an HHMI Early Career Physician Scientist Award to V.K.M. NR 48 TC 296 Z9 308 U1 4 U2 39 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 16 PY 2010 VL 467 IS 7313 BP 291 EP U67 DI 10.1038/nature09358 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 650CF UT WOS:000281824900031 PM 20693986 ER PT J AU Kim, HJ Verbinnen, B Tang, XL Lu, LR Cantor, H AF Kim, Hye-Jung Verbinnen, Bert Tang, Xiaolei Lu, Linrong Cantor, Harvey TI Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance SO NATURE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; AUTOIMMUNE-DISEASE; B-CELLS; SUPPRESSION; T-HELPER-2; GENERATION; EXPANSION; IL-15; IL-21; MICE AB The ability to produce vigorous immune responses that spare self tissues and organs depends on the elimination of autoreactive T and B cells. However, purging of immature and mature self-reactive T and B cells is incomplete and may also require the involvement of cells programmed to suppress immune responses(1). Regulatory T cells (T-reg) belonging to the CD4(+) T-cell subset may have a role in preventing untoward inflammatory responses, but T-cell subsets programmed to inhibit the development of autoantibody formation and systemic-lupus-erythematosus-like disease have not yet been defined(2). Here we delineate a CD8(+) regulatory T-cell lineage that is essential for the maintenance of self tolerance and prevention of murine autoimmune disease. Genetic disruption of the inhibitory interaction between these CD8(+) T cells and their target Qa-1(+) follicular T-helper cells results in the development of a lethal systemic-lupus-erythematosus-like autoimmune disease. These findings define a sublineage of CD8 T cells programmed to suppress rather than activate immunity that represents an essential regulatory element of the immune response and a guarantor of self tolerance. C1 [Kim, Hye-Jung; Verbinnen, Bert; Tang, Xiaolei; Cantor, Harvey] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Kim, Hye-Jung; Verbinnen, Bert; Tang, Xiaolei; Cantor, Harvey] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lu, Linrong] Zhejiang Univ, Sch Med, Inst Immunol, Hangzhou 310058, Zhejiang, Peoples R China. RP Cantor, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM Harvey_Cantor@dfci.harvard.edu RI Lu, Linrong/A-1429-2013; OI Lu, Linrong/0000-0002-0171-4115 FU NIH [AI 037562]; Lupus Research Institute; Schecter Research Foundation; National Research Service [DFCI/NCI T32 CA070083, HSPH/NCI T32 CA009382]; Belgian American Educational Foundation FX We thank R. Bronson (DF/HCC Rodent Histopathology Core) for histology analysis, R. Gelman and J. Yang for help with statistical analyses, C. Daniel and T. Kreslavsky for cytometry support and critical discussions, M. Iannacone and U. von Andrian for LCMV, X. Wang for technical assistance, M. Call, D. A. Alvarez Arias, T. Kadakia and A. Angel for manuscript and figure preparation. This work was supported in part by NIH Research Grant AI 037562, the Lupus Research Institute and a gift from the Schecter Research Foundation to H.C.; National Research Service Award Fellowships (DFCI/NCI T32 CA070083) to H.-J.K. and (HSPH/NCI T32 CA009382) to X.T.; and a Belgian American Educational Foundation Fellowship to B.V. NR 23 TC 145 Z9 152 U1 1 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 16 PY 2010 VL 467 IS 7313 BP 328 EP U107 DI 10.1038/nature09370 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 650CF UT WOS:000281824900039 PM 20844537 ER PT J AU Ji, H Ehrlich, LIR Seita, J Murakami, P Doi, A Lindau, P Lee, H Aryee, MJ Irizarry, RA Kim, K Rossi, DJ Inlay, MA Serwold, T Karsunky, H Ho, LN Daley, GQ Weissman, IL Feinberg, AP AF Ji, Hong Ehrlich, Lauren I. R. Seita, Jun Murakami, Peter Doi, Akiko Lindau, Paul Lee, Hwajin Aryee, Martin J. Irizarry, Rafael A. Kim, Kitai Rossi, Derrick J. Inlay, Matthew A. Serwold, Thomas Karsunky, Holger Ho, Lena Daley, George Q. Weissman, Irving L. Feinberg, Andrew P. TI Comprehensive methylome map of lineage commitment from haematopoietic progenitors SO NATURE LA English DT Article ID CPG ISLAND SHORES; DNA METHYLTRANSFERASE; TRANSCRIPTION FACTOR; STEM-CELLS; METHYLATION; MICE; GENE; DEMETHYLATION; CYTOKINES; MEIS1 AB Epigenetic modifications must underlie lineage-specific differentiation as terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Haematopoiesis provides a well-defined model to study epigenetic modifications during cell-fate decisions, as multipotent progenitors (MPPs) differentiate into progressively restricted myeloid or lymphoid progenitors. Although DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs(1), a comprehensive DNA methylation map of haematopoietic progenitors, or of any multipotent/oligopotent lineage, does not exist. Here we examined 4.6 million CpG sites throughout the genome for MPPs, common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Marked epigenetic plasticity accompanied both lymphoid and myeloid restriction. Myeloid commitment involved less global DNA methylation than lymphoid commitment, supported functionally by myeloid skewing of progenitors following treatment with a DNA methyltransferase inhibitor. Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands. Many examples of genes and pathways not previously known to be involved in choice between lymphoid/myeloid differentiation have been identified, such as Arl4c and Jdp2. Several transcription factors, including Meis1, were methylated and silenced during differentiation, indicating a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome seems to be important in haematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation and defines a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions. C1 [Ji, Hong; Murakami, Peter; Doi, Akiko; Lee, Hwajin; Irizarry, Rafael A.; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. [Ji, Hong; Murakami, Peter; Doi, Akiko; Lee, Hwajin; Irizarry, Rafael A.; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Ehrlich, Lauren I. R.; Seita, Jun; Lindau, Paul; Rossi, Derrick J.; Inlay, Matthew A.; Serwold, Thomas; Karsunky, Holger; Ho, Lena; Weissman, Irving L.] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Aryee, Martin J.; Irizarry, Rafael A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Aryee, Martin J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [Kim, Kitai; 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. [Kim, Kitai; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Kitai; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Kim, Kitai; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Kim, Kitai; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Feinberg, AP (reprint author), Johns Hopkins Univ, Sch Med, Ctr Epigenet, 570 Rangos,725 N Wolfe St, Baltimore, MD 21205 USA. EM afeinberg@jhu.edu OI Seita, Jun/0000-0002-3008-3615 FU National Institutes of Health [R37CA053458, P50HG003233, R01AI047457, R01AI047458, R00AGO29760, CA09151, F32AI058521]; Thomas and Stacey Siebel Foundation; Leukemia and Lymphoma Society; California Institute for Regenerative Medicine [T1-00001] FX We thank L. Jerabek for laboratory management, C. Richter and N. Teja for antibody production, A. Mosley, J. Dollaga and D. Escoto for animal care, E. Zuo and the Stanford PAN facility for microarray processing, and E. Briem and A. N. Allen for CHARM array processing. This investigation was supported by National Institutes of Health grants R37CA053458 and P50HG003233 (to A. P. F), R01AI047457 and R01AI047458 (to I.L.W.), and a grant from the Thomas and Stacey Siebel Foundation (to I.L.W). L.I.R.E. was supported by Special Fellow Career Development award from the Leukemia and Lymphoma Society; J. S. was supported by a fellowship from the California Institute for Regenerative Medicine (T1-00001); D.J.R. was supported by National Institutes of Health grant R00AGO29760; M.A.I. was supported by National Institutes of Health grant CA09151 and a fellowship from the California Institute for Regenerative Medicine (T1-00001); T.S. was supported by a fellowship from the National Institutes of Health (F32AI058521). NR 30 TC 312 Z9 316 U1 1 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 16 PY 2010 VL 467 IS 7313 BP 338 EP U120 DI 10.1038/nature09367 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 650CF UT WOS:000281824900041 PM 20720541 ER PT J AU Sabatine, MS Jaffer, FA Staats, PN Stone, JR AF Sabatine, Marc S. Jaffer, Farouc A. Staats, Paul N. Stone, James R. TI A Woman, 3 Weeks Post Partum, with Substernal Chest Pain Postpartum coronary-artery dissection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; SUDDEN-DEATH; INTRAVASCULAR ULTRASOUND; AORTIC DISSECTION; TERM PROGNOSIS; FOLLOW-UP; PREGNANCY; THERAPY; ANEURYSM; PREECLAMPSIA C1 [Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Sabatine, Marc S.; Jaffer, Farouc A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Staats, Paul N.; Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sabatine, Marc S.; Jaffer, Farouc A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Staats, Paul N.; Stone, James R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. NR 58 TC 7 Z9 9 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 16 PY 2010 VL 363 IS 12 BP 1164 EP 1173 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 649TD UT WOS:000281795800013 PM 20843252 ER PT J AU Biederman, J Wozniak, J Faraone, SV AF Biederman, Joseph Wozniak, Janet Faraone, Stephen V. TI Pediatric Mental Health Care Dysfunction Disorder?. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID BIPOLAR DISORDER C1 [Biederman, Joseph; Wozniak, Janet] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 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 16 PY 2010 VL 363 IS 12 BP 1187 EP 1187 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 649TD UT WOS:000281795800021 PM 20843258 ER PT J AU Bartlett, JD Dobeck, JM Tye, CE Perez-Moreno, M Stokes, N Reynolds, AB Fuchs, E Skobe, Z AF Bartlett, John D. Dobeck, Justine M. Tye, Coralee E. Perez-Moreno, Mirna Stokes, Nicole Reynolds, Albert B. Fuchs, Elaine Skobe, Ziedonis TI Targeted p120-Catenin Ablation Disrupts Dental Enamel Development SO PLOS ONE LA English DT Article ID RAT INCISOR AMELOGENESIS; RHO-FAMILY GTPASES; E-CADHERIN; P120 CATENIN; SECRETORY AMELOBLASTS; TOOTH DEVELOPMENT; TRANSCRIPTION FACTOR; ACTIN CYTOSKELETON; P-CADHERIN; EXPRESSION AB Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E-and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows. C1 [Bartlett, John D.; Dobeck, Justine M.; Tye, Coralee E.; Skobe, Ziedonis] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. [Bartlett, John D.; Tye, Coralee E.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Perez-Moreno, Mirna] Ctr Nacl Invest Oncol, Madrid, Spain. [Stokes, Nicole; Fuchs, Elaine] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. [Reynolds, Albert B.] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. EM jbartlett@forsyth.org OI Perez-Moreno, Mirna/0000-0002-0170-6406 FU National Institutes of Health (NIH) [AR27833, R01CA55724]; Forsyth Institute FX This work was supported by National Institutes of Health (NIH) grants AR27833 (E.F.) and R01CA55724 (A.B.R.) and by the Forsyth Institute (www.forsyth.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 18 Z9 18 U1 1 U2 3 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 16 PY 2010 VL 5 IS 9 AR e12703 DI 10.1371/journal.pone.0012703 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 650QH UT WOS:000281864100005 ER PT J AU Uhler, LM Kumarasamy, N Mayer, KH Saxena, A Losina, E Muniyandi, M Stoler, AW Lu, ZG Walensky, RP Flanigan, TP Bender, MA Freedberg, KA Swaminathan, S AF Uhler, Lauren M. Kumarasamy, Nagalingeswaran Mayer, Kenneth H. Saxena, Anjali Losina, Elena Muniyandi, Malaisamy Stoler, Adam W. Lu, Zhigang Walensky, Rochelle P. Flanigan, Timothy P. Bender, Melissa A. Freedberg, Kenneth A. Swaminathan, Soumya CA CEPAC Int Investigators TI Cost-Effectiveness of HIV Testing Referral Strategies among Tuberculosis Patients in India SO PLOS ONE LA English DT Article ID RESOURCE-LIMITED SETTINGS; ANTIRETROVIRAL THERAPY; SEXUAL-BEHAVIOR; COTE-DIVOIRE; COTRIMOXAZOLE PROPHYLAXIS; HIV-1-INFECTED ADULTS; RANDOMIZED-TRIAL; SOUTH-AFRICA; VIRAL LOAD; IMPACT AB Background: Indian guidelines recommend routine referral for HIV testing of all tuberculosis (TB) patients in the nine states with the highest HIV prevalence, and selective referral for testing elsewhere. We assessed the clinical impact and cost-effectiveness of alternative HIV testing referral strategies among TB patients in India. Methods and Findings: We utilized a computer model of HIV and TB disease to project outcomes for patients with active TB in India. We compared life expectancy, cost, and cost-effectiveness for three HIV testing referral strategies: 1) selective referral for HIV testing of those with increased HIV risk, 2) routine referral of patients in the nine highest HIV prevalence states with selective referral elsewhere (current standard), and 3) routine referral of all patients for HIV testing. TB-related data were from the World Health Organization. HIV prevalence among TB patients was 9.0% in the highest prevalence states, 2.9% in the other states, and 4.9% overall. The selective referral strategy, beginning from age 33.50 years, had a projected discounted life expectancy of 16.88 years and a mean lifetime HIV/TB treatment cost of US$ 100.The current standard increased mean life expectancy to 16.90 years with additional per-person cost of US$ 10; the incremental cost-effectiveness ratio was US$650/year of life saved (YLS) compared to selective referral. Routine referral of all patients for HIV testing increased life expectancy to 16.91 years, with an incremental cost-effectiveness ratio of US$730/YLS compared to the current standard. For HIV-infected patients cured of TB, receiving antiretroviral therapy increased survival from 4.71 to 13.87 years. Results were most sensitive to the HIV prevalence and the cost of second-line antiretroviral therapy. Conclusions: Referral of all patients with active TB in India for HIV testing will be both effective and cost-effective. While effective implementation of this strategy would require investment, routine, voluntary HIV testing of TB patients in India should be recommended. C1 [Uhler, Lauren M.; Saxena, Anjali; Stoler, Adam W.; Lu, Zhigang; 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. [Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res CFAR, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Kumarasamy, Nagalingeswaran] YR Gaitonde Ctr AIDS Res & Educ, Chennai, Tamil Nadu, India. [Mayer, Kenneth H.; Flanigan, Timothy P.] Brown Univ, Miriam Hosp, Providence, RI USA. [Muniyandi, Malaisamy; Swaminathan, Soumya] Indian Council Med Res, TB Res Ctr, Chennai, Tamil Nadu, India. [Bender, Melissa A.] NYU, Sch Med, Div Infect Dis, New York, NY USA. RP Uhler, LM (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM luhler@partners.org; kfreedberg@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X; Lipsitch, Marc/0000-0003-1504-9213 FU U.S. National Institute of Allergy and Infectious Disease [R01 AI058736, K24 AI062476]; Doris Duke Charitable Foundation [2007015]; Indian Council of Medical Research and Central TB Division, Ministry of Health, Government of India FX This work was supported in part by the U.S. National Institute of Allergy and Infectious Disease (R01 AI058736 and K24 AI062476), the Doris Duke Charitable Foundation (Operations Research on AIDS Care and Treatment in Africa (ORACTA) Award 2007015), and the Indian Council of Medical Research and Central TB Division, Ministry of Health, Government of India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 8 Z9 8 U1 0 U2 0 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 16 PY 2010 VL 5 IS 9 AR e12747 DI 10.1371/journal.pone.0012747 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 650QH UT WOS:000281864100009 ER PT J AU Adeyemo, MA Spiegel, BMR Chang, L AF Adeyemo, M. A. Spiegel, B. M. R. Chang, L. TI Meta-analysis: do irritable bowel syndrome symptoms vary between men and women? SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID FUNCTIONAL GASTROINTESTINAL DISORDERS; HEALTH-CARE SEEKING; GENDER-RELATED DIFFERENCES; ROME-II CRITERIA; QUALITY-OF-LIFE; MENSTRUAL-CYCLE; COLONIC TRANSIT; RISK-FACTORS; POSTMENOPAUSAL WOMEN; MANNING CRITERIA AB P>Background Studies suggest that sex and gender-related differences exist in irritable bowel syndrome (IBS), but data is often conflicting. Aim To evaluate gender differences and the effect of menstrual cycle and menopausal status on IBS symptoms. Methods We performed a systematic review of MEDLINE to search for studies comparing IBS symptoms between gender, menstrual cycle phases and menopausal states in IBS and/or healthy individuals. We performed meta-analyses to compare the relative risk (RR) of individual IBS symptoms between men and women. Results Twenty-two studies measured gender differences in IBS symptoms. Women were more likely to report abdominal pain (RR = 1.12, 95% CI: 1.02, 1.22) and constipation-related symptoms (RR = 1.12, 95% CI: 1.02, 1.23) than men (all P < 0.05). However, men with IBS were more likely to report diarrhoea-related symptoms than women with IBS (RR = 0.84, 95% CI: 0.75, 0.94, P < 0.05). A systematic review of 13 studies demonstrated that both IBS and healthy women reported increased IBS symptoms during menses vs. other phases. There were insufficient data to determine the effect of menopause and hormone supplementation on IBS symptoms. Conclusions In the general and IBS populations, gender differences in IBS symptoms exist, although these differences are modest. Studies suggest that female sex hormones influence the severity of IBS symptoms, but more studies are needed. C1 [Adeyemo, M. A.; Chang, L.] Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. [Spiegel, B. M. R.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Div Digest Dis, Los Angeles, CA 90024 USA. [Spiegel, B. M. R.] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ CORE, Los Angeles, CA 90073 USA. RP Chang, L (reprint author), Ctr Neurobiol Stress, CHS 47-122,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM linchang@ucla.edu FU Takeda; Rose; Prometheus; Amgen; Shire; Novartis; NIH [P50 DK64539, R24 AT002681] FX Declaration of personal interests: The authors thank Melissa Alberto and Teresa Olivas for their assistance in the preparation of the work. Mopelola Adeyemo has nothing to declare. Brennan Spiegel has served as a consultant for Prometheus Laboratories, Astra-Zeneca, TAP, Takeda, Ironwood, and Novartis. He has received research funding from Takeda, Rose, Prometheus, Amgen, Shire, and Novartis. Lin Chang has served as a consultant for Prometheus Laboratories, Takeda, Forest, Albireo, McNeil, Rose Pharma, GlaxoSmithKline, Salix, Ocera and Movetis. She has received research funding from Takeda, Rose and Prometheus. Declaration of funding interests: This study was funded by NIH Grants Nos P50 DK64539 and R24 AT002681. NR 109 TC 57 Z9 61 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 EI 1365-2036 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD SEP 15 PY 2010 VL 32 IS 6 BP 738 EP 755 DI 10.1111/j.1365-2036.2010.04409.x PG 18 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 639JX UT WOS:000280972200004 PM 20662786 ER PT J AU Gastaldelli, A Harrison, S Belfort-Aguiar, R Hardies, J Balas, B Schenker, S Cusi, K AF Gastaldelli, A. Harrison, S. Belfort-Aguiar, R. Hardies, J. Balas, B. Schenker, S. Cusi, K. TI Pioglitazone in the treatment of NASH: the role of adiponectin SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HEPATIC INSULIN-RESISTANCE; ACTIVATED PROTEIN-KINASE; PLACEBO-CONTROLLED TRIAL; FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; DIABETES-MELLITUS; FIBROSIS; GLUCOSE; MICE; METABOLISM AB P>Background Plasma adiponectin is decreased in NASH patients and the mechanism(s) for histological improvement during thiazolidinedione treatment remain(s) poorly understood. Aim To evaluate the relationship between changes in plasma adiponectin following pioglitazone treatment and metabolic/histological improvement. Methods We measured in 47 NASH patients and 20 controls: (i) fasting glucose, insulin, FFA and adiponectin concentrations; (ii) hepatic fat content by magnetic resonance spectroscopy; and (iii) peripheral/hepatic insulin sensitivity (by double-tracer oral glucose tolerance test). Patients were then treated with pioglitazone (45 mg/day) or placebo and all measurements were repeated after 6 months. Results Patients with NASH had decreased plasma adiponectin levels independent of the presence of obesity. Pioglitazone increased 2.3-fold plasma adiponectin and improved insulin resistance, glucose tolerance and glucose clearance, steatosis and necroinflammation (all P < 0.01-0.001 vs. placebo). In the pioglitazone group, plasma adiponectin was significantly associated (r = 0.52, P = 0.0001) with hepatic insulin sensitivity and with the change in both variables (r = 0.44, P = 0.03). Increase in adiponectin concentration was related also to histological improvement, in particular, to hepatic steatosis (r = -0.46, P = 0006) and necroinflammation (r = -0.56, P < 0.0001) but importantly also to fibrosis (r = -0.29, P = 0.03). Conclusions Adiponectin exerts an important metabolic role at the level of the liver, and its increase during pioglitazone treatment is critical to reverse insulin resistance and improve liver histology in NASH patients. C1 [Gastaldelli, A.; Belfort-Aguiar, R.; Balas, B.; Cusi, K.] Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, San Antonio, TX 78284 USA. [Gastaldelli, A.] CNR, Natl Res Council, Inst Clin Physiol, I-00185 Rome, Italy. [Harrison, S.] Brooke Army Med Ctr, Div Gastroenterol, San Antonio, TX USA. [Hardies, J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med & Radiol, San Antonio, TX 78284 USA. [Schenker, S.] Univ Texas Hlth Sci Ctr San Antonio, Div Gastroenterol, San Antonio, TX 78284 USA. [Cusi, K.] Brooke Army Med Ctr, Div Diabet, Audie L Murphy Vet Adm Med Ctr, San Antonio, TX USA. RP Cusi, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, Room 3-380S,7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM cusi@uthscsa.edu RI Hardies, Lou /F-2102-2010; Gastaldelli, Amalia/H-3319-2014 OI Gastaldelli, Amalia/0000-0003-2594-1651 FU Veterans Affairs Medical Research Fund; National Center for Research Resources [UL 1RR025767]; Italian National Research Council; Takeda Pharmaceuticals FX The authors thank the study volunteers, the nursing staff, and the nutrition and laboratory staff for their assistance in performing the described studies. Declaration of personal interests: Gastaldelli A, Harrison S, Belfort R, Hardies J, Balas B, Schenker S and Cusi K have no conflicts of interest. Declaration of funding interests: The project described (and Cusi K) was supported by the Veterans Affairs Medical Research Fund and by Award Number UL 1RR025767 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources of the National Institutes of Health. A. G. was supported by the Italian National Research Council. Partial support was received for the original study from Takeda Pharmaceuticals. NR 29 TC 46 Z9 51 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD SEP 15 PY 2010 VL 32 IS 6 BP 769 EP 775 DI 10.1111/j.1365-2036.2010.04405.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 639JX UT WOS:000280972200007 PM 20662773 ER PT J AU O'Reilly, EJ Gao, XA Weisskopf, MG Chen, HL Schwarzschild, MA Spiegelman, D Ascherio, A AF O'Reilly, Ellis J. Gao, Xiang Weisskopf, Marc G. Chen, Honglei Schwarzschild, Michael A. Spiegelman, Donna Ascherio, Alberto TI Plasma Urate and Parkinson's Disease in Women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; Parkinson disease; uric acid ID URIC-ACID LEVELS; RISK; CONSUMPTION; PREDICTOR; CAFFEINE; ESTROGEN; NEURONS; HEALTH AB Plasma urate has been consistently associated with a lower risk of Parkinson's disease in men, but it is less clear if this relation exists in women. Between 1990 and 2004, the authors conducted a nested case-control study among participants of the female-only Nurses' Health Study. In controls (n = 504), plasma urate was positively associated with age, body mass index, alcohol consumption, hypertension, and use of diuretics and was inversely associated with physical activity and postmenopausal hormone use, as expected. Mean urate levels were 5.04 mg/dL for cases (n = 101) and 4.86 mg/dL for controls (P = 0.17). The age-, smoking-, and caffeine-adjusted rate ratio comparing women in the highest (>= 5.8 mg/dL) with those in the lowest (<4.0 mg/dL) quartile was 1.33 (95% confidence interval: 0.69, 2.57; P(trend) = 0.4). Further adjustment for body mass index, physical activity, history of hypertension, and postmenopausal hormone use did not change the results. Unlike in men, these findings do not support the hypothesis that urate is strongly associated with lower rates of Parkinson's disease among women. C1 [O'Reilly, Ellis J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [O'Reilly, Ellis J.; Weisskopf, Marc G.; Spiegelman, Donna; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Weisskopf, Marc G.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gao, Xiang; Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA USA. RP O'Reilly, EJ (reprint author), Room 305,Bldg 2,655 Huntington Ave, Boston, MA 02115 USA. EM eoreilly@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU National Institutes of Health [K24NS060991]; National Institute of Environmental Health Sciences [Z01-ES-101986] FX The study was supported in part by grant K24NS060991 (M. A. S.) and the Intramural Research Program of the National Institutes of Health and by grant Z01-ES-101986 (H. C.) from the National Institute of Environmental Health Sciences. NR 20 TC 24 Z9 27 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 2010 VL 172 IS 6 BP 666 EP 670 DI 10.1093/aje/kwq195 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 651TD UT WOS:000281949100008 PM 20682521 ER PT J AU Segal, AR Brunner, JE Burch, FT Jackson, JA AF Segal, Alissa R. Brunner, Jack E. Burch, F. Taylor Jackson, Jeffrey A. TI Use of concentrated Insulin human regular (U-500) for patients with diabetes SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE Diabetes mellitus; Dosage; Drug administration; Errors, medication; Hypoglycemia; Insulin human; Insulins; Obesity; Pharmacodynamics; Pharmacokinetics; Toxicity ID CLINICAL-COURSE; GLUCOSE CONTROL; THERAPY; COMPLICATIONS; ABSORPTION; MANAGEMENT; RESISTANCE; MELLITUS; DISEASE AB Purpose. The efficacy and safety of and key clinical considerations for using U-500 insulin human regular in the treatment of high-dose insulin-treated patients in a wide variety of settings are examined. Summary. U-500 regular insulin has been available in the United States since 1952, but only recently has it become more commonly prescribed for patients requiring large amounts of insulin to improve their blood glucose control. This use coincides with the increasing rates of obesity and type 2 diabetes associated with significant insulin resistance, which can necessitate the need for doses of insulin exceeding 200 units/day. However, many health care professionals are relatively unfamiliar with this concentrated insulin formulation. U-500 regular insulin has a pharmacokinetic and pharmacodynamic profile that differs from U-100 human insulins and analogues. Although no randomized clinical trials using U-500 insulin have been performed, eight case series (involving 160 patients) have been published. Rare or infrequent occurrences of hypoglycemia with U-500 insulin have been reported. Of the medication errors associated with U-500 insulin, administration and dispensing errors occurred most frequently. With the increase in prescribing of U-500 insulin, pharmacists must be aware of the complex issues involved with appropriate prescribing, dispensing, and provision of patient education to maximize patient safety and avoid administration errors and dosing confusion. Conclusion. U-500 insulin is efficacious and safe for patients with type 2 diabetes who require a high dosage of insulin to control hyperglycemia. However, health care professionals should be well educated and vigilant about patient safety issues regarding the drug's prescription, dosing, and administration. C1 [Segal, Alissa R.] Massachusetts Coll Pharm & Hlth Sci, Dept Pharm Practice, Boston, MA 02115 USA. [Segal, Alissa R.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Brunner, Jack E.] Endocrine & Diabet Care Ctr, Toledo, OH USA. [Burch, F. Taylor; Jackson, Jeffrey A.] Lilly USA LLC, Endocrine, US Med Div, Indianapolis, IN USA. [Jackson, Jeffrey A.] Indiana Univ, Sch Med, Indianapolis, IN USA. RP Segal, AR (reprint author), Massachusetts Coll Pharm & Hlth Sci, Dept Pharm Practice, 179 Longwood Ave, Boston, MA 02115 USA. EM alissa.segal@mcphs.edu FU Amylin Pharmaceuticals; Lilly USA, LLC; GlaxoSmithKline; Merck; Novartis; Bristol-Myers Squibb; Novo Nordisk; AstraZeneca; Pfizer; sanofi aventis; Roche FX Dr. Segal is a consultant for Lilly USA, LLC. Dr. Brunner serves on the speakers' bureau of and receives research support from Amylin Pharmaceuticals, Lilly USA, LLC, GlaxoSmithKline, Merck, Novartis, Bristol-Myers Squibb, Novo Nordisk, AstraZeneca, Pfizer, sanofi aventis, and Roche. Dr. Burch and Dr. Jackson are full-time employees and stockholders of Lilly USA. NR 56 TC 24 Z9 24 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 EI 1535-2900 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD SEP 15 PY 2010 VL 67 IS 18 BP 1526 EP 1535 DI 10.2146/ajhp090554 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 858BS UT WOS:000297771500013 PM 20811030 ER PT J AU Rauch, P Moore, C AF Rauch, Paula Moore, Cynthia TI A Population-Based Estimate of Cancer Survivors Residing With Minor Children SO CANCER LA English DT Editorial Material ID BREAST-CANCER; PARENTAL CANCER; ADJUSTMENT; ADOLESCENTS; INFORMATION C1 [Rauch, Paula; Moore, Cynthia] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Rauch, P (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,YAW 6900, Boston, MA 02114 USA. EM prauch@partners.org NR 16 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 15 PY 2010 VL 116 IS 18 BP 4218 EP 4220 DI 10.1002/cncr.25360 PG 3 WC Oncology SC Oncology GA 646AS UT WOS:000281507900004 PM 20586038 ER PT J AU Abramson, JS Hellmann, M Barnes, JA Hammerman, P Toomey, C Takvorian, T Muzikansky, A Hochberg, EP AF Abramson, Jeremy S. Hellmann, Matthew Barnes, Jeffrey A. Hammerman, Peter Toomey, Christiana Takvorian, Tak Muzikansky, Alona Hochberg, Ephraim P. TI Intravenous Methotrexate as Central Nervous System (CNS) Prophylaxis Is Associated With a Low Risk of CNS Recurrence in High-Risk Patients With Diffuse Large B-Cell Lymphoma SO CANCER LA English DT Article DE diffuse large B-cell lymphoma; central nervous system lymphoma; central nervous system prophylaxis; methotrexate ID NON-HODGKINS-LYMPHOMA; STUDY-GROUP DSHNHL; ELDERLY-PATIENTS; INTRATHECAL CHEMOTHERAPY; AGGRESSIVE LYMPHOMA; INTERMEDIATE-GRADE; INVOLVEMENT; RITUXIMAB; CHOP; RELAPSE AB BACKGROUND: The outcome of patients with systemic diffuse large B-cell lymphoma (DLBCL) had improved over the past decade with the addition of monoclonal antibody therapy. Unfortunately, approximately 5% of these patients still developed a secondary central nervous system (CNS) recurrence followed invariably by rapid death. This rate is substantially increased in patients with certain high-risk features. Although prophylaxis against CNS recurrence with either intrathecal or intravenous methotrexate is commonly used for such patients, to the authors' knowledge, there is no standard of care. Retrospectively evaluated was the role of high-dose systemic methotrexate combined with standard cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (R-CHOP) chemotherapy to decrease CNS recurrence in high-risk patients. METHODS: A total of 65 patients with DLBCL and CNS risk factors were identified at the study institution between 2000 and 2008 who received intravenous methotrexate as CNS prophylaxis concurrent with standard systemic therapy with curative intent. CNS recurrence rate, progression-free survival, and overall survival were calculated. RESULTS: Patients received a median of 3 cycles of methotrexate at a dose of 3.5 gm/m(2) with leucovorin rescue. The complete response rate was 86%, with 6% partial responses. At a median follow-up of 33 months, there were only 2 CNS recurrences (3%) in this high-risk population. The 3-year progression-free and overall survival rates were 76% and 78%, respectively. Complications associated with methotrexate therapy included transient renal dysfunction in 7 patients and a delay in systemic chemotherapy in 8 patients. CONCLUSIONS: Intravenous methotrexate can be safely administered concurrently with R-CHOP and is associated with a low risk of CNS recurrence in high-risk patients. Cancer 2010;116:4283-90. (C) 2010 American Cancer Society. C1 [Abramson, Jeremy S.; Hellmann, Matthew; Barnes, Jeffrey A.; Hammerman, Peter; Toomey, Christiana; Takvorian, Tak; Hochberg, Ephraim P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Abramson, Jeremy S.; Hellmann, Matthew; Barnes, Jeffrey A.; Hammerman, Peter; Takvorian, Tak; Hochberg, Ephraim P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM jabramson@partners.org OI Abramson, Jeremy/0000-0001-8467-9257 FU Enzon pharmaceuticals FX Dr. Hochberg has received consulting and speaking fees from Enzon pharmaceuticals. NR 25 TC 66 Z9 69 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 15 PY 2010 VL 116 IS 18 BP 4283 EP 4290 DI 10.1002/cncr.25278 PG 8 WC Oncology SC Oncology GA 646AS UT WOS:000281507900012 PM 20564149 ER PT J AU Ibrahim, N He, L Leong, CO Xing, DY Karlan, BY Swisher, EM Rueda, BR Orsulic, S Ellisen, LW AF Ibrahim, Nageatte He, Lei Leong, Chee-Onn Xing, Deyin Karlan, Beth Y. Swisher, Elizabeth M. Rueda, Bo R. Orsulic, Sandra Ellisen, Leif W. TI BRCA1-Associated Epigenetic Regulation of p73 Mediates an Effector Pathway for Chemosensitivity in Ovarian Carcinoma SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTIONAL REPRESSOR ZEB; CPG ISLAND METHYLATION; KINASE C-ABL; DNA-DAMAGE; P53 FAMILY; MOLECULAR CHARACTERIZATION; APOPTOTIC RESPONSE; IONIZING-RADIATION; CLINICAL-RELEVANCE; INDUCE APOPTOSIS AB The majority of tumors arising in BRCA1 mutation carriers exhibit inactivation of p53, a key effector of cell death after DNA damage. Despite the loss of p53, BRCA1-deficient tumor cells exhibit increased sensitivity to cisplatin, and patients with BRCA1-associated ovarian carcinomas experience improved outcomes with platinum-based chemotherapy compared with sporadic cases. Although it is known that chemosensitivity in BRCA1-associated cancers is associated with unrepaired DNA damage, the specific effector pathway mediating the cellular response to platinum-induced damage in these tumors is poorly understood. Here, we show that the p53-related gene p73, encoding a proapoptotic protein that is linked to chemosensitivity in many settings, is upregulated through a novel epigenetic mechanism in both human and murine models of BRCA1-associated ovarian carcinoma. BRCA1-deficient ovarian carcinoma cells exhibit hypermethylation within a p73 regulatory region, which includes the binding site for the p73 transcriptional repressor ZEB1, leading to the abrogation of ZEB1 binding and increased expression of transactivating p73 isoforms (TAp73). Cisplatin chemotherapy induces TAp73 target genes specifically in BRCA1-deficient cells, and knockdown of TAp73 in these cells causes chemoresistance while having little or no effect on BRCA1-expressing tumor cells. In primary ovarian carcinomas, ZEB1 binding site methylation and TAp73 expression correlate with BRCA1 status and with clinical response. Together, these findings uncover a novel regulatory mechanism that supports the contribution of TAp73 as an important mediator of the response to platinum chemotherapy in a subset of ovarian carcinomas. TAp73 might represent a response predictor and potential therapeutic target for enhancing chemosensitivity in this disease. Cancer Res; 70(18); 7155-65. (C)2010 AACR. C1 [Ibrahim, Nageatte; He, Lei; Leong, Chee-Onn; Xing, Deyin; Rueda, Bo R.; Orsulic, Sandra; Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA USA. [Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Karlan, Beth Y.] Cedars Sinai Med Ctr, Womens Canc Res Inst, Los Angeles, CA 90048 USA. [Swisher, Elizabeth M.] Univ Washington, Med Ctr, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Ibrahim, Nageatte; He, Lei; Leong, Chee-Onn; Xing, Deyin; Rueda, Bo R.; Orsulic, Sandra; Ellisen, Leif W.] MGH Canc Ctr, Boston, MA 02114 USA. RP Ellisen, LW (reprint author), MGH Canc Ctr, GRJ-904,55 Fruit St, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu RI He, Lei/G-6018-2011 FU MGH ECOR Fund for Medical Discovery [RO1 CA103924]; American Cancer Society [SIOP-06-258-01-CCE]; Milken Family Foundation [P50CA105009]; Ovarian Cancer Research Fund; Ovarian Cancer Education and Awareness Network; Advanced Medical Research Foundation FX MGH ECOR Fund for Medical Discovery (C-O. Leong), RO1 CA103924 (S. Orsulic), American Cancer Society Early Detection Professorship grant SIOP-06-258-01-CCE (B.Y. Karlan), Milken Family Foundation (B.Y. Karlan), P50CA105009 (S. Orsulic and B.R. Rueda), Ovarian Cancer Research Fund (S. Orsulic and B.R. Rueda), Ovarian Cancer Education and Awareness Network (B.R. Rueda), and Advanced Medical Research Foundation (B.R. Rueda). NR 48 TC 22 Z9 22 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2010 VL 70 IS 18 BP 7155 EP 7165 DI 10.1158/0008-5472.CAN-10-0668 PG 11 WC Oncology SC Oncology GA 651GI UT WOS:000281914900016 PM 20807817 ER PT J AU Guo, SQ Scadden, DT AF Guo, Shangqin Scadden, David T. TI A microRNA regulating adult hematopoietic stem cells SO CELL CYCLE LA English DT Editorial Material ID PATHWAY; EXPRESSION C1 [Scadden, David T.] Harvard Univ, Sch Med, Ctr Regenerat Med,Dept Stem Cell & Regenerat Biol, Massachusetts Gen Hosp,Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Guo, Shangqin] Yale Univ, Yale Stem Cell Ctr, Dept Genet, New Haven, CT USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Ctr Regenerat Med,Dept Stem Cell & Regenerat Biol, Massachusetts Gen Hosp,Harvard Stem Cell Inst, Cambridge, MA 02138 USA. EM dscadden@mgh.harvard.edu NR 11 TC 3 Z9 3 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP 15 PY 2010 VL 9 IS 18 BP 3637 EP 3638 DI 10.4161/cc.9.18.13174 PG 2 WC Cell Biology SC Cell Biology GA 651FD UT WOS:000281909900003 PM 20855952 ER PT J AU Wolfer, A Ramaswamy, S AF Wolfer, Anita Ramaswamy, Sridhar TI Prognostic signatures, cancer metastasis and MYC SO CELL CYCLE LA English DT Editorial Material ID TUMORS C1 [Wolfer, Anita; Ramaswamy, Sridhar] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Wolfer, Anita; Ramaswamy, Sridhar] Harvard Univ, Sch Med, Boston, MA USA. [Ramaswamy, Sridhar] Broad Inst, Cambridge, MA USA. [Ramaswamy, Sridhar] Harvard Stem Cell Inst, Cambridge, MA USA. RP Ramaswamy, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM sridhar@mgh.harvard.edu FU NCI NIH HHS [K08 CA100339-06] NR 14 TC 6 Z9 6 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP 15 PY 2010 VL 9 IS 18 BP 3639 EP 3639 DI 10.4161/cc.9.18.13220 PG 1 WC Cell Biology SC Cell Biology GA 651FD UT WOS:000281909900004 PM 20930551 ER PT J AU Horberg, MA Aberg, JA Cheever, LW Renner, P Kaleba, EO Asch, SM AF Horberg, Michael A. Aberg, Judith A. Cheever, Laura W. Renner, Philip Kaleba, Erin O'Brien Asch, Steven M. TI Development of National and Multiagency HIV Care Quality Measures SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-DISEASES-SOCIETY; IMMUNIZATION PRACTICES ACIP; PNEUMOCYSTIS-CARINII-PNEUMONIA; UNITED-STATES; MEDICINE ASSOCIATION; ADVISORY-COMMITTEE; OPPORTUNISTIC INFECTIONS; PNEUMOCOCCAL DISEASE; RISK-FACTORS AB Background. Human immunodeficiency virus (HIV) is now a complex, chronic disease requiring high quality care. Demonstration of quality HIV care requires uniform, aligned HIV care quality measurement. Methods. In September 2007, the National Committee for Quality Assurance, under contract with the Health Resources and Services Administration, the Physician Consortium for Performance Improvement of the American Medical Association, and HIV Medicine Association of the Infectious Disease Society of America jointly sponsored and convened an expert panel as a HIV/AIDS Work Group to draft national HIV/AIDS performance measures for individual patient-level and system-level quality improvement. Results. A total of 17 measures were developed to assess processes and outcomes of HIV/AIDS care for patients established in care, defined as having at least 2 visits in a 12-month period; thus, measures of HIV screening, testing, linkage, and access to care were not included. As a set, the measures assess a wide range of care, including patient retention, screening and prophylaxis for opportunistic infections, immunization, and initiation and monitoring of potent antiretroviral therapy. Since development, the HIV/AIDS measures' specifications have been fully determined and are being beta tested, and a majority have been endorsed by the National Quality Forum and have been adopted and implemented by the sponsoring organizations. Conclusions. HIV care quality measurement should be assessed with greater uniformity. The measures presented offer opportunities for such alignment. C1 [Horberg, Michael A.] Kaiser Permanente, HIV AIDS, HIV Interreg Initiat, Oakland, CA 94612 USA. [Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Asch, Steven M.] RAND Corp, Los Angeles, CA USA. [Aberg, Judith A.] NYU, Sch Med, Dept Med, New York, NY USA. [Cheever, Laura W.] US Hlth Resources & Serv Adm, HIV AIDS Bur, Rockville, MD 20857 USA. [Renner, Philip] Natl Comm Qual Assurance, Washington, DC USA. [Kaleba, Erin O'Brien] Alliance Chicago Community Hlth Serv, Chicago, IL USA. RP Horberg, MA (reprint author), Kaiser Permanente, HIV AIDS, HIV Interreg Initiat, 2000 Broadway, Oakland, CA 94612 USA. EM michael.horberg@kp.org FU National Committee for Quality Assurance; Physician Consortium for Performance Improvement of the American Medical Association; HIV Medicine Association of the Infectious Diseases Society of America; Health Resources and Services Administration FX Financial support. National Committee for Quality Assurance, the Physician Consortium for Performance Improvement of the American Medical Association, the HIV Medicine Association of the Infectious Diseases Society of America, and the Health Resources and Services Administration. NR 48 TC 39 Z9 39 U1 0 U2 2 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 SEP 15 PY 2010 VL 51 IS 6 BP 732 EP 738 DI 10.1086/655893 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 641QA UT WOS:000281143400015 PM 20715924 ER PT J AU van Zundert, B Zhao, JP Constantine-Paton, M AF van Zundert, Brigitte Zhao, Jiang-Ping Constantine-Paton, Martha TI Synaptic Drive at Developing Synapses: Transient Upregulation of Kainate Receptors SO DEVELOPMENTAL NEUROBIOLOGY LA English DT Article DE AMPA; NMDA; kainate; GABA; superior colliculus ID SUPERIOR COLLICULUS; THALAMOCORTICAL SYNAPSES; BARREL CORTEX; HIPPOCAMPAL-NEURONS; NMDA RECEPTORS; AMPA RECEPTORS; BIPOLAR CELLS; ACTIVATION; TRANSMISSION; GLUTAMATE AB At the onset of a period of intense synaptic refinement initiated by synchronized eye opening (EO), rapid changes in postsynaptic NMDA receptor and AMPA receptor currents (NMDARcs and AMPARcs) occur within the superficial visual layers of the rodent superior colliculus (sSC; Lu and Constantine-Paton [2004]: Neuron 43:237-249). Subsequently, evoked non-NMDARc amplitudes increase, but by 2 weeks after EO (AEO) they decrease significantly. Here, using whole-cell patch-clamp recording, we demonstrate that small, slowly desensitizing excitatory kainate receptor currents (KARcs) are responsible for the rise and subsequent fall in non-NMDARcs. The increase in KAR transmission parallels inhibitory GABA(A) responses that plateau at 7 days AEO. By 2 weeks AEO, KARcs are gone. AMPARcs remain unchanged during the appearance and disappearance of the KARcs, despite increases in sSC neuropil activity and continued refinement of inputs to individual sSC neurons. We suggest that in the interval of heightened activity, before SC inhibition matures, many AMPARcs desensitize and are relatively ineffective at relieving the Mg(2+) block on NMDARs. This transient appearance of slowly desensitizing, long-duration KARcs may provide increased membrane depolarization necessary for NMDAR function and continuation of synaptic refinement. (C) 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 737-750, 2010 C1 [van Zundert, Brigitte; Zhao, Jiang-Ping; Constantine-Paton, Martha] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [van Zundert, Brigitte; Zhao, Jiang-Ping; Constantine-Paton, Martha] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [van Zundert, Brigitte] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Day Lab Neuromuscular Res,Dept Neurol, Boston, MA 02115 USA. [van Zundert, Brigitte] Univ Andres Bello, Fac Med, Santiago, Chile. [van Zundert, Brigitte] Univ Andres Bello, Fac Biol Sci, Ctr Biomed Res, Santiago, Chile. RP van Zundert, B (reprint author), MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM bvanzundert@unab.cl FU NIH [EY01407]; Fondecyts [1070494, 1101012]; Pierre L. de Bourknecht ALS Research Fund FX Contract grant sponsor: NIH; contract grant number: EY01407.; Contract grant sponsor: Fondecyts; contract grant numbers: 1070494, 1101012.; Contract grant sponsor: The Pierre L. de Bourknecht ALS Research Fund. NR 44 TC 3 Z9 3 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1932-8451 J9 DEV NEUROBIOL JI Dev. Neurobiol. PD SEP 15 PY 2010 VL 70 IS 11 BP 737 EP 750 DI 10.1002/dneu.20807 PG 14 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 645AP UT WOS:000281423600001 PM 20518018 ER PT J AU Chen, P Burdette, AJ Porter, JC Ricketts, JC Fox, SA Nery, FC Hewett, JW Berkowitz, LA Breakefield, XO Caldwell, KA Caldwell, GA AF Chen, Pan Burdette, Alexander J. Porter, J. Christopher Ricketts, John C. Fox, Stacey A. Nery, Flavia C. Hewett, Jeffrey W. Berkowitz, Laura A. Breakefield, Xandra O. Caldwell, Kim A. Caldwell, Guy A. TI The early-onset torsion dystonia-associated protein, torsinA, is a homeostatic regulator of endoplasmic reticulum stress response SO HUMAN MOLECULAR GENETICS LA English DT Article ID CAENORHABDITIS-ELEGANS; NUCLEAR-ENVELOPE; ER STRESS; C-ELEGANS; SECRETORY PATHWAY; PC12 CELLS; GENE DYT1; MUTANT; DISEASE; AGGREGATION AB Early-onset torsion dystonia is the most severe heritable form of dystonia, a human movement disorder that typically starts during a developmental window in early adolescence. Deletion in the DYT1 gene, encoding the torsinA protein, is responsible for this dominantly inherited disorder, which is non-degenerative and exhibits reduced penetrance among carriers. Here, we explore the hypothesis that deficits in torsinA function result in an increased vulnerability to stress associated with protein folding and processing in the endoplasmic reticulum (ER), where torsinA is located. Using an in vivo quantitative readout for the ER stress response, we evaluated the consequences of torsinA mutations in transgenic nematodes expressing variants of human torsinA. This analysis revealed that, normally, torsinA serves a protective function to maintain a homeostatic threshold against ER stress. Furthermore, we show that the buffering capacity of torsinA is greatly diminished by the DYT1-associated deletion or mutations that prevent its translocation to the ER, block ATPase activity, or increase the levels of torsinA in the nuclear envelope versus ER. Combinations of transgenic Caenorhabditis elegans designed to mimic clinically relevant genetic modifiers of disease susceptibility also exhibit a direct functional correlation to changes in the ER stress response. Furthermore, using mouse embryonic fibroblasts (MEFs) from torsinA knockout mice, we demonstrated that loss of endogenous torsinA results in enhanced sensitivity to ER stress. This study extends our understanding of molecular mechanisms underlying dystonia, and establishes a new functional paradigm to evaluate therapeutic strategies to compensate for reduced torsinA activity in the ER as a means to restore homeostatic balance and neuronal function. C1 [Chen, Pan; Burdette, Alexander J.; Porter, J. Christopher; Ricketts, John C.; Fox, Stacey A.; Berkowitz, Laura A.; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA. [Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA. [Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Dept Neurol, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA. [Nery, Flavia C.; Hewett, Jeffrey W.; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Nery, Flavia C.; Hewett, Jeffrey W.; Breakefield, Xandra O.] Harvard Univ, Program Neurosci, Sch Med, Boston, MA 02114 USA. RP Caldwell, GA (reprint author), Univ Alabama, Dept Biol Sci, POB 870344, Tuscaloosa, AL 35487 USA. EM gcaldwel@bama.ua.edu FU National Institutes of Health National Center for Research Resources; Bachmann-Strauss Dystonia and Parkinson Foundation; NINDS [NS037409]; Jack Fasciana Fund for Support of Dystonia Research; QRxPharma, Ltd.; Modern Movers, Inc.; Parkinson Association of Alabama; Alabama Dystonia Support Group of Birmingham FX All C. elegans mutant strains came from the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health National Center for Research Resources. This work was supported by grants from the Bachmann-Strauss Dystonia and Parkinson Foundation (X.O.B., K. A. C. and G. A. C.), NINDS NS037409 (X.O.B.), the Jack Fasciana Fund for Support of Dystonia Research (X.O.B.) and a sponsored research agreement from QRxPharma, Ltd. (K. A. C. and G. A. C.). Thanks to Dr Mark Ricketts and Modern Movers, Inc. for generous scholarship support and donation of equipment funds, respectively. S. A. F. was supported by a scholarship from the Parkinson Association of Alabama. J.C.R. was an Alabama Dystonia Scholar supported by members and friends of the Alabama Dystonia Support Group of Birmingham. NR 61 TC 46 Z9 47 U1 0 U2 4 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 SEP 15 PY 2010 VL 19 IS 18 BP 3502 EP 3515 DI 10.1093/hmg/ddq266 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 644AU UT WOS:000281343600002 PM 20584926 ER PT J AU Jacobs, EJ Chanock, SJ Fuchs, CS LaCroix, A McWilliams, RR Steplowski, E Stolzenberg-Solomon, RZ Arslan, AA Bueno-de-Mesquita, HB Gross, M Helzlsouer, K Petersen, G Zheng, W Agalliu, I Allen, NE Amundadottir, L Boutron-Ruault, MC Buring, JE Canzian, F Clipp, S Dorronsoro, M Gaziano, JM Giovannucci, EL Hankinson, SE Hartge, P Hoover, RN Hunter, DJ Jacobs, KB Jenab, M Kraft, P Kooperberg, C Lynch, SM Sund, M Mendelsohn, JB Mouw, T Newton, CC Overvad, K Palli, D Peeters, PHM Rajkovic, A Shu, XO Thomas, G Tobias, GS Trichopoulos, D Virtamo, J Wactawski-Wende, J Wolpin, BM Yu, K Zeleniuch-Jacquotte, A AF Jacobs, Eric J. Chanock, Stephen J. Fuchs, Charles S. LaCroix, Andrea McWilliams, Robert R. Steplowski, Emily Stolzenberg-Solomon, Rachael Z. Arslan, Alan A. Bueno-de-Mesquita, H. Bas Gross, Myron Helzlsouer, Kathy Petersen, Gloria Zheng, Wei Agalliu, Ilir Allen, Naomi E. Amundadottir, Laufey Boutron-Ruault, Marie-Christine Buring, Julie E. Canzian, Federico Clipp, Sandra Dorronsoro, Miren Gaziano, J. Michael Giovannucci, Edward L. Hankinson, Susan E. Hartge, Patricia Hoover, Robert N. Hunter, David J. Jacobs, Kevin B. Jenab, Mazda Kraft, Peter Kooperberg, Charles Lynch, Shannon M. Sund, Malin Mendelsohn, Julie B. Mouw, Tracy Newton, Christina C. Overvad, Kim Palli, Domenico Peeters, Petra H. M. Rajkovic, Aleksandar Shu, Xiao-Ou Thomas, Gilles Tobias, Geoffrey S. Trichopoulos, Dimitrios Virtamo, Jarmo Wactawski-Wende, Jean Wolpin, Brian M. Yu, Kai Zeleniuch-Jacquotte, Anne TI Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BASE-LINE CHARACTERISTICS; SINGLE BRCA2 MUTATION; COLORECTAL-CANCER; HIGH PREVALENCE; WOMENS HEALTH; BREAST; ADENOCARCINOMA; MORTALITY; DESIGN; POLYMORPHISMS AB A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate-adjusted odds ratios (ORs) = 1.76, 95% confidence interval (Cl) = 1.19-2.61]. A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% Cl = 1.12-1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% Cl = 0.52-1.31), breast cancer (OR = 1.21, 95% Cl = 0.97-1.51) or colorectal cancer (OR = 1.17, 95% Cl = 0.93-1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study. C1 [Jacobs, Eric J.; Newton, Christina C.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [Chanock, Stephen J.; Amundadottir, Laufey] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [LaCroix, Andrea; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [McWilliams, Robert R.] Mayo Clin, Coll Med, Dept Oncol, Rochester, MN USA. [Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA. [Arslan, Alan A.] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Environm Med, New York, NY USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA. [Helzlsouer, Kathy] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Petersen, Gloria] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Agalliu, Ilir] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Allen, Naomi E.] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Boutron-Ruault, Marie-Christine] INSERM, F-75654 Paris 13, France. [Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, Villejuif, France. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med & Aging, Boston, MA 02115 USA. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Canzian, Federico] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Clipp, Sandra] George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Phys Hlth Study, Div Aging Cardiovasc Dis & Prevent Med, Boston, MA 02115 USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giovannucci, Edward L.] Harvard Univ, Sch Med, Dept Nutr, Boston, MA USA. [Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Kraft, Peter; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Jacobs, Kevin B.] BioInformed LLC, Gaithersburg, MD USA. [Jacobs, Kevin B.] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Jenab, Mazda] Int Agcy Res Canc, F-69372 Lyon, France. [Lynch, Shannon M.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Sund, Malin] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden. [Mouw, Tracy; Peeters, Petra H. M.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England. [Overvad, Kim] Aarhus Univ Hosp, Dept Cardiol, Aalborg Hosp, Aalborg, Denmark. [Overvad, Kim] Aarhus Univ Hosp, Dept Clin Epidemiol, Aalborg Hosp, Aalborg, Denmark. [Palli, Domenico] Canc Res & Prevent Inst ISPO Florence, Mol & Nutr Epidemiol Unit, Florence, Italy. [Peeters, Petra H. M.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Rajkovic, Aleksandar] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. [Trichopoulos, Dimitrios] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Jacobs, EJ (reprint author), Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. EM ejacobs@cancer.org RI Boutron Ruault, Marie-Christine/G-3705-2013; Boutron, Marie-Christine/K-8168-2013; Boutron-Ruault, Marie-Christine/H-3936-2014; Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016; OI Amundadottir, Laufey/0000-0003-1859-8971; Tobias, Geoffrey/0000-0002-2878-8253; Sund, Malin/0000-0002-7516-9543; PALLI, Domenico/0000-0002-5558-2437; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NCI NIH HHS [R01 CA082729, R01 CA097193, R01 CA124908, R37 CA070867, U01 CA098710-04] NR 36 TC 37 Z9 37 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 15 PY 2010 VL 127 IS 6 BP 1421 EP 1428 DI 10.1002/ijc.25148 PG 8 WC Oncology SC Oncology GA 643ZL UT WOS:000281340100017 PM 20049842 ER PT J AU Margolis, M Kaiser, L Christie, J AF Margolis, Mitchell Kaiser, Larry Christie, Jason TI Patient Decisions to Undergo Surgery for Early-Stage Lung Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID RACIAL-DIFFERENCES; BELIEF C1 [Margolis, Mitchell] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kaiser, Larry] Univ Texas Houston Hlth Sci Ctr, Houston, TX USA. [Christie, Jason] Univ Penn, Philadelphia, PA 19104 USA. RP Margolis, M (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. EM mitchell.margolis@va.gov NR 5 TC 0 Z9 0 U1 0 U2 0 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 15 PY 2010 VL 304 IS 11 BP 1165 EP 1165 DI 10.1001/jama.2010.1311 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 649LF UT WOS:000281770600002 PM 20841526 ER PT J AU Jena, AB Baldwin, DC Daugherty, SR Meltzer, DO Arora, VM AF Jena, Anupam B. Baldwin, DeWitt C., Jr. Daugherty, Steven R. Meltzer, David O. Arora, Vineet M. TI Presenteeism Among Resident Physicians SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID SICK; WORK C1 [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Baldwin, DeWitt C., Jr.] Accreditat Council Grad Med Educ, Chicago, IL USA. [Daugherty, Steven R.] Rush Med Coll, Dept Psychol, Chicago, IL 60612 USA. [Meltzer, David O.; Arora, Vineet M.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Jena, AB (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM varora@medicine.bsd.uchicago.edu RI Meltzer, David/C-2926-2009 OI Meltzer, David/0000-0003-2790-7393 NR 5 TC 28 Z9 30 U1 1 U2 8 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 15 PY 2010 VL 304 IS 11 BP 1166 EP 1168 DI 10.1001/jama.2010.1315 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 649LF UT WOS:000281770600006 PM 20841527 ER PT J AU Lindenhovius, ALC Doornberg, JN Ring, D Jupiter, JB AF Lindenhovius, Anneluuk L. C. Doornberg, Job N. Ring, David Jupiter, Jesse B. TI Health Status After Open Elbow Contracture Release SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID QUALITY-OF-LIFE; ULNAR NERVE; POSTTRAUMATIC CONTRACTURE; OPERATIVE RELEASE; ADULT ATTACHMENT; PAIN INTENSITY; STIFF ELBOW; DISABILITY; DEPRESSION; FLEXION AB Background: Operative contracture release may improve motion of a posttraumatic stiff elbow. In this study, we tested the hypothesis that improvement in ulnohumeral motion after elbow contracture release leads to improvement in general health status and decreases upper-extremity-specific disability. Methods: Twenty-three patients with posttraumatic loss of >= 30 degrees of elbow flexion or extension who elected to have an open elbow capsulectomy completed the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) and the Short Form-36 (SF-36) preoperatively and at least one year postoperatively. Pain was measured with use of the American Shoulder and Elbow Surgeons (ASES) Elbow Evaluation instrument. Four patients underwent additional, subsequent procedures to address residual elbow stiffness. Results: One patient who needed several additional procedures, including a total elbow arthroplasty, was considered to have had a failure of the operative contracture release and was excluded from the analysis; this left twenty-two patients in the study. On the average, the arc of flexion and extension improved from 51 degrees preoperatively to 106 degrees postoperatively; the DASH score, from 38 points to 18 points; the SF-36 Physical Component Summary (PCS) score, from 39 points to 49 points (all p < 0.05); and the SF-36 Mental Component Summary (MCS) score, from 49 points to 54 points (p < 0.05). There was no significant correlation between the improvement in the arc of flexion and extension and the improvement in the DASH (p = 0.53), PCS (p = 0.73), or MCS (p = 0.41) score. There also was no correlation between the final arc of flexion and extension and the final DASH score (p = 0.39 for the total score, p = 0.52 for the PCS score, and p = 0.42 for the MCS score). Conclusions: Health status and disability scores improve after open elbow contracture release, but the improvements do not correlate with the improvement in elbow motion. Among multiple objective and subjective factors, pain was a strong predictor of the final general health status and arm-specific disability. C1 [Lindenhovius, Anneluuk L. C.; Doornberg, Job N.; Ring, David; Jupiter, Jesse B.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Lindenhovius, ALC (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, 55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 32 TC 24 Z9 25 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP 15 PY 2010 VL 92A IS 12 BP 2187 EP 2195 DI 10.2106/JBJS.H.01594 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 649PQ UT WOS:000281785100007 PM 20844161 ER PT J AU Hang, L Setiawan, T Blum, AM Urban, J Stoyanoff, K Arihiro, S Reinecker, HC Weinstock, JV AF Hang, Long Setiawan, Tommy Blum, Arthur M. Urban, Joseph Stoyanoff, Korynn Arihiro, Seiji Reinecker, Hans-Christian Weinstock, Joel V. TI Heligmosomoides polygyrus Infection Can Inhibit Colitis through Direct Interaction with Innate Immunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; INFLAMMATORY-BOWEL-DISEASE; INTESTINAL HOMEOSTASIS; IL-10-DEFICIENT MICE; DENDRITIC CELLS; HELMINTHS; MECHANISM; RESPONSES AB Less developed countries have a low incidence of immunological diseases like inflammatory bowel disease (IBD), perhaps prevented by the high prevalence of helminth infections in their populations. In the Rag IL-10(-/-) T cell transfer model of colitis, Heligmosomoides polygyrus, an intestinal helminth, prevents and reverses intestinal inflammation. This model of colitis was used to explore the importance of innate immunity in H. polygyrus protection from IBD. Rag mice briefly exposed to H. polygyrus before reconstitution with IL-10(-/-) colitogenic T cells are protected from colitis. Exposure to H. polygyrus before introduction of IL-10(-/-) and OT2 T cells reduced the capacity of the intestinal mucosa to make IFN-gamma and IL-17 after either anti-CD3 mAb or OVA stimulation. This depressed cytokine response was evident even in the absence of colitis, suggesting that the downmodulation in proinflammatory cytokine secretion was not just secondary to improvement in intestinal inflammation. Following H. polygyrus infection, dendritic cells (DCs) from the lamina propria of Rag mice displayed decreased expression of CD80 and CD86, and heightened expression of plasmacytoid dendritic cell Ag-1 and CD40. They were also less responsive to lamina proprias, producing less IL-12p40 and IL-10. Also diminished was their capacity to present OVA to OT2 T cells. These experiments infer that H. polygyrus does not require direct interactions with Tor B cells to render animals resistant to colitis. DCs have an important role in driving both murine and human IBD. Data suggest that phenotypic alternations in mucosal DC function are part of the regulatory process. The Journal of Immunology, 2010, 185: 3184-3189. C1 [Hang, Long; Setiawan, Tommy; Blum, Arthur M.; Stoyanoff, Korynn; Weinstock, Joel V.] Tufts Med Ctr, Div Gastroenterol Hepatol, Dept Internal Med, Boston, MA 02111 USA. [Arihiro, Seiji; Reinecker, Hans-Christian] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02111 USA. [Urban, Joseph] ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA. RP Weinstock, JV (reprint author), Tufts Med Ctr, Div Gastroenterol, Box 233,800 Washington St, Boston, MA 02111 USA. EM jweinstock2@tufts-nemc.org OI Urban, Joseph/0000-0002-1590-8869 FU National Institutes of Health [DK38327, DK058755]; Broad Foundation; Schneider Family; Friedman Family; Gilman Family FX This work was supported by Grants DK38327 and DK058755 from the National Institutes of Health, the Broad Foundation, the Schneider Family, the Friedman Family, and the Gilman Family. NR 27 TC 47 Z9 50 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2010 VL 185 IS 6 BP 3184 EP 3189 DI 10.4049/jimmunol.1000941 PG 6 WC Immunology SC Immunology GA 646RI UT WOS:000281559300009 PM 20702728 ER PT J AU Garay, J D'Angelo, JA Park, Y Summa, CM Aiken, ML Morales, E Badizadegan, K Fiebiger, E Dickinson, BL AF Garay, Jone D'Angelo, June A. Park, YongKeun Summa, Christopher M. Aiken, Martha L. Morales, Eric Badizadegan, Kamran Fiebiger, Edda Dickinson, Bonny L. TI Crosstalk Between PKA and Epac Regulates the Phenotypic Maturation and Function of Human Dendritic Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR EXPRESSION; DEPENDENT PROTEIN-KINASE; CHOLERA-TOXIN; IMMUNE-RESPONSES; CYCLIC-AMP; PEYERS-PATCHES; LYMPH-NODES; PERIPHERAL TOLERANCE; BINDING PROTEINS; STEADY-STATE AB The cAMP-dependent signaling pathways that orchestrate dendritic cell ( DC) maturation remain to be defined in detail. Although cAMP was previously thought to signal exclusively through protein kinase A (PKA), it is now clear that cAMP also activates exchange protein activated by cAMP ( Epac), a second major cAMP effector. Whether cAMP signaling via PKA is sufficient to drive DC maturation or whether Epac plays a role has not been examined. In this study, we used cAMP analogs to selectively activate PKA or Epac in human monocyte-derived DCs and examined the effect of these signaling pathways on several hallmarks of DC maturation. We show that PKA activation induces DC maturation as evidenced by the increased cell-surface expression of MHC class II, costimulatory molecules, and the maturation marker CD83. PKA activation also reduces DC endocytosis and stimulates chemotaxis to the lymph node-associated chemokines CXCL12 and CCL21. Although PKA signaling largely suppresses cytokine production, the net effect of PKA activation translates to enhanced DC activation of allogeneic T cells. In contrast to the stimulatory effects of PKA, Epac signaling has no effect on DC maturation or function. Rather, Epac suppresses the effects of PKA when both pathways are activated simultaneously. These data reveal a previously unrecognized crosstalk between the PKA and Epac signaling pathways in DCs and raise the possibility that therapeutics targeting PKA may generate immunogenic DCs, whereas those that activate Epac may produce tolerogenic DCs capable of attenuating allergic or autoimmune disease. The Journal of Immunology, 2010, 185: 3227-3238. C1 [Garay, Jone; D'Angelo, June A.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA 70112 USA. [Park, YongKeun] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. [Summa, Christopher M.; Aiken, Martha L.; Morales, Eric; Dickinson, Bonny L.] Childrens Hosp, Res Inst Children, New Orleans, LA 70118 USA. [Dickinson, Bonny L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA 70118 USA. [Summa, Christopher M.] Univ New Orleans, Dept Comp Sci, New Orleans, LA 70148 USA. [Badizadegan, Kamran] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Fiebiger, Edda] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Gastroenterol & Nutr, Boston, MA 02115 USA. RP Dickinson, BL (reprint author), W Virginia Sch Osteopath Med, 400 N Lee St, Lewisburg, WV 24901 USA. EM bdickinson@osteo.wvsom.edu RI Park, YongKeun/B-9017-2009 FU Louisiana Board of Regents; Louisiana State University Health Science Center; National Institutes of Health [P41-RR02594, R01AI075037]; Research Institute for Children FX This work was supported by Grant NSF(2008)-PFUND-101 from the Louisiana Board of Regents ( to B. L. D.), a Louisiana State University Health Science Center Research Enhancement Fund New Project Grant ( to B. L. D.), National Institutes of Health Grant P41-RR02594 awarded to the Massachusetts Institute of Technology Laser Biomedical Research Center, National Institutes of Health Grant R01AI075037 ( to E. F.), and funds from the Research Institute for Children. NR 78 TC 20 Z9 21 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 SEP 15 PY 2010 VL 185 IS 6 BP 3227 EP 3238 DI 10.4049/jimmunol.0903066 PG 12 WC Immunology SC Immunology GA 646RI UT WOS:000281559300014 PM 20729327 ER PT J AU Brady, BL Oropallo, MA Yang-Iott, KS Serwold, T Hochedlinger, K Jaenisch, R Weissman, IL Bassing, CH AF Brady, Brenna L. Oropallo, Michael A. Yang-Iott, Katherine S. Serwold, Thomas Hochedlinger, Konrad Jaenisch, Rudolf Weissman, Irving L. Bassing, Craig H. TI Position-Dependent Silencing of Germline V beta Segments on TCR beta Alleles Containing Preassembled V beta DJ beta C beta 1 Genes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL DEVELOPMENT; ANTISENSE INTERGENIC TRANSCRIPTION; V(D)J RECOMBINATION; CHAIN GENE; THYMOCYTE DIFFERENTIATION; CHROMATIN CHANGES; EXCLUSION; EXPRESSION; LOCUS; REARRANGEMENT AB The genomic organization of TCR beta loci enables V beta-to-DJ beta 2 rearrangements on alleles with assembled V beta DJ beta C beta 1 genes, which could have deleterious physiologic consequences. To determine whether such V beta rearrangements occur and, if so, how they might be regulated, we analyzed mice with TCR beta alleles containing preassembled functional V beta DJ beta C beta 1 genes. V beta 10 segments were transcribed, rearranged, and expressed in thymocytes when located immediately upstream of a V beta 1DJ beta C beta 1 gene, but not on alleles with a V beta 14DJ beta C beta 1 gene. Germline V beta 10 transcription was silenced in mature alpha beta T cells. This allele-dependent and developmental stage-specific silencing of V beta 10 correlated with increased CpG methylation and decreased histone acetylation over the V beta 10 promoter and coding region. Transcription, rearrangement, and expression of the V beta 4 and V beta 16 segments located upstream of V beta 10 were silenced on alleles containing either V beta DJ beta C beta 1 gene; sequences within V beta 4, V beta 16, and the V beta 4/V beta 16-V beta 10 intergenic region exhibited constitutive high CpG methylation and low histone acetylation. Collectively, our data indicate that the position of V beta segments relative to assembled V beta DJ beta C beta 1 genes influences their rearrangement and suggest that DNA sequences between V beta segments may form boundaries between active and inactive V beta chromatin domains upstream of V beta DJ beta C beta genes. The Journal of Immunology, 2010, 185: 3564-3573. C1 [Brady, Brenna L.; Oropallo, Michael A.; Bassing, Craig H.] Childrens Hosp Philadelphia, Immunol Grad Grp, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Brady, Brenna L.; Yang-Iott, Katherine S.; Bassing, Craig H.] Childrens Hosp Philadelphia, Div Canc Pathobiol, Dept Pathol & Lab Med, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Brady, Brenna L.; Yang-Iott, Katherine S.; Bassing, Craig H.] Univ Penn, Abramson Family Canc Res Inst, Sch Med, Philadelphia, PA 19104 USA. [Serwold, Thomas] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Joslin Diabet Ctr, Boston, MA 02114 USA. [Hochedlinger, Konrad] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Canc Ctr, Boston, MA 02114 USA. [Hochedlinger, Konrad] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Jaenisch, Rudolf] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Weissman, Irving L.] Stanford Univ, Sch Med, Beckman Ctr, Dept Pathol, Stanford, CA 94305 USA. [Weissman, Irving L.] Stanford Univ, Sch Med, Dept Dev Biol, Beckman Ctr, Stanford, CA 94305 USA. RP Bassing, CH (reprint author), Childrens Hosp Philadelphia, Immunol Grad Grp, Ctr Childhood Canc Res, 4054 Colket Translat Res Bldg,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bassing@email.chop.edu FU Department of Pathology and Laboratory Medicine; Center for Childhood Cancer Research of the Children's Hospital of Philadelphia; Abramson Family Cancer Research Institute; University of Pennsylvania [TG GM-07229] FX This work was supported by the Department of Pathology and Laboratory Medicine and the Center for Childhood Cancer Research of the Children's Hospital of Philadelphia (to C.H.B.) and the Abramson Family Cancer Research Institute (to C.H.B.). B.L.B. is supported by Training Grant TG GM-07229 of the University of Pennsylvania. C.H.B. was a Pew Scholar in the Biomedical Sciences. NR 46 TC 12 Z9 12 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 SEP 15 PY 2010 VL 185 IS 6 BP 3564 EP 3573 DI 10.4049/jimmunol.0903098 PG 10 WC Immunology SC Immunology GA 646RI UT WOS:000281559300050 PM 20709953 ER PT J AU Boulware, DR Bonham, SC Meya, DB Wiesner, DL Park, GS Kambugu, A Janoff, EN Bohjanen, PR AF Boulware, David R. Bonham, Shulamith C. Meya, David B. Wiesner, Darin L. Park, Gregory S. Kambugu, Andrew Janoff, Edward N. Bohjanen, Paul R. TI Paucity of Initial Cerebrospinal Fluid Inflammation in Cryptococcal Meningitis Is Associated with Subsequent Immune Reconstitution Inflammatory Syndrome SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; COLONY-STIMULATING FACTOR; T-CELLS; NEOFORMANS INFECTION; DENDRITIC CELLS; CASE-DEFINITION; EARLY MORTALITY; AMPHOTERICIN-B; IFN-GAMMA; ACTIVATION AB Background. Cryptococcal meningitis (CM)-related immune reconstitution inflammatory syndrome (IRIS) complicates antiretroviral therapy (ART) in 20%-40% of ART-naive persons with AIDS and prior CM. Pathogenesis is unknown. Methods. We compared initial cerebrospinal fluid (CSF) cultures, inflammatory markers, and cytokine profiles in ART-naive patients with AIDS who did or did not subsequently develop IRIS after starting ART. We also compared results obtained at IRIS events or CM relapse. Results. Of 85 subjects with CM, 33 (39%) developed CM-related IRIS and 5 (6%) developed culture-positive CM relapse. At CM diagnosis, subjects subsequently developing IRIS had less inflammation, with decreased CSF leukocytes, protein, interferon-gamma, interleukin-6, interleukin-8, and tumor necrosis factor-alpha, compared with subjects not developing IRIS (P<.05, for each). Initial CSF white blood cell counts <= 25 cells/mu L and protein levels <= 50 mg/dL were associated with development of IRIS (odds ratio, 7.2 [95% confidence interval, 2.7-18.7]; P<.001). Compared with baseline levels, we identified CSF elevations of interferon-gamma, tumor necrosis factor-alpha, granulocyte colony-stimulating factor, vascular-endothelial growth factor, and eotaxin (CCL11) (P<.05, for each) at the time of IRIS but minimal inflammatory changes in those with CM relapse. Conclusions. Patients who subsequently develop CM-related IRIS exhibit less initial CSF inflammation at the time of CM diagnosis, compared with those who do not develop IRIS. The inflammatory CSF cytokine profiles observed at time of IRIS can distinguish IRIS from CM relapse. C1 [Boulware, David R.; Bonham, Shulamith C.; Meya, David B.; Kambugu, Andrew; Bohjanen, Paul R.] Univ Minnesota, Dept Med, Div Infect Dis & Int Med, Minneapolis, MN 55455 USA. [Boulware, David R.; Bonham, Shulamith C.; Wiesner, Darin L.; Park, Gregory S.; Bohjanen, Paul R.] Univ Minnesota, Ctr Infect Dis & Microbiol Translat Res, Minneapolis, MN 55455 USA. [Wiesner, Darin L.; Bohjanen, Paul R.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. [Meya, David B.; Kambugu, Andrew] Makerere Univ, Infect Dis Inst, Kampala, Uganda. [Janoff, Edward N.] Univ Colorado, Denver Sch Med, Denver Vet Affairs Med Ctr, Mucosal & Vaccine Res Program Colorado,Div Infect, Denver, CO 80202 USA. RP Boulware, DR (reprint author), MMC 250,420 Delaware St SE, Minneapolis, MN 55455 USA. EM boulw001@umn.edu RI Boulware, David/B-5516-2011; Boulware, David/I-4533-2013; Bohjanen, Paul/B-2329-2015; OI Bohjanen, Paul/0000-0002-2772-3597; Meya, David/0000-0002-4138-240X; Boulware, David/0000-0002-4715-0060 FU NCRR NIH HHS [K12 RR023247, K12 RR023247-04, K12RR023247-04]; NIAID NIH HHS [K23 AI073192, K23 AI073192-01A2, K23AI073192-01A2, L30 AI066779, L30 AI066779-03, L30AI066779, R03 AI078750, R03 AI078750-02, R03AI078750-01, T32 AI055433, T32 AI055433-05, T32AI055433-05] NR 45 TC 81 Z9 82 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 15 PY 2010 VL 202 IS 6 BP 962 EP 970 DI 10.1086/655785 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 640YV UT WOS:000281091200019 PM 20677939 ER PT J AU Gascon, E Gaillard, S Malapert, P Liu, Y Rodat-Despoix, L Samokhvalov, IM Delmas, P Helmbacher, F Maina, F Moqrich, A AF Gascon, Eduardo Gaillard, Stephane Malapert, Pascale Liu, Yang Rodat-Despoix, Lise Samokhvalov, Igor M. Delmas, Patrick Helmbacher, Francoise Maina, Flavio Moqrich, Aziz TI Hepatocyte Growth Factor-Met Signaling Is Required for Runx1 Extinction and Peptidergic Differentiation in Primary Nociceptive Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article ID DORSAL-ROOT GANGLIA; GENE-RELATED PEPTIDE; SENSORY NEURONS; NEURAL CREST; DRG NEURONS; CELL FATE; RECEPTOR; SPECIFICATION; EXPRESSION; SURVIVAL AB Nociceptors in peripheral ganglia display a remarkable functional heterogeneity. They can be divided into the following two major classes: peptidergic and nonpeptidergic neurons. Although RUNX1 has been shown to play a pivotal role in the specification of nonpeptidergic neurons, the mechanisms driving peptidergic differentiation remain elusive. Here, we show that hepatocyte growth factor (HGF)-Met signaling acts synergistically with nerve growth factor-tyrosine kinase receptor A to promote peptidergic identity in a subset of prospective nociceptors. We provide in vivo evidence that a population of peptidergic neurons, derived from the RUNX1 lineage, require Met activity for the proper extinction of Runx1 and optimal activation of CGRP(calcitonin gene-related peptide). Moreover, we show that RUNX1 in turn represses Met expression in nonpeptidergic neurons, revealing a bidirectional cross talk between Met and RUNX1. Together, our novel findings support a model in which peptidergic versus nonpeptidergic specification depends on a balance between HGF-Met signaling and Runx1 extinction/maintenance. C1 [Gascon, Eduardo; Gaillard, Stephane; Malapert, Pascale; Helmbacher, Francoise; Maina, Flavio; Moqrich, Aziz] Univ Aix Marseille 2, CNRS, UMR 6216, Inst Biol Dev Marseille Luminy, F-13288 Marseille 09, France. [Liu, Yang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Liu, Yang] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Samokhvalov, Igor M.] RIKEN, Ctr Dev Biol, Lab Stem Cell Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan. [Rodat-Despoix, Lise; Delmas, Patrick] Univ Aix Marseille 2, CNRS, UMR 6231, Ctr Rech Neurobiol & Neurophysiol Marseille, F-13344 Marseille, France. RP Moqrich, A (reprint author), Univ Aix Marseille 2, CNRS, UMR 6216, Inst Biol Dev Marseille Luminy, Campus Luminy Case 907, F-13288 Marseille 09, France. EM moqrich@ibdml.univ-mrs.fr OI moqrich, aziz/0000-0002-1937-1675; Gascon, Eduardo/0000-0002-2625-5509; HELMBACHER, Francoise/0000-0001-6822-1246 FU Centre National de la Recherche Scientifique; Action Thematique et Incitative sur Programme; Agence Nationale pour la Recherche [ANR-Neuro-2006]; Fondation pour le Recherche Medicale; Association Francaise contre les Myopathies FX This work was supported by grants from Centre National de la Recherche Scientifique: Action Thematique et Incitative sur Programme, Agence Nationale pour la Recherche (ANR-Neuro-2006) (to A.M.), Fondation pour le Recherche Medicale (to E.G.), and Association Francaise contre les Myopathies (to F.M.). We thank A. Patapoutian, J. Ewbank, and Q. Ma for comments on the manuscript, F. Lamballe and M. Genestine for kindly providing mice, S. S. Thorgeirsson for the metflx/flx mice, Tom Jessell and Louis Reichardt for the RUNX1 and TrkA antibodies, and Prof. A. Friedman for the human Runx1 plasmid. E.G., S.G., and A.M. conceived the experiments; E.G. and S.G. performed all the experiments; P.M., Y.L., P.D., L.R.-D., I.M.S., F.H., and F.M. provided intellectual, technical, and logistical contribution; and E.G., S.G., and A.M. cowrote the paper. NR 37 TC 19 Z9 19 U1 0 U2 3 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 15 PY 2010 VL 30 IS 37 BP 12414 EP 12423 DI 10.1523/JNEUROSCI.3135-10.2010 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 649UF UT WOS:000281798700019 PM 20844136 ER PT J AU Chen, DH Raskind, WH Parson, WW Sonnen, JA Vu, T Zheng, YL Matsushita, M Wolff, J Lipe, H Bird, TD AF Chen, Dong-Hui Raskind, Wendy H. Parson, William W. Sonnen, Joshua A. Vu, Tiffany Zheng, YunLin Matsushita, Mark Wolff, John Lipe, Hillary Bird, Thomas D. TI A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: Phenotypic spectrum and structural study of FHL1 mutations SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE X-linked myopathy; Scapuloperoneal; FHL1; Neurogenetics; Muscular dystrophy; Genetic diagnosis ID REDUCING BODY MYOPATHY; ELECTROSTATIC ENERGIES; BINDING PROTEIN; GENE; DOMINANT AB An X-linked myopathy was recently associated with mutations in the four-and-a-half-LIM domains 1 (FHL1) gene. We identified a family with late onset, slowly progressive weakness of scapuloperoneal muscles in three brothers and their mother. A novel missense mutation in the LIM2 domain of FHL1 (W122C) co-segregated with disease in the family. The phenotype was less severe than that in other reported families. Muscle biopsy revealed myopathic changes with FHL1 inclusions that were ubiquitin- and desmin-positive. This mutation provides additional evidence for X-linked myopathy caused by a narrow spectrum of mutations in FHL1, mostly in the LIM2 domain. Molecular dynamics (MD) simulations of the newly identified mutation and five previously published missense mutations in the LIM2 domain revealed no major distortions of the protein structure or disruption of zinc binding. There were, however, increases in the nonpolar, solvent-accessible surface area in one or both of two clusters of residues, suggesting that the mutant proteins have a variably increased propensity to aggregate. Review of the literature shows a wide range of phenotypes associated with mutations in FHL1. However, recognizing the typical scapuloperoneal phenotype and X-linked inheritance pattern will help clinicians arrive at the correct diagnosis. Published by Elsevier B.V. C1 [Chen, Dong-Hui; Lipe, Hillary; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Raskind, Wendy H.; Vu, Tiffany; Zheng, YunLin; Matsushita, Mark; Wolff, John; Bird, Thomas D.] Univ Washington, Dept Med, Seattle, WA USA. [Raskind, Wendy H.; Bird, Thomas D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Parson, William W.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Sonnen, Joshua A.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Wolff, John; Lipe, Hillary; Bird, Thomas D.] Vet Affairs Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Raskind, Wendy H.] Vet Affairs Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. RP Bird, TD (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-182 GRECC, Seattle, WA 98108 USA. EM tomnroz@uw.edu RI Sonnen, 37382016/H-3738-2016 OI Sonnen, 37382016/0000-0001-9267-8705 FU Veterans Affairs; National Institutes of Health [NS069719]; National Science Foundation [MCB-0641640] FX This research was supported by the Veterans Affairs Medical Research funds (TDB, HL, WHR, and JW), National Institutes of Health grant NS069719 (WHR), and National Science Foundation grant MCB-0641640 (WWP). Randy Small, Department of Pathology, University of Washington, provided technical assistance for the histopathology studies. NR 24 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD SEP 15 PY 2010 VL 296 IS 1-2 BP 22 EP 29 DI 10.1016/j.jns.2010.06.017 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 643CY UT WOS:000281272300004 PM 20633900 ER PT J AU Huang, JH Burke, PS Cung, TDH Pereyra, F Toth, I Walker, BD Borges, L Lichterfeld, M Yu, XG AF Huang, Jinghe Burke, Patrick S. Cung, Thai Duong Hong Pereyra, Florencia Toth, Ildiko Walker, Bruce D. Borges, Luis Lichterfeld, Mathias Yu, Xu G. TI Leukocyte Immunoglobulin-Like Receptors Maintain Unique Antigen-Presenting Properties of Circulating Myeloid Dendritic Cells in HIV-1-Infected Elite Controllers SO JOURNAL OF VIROLOGY LA English DT Article ID CD8(+) T-CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; CHRONIC HIV-1 INFECTION; CLASS-I MOLECULES; INHIBITORY RECEPTOR; MYELOMONOCYTIC CELLS; TRANSLATING INNATE; ADAPTIVE IMMUNITY; CUTTING EDGE; ACTIVATION AB Elite controllers maintain undetectable levels of HIV-1 replication in the absence of antiretroviral therapy, but the correlates of immune protection in this patient population are ill defined. Here, we demonstrate that in comparison to patients with progressive HIV-1 infection or healthy persons not infected with HIV-1, elite controllers have circulating myeloid dendritic cells with significantly increased antigen-presenting properties, while their ability to secrete proinflammatory cytokines is substantially diminished. This unique functional profile is associated with a distinct surface expression pattern of immunomodulatory leukocyte-immunoglobulin- like receptors (LILR) and a strong and selective upregulation of LILRB1 and LILRB3. Blockade of these two receptors by monoclonal antibodies or short interfering RNA (siRNA) abrogated the specific antigen-presenting properties of dendritic cells, implying an important regulatory role of these molecules. These data reveal previously unrecognized innate components of immune protection against HIV-1 in elite controllers and offer novel perspectives for the manipulation of host immunity for the prevention and treatment of HIV-1 infection. C1 [Huang, Jinghe; Burke, Patrick S.; Cung, Thai Duong Hong; Pereyra, Florencia; Toth, Ildiko; Walker, Bruce D.; Yu, Xu G.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Borges, Luis] Amgen Inc, Seattle, WA USA. [Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. RP Yu, XG (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, 149 13th St,Room 5219, Boston, 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 (grants AI078799 and AI074415 to X.G.Y.). X.G.Y. and M.L. are both recipients of a 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 49 TC 36 Z9 37 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP 15 PY 2010 VL 84 IS 18 BP 9463 EP 9471 DI 10.1128/JVI.01009-10 PG 9 WC Virology SC Virology GA 641FP UT WOS:000281110500047 PM 20631139 ER PT J AU Zhang, X Zhou, YL Klibanski, A AF Zhang, Xun Zhou, Yunli Klibanski, Anne TI Isolation and characterization of novel pituitary tumor related genes: A cDNA representational difference approach SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Review DE cDNA representational difference analysis; Clinically non-functioning pituitary tumors; Maternally Expressed Gene 3 (MEG3) ID INTERACTING-PROTEIN GENE; INHIBITS ADIPOCYTE DIFFERENTIATION; DLK1-GTL2 IMPRINTED DOMAIN; FACTOR-II GENE; WILMS-TUMOR; H19 GENE; METHYLATED REGION; SUPPRESSOR GENE; FREQUENT LOSS; HUMAN HOMOLOG AB Recently, progress has been made in understanding human pituitary tumor pathogenesis by the investigation of differences in gene expression between normal pituitary tissue and pituitary tumors. A number of approaches, including differential display (DD), representational difference analysis (RDA), and microarray analysis have been used and several molecular targets potentially associated with pituitary tumor development and invasion have been identified. We have used RDA to compare gene expression patterns between normal human pituitary and clinically non-functioning pituitary adenomas, and identified genes with growth suppression function which are expressed in the normal pituitary but not in pituitary tumors. In particular, we have focused on an imprinted gene, Maternally Expressed Gene 3 (MEG3), which is specifically associated with clinically non-functioning pituitary adenomas of a gonadotroph lineage. MEG3 functions to suppress tumor cell growth, increase protein expression of the tumor suppressor p53, and selectively activate p53 target genes. Interestingly. MEG3 does not encode a protein but a non-coding RNA. Therefore, these studies have revealed novel mechanisms for the function of a non-coding RNA in pituitary physiology and tumorigenesis. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org FU NIH [R01DK40947]; Guthart Family Foundation; Jarislowsky Foundation FX The research in our laboratory has been supported by NIH Grant R01DK40947, The Guthart Family Foundation and the Jarislowsky Foundation. NR 83 TC 10 Z9 12 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD SEP 15 PY 2010 VL 326 IS 1-2 SI SI BP 40 EP 47 DI 10.1016/j.mce.2010.02.040 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 642MU UT WOS:000281219700008 PM 20211686 ER PT J AU Simon, KC Gao, XA Chen, HL Schwarzschild, MA Ascherio, A AF Simon, Kelly Claire Gao, Xiang Chen, Honglei Schwarzschild, Michael A. Ascherio, Alberto TI Calcium Channel Blocker Use and Risk of Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE calcium channel blockers; Parkinson's disease; antihypertensive ID NEURONAL VULNERABILITY; ANTIHYPERTENSIVES AB We investigated whether the use of calcium channel blockers (CCBs) was associated with a reduced risk of Parkinson's disease (PD) in two large prospective cohorts: the Nurses' Health Study (NHS) and Health Professionals' Follow- Up Study (HPFS). Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) to assess the association between use of CCBs and risk of PD adjusting for potential confounders. We identified 514 incident cases of PD during follow-up. No association between baseline use of CCBs (RR 5 1.18, 95% CI: 0.731.92), frequency of use or duration of use of CCBs and PD risk was observed (P > 0.2 for all). These findings do not support a role for CCBs in providing neuroprotection against development of PD. (C) 2010 Movement Disorder Society C1 [Simon, Kelly Claire; Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Simon, KC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2,3rd Floor, Boston, MA 02115 USA. EM ksimon@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU NIH/NINDS [R01 NS048517]; National Institute of Environmental Health Sciences; National Institute of Health [Z01ES101986]; National Institute of Health/National Research Service [T32 ES016645-01]; NHI/NINDS [R01 NS062879-01A2]; National Institute of Environmental Health Sciences, NIH [Z01ES101986]; Department of Defense/USAMRAA; RJG Foundation; Fox Foundation; American Parkinson's Disease Association; Parkinson's Disease Foundation; The Parkinson Study Group; University of Rochester; Harvard University; DoD (Department of the Army) [W81XWH-05-1-0117; 20052009] FX This work was supported by grant NIH/NINDS R01 NS048517 and in part by the Intramural Research Program of the National Institute of Environmental Health Sciences, the National Institute of Health (Z01ES101986).; K.C.S. was supported in 2009 by a National Institute of Health/National Research Service Award grant (T32 ES016645-01). X.G.: Advisory boards: Monitoring Committee of the Parkinson Study Group; Employment: Instructor in Medicine at Harvard Medical School; Research Scientist at Harvard School of Public Health; Associate Epidemiologist, Brigham and Women's Hospital; Grants: NHI/NINDS grant "Prospective study of restless legs syndrome'' (R01 NS062879-01A2), role: PI. H.C. is an employee of the federal government and has received funding from the intramural research program of the National Institute of Environmental Health Sciences, NIH (Z01ES101986). M.A.S.: Employment: Massachusetts General Hospital, Harvard University; Grant support: NIH/NINDS, Department of Defense/USAMRAA, RJG Foundation, Hartford Foundation/American Federation for Aging Research, Michael J. Fox Foundation, American Parkinson's Disease Association, Parkinson's Disease Foundation, The Parkinson Study Group, University of Rochester, Harvard University; Honoraria: Emory University, University of Pennsylvania. A.A.: Scientific advisory boards: Michael J. Fox Foundation 2008-2009; Editorial advisory boards: Neurology, Associate Editor 2008-2009; Annals of Neurology, Associate Editor 2008-2009; Honoraria: From Merck-Serono for scientific presentation 2009-12-15; Grants: DoD (Department of the Army) W81XWH-05-1-0117; 20052009; Role: PI; NIH R01 NS045893; 2006-2011; Role: PI; NIH R01 NS047467; 2005-2009; Role: PI; NIH R01 NS48517; 2005-2010; Role: PI; NIH/NINDS R01 NS042194; 2005-2010; Role: PI; NIH R01 NS046635; 2008-2013; Role: PI; DoD: No Award Number; 2008-2011; Role: PI; Michael J. Fox Foundation: No Award Number; 2008-2012; Role: Co-PI. NR 11 TC 20 Z9 20 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2010 VL 25 IS 12 BP 1818 EP 1822 DI 10.1002/mds.23191 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 655VN UT WOS:000282283100007 PM 20669249 ER PT J AU Hyson, HC Kieburtz, K Shoulson, I McDermott, M Ravina, B de Blieck, EA Cudkowicz, ME Ferrante, RJ Como, P Frank, S Zimmerman, C Cudkowicz, ME Ferrante, K Newhall, K Jennings, D Kelsey, T Walker, F Hunt, V Daigneault, S Goldstein, M Weber, J Watts, A Beal, MF Browne, SE Metakis, LJ AF Hyson, H. Christopher Kieburtz, Karl Shoulson, Ira McDermott, Michael Ravina, Bernard de Blieck, Elisabeth A. Cudkowicz, Merit E. Ferrante, Robert J. Como, Peter Frank, Sam Zimmerman, Carol Cudkowicz, Merit E. Ferrante, Kimberly Newhall, Kristyn Jennings, Danna Kelsey, Tammie Walker, Francis Hunt, Vicki Daigneault, Susan Goldstein, Michele Weber, Joseph Watts, Arthur Beal, M. Flint Browne, Susan E. Metakis, Linda J. CA Huntington Study Grp Pre2CARE inve TI Safety and Tolerability of High-Dosage Coenzyme Q(10) in Huntington's Disease and Healthy Subjects SO MOVEMENT DISORDERS LA English DT Article DE Huntington's disease; coenzyme Q10; safety; tolerability ID ENERGY-METABOLISM; TRIAL AB Coenzyme Q10 (CoQ(10)), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ(10) dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ(10) in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ(10), increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ(10) blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ(10). The most common adverse events seen were GI symptoms. Mean (+/- SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.2661.27 mu g/mL (baseline, n = 28), 5.59 +/- 2.24 mu g/mL (1,200 mg/day, week 4, n = 26), 6.38 +/- 3.25 mu g/mL (2,400 mg/day, week 8, n = 25), 7.49 +/- 4.09 mu g/mL (3,600 mg/day, week 12, n = 23), and 6.78 +/- 3.36 mu g/mL (3,600 mg/day, week 20, n = 20). CoQ10 was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned. (C) 2010 Movement Disorder Society C1 [Hyson, H. Christopher] Univ Western Ontario, London, ON N6A 3K7, Canada. [Como, Peter; Frank, Sam; Zimmerman, Carol] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Cudkowicz, Merit E.; Cudkowicz, Merit E.; Ferrante, Kimberly; Newhall, Kristyn] Massachusetts Gen Hosp, Charlestown, MA USA. [Ferrante, Robert J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Ferrante, Robert J.] Edith Nourse Rogers Vet Adm Hosp, Bedford, MA USA. [Jennings, Danna; Kelsey, Tammie] Inst Neurodegenerat Disorders, New Haven, CT USA. [Walker, Francis; Hunt, Vicki] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Beal, M. Flint; Browne, Susan E.; Metakis, Linda J.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. RP Hyson, HC (reprint author), Univ Hosp, Room A10-325,339 Windermere Rd, London, ON N6A 5A5, Canada. EM chyson@uwo.ca OI Ferrante, Kimberly/0000-0002-6069-9226 FU High Q foundation FX We thank the High Q foundation for its financial support for carrying out this study. We also thank the following manufacturers for donating the product used in this study: Enzymatic Therapy Inc., Tishcon Corporation, and Health Wright Products Inc. NR 10 TC 38 Z9 40 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2010 VL 25 IS 12 BP 1924 EP 1928 DI 10.1002/mds.22408 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 655VN UT WOS:000282283100022 ER PT J AU Cipriani, S Desjardins, CA Burdett, TC Xu, Y Xu, K Schwarzschild, MA AF Cipriani, S. Desjardins, C. A. Burdett, T. C. Xu, Y. Xu, K. Schwarzschild, M. A. TI Astrocyte-Dependent Protection by Inosine and Urate in a Cellular Model of Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract C1 [Cipriani, S.; Desjardins, C. A.; Burdett, T. C.; Xu, Y.; Xu, K.; Schwarzschild, M. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2010 VL 25 SU 3 BP S723 EP S723 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 655WO UT WOS:000282286300504 ER PT J AU Marsh, L AF Marsh, L. TI Depression and Cognitive Dysfunction in PD: What is the Relationship? SO MOVEMENT DISORDERS LA English DT Meeting Abstract C1 [Marsh, L.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2010 VL 25 SU 3 BP S588 EP S588 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 655WO UT WOS:000282286300074 ER PT J AU Marsh, L AF Marsh, L. TI Neuropsychiatric Issues in Advancing PD: Clinical Spectrum and Resulting QOL Implications SO MOVEMENT DISORDERS LA English DT Meeting Abstract C1 [Marsh, L.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2010 VL 25 SU 3 BP S570 EP S570 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 655WO UT WOS:000282286300007 ER PT J AU Pan, C Hwang, H Zhang, J Hancock, A Shi, M Chung, K Leverenz, J Zabetian, C Peskind, E Jankovic, J Quinn, J Galasko, D Zhang, J AF Pan, C. Hwang, H. Zhang, J. Hancock, A. Shi, M. Chung, K. Leverenz, J. Zabetian, C. Peskind, E. Jankovic, J. Quinn, J. Galasko, D. Zhang, J. TI Identification of Plasma Glycoproteins Unique to Diagnosis and Correlated with Severity of Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract C1 [Pan, C.; Hwang, H.; Zhang, J.; Hancock, A.; Shi, M.; Zhang, J.] Univ Washington, Seattle, WA 98195 USA. [Chung, K.] Portland VA Med Ctr, Portland, OR USA. [Jankovic, J.] Baylor Coll Med, Houston, TX 77030 USA. [Quinn, J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Galasko, D.] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2010 VL 25 SU 3 BP S663 EP S663 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 655WO UT WOS:000282286300321 ER PT J AU Schmidt, PN Okun, MS Siderowf, A Nutt, JG O'Conner, GT Bloem, BR Olmstead, EM Guttman, M Simuni, T Cheng, E Parashos, S Marsh, L Malaty, IA Giladi, N Wu, S Oberdorf, J AF Schmidt, P. N. Okun, M. S. Siderowf, A. Nutt, J. G. O'Conner, G. T. Bloem, B. R. Olmstead, E. M. Guttman, M. Simuni, T. Cheng, E. Parashos, S. Marsh, L. Malaty, I. A. Giladi, N. Wu, S. Oberdorf, J. TI Are Results from PD Trials Generalizable? The NPF Database Reveals a Mismatch Between Typical Clinic Populations and Subjects in PD Trials SO MOVEMENT DISORDERS LA English DT Meeting Abstract C1 [Okun, M. S.; Malaty, I. A.; Wu, S.] Univ Florida, Gainesville, FL 32611 USA. [Siderowf, A.] Univ Penn, Philadelphia, PA 19104 USA. [Nutt, J. G.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [O'Conner, G. T.; Olmstead, E. M.] Dartmouth Med Sch, Hanover, NH USA. [Bloem, B. R.] Radboud Univ Nijmegen, Nijmegen, Netherlands. [Guttman, M.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Simuni, T.] Northwestern Univ, Evanston, IL 60208 USA. [Cheng, E.] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Giladi, N.] Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. RI Bloem, Bastiaan/E-3812-2010; Bloem, B.R./H-8013-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2010 VL 25 SU 3 BP S640 EP S640 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 655WO UT WOS:000282286300252 ER PT J AU Schwarzschild, MA Marek, K Eberly, S Oakes, D Shoulson, I Jennings, D Seibyl, J Ascherio, A AF Schwarzschild, M. A. Marek, K. Eberly, S. Oakes, D. Shoulson, I. Jennings, D. Seibyl, J. Ascherio, A. TI Serum Urate and Probability of Dopaminergic Deficit in Early Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract C1 [Schwarzschild, M. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eberly, S.; Oakes, D.; Shoulson, I.] Univ Rochester, Rochester, NY 14627 USA. [Ascherio, A.] Harvard Univ, Sch Publ Hlth, Channing Lab, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Ascherio, A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2010 VL 25 SU 3 BP S660 EP S660 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 655WO UT WOS:000282286300313 ER PT J AU Watson, GS Thomas, S Zabetian, CP Gerton, BK Kim, HM Samii, A Schantz, A Leverenz, JB AF Watson, G. S. Thomas, S. Zabetian, C. P. Gerton, B. K. Kim, H. M. Samii, A. Schantz, A. Leverenz, J. B. TI How Well Can Screening Instruments Discriminate Among PD Patients with Normal Cognition, Mild Impairments, and Dementia? SO MOVEMENT DISORDERS LA English DT Meeting Abstract C1 [Watson, G. S.; Samii, A.; Schantz, A.] Univ Washington, VA Puget Sound HCS, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP 15 PY 2010 VL 25 SU 3 BP S692 EP S692 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 655WO UT WOS:000282286300407 ER PT J AU Holt, SK Kwon, EM Koopmeiners, JS Lin, DW Feng, ZD Ostrander, EA Peters, U Stanford, JL AF Holt, Sarah K. Kwon, Erika M. Koopmeiners, Joseph S. Lin, Daniel W. Feng, Ziding Ostrander, Elaine A. Peters, Ulrike Stanford, Janet L. TI Vitamin D Pathway Gene Variants and Prostate Cancer Prognosis SO PROSTATE LA English DT Article DE vitamin D receptor; 1-alpha-hydroxylase; 24-hydroxylase; prostatic neoplasms; outcomes ID D-RECEPTOR GENE; RADICAL PROSTATECTOMY; 25-HYDROXYVITAMIN D-1-ALPHA-HYDROXYLASE; UNITED-STATES; COLON-CANCER; RISK; POLYMORPHISMS; ASSOCIATION; EXPRESSION; DIAGNOSIS AB BACKGROUND. Observational studies linking vitamin D deficiency with increased prostate cancer (PCa) mortality and the pleiotropic anticancer effects of vitamin D in malignant prostate cell lines have initiated trials examining potential therapeutic benefits of vitamin D metabolites. There have been some successes but efforts have been hindered by risk of inducing hypercalcemia. A limited number of studies have investigated associations between variants in vitamin D pathway genes with aggressive forms of PCa. Increased understanding of relevant germline genetic variation with disease outcome could aid in the development of vitamin-D-based therapies. METHODS. We undertook a comprehensive analysis of 48 tagging single-nucleotide polymorphisms (tagSNPs) in genes encoding for vitamin D receptor (VDR), vitamin D activating enzyme 1-alpha-hydroxylase (CYP27B1), and deactivating enzyme 24-hydroxylase (CYP24A1) in a cohort of 1,294 Caucasian cases with an average of 8 years of follow-up. Disease recurrence/progression and PCa-specific mortality risks were estimated using adjusted Cox proportional hazards regression. RESULTS. There were 139 cases with recurrence/progression events and 57 cases who died of PCa. Significantly altered risks of recurrence/progression were observed in relation to genotype for two VDR tagSNPs (rs6823 and rs2071358) and two CYP24A1 tagSNPs (rs927650 and rs2762939). Three VDR tagSNPs (rs3782905, rs7299460, and rs11168314), one CYP27B1 tagSNP (rs3782130), and five CYP24A1 tagSNPs (rs3787557, rs4809960, rs2296241, rs2585428, and rs6022999) significantly altered risks of PCa death. CONCLUSIONS. Genetic variations in vitamin D pathway genes were found to alter both risk of recurrence/progression and PCa-specific mortality. Prostate 70: 1448-1460, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Holt, Sarah K.; Koopmeiners, Joseph S.; Feng, Ziding; Peters, Ulrike; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Kwon, Erika M.] Johns Hopkins Univ, Sch Med, Program Human Genet & Mol Biol, Baltimore, MD USA. [Lin, Daniel W.] Univ Washington, Dept Urol, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Feng, Ziding] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Peters, Ulrike; Stanford, Janet L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Holt, SK (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Mailstop M4-A402,POB 19024, Seattle, WA 98109 USA. EM skholt@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU National Cancer Institute [RO1-CA056678, RO1-CA092579, RO1-CA082664, P50-CA097186] FX Grant sponsor: National Cancer Institute; Grant numbers: RO-CA056678, RO1-CA092579, RO1-CA082664, P50-CA097186.; This work was supported by grants RO1-CA056678, RO1-CA092579, RO1-CA082664, and P50-CA097186 from the National Cancer Institute; additional support was provided by the Fred Hutchinson Cancer Research Center, the Intramural Program of the National Human Genome Research Institute, and the Prostate Cancer Foundation Young Investigator Award Grant. NR 50 TC 40 Z9 40 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD SEP 15 PY 2010 VL 70 IS 13 BP 1448 EP 1460 DI 10.1002/pros.21180 PG 13 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 646LM UT WOS:000281542100009 PM 20687218 ER PT J AU Kulkarni, RN AF Kulkarni, Rohit N. TI GIP: No Longer the Neglected Incretin Twin? SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID GASTRIC-INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE-1; RECEPTOR KNOCKOUT MICE; BETA-CELL SURVIVAL; ENTEROINSULAR AXIS; PHYSIOLOGICAL INCRETIN; GLUCOSE-INTOLERANCE; DIABETES-MELLITUS; INSULIN RELEASE; DISEASE AB In the design of therapeutics to treat type 2 diabetes, researchers have exploited the observation that oral ingestion of nutrients leads to the secretion of glucose homeostasis-regulating incretin hormones (for example, glucagon-like-peptide-1) from the gut. Here, we discuss two recent papers that suggest that the "other" incretin hormone, gastric inhibitory polypeptide (GIP), also is important in the regulation of glucose homeostasis. These findings warrant further studies to unravel the mechanism of action of GIP in beta-cells of the endocrine pancreas and to evaluate the possibility of designing novel therapeutics that target both incretin hormones. C1 Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA 02215 USA. EM Rohit.Kulkarni@joslin.harvard.edu FU U.S. National Institutes of Health [DK RO1 67536]; American Diabetes Association FX I thank K. Parlee for excellent assistance with manuscript preparation and gratefully acknowledge support from the U.S. National Institutes of Health (grant DK RO1 67536) and the American Diabetes Association. NR 43 TC 6 Z9 6 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD SEP 15 PY 2010 VL 2 IS 49 AR 49ps47 DI 10.1126/scitranslmed.3001027 PG 5 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 735SJ UT WOS:000288437200002 PM 20844284 ER PT J AU Sponseller, PD Zimmerman, RM Ko, PS ter Gunne, AFP Mohamed, AS Chang, TL Kebaish, KM AF Sponseller, Paul D. Zimmerman, Ryan M. Ko, Phebe S. ter Gunne, Albert F. Pull Mohamed, Ahmed S. Chang, Tai-Li Kebaish, Khaled M. TI Low Profile Pelvic Fixation With the Sacral Alar Iliac Technique in the Pediatric Population Improves Results at Two-Year Minimum Follow-up SO SPINE LA English DT Article DE pelvic obliquity; pelvic fixation; scoliosis ID NEUROMUSCULAR SPINAL DEFORMITY; UNIT ROD; LUMBOSACRAL FIXATION; INSTRUMENTATION; SCREWS; S1 AB Study Design. Retrospective review. Objective. Anchor stability and prominence are problems with pelvic fixation in pediatric spinal deformity surgery. We compared the new sacral alar iliac (SAI) fixation technique (with a starting point in the sacral ala and inline anchors deep under the midline muscle flap) with other methods of screw fixation. Summary of Background Data. Iliac anchors have been shown to provide the best form of pelvic fixation. A trajectory from the posterior sacral surface to the iliac wings has recently been described. To our knowledge, no clinical series has compared this method of pelvic fixation in children to others. Methods. Of 32 consecutive pediatric patients who underwent SAI fixation, 2 died and 26 returned for follow-up (>2 years). Mean age at surgery was 14 years. Average screw size was 67 mm long and 7 to 9 mm in diameter. Clinical examinations, radiographs, and computed tomography scans were analyzed. Outcomes included pain over the implants, screw placement, implant prominence, radiographic lucency, need for revision, and infection. SAI patients were compared with 27 previous patients who had pelvic fixation via other screw techniques. Results. For SAI fixation, correction of pelvic obliquity and Cobb angles were 20 degrees +/- 11 degrees (70%) and 42 degrees +/- 25 degrees (67%), respectively. For other pelvic fixation methods, those values were 10 degrees +/- 9 degrees (50%), and 46 degrees +/- 16 degrees (60%), respectively. Compared with other screws, SAI screws provided significantly better pelvic obliquity correction (P = 0.002) but no difference in Cobb correction. There were 2 lucencies adjacent to screws in both groups. Computed tomography scans of 18 SAI patients showed no intrapelvic protrusion, but 1 screw extended laterally (<5 mm). One early SAI patient required revision with larger screws, which relieved pain; there was 1 revision in the comparison group. SAI patients had no deep infections, implant prominence, late skin breakdown, or anchor migration; traditional patients had 3 deep infections (P = 0.09) and 3 instances of implant prominence, skin breakdown, or anchor migration. Conclusion. SAI pelvic fixation produces better correction of pelvic obliquity than do previous techniques. Radiographic and clinical anchor stability is satisfactory at 2-year follow-up. C1 [Sponseller, Paul D.; Ko, Phebe S.; ter Gunne, Albert F. Pull; Mohamed, Ahmed S.; Kebaish, Khaled M.] Johns Hopkins Univ, Dept Orthopaed Surg, Baltimore, MD USA. [Zimmerman, Ryan M.] Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, Boston, MA 02114 USA. [Chang, Tai-Li] Hosp Special Surg, New York, NY 10021 USA. RP Kebaish, KM (reprint author), Care of Henze EP, Johns Hopkins Bayview Med Ctr, Editorial Serv, Dept Orthopaed Surg, 4940 Eastern Ave,A665, Baltimore, MD 21224 USA. EM ehenze1@jhmi.edu OI Pull ter Gunne, Albert/0000-0001-5743-4000 NR 14 TC 20 Z9 27 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD SEP 15 PY 2010 VL 35 IS 20 BP 1887 EP 1892 DI 10.1097/BRS.0b013e3181e03881 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 650RG UT WOS:000281868300011 PM 20802390 ER PT J AU Lutton, BV Cho, PS Hirsh, EL Ferguson, KK Teague, AGS Hanekamp, JS Chi, N Goldman, SN Messina, DJ Houser, S Yeap, BY Popma, SH Sachs, DH Huang, CA AF Lutton, Bram V. Cho, Patricia S. Hirsh, Erica L. Ferguson, Kelly K. Teague, Alexander G. S. Hanekamp, John S. Chi, Nina Goldman, Stephanie N. Messina, Darin J. Houser, Stuart Yeap, Beow Y. Popma, Sicco H. Sachs, David H. Huang, Christene A. TI Approaches to Avoid Immune Responses Induced by Repeated Subcutaneous Injections of Allogeneic Umbilical Cord Tissue-Derived Cells SO TRANSPLANTATION LA English DT Article DE Umbilical cord tissue derived cells; Immunogenicity; Miniature swine; Cellular therapy ID MESENCHYMAL STEM-CELLS; MINIATURE SWINE; RENAL-ALLOGRAFTS; TRANSPLANTATION TOLERANCE; RAT-BRAIN; IMMUNOGENICITY; INDUCTION; SURVIVAL; THERAPY; DISEASE AB Background. Cellular treatments for repairing diseased tissues represent a promising clinical strategy. Umbilical cord tissue-derived cells (UTC) are a unique source of cells with a low immunogenic profile and potential for tissue repair. By using UTC from miniature swine, we previously demonstrated that despite their low immunogenic phenotype, UTC could induce an immune response under certain inflammatory conditions and after multiple subcutaneous (SC) injections. Given that repeat dosing of cells may be necessary to achieve a lasting therapeutic benefit, in this study, we examined approaches to avoid an immune response to multiple SC injections of UTC. Methods. By using in vitro and in vivo measures of sensitization to SC cellular injections, we assessed the effects of varying the location of administration site, prolongation of timing between injections, and use of immunosuppressive treatments on repeated cellular injections in Massachusetts General Hospital major histocompatibility complex-defined miniature swine. Results. Although under normal conditions, a single SC injection of major histocompatibility complex-mismatched UTC did not induce a detectable immune response, multiple SC injections of UTC demonstrated rapid humoral and cell-mediated immune responses. Avoidance of an immune response to repeat SC injection was achieved by concurrent immunosuppression with each dose of UTC. Conclusions. UTC and other similar cell types believed to be nonimmunogenic have the potential to induce immune responses under certain conditions. These studies provide important considerations and guidelines for preclinical studies investigating allogeneic cellular therapies. C1 [Lutton, Bram V.; Cho, Patricia S.; Hirsh, Erica L.; Ferguson, Kelly K.; Teague, Alexander G. S.; Hanekamp, John S.; Sachs, David H.; Huang, Christene A.] Massachusetts Gen Hosp East, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Goldman, Stephanie N.; Messina, Darin J.; Popma, Sicco H.] Cell Therapy Co, Radnor, PA USA. [Houser, Stuart] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Huang, CA (reprint author), Massachusetts Gen Hosp East, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA. EM Huangc@helix.mgh.harvard.edu OI Sabins, Nina/0000-0001-7983-8962; Ferguson, Kelly/0000-0001-8467-3250 FU Centocor R&D Inc., Stem Cell Internal Venture FX This work was supported in part by Centocor R&D Inc., Stem Cell Internal Venture (sponsored research agreement). NR 18 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 15 PY 2010 VL 90 IS 5 BP 494 EP 501 DI 10.1097/TP.0b013e3181c6ff73 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 646YQ UT WOS:000281582000005 PM 21451445 ER PT J AU Rabito, C Halpern, EF Scott, J Tolkoff-Rubin, N AF Rabito, Carlos Halpern, Elkan F. Scott, James Tolkoff-Rubin, Nina TI Accurate, Fast, and Convenient Measurement of Glomerular Filtration Rate in Potential Renal Transplant Donors SO TRANSPLANTATION LA English DT Article DE Glomerular filtration rate; (99m)Tc-DTPA; (125)I-iothalamate; Estimated GFR ID CHRONIC KIDNEY-DISEASE; INJECTION INULIN-CLEARANCE; SINGLE-INJECTION; SERUM CREATININE; EQUATIONS; CHILDREN; EGFR; CKD; RECOMMENDATIONS; PROGRESSION AB Background. Measurement of glomerular filtration rate (GFR) is essential in the risk evaluation of potential kidney donors. The optimal method of measuring GFR involves using clearance techniques. However, clearance techniques are technically complex and time consuming. The goal of this study is to evaluate a different method of measuring GFR, one that retains the accuracy of a clearance technique and adds the convenience of a plasma creatinine measurement. Methods. Fifty subjects, including both normal and patients with different degrees of renal dysfunction, were included in the initial validation study. GFR was measured simultaneously using a continuous infusion of (125)I-iothalamate and external radioactivity measurement after a single intravenous injection of (99m)Tc-labeled diethylenetriaminepentaacetic acid ((99m)Tc-DTPA). After validation, the renal function of 80 potential renal transplant donors was measured using only external radiation detection. Results. External radioactivity decreases versus time with first-order kinetics. The rate of clearance of (99m)Tc-DTPA was measured as the slope (kappa) of the natural logarithm of external radioactivity corrected for radioactive decay versus time. There was an excellent correlation between kappa and simultaneous GFR measurements done with (125)I-iothalamate. Nonlinear regression analysis of kappa GFR values obtained in potential renal transplant donors versus frequencies indicates a mean value and variance similar to normal reported values obtained with clearance techniques. Estimated GFR and 24-hr plasma creatinine clearance underestimate GFR with greater variance. Conclusions. Measurements of external whole tissue radioactivity after intravenous injection of (99m)Tc-DTPA represents an accurate, fast, and convenient way to measure total and individual kidney GFR, addressing an important concern during the risk evaluation of potential renal transplant donors. C1 [Rabito, Carlos; Scott, James] Harvard Univ, Massachusetts Gen Hosp, Div Nucl Med, Sch Med,Dept Radiol, Boston, MA 02114 USA. [Halpern, Elkan F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Tech Assessment,Dept Radiol, Boston, MA 02114 USA. [Tolkoff-Rubin, Nina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Nephrol Div, Boston, MA 02114 USA. RP Rabito, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Nucl Med, Sch Med,Dept Radiol, White Bldg,Room 427,55 Fruit St, Boston, MA 02114 USA. EM Crabito@partners.org NR 49 TC 5 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 15 PY 2010 VL 90 IS 5 BP 510 EP 517 DI 10.1097/TP.0b013e3181e9139d PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 646YQ UT WOS:000281582000007 PM 20595931 ER PT J AU Mir, SE Hamer, PCD Krawczyk, PM Balaj, L Claes, A Niers, JM Van Tilborg, AAG Zwinderman, AH Geerts, D Kaspers, GJL Vandertop, WP Cloos, J Tannous, BA Wesseling, P Aten, JA Noske, DP Van Noorden, CJF Wurdinger, T AF Mir, Shahryar E. Hamer, Philip C. De Witt Krawczyk, Przemek M. Balaj, Leonora Claes, An Niers, Johanna M. Van Tilborg, Angela A. G. Zwinderman, Aeilko H. Geerts, Dirk Kaspers, Gertjan J. L. Vandertop, W. Peter Cloos, Jacqueline Tannous, Bakhos A. Wesseling, Pieter Aten, Jacob A. Noske, David P. Van Noorden, Cornelis J. F. Wurdinger, Thomas TI In Silico Analysis of Kinase Expression Identifies WEE1 as a Gatekeeper against Mitotic Catastrophe in Glioblastoma SO CANCER CELL LA English DT Article ID DNA-DAMAGE CHECKPOINT; TUMOR STEM-CELLS; RANDOMIZED PHASE-III; DOUBLE-STRAND BREAKS; PROTEIN-KINASE; MALIGNANT GLIOMAS; GENE-EXPRESSION; G(2) CHECKPOINT; LUNG-CANCER; COPY NUMBER AB Kinases execute pivotal cellular functions and are therefore widely investigated as potential targets in anticancer treatment. Here we analyze the kinase gene expression profiles of various tumor types and reveal the wee1 kinase to be overexpressed in glioblastomas. We demonstrate that WEE1 is a major regulator of the G(2) checkpoint in glioblastoma cells. Inhibition of WEE1 by siRNA or small molecular compound in cells exposed to DNA damaging agents results in abrogation of the G(2) arrest, premature termination of DNA repair, and cell death. Importantly, we show that the small-molecule inhibitor of WEE1 sensitizes glioblastoma to ionizing radiation in vivo. Our results suggest that inhibition of WEE1 kinase holds potential as a therapeutic approach in treatment of glioblastoma. C1 [Mir, Shahryar E.; Hamer, Philip C. De Witt; Balaj, Leonora; Niers, Johanna M.; Kaspers, Gertjan J. L.; Vandertop, W. Peter; Cloos, Jacqueline; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Neurooncol Res Grp, Dept Neurosurg, NL-1081 HV Amsterdam, Netherlands. [Mir, Shahryar E.; Hamer, Philip C. De Witt; Balaj, Leonora; Niers, Johanna M.; Kaspers, Gertjan J. L.; Vandertop, W. Peter; Cloos, Jacqueline; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Neurooncol Res Grp, Dept Pediat Oncol Hematol, NL-1081 HV Amsterdam, Netherlands. [Krawczyk, Przemek M.; Van Tilborg, Angela A. G.; Aten, Jacob A.; Van Noorden, Cornelis J. F.] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1100 DD Amsterdam, Netherlands. [Geerts, Dirk] Univ Amsterdam, Acad Med Ctr, Dept Human Genet, NL-1100 DD Amsterdam, Netherlands. [Zwinderman, Aeilko H.] Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol & Biostat, NL-1100 DD Amsterdam, Netherlands. [Claes, An; Wesseling, Pieter] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 GA Nijmegen, Netherlands. [Niers, Johanna M.; Tannous, Bakhos A.; Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02113 USA. [Niers, Johanna M.; Tannous, Bakhos A.; Wurdinger, Thomas] Harvard Univ, Sch Med, Charlestown, MA 02113 USA. RP Wurdinger, T (reprint author), Vrije Univ Amsterdam Med Ctr, Neurooncol Res Grp, Dept Neurosurg, NL-1081 HV Amsterdam, Netherlands. EM t.wurdinger@vumc.nl RI Wesseling, P./H-8114-2014; van Tilborg, Angela/M-5704-2015; De Witt Hamer, Philip/E-7630-2013; OI Wesseling, P./0000-0001-5453-5201; van Tilborg, Angela/0000-0003-3968-5345; De Witt Hamer, Philip/0000-0003-2988-8544; Geerts, Dirk/0000-0002-6386-8187 FU Accelerate Brain Cancer Cure; Dutch Cancer Society FX This study was supported by grants from the Accelerate Brain Cancer Cure and the Dutch Cancer Society. We thank Z. Kwidama, L. Wedekind, M. Ubels, and W. Tigchelaar for technical assistance, S. Heukelom and P. Koken from the Department of Radiotherapy, VUmc, for use of the irradiation source, and J. Skog for CD133 analysis. NR 68 TC 106 Z9 108 U1 2 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD SEP 14 PY 2010 VL 18 IS 3 BP 244 EP 257 DI 10.1016/j.ccr.2010.08.011 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 650VM UT WOS:000281881500007 PM 20832752 ER PT J AU Yang, QK Deng, XM Lu, BW Cameron, M Fearns, C Patricelli, MP Yates, JR Gray, NS Lee, JD AF Yang, Qingkai Deng, Xianming Lu, Bingwen Cameron, Michael Fearns, Colleen Patricelli, Matthew P. Yates, John R., III Gray, Nathanael S. Lee, Jiing-Dwan TI Pharmacological Inhibition of BMK1 Suppresses Tumor Growth through Promyelocytic Leukemia Protein SO CANCER CELL LA English DT Article ID SIGNAL-REGULATED KINASE-5; MAMMALIAN MAP KINASE; CANCER-CELLS; GENE-EXPRESSION; NUCLEAR-BODIES; PML; BMK1/ERK5; PATHWAY; ERK5; P53 AB BMK1 is activated by mitogens and oncogenic signals and, thus, is strongly implicated in tumorigenesis. We found that BMK1 interacted with promyelocytic leukemia protein (PML), and inhibited its tumor-suppressor function through phosphorylation. Furthermore, activated BMK1 notably inhibited PML-dependent activation of p21. To further investigate the BMK-mediated inhibition of the tumor suppressor activity of PML in tumor cells, we developed a small-molecule inhibitor of the kinase activity of BMK1, XMD8-92. Inhibition of BMK1 by XMD8-92 blocked tumor cell proliferation in vitro and significantly inhibited tumor growth in vivo by 95%, demonstrating the efficacy and tolerability of BMK1-targeted cancer treatment in animals. C1 [Yang, Qingkai; Lee, Jiing-Dwan] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Lu, Bingwen; Yates, John R., III] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA. [Fearns, Colleen] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Patricelli, Matthew P.] Act X Biosci, La Jolla, CA 92037 USA. [Deng, Xianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cameron, Michael] Scripps Florida, Translat Res Inst Drug Metab & Pharmacokinet, Jupiter, FL 33458 USA. RP Lee, JD (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM jdlee@scripps.edu OI Yang, Qingkai/0000-0001-6628-5393 FU National Institutes of Health [CA079871, CA114059]; University of California [15RT-0104]; Novartis FX We thank Dr. G. Blandino, Dr. M. Kim, and Dr. P.P. Pandolfi for the PML null and control cell lines. We also thank Ambit Biosciences for performing the KinomeScan kinase selectivity profiling. This work was supported by the National Institutes of Health (CA079871 and CA114059 to J.-D.L) and by funds from the Tobacco-Related Disease, Research Program of the University of California, 15RT-0104 (J.-D.L.). The Gray lab receives funding from Novartis. M.P.P. is an employee of ActivX Biosciences, Inc., a wholly owned subsidiary of Kyorin Pharmaceuticals. NR 43 TC 77 Z9 80 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD SEP 14 PY 2010 VL 18 IS 3 BP 258 EP 267 DI 10.1016/j.ccr.2010.08.008 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 650VM UT WOS:000281881500008 PM 20832753 ER PT J AU Espinosa, L Cathelin, S D'Altri, T Trimarchi, T Statnikov, A Guiu, J Rodilla, V Ingles-Esteve, J Nomdedeu, J Bellosillo, B Besses, C Abdel-Wahab, O Kucine, N Sun, SC Song, GC Mullighan, CC Levine, RL Rajewsky, K Aifantis, I Bigas, A AF Espinosa, Lluis Cathelin, Severine D'Altri, Teresa Trimarchi, Thomas Statnikov, Alexander Guiu, Jordi Rodilla, Veronica Ingles-Esteve, Julia Nomdedeu, Josep Bellosillo, Beatriz Besses, Carles Abdel-Wahab, Omar Kucine, Nicole Sun, Shao-Cong Song, Guangchan Mullighan, Charles C. Levine, Ross L. Rajewsky, Klaus Aifantis, Iannis Bigas, Anna TI The Notch/Hes1 Pathway Sustains NF-kappa B Activation through CYLD Repression in T Cell Leukemia SO CANCER CELL LA English DT Article ID DEUBIQUITINATING ENZYME CYLD; SIGNALING PATHWAY; MULTIPLE-MYELOMA; TRANSCRIPTION FACTORS; KINASE TAK1; IN-VIVO; NOTCH1; GENE; MUTATIONS; LYMPHOMA AB It was previously shown that the NF-kappa B pathway is downstream of oncogenic Notch1 in T cell acute lymphoblastic leukemia (T-ALL). Here, we visualize Notch-induced NF-kappa B activation using both human T-ALL cell lines and animal models. We demonstrate that Hes1, a canonical Notch target and transcriptional repressor, is responsible for sustaining IKK activation in T-ALL. Hes1 exerts its effects by repressing the deubiquitinase CYLD, a negative IKK complex regulator. CYLD expression was found to be significantly suppressed in primary T-ALL. Finally, we demonstrate that IKK inhibition is a promising option for the targeted therapy of T-ALL as specific suppression of IKK expression and function affected both the survival of human T-ALL cells and the maintenance of the disease in vivo. C1 [Espinosa, Lluis; D'Altri, Teresa; Guiu, Jordi; Rodilla, Veronica; Ingles-Esteve, Julia; Bigas, Anna] Hosp del Mar, IMIM, Canc Res Program, Barcelona 08003, Spain. [Cathelin, Severine; Trimarchi, Thomas; Aifantis, Iannis] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. [Statnikov, Alexander] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Statnikov, Alexander] NYU, Sch Med, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA. [Statnikov, Alexander] NYU, Sch Med, Dept Med, New York, NY 10016 USA. [Nomdedeu, Josep] Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona 08025, Spain. [Bellosillo, Beatriz] Hosp del Mar, Dept Pathol, Barcelona 08003, Spain. [Besses, Carles] Hosp del Mar, Dept Hematol, Barcelona 08003, Spain. [Abdel-Wahab, Omar; Kucine, Nicole; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Kucine, Nicole] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA. [Sun, Shao-Cong] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. [Song, Guangchan; Mullighan, Charles C.] St Judes Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Rajewsky, Klaus] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Espinosa, L (reprint author), Hosp del Mar, IMIM, Canc Res Program, Barcelona 08003, Spain. EM lespinosa@imim.es; iannis.aifantis@nyumc.org; abigas@imim.es RI Besses, Carles/B-3738-2011; BIGAS, ANNA/A-7457-2014 FU FPI [BES-2008-005708]; FPU [AP2008-01883]; FIMIM; Hope Street Kids Foundation; Instituto de Salud Carlos III [PI041890]; Fundacion Mutua Madrilena; RTICCS/FEDER [RD06/0020/0098]; National Institutes of Health [R01CA133379, R01CA105129, R01CE149655, R21CA141399, R56LM007948, 1UL1RR029893]; American Cancer Society [RSG0806801]; Irma T. Hirschl Trust; The Dana Foundation; Mallinckrodt Foundation; Alex's Lemonade Stand Foundation; Leukemia and Lymphoma Society; Gabrielle's Angels Foundation; [MEC2007-60080] FX We are grateful to the NYU Flow Facility for expert cell sorting, the NYU Cancer Institute Genomics Facility for help with micro-array processing, and the Meruelo Lab (NYU) for animal imaging. Adriana Heguy and the Geoffrey Beene Translational Oncology Core for assistance with sequencing and methylation analysis. Drs. T. Look and H. von Boehmer for gene expression database sharing. Drs. M. Schmidt-Supprian and A. Klinakis for valuable animal model advice. M. Caudy (Cornell University), A. Pfeifer (University of Bonn), M. Karin (UCSD), A. Cerutti (IMIM), R. Kageyama (Kyoto University), and R. Gimeno (Research Institute Hospital Vall d'Hebron) for valuable reagents and BAYER for providing the BAY65-1185. We thank C. Recasens, J. Gonzalez (IMIM), Philmo Oh, and Camille Lobry (NYU) for experimental advice, F. Torres (UAB) for statistical analysis. J.G., T.D., and V.R. are recipients of FPI (BES-2008-005708), FPU (AP2008-01883), and FIMIM predoctoral fellowship, respectively. L.E. is an investigator at the Carlos III program and, S.C. is supported by the Hope Street Kids Foundation. This work was supported by Instituto de Salud Carlos III Grant PI041890 and Fundacion Mutua Madrilena to L.E., by MEC2007-60080 and RTICCS/FEDER (RD06/0020/0098) to A.B., by the National Institutes of Health grants R01CA133379, R01CA105129, R01CE149655, R21CA141399 (to I.A.), R56LM007948, 1UL1RR029893 (to A.S.), the American Cancer Society (RSG0806801 to I.A.), the Irma T. Hirschl Trust, The Dana Foundation, The Mallinckrodt Foundation, the Alex's Lemonade Stand Foundation, The Leukemia and Lymphoma Society (TAP grant to I.A.), and the Gabrielle's Angels Foundation (R.L.L. and I.A.). I.A. is a Howard Hughes Medical Institute Early Career Scientist. NR 51 TC 122 Z9 133 U1 1 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD SEP 14 PY 2010 VL 18 IS 3 BP 268 EP 281 DI 10.1016/j.ccr.2010.08.006 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 650VM UT WOS:000281881500009 PM 20832754 ER PT J AU James, S Budaj, A Aylward, P Buck, KK Cannon, CP Cornel, JH Harrington, RA Horrow, J Katus, H Keltai, M Lewis, BS Parikh, K Storey, RF Szummer, K Wojdyla, D Wallentin, L AF James, Stefan Budaj, Andrzej Aylward, Philip Buck, Kristen K. Cannon, Christopher P. Cornel, Jan H. Harrington, Robert A. Horrow, Jay Katus, Hugo Keltai, Matyas Lewis, Basil S. Parikh, Keyur Storey, Robert F. Szummer, Karolina Wojdyla, Daniel Wallentin, Lars TI Ticagrelor Versus Clopidogrel in Acute Coronary Syndromes in Relation to Renal Function Results From the Platelet Inhibition and Patient Outcomes (PLATO) Trial SO CIRCULATION LA English DT Article DE acute coronary syndrome; bleeding; clopidogrel; mortality; myocardial infarction; renal function ID CHRONIC KIDNEY-DISEASE; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; IMPACT; RISK; CLASSIFICATION; INSUFFICIENCY; EPTIFIBATIDE; DYSFUNCTION; EVENTS AB Background-Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates. Methods and Results-Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n = 3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal renal function (n = 11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to 1.02). In patients with chronic kidney disease, ticagrelor reduced total mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding rates, fatal bleedings, and non-coronary bypass-related major bleedings were not significantly different between the 2 randomized groups (15.1% versus 14.3%; HR, 1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54; and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between creatinine clearance and randomized treatment on any of the outcome variables were nonsignificant. Conclusions-In acute coronary syndrome patients with chronic kidney disease, ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non-procedure-related bleeding. C1 [James, Stefan] Univ Uppsala Hosp, Uppsala Clin Res Ctr, S-75185 Uppsala, Sweden. [Budaj, Andrzej] Grochowski Hosp, Postgrad Med Sch, Warsaw, Poland. [Aylward, Philip] Flinders Med Ctr, Bedford Pk, SA, Australia. [Buck, Kristen K.; Horrow, Jay] AstraZeneca Res & Dev, Wilmington, DE USA. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Cornel, Jan H.] Med Ctr Alkmaar, Alkmaar, Netherlands. [Harrington, Robert A.; Wojdyla, Daniel] Duke Clin Res Inst, Durham, NC USA. [Katus, Hugo] Univ Klinikum Heidelberg, Heidelberg, Germany. [Keltai, Matyas] Semmelweis Univ, Hungarian Inst Cardiol, Budapest, Hungary. [Lewis, Basil S.] Lady Davis Carmel Med Ctr, Haifa, Israel. [Parikh, Keyur] Heart Care Clin, Ahmadabad, Gujarat, India. [Storey, Robert F.] Univ Sheffield, Sheffield, S Yorkshire, England. [Szummer, Karolina] Karolinska Univ Hosp, Stockholm, Sweden. RP James, S (reprint author), Univ Uppsala Hosp, Uppsala Clin Res Ctr, S-75185 Uppsala, Sweden. EM Stefan.james@ucr.uu.sc RI Katus, Hugo/P-1712-2016 FU AstraZeneca; Sanofi-Aventis; Eli Lilly; Boehringer Ingelheim; Glaxo Smith Kline; The Medicines Co; CSL Biotherapies; Bristol-Myers Squibb; Merck; Pfizer; Schering-Plough; Accumetrics; Bristol-Myers Squibb/Sanofi Partnership; Intekrin Therapeutics; Merck/Schering-Plough Partnership; Novartis; Takeda; Portola Pharmaceuticals; Millenium Pharmaceuticals; Dynabyte; Eli Lilly/Daiichi Sankyo alliance; Teva; Athera FX The PLATO study was funded by AstraZeneca. Support for the analysis and interpretation of results and preparation of the manuscript was provided through funds to the Uppsala Clinical Research Center and Duke Clinical Research Institute as part of the Clinical Study Agreement.; Dr James has received research grants and advisory board fees from AstraZeneca and honoraria from AstraZeneca, Bristol-Myers Squibb, Schering-Plough, and Eli Lilly. Dr Budaj has received consulting fees from Sanofi-Aventis, Eli Lilly, Boehringer Ingelheim, AstraZeneca, and Glaxo Smith Kline. Dr Aylward has received research grants and advisory board and speaker fees from Boehringer Ingelheim, Sanofi-Aventis, AstraZeneca, Eli Lilly, The Medicines Co, CSL Biotherapies, Bristol-Myers Squibb, Merck, Pfizer, Schering-Plough, and Servier. Dr Cannon has received research grants from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, Glaxo Smith Kline, Intekrin Therapeutics, Merck, Merck/Schering-Plough Partnership, Novartis, and Takeda; Dr Cannon reports equity ownership interest in Automedics. Dr Harrington has received consulting fees from Bristol-Myers Squibb, Sanofi-Aventis, Portola Pharmaceuticals, Schering-Plough, AstraZeneca, and Eli Lilly and grant support from Millenium Pharmaceuticals, Schering-Plough, The Medicines Co, Portola Pharmaceuticals, AstraZeneca, and Bristol-Myers Squibb. Dr Lewis has received consulting fees from Bristol-Myers Squibb and Sanofi-Aventis and grant support from Boehringer Ingelheim. Dr Keltai has received consulting fees from AstraZeneca. Dr Storey has received research grants from AstraZeneca, Dynabyte, the Eli Lilly/Daiichi Sankyo alliance, and Schering-Plough, as well as honoraria or consultant fees from AstraZeneca, Eli Lilly/Daiichi Sankyo, Novartis, Schering-Plough, Eli Lilly/Daiichi Sankyo, Teva, and The Medicines Co. Dr Wallentin has received research grants from AstraZeneca, Boehringer Ingelheim, Bristol- Myers Squibb, Glaxo Smith Kline, and Schering- Plough, as well as honoraria or consultant fees from AstraZeneca, Boehringer Ingelheim, Bristol- Myers Squibb, Glaxo Smith Kline, Schering- Plough, Eli Lilly, Regado, and Athera. Drs Horrow and Buck are employees of AstraZeneca. The other authors report no conflicts. NR 18 TC 168 Z9 184 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 14 PY 2010 VL 122 IS 11 BP 1056 EP 1067 DI 10.1161/CIRCULATIONAHA.109.933796 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 650UJ UT WOS:000281877800002 PM 20805430 ER PT J AU Bangalore, S Bhatt, DL Rother, J Alberts, MJ Thornton, J Wolski, K Goto, S Hirsch, AT Smith, SC Aichner, FT Topakian, R Cannon, CP Steg, PG AF Bangalore, Sripal Bhatt, Deepak L. Roether, Joachim Alberts, Mark J. Thornton, Julic Wolski, Kathy Goto, Shinya Hirsch, Alan T. Smith, Sidney C. Aichner, Franz T. Topakian, Raffi Cannon, Christopher P. Steg, P. Gabriel CA REACH Registry Investigators TI Late Outcomes After Carotid Artery Stenting Versus Carotid Endarterectomy Insights From a Propensity-Matched Analysis of the Reduction of Atherothrombosis for Continued Health (REACH) Registry SO CIRCULATION LA English DT Article DE carotid arteries; endarterectomy; prognosis; stents ID RANDOMIZED CONTROLLED-TRIAL; ENDOVASCULAR TREATMENT; SCORE METHODS; STENOSIS; STROKE; ANGIOPLASTY; RISK; OUTPATIENTS; PREVENTION; UPDATE AB Background-In patients with carotid artery disease, carotid endarterectomy (CEA) and carotid stenting (CAS) are treatment options. Controversy exists as to the relative efficacy of the 2 techniques in preventing late events. Methods and Results-The Reduction of Atherothrombosis for Continued Health (REACH) Registry recruited >68 000 outpatients >= 45 years of age with established atherothrombotic disease or >= 3 risk factors for atherothrombosis. Patients with CAS or CEA were chosen and followed up prospectively for the occurrence of cardiovascular events. Propensity score matching was performed to assemble a cohort of patients in whom all baseline covariates would be well balanced. Primary outcome was defined as death or stroke at the 2-year follow-up. Secondary outcome was stroke or transient ischemic attack. Tertiary outcome was a composite of death, myocardial infarction, or stroke and the individual outcomes. Of the 68 236 patients with atherothrombosis, 3412 patients (5%) had a history of carotid artery revascularization (70% asymptomatic carotid stenosis), 1025 (30%) with CAS and 2387 (70%) with CEA. Propensity score analyses matched 836 CAS patients with 836 CEA patients. At the end of 2 years of follow-up, in the propensity score-matched cohort, CAS was associated with a risk similar to CEA for the primary (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.57 to 1.26), secondary (HR, 1.20; 95% CI, 0.73 to 1.96), and tertiary (HR, 0.72; 95% CI, 0.51 to 1.01) composite outcome, death (HR, 0.63; 95% CI, 0.40 to 1.00), and stroke (HR, 1.48; 95% CI, 0.79 to 2.80). Conclusion-In a real-world cohort of patients with a history of carotid artery revascularization, CAS was comparable to CEA for late outcomes. (Circulation. 2010;122:1091-1100.) C1 [Bangalore, Sripal] New York Univ Sch Med, Leon H Charney Div Cardiol, New York, NY USA. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Bangalore, Sripal] Harvard Clin Res Inst, Boston, MA USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA 02115 USA. [Roether, Joachim] Acad Teaching Hosp Hamburg Med Sch, Dept Neurol, Asklepios Klin Altona, Hamburg, Germany. [Alberts, Mark J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Thornton, Julic; Wolski, Kathy] Cleveland Clin, Cleveland, OH 44106 USA. [Goto, Shinya] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Smith, Sidney C.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Aichner, Franz T.; Topakian, Raffi] Acad Teaching Hosp Wagner Jauregg, Linz, Austria. [Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Steg, P. Gabriel] Univ Paris 07, Ctr Hosp Bichat Claude Bernard, AP HP, INSERM U 698, Paris, France. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 75 Francis St,PBB-146, Boston, MA 02115 USA. EM dlbhattmd@post.harvard.edu RI Bangalore, Sripal/B-6246-2013; OI Bangalore, Sripal/0000-0001-9485-0652 FU Sanofi-Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); Eisai; Ethicon; Heartscape; The Medicines Co.; Bayer vital; Boehringer-Ingelheim; Lundbeck; Astellas; Otsuka; DaiichiSankyo; Schering-Plough; Schering-Plough, GlaxoSmithKline; Novartis; Teijin; Towa-Eiyo; Bayer; Pfizer; Banyu; Mochida; Johnson and Johnson; Kowa; Avot Vascular; Tanabe Mitsubishi,; Accumetrics; InteKrin; Merck; Takeda; Servier; DaiichiSankyo-Lilly; Medtronic; Roche FX The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan) and is endorsed by the World Heart Federation.; Dr Bhatt has received research grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi-Aventis, and The Medicines Co. Dr Rother has received consulting/Advisory Board fees from Bayer vital, Boehringer-Ingelheim, Bristol-Myers Squibb, Sanofi-Aventis, and Lundbeck. Dr Goto has received research grants from Sanofi-Aventis, Astellas, Eisai, and Otsuka, as well as honoraria or consulting fees from Sanofi-Aventis, Eisai, Otsuka, DaiichiSankyo, Schering-Plough, GlaxoSmithKline, Novartis, Asteras, Teijin, Towa-Eiyo, Bayer, Pfizer, Banyu, Mochida, Johnson and Johnson, Kowa, Avot Vascular, Tanabe Mitsubishi, and AstraZeneca. Dr Cannon has received research grants from Accumetrics, AstraZeneca, GlaxoSmithKline, InteKrin, Merck, and Takeda. He has served on advisory boards (but donates funds to charity) for Alnylam, Bristol-Myers Squibb/Sanofi Partnership, and Novartis. He has developed an independent educational conference with honorarium from Pfizer. He holds equity in Automedics Medical. Dr Steg has received a research grant from Servier (2009-2014) and consulting/Advisory Board fees from Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, DaiichiSankyo-Lilly, GlaxoSmithKline, Medtronic, Otsuka, Roche, Sanofi-Aventis, Servier, and The Medicines Co; Dr Steg holds stock in Aterovax. The other authors report no conflicts. NR 31 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 14 PY 2010 VL 122 IS 11 BP 1091 EP 1100 DI 10.1161/CIRCULATIONAHA.109.933341 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 650UJ UT WOS:000281877800006 PM 20805431 ER PT J AU Bonello, L Tantry, US Marcucci, R Blindt, R Angiolillo, DJ Becker, R Bhatt, DL Cattaneo, M Collet, JP Cuisset, T Gachet, C Montalescot, G Jennings, LK Kereiakes, D Sibbing, D Trenk, D Van Werkum, JW Paganelli, F Price, MJ Waksman, R Gurbel, PA AF Bonello, Laurent Tantry, Udaya S. Marcucci, Rossella Blindt, Ruediger Angiolillo, Dominick J. Becker, Richard Bhatt, Deepak L. Cattaneo, Marco Collet, Jean Philippe Cuisset, Thomas Gachet, Christian Montalescot, Gilles Jennings, Lisa K. Kereiakes, Dean Sibbing, Dirk Trenk, Dietmar Van Werkum, Jochem W. Paganelli, Franck Price, Matthew J. Waksman, Ron Gurbel, Paul A. CA Working Grp High On-Treatment TI Consensus and Future Directions on the Definition of High On-Treatment Platelet Reactivity to Adenosine Diphosphate SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE adenosine diphosphate; percutaneous coronary intervention; platelet reactivity; thrombotic events ID PERCUTANEOUS CORONARY INTERVENTION; VASODILATOR-STIMULATED PHOSPHOPROTEIN; OF-CARE ASSAY; ADVERSE CARDIOVASCULAR EVENTS; CLOPIDOGREL-TREATED PATIENTS; ACUTE MYOCARDIAL-INFARCTION; ELUTING STENT IMPLANTATION; STABLE ANGINA-PECTORIS; ANTIPLATELET THERAPY; ARTERY-DISEASE AB The addition of clopidogrel to aspirin treatment reduces ischemic events in a wide range of patients with cardiovascular disease. However, recurrent ischemic event occurrence during dual antiplatelet therapy, including stent thrombosis, remains a major concern. Platelet function measurements during clopidogrel treatment demonstrated a variable and overall modest level of P2Y12 inhibition. High on-treatment platelet reactivity to adenosine diphosphate ( ADP) was observed in selected patients. Multiple studies have now demonstrated a clear association between high on-treatment platelet reactivity to ADP measured by multiple methods and adverse clinical event occurrence. However, the routine measurement of platelet reactivity has not been widely implemented and recommended in the guidelines. Reasons for the latter include: 1) a lack of consensus on the optimal method to quantify high on-treatment platelet reactivity and the cutoff value associated with clinical risk; and 2) limited data to support that alteration of therapy based on platelet function measurements actually improves outcomes. This review provides a consensus opinion on the definition of high on-treatment platelet reactivity to ADP based on various methods reported in the literature and proposes how this measurement may be used in the future care of patients. C1 [Gurbel, Paul A.] Sinai Hosp Baltimore, Sinai Ctr Thrombosis Res, Cardiac Catheterizat Lab, Baltimore, MD 21215 USA. [Bonello, Laurent; Paganelli, Franck] Hosp Univ Nord, Dept Cardiol, INSERM, Fac Med,Unite Mixte Rech UMRS 608, Marseille, France. [Cuisset, Thomas] CHU Timone, Dept Cardiol, Marseille, France. [Collet, Jean Philippe; Montalescot, Gilles] CHU Pitie Salpetriere, Inst Cardiol, Paris, France. [Gachet, Christian] Univ Strasbourg, INSERM, Etab Francais Sang Alsace, UMRS 949, Strasbourg, France. [Marcucci, Rossella] Univ Florence, Dept Med, Ctr Atherothrombot Dis, Florence, Italy. [Marcucci, Rossella] Univ Florence, Surg Crit Area, Florence, Italy. [Cattaneo, Marco] Univ Milan, Osped San Paolo, Unita Med 3, Milan, Italy. [Blindt, Ruediger] Univ Hosp Aachen, Dept Cardiol, Aachen, Germany. [Sibbing, Dirk] Tech Univ Munich, Klinikum Rechts Isar, Deutsch Herzzentrum Munchen, D-8000 Munich, Germany. [Sibbing, Dirk] Tech Univ Munich, Klinikum Rechts Isar, Med Klin 1, D-8000 Munich, Germany. [Trenk, Dietmar] Herz Zentrum Bad Krozingen, Bad Krozingen, Germany. [Van Werkum, Jochem W.] St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Div Cardiol, Dept Med, Jacksonville, FL USA. [Becker, Richard] Duke Univ, Sch Med, Duke Clin Res Inst, Div Cardiol, Durham, NC USA. [Cattaneo, Marco] Duke Univ, Sch Med, Duke Clin Res Inst, Div Hematol, Durham, NC USA. [Cattaneo, Marco] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cattaneo, Marco] VA Boston Healthcare Syst, Boston, MA USA. [Jennings, Lisa K.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Kereiakes, Dean] Christ Hosp Heart, Cincinnati, OH USA. [Kereiakes, Dean] Carl & Edyth Lindner Ctr Res & Educ, Vasc Ctr, Cincinnati, OH USA. [Price, Matthew J.] Scripps Clin, Div Cardiovasc Dis, La Jolla, CA 92037 USA. [Waksman, Ron] Washington Hosp Ctr, Div Cardiol, Dept Internal Med, Washington, DC 20010 USA. RP Gurbel, PA (reprint author), Sinai Hosp Baltimore, Sinai Ctr Thrombosis Res, Cardiac Catheterizat Lab, 2401 W Belvedere Ave, Baltimore, MD 21215 USA. EM pgurbel@lifebridgehealth.org RI Gachet, Christian/H-9156-2016; OI Marcucci, Rossella/0000-0001-9549-7176; Cattaneo, Marco/0000-0002-7343-4534 FU Bristol-Myers Squibb; Sanofi-Aventis; Eli Lilly and Company; Daiichi Sankyo, Inc.; GlaxoSmithKline; Otsuka; Boston Scientific; Accumetrics; Medicines Company; AstraZeneca; Eisai; Portola Pharmaceutical; Schering-Plough; Johnson Johnson; Bayer; Merck; Ethicon; Heartscape; Eli Lilly; Federation Francaise de Cardiologie; Societe Francaise de Cardiologie; Fondation de France; INSERM; Medtronic; Guerbet Medical; Cordis; Stago; Abbott Vascular; Centocor; ITC Edison; Pfizer; Menarini; Novartis; Portola; Boehringer Ingelheim; Merck Sharpe and Dohme; Amylin Pharmaceuticals; Medpace; REVA Medical Inc.; Dynabyte; Siemens; Biotronik; Sanofi-Aventis/Bristol-Myers Squibb; Millenium; National Institutes of Health; Hemoscope; Eli Lilly/Daiichi Sankyo Inc.; Porotola FX Dr. Marcucci has received an honorary fee as a consultant for Ely-Lilly. Dr. Angiolillo has received lecture fees from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly and Company, and Daiichi Sankyo, Inc.; honoraria for serving on the advisory boards of Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly and Company, Daiichi Sankyo Inc., AstraZeneca, The Medicines Company, Portola Pharmaceuticals, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, Merck, and Evolva Pharmaceuticals; and research grants from GlaxoSmithKline, Otsuka, Boston Scientific, Accumetrics, Eli Lilly and Company, Daiichi Sankyo Inc., The Medicines Company, AstraZeneca, Eisai, Portola Pharmaceutical, Schering-Plough, and Johnson & Johnson. Dr. Becker has received research grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Johnson & Johnson, The Medicines Company, Schering-Plough, and Merck and has served on the scientific advisory boards of Eli Lilly and Daiichi Sankyo Inc.; his institution performs clinical research supported by AstraZeneca. Dr. Bhatt has received research grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi-Aventis, and The Medicines Company. Dr. Cattaneo has received lecture honoraria from Eli Lilly/Daiichi Sankyo Inc., AstraZeneca, and The Medicines Company. Dr. Collet has received research grants from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Federation Francaise de Cardiologie, Societe Francaise de Cardiologie, Fondation de France, INSERM, Medtronic, Guerbet Medical, Cordis, and Stago; consultant fees from Sanofi-Aventis, Eli Lilly, and Bristol-Myers Squibb; and lecture fees from Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly. Dr. Gachet has received research grants from Stago, Sanofi-Aventis, Bristol-Myers Squibb, and Servier and honoraria from Sanofi-Aventis, Bristol-Myers Squibb, Servier, and Eli Lilly, and has also served on the scientific advisory boards of Sanofi-Aventis and Bristol-Myers Squibb. Dr. Montalescot has received research grants from Abbott Vascular, Bristol-Myers Squibb, Boston Scientific, Cordis, Federation Francaise de Cardiologie, Societe Francaise de Cardiologie, Fondation de France, Guerbet Medical, INSERM, Medtronic, Sanofi-Aventis, Eli Lilly, Stago, Centocor, ITC Edison, and Pfizer; consulting fees from AstraZeneca, Eisai, Menarini, Novartis, Pfizer, Portola, Schering-Plough, Sanofi-Aventis, Eli Lilly, Bristol-Myers Squibb, The Medicines Company, Daiichi Sankyo Inc., Bayer, and Boehringer Ingelheim; and lecture fees from Abbott Vascular, Cordis, Menarini, Pfizer, Schering-Plough, Sanofi-Aventis, Eli Lilly, Bristol-Myers Squibb, Merck Sharpe and Dohme, GlaxoSmithKline, Accumetrics, AstraZeneca, and Daiichi Sankyo Inc. Dr. Jennings has served as a consultant for AstraZeneca, Daiichi Sankyo Inc., Schering-Plough/Merck, Sanofi-Aventis/Bristol-Myers Squibb, and Portola; has received grant support from AstraZeneca and Schering-Plough/Merck; and has served on the Speakers' Bureaus of Sanofi-Aventis and Bristol-Myers Squibb. Dr. Kereiakes has received modest grant and/or research support from Abbott Vascular, Amylin Pharmaceuticals, and Boston Scientific; has received modest consulting fees from Eli Lilly, Boston Scientific, Abbott Vascular, Medpace, and REVA Medical Inc.; and has served on the Speakers' Bureau for Eli Lilly. Dr. Sibbing has received speaker fees from Dynabyte and The Medicines Company, as well as fees for advisory board activities from Eli Lilly. Dr.; Trenk has received grants/research support from and served on the Speakers' Bureaus of Eli Lilly and Daiichi Sanko Inc. Dr. Van Werkum has received speaker fees from Accumetrics and Siemens and has been a consultant for and served on the advisory board of The Medicines Company. Dr. Paganelli has received lecture fees from Sanofi-Aventis. Dr. Price has received research grants/support from Bristol-Myers Squibb/Sanofi-Aventis and Accumetrics and consulting and/or speaker fees from AstraZeneca, Daiichi Sankyo Inc./Eli Lilly, Bristol-Myers Squibb/Sanofi-Aventis, The Medicines Company, and Accumetrics. Dr. Waksman has received consulting and speaker fees from Biotronik, Medtronic, and Boston Scientific and research grants from Eli Lilly, Sanofi-Aventis/Bristol-Myers Squibb, Biotronik, Boston Scientific, The Medicines Company, GlaxoSmithKline, and Schering-Plough. Dr. Gurbel has received research grants from Schering-Plough, Millenium, AstraZeneca, National Institutes of Health, Hemoscope, Medtronic, Eli Lilly/Daiichi Sankyo Inc., Sanofi-Aventis, Porotola, Bristol-Myers Squibb, Boston Scientific, Bayer, and Pozen; and honoraria from Schering-Plough, Portola, AstraZeneca, Bayer, and Medtronic. All other authors have reported that they have no relationships to disclose. NR 100 TC 650 Z9 681 U1 5 U2 42 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 14 PY 2010 VL 56 IS 12 BP 919 EP 933 DI 10.1016/j.jacc.2010.04.047 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647KJ UT WOS:000281617100001 PM 20828644 ER PT J AU Mejia, NI Nardin, R AF Mejia, Nicte I. Nardin, Rachel TI Dying young Eliminating racial disparities in neuromuscular disease outcomes SO NEUROLOGY LA English DT Editorial Material ID QUALITY-OF-CARE; SOCIOECONOMIC-STATUS; UNITED-STATES C1 [Mejia, Nicte I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mejia, Nicte I.; Nardin, Rachel] Cambridge Hosp, Cambridge, MA 02139 USA. [Mejia, Nicte I.] Harvard Univ, Sch Med, Boston, MA USA. RP Mejia, NI (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WACC 835, Boston, MA 02114 USA. EM nmejia@partners.org NR 15 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 14 PY 2010 VL 75 IS 11 BP 948 EP 949 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 653BP UT WOS:000282058600003 PM 20837962 ER PT J AU Perloff, MD LeRoy, AM Ensrud, ER AF Perloff, Michael D. LeRoy, Andree M. Ensrud, Erik R. TI Teaching Video NeuroImages: The elusive L5 reflex SO NEUROLOGY LA English DT Editorial Material C1 [Perloff, Michael D.] Boston Univ, Sch Med, Med Ctr, Dept Neurol, Boston, MA 02118 USA. [LeRoy, Andree M.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept PM&R, Boston, MA USA. [Ensrud, Erik R.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Dept Neurol, Jamaica Plain, MA USA. RP Perloff, MD (reprint author), Boston Univ, Sch Med, Med Ctr, Dept Neurol, 72 E Concord St,C3, Boston, MA 02118 USA. EM Michael.Perloff@nyumc.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 14 PY 2010 VL 75 IS 11 BP E50 EP E50 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 653BP UT WOS:000282058600020 PM 20837959 ER PT J AU Luthi-Carter, R Kazantsev, AG AF Luthi-Carter, Ruth Kazantsev, Aleksey G. TI Reply to Valenza and Cattaneo: SIRT2-mediated neuroprotection and cholesterol dyshomeostasis in Huntington's disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID ENDOCYTOSIS C1 [Kazantsev, Aleksey G.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Luthi-Carter, Ruth] Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland. [Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Kazantsev, AG (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. EM akazantsev@partners.org NR 6 TC 1 Z9 1 U1 0 U2 1 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 14 PY 2010 VL 107 IS 37 BP 16000 EP 16000 DI 10.1073/pnas.1009871107 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 649UI UT WOS:000281799000004 ER PT J AU Tanwar, PS Zhang, LH Tanaka, Y Taketo, MM Donahoe, PK Teixeira, JM AF Tanwar, Pradeep S. Zhang, LiHua Tanaka, Yoshihiro Taketo, Makoto M. Donahoe, Patricia K. Teixeira, Jose M. TI Focal Mullerian duct retention in male mice with constitutively activated beta-catenin expression in the Mullerian duct mesenchyme SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE anti-Mullerian hormone; epididymis; Mullerian inhibiting substance type II receptor (MISRII or MISR2); spermatocele; epididymis ID FEMALE REPRODUCTIVE-TRACT; INHIBITING SUBSTANCE; SEXUAL DEVELOPMENT; SERTOLI-CELLS; FETAL TESTIS; CYCLIN D1; REGRESSION; DIFFERENTIATION; RECEPTOR; PATHWAY AB Mullerian-inhibiting substance (MIS), which is produced by fetal Sertoli cells shortly after commitment of the bipotential gonads to testicular differentiation, causes Mullerian duct (MD) regression. In the fetal female gonads, MIS is not expressed and the MDs will differentiate into the internal female reproductive tract. We have investigated whether dysregulated beta-catenin activity affects MD regression by expressing a constitutively activated nuclear form of beta-catenin in the MD mesenchyme. We show that constitutively activated (CA) beta-catenin causes focal retention of MD tissue in the epididymides and vasa deferentia. In adult mutant mice, the retained MD tissues express alpha-smooth muscle actin and desmin, which are markers for uterine differentiation. MD retention inhibited the folding complexity of the developing epididymides and usually led to obstructive azoospermia by spermatoceles. The MDs of urogenital ridges from mutant female embryos showed less regression with added MIS in organ culture compared with control MDs when analyzed by whole mount in situ hybridization for Wnt7a as a marker for the MD epithelium. CA beta-catenin did not appear to affect expression of either MIS in the embryonic testes or its type II receptor (AMHR2) in the MD mesenchyme nor did it inhibit pSmad1/5/8 nuclear accumulation, suggesting that dysregulated beta-catenin must inhibit MD regression independently of MIS signaling. These studies suggest that dysregulated Wnt/beta-catenin signaling in the MD mesenchyme might also be a contributing factor in persistent Mullerian duct syndrome, a form of male pseudohermaphroditism, and development of spermatoceles. C1 [Donahoe, Patricia K.] Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs, Boston, MA 02114 USA. [Tanwar, Pradeep S.; Zhang, LiHua; Tanaka, Yoshihiro; Teixeira, Jose M.] Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Taketo, Makoto M.] Kyoto Univ, Dept Pharmacol, Grad Sch Med, Kyoto 6068501, Japan. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs, Boston, MA 02114 USA. EM pdonahoe@partners.org; teixeira@helix.mgh.harvard.edu OI Teixeira, Jose/0000-0002-6438-5064 FU National Institutes of Health [HD057201]; Vincent Memorial research funds FX We thank Dr. Richard Behringer (MD Anderson, Houston, TX) for supplying us with the Amhr2-Cre mice and Dr. Barry Hinton for his help with the analysis of the epididymides. These studies were supported in part by National Institutes of Health Grant HD057201 (to J.M.T.) and by Vincent Memorial research funds. NR 46 TC 17 Z9 17 U1 0 U2 0 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 14 PY 2010 VL 107 IS 37 BP 16142 EP 16147 DI 10.1073/pnas.1011606107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 649UI UT WOS:000281799000032 PM 20805501 ER PT J AU Daniel, C Wennhold, K Kim, HJ von Boehmer, H AF Daniel, Carolin Wennhold, Kerstin Kim, Hye-Jung von Boehmer, Harald TI Enhancement of antigen-specific Treg vaccination in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antigen-specific Treg conversion; Foxp3; IL-2/IL-2ab complexes; mammalian target of rapamycin; prospective tolerance ID REGULATORY T-CELLS; TRANSCRIPTION FACTOR FOXP3; GENE-EXPRESSION; DNA METHYLATION; P2X RECEPTORS; INDUCTION; MTOR; DEMETHYLATION; STIMULATION; COMMITMENT AB The conversion of naive T cells into Treg can be achieved in vivo by delivery of antigen under subimmunogenic conditions. Here we have examined several drugs for their ability to enhance the conversion process in vivo and have found that the rapamycin analog everolimus potently enhances Treg conversion by interfering with T-cell costimulation, reducing cell division and thereby activation of DNA methyltransferase 1 as well as by reducing T-cell activation through the ATP-gated P2x7 receptor controlling Ca2(+) influx. The resulting Tregs exhibit increased stability of Foxp3 expression even when generated in TGF beta-containing media in vitro. Thus the mammalian target of rapamycin (mTOR) inhibitor everolimus in addition to inhibiting immune responses enhances Treg conversion by several distinct pathways. The converted Tregs can be further expanded by injection of IL-2/IL-2ab complexes. These complexes also increase the number of CD25(+)Foxp3(-) cells that, however, do not represent cytokine secreting effector cells but anergic cells, some of which can secrete IL-10 and can themselves be considered regulatory T cells as well. The combined use of everolimus and IL-2/IL-2ab complexes in vivo makes it feasible to achieve highly effective antigen-driven conversion of naive T cells into Treg and their expansion in vivo and thereby the described protocols constitute important tools to achieve immunological tolerance by Treg vaccination. C1 [Daniel, Carolin; Wennhold, Kerstin; Kim, Hye-Jung; von Boehmer, Harald] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Daniel, Carolin; Wennhold, Kerstin; Kim, Hye-Jung; von Boehmer, Harald] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu RI Daniel, Carolin/M-4624-2014 OI Daniel, Carolin/0000-0003-4698-7069 FU National Institutes of Health [NIH-AI-53102]; Leopoldina research fellowship [BMBF-LPD 9901/8-184]; Federal State of Hessen, Germany FX These studies were supported by National Institutes of Health Grant NIH-AI-53102 (to H.v.B.). C.D. was supported by a Leopoldina research fellowship (BMBF-LPD 9901/8-184) and by the LOEWE (Lipid Signaling Forschungszentrum Frankfurt) program of the Federal State of Hessen, Germany. NR 33 TC 51 Z9 51 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 14 PY 2010 VL 107 IS 37 BP 16246 EP 16251 DI 10.1073/pnas.1007422107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 649UI UT WOS:000281799000050 PM 20805478 ER PT J AU Nascimento, E Fernandes, DF Vieira, EP Campos-Neto, A Ashman, JA Alves, FP Coler, RN Bogatzki, LY Kahn, SJ Beckmann, AM Pine, SO Cowgill, KD Reed, SG Piazza, FM AF Nascimento, Evaldo Fernandes, Demetrios F. Vieira, Edva P. Campos-Neto, Antonio Ashman, Jill A. Alves, Fabiana P. Coler, Rhea N. Bogatzki, Lisa Y. Kahn, Stuart J. Beckmann, Anna Marie Pine, Samuel O. Cowgill, Karen D. Reed, Steven G. Piazza, Franco M. TI A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine when used in combination with meglumine antimoniate for the treatment of cutaneous leishmaniasis SO VACCINE LA English DT Article DE Leishmaniasis vaccines; Adjuvants; Immunologic; Leishmaniasis; Cutaneous ID LIPID-A; IMMUNOTHERAPY; CHEMOTHERAPY; ADJUVANT AB Forty-four adult patients with cutaneous leishmaniasis (CL) were enrolled in a randomized, double-blind, controlled, dose-escalating clinical trial and were randomly assigned to receive three injections of either the LEISH-F1 + MPL-SE vaccine (consisting of 5, 10, or 20 recombinant Leishmania polyprotein LEISH-F1 antigen + 25 mu g MPL (R)-SE adjuvant) (n =27), adjuvant alone (n = 8), or saline placebo (n = 9). The study injections were given subcutaneously on Days 0, 28, and 56, and the patients were followed through Day 336 for safety, immunological, and clinical evolution endpoints. All patients received chemotherapy with meglumine antimoniate starting on Day 0. The vaccine was safe and well tolerated. Nearly all vaccine recipients and no adjuvant-alone or placebo recipients demonstrated an IgG antibody response to LEISH-F1 at Day 84. Also at Day 84, 80% of vaccine recipients were clinically cured, compared to 50% and 38% of adjuvant-alone and placebo recipients. The LEISH-F1 + MPL-SE vaccine was safe and immunogenic in CL patients and appeared to shorten their time to cure when used in combination with meglumine antimoniate chemotherapy. (c) 2010 Elsevier Ltd. All rights reserved. C1 [Ashman, Jill A.; Alves, Fabiana P.; Coler, Rhea N.; Bogatzki, Lisa Y.; Kahn, Stuart J.; Beckmann, Anna Marie; Pine, Samuel O.; Cowgill, Karen D.; Reed, Steven G.; Piazza, Franco M.] IDRI, Seattle, WA 98104 USA. [Nascimento, Evaldo] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [Nascimento, Evaldo] Hosp Santa Casa Belo Horizonte, Ctr Ensino & Pesquisa, Belo Horizonte, MG, Brazil. [Nascimento, Evaldo; Fernandes, Demetrios F.] Hosp Municipal Januaria, Januaria, MG, Brazil. [Campos-Neto, Antonio] Forsyth Inst, Boston, MA USA. RP Piazza, FM (reprint author), IDRI, 1124 Columbia St,Suite 400, Seattle, WA 98104 USA. EM fpiazza@idri.org FU Bill and Melinda Gates Foundation [631, 39129] FX Funding: This work was supported by Grants 631 and 39129 from the Bill and Melinda Gates Foundation. NR 26 TC 36 Z9 36 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 14 PY 2010 VL 28 IS 40 BP 6581 EP 6587 DI 10.1016/j.vaccine.2010.07.063 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 656ZF UT WOS:000282379000005 PM 20688040 ER PT J AU Sohn, IB Kim, Y Noh, YC Lee, IW Kim, JK Lee, H AF Sohn, Ik-Bu Kim, Youngseop Noh, Young-Chul Lee, In Won Kim, Jun Ki Lee, Ho TI Femtosecond laser and arc discharge induced microstructuring on optical fiber tip for the multidirectional firing SO OPTICS EXPRESS LA English DT Article ID PHOTONIC DEVICES; FABRICATION AB Most optical fibers are designed for forward firing i.e. the light is emitted at the distal end along the optical axis of the fiber. In some applications such as the laser surgery and laser scanners, side firing of the optical fiber is required. In this paper, we present the microstructuring of an optical fiber tip using the femtosecond laser and an arc discharging process for the multidirectional firing of the beam. The distal end of the optical fiber with diameter of 125 mu m was machined into a conical structure using a femtosecond laser. The surface of the machined tip was exposed to the arc discharge using a fiber splicer. The arc discharge leads to the melting and re-solidification of the fiber tip. This results in a smoothing of laser-induced conical microstructure at the tip of the fiber. We were able to demonstrate the multidirectional (circumferential) emission of the light from the developed fiber tip. (C) 2010 Optical Society of America C1 [Sohn, Ik-Bu; Kim, Youngseop; Noh, Young-Chul; Lee, In Won] Gwangju Inst Sci & Technol, Adv Photon Res Inst, Kwangju 500712, South Korea. [Kim, Jun Ki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kim, Jun Ki] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Lee, Ho] Kyungpook Natl Univ, Sch Mech Engn, Taegu 702701, South Korea. RP Sohn, IB (reprint author), Gwangju Inst Sci & Technol, Adv Photon Res Inst, 261 Cheomdan Gwagiro, Kwangju 500712, South Korea. EM optin@gist.ac.kr; holee@knu.ac.kr FU Gwangju Institute of Science Technology; Korea Government (MEST) [20090091571] FX This work was partially supported by the Asian Laser Center Program through a grant provided by the Gwangju Institute of Science & Technology and partially supported by National Research Foundation grant funded by the Korea Government (MEST: No 20090091571). NR 10 TC 12 Z9 12 U1 0 U2 3 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 13 PY 2010 VL 18 IS 19 BP 19755 EP 19760 DI 10.1364/OE.18.019755 PG 6 WC Optics SC Optics GA 649NX UT WOS:000281779600027 PM 20940870 ER PT J AU Teerlink, JR AF Teerlink, John R. TI Ivabradine in heart failure-no paradigm SHIFT ... yet SO LANCET LA English DT Editorial Material ID CARDIAC-INSUFFICIENCY BISOPROLOL; PLACEBO-CONTROLLED TRIAL; RATE REDUCTION; RANDOMIZED-TRIAL; I-F; CARVEDILOL; DISEASE; DYSFUNCTION; METOPROLOL; CIBIS C1 [Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Teerlink, JR (reprint author), Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. EM john.teerlink@ucsf.edu RI Teerlink, John/D-2986-2012 NR 19 TC 25 Z9 27 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD SEP 11 PY 2010 VL 376 IS 9744 BP 847 EP 849 DI 10.1016/S0140-6736(10)61314-1 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 653DW UT WOS:000282069100004 PM 20801501 ER PT J AU Fiskerstrand, T H'mida-Ben Brahim, D Johanssond, 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 Bindoff, LA Koenig, M Knappskog, PM AF Fiskerstrand, Torunn H'mida-Ben Brahim, Dorra Johanssond, Stefan M'zahem, Abderrahim Haukanes, Bjorn Ivar Drouot, Nathalie Zimmermann, Julian Cole, Andrew J. Vedeler, Christian Bredrup, Cecilie Assoum, Mirna Tazir, Meriem Klockgether, Thomas Hamri, Abdelmadjid Steen, Vidar M. Boman, Helge Bindoff, Laurence A. Koenig, Michel Knappskog, Per M. TI Mutations in ABHD12 Cause the Neurodegenerative Disease PHARC: An Inborn Error of Endocannabinoid Metabolism SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MICROGLIAL CELLS; 2-ARACHIDONOYLGLYCEROL; BLOCKADE; ENZYMES; SYSTEM; 2-AG; ACID AB Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a neurodegenerative disease marked by early-onset cataract and hearing loss, retinitis pigmentosa, and involvement of both the central and peripheral nervous systems, including demyelinating sensorimotor polyneuropathy and cerebellar ataxia. Previously, we mapped this Refsum-like disorder to a 16 Mb region on chromosome 20. Here we report that mutations in the ABHD12 gene cause PHARC disease and we describe the clinical manifestations in a total of 19 patients from four different countries. The ABHD12 enzyme was recently shown to hydrolyze 2-arachidonoyl glycerol (2-AG), the main endocannabinoid lipid transmitter that acts on cannabinoid receptors CB1 and CB2. Our data therefore represent an example of an inherited disorder related to endocannabinoid metabolism. The endocannabinoid system is involved in a wide range of physiological processes including neurotransmission, mood, appetite, pain appreciation, addiction behavior, and inflammation, and several potential drugs targeting these pathways are in development for clinical applications. Our findings show that ABHD12 performs essential functions in both the central and peripheral nervous systems and the eye. Any future drug-mediated interference with this enzyme should consider the potential risk of long-term adverse effects. C1 [Fiskerstrand, Torunn; Johanssond, Stefan; Haukanes, Bjorn Ivar; Steen, Vidar M.; Boman, Helge; Knappskog, Per M.] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. [H'mida-Ben Brahim, Dorra; Drouot, Nathalie; Assoum, Mirna; Koenig, Michel] Univ Strasbourg, CNRS, INSERM, IGBMC, F-67000 Illkirch Graffenstaden, France. [M'zahem, Abderrahim; Hamri, Abdelmadjid] Univ Benbadis, Ctr Hosp, Constantine 25000, Algeria. [Zimmermann, Julian; Klockgether, Thomas] Univ Klinikum, Klin & Poliklin Neurol, D-53105 Bonn, Germany. [Cole, Andrew J.] Massachusetts Gen Hosp, MGH Epilepsy Serv, Boston, MA 02114 USA. [Cole, Andrew J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vedeler, Christian; Bindoff, Laurence A.] Haukeland Hosp, Dept Neurol, N-5021 Bergen, Norway. [Vedeler, Christian; Steen, Vidar M.; Bindoff, Laurence A.; Knappskog, Per M.] Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway. [Bredrup, Cecilie] Haukeland Hosp, Dept Ophthalmol, N-5021 Bergen, Norway. [Tazir, Meriem] Ctr Hosp Univ Mustapha, Serv Neurol, Algiers 16000, Algeria. [Klockgether, Thomas] DZNE, D-53105 Bonn, Germany. [H'mida-Ben Brahim, Dorra] CHU Farhat Hached, Serv Cytogenet Genet Mol & Biol Reprod, Sousse 4000, Tunisia. RP Fiskerstrand, T (reprint author), Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. EM torunn.fiskerstrand@helse-bergen.no; mkoenig@igbmc.fr RI LABO, U827/A-8632-2008; Johansson, Stefan/C-4394-2011; OI Johansson, Stefan/0000-0002-2298-7008; Haukanes, Bjorn Ivar/0000-0003-1559-3366; Bindoff, Laurence/0000-0003-0988-276X FU Helse Vest (Western Norway Regional Health Authority) [911308]; Agence Nationale pour la Recherche-Maladies Rares, France [ANR-05-MRAR-013-01]; French association Connaitre les Syndromes Cerebelleux; Centre National de la Recherche Scientifique (CNRS) FX This work was supported by grants from Helse Vest (Western Norway Regional Health Authority, 911308, to P.K., T.F., H.B., V.M.S, and B.I.H.) and from the Agence Nationale pour la Recherche-Maladies Rares (ANR-05-MRAR-013-01, France, to M.K.). D.H.-B.B. was supported by the French association Connaitre les Syndromes Cerebelleux. M.A. was supported by a BDI fellowship from the Centre National de la Recherche Scientifique (CNRS). We thank John Walker and Andrew Su for the kind permission to replot (Figure 2) gene expression data from GNF: Mouse Gene Atlas V3. The technical assistance of Jorunn Skeie Bringsli, Guri Matre, Hilde Rusaas, Sigrid Erdal, Paal Borge, Christine Stansberg, Bard Kjersem, Christelle Thibault, Serge Vicaire, Jone Vignes, and Ingrid Bauer was highly appreciated. We thank the patients and their families for participating in this study. NR 23 TC 66 Z9 68 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP 10 PY 2010 VL 87 IS 3 BP 410 EP 417 DI 10.1016/j.ajhg.2010.08.002 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 651JH UT WOS:000281923500011 PM 20797687 ER PT J AU Goebel, M Stengel, A Wang, LX Coskun, T Alsina-Fernandez, J Rivier, J Tache, Y AF Goebel, Miriam Stengel, Andreas Wang, Lixin Coskun, Tamer Alsina-Fernandez, Jorge Rivier, Jean Tache, Yvette TI Pattern of Fos expression in the brain induced by selective activation of somatostatin receptor 2 in rats SO BRAIN RESEARCH LA English DT Article DE Somatostatin receptor; Brain; Oxytocin; Vasopressin ID GENE-RELATED PEPTIDE; TRIGEMINAL SUBNUCLEUS CAUDALIS; LATERAL PARABRACHIAL NUCLEUS; NERVOUS-SYSTEM REGULATION; ARCUATE NUCLEUS; NEUROPEPTIDE-Y; GROWTH-HORMONE; IN-VITRO; C-FOS; SPINAL-CORD AB Central activation of somatostatin (sst) receptors by oligosomatostatin analogs inhibits growth hormone and stress-related rise in catecholamine plasma levels while stimulating grooming, feeding behaviors, gastric transit and acid secretion, which can be mimicked by selective sst(2) receptor agonist. To evaluate the pattern of neuronal activation induced by peptide sst receptor agonists, we assessed Fos-expression in rat brain after intracerebroventricular (icv) injection of a newly developed selective sst(2) agonist compared to the oligosomatostatin ODT8-SST, a pan-sst(1-5) agonist. Ninety min after injection of vehicle (10 mu l) or previously established maximal orexigenic dose of peptides (1 mu g = 1 nmol/rat), brains were assessed for Fos-immunohistochemistry and doublelabeling. Food and water were removed after injection. The sst(2) agonist and ODT8-SST induced a similar Fos distribution pattern except in the arcuate nucleus where only the sst(2) agonist increased Fos. Compared to ODT8-SST, the sst(2) agonist induced higher Fos-expression by 3.7-times in the basolateral amygdaloid nucleus, 1.2-times in the supraoptic nucleus (SON), 1.6-times in the magnocellular paraventricular hypothalamic nucleus (mPVN), 4.1-times in the external lateral parabrachial nucleus, and 2.6-times in both the inferior olivary nucleus and superficial layer of the caudal spinal trigeminal nucleus. Doublelabeling in the hypothalamus showed that ODT8-SST activates 36% of oxytocin, 63% of vasopressin and 79% of sst(2) immunoreactive neurons in the mPVN and 28%, 55% and 25% in the SON, respectively. Selective activation of sst(2) receptor results in a more robust neuronal activation than the pan-sst(1-5) agonist in various brain regions that may have relevance in sst(2) mediated alterations of behavioral, autonomic and endocrine functions. Published by Elsevier B.V. C1 [Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, Los Angeles, CA 90073 USA. [Goebel, Miriam; Stengel, Andreas; Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis,Dept Med, CURE Digest Dis Res Ctr,Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. [Coskun, Tamer; Alsina-Fernandez, Jorge] Eli Lilly & Co, Biotechnol Discovery Res, Indianapolis, IN 46285 USA. [Rivier, Jean] Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU German Research Foundation [GO 1718/1-1, STE 1765/1-1]; VA Research Career Scientist Award; NIH, Center [R01 DK- 33061, DK-41301] FX This work was supported by German Research Foundation fellowship grants GO 1718/1-1 (M.G.) and STE 1765/1-1 (AS.), the VA Research Career Scientist Award (Y.T.), the NIH R01 DK- 33061 (Y.T.) and Center grant DK-41301 (Animal Core, Y.T.). J.R. is the Dr. Frederik Paulsen Chair in Neurosciences Professor. We are grateful to Mrs. Honghui Liang for her excellent technical support and Ms. Eugenia Hu for reviewing the manuscript. NR 109 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 10 PY 2010 VL 1351 BP 150 EP 164 DI 10.1016/j.brainres.2010.07.024 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 653UD UT WOS:000282121500015 PM 20637739 ER PT J AU Sebro, R Rogus, JJ AF Sebro, Ronnie Rogus, John J. TI The power of the Transmission Disequilibrium Test in the presence of population stratification SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE Transmission Disequilibrium Test; population stratification; power ID COMPLEX HUMAN-DISEASES; LINKAGE DISEQUILIBRIUM; DIABETES-MELLITUS; ASSOCIATION AB The Transmission Disequilibrium Test (TDT) is a family-based test for association based on the rate of transmission of alleles from heterozygous parents to affected offspring, and has gained popularity as this test preserves the Type I error rate. Population stratification results in a decreased number of heterozygous parents compared to that expected assuming Hardy-Weinberg Equilibrium (Wahlund Effect). We show that population stratification changes the relative proportion of the informative mating types. The decrease in the number of heterozygous parents and the change in the relative proportion of the informative mating types result in significant changes to the sample sizes required to achieve the power desired. We show examples of the changes in sample sizes, and provide an easy method for estimating TDT sample sizes in the presence of population stratification. This method potentially aids in reducing the number of false-negative association studies. European Journal of Human Genetics (2010) 18, 1032-1038; doi:10.1038/ejhg.2010.57; published online 5 May 2010 C1 [Sebro, Ronnie] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Sebro, Ronnie] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Rogus, John J.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. RP Sebro, R (reprint author), Univ Calif San Francisco, Inst Human Genet, 513 Parnassus Ave,Suite S965,Box 0794, San Francisco, CA 94143 USA. EM rsebro@radmail.ucsf.edu FU Howard Hughes Medical Institute FX We thank Dr Nan Laird, Dr Christoph Lange, Dr Neil Risch and the reviewers for their valuable comments in preparing this manuscript. Ronnie Sebro was supported by a Howard Hughes Medical Institute Pre-Doctoral Fellowship. NR 19 TC 5 Z9 6 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD SEP 10 PY 2010 VL 18 IS 9 BP 1032 EP 1038 DI 10.1038/ejhg.2010.57 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 641ID UT WOS:000281117400012 PM 20442746 ER PT J AU Zhang, C Browne, A Child, D Tanzi, RE AF Zhang, Can Browne, Andrew Child, Daniel Tanzi, Rudolph E. TI Curcumin Decreases Amyloid-beta Peptide Levels by Attenuating the Maturation of Amyloid-beta Precursor Protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALZHEIMERS-DISEASE; IN-VIVO; SECRETASE CLEAVAGE; TRANSGENIC MOUSE; APP METABOLISM; GENERATION; HYPOTHESIS; EXPRESSION; OLIGOMERS; PATHOLOGY AB Alzheimer disease (AD) is a devastating neurodegenerative disease with no cure. The pathogenesis of AD is believed to be driven primarily by amyloid-beta (A beta), the principal component of senile plaques. A beta is an similar to 4-kDa peptide generated via cleavage of the amyloid-beta precursor protein (APP). Curcumin is a compound in the widely used culinary spice, turmeric, which possesses potent and broad biological activities, including anti-inflammatory and antioxidant activities, chemopreventative effects, and effects on protein trafficking. Recent in vivo studies indicate that curcumin is able to reduce A beta-related pathology in transgenic AD mouse models via unknown molecular mechanisms. Here, we investigated the effects of curcumin on A beta levels and APP processing in various cell lines and mouse primary cortical neurons. We show for the first time that curcumin potently lowers A beta levels by attenuating the maturation of APP in the secretory pathway. These data provide a mechanism of action for the ability of curcumin to attenuate amyloid-beta pathology. C1 [Tanzi, Rudolph E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,MassGen Inst Neurodegenerat Dis, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,MassGen Inst Neurodegenerat Dis, Dept Neurol,Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu FU Cure Alzheimer's Fund; Massachusetts General Hospital; Harvard NeuroDiscovery Center; Massachusetts Alzheimer's Disease Research Center FX This work was supported by the Cure Alzheimer's Fund, the Funds for Medical Discovery from Massachusetts General Hospital, and a Neurodegenerative Disease Pilot Study Grant from the Harvard NeuroDiscovery Center and Massachusetts Alzheimer's Disease Research Center. NR 39 TC 76 Z9 81 U1 1 U2 13 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 10 PY 2010 VL 285 IS 37 BP 28472 EP 28480 DI 10.1074/jbc.M110.133520 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647CR UT WOS:000281594000010 PM 20622013 ER PT J AU Goodwin, PJ Meyerhardt, JA Hursting, SD AF Goodwin, Pamela J. Meyerhardt, Jeffrey A. Hursting, Stephen D. TI Host Factors and Cancer Outcome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BREAST-CANCER; TRIAL C1 [Goodwin, Pamela J.] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Goodwin, Pamela J.] Univ Toronto, Princess Margaret Hosp, Toronto, ON M5G 1X5, Canada. [Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hursting, Stephen D.] Univ Texas Austin, Austin, TX 78712 USA. [Hursting, Stephen D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Goodwin, PJ (reprint author), Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. RI Goodwin, Pamela/K-1477-2013 NR 18 TC 9 Z9 11 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 10 PY 2010 VL 28 IS 26 BP 4019 EP 4021 DI 10.1200/JCO.2010.31.5143 PG 3 WC Oncology SC Oncology GA 648ET UT WOS:000281673900001 PM 20697081 ER PT J AU Coate, L Cuffe, S Horgan, A Hung, RJ Christiani, D Liu, G AF Coate, Linda Cuffe, Sinead Horgan, Anne Hung, Rayjean J. Christiani, David Liu, Geoffrey TI Germline Genetic Variation, Cancer Outcome, and Pharmacogenetics SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID NONPOLYPOSIS COLORECTAL-CANCER; HEREDITARY BREAST-CANCER; GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; ACUTE LYMPHOBLASTIC-LEUKEMIA; DIHYDROPYRIMIDINE DEHYDROGENASE-DEFICIENCY; EPITHELIAL OVARIAN-CANCER; GENOME-WIDE ASSOCIATION; DNA-REPAIR GENES; FC-GAMMA-RIIIA AB Studies of the role of germline or inherited genetic variation on cancer outcome can fall into three distinct categories. First, the impact of highly penetrant but lowly prevalent mutations of germline DNA on cancer prognosis has been studied extensively for BRCA1 and BRCA2 mutations as well as mutations related to hereditary nonpolyposis colorectal cancer syndrome. These mainly modest-sized analyses have produced conflicting results. Although some associations have been observed, they may not be independent of other known clinical or molecular prognostic factors. Second, the impact of germline polymorphisms on cancer prognosis is a burgeoning field of research. However, a deeper understanding of potentially confounding somatic changes and larger multi-institutional, multistage studies may be needed before consistent results are seen. Third, research examining the impact of germline genetic variation on differential treatment response or toxicity (pharmacogenetics) has produced some proof-of-principle results. Putative germline pharmacogenetic predictors of outcome include DPYD polymorphisms and fluorouracil toxicity, UGT1A1 variation and irinotecan toxicity, and CYP2D6 polymorphisms and tamoxifen efficacy, with emerging data on predictors of molecularly targeted or biologic drugs. Here we review data pertaining to these germline outcome and germline toxicity relationships. C1 [Liu, Geoffrey] Princess Margaret Hosp, Dept Med Oncol, Univ Hlth Network, Toronto, ON M5G 2M9, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Harvard Univ, Harvard Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. Univ Toronto, Toronto, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Liu, G (reprint author), Princess Margaret Hosp, Dept Med Oncol, Univ Hlth Network, 610 Univ Ave,Room 7-124, Toronto, ON M5G 2M9, Canada. EM geoffrey.liu@uhn.on.ca RI Hung, Rayjean/A-7439-2013 FU Alan B. Brown Chair in Molecular Genomics and Cancer Care Ontario Research Chair in Experimental Therapeutics and Population Studies; Ontario Institute for Cancer Research; Posluns Family Foundation, Toronto, Ontario, Canada FX Supported in part by the Alan B. Brown Chair in Molecular Genomics and Cancer Care Ontario Research Chair in Experimental Therapeutics and Population Studies (G. L.), operating grants from the Ontario Institute for Cancer Research, and the Posluns Family Foundation, Toronto, Ontario, Canada. NR 126 TC 43 Z9 44 U1 0 U2 4 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 10 PY 2010 VL 28 IS 26 BP 4029 EP 4037 DI 10.1200/JCO.2009.27.2336 PG 9 WC Oncology SC Oncology GA 648ET UT WOS:000281673900003 PM 20679599 ER PT J AU Ferrone, C Dranoff, G AF Ferrone, Cristina Dranoff, Glenn TI Dual Roles for Immunity in Gastrointestinal Cancers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID FAMILIAL ADENOMATOUS POLYPOSIS; COLITIS-ASSOCIATED CANCER; NF-KAPPA-B; HELICOBACTER-PYLORI; HEPATOCELLULAR-CARCINOMA; T-CELLS; COLORECTAL-CANCER; INTERLEUKIN-10 RECEPTOR; ULCERATIVE-COLITIS; LYMPHOCYTES INDUCE AB Histopathologic examination reveals that most human tumors are associated with diverse immune cell infiltrates, but the roles of host reactions in disease pathogenesis and prognosis remain to be fully clarified. Recent investigations in genetically engineered murine tumor models have uncovered dual functions for immune responses during cancer development and progression. Alterations in tumor cell gene expression profiles and coding sequences may trigger the activation of cytotoxic lymphocytes, which act to restrain tumor growth. In contrast, persistent inflammatory reactions, which may be driven by infection, environmental toxins, or impaired immune regulation, create a microenvironment that fosters tumor cell growth, survival, invasion, and dissemination. The dynamic interplay of these competing responses appears to be a critical event in cancer pathogenesis, with tumor promotion and immune evasion proving dominant in clinically evident disease. Nonetheless, longitudinal studies of patient cohorts have demonstrated that particular histopathologic and genetic signatures of cytotoxic lymphocyte reactions provide important prognostic information. Here, we discuss the dual roles of immunity in cancer development, focusing on gastrointestinal malignancies, given the depth of recent insights into the mechanisms underlying these tumors. C1 [Dranoff, Glenn] Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Canc Vaccine Ctr, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 520C, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu FU NCI NIH HHS [R01 CA143083] NR 89 TC 51 Z9 53 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 10 PY 2010 VL 28 IS 26 BP 4045 EP 4051 DI 10.1200/JCO.2010.27.9992 PG 7 WC Oncology SC Oncology GA 648ET UT WOS:000281673900005 PM 20644090 ER PT J AU Meyerhardt, JA Ma, J Courneya, KS AF Meyerhardt, Jeffrey A. Ma, Jing Courneya, Kerry S. TI Energetics in Colorectal and Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID BODY-MASS INDEX; ANDROGEN-DEPRIVATION THERAPY; QUALITY-OF-LIFE; III COLON-CANCER; RANDOMIZED CONTROLLED-TRIAL; TREATMENT-RELATED TOXICITY; PHYSICAL-ACTIVITY; RADICAL PROSTATECTOMY; RADIATION-THERAPY; INFORMED CHOICES AB For decades, extensive research has explored the association between factors related to energy balance and the development of both colorectal cancer and prostate cancer. Physical inactivity, obesity, higher red meat consumption or Western pattern diet, insulin and insulin-like growth factors (IGFs) appear to increase the risk of colorectal cancer while obesity, high animal fat intake, insulin and IGFs have been associated with increasing prostate cancer risk and/or aggressiveness. Recently, there are growing observational data on the relationship between energetic host factors and progression of these cancers. While there are no large randomized trials in either colorectal cancer or prostate cancer assessing these factors on disease progression or disease-related mortality, the data supporting associations between some of these factors and colorectal or prostate cancer survivorship are getting more compelling. This article will evaluate the emerging data on energy balance in patients with colorectal or prostate cancer. C1 [Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Alberta, Edmonton, AB, Canada. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jmeyerhardt@partners.org FU Canada Research Chairs Program; National Cancer Institute [R01 CA118553, P50 CA127003, P01CA87969, P01 CA55075] FX Supported by the Canada Research Chairs Program (K.S.C.); and Grants No. R01 CA118553, P50 CA127003, P01CA87969, and P01 CA55075 (J.A.M.) from the National Cancer Institute. NR 85 TC 30 Z9 30 U1 0 U2 7 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 10 PY 2010 VL 28 IS 26 BP 4066 EP 4073 DI 10.1200/JCO.2009.26.8797 PG 8 WC Oncology SC Oncology GA 648ET UT WOS:000281673900008 PM 20644082 ER PT J AU Giovannucci, E Chan, AT AF Giovannucci, Edward Chan, Andrew T. TI Role of Vitamin and Mineral Supplementation and Aspirin Use in Cancer Survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CIRCULATING 25-HYDROXYVITAMIN-D LEVELS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PREVENT COLORECTAL ADENOMAS; PROSTATE-CANCER; FOLIC-ACID; BREAST-CANCER; LUNG-CANCER; RANDOMIZED-TRIAL; DIETARY-FOLATE; UNITED-STATES AB Multivitamins and multiminerals are widely used in the United States, but their efficacy and, perhaps more importantly, the potential for harm in individuals who have cancer have received relatively little study. Beyond their general effects on health, the use of vitamins and minerals by patients with cancer has unique implications because of their potential direct effects on existing cancers, effects on factors that may influence carcinogenesis, such as immunity, and interactions with treatment. Some evidence suggests that vitamin D at higher than standard doses may improve cancer-specific and overall survival for several cancer sites. Besides vitamin D, there is little evidence that nutritional supplements lower the risk of recurrence or improve survival from cancer, although some benefits may be possible in specific subgroups. Some data suggest that higher than standard doses of some vitamins or minerals could even enhance carcinogenesis or worsen survival in patients with cancer. For example, evidence suggests that although folate supplementation administered in preneoplastic stages may lower the risk of colorectal cancer, excessive folic acid in patients with established cancer may be harmful. For prostate cancer, some preliminary evidence indicates that excess consumption of one or a combination of components in a multivitamin/multimineral may accelerate cancer progression and increase fatality. Use of aspirin is proven to lower risk of colorectal cancer, and recent evidence suggests that aspirin use in patients with colorectal cancer improves cancer-specific and overall survival, especially in patients with tumors that express cyclooxygenase-2 (COX-2). The potential beneficial or adverse effects of dietary supplements and aspirin in survivors of cancer warrant further study. C1 [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Giovannucci, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM egiovann@hsph.harvard.edu FU NCI NIH HHS [R01 CA137178] NR 50 TC 27 Z9 27 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2010 VL 28 IS 26 BP 4081 EP 4085 DI 10.1200/JCO.2009.27.3219 PG 5 WC Oncology SC Oncology GA 648ET UT WOS:000281673900010 PM 20697066 ER PT J AU Gao, DM Wan, LX Inuzuka, H Berg, AH Tseng, A Zhai, B Shaik, S Bennett, E Tron, AE Gasser, JA Lau, A Gygi, SP Harper, JW DeCaprio, JA Toker, A Wei, WY AF Gao, Daming Wan, Lixin Inuzuka, Hiroyuki Berg, Anders H. Tseng, Alan Zhai, Bo Shaik, Shavali Bennett, Eric Tron, Adriana E. Gasser, Jessica A. Lau, Alan Gygi, Steven P. Harper, J. Wade DeCaprio, James A. Toker, Alex Wei, Wenyi TI Rictor Forms a Complex with Cullin-1 to Promote SGK1 Ubiquitination and Destruction SO MOLECULAR CELL LA English DT Article ID PROTEIN-KINASE; MTOR COMPLEX; PHOSPHORYLATION ANALYSIS; AKT PHOSPHORYLATION; SURVIVAL SIGNALS; E3 LIGASE; SERUM; DEGRADATION; RAPTOR; DOWNSTREAM AB The Rictor/mTOR complex (also known as mTORC2) plays a critical role in cellular homeostasis by phosphorylating AGC kinases such as Akt and SGK at their hydrophobic motifs to activate downstream signaling. However, the regulation of mTORC2 and whether it has additional function(s) remain largely unknown. Here, we report that Rictor associates with Cullin-1 to form a functional E3 ubiquitin ligase. Rictor, but not Raptor or mTOR alone, promotes SGK1 ubiquitination. Loss of Rictor/Cullin-1-mediated ubiquitination leads to increased SGK1 protein levels as detected in Rictor null cells. Moreover, as part of a feedback mechanism, phosphorylation of Rictor at 11135 by multiple AGC kinases disrupts the interaction between Rictor and Cullin-1 to impair SGK1 ubiquitination. These findings indicate that the Rictor/Cullin-1 E3 ligase activity is regulated by a specific signal relay cascade and that misregulation of this mechanism may contribute to the frequent overexpression of SGK1 in various human cancers. C1 [Gao, Daming; Wan, Lixin; Inuzuka, Hiroyuki; Berg, Anders H.; Tseng, Alan; Shaik, Shavali; Gasser, Jessica A.; Lau, Alan; Toker, Alex; Wei, Wenyi] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Zhai, Bo; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Bennett, Eric; Harper, J. Wade] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Tron, Adriana E.; DeCaprio, James A.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wei, WY (reprint author), Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. EM wwei2@bidmc.harvard.edu RI Wan, Lixin/F-2124-2011 FU DOD; National Institutes of Health [CA122099, GM089763] FX We thank Lewis Cantley, Qing Zhang, Christoph Schorl, Ben Liu, and Susan Glueck for critical reading of the manuscript; Christoph Geisen, Brendan Manning, John Blenis, Yue Xiong, Bing Su, Suzanne Conzan, and Mark Magnuson for providing reagents; Brendan Manning for sharing unpublished data; and members of the Wei, DeCaprio, Harper, and Toker labs for useful discussions. W.W. is a Kimmel Scholar, V Scholar, and Karin Grunebaum Cancer Research Foundation Fellow. This work was supported in part by the DOD Prostate New Investigator award to W.W. and by grants from the National Institutes of Health (A.T., CA122099; W.W., GM089763). NR 48 TC 37 Z9 38 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD SEP 10 PY 2010 VL 39 IS 5 BP 797 EP 808 DI 10.1016/j.molcel.2010.08.016 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 651QA UT WOS:000281941000016 PM 20832730 ER PT J AU Dosenbach, NUF Nardos, B Cohen, AL Fair, DA Power, JD Church, JA Nelson, SM Wig, GS Vogel, AC Lessov-Schlaggar, CN Barnes, KA Dubis, JW Feczko, E Coalson, RS Pruett, JR Barch, DM Petersen, SE Schlaggar, BL AF Dosenbach, Nico U. F. Nardos, Binyam Cohen, Alexander L. Fair, Damien A. Power, Jonathan D. Church, Jessica A. Nelson, Steven M. Wig, Gagan S. Vogel, Alecia C. Lessov-Schlaggar, Christina N. Barnes, Kelly Anne Dubis, Joseph W. Feczko, Eric Coalson, Rebecca S. Pruett, John R., Jr. Barch, Deanna M. Petersen, Steven E. Schlaggar, Bradley L. TI Prediction of Individual Brain Maturity Using fMRI SO SCIENCE LA English DT Article ID RESTING HUMAN BRAIN; FUNCTIONAL CONNECTIVITY; COGNITIVE CONTROL; PATTERN-ANALYSIS; CHILDREN; CORTEX; REPRESENTATIONS; NETWORKS; ABILITY; HUMANS AB Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals' brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain's major functional networks. C1 [Dosenbach, Nico U. F.; Nardos, Binyam; Cohen, Alexander L.; Power, Jonathan D.; Church, Jessica A.; Nelson, Steven M.; Wig, Gagan S.; Vogel, Alecia C.; Barnes, Kelly Anne; Dubis, Joseph W.; Coalson, Rebecca S.; Petersen, Steven E.; Schlaggar, Bradley L.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Fair, Damien A.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Nelson, Steven M.; Barch, Deanna M.; Petersen, Steven E.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA. [Wig, Gagan S.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Wig, Gagan S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Lessov-Schlaggar, Christina N.; Feczko, Eric; Pruett, John R., Jr.; Barch, Deanna M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Coalson, Rebecca S.; Barch, Deanna M.; Petersen, Steven E.; Schlaggar, Bradley L.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Petersen, Steven E.; Schlaggar, Bradley L.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Schlaggar, Bradley L.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP Dosenbach, NUF (reprint author), Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. EM ndosenbach@wustl.edu; schlaggarb@neuro.wustl.edu RI Nelson, Steven/C-1003-2009; Church, Jessica/E-2836-2010; Cohen, Alexander/A-6865-2009; Barch, Deanna/G-8638-2013; Church, Jessica/L-2659-2016 OI Cohen, Alexander/0000-0001-6557-5866; Church, Jessica/0000-0003-1369-9116 FU NIH [NS55582, NS053425, HD057076, NS00169011, NS51281, NS32979, NS41255, NS46424, DA027046]; John Merck Scholars Fund; Burroughs-Wellcome Fund; Dana Foundation; Ogle Family Fund; McDonnell Center; Simons Foundation; American Hearing Research Foundation; Diabetes Research Center at Washington University FX This work was supported by NIH grants NS55582, NS053425, HD057076, and NS00169011 (B.L.S.); NS51281, NS32979, NS41255, and NS46424 (S.E.P.); DA027046 (C.N.L.-S.); EY16336 (J.R.P.); and MH62130 (D.M.B.) and by the John Merck Scholars Fund (B.L.S.), Burroughs-Wellcome Fund (B.L.S.), Dana Foundation (B.L.S.), Ogle Family Fund (B.L.S.), McDonnell Center (S.E.P. and B.L.S.), Simons Foundation (S.E.P.), American Hearing Research Foundation (J. E. C. Lieu), and Diabetes Research Center at Washington University (T. G. Hershey). We thank J. E. C. Lieu, C. E. Pizoli, and T. G. Hershey for providing data and F. M. Miezin, J. Harwell, A. Z. Snyder, and H. M. Lugar for help with data analysis. NR 37 TC 571 Z9 581 U1 17 U2 109 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 SEP 10 PY 2010 VL 329 IS 5997 BP 1358 EP 1361 DI 10.1126/science.1194144 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647YR UT WOS:000281657300043 PM 20829489 ER PT J AU Husain, SS Stewart, D Desai, R Hamouda, AK Li, SGD Kelly, E Dostalova, Z Zhou, XJ Cotten, JF Raines, DE Olsen, RW Cohen, JB Forman, SA Miller, KW AF Husain, S. Shaukat Stewart, Deirdre Desai, Rooma Hamouda, Ayman K. Li, S. Guo-Dong Kelly, Elizabeth Dostalova, Zuzana Zhou, Xiaojuan Cotten, Joseph F. Raines, Douglas E. Olsen, Richard W. Cohen, Jonathan B. Forman, Stuart A. Miller, Keith W. TI p-Trifluoromethyldiazirinyl-etomidate: A Potent Photoreactive General Anesthetic Derivative of Etomidate That Is Selective for Ligand-Gated Cationic Ion Channels SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; GABA(A) RECEPTOR; BINDING-SITE; AMINO-ACID; A RECEPTOR; GLYCINE RECEPTORS; IDENTIFICATION; SUBUNIT; AGONIST; MODULATION AB We synthesized the R- and S-enantiomers of ethyl 1-(1-(4-(3-((trilluoromethyl)-3H-diazirin-3-yl)-phenyl)ethyl)-1H-imidazole-5-carboxylate (trifluoromethyldiazirinyl-etomidate), or TFD-etomidate, a novel photoactivable derivative of the stereoselective general anesthetic etomidate (R-(2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate)). Anesthetic potency was similar to etomidate's, but stereoselectivity was reversed and attenuated. Relative to etomidate, TFD-etomidate was a more potent inhibitor of the excitatory receptors, nAChR (nicotinic acetylcholine receptor) ((alpha 1)(2)beta 1 delta 1 gamma 1) and 5-HT(3A)R (serotonin type 3A receptor), causing significant inhibition at anesthetic concentrations. S- but not R-TFD-etomiclate enhanced currents elicited from inhibitory alpha 1 beta 2 gamma 2L GABA(A) Rs by low concentrations of GABA, but with a lower efficacy than R-etomidate, and site-directed mutagenesis suggests they act at different sites. [(3)H]TFD-etomidate photolabeled the alpha-subunit of the nAChR in a manner allosterically regulated by agonists and noncompetitive inhibitors. TFD-etomidate's novel pharmacology is unlike that of etomidate derivatives with photoactivable groups in the ester position, which behave like etomidate, suggesting that it will further enhance our understanding of anesthetic mechanisms. C1 [Husain, S. Shaukat; Stewart, Deirdre; Desai, Rooma; Kelly, Elizabeth; Dostalova, Zuzana; Zhou, Xiaojuan; Cotten, Joseph F.; Raines, Douglas E.; Forman, Stuart A.; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Hamouda, Ayman K.; Cohen, Jonathan B.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Li, S. Guo-Dong; Olsen, Richard W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 32 Fruit St, Boston, MA 02114 USA. EM k_miller@helix.mgh.harvard.edu OI Hamouda, Ayman/0000-0001-7819-3074 FU National Institute for General Medical Sciences [GM 58448]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital FX This research was supported by a grant from the National Institute for General Medical Sciences to K.W.M. (GM 58448) and by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. We thank Dr. Niall Hamilton, Organon Laboratories, UK, for a kind gift of R-(+)-etomidate. NR 40 TC 12 Z9 12 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 9 PY 2010 VL 53 IS 17 BP 6432 EP 6444 DI 10.1021/jm100498u PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 644TM UT WOS:000281404200016 PM 20704351 ER PT J AU Burgess, SJ Kelly, JX Shomloo, S Wittlin, S Brun, R Liebmann, K Peyton, DH AF Burgess, Steven J. Kelly, Jane X. Shomloo, Shawheen Wittlin, Sergio Brun, Reto Liebmann, Katherine Peyton, David H. TI Synthesis, Structure-Activity Relationship, and Mode-of-Action Studies of Antimalarial Reversed Chloroquine Compounds SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BETA-HEMATIN FORMATION; PLASMODIUM-FALCIPARUM CHLOROQUINE; MALARIA PARASITES; QUINOLINE ANTIMALARIALS; RESISTANCE TRANSPORTER; DRUG RESISTANCE; IN-VITRO; MECHANISM; ASSAY; INHIBITION AB We have previously shown that a "reversed chloroquine (RCQ)" molecule, composed of a chloroquine-like moiety and a resistance reversal-like moiety, can overcome chloroquine resistance in P. falciparum (Burgess, S. J.; Selzer; A.; Kelly, J. X.; Smilkstein, M. J.; Riscoe, M. K.; Peyton, D. H. J. Med. Chem. 2006, 49, 5623. Andrews, S.; Burgess, S. J.; Skaalrud, D.; Kelly, J. X.; Peyton, D. H. J. Med. Chem. 2010, 53, 916). Here, we present an investigation into the structure-activity relationship of the RCQ structures, resulting in an orally active molecule with good in vitro and in vivo antimalarial activity. We also present evidence of the mode of action, indicating that the RCQ molecules inhibit hemozoin formation in the parasite's digestive vacuole in a manner similar to that of chloroquine. C1 [Burgess, Steven J.; Kelly, Jane X.; Shomloo, Shawheen; Liebmann, Katherine; Peyton, David H.] Portland State Univ, Dept Chem, Portland, OR 97207 USA. [Burgess, Steven J.; Shomloo, Shawheen; Peyton, David H.] DesignMedix Inc, Portland, OR 97201 USA. [Kelly, Jane X.] Portland VA Med Ctr, Portland, OR 97239 USA. [Wittlin, Sergio; Brun, Reto] Swiss Trop & Publ Hlth Inst, Basel, Switzerland. [Wittlin, Sergio; Brun, Reto] Univ Basel, Basel, Switzerland. RP Peyton, DH (reprint author), Portland State Univ, Dept Chem, POB 751, Portland, OR 97207 USA. EM peytond@pdx.edu FU The Medical Research Foundation of Oregon [0530]; National Institutes of Health [AI067837, AI072923]; Murdock Charitable Trust FX The authors thank the following for supporting this research: The Medical Research Foundation of Oregon (Grant 0530) and the National Institutes of Health (Grants ) to D.H.P., as well as the Murdock Charitable Trust for a grant for the NMR instruments. The authors also thank Westin Morrill for his help in preparing this manuscript. NR 43 TC 29 Z9 29 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 9 PY 2010 VL 53 IS 17 BP 6477 EP 6489 DI 10.1021/jm1006484 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 644TM UT WOS:000281404200020 PM 20684562 ER PT J AU Kounnas, MZ Danks, AM Cheng, SA Tyree, C Ackerman, E Zhang, XL Ahn, K Nguyen, P Comer, D Mao, L Yu, CZ Pleynet, D Digregorio, PJ Velicelebi, G Stauderman, KA Comer, WT Mobley, WC Li, YM Sisodia, SS Tanzi, RE Wagner, SL AF Kounnas, Maria Z. Danks, Anne M. Cheng, Soan Tyree, Curtis Ackerman, Elizabeth Zhang, Xulun Ahn, Kwangwook Nguyen, Phuong Comer, Dan Mao, Long Yu, Chengzhi Pleynet, David Digregorio, Paul J. Velicelebi, Gonul Stauderman, Kenneth A. Comer, William T. Mobley, William C. Li, Yue-Ming Sisodia, Sangram S. Tanzi, Rudolph E. Wagner, Steven L. TI Modulation of gamma-Secretase Reduces beta-Amyloid Deposition in a Transgenic Mouse Model of Alzheimer's Disease SO NEURON LA English DT Article ID IN-VIVO; INTRACELLULAR DOMAIN; A-BETA; NOTCH; INHIBITORS; COMPLEX; BRAIN; DIFFERENTIATION; PRESENILIN-1; PATHOLOGY AB Alzheimer's disease (AD) is characterized pathologically by the abundance of senile plaques and neurofibrillary tangles in the brain. We synthesized over 1200 novel gamma-secretase modulator (GSM) compounds that reduced A beta(42) levels without inhibiting epsilon-site cleavage of APP and Notch, the generation of the APP and Notch intracellular domains, respectively. These compounds also reduced A beta(40) levels while concomitantly elevating levels of A beta(38) and A beta(37). Immobilization of a potent GSM onto an agarose matrix quantitatively recovered Pen-2 and to a lesser degree PS-1 NTFs from cellular extracts. Moreover, oral administration (once daily) of another potent GSM to Tg 2576 transgenic AD mice displayed dose-responsive lowering of plasma and brain A beta(42); chronic daily administration led to significant reductions in both diffuse and neuritic plaques. These effects were observed in the absence of Notch-related changes (e.g., intestinal proliferation of goblet cells), which are commonly associated with repeated exposure to functional gamma-secretase inhibitors (GSIs). C1 [Zhang, Xulun; Sisodia, Sangram S.] Univ Chicago, Ctr Mol Neurobiol, Chicago, IL 60637 USA. [Ahn, Kwangwook; Li, Yue-Ming] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. [Kounnas, Maria Z.; Danks, Anne M.; Cheng, Soan; Tyree, Curtis; Ackerman, Elizabeth; Nguyen, Phuong; Comer, Dan; Mao, Long; Yu, Chengzhi; Pleynet, David; Digregorio, Paul J.; Velicelebi, Gonul; Stauderman, Kenneth A.; Comer, William T.; Wagner, Steven L.] TorreyPines Therapeut Inc, La Jolla, CA 92037 USA. [Mobley, William C.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92037 USA. RP Wagner, SL (reprint author), Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92037 USA. EM slwagner@ucsd.edu FU Eisai, Co. Ltd.; NIH [RO1 AG026660]; John Adler Foundation FX The authors wish to thank Nicolas Patch for technical support, Pat Baskin for critical review of the manuscript, and Eisai, Co. Ltd. and the NIH grant RO1 AG026660 (to Y.-M.L.) and the John Adler Foundation (to S.S.S.) for financial support. M.Z.K. and W.T.C. are employees of Neurogenetic Pharmaceuticals, Inc. (NGP), and W.T.C., R.E.T., and S.L.W. are shareholders and cofounders of NGP. NR 40 TC 131 Z9 133 U1 1 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 9 PY 2010 VL 67 IS 5 BP 769 EP 780 DI 10.1016/j.neuron.2010.08.018 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 651PF UT WOS:000281938900012 PM 20826309 ER PT J AU Attar, EC Hasserjian, RP AF Attar, Eyal C. Hasserjian, Robert P. TI Case 27-2010: A 73-Year-Old Woman with Chronic Anemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RISK MYELODYSPLASTIC SYNDROMES; ACUTE MYELOID-LEUKEMIA; CELL TRANSPLANTATION; DELETED REGION; 5Q DELETION; PHASE-III; IDENTIFICATION; LENALIDOMIDE; AZACITIDINE; 5Q-SYNDROME C1 [Attar, Eyal C.] Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Attar, Eyal C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hasserjian, Robert P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Attar, EC (reprint author), Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. NR 20 TC 1 Z9 1 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 9 PY 2010 VL 363 IS 11 BP 1060 EP 1068 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 647HS UT WOS:000281609700011 PM 20825319 ER PT J AU Pozzi, S Raje, N AF Pozzi, Samantha Raje, Noopur TI Bisphosphonates and Atypical Femoral Fractures SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID OSTEONECROSIS; JAW C1 [Pozzi, Samantha; Raje, Noopur] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Raje, N (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM nraje@partners.org RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 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 9 PY 2010 VL 363 IS 11 BP 1083 EP 1084 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 647HS UT WOS:000281609700017 PM 20848678 ER PT J AU Rydzak, CE Cotich, KL Sax, PE Hsu, HE Wang, BX Losina, E Freedberg, KA Weinstein, MC Goldie, SJ AF Rydzak, Chara E. Cotich, Kara L. Sax, Paul E. Hsu, Heather E. Wang, Bingxia Losina, Elena Freedberg, Kenneth A. Weinstein, Milton C. Goldie, Sue J. CA CEPAC Investigators TI Assessing the Performance of a Computer-Based Policy Model of HIV and AIDS SO PLOS ONE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; CD4 CELL COUNTS; MULTIPLE VIROLOGICAL FAILURES; MYCOBACTERIUM-AVIUM COMPLEX; SEQUENTIAL 3-DRUG REGIMENS; WOMENS INTERAGENCY HIV; SOCIETY-USA PANEL; COST-EFFECTIVENESS; UNITED-STATES; OPPORTUNISTIC INFECTIONS AB Background: Model-based analyses, conducted within a decision analytic framework, provide a systematic way to combine information about the natural history of disease and effectiveness of clinical management strategies with demographic and epidemiological characteristics of the population. Among the challenges with disease-specific modeling include the need to identify influential assumptions and to assess the face validity and internal consistency of the model. Methods and Findings: We describe a series of exercises involved in adapting a computer-based simulation model of HIV disease to the Women's Interagency HIV Study (WIHS) cohort and assess model performance as we re-parameterized the model to address policy questions in the U.S. relevant to HIV-infected women using data from the WIHS. Empiric calibration targets included 24-month survival curves stratified by treatment status and CD4 cell count. The most influential assumptions in untreated women included chronic HIV-associated mortality following an opportunistic infection, and in treated women, the 'clinical effectiveness' of HAART and the ability of HAART to prevent HIV complications independent of virologic suppression. Good-fitting parameter sets required reductions in the clinical effectiveness of 1(st) and 2(nd) line HAART and improvements in 3(rd) and 4(th) line regimens. Projected rates of treatment regimen switching using the calibrated cohort-specific model closely approximated independent analyses published using data from the WIHS. Conclusions: The model demonstrated good internal consistency and face validity, and supported cohort heterogeneities that have been reported in the literature. Iterative assessment of model performance can provide information about the relative influence of uncertain assumptions and provide insight into heterogeneities within and between cohorts. Description of calibration exercises can enhance the transparency of disease-specific models. C1 [Rydzak, Chara E.; Hsu, Heather E.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rydzak, Chara E.; Cotich, Kara L.; Freedberg, Kenneth A.; Weinstein, Milton C.; Goldie, Sue J.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Sax, Paul E.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Hsu, Heather E.; Wang, Bingxia; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Rydzak, CE (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM sue_goldie@harvard.edu OI Lipsitch, Marc/0000-0003-1504-9213 FU National Institute of Allergy and Infectious Diseases [R37 AI042006, K24 AI062476] FX Supported by the National Institute of Allergy and Infectious Diseases (R37 AI042006, K24 AI062476). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 69 TC 3 Z9 3 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 9 PY 2010 VL 5 IS 9 AR e12647 DI 10.1371/journal.pone.0012647 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 648IW UT WOS:000281687200012 ER PT J AU Chung, DC AF Chung, Daniel C. TI Molecular biology of neuroendocrine tumours SO REGULATORY PEPTIDES LA English DT Meeting Abstract CT 18th International Symposium on Regulatory Peptides CY SEP 05-08, 2010 CL Belfast, UNITED KINGDOM C1 [Chung, Daniel C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD SEP 9 PY 2010 VL 164 IS 1 SI SI BP 3 EP 4 DI 10.1016/j.regpep.2010.07.011 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 647ZK UT WOS:000281659200011 PM 26009325 ER PT J AU Stylianopoulos, T Poh, MZ Insin, N Bawendi, MG Fukumura, D Munn, LL Jain, RK AF Stylianopoulos, Triantafyllos Poh, Ming-Zher Insin, Numpon Bawendi, Moungi G. Fukumura, Dai Munn, Lance L. Jain, Rakesh K. TI Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions SO BIOPHYSICAL JOURNAL LA English DT Article ID HYDRODYNAMIC TRANSPORT-PROPERTIES; HARD-SPHERE DISPERSIONS; REYNOLDS-NUMBER FLOW; QUANTUM DOTS; FIBROUS MEMBRANES; IN-VIVO; TUMOR INTERSTITIUM; HINDERED TRANSPORT; MOBILITY FUNCTIONS; HEPARAN-SULFATE AB Diffusive transport of macromolecules and nanoparticles in charged fibrous media is of interest in many biological applications, including drug delivery and separation processes. Experimental findings have shown that diffusion can be significantly hindered by electrostatic interactions between the diffusing particle and charged components of the extracellular matrix. The implications, however, have not been analyzed rigorously. Here, we present a mathematical framework to study the effect of charge on the diffusive transport of macromolecules and nanoparticles in the extracellular matrix of biological tissues. The model takes into account steric, hydrodynamic, and electrostatic interactions. We show that when the fiber size is comparable to the Debye length, electrostatic forces between the fibers and the particles result in slowed diffusion. However, as the fiber diameter increases the repulsive forces become less important. Our results explain the experimental observations that neutral particles diffuse faster than charged particles. Taken together, we conclude that optimal particles for delivery to tumors should be initially cationic to target the tumor vessels and then change to neutral charge after exiting the blood vessels. C1 [Stylianopoulos, Triantafyllos; Poh, Ming-Zher; Fukumura, Dai; Munn, Lance L.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Stylianopoulos, Triantafyllos; Poh, Ming-Zher; Fukumura, Dai; Munn, Lance L.; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Insin, Numpon; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. EM lance@steele.mgh.harvard.edu; jain@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Stylianopoulos, Triantafyllos/0000-0002-3093-1696; Poh, Ming-Zher/0000-0002-3510-1923 FU National Institutes of Health [5PO1CA080124, RO1CA126642]; Susan G. Komen Breast Cancer Foundation [KG091281] FX This work was supported by the National Institutes of Health (5PO1CA080124 and RO1CA126642). T.S. was supported by a postdoctoral research fellowship from the Susan G. Komen Breast Cancer Foundation (KG091281). NR 44 TC 95 Z9 96 U1 7 U2 45 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP 8 PY 2010 VL 99 IS 5 BP 1342 EP 1349 DI 10.1016/j.bpj.2010.06.016 PG 8 WC Biophysics SC Biophysics GA 648VC UT WOS:000281721500003 PM 20816045 ER PT J AU Brothers, KJ Wu, S DiVall, SA Messmer, MR Kahn, CR Miller, RS Radovick, S Wondisford, FE Wolfe, A AF Brothers, Kathryn J. Wu, Sheng DiVall, Sara A. Messmer, Marcus R. Kahn, C. Ronald Miller, Ryan S. Radovick, Sally Wondisford, Fredric E. Wolfe, Andrew TI Rescue of Obesity-Induced Infertility in Female Mice due to a Pituitary-Specific Knockout of the Insulin Receptor SO CELL METABOLISM LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; GROWTH-FACTOR-I; GONADOTROPIN-RELEASING-HORMONE; DIET-INDUCED OBESITY; LUTEINIZING-HORMONE; IGF-I; LEPTIN RESISTANCE; CELLS; RAT; EXPRESSION AB Obesity is associated with insulin resistance in metabolic tissues such as adipose, liver, and muscle, but it is unclear whether nonclassical target tissues, such as those of the reproductive axis, are also insulin resistant. To determine if the reproductive axis maintains insulin sensitivity in obesity in vivo, murine models of diet-induced obesity (DIO) with and without intact insulin signaling in pituitary gonadotrophs were created. Diet-induced obese wildtype female mice (WT DIO) were infertile and experienced a robust increase in luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) or insulin stimulation. By contrast, both lean and obese mice with a pituitary-specific knockout of the insulin receptor (PitIRKO) exhibited reproductive competency, indicating that insulin signaling in the pituitary is required for the reproductive impairment seen in DIO and that the gonadotroph maintains insulin sensitivity in a setting of peripheral insulin resistance. C1 [Wu, Sheng; DiVall, Sara A.; Miller, Ryan S.; Radovick, Sally; Wolfe, Andrew] Johns Hopkins Univ, Sch Med, Div Pediat Endocrinol, Baltimore, MD 21287 USA. [Messmer, Marcus R.; Wondisford, Fredric E.] Johns Hopkins Univ, Sch Med, Div Metab, Baltimore, MD 21287 USA. [Brothers, Kathryn J.; Wondisford, Fredric E.; Wolfe, Andrew] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21287 USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Wolfe, A (reprint author), Johns Hopkins Univ, Sch Med, Div Pediat Endocrinol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM awolfe3@jhmi.edu FU NIH [RO1HD044608, RO1 DK33201]; Eunice Kennedy Shriver NICHD/NIH [U54 HD58820]; NICHD (SCCPIR) [U54-HD28934] FX This work was supported by NIH RO1HD044608, granted to A.W., along with the Eunice Kennedy Shriver NICHD/NIH through cooperative agreement (U54 HD58820 granted to A.W., FEW., and S.R.) as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research. Serum levels measured on the Luminex platform were done with support from the DRTC Integrated Physiology Core at Johns Hopkins. Support was also received from NIH RO1 DK33201 to C.R.K. Serum testosterone levels were measured by the University of Virginia as part of NICHD (SCCPIR) Grant U54-HD28934, University of Virginia Center for Research in Reproduction. NR 38 TC 52 Z9 53 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD SEP 8 PY 2010 VL 12 IS 3 BP 295 EP 305 DI 10.1016/j.cmet.2010.06.010 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 648OH UT WOS:000281703300013 PM 20816095 ER PT J AU Mayo, L Dionne-Odom, J Talbot, EA Adamski, C Bean, C Daly, ER Gao, F Gougelet, R Montero, J Morse, D Smith, J Berry, R McGarry, F Wimsatt, M Stamm, L Madoff, L Gauthier, C Nalipinski, M Hoffmaster, AR Shadomy, SV Pesik, NT Smith, TL Rose, LJ Martinez, K Burrer, SL Stauffer, K AF Mayo, L. Dionne-Odom, J. Talbot, E. A. Adamski, C. Bean, C. Daly, E. R. Gao, F. Gougelet, R. Montero, J. Morse, D. Smith, J. Berry, R. McGarry, F. Wimsatt, M. Stamm, L. Madoff, L. Gauthier, C. Nalipinski, M. Hoffmaster, A. R. Shadomy, S. V. Pesik, N. T. Smith, T. L. Rose, L. J. Martinez, K. Burrer, S. L. Stauffer, K. CA Ctr Dis Control Prevent TI Gastrointestinal Anthrax After an Animal-Hide Drumming Event-New Hampshire and Massachusetts, 2009 (Reprinted from MMWR, vol 59, pg 872-877, 2010) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 [Mayo, L.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Dionne-Odom, J.; Talbot, E. A.; Adamski, C.; Bean, C.; Daly, E. R.; Gao, F.; Gougelet, R.; Montero, J.; Morse, D.; Smith, J.] New Hampshire Dept Hlth & Human Serv, Concord, NH 03301 USA. [Stamm, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Madoff, L.; Gauthier, C.] Massachusetts Dept Publ Hlth, Boston, MA 02111 USA. [Martinez, K.] NIOSH, Washington, DC 20201 USA. [Burrer, S. L.; Stauffer, K.] CDC, EIS, Atlanta, GA 30333 USA. RP Mayo, L (reprint author), Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 8 PY 2010 VL 304 IS 10 BP 1061 EP 1064 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 646RM UT WOS:000281559800009 ER PT J AU Marso, SP House, JA Rumsfeld, JS AF Marso, Steven P. House, John A. Rumsfeld, John S. TI Bleeding Avoidance Strategies and Percutaneous Coronary Intervention Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID VASCULAR CLOSURE DEVICES; CATHETERIZATION C1 [Marso, Steven P.; House, John A.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Marso, SP (reprint author), St Lukes Mid Amer Heart Inst, Kansas City, MO USA. EM smarso@saint-lukes.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 8 PY 2010 VL 304 IS 10 BP 1068 EP 1069 DI 10.1001/jama.2010.1256 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 646RM UT WOS:000281559800013 ER PT J AU Hong, CS Atlas, SJ Chang, YC Subramanian, SV Ashburner, JM Barry, MJ Grant, RW AF Hong, Clemens S. Atlas, Steven J. Chang, Yuchiao Subramanian, S. V. Ashburner, Jeffrey M. Barry, Michael J. Grant, Richard W. TI Relationship Between Patient Panel Characteristics and Primary Care Physician Clinical Performance Rankings SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PAY-FOR-PERFORMANCE; MEDICARE MANAGED CARE; CASE-MIX ADJUSTMENT; QUALITY-OF-CARE; HEALTH-CARE; REGIONAL-VARIATIONS; RACIAL DISPARITIES; UNITED-STATES; CONSEQUENCES; ASSOCIATIONS AB Context Physicians have increasingly become the focus of clinical performance measurement. Objective To investigate the relationship between patient panel characteristics and relative physician clinical performance rankings within a large academic primary care network. Design, Setting, and Participants Cohort study using data from 125 303 adult patients who had visited any of the 9 hospital-affiliated practices or 4 community health centers between January 1, 2003, and December 31, 2005, (162 primary care physicians in 1 physician organization linked by a common electronic medical record system in Eastern Massachusetts) to determine changes in physician quality ranking based on an aggregate of Health Plan Employer and Data Information Set (HEDIS) measures after adjusting for practice site, visit frequency, and patient panel characteristics. Main Outcome Measures Composite physician clinical performance score based on 9 HEDIS quality measures (reported by percentile, with lower scores indicating higher quality). Results Patients of primary care physicians in the top quality performance tertile compared with patients of primary care physicians in the bottom quality tertile were older (51.1 years [95% confidence interval {CI}, 49.6-52.6 years] vs 46.6 years [95% CI, 43.8-49.5 years], respectively; P<.001), had a higher number of comorbidities (0.91 [95% CI, 0.83-0.98] vs 0.80 [95% CI, 0.66-0.95]; P=.008), and made more frequent primary care practice visits (71.0% [95% CI, 68.5%-73.5%] vs 61.8% [95% CI, 57.3%-66.3%] with >3 visits/year; P=.003). Top tertile primary care physicians compared with the bottom tertile physicians had fewer minority patients (13.7% [95% CI, 10.6%-16.7%] vs 25.6% [95% CI, 20.2%-31.1%], respectively; P<.001), non-English-speaking patients (3.2% [95% CI, 0.7%-5.6%] vs 10.2% [95% CI, 5.5%-14.9%]; P<.001), and patients with Medicaid coverage or without insurance (9.6% [95% CI, 7.5%-11.7%] vs 17.2% [95% CI, 13.5%-21.0%]; P<.001). After accounting for practice site and visit frequency differences, adjusting for patient panel factors resulted in a relative mean change in physician rankings of 7.6 percentiles (95% CI, 6.6-8.7 percentiles) per primary care physician, with more than one-third (36%) of primary care physicians (59/162) reclassified into different quality tertiles. Conclusion Among primary care physicians practicing within the same large academic primary care system, patient panels with greater proportions of underinsured, minority, and non-English-speaking patients were associated with lower quality rankings for primary care physicians. JAMA. 2010; 304(10): 1107-1113 C1 [Hong, Clemens S.; Atlas, Steven J.; Chang, Yuchiao; Ashburner, Jeffrey M.; Barry, Michael J.; Grant, Richard W.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02115 USA. [Hong, Clemens S.; Atlas, Steven J.; Chang, Yuchiao; Barry, Michael J.; Grant, Richard W.] Harvard Univ, Sch Med, Boston, MA USA. [Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Hong, CS (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02115 USA. EM cshong@partners.org OI Grant, Richard/0000-0002-6164-8025 FU National Institutes of Health [T32 HP12706, NIDDK K23 DK067452, NHLBI K25 HL081275]; Agency for Healthcare Research and Quality [R18 HS018161] FX Dr Hong is supported by National Research Service Award grant T32 HP12706 from the National Institutes of Health. Dr Grant is supported by career development grant NIDDK K23 DK067452 from the National Institutes of Health. Dr Atlas is supported by grant R18 HS018161 from the Agency for Healthcare Research and Quality. Dr Subramanian is supported by career development grant NHLBI K25 HL081275 from the National Institutes of Health. NR 36 TC 50 Z9 50 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 8 PY 2010 VL 304 IS 10 BP 1107 EP 1113 DI 10.1001/jama.2010.1287 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 646RM UT WOS:000281559800021 PM 20823437 ER PT J AU Myers, AP Cantley, LC AF Myers, Andrea P. Cantley, Lewis C. TI Targeting a Common Collaborator in Cancer Development SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID HER2/NEU-OVEREXPRESSING METASTATIC BREAST; MONOCLONAL-ANTIBODY; PI3K PATHWAY; PIK3CA GENE; PHASE-II; AMPLIFICATION; MUTATIONS; OVARIAN AB In this issue of Science Translational Medicine, Wallin et al. have identified a subset of breast and ovarian cancer cell lines that show synergistic response to the combination of doxorubicin and GDC-0941, a class IA phosphatidylinositol 3-kinase (PI3K) inhibitor. Here, we discuss the potential implications of these data on the clinical development of PI3K pathway inhibitors as cancer therapeutics. C1 [Myers, Andrea P.] Dana Farber Canc Inst, Div Womens Cancers, Dept Med Oncol, Boston, MA 02115 USA. [Myers, Andrea P.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Dept Med, Boston, MA 02115 USA. [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Myers, AP (reprint author), Dana Farber Canc Inst, Div Womens Cancers, Dept Med Oncol, Boston, MA 02115 USA. EM apmyers@partners.org RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU Stand Up To Cancer Foundation; National Institutes of Health; Dana-Farber/Harvard Cancer Center FX The authors acknowledge the Stand Up To Cancer Foundation, the National Institutes of Health, and the Dana-Farber/Harvard Cancer Center for grant support to study the PI3K pathway in women's cancers. A.P.M. also receives funding from the Dana-Farber/Harvard Cancer Center. NR 28 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD SEP 8 PY 2010 VL 2 IS 48 AR 48ps45 DI 10.1126/scitranslmed.3001251 PG 4 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 735SG UT WOS:000288436900001 PM 20826838 ER PT J AU Guan, R Han, D Harrison, SC Kirchhausen, T AF Guan, Rong Han, Dai Harrison, Stephen C. Kirchhausen, Tomas TI Structure of the PTEN-like Region of Auxilin, a Detector of Clathrin-Coated Vesicle Budding SO STRUCTURE LA English DT Article ID PLASMA-MEMBRANE; PITS; DISSOCIATION; PROTEIN; DOMAIN; SYNAPTOTAGMIN; ENDOCYTOSIS; MECHANISM; ATPASE; BRAIN AB Auxilin, a J-domain containing protein, recruits the Hsc70 uncoating ATPase to newly budded clathrin-coated vesicles. The timing of auxilin arrival determines that uncoating will commence only after the clathrin lattice has fully assembled and after membrane fission is complete. Auxilin has a region resembling PTEN, a PI3P phosphatase. We have determined the crystal structure of this region of bovine auxilin 1; it indeed resembles PTEN closely. A change in the structure of the P loop accounts for the lack of phosphatase activity. Inclusion of phosphatidylinositol phosphates substantially enhances liposome binding by wild-type auxilin, but not by various mutants bearing changes in loops of the C2 domain. Nearly all these mutations also prevent recruitment of auxilin to newly budded coated vesicles. We propose a specific geometry for auxilin association with a membrane bilayer and discuss implications of this model for the mechanism by which auxilin detects separation of a vesicle from its parent membrane. C1 [Guan, Rong; Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Han, Dai; Harrison, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Jack & Eileen Connors Struct Biol Lab, Boston, MA 02115 USA. [Harrison, Stephen C.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Guan, Rong; Kirchhausen, Tomas] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Guan, Rong; Kirchhausen, Tomas] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu FU NIH [GM36548, U54 AI057159] FX We thank the staff of beamline 241D-E at APS and members of our laboratories for support. We thank Emanuele Cocucci for help setting up the TIRF experiments and Eric Marino for technical support with the fluorescence microscopes. The work was funded in part by NIH grants GM36548 (T.K.) and U54 AI057159 (NERCE Imaging Resource) (T.K.). R.G. was an American Heart Association Postdoctoral Fellow and D.H. was a Helen Hay Whitney Postdoctoral Fellow. S.C.H. is an Investigator in the Howard Hughes Medical Institute. NR 29 TC 21 Z9 21 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD SEP 8 PY 2010 VL 18 IS 9 BP 1191 EP 1198 DI 10.1016/j.str.2010.06.016 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 650GE UT WOS:000281836400015 PM 20826345 ER PT J AU Werner, RM AF Werner, Rachel M. TI Does Pay-for-Performance Steal From the Poor and Give to the Rich? SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID QUALITY-OF-CARE; HOSPITAL FINANCIAL CONDITION C1 [Werner, Rachel M.] Univ Penn, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Werner, RM (reprint author), Univ Penn, 1230 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rwerner@upenn.edu NR 12 TC 6 Z9 6 U1 1 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 7 PY 2010 VL 153 IS 5 BP 340 EP 341 DI 10.7326/0003-4819-153-5-201009070-00010 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 647GF UT WOS:000281605500009 PM 20820044 ER PT J AU Fagenholz, PJ AF Fagenholz, Peter J. TI When is restraint appropriate? An American view SO BRITISH MEDICAL JOURNAL LA English DT Letter ID CARE C1 Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. EM pfagenholz@partners.org NR 3 TC 0 Z9 0 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BRIT MED J JI Br. Med. J. PD SEP 7 PY 2010 VL 341 AR c4702 DI 10.1136/bmj.c4702 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 649ZI UT WOS:000281814900003 PM 20823018 ER PT J AU Lubitz, SA Sinner, MF Lunetta, KL Makino, S Pfeufer, A Rahman, R Veltman, CE Barnard, J Bis, JC Danik, SP Sonni, A Shea, MA del Monte, F Perz, S Muller, M Peters, A Greenberg, SM Furie, KL van Noord, C Boerwinkle, E Stricker, BHC Witteman, J Smith, JD Chung, MK Heckbert, SR Benjamin, EJ Rosand, J Arking, DE Alonso, A Kaab, S Ellinor, PT AF Lubitz, Steven A. Sinner, Moritz F. Lunetta, Kathryn L. Makino, Seiko Pfeufer, Arne Rahman, Rosanna Veltman, Caroline E. Barnard, John Bis, Joshua C. Danik, Stephan P. Sonni, Akshata Shea, Marisa A. del Monte, Federica Perz, Siegfried Mueller, Martina Peters, Annette Greenberg, Steven M. Furie, Karen L. van Noord, Charlotte Boerwinkle, Eric Stricker, Bruno H. C. Witteman, Jacqueline Smith, Jonathan D. Chung, Mina K. Heckbert, Susan R. Benjamin, Emelia J. Rosand, Jonathan Arking, Dan E. Alonso, Alvaro Kaeaeb, Stefan Ellinor, Patrick T. TI Independent Susceptibility Markers for Atrial Fibrillation on Chromosome 4q25 SO CIRCULATION LA English DT Article DE atrial fibrillation; electrophysiology; genetics; epidemiology; risk factors ID ATHEROSCLEROSIS RISK; COMMON VARIANTS; HUMAN GENOME; PR INTERVAL; ASSOCIATION; POPULATION; DESIGN; METAANALYSIS; OBJECTIVES; ROTTERDAM AB Background-Genetic variants on chromosome 4q25 are associated with atrial fibrillation (AF). We sought to determine whether there is more than 1 susceptibility signal at this locus. Methods and Results-Thirty-four haplotype-tagging single-nucleotide polymorphisms (SNPs) at the 4q25 locus were genotyped in 790 case and 1177 control subjects from Massachusetts General Hospital and tested for association with AF. We replicated SNPs associated with AF after adjustment for the most significantly associated SNP in 5066 case and 30 661 referent subjects from the German Competence Network for Atrial Fibrillation, Atherosclerosis Risk In Communities Study, Cleveland Clinic Lone AF Study, Cardiovascular Health Study, and Rotterdam Study. All subjects were of European ancestry. A multimarker risk score composed of SNPs that tagged distinct AF susceptibility signals was constructed and tested for association with AF, and all results were subjected to meta-analysis. The previously reported SNP, rs2200733, was most significantly associated with AF (minor allele odds ratio 1.80, 95% confidence interval 1.50 to 2.15, P = 1.2x10(-20)) in the discovery sample. Adjustment for rs2200733 genotype revealed 2 additional susceptibility signals marked by rs17570669 and rs3853445. A graded risk of AF was observed with an increasing number of AF risk alleles at SNPs that tagged these 3 susceptibility signals. Conclusions-We identified 2 novel AF susceptibility signals on chromosome 4q25. Consideration of multiple susceptibility signals at chromosome 4q25 identifies individuals with an increased risk of AF and may localize regulatory elements at the locus with biological relevance in the pathogenesis of AF. (Circulation. 2010;122:976-984.) C1 [Danik, Stephan P.; Shea, Marisa A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.; Makino, Seiko; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Sinner, Moritz F.; Mueller, Martina; Kaeaeb, Stefan] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Mueller, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Lunetta, Kathryn L.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Pfeufer, Arne] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, Munich, Germany. [Pfeufer, Arne] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Perz, Siegfried] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Neuherberg, Germany. [Mueller, Martina; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. [Rahman, Rosanna; Sonni, Akshata; Greenberg, Steven M.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. [Veltman, Caroline E.; van Noord, Charlotte; Stricker, Bruno H. C.; Witteman, Jacqueline] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Barnard, John] Cleveland Clin, Dept Quantitat Hlth Sci, Inst Heart & Vasc, Dept Mol Cardiol,Lerner Res Inst, Cleveland, OH 44106 USA. [Smith, Jonathan D.] Cleveland Clin, Dept Cell Biol, Inst Heart & Vasc, Dept Mol Cardiol,Lerner Res Inst, Cleveland, OH 44106 USA. [Chung, Mina K.] Cleveland Clin, Dept Cardiovasc Med, Inst Heart & Vasc, Dept Mol Cardiol,Lerner Res Inst, Cleveland, OH 44106 USA. [Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA USA. [del Monte, Federica] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [van Noord, Charlotte] Dutch Med Evaluat Board, The Hague, Netherlands. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Stricker, Bruno H. C.] Inspectorate Hlth Care, The Hague, Netherlands. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Grp Hlth, Ctr Hlth Studies, Seattle, WA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM pellinor@partners.org RI Alonso, Alvaro/A-4917-2010; Kaab, Stefan/H-3915-2012; Pfeufer, Arne/B-6634-2013; Peters, Annette/A-6117-2011; OI Alonso, Alvaro/0000-0002-2225-8323; Lunetta, Kathryn/0000-0002-9268-810X; Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health (NIH) [R01NS059727, P50NS051343, T32HL007575, RO1HL092577, RC1HL101056, DA027021]; German Federal Ministry of Education and Research (BMBF); German National Competence Network on Atrial Fibrillation (AFNET); Leducq Foundation [07-CVD 03, 01GS0499, 01GI0204, 01GS0838]; Helmholtz Zentrum Munchen; National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, RC1 HL101056]; National Human Genome Research Institute [U01HG004402]; NIH [HHSN268200625226C]; American Heart Association [09SDG2280087]; NHLBI/NIH [1RC1HL099452]; NHLBI [R01 HL090620, 1UL-RR024989, P50 HL077107, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01HL087652]; Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic; National Center for Research [M01-RR00425]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Netherlands Organization of Scientific Research [175.010.2005.011]; Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission; Municipality of Rotterdam FX MGH: This study was funded by grants to Dr Ellinor from the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke and grants from the National Institutes of Health (NIH) to Dr Rosand (R01NS059727), Dr Furie (P50NS051343), Dr Lubitz (T32HL007575), and Drs Ellinor and Benjamin (RO1HL092577, RC1HL101056, and DA027021). AFNET: The study was also supported by the German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN), the German National Competence Network on Atrial Fibrillation (AFNET), the Leducq Foundation (07-CVD 03) by grants to Dr Kaab (01GS0499, 01GI0204, and 01GS0838). KORA S4: The KORA platform is funded by the Helmholtz Zentrum Munchen, the BMBF partly in the context of the NGFN, and the State of Bavaria, and as part of LMUinnovativ. ARIC: ARIC is conducted as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, and RC1 HL101056; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. The present analysis was also supported by American Heart Association grant 09SDG2280087 and NHLBI/NIH grant 1RC1HL099452. CCAF: The CCAF is supported by R01 HL090620 from the NHLBI (Drs Chung, Barnard, and Smith); NIH/National Center for Research Resources, Clinical Translational Science Award 1UL-RR024989 (Dr Chung); Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic (Dr Chung); and P50 HL077107 from the NHLBI (Dr Barnard). CHS: The CHS research reported in this article was supported by contract Nos. N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133 and grant Nos. U01 HL080295 and R01HL087652 from the NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke. DNA handling and genotyping were supported in part by National Center for Research Resources grant M01-RR00425 to the Cedars-Sinai General Clinical Research Center Genotyping Core and by National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. RS: The genome-wide association database of the RS was funded through the Netherlands Organization of Scientific Research (No. 175.010.2005.011). The RS is supported by the Erasmus Medical Center and Erasmus University, Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. NR 35 TC 76 Z9 81 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 7 PY 2010 VL 122 IS 10 BP 976 EP U66 DI 10.1161/CIRCULATIONAHA.109.886440 PG 21 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 652PJ UT WOS:000282020600006 PM 20733104 ER PT J AU Moslehi, J Minamishima, YA Shi, JR Neuberg, D Charytan, DM Padera, RF Signoretti, S Liao, R Kaelin, WG AF Moslehi, Javid Minamishima, Yoji Andrew Shi, Jianru Neuberg, Donna Charytan, David M. Padera, Robert F. Signoretti, Sabina Liao, Ronglih Kaelin, William G., Jr. TI Loss of Hypoxia-Inducible Factor Prolyl Hydroxylase Activity in Cardiomyocytes Phenocopies Ischemic Cardiomyopathy SO CIRCULATION LA English DT Article DE cardiomyopathy; hibernation; hypoxia; ischemia; myocardium ID HEART-FAILURE; MYOCARDIAL-INFARCTION; REPERFUSION INJURY; IN-VIVO; HIF; INACTIVATION; HIF-1-ALPHA; ACTIVATION; INHIBITION; INDUCTION AB Background-Ischemic cardiomyopathy is the major cause of heart failure and a significant cause of morbidity and mortality. The degree of left ventricular dysfunction in this setting is often out of proportion to the amount of overtly infarcted tissue, and how decreased delivery of oxygen and nutrients leads to impaired contractility remains incompletely understood. The Prolyl Hydroxylase Domain-Containing Protein (PHD) prolyl hydroxylases are oxygen-sensitive enzymes that transduce changes in oxygen availability into changes in the stability of the hypoxia-inducible factor transcription factor, a master regulator of genes that promote survival in a low-oxygen environment. Methods and Results-We found that cardiac-specific PHD inactivation causes ultrastructural, histological, and functional changes reminiscent of ischemic cardiomyopathy over time. Moreover, long-term expression of a stabilized hypoxia-inducible factor alpha variant in cardiomyocytes also led to dilated cardiomyopathy. Conclusion-Sustained loss of PHD activity and subsequent hypoxia-inducible factor activation, as would occur in the setting of chronic ischemia, are sufficient to account for many of the changes in the hearts of individuals with chronic coronary artery disease. (Circulation. 2010;122:1004-1016.) C1 [Moslehi, Javid; Minamishima, Yoji Andrew; Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Moslehi, Javid; Shi, Jianru; Liao, Ronglih] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Charytan, David M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM William_kaelin@dfci.harvard.edu RI Minamishima, Yoji/E-5380-2010 OI Minamishima, Yoji/0000-0001-7995-9318 FU National Institutes of Health [T32HL007604-24, K08HL097031]; Heart Failure Society of America; Brigham and Women's Hospital FX Dr Moslehi was supported by National Institutes of Health training grants for cardiovascular research (T32HL007604-24 and K08HL097031), a Heart Failure Society of America Research Fellowship, and the Watkins Cardiovascular Discovery Award (from Brigham and Women's Hospital). Dr Kaelin was supported by the National Institutes of Health, is a Howard Hughes Medical Institute Investigator, and is a Doris Duke Distinguished Clinical Scientist. NR 45 TC 56 Z9 60 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 7 PY 2010 VL 122 IS 10 BP 1004 EP U108 DI 10.1161/CIRCULATIONAHA.109.922427 PG 21 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 652PJ UT WOS:000282020600009 PM 20733101 ER PT J AU Hoen, PW Whooley, MA Martens, EJ Na, B van Melle, JP de Jonge, P AF Hoen, Petra W. Whooley, Mary A. Martens, Elisabeth J. Na, Beeya van Melle, Joost P. de Jonge, Peter TI Differential Associations Between Specific Depressive Symptoms and Cardiovascular Prognosis in Patients With Stable Coronary Heart Disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE depression; stable coronary heart disease and prognosis ID POSTMYOCARDIAL INFARCTION DEPRESSION; ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-LIFE; RATE-VARIABILITY; BLOOD-INSTITUTE; NATIONAL-HEART; ARTERY-DISEASE; RISK-FACTOR; MORTALITY; METAANALYSIS AB Objectives The purpose of this research was to evaluate the relationship between cognitive and somatic depressive symptoms and cardiovascular prognosis. Background Depression in patients with stable coronary heart disease (CHD) is associated with poor cardiac prognosis. Whether certain depressive symptoms are more cardiotoxic than others is unknown. Methods In the Heart and Soul Study, 1,019 patients with stable CHD were assessed using the Patient Health Questionnaire to determine the presence of the 9 depressive symptoms included in the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. The mean age of the patients was 67 years, and 82% were men. A comparison was made on a new cardiovascular event (myocardial infarction, stroke, transient ischemic attack, or congestive heart failure) or death (mean follow-up duration 6.1 +/- 2.0 years) on the basis of cognitive and somatic sum scores and for patients with or without each of those specific depressive symptoms. Demographic characteristics, cardiac risk factors, and cardiac medications were controlled for. Results After adjustment for demographic data and cardiac risk factors, each somatic symptom was associated with 14% greater risk for events (hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.05 to 1.24; p = 0.002). Fatigue (HR: 1.34; 95% CI: 1.07 to 1.67; p = 0.01), appetite problems (HR: 1.46; 95% CI: 1.12 to 1.91; p = 0.005), and sleeping difficulties (HR: 1.26; 95% CI: 1.00 to 1.58; p = 0.05) were most strongly predictive of cardiovascular events. In contrast, cognitive symptoms (HR: 1.08; 95% CI: 0.99 to 1.17; p = 0.09) were not significantly associated with cardiovascular events. Conclusions In patients with stable CHD, somatic symptoms of depression were more strongly predictive of cardiovascular events than cognitive symptoms, although the CIs surrounding these estimates had substantial overlap. These findings are highly consistent with those of previous studies. Further research is needed to understand the pathophysiological processes by which somatic depressive symptoms contribute to prognosis in patients with CHD. (J Am Coll Cardiol 2010;56:838-44) (C) 2010 by the American College of Cardiology Foundation C1 [Hoen, Petra W.] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychiat Epidemiol, Dept Psychiat, NL-9713 GZ Groningen, Netherlands. [van Melle, Joost P.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 GZ Groningen, Netherlands. [Martens, Elisabeth J.; de Jonge, Peter] Tilburg Univ, Dept Med Psychol, NL-5000 LE Tilburg, Netherlands. [Whooley, Mary A.; Na, Beeya] San Francisco VA Med Ctr, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Hoen, PW (reprint author), Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychiat Epidemiol, Dept Psychiat, CC72,Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM p.w.hoen@med.umcg.nl RI de Jonge, peter/L-6395-2013 OI de Jonge, peter/0000-0002-0866-6929 FU U.S. Department of Veterans Affairs; U.S. Department of Veterans Affairs Health Services Research and Development Service; National Heart, Lung, and Blood Institute [R01 HL079235]; American Federation for Aging Research; Robert Wood Johnson Foundation; Ischemia Research and Education Foundation; Nancy Kirwan Heart Research Fund; Dutch Medical Research Council [016.086.397] FX The Heart and Soul Study was supported by the U.S. Department of Veterans Affairs Epidemiology Merit Review Program; the U.S. Department of Veterans Affairs Health Services Research and Development Service; grant R01 HL079235 from the National Heart, Lung, and Blood Institute; the Paul Beeson Scholars Program of the American Federation for Aging Research; the Generalist Physician Faculty Scholars Program of the Robert Wood Johnson Foundation; the Ischemia Research and Education Foundation; and the Nancy Kirwan Heart Research Fund. The funding organizations had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. Dr. de Jonge was supported by VIDI grant 016.086.397 from the Dutch Medical Research Council. All other authors have reported that they have no relationships to disclose. NR 38 TC 62 Z9 62 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 7 PY 2010 VL 56 IS 11 BP 838 EP 844 DI 10.1016/j.jacc.2010.03.080 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645IT UT WOS:000281448500003 PM 20813281 ER PT J AU Panizzon, MS Hauger, R Dale, AM Eaves, LJ Eyler, LT Fischl, B Fennema-Notestine, C Franz, CE Grant, MD Jak, AJ Jacobson, KC Lyons, MJ Mendoza, SP Neale, MC Prom-Wormley, EC Seidman, LJ Tsuang, MT Xian, H Kremen, WS AF Panizzon, M. S. Hauger, R. Dale, A. M. Eaves, L. J. Eyler, L. T. Fischl, B. Fennema-Notestine, C. Franz, C. E. Grant, M. D. Jak, A. J. Jacobson, K. C. Lyons, M. J. Mendoza, S. P. Neale, M. C. Prom-Wormley, E. C. Seidman, L. J. Tsuang, M. T. Xian, H. Kremen, W. S. TI Testosterone modifies the effect of APOE genotype on hippocampal volume in middle-aged men SO NEUROLOGY LA English DT Article ID VIETNAM ERA TWIN; ADULT MALE TWINS; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; OLDER MEN; RISK; HORMONES; SEGMENTATION; HERITABILITY; PREVALENCE AB Background: The APOE epsilon 4 allele is an established risk factor for Alzheimer disease (AD), yet findings are mixed for how early its effects are manifest. One reason for the mixed results could be the presence of interaction effects with other AD risk factors. Increasing evidence indicates that testosterone may play a significant role in the development of AD. The aim of the present study was to examine the potential interaction of testosterone and APOE genotype with respect to hippocampal volume in middle age. Methods: Participants were men from the Vietnam Era Twin Study of Aging (n = 375). The mean age was 55.9 years (range 51-59). Between-group comparisons were performed utilizing a hierarchical linear mixed model that adjusted for the nonindependence of twin data. Results: A significant interaction was observed between testosterone and APOE genotype (epsilon 4-negative vs epsilon 4-positive). Those with both low testosterone (>= 1 SD below the mean) and an epsilon 4-positive status had the smallest hippocampal volumes, although comparisons with normal testosterone groups were not significant. However, individuals with low testosterone and epsilon 4-negative status had significantly larger hippocampal volumes relative to all other groups. A main effect of APOE genotype on hippocampal volume was observed, but only when the APOE-by-testosterone interaction was present. Conclusions: These findings demonstrate an interaction effect between testosterone and the APOE epsilon 4 allele on hippocampal volume in middle-aged men, and they may suggest 2 low testosterone subgroups. Furthermore, these results allude to potential gene-gene interactions between APOE and either androgen receptor polymorphisms or genes associated with testosterone production. Neurology (R) 2010; 75: 874-880 C1 [Panizzon, M. S.; Hauger, R.; Eyler, L. T.; Fennema-Notestine, C.; Franz, C. E.; Jak, A. J.; Tsuang, M. T.; Kremen, W. S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Dale, A. M.; Fennema-Notestine, C.] Univ Calif San Diego, Dept Radiol, La Jolla, CA USA. [Dale, A. M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA USA. [Tsuang, M. T.; Kremen, W. S.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA USA. [Hauger, R.; Eyler, L. T.; Kremen, W. S.] San Diego Vet Adm Healthcare Syst, San Diego, CA USA. [Neale, M. C.; Prom-Wormley, E. C.] Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA. [Fischl, B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fischl, B.; Seidman, L. J.] Harvard Univ, Sch Med, Boston, MA USA. [Fischl, B.] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Grant, M. D.; Lyons, M. J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Jacobson, K. C.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Mendoza, S. P.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. [Tsuang, M. T.] Harvard Univ, Sch Med, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Tsuang, M. T.] Sch Publ Hlth, Boston, MA USA. [Xian, H.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Panizzon, MS (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,MC 0738, La Jolla, CA 92093 USA. EM mspanizz@ucsd.edu RI Lyons, Michael/B-6119-2011; Jacobson, Kristen/D-2064-2009; Dale, Anders/A-5180-2010; OI Prom-Wormley, Elizabeth/0000-0001-9230-9723; Lyons, Michael/0000-0001-6516-9219 FU NIH/NIA [R01 AG018386, RO1 AG018384, RO1 AG022381, RO1 AG022982, R01 AG018384, R01 AG022381, R01 AG022982]; GE Healthcare; NIH [R01MH079752-04, P50MH081755-03, R01AG031224-02, R01EB009282-02, R01AG012674-12, P50AG005131-26, P50DA026306-01A1, RC2DA029475-01, R01AG022381-07, NIAID 1UH2AI083263, NIDA U01 DA024413, NICHD R01 049685, NRSA T32 MH20030, NIMH R01 NIA 022982, NIDA R01 DA23668]; UC San Diego Academic Senate; VA VISN 22 Mental Illness Research Education and Clinical Center; Ellison Medical Foundation; US Department of Veterans Affairs; Alzheimer's Association; Massachusetts Department of Mental Health, UCLA; Sidney Baer Foundation FX Supported by the NIH/NIA (R01 AG018386, RO1 AG018384, RO1 AG022381, and RO1 AG022982) (VETSA project). Presented in part at the annual meeting of the International Society of Psychoneuroendocrinology, San Francisco, CA, July 2009. The US Department of Veterans Affairs has provided support for the development and maintenance of the Vietnam Era Twin Registry.; Dr. Panizzon has received fellowship support from the NIH/NIA (R01 AG018386, R01 AG018384, R01 AG022381, and R01 AG022982). Dr. Hauger reports no disclosures. Dr. Dale is a founder, holds equity in, and serves on the scientific advisory board of CorTechs Laboratories, Inc.; and receives research support from GE Healthcare, and the NIH (R01MH079752-04 [coinvestigator], P50MH081755-03 [Project PI], R01AG031224-02 [PI], R01EB009282-02 [coinvestigator], R01AG012674-12 [coinvestigator], P50AG005131-26 [coinvestigator], P50DA026306-01A1 [coinvestigator], RC2DA029475-01 [CoPI], and R01AG022381-07 [coinvestigator]). Dr. Eaves receives research support from the NIH (NIAID 1UH2AI083263 [coinvestigator], NIDA U01 DA024413 [coinvestigator], NICHD R01 049685 [coinvestigator], R01 AG022381 [coinvestigator], NRSA T32 MH20030 [coinvestigator], NIMH R01 NIA 022982 [coinvestigator], NIDA R01 DA23668 [coinvestigator], NIA R01 AG18384 [coinvestigator]). Dr. Eyler receives research support from the NIH (MH083968-01 [PI], AG022381-07 [coinvestigator], MH091755-01 [coinvestigator], and MH036840-21 [coinvestigator]), UC San Diego Academic Senate, and from VA VISN 22 Mental Illness Research Education and Clinical Center. Dr. Fischl has served as a consultant for Cephalon, Inc.; and receives research support from the NIH (P41-RR14075 [Project Leader], U24 RR021382 [PI of Subcontract], R01EB006758 [PI], R01AG02238 [PI of subcontract], and R01NS052585 [PI]), and from the Ellison Medical Foundation. Dr. Fennema-Notestine receives research support from the NIH (R21 NS069355 [PI], N01 MH22005 [coinvestigator], P30 MH062512 [coinvestigator], P50 DA026306 [coinvestigator], R01 MH079752 [coinvestigator], R01 AG031224 [coinvestigator], R01 AG022381 [coinvestigator], U24 RR021992 [coinvestigator], R01 MH084796 [coinvestigator], U24 RR21382 [coinvestigator], U24 RR019701 [coinvestigator], and R01 AG024506 [coinvestigator]), the US Department of Veterans Affairs, and the Alzheimer's Association. Dr. Franz receives research support from the NIH (NIA R01 AG018386 [coinvestigator], R01 AG022381 [coinvestigator], and R01 AG022982 [coinvestigator]). Dr. Grant reports no disclosures. Dr. Jak receives research support from the NIH (NIA 5 RO1 AG12674 [coinvestigator] and NIMH 1R43AG032629-01A1 SBIR [coinvestigator]), the US Department of Veterans Affairs, and the Alzheimer's Association. Dr. Jacobson serves as a consultant for the NIH (PhenX project); served as Editor for Special Issue of Behavior Genetics; and receives research from the NIH (1DP2 OD003021 [PI], NIMH 5R01 MH058354 [PI of subcontract], NIA 1R01 AG018386 [PI of subcontract], NIMH 1R01 MH080109 [coinvestigator], and NIMH/NIA 5R01 AG022982 [PI of subcontract]). Dr. Lyons serves as an Associate Editor of Behavior Genetics; and receives research support from the NIH (NIA 5R01AG018384 [PI]). Dr. Mendoza receives research support from the NIH (NCRR RR00169 [Staff Scientist], NCRR RR019970 [coinvestigator], and NICHD R01 HD053555 [Co-PI]) and from the California National Primate Research Center (NIH). Dr. Neale receives research support from the NIH (DA26119 [PI], DA-18673 [PI], and AG-22381 [PI subcontract]). Dr. PromWormley has received support from the NIH/NIMH (Training Grant MH-20030). Dr.; Seidman serves as an Associate Editor of Neuropsychology; and receives research support from the NIH (NIMH 1 P50 MH080272-01 [PI clinical core], NIMH 1 U01 MH081928-01A1 [PI], NIMH 5R01 MH56956 [coinvestigator], NIMH 4RO1 MH040799 [coinvestigator], NIMH R21 MH083205 [coinvestigator], NIMH 1 RO1 MH078113-01A2 [coinvestigator], and 121 MH082235 [coinvestigator]), the Massachusetts Department of Mental Health, UCLA, and from the Sidney Baer Foundation. Dr. Tsuang serves as Editor-inChief of the American Journal Medical Genetics Part B, Neuropsychiatric Genetics; is an inventor on patents re: Biomarkers for Psychosis; receives royalties from the publication of Textbook of Psychiatric Epidemiology, 2nd ed. (Wiley-Liss, 2002); and receives research support from the NIH (R21 MH85240 [PI], R01 MH085560 [PI], and R01 MH081861 [PI]). Dr. Xian receives research support from the NIH (NIA R01 AG18386-5 [coinvestigator], NIDA R01 DA020810 [PI], NHGRI 5 U01 HG04422-2 [coinvestigator], and NIDA 2 R01 DA014262-06 [coinvestigator]). Dr. Kremen serves on the editorial board of Neuropsychology Review; is an inventor on a patent re: Detection and Validation of Biomarkers for Neuropsychiatric Disorders (NeuroMark Genomics, Inc.); and serves as a grant reviewer on study section for the US Veterans Administration. NR 40 TC 21 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 7 PY 2010 VL 75 IS 10 BP 874 EP 880 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 648KJ UT WOS:000281692200007 PM 20819998 ER PT J AU Nohadani, O Seco, J Bortfeld, T AF Nohadani, Omid Seco, Joao Bortfeld, Thomas TI Motion management with phase-adapted 4D-optimization SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DIRECT-APERTURE OPTIMIZATION; MODULATED RADIATION-THERAPY; MONTE-CARLO; IMRT OPTIMIZATION; ROBUST OPTIMIZATION; DOSE CALCULATION; RADIOTHERAPY; UNCERTAINTY AB Cancer treatment with ionizing radiation is often compromised by organ motion, in particular for lung cases. Motion uncertainties can significantly degrade an otherwise optimized treatment plan. We present a spatiotemporal optimization method, which takes into account all phases of breathing via the corresponding 4D-CTs and provides a 4D-optimal plan that can be delivered throughout all breathing phases. Monte Carlo dose calculations are employed to warrant for highest dosimetric accuracy, as pertinent to study motion effects in lung. We demonstrate the performance of this optimization method with clinical lung cancer cases and compare the outcomes to conventional gating techniques. We report significant improvements in target coverage and in healthy tissue sparing at a comparable computational expense. Furthermore, we show that the phase-adapted 4D-optimized plans are robust against irregular breathing, as opposed to gating. This technique has the potential to yield a higher delivery efficiency and a decisively shorter delivery time. C1 [Nohadani, Omid] Purdue Univ, Sch Ind Engn, W Lafayette, IN 47907 USA. [Seco, Joao; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Seco, Joao; Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nohadani, O (reprint author), Purdue Univ, Sch Ind Engn, W Lafayette, IN 47907 USA. EM nohadani@purdue.edu; jseco@partners.org; tbortfeld@partners.org RI Seco, Joao/J-4451-2012; Nohadani, Omid/N-8177-2013 FU National Cancer Institute of the United States [R01-CA118200, R01-CA103904] FX We would like to thank N Choi for providing the lung patient data. We are also very grateful to H Paganetti for providing some of the computational resources. This work was supported by the National Cancer Institute of the United States under grants R01-CA118200 and R01-CA103904. NR 26 TC 20 Z9 20 U1 0 U2 2 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 7 PY 2010 VL 55 IS 17 BP 5189 EP 5202 DI 10.1088/0031-9155/55/17/019 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 639HU UT WOS:000280966600019 PM 20714043 ER PT J AU Fuchs, TA Brill, A Duerschmied, D Schatzberg, D Monestier, M Myers, DD Wrobleski, SK Wakefield, TW Hartwig, JH Wagner, DD AF Fuchs, Tobias A. Brill, Alexander Duerschmied, Daniel Schatzberg, Daphne Monestier, Marc Myers, Daniel D., Jr. Wrobleski, Shirley K. Wakefield, Thomas W. Hartwig, John H. Wagner, Denisa D. TI Extracellular DNA traps promote thrombosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neutrophils; platelets; histones; red blood cells; chromatin ID VENOUS THROMBOSIS; MITOCHONDRIAL-DNA; NEUTROPHILS; MECHANISMS; BINDING; BLOOD; CELLS; INTERLEUKIN-8; INFLAMMATION; DEGRADATION AB Neutrophil extracellular traps (NETs) are part of the innate immune response to infections. NETs are a meshwork of DNA fibers comprising histones and antimicrobial proteins. Microbes are immobilized in NETs and encounter a locally high and lethal concentration of effector proteins. Recent studies show that NETs are formed inside the vasculature in infections and noninfectious diseases. Here we report that NETs provide a heretofore unrecognized scaffold and stimulus for thrombus formation. NETs perfused with blood caused platelet adhesion, activation, and aggregation. DNase or the anticoagulant heparin dismantled the NET scaffold and prevented thrombus formation. Stimulation of platelets with purified histones was sufficient for aggregation. NETs recruited red blood cells, promoted fibrin deposition, and induced a red thrombus, such as that found in veins. Markers of extracellular DNA traps were detected in a thrombus and plasma of baboons subjected to deep vein thrombosis, an example of inflammation-enhanced thrombosis. Our observations indicate that NETs are a previously unrecognized link between inflammation and thrombosis and may further explain the epidemiological association of infection with thrombosis. C1 [Fuchs, Tobias A.; Brill, Alexander; Duerschmied, Daniel; Schatzberg, Daphne; Wagner, Denisa D.] Immune Dis Inst, Boston, MA 02115 USA. [Fuchs, Tobias A.; Brill, Alexander; Duerschmied, Daniel; Schatzberg, Daphne; Wagner, Denisa D.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Fuchs, Tobias A.; Brill, Alexander; Duerschmied, Daniel; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Monestier, Marc] Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA. [Myers, Daniel D., Jr.; Wrobleski, Shirley K.; Wakefield, Thomas W.] Univ Michigan, Med Ctr, Vasc Surg Sect, Ann Arbor, MI 48109 USA. [Myers, Daniel D., Jr.] Univ Michigan, Med Ctr, Unit Lab Anim Med, Ann Arbor, MI 48109 USA. [Hartwig, John H.] Brigham & Womens Hosp, Translat Med Div, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Immune Dis Inst, Boston, MA 02115 USA. EM wagner@idi.harvard.edu RI Fuchs, Tobias/F-1189-2013 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [P01 HL056949, R01 HL095091, R01 HL070766]; Deutsche Forschungsgemeinschaft, Germany [FU 742/1-1] FX We thank Drs. Richard Hynes and Bernhard Lammle for critical reading of the manuscript and helpful discussions, and Lesley Cowan for help preparing the manuscript. This research was supported by National Heart, Lung, and Blood Institute of the National Institutes of Health Grants P01 HL056949 (to D. D. W. and J.H.H.), R01 HL095091 (to T. W. W. and D. D. W.), and R01 HL070766 (to T. W. W.), and a fellowship from the Deutsche Forschungsgemeinschaft, Germany (FU 742/1-1) (to T.A.F.). NR 42 TC 470 Z9 484 U1 7 U2 34 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 7 PY 2010 VL 107 IS 36 BP 15880 EP 15885 DI 10.1073/pnas.1005743107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647RY UT WOS:000281637800047 PM 20798043 ER PT J AU Krishnan, L Li, XA Naraharisetty, HL Hare, S Cherepanov, P Engelman, A AF Krishnan, Lavanya Li, Xiang Naraharisetty, Hema L. Hare, Stephen Cherepanov, Peter Engelman, Alan TI Structure-based modeling of the functional HIV-1 intasome and its inhibition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV/AIDS; integrase; integration; drug resistance; raltegravir ID STRAND TRANSFER INHIBITORS; SARCOMA-VIRUS INTEGRASE; VIRAL-DNA BINDING; PHOTO-CROSS-LINKING; CRYSTAL-STRUCTURE; PREINTEGRATION COMPLEXES; TYPE-1 INTEGRASE; IN-VITRO; PROTEIN; DOMAINS AB The intasome is the basic recombination unit of retroviral integration, comprising the integrase protein and the ends of the viral DNA made by reverse transcription. Clinical inhibitors preferentially target the DNA-bound form of integrase as compared with the free protein, highlighting the critical requirement for detailed understanding of HIV-1 intasome structure and function. Although previous biochemical studies identified integrase residues that contact the DNA, structural details of protein-protein and protein-DNA interactions within the functional intasome were lacking. The recent crystal structure of the prototype foamy virus (PFV) integrase-viral DNA complex revealed numerous details of this related integration machine. Structures of drug-bound PFV intasomes moreover elucidated the mechanism of inhibitor action. Herein we present a model for the HIV-1 intasome assembled using the PFV structure as template. Our results pinpoint previously identified protein-DNA contacts within the quaternary structure and reveal hitherto unknown roles for Arg20 and Lys266 in DNA binding and integrase function. Models for clinical inhibitors bound at the HIV-1 integrase active site were also constructed and compared with previous studies. Our findings highlight the structural basis for HIV-1 integration and define the mechanism of its inhibition, which should help in formulating new drugs to inhibit viruses resistant to first-in-class compounds. C1 [Hare, Stephen; Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, London W2 1PG, England. [Krishnan, Lavanya; Li, Xiang; Naraharisetty, Hema L.; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Cherepanov, P (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, London W2 1PG, England. EM p.cherepanov@imperial.ac.uk; alan_engelman@dfci.harvard.edu RI Li, Xiang/C-4588-2011; Cherepanov, Peter/F-6859-2010; OI Cherepanov, Peter/0000-0002-0634-538X; Hare, Stephen/0000-0003-2951-1595 FU UK Medical Research Council [G0900116]; US National Institutes of Health [AI070042]; Harvard University Center for AIDS Research; National Institutes of Health [P30AI060354] FX This work was supported by UK Medical Research Council Grant G0900116 (to P. C.), US National Institutes of Health Grant AI070042 (to A. E.), and the Harvard University Center for AIDS Research, a National Institutes of Health-funded program (P30AI060354) that is supported by multiple National Institutes of Health Institutes and Centers (National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Child Health and Human Development, National Heart, Lung, and Blood Institute, and National Center for Complementary and Alternative Medicine). NR 54 TC 126 Z9 129 U1 1 U2 11 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 7 PY 2010 VL 107 IS 36 BP 15910 EP 15915 DI 10.1073/pnas.1002346107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647RY UT WOS:000281637800052 PM 20733078 ER PT J AU Nossa, CW Oberdorf, WE Yang, LY Aas, JA Paster, BJ DeSantis, TZ Brodie, EL Malamud, D Poles, MA Pei, ZH AF Nossa, Carlos W. Oberdorf, William E. Yang, Liying Aas, Jorn A. Paster, Bruce J. DeSantis, Todd Z. Brodie, Eoin L. Malamud, Daniel Poles, Michael A. Pei, Zhiheng TI Design of 16S rRNA gene primers for 454 pyrosequencing of the human foregut microbiome SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Foregut; Microbiome; 16S; 454 sequencing; Primer ID DISTAL ESOPHAGUS; BACTERIAL BIOTA; DNA; DIVERSITY; SEQUENCES; AMPLIFICATION AB AIM: To design and validate broad-range 16S rRNA primers for use in high throughput sequencing to classify bacteria isolated from the human foregut microbiome. METHODS: A foregut microbiome dataset was constructed using 16S rRNA gene sequences obtained from oral, esophageal, and gastric microbiomes produced by Sanger sequencing in previous studies represented by 219 bacterial species. Candidate primers evaluated were from the European rRNA database. To assess the effect of sequence length on accuracy of classification, 16S rRNA genes of various lengths were created by trimming the full length sequences. Sequences spanning various hypervariable regions were selected to simulate the amplicons that would be obtained using possible primer pairs. The sequences were compared with full length 16S rRNA genes for accuracy in taxonomic classification using online software at the Ribosomal Database Project (RDP). The universality of the primer set was evaluated using the RDP 16S rRNA database which is comprised of 433306 16S rRNA genes, represented by 36 phyla. RESULTS: Truncation to 100 nucleotides (nt) downstream from the position corresponding to base 28 in the Escherichia coli 165 rRNA gene caused misclassification of 87 (39.7%) of the 219 sequences, compared with misclassification of only 29 (13.2%) sequences with truncation to 350 nt. Among 350-nt sequence reads within various regions of the 165 rRNA gene, the reverse read of an amplicon generated using the 343F/798R primers had the least (8.2%) effect on classification. In comparison, truncation to 900 nt mimicking single pass Sanger reads misclassified 5.0% of the 219 sequences. The 343F/798R amplicon accurately assigned 91.8% of the 219 sequences at the species level. Weighted by abundance of the species in the esophageal dataset, the 343F/798R amplicon yielded similar classification accuracy without a significant loss in species coverage (92%). Modification of the 343F/798R primers to 347F/803R increased their universality among foregut species. Assuming that a typical polymerase chain reaction can tolerate 2 mismatches between a primer and a template, the modified 347F and 803R primers should be able to anneal 98% and 99.6% of all 16S rRNA genes in the RDP database. CONCLUSION: 347F/803R is the most suitable pair of primers for classification of foregut 16S rRNA genes but also possess universality suitable for analyses of other complex microbionnes. (C) 2010 Baishideng. All rights reserved. C1 [Pei, Zhiheng] Dept Vet Affairs New York Harbor Hlth Syst, New York, NY 10010 USA. [Nossa, Carlos W.; Oberdorf, William E.; Poles, Michael A.] NYU, Sch Med, Dept Med, New York, NY 10016 USA. [Yang, Liying] NYU, Dept Pathol, Sch Med, New York, NY 10016 USA. [Aas, Jorn A.; Paster, Bruce J.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. [Aas, Jorn A.] Univ Oslo, Fac Dent, N-0316 Oslo, Norway. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [DeSantis, Todd Z.; Brodie, Eoin L.] Univ Calif Berkeley, Lawrence Berkeley Lab, Ctr Environm Biotechnol, Berkeley, CA 94720 USA. [Malamud, Daniel] NYU, Coll Dent, New York, NY 10016 USA. [Pei, Zhiheng] NYU, Dept Pathol & Med, Sch Med, New York, NY 10016 USA. RP Pei, ZH (reprint author), Dept Vet Affairs New York Harbor Hlth Syst, 423 E 23rd St, New York, NY 10010 USA. EM zhiheng.pei@nyumc.org RI Brodie, Eoin/A-7853-2008; OI Brodie, Eoin/0000-0002-8453-8435; Malamud, Daniel/0000-0002-9094-4122 FU NIH Roadmap Initiative [UH2CA140233]; National Cancer Institute [UH2CA140233]; National Institute of Allergy and Infectious Diseases [R01AI063477]; National Institute of Dental and Craniofacial Research [DE-11443, U19DE018385] FX Supported by (in part) Grants UH2CA140233 from the Human Microbiome Project of the NIH Roadmap Initiative and National Cancer Institute; R01AI063477 from the National Institute of Allergy and Infectious Diseases; DE-11443 from the National Institute of Dental and Craniofacial Research; and U19DE018385 from the National Institute of Dental & Craniofacial Research NR 32 TC 102 Z9 104 U1 1 U2 44 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD SEP 7 PY 2010 VL 16 IS 33 BP 4135 EP 4144 DI 10.3748/wjg.v16.i33.4135 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 647PH UT WOS:000281630300004 PM 20806429 ER PT J AU Furlong, CE Suzuki, SM Stevens, RC Marsillach, J Richter, RJ Jarvik, GP Checkoway, H Samii, A Costa, LG Griffith, A Roberts, JW Yearout, D Zabetian, CP AF Furlong, C. E. Suzuki, S. M. Stevens, R. C. Marsillach, J. Richter, R. J. Jarvik, G. P. Checkoway, H. Samii, A. Costa, L. G. Griffith, A. Roberts, J. W. Yearout, D. Zabetian, C. P. TI Human PON1, a biomarker of risk of disease and exposure SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT 10th International Meeting on Cholinesterases CY SEP 20-25, 2009 CL Sibenik, CROATIA SP Inst Med Res & Occupat Hlth, Croatian Soc Biochem & Mole Biol, Croatian Acad Sci & Arts DE Paraoxonase 1; Parkinson disease; Organophosphate; Therapy for OP poisoning; Chlorpyrifos/chlorpyrifos oxon; Diazinon/diazoxon ID HUMAN-SERUM PARAOXONASE; CORONARY-HEART-DISEASE; APOLIPOPROTEIN-A-I; PARKINSONS-DISEASE; GENE POLYMORPHISMS; CARDIOVASCULAR-DISEASE; Q192R POLYMORPHISM; CHLORPYRIFOS-OXON; VASCULAR-DISEASE; MOLECULAR-BASIS AB Human paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme that exhibits a broad substrate specificity. In addition to protecting against exposure to some organophosphorus (OP) pesticides by hydrolyzing their toxic oxon metabolites. PON1 is important in protecting against vascular disease by metabolizing oxidized lipids. Recently, PON1 has also been shown to play a role in inactivating the quorum sensing factor N-(3-oxododecanoyl)-L-homoserine lactone (3OC12-HSL) of Pseudomonas aeruginosa. Native, untagged engineered recombinant human PON1 (rHuPON1) expressed in Escherichia coli and purified by conventional column chromatographic purification is stable, active, and capable of protecting PON1 knockout mice (PON1(-/-)) from exposure to high levels of the OP compound diazoxon. The bacterially derived rHuPON1 can be produced in large quantities and lacks the glycosylation of eukaryotic systems that can produce immunogenic complications when inappropriately glycosylated recombinant proteins are used as therapeutics. Previous studies have shown that the determination of PON1 status, which reveals both PON1(192) functional genotype and serum enzyme activity level, is required for a meaningful evaluation of PON1's role in risk of disease or exposure. We have developed a new two-substrate assay/analysis protocol that provides PON1 status without use of toxic OP substrates, allowing for use of this protocol in non-specialized laboratories. Factors were also determined for inter-converting rates of hydrolysis of different substrates. PON1 status also plays an important role in revealing changes in HDL-associated PON1 activities in male patients with Parkinson disease (PD). Immunolocalization studies of PONs 1, 2 and 3 in nearly all mouse tissues suggest that the functions of PONs 1 and 3 extend beyond the plasma and the HDL particle. (C) 2010 Published by Elsevier Ireland Ltd. C1 [Furlong, C. E.; Suzuki, S. M.; Stevens, R. C.; Marsillach, J.; Richter, R. J.; Jarvik, G. P.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Furlong, C. E.; Suzuki, S. M.; Stevens, R. C.; Marsillach, J.; Richter, R. J.; Jarvik, G. P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Checkoway, H.; Costa, L. G.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Checkoway, H.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Samii, A.; Yearout, D.; Zabetian, C. P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Samii, A.; Yearout, D.; Zabetian, C. P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Costa, L. G.] Univ Parma, Dept Human Anat Pharmacol & Forens Sci, I-43100 Parma, Italy. [Griffith, A.] Evergreen Hosp Med Ctr, Kirkland, WA USA. [Roberts, J. W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. RP Furlong, CE (reprint author), Univ Washington, Dept Med, Div Med Genet, Box 357720, Seattle, WA 98195 USA. EM clem@u.washington.edu RI Jarvik, Gail/N-6476-2014; Marsillach, Judit/I-1329-2015; OI Jarvik, Gail/0000-0002-6710-8708; Marsillach, Judit/0000-0002-3061-6266; Zabetian, Cyrus/0000-0002-7739-4306 FU NHLBI NIH HHS [HL67406, R01 HL067406, R01 HL067406-07]; NIEHS NIH HHS [ES04696, ES07033, ES09601, ES09883, P01 ES009601, P01 ES009601-10, P30 ES007033, P30 ES007033-14S1, P42 ES004696, P42 ES004696-23, P42 ES004696-235868, R01 ES009883, R01 ES009883-09A1]; NINDS NIH HHS [R01 NS065070-03, P50 NS062684, P50 NS062684-01A16218, R01 NS065070, R01 NS065070-01A1, R01 NS065070-02] NR 77 TC 44 Z9 46 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD SEP 6 PY 2010 VL 187 IS 1-3 SI SI BP 355 EP 361 DI 10.1016/j.cbi.2010.03.033 PG 7 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 641EW UT WOS:000281108600065 PM 20338154 ER PT J AU Pham, SV Pham, PCT Pham, PMT Miller, JM Pham, PTT Pham, PAT AF Pham, Son V. Pham, Phuong-Chi T. Pham, Phuong-Mai T. Miller, Jeffrey M. Pham, Phuong-Thu T. Pham, Phuong-Anh T. TI Antithrombotic strategies in patients undergoing percutaneous coronary intervention for acute coronary syndrome SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Review DE acute coronary syndrome; percutaneous coronary intervention; aspirin; clopidogrel; glycoprotein IIb/IIIa inhibitors; bivalirudin AB In patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS), both periprocedural acute myocardial infarction and bleeding complications have been shown to be associated with early and late mortality. Current standard antithrombotic therapy after coronary stent implantation consists of lifelong aspirin and clopidogrel for a variable period depending in part on the stent type. Despite its well-established efficacy in reducing cardiac-related death, myocardial infarction, and stroke, dual antiplatelet therapy with aspirin and clopidogrel is not without shortcomings. While clopidogrel may be of little beneficial effect if administered immediately prior to PCI and may even increase major bleeding risk if coronary artery bypass grafting is anticipated, early discontinuation of the drug may result in insufficient antiplatelet coverage with thrombotic complications. Optimal and rapid inhibition of platelet activity to suppress ischemic and thrombotic events while minimizing bleeding complications is an important therapeutic goal in the management of patients undergoing percutaneous coronary intervention. In this article we present an overview of the literature on clinical trials evaluating the different aspects of antithrombotic therapy in patients undergoing PCI and discuss the emerging role of these agents in the contemporary era of early invasive coronary intervention. Clinical trial acronyms and their full names are provided in Table 1. C1 [Pham, Phuong-Thu T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Nephrol Div,Kidney & Pancreas Transplant Program, Los Angeles, CA 90095 USA. [Pham, Phuong-Anh T.] Mercy Gen Hosp, Inst Heart & Vasc, Dept Cardiol, Sacramento, CA USA. [Pham, Son V.] Bay Pines VA Med Ctr, Dept Cardiol, Bay Pines, FL USA. [Pham, Phuong-Chi T.] Univ Calif Los Angeles, Olive View Med Ctr, Dept Med, Div Nephrol, Los Angeles, CA 90095 USA. [Miller, Jeffrey M.] Univ Calif Los Angeles, Olive View Med Ctr, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. [Pham, Phuong-Mai T.] Greater Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. RP Pham, PTT (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Nephrol Div,Kidney & Pancreas Transplant Program, Los Angeles, CA 90095 USA. EM ppham@mednet.ucla.edu NR 53 TC 1 Z9 3 U1 0 U2 3 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-8881 J9 DRUG DES DEV THER JI Drug Des. Dev. Ther. PD SEP 6 PY 2010 VL 4 BP 203 EP 220 DI 10.2147/DDDT.S12056 PG 18 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V20YU UT WOS:000208176100001 PM 20856846 ER PT J AU Karumanchi, SA Thadhani, R AF Karumanchi, S. Ananth Thadhani, Ravi TI A complement to kidney disease: CFHR5 nephropathy SO LANCET LA English DT Editorial Material ID H-RELATED PROTEIN-5 C1 [Karumanchi, S. Ananth] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA. RP Thadhani, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu FU Howard Hughes Medical Institute; NIEHS NIH HHS [P30 ES002109] NR 9 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD SEP 4 PY 2010 VL 376 IS 9743 BP 748 EP 750 DI 10.1016/S0140-6736(10)60967-1 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 650EC UT WOS:000281831000006 PM 20800272 ER PT J AU Won, JS Im, YB Kim, J Singh, AK Singh, I AF Won, Je-Seong Im, Yeong-Bin Kim, Jinsu Singh, Avtar K. Singh, Inderjit TI Involvement of AMP-activated-protein-kinase (AMPK) in neuronal amyloidogenesis SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE AMPK; Amyloid-beta; Amyloid precursor protein; Cholesterol; Lipid rafts; Sphingomyelin ID LIPID RAFTS; DISEASE; APP; CHOLESTEROL; GENERATION; OBESITY AB AMP-activated-protein-kinase (AMPK) is a key sensor and regulator of cellular and whole-body energy metabolism and plays a key role in regulation of lipid metabolism. Since lipid metabolism has been implicated in neuronal amyloid-beta (A beta) homeostasis and onset of Alzheimer's disease, we investigated the involvement of AMPK in neuronal lipid metabolism and A beta production. We observed in cultured rat cortical neurons that AD production was significantly reduced when the neurons were stimulated with AMPK activator, 5-aminoimidazole-4-carboxamide-1-D-ribofuranoside (AICAR), but increased when AMPK alpha 2 was knocked out, thus indicating the role of AMPK in amyloidogenesis. Although the detailed mechanisms by which AMPK regulates A beta generation is not well understood, AMPK-mediated alterations in cholesterol and sphingomyelin homeostasis and in turn the altered distribution of A beta precursor-protein (APP) in cholesterol and sphingomyelin rich membrane lipid rafts participate in A beta generation. Taken together, this is the first report on the role of AMPK in regulation of neuronal amyloidogenesis. (C) 2010 Published by Elsevier Inc. C1 [Won, Je-Seong; Im, Yeong-Bin; Kim, Jinsu; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Charles P Darby Children Res Inst, Charleston, SC 29425 USA. [Won, Je-Seong] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson Vet Adm Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, Charles P Darby Children Res Inst, 504D,173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu FU National Institute of Health [NS-22576, NS-34741, NS-37766, AG-25307, RR018823, RR015455] FX We thank Ms. Joyce Bryan for laboratory assistance and Ms. Chara Williams for secretarial assistance. This study was supported in part by grants from National Institute of Health (NS-22576, NS-34741, NS-37766, AG-25307, RR018823 and RR015455). We would like to thank Dr. Benoit Viollet in INSERM U567 for providing AMP-K alpha 2 knockout mice. NR 18 TC 32 Z9 37 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 3 PY 2010 VL 399 IS 4 BP 487 EP 491 DI 10.1016/j.bbrc.2010.07.081 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 650HQ UT WOS:000281840200005 PM 20659426 ER PT J AU Gagnon, E Xu, CQ Yang, W Chu, HH Call, ME Chou, JJ Wucherpfennig, KW AF Gagnon, Etienne Xu, Chenqi Yang, Wei Chu, H. Hamlet Call, Matthew E. Chou, James J. Wucherpfennig, Kai W. TI Multilayered Control of T Cell Receptor Phosphorylation Response SO CELL LA English DT Letter ID MEMBRANE; BINDING; ACTIVATION; MOTIF C1 [Gagnon, Etienne; Chu, H. Hamlet; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Xu, Chenqi; Yang, Wei] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. [Call, Matthew E.; Chou, James J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu RI Chou, James/N-9840-2013 FU NHLBI NIH HHS [R01 HL084329] NR 10 TC 12 Z9 13 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 3 PY 2010 VL 142 IS 5 BP 669 EP 671 DI 10.1016/j.cell.2010.08.019 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 646FL UT WOS:000281523200007 PM 20813252 ER PT J AU Bendlin, BB Newman, LM Ries, ML Puglielli, L Carlsson, CM Sager, MA Rowley, HA Gallagher, CL Willette, AA Alexander, AL Asthana, S Johnson, SC AF Bendlin, Barbara B. Newman, Lisa M. Ries, Michele L. Puglielli, Luigi Carlsson, Cynthia M. Sager, Mark A. Rowley, Howard A. Gallagher, Catherine L. Willette, Auriel A. Alexander, Andrew L. Asthana, Sanjay Johnson, Sterling C. TI NSAIDs may protect against age-related brain atrophy SO FRONTIERS IN AGING NEUROSCIENCE LA English DT Article DE Alzheimer's disease; aging; risk factors; volumetric MRI; NSAIDs ID RANDOMIZED CONTROLLED-TRIAL; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ALZHEIMER-TYPE PATHOLOGY; BETA-AMYLOID BURDEN; COGNITIVE DECLINE; CHRONIC NEUROINFLAMMATION; APOLIPOPROTEIN-E; TRANSGENIC MICE; GENETIC RISK; DISEASE PROGRESSION AB The use of non-steroidal anti-inflammatory drugs (NSAIDs) in humans is associated with brain differences including decreased number of activated microglia. In animals, NSAIDs are associated with reduced microglia, decreased amyloid burden, and neuronal preservation. Several studies suggest NSAIDs protect brain regions affected in the earliest stages of AD, including hippocampal and parahippocampal regions. In this cross-sectional study, we examined the protective effect of NSAID use on gray matter volume in a group of middle-aged and older NSAID users (n = 25) compared to non-user controls (n = 50). All participants underwent neuropsychological testing and T1-weighted magnetic resonance imaging. Non-user controls showed smaller volume in portions of the left hippocampus compared to NSAID users. Age-related loss of volume differed between groups, with controls showing greater medial temporal lobe volume loss with age compared to NSAID users. These results should be considered preliminary, but support previous reports that NSAIDs may modulate age-related loss of brain volume. C1 [Bendlin, Barbara B.; Newman, Lisa M.; Ries, Michele L.; Puglielli, Luigi; Carlsson, Cynthia M.; Sager, Mark A.; Gallagher, Catherine L.; Asthana, Sanjay; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Bendlin, Barbara B.; Newman, Lisa M.; Ries, Michele L.; Puglielli, Luigi; Carlsson, Cynthia M.; Sager, Mark A.; Rowley, Howard A.; Gallagher, Catherine L.; Willette, Auriel A.; Asthana, Sanjay; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Willette, Auriel A.] Univ Wisconsin, Dept Psychol, Harlow Primate Lab, Madison, WI 53706 USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Psychiat, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Alexander, Andrew L.] Waisman Lab Brain Imaging & Behav, Madison, WI USA. RP Bendlin, BB (reprint author), Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM bbb@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU National Institutes of Health [AG021155, MH62015, R01 AG27161, P50 AG033514]; Merit Review Grant from the Department of Veterans Affairs FX This work was supported by the National Institutes of Health (AG021155 to Sterling C. Johnson, MH62015 to Andrew L. Alexander, and R01 AG27161 to Mark A. Sager, and P50 AG033514); a Merit Review Grant from the Department of Veterans Affairs (to Sterling C. Johnson), and by the facilities and resources at the William S. Middleton Memorial Veterans Hospital (GRECC manuscript number 2010-15). The authors gratefully acknowledge the assistance of Brent Thiel, Britta Jabbar, Michele Fitzgerald, Erik Kastman, Amy Hawley, and Sandra Harding at the University of Wisconsin-Madison for their roles in data collection and technical assistance. In addition, we would like to acknowledge the kind support of researchers and staff at the Waisman Center, University of Wisconsin-Madison, where MR imaging took place. Finally, we extend thanks to our volunteers who participated in this research. NR 62 TC 3 Z9 3 U1 0 U2 6 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-4365 J9 FRONT AGING NEUROSCI JI Front. Aging Neurosci. PD SEP 3 PY 2010 VL 2 AR 35 DI 10.3389/fnagi.2010.00035 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA V26QS UT WOS:000208560700001 ER PT J AU Qin, JZ Van Buren, D Huang, HS Zhong, L Mostoslavsky, R Akbarian, S Hock, H AF Qin, Jinzhong Van Buren, Denille Huang, Hsien-Sung Zhong, Lei Mostoslavsky, Raul Akbarian, Schahram Hock, Hanno TI Chromatin Protein L3MBTL1 Is Dispensable for Development and Tumor Suppression in Mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; POLYCOMB GROUP PROTEIN; HISTONE LYSINE METHYLATION; SEX-COMB; ZINC-FINGER; BINDING MODULES; HUMAN HOMOLOG; MBT REPEATS; MIDLEG SCM; GENE AB L3MBTL1, a paralogue of Drosophila tumor suppressor lethal(3)malignant brain tumor (l(3)mbt), binds histones in a methylation state-dependent manner and contributes to higher order chromatin structure and transcriptional repression. It is the founding member of a family of MBT domain-containing proteins that has three members in Drosophila and nine in mice and humans. Knockdown experiments in cell lines suggested that L3MBTL1 has non-redundant roles in the suppression of oncogene expression. We generated a mutant mouse strain that lacks exons 13-20 of L3mbtl1. Markedly reduced levels of a mutant mRNA with an out-of-frame fusion of exons 12 and 21 were expressed, but a mutant protein was undetectable by Western blot analysis. L3MBTL1(-/-) mice developed and reproduced normally. The highest expression of L3MBTL1 was detected in the brain, but its disruption did not affect brain development, spontaneous movement, and motor coordination. Despite previous implications of L3mbtl1 in the biology of hematopoietic transcriptional regulators, lack of L3MBTL1 did not result in deficiencies in lymphopoiesis or hematopoiesis. In contrast with its demonstrated biochemical activities, embryonic stem (ES) cells lacking L3MBTL1 displayed no abnormalities in H4 lysine 20 (H4K20) mono-, di-, or trimethylation; had normal global chromatin density as assessed by micrococcal nuclease digests; and expressed normal levels of c-myc. Embryonic fibroblasts lacking L3MBTL1 displayed unaltered cell cycle arrest and down-regulation of cyclin E expression after irradiation. In cohorts of mice followed for more than 2 years, lack of L3MBTL1 did not alter normal lifespan or survival with or without sublethal irradiation. C1 [Qin, Jinzhong; Van Buren, Denille; Zhong, Lei; Mostoslavsky, Raul; Hock, Hanno] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Qin, Jinzhong; Van Buren, Denille; Hock, Hanno] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Qin, Jinzhong; Zhong, Lei; Mostoslavsky, Raul; Hock, Hanno] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hock, Hanno] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Huang, Hsien-Sung; Akbarian, Schahram] Univ Massachusetts, Brudnick Neuropsychiat Res Inst, Worcester, MA 01604 USA. RP Hock, H (reprint author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St,CPZN-4212, Boston, MA 02114 USA. EM Hock.Hanno@mgh.harvard.edu OI Huang, Hsien-Sung/0000-0003-2657-3635 FU NICHD, National Institutes of Health [HD 048489]; V Foundation; Kimmel Foundation; Ellison Foundation; Harvard Stem Cell Institute; Medical Discovery Award FX This work was supported, in whole or in part, by National Institutes of Health Grant HD 048489 from the NICHD (to S. A.). This work was also supported by a V Foundation Scholar Award and a Kimmel Foundation Scholar Award (to R. M.), a contribution from the Ellison Foundation to Massachusetts General Hospital (MGH) startup funds (to H. H.), and the Harvard Stem Cell Institute (to H. H.).; The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S4.; Recipient of an MGH Executive Committee on Research Fund for Medical Discovery Award. NR 48 TC 20 Z9 22 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 3 PY 2010 VL 285 IS 36 BP 27767 EP 27775 DI 10.1074/jbc.M110.115410 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 644TL UT WOS:000281404100032 PM 20592034 ER PT J AU Snow, JW Kim, J Currie, CR Xu, JA Orkin, SH AF Snow, Jonathan W. Kim, Jonghwan Currie, Caroline R. Xu, Jian Orkin, Stuart H. TI Sumoylation Regulates Interaction of FOG1 with C-terminal-binding Protein (CTBP) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; ERYTHROID-DIFFERENTIATION; SUMO MODIFICATION; MAMMALIAN-CELLS; FINGER PROTEIN; REPRESSION; HEMATOPOIESIS; ACTIVATION; GENE; LINEAGE AB Erythropoietic and megakaryocytic programs are specified from multipotential progenitors by the transcription factor GATA1. FOG1, a GATA1-interaction partner, is critical for GATA1 function in several contexts by bringing multiple complexes into association with GATA1 to facilitate activation or repression of target genes. To further elucidate regulation of these associations by cellular and extracellular cues, we examined FOG1 for post-translational modifications. We found that FOG1 is SUMOylated and phosphorylated in erythroid cells in a differentiation-dependent manner. Removal of the SUMOylation sites in FOG1 does not impair nuclear localization, protein stability, or chromatin occupancy. However, SUMOylation of FOG1 modulates interactions with C-terminal binding protein family members, specifically promoting CTBP1 binding. Phosphorylation of FOG1 modulates SUMOylation and, therefore, indirectly regulates the CTBP interaction. Post-translational modification of FOG1 may contribute to control of co-occupancy by CTBP family members, the NuRD complex, and GATA1 at differentially regulated genes. C1 [Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Snow, Jonathan W.; Kim, Jonghwan; Currie, Caroline R.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Snow, Jonathan W.; Kim, Jonghwan; Xu, Jian; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kim, Jonghwan; Xu, Jian; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM orkin@bloodgroup.tch.harvard.edu FU National Institutes of Health [HL32259]; Leukemia and Lymphoma Society FX This work was supported, in whole or in part, by National Institutes of Health Grant HL32259 (to S. H. O.).; Supported in part by a Leukemia and Lymphoma Society Fellowship. NR 63 TC 12 Z9 12 U1 0 U2 3 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 3 PY 2010 VL 285 IS 36 BP 28064 EP 28075 DI 10.1074/jbc.M109.096909 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 739TZ UT WOS:000288742300005 PM 20587419 ER PT J AU Yamamoto, D Shima, K Matsuo, K Nishioka, T Chen, CY Hu, GF Sasaki, A Tsuji, T AF Yamamoto, Daisuke Shima, Kaori Matsuo, Kou Nishioka, Takashi Chen, Chang Yan Hu, Guo-fu Sasaki, Akira Tsuji, Takanori TI Ornithine Decarboxylase Antizyme Induces Hypomethylation of Genome DNA and Histone H3 Lysine 9 Dimethylation (H3K9me2) in Human Oral Cancer Cell Line SO PLOS ONE LA English DT Article ID METHYLTRANSFERASE ACTIVITY; METHYLATION PATTERNS; NEUROSPORA-CRASSA; G9A; CHROMATIN; PROTEIN; GENES; POLYAMINES; HP1; DIFFERENTIATION AB Background: Methylation of CpG islands of genome DNA and lysine residues of histone H3 and H4 tails regulates gene transcription. Inhibition of polyamine synthesis by ornithine decarboxylase antizyme-1 (OAZ) in human oral cancer cell line resulted in accumulation of decarboxylated S-adenosylmethionine (dcSAM), which acts as a competitive inhibitor of methylation reactions. We anticipated that accumulation of dcSAM impaired methylation reactions and resulted in hypomethylation of genome DNA and histone tails. Methodology/Principal Findings: Global methylation state of genome DNA and lysine residues of histone H3 and H4 tails were assayed by Methylation by Isoschizomers (MIAMI) method and western blotting, respectively, in the presence or absence of OAZ expression. Ectopic expression of OAZ mediated hypomethylation of CpG islands of genome DNA and histone H3 lysine 9 dimethylation (H3K9me2). Protein level of DNA methyltransferase 3B (DNMT3B) and histone H3K9me specific methyltransferase G9a were down-regulated in OAZ transfectant. Conclusions/Significance: OAZ induced hypomethylation of CpG islands of global genome DNA and H3K9me2 by down-regulating DNMT3B and G9a protein level. Hypomethylation of CpG islands of genome DNA and histone H3K9me2 is a potent mechanism of induction of the genes related to tumor suppression and DNA double strand break repair. C1 [Yamamoto, Daisuke; Nishioka, Takashi; Chen, Chang Yan; Tsuji, Takanori] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Sch Med, Boston, MA 02215 USA. [Yamamoto, Daisuke; Sasaki, Akira] Okayama Univ, Dept Oral & Maxillofacial Surg, Grad Sch, Okayama, Japan. [Shima, Kaori] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Matsuo, Kou] Kyushu Dent Coll, Div Oral Pathol, Dept Biosci, Kitakyushu, Fukuoka 803, Japan. [Hu, Guo-fu] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Yamamoto, D (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Sch Med, Boston, MA 02215 USA. EM ttsuji@bidmc.harvard.edu FU National Institutes of Health (National Cancer Institute) [RO1-CA10044] FX National Institutes of Health (National Cancer Institute) Research Grant RO1-CA10044 for Takanori Tsuji. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 17 Z9 19 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 3 PY 2010 VL 5 IS 9 AR e12554 DI 10.1371/journal.pone.0012554 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647OL UT WOS:000281627700007 PM 20838441 ER PT J AU Heher, EC Goes, NB Spitzer, TR Raje, NS Humphreys, BD Anderson, KC Richardson, PG AF Heher, Eliot C. Goes, Nelson B. Spitzer, Thomas R. Raje, Noopur S. Humphreys, Benjamin D. Anderson, Kenneth C. Richardson, Paul G. TI Kidney disease associated with plasma cell dyscrasias SO BLOOD LA English DT Review ID IMMUNOGLOBULIN LIGHT-CHAINS; IMPAIRED RENAL-FUNCTION; PRIMARY SYSTEMIC AMYLOIDOSIS; REFRACTORY MULTIPLE-MYELOMA; HIGH-DOSE DEXAMETHASONE; PROXIMAL TUBULE CELLS; PROTEASOME INHIBITION; DEPOSITION DISEASE; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHIES AB Plasma cell dyscrasias are frequently encountered malignancies often associated with kidney disease through the production of monoclonal immunoglobulin (Ig). Paraproteins can cause a remarkably diverse set of pathologic patterns in the kidney and recent progress has been made in explaining the molecular mechanisms of paraprotein-mediated kidney injury. Other recent advances in the field include the introduction of an assay for free light chains and the use of novel antiplasma cell agents that can reverse renal failure in some cases. The role of stem cell transplantation, plasma exchange, and kidney transplantation in the management of patients with paraprotein-related kidney disease continues to evolve. (Blood. 2010;116(9):1397-1404) C1 [Heher, Eliot C.; Goes, Nelson B.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Spitzer, Thomas R.; Raje, Noopur S.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Humphreys, Benjamin D.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. [Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Heher, EC (reprint author), Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St, Boston, MA 02114 USA. EM eheher@partners.org FU AstraZeneca; Genzyme; Celgene; Novartis; Millennium; Amgen FX This study was supported in part by a grant from AstraZeneca (N.S.R.), a grant from Genzyme (B. D. H.), and grants from Celgene, Novartis, and Millennium (K. C. A.).; N.S.R. reports receiving consulting/advisory board fees from Amgen, Celgene, and Novartis. K. C. A. reports receiving consulting/advisory board fees. P. G. R. reports receiving consulting/advisory board fees from Millennium, Celgene, and Johnson & Johnson. The remaining authors declare no competing financial interests. NR 95 TC 26 Z9 31 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 2 PY 2010 VL 116 IS 9 BP 1397 EP 1404 DI 10.1182/blood-2010-03-258608 PG 8 WC Hematology SC Hematology GA 646VT UT WOS:000281572700006 PM 20462963 ER PT J AU Kolitz, JE George, SL Marcucci, G Vij, R Powell, BL Allen, SL DeAngelo, DJ Shea, TC Stock, W Baer, MR Hars, V Maharry, K Hoke, E Vardiman, JW Bloomfield, CD Larson, RA AF Kolitz, Jonathan E. George, Stephen L. Marcucci, Guido Vij, Ravi Powell, Bayard L. Allen, Steven L. DeAngelo, Daniel J. Shea, Thomas C. Stock, Wendy Baer, Maria R. Hars, Vera Maharry, Kati Hoke, Eva Vardiman, James W. Bloomfield, Clara D. Larson, Richard A. CA Canc Leukemia Grp B TI P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808 SO BLOOD LA English DT Article ID MULTIDRUG-RESISTANCE MODULATOR; ACUTE MYELOGENOUS LEUKEMIA; SOUTHWEST-ONCOLOGY-GROUP; PHASE-I; ELDERLY-PATIENTS; SDZ PSC-833; CYTARABINE; DAUNORUBICIN; AML; EXPRESSION AB Cancer and Leukemia Group B 19808 (CALGB 19808) is the only randomized trial of a second-generation P-glycoprotein (Pgp) modulator in untreated patients with acute myeloid leukemia (AML) younger than age 60 years. We randomly assigned 302 patients to receive induction chemotherapy regimens consisting of cytosine arabinoside (Ara-C; A), daunorubicin (D), and etoposide (E), without (ADE) or with (ADEP) PSC-833 (P). The incidence of complete remission was 75% with both regimens. Reversible grade 3 and 4 liver and mucosal toxicities were significantly more common with ADEP. Therapy-related mortality was 7% and did not differ by induction arm. Excess cardiotoxicity was not seen with high doses of D in ADE. The median disease-free survival was 1.34 years in the ADE arm and 1.09 years in the ADEP arm (P = .74, log-rank test); the median overall survival was 1.86 years in the ADE arm and 1.69 years in the ADEP arm (P = .82). There was no evidence of a treatment difference within any identifiable patient subgroup. Inhibition of Pgp-mediated drug efflux by PSC-833 did not improve clinical outcomes in younger patients with untreated AML. This trial was registered at www.clinicaltrials.gov as #NCT00006363. (Blood. 2010;116(9):1413-1421) C1 [Kolitz, Jonathan E.] Hofstra Univ, Monter Canc Ctr, Dept Med,Sch Med, Don Monti Div Oncol Hematol,N Shore Univ Hosp, Lake Success, NY 11042 USA. [George, Stephen L.; Hars, Vera; Maharry, Kati; Hoke, Eva] Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. [Marcucci, Guido; Maharry, Kati; Bloomfield, Clara D.] Ohio State Univ, Columbus, OH 43210 USA. [Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA. [Powell, Bayard L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Allen, Steven L.] N Shore Univ Hosp, Albert Einstein Coll Med, Lake Success, NY USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shea, Thomas C.] Univ N Carolina, Chapel Hill, NC USA. [Stock, Wendy; Vardiman, James W.; Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. [Baer, Maria R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Baer, Maria R.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Kolitz, JE (reprint author), Hofstra Univ, Monter Canc Ctr, Dept Med,Sch Med, Don Monti Div Oncol Hematol,N Shore Univ Hosp, 450 Lakeville Rd, Lake Success, NY 11042 USA. EM kolitz@nshs.edu OI Allen, Steven/0000-0002-3482-3182; Larson, Richard/0000-0001-9168-3203 FU National Cancer Institute [CA31946, CA33601]; Leukemia Clinical Research Foundation; National Cancer Institute, North Shore University Hospital, New York University School of Medicine [CA35279]; National Cancer Institute, CALGB Statistical Center [CA33601]; National Cancer Institute, Ohio State University [CA77658]; National Cancer Institute, Washington University School of Medicine [CA77440]; National Cancer Institute, Comprehensive Cancer Center of Wake Forest University [CA03927]; National Cancer Institute, North Shore University Hospital, Albert Einstein College of Medicine [CA35279]; National Cancer Institute, Dana-Farber Cancer Institute [CA32291]; National Cancer Institute, University of North Carolina at Chapel Hill [CA47559]; National Cancer Institute, University of Chicago [CA41287]; National Cancer Institute, University of Maryland Greenebaum Cancer Center [CA31983]; National Cancer Institute, Roswell Park Cancer Institute [CA02599] FX This work was supported by the National Cancer Institute to the Cancer and Leukemia Group B (grant CA31946; Richard L. Schilsky, MD, chairman) and to the CALGB Statistical Center (grant CA33601; Stephen George, PhD) and by The Leukemia Clinical Research Foundation. Institutions were supported by the National Cancer Institute (grant CA35279, North Shore University Hospital, New York University School of Medicine; grant CA33601, CALGB Statistical Center; grant CA77658, The Ohio State University; grant CA77440, Washington University School of Medicine; grant CA03927, Comprehensive Cancer Center of Wake Forest University; grant CA35279, North Shore University Hospital, Albert Einstein College of Medicine; grant CA32291, Dana-Farber Cancer Institute; grant CA47559, University of North Carolina at Chapel Hill; grant CA41287, University of Chicago; grant CA31983, University of Maryland Greenebaum Cancer Center; grant CA02599, Roswell Park Cancer Institute). NR 38 TC 59 Z9 61 U1 3 U2 8 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 2 PY 2010 VL 116 IS 9 BP 1413 EP 1421 DI 10.1182/blood-2009-07-229492 PG 9 WC Hematology SC Hematology GA 646VT UT WOS:000281572700008 PM 20522709 ER PT J AU Ikeda, H Hideshima, T Fulciniti, M Perrone, G Miura, N Yasui, H Okawa, Y Kiziltepe, T Santo, L Vallet, S Cristea, D Calabrese, E Gorgun, G Raje, NS Richardson, P Munshi, NC Lannutti, BJ Puri, KD Giese, NA Anderson, KC AF Ikeda, Hiroshi Hideshima, Teru Fulciniti, Mariateresa Perrone, Giulia Miura, Naoya Yasui, Hiroshi Okawa, Yutaka Kiziltepe, Tanyel Santo, Loredana Vallet, Sonia Cristea, Diana Calabrese, Elisabetta Gorgun, Gullu Raje, Noopur S. Richardson, Paul Munshi, Nikhil C. Lannutti, Brian J. Puri, Kamal D. Giese, Neill A. Anderson, Kenneth C. TI PI3K/p110 delta is a novel therapeutic target in multiple myeloma SO BLOOD LA English DT Article ID P70 S6 KINASE; BONE-MARROW; PHOSPHATIDYLINOSITOL 3'-KINASE/AKT; SYNERGISTIC CYTOTOXICITY; CANCER CELLS; IN-VITRO; BORTEZOMIB; APOPTOSIS; AUTOPHAGY; PATHWAY AB In this study, we demonstrate expression and examined the biologic sequelae of PI3K/p110 delta signaling in multiple myeloma (MM). Knockdown of p110 delta by small interfering RNA caused significant inhibition of MM cell growth. Similarly, p110 delta specific small molecule inhibitor CAL-101 triggered cytotoxicity against LB and INA-6 MM cell lines and patient MM cells, associated with inhibition of Akt phosphorylation. In contrast, CAL-101 did not inhibit survival of normal peripheral blood mononuclear cells. CAL-101 overcame MM cell growth conferred by interleukin-6, insulin-like growth factor-1, and bone marrow stromal cell coculture. Interestingly, inhibition of p110 delta potently induced autophagy. The in vivo inhibition of p110 delta with IC488743 was evaluated in 2 murine xenograft models of human MM: SCID mice bearing human MM cells subcutaneously and the SCID-hu model, in which human MM cells are injected within a human bone chip implanted subcutaneously in SCID mice. IC488743 significantly inhibited tumor growth and prolonged host survival in both models. Finally, combined CAL-101 with bortezomib induced synergistic cytotoxicity against MM cells. Our studies therefore show that PI3K/p110 delta is a novel therapeutic target in MM and provide the basis for clinical evaluation of CAL-101 to improve patient outcome in MM. (Blood. 2010;116(9):1460-1468) C1 [Ikeda, Hiroshi; Hideshima, Teru; Fulciniti, Mariateresa; Perrone, Giulia; Miura, Naoya; Yasui, Hiroshi; Okawa, Yutaka; Kiziltepe, Tanyel; Santo, Loredana; Vallet, Sonia; Cristea, Diana; Calabrese, Elisabetta; Gorgun, Gullu; Raje, Noopur S.; Richardson, Paul; Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Ikeda, Hiroshi; Hideshima, Teru; Fulciniti, Mariateresa; Perrone, Giulia; Miura, Naoya; Yasui, Hiroshi; Okawa, Yutaka; Kiziltepe, Tanyel; Santo, Loredana; Vallet, Sonia; Cristea, Diana; Calabrese, Elisabetta; Gorgun, Gullu; Raje, Noopur S.; Richardson, Paul; Munshi, Nikhil C.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Lebow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Ikeda, Hiroshi; Yasui, Hiroshi] Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. [Munshi, Nikhil C.] Boston VA Healthcare Syst, W Roxbury, MA USA. [Lannutti, Brian J.; Puri, Kamal D.; Giese, Neill A.] Calistoga Pharmaceut Inc, Seattle, WA USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU National Institutes of Health [IP50 CA10070, PO-1 CA78378, RO-1 CA50947]; Multiple Myeloma Research Foundation; LeBow Family Fund FX This work was supported by the National Institutes of Health Specialized Programs of Research Excellence (grants IP50 CA10070, PO-1 CA78378, and RO-1 CA50947), the Multiple Myeloma Research Foundation (T. H., K. C. A.), and the LeBow Family Fund to Cure Myeloma (K. C. A.). NR 45 TC 98 Z9 103 U1 0 U2 10 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 2 PY 2010 VL 116 IS 9 BP 1460 EP 1468 DI 10.1182/blood-2009-06-222943 PG 9 WC Hematology SC Hematology GA 646VT UT WOS:000281572700013 PM 20505158 ER PT J AU Roccaro, AM Sacco, A Jia, XY Azab, AK Maiso, P Ngo, HT Azab, F Runnels, J Quang, P Ghobrial, IM AF Roccaro, Aldo M. Sacco, Antonio Jia, Xiaoying Azab, Abdel Kareem Maiso, Patricia Ngo, Hai T. Azab, Feda Runnels, Judith Quang, Phong Ghobrial, Irene M. TI microRNA-dependent modulation of histone acetylation in Waldenstrom macroglobulinemia SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIPLE-MYELOMA; DEACETYLASE INHIBITORS; CANCER; CELLS; GENE; EXPRESSION; GROWTH; EPIGENETICS; EPIGENOME AB Waldenstrom macroglobulinemia (WM) cells present with increased expression of microRNA-206 (miRNA-206) and reduced expression of miRNA-9*. Predicted miRNA-206- and -9*-targeted genes include histone deacetylases (HDACs) and histone acetyl transferases (HATs), indicating that these miRNAs may play a role in regulating histone acetylation. We were able to demonstrate that primary WM cells are characterized by unbalanced expression of HDACs and HATs, responsible for decreased acetylated histone-H3 and -H4, and increased HDAC activity. We next examined whether miRNA-206 and -9* modulate the aberrant expression of HDAC and HATs in WM cells leading to increased transcriptional activity. We found that restoring miRNA-9* levels induced toxicity in WM cells, supported by down-modulation of HDAC4 and HDAC5 and up-regulation of acetyl-histone-H3 and -H4. These, together with inhibited HDAC activity, led to induction of apoptosis and autophagy in WM cells. To further confirm that miRNA-9*-dependent modulation of histone acetylation is responsible for induction of WM cytotoxicity, a novel class of HDAC inhibitor (LBH589) was used; we confirmed that inhibition of HDAC activity leads to toxicity in this disease. These findings confirm that histone-modifying genes and HDAC activity are deregulated in WM cells, partially driven by the aberrant expression of miRNA-206 and -9* in the tumor clone. (Blood. 2010;116(9):1506-1514) C1 [Ghobrial, Irene M.] Dana Farber Canc Inst, Kirsch Lab Waldenstrom Macroglobulinemia, Boston, MA 02115 USA. [Roccaro, Aldo M.; Sacco, Antonio; Jia, Xiaoying; Azab, Abdel Kareem; Maiso, Patricia; Ngo, Hai T.; Azab, Feda; Runnels, Judith; Quang, Phong; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Kirsch Lab Waldenstrom Macroglobulinemia, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Maiso, Patricia/0000-0003-3745-1924; Roccaro, Aldo/0000-0002-1872-5128 FU Kirsch Laboratory for WM; Heje Fellowship for WM; National Institutes of Health [1R01FD003743-01, 1R01CA154648-01]; Millennium; Novartis FX This work was supported in part by the Kirsch Laboratory for WM and The Heje Fellowship for WM, as well as the National Institutes of Health (grants 1R01FD003743-01 and 1R01CA154648-01).; I.M.G. was previously on speakers bureaus and received honoraria from Millennium, Celgene, and Novartis (September 2009) and received research funding from Millennium and Novartis. The remaining authors declare no competing financial interests. NR 37 TC 52 Z9 55 U1 5 U2 24 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 2 PY 2010 VL 116 IS 9 BP 1506 EP 1514 DI 10.1182/blood-2010-01-265686 PG 9 WC Hematology SC Hematology GA 646VT UT WOS:000281572700018 PM 20519629 ER PT J AU Hu, WG Jin, R Zhang, JY You, T Peng, ZH Ge, XW Bronson, RT Halperin, JA Loscalzo, J Qin, XB AF Hu, Weiguo Jin, Richard Zhang, Jinyan You, Tao Peng, Zhihai Ge, Xiaowen Bronson, Roderick T. Halperin, Jose A. Loscalzo, Joseph Qin, Xuebin TI The critical roles of platelet activation and reduced NO bioavailability in fatal pulmonary arterial hypertension in a murine hemolysis model SO BLOOD LA English DT Article ID SICKLE-CELL-DISEASE; REGULATOR CD59 PROTECTS; RED-BLOOD-CELLS; NITRIC-OXIDE; ENDOTHELIAL-CELLS; MOUSE MODELS; P-SELECTIN; IN-VIVO; DEATH; MICE AB Pulmonary arterial hypertension (PAH) is suspected to be a strong mortality determinant of hemolytic disorders. However, direct contribution of acute intravascular hemolysis to fatal PAH has not been investigated. The roles of nitric oxide (NO) insufficiency and platelet activation in hemolysis-associated fatal PAH have been suspected but not been experimentally studied. We recently generated a unique intravascular hemolysis mouse model in which the membrane toxin, intermedilysin (ILY), exclusively lyses the erythrocytes of transgenically expressing human CD59 mice (ThCD59(RBC)), thereby inducing ILY-dose-dependent massive hemolysis. Using this murine hemolysis model, we found that the acute increase in pulmonary arterial pressure leading to right ventricle failure caused sudden death. Reduced NO bioavailability and massive platelet activation/aggregation leading to the formation of massive thrombosis specifically in the pulmonary microvasculature played the critical roles in pathogenesis of acute hemolysis-associated fatal PAH. Therapeutic interventions enhancing NO bioactivity or inhibiting platelet activation prevented sudden death or prolonged survival time via the suppression of the acute increase in pulmonary arterial pressure and improvement of right ventricle function. These findings further highlight the importance of the inhibition of platelet activation and the enhancement of NO bioavailability for the treatment and prevention of hemolysis-associated (fatal) PAH. (Blood. 2010; 116(9):1613-1622) C1 [Hu, Weiguo; Zhang, Jinyan; You, Tao; Ge, Xiaowen; Halperin, Jose A.; Qin, Xuebin] Harvard Univ, Sch Med, Lab Translat Res, Cambridge, MA 02139 USA. [Hu, Weiguo; Jin, Richard; Halperin, Jose A.; Loscalzo, Joseph; Qin, Xuebin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Zhang, Jinyan; Peng, Zhihai] Jiaotong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Gen Surg, Shanghai, Peoples R China. [You, Tao] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Musculoskeletal Oncol, Guangzhou 510275, Guangdong, Peoples R China. [Bronson, Roderick T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Qin, XB (reprint author), Harvard Univ, Sch Med, Lab Translat Res, 1 Kendall Sq,Bldg 600,3rd Floor, Cambridge, MA 02139 USA. EM xuebin_qin@hms.harvard.edu FU National Institutes of Health [RO1AI061174]; American Heart Association [0435483N, HL 61795, NO1 HV 28178, PO1 81857, U54 HL70819]; P.R.C. National Key Technology RD Program [2008BAI60B03]; China Oversea Scholarship [2008638052] FX This work was supported by National Institutes of Health grant RO1AI061174 (X.Q.) and by a Scientist Development grant from American Heart Association 0435483N (X.Q.); HL 61795, NO1 HV 28178, PO1 81857, U54 HL70819 (J.L.); P.R.C. National Key Technology R&D Program (2008BAI60B03; Z.P.); and the China Oversea Scholarship (2008638052; Y.T.). NR 45 TC 35 Z9 37 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 2 PY 2010 VL 116 IS 9 BP 1613 EP 1622 DI 10.1182/blood-2010-01-267112 PG 10 WC Hematology SC Hematology GA 646VT UT WOS:000281572700030 PM 20511540 ER PT J AU Milbury, CA Lee, JC Cannone, JJ Gaffney, PM Gutell, RR AF Milbury, Coren A. Lee, Jung C. Cannone, Jamie J. Gaffney, Patrick M. Gutell, Robin R. TI Fragmentation of the large subunit ribosomal RNA gene in oyster mitochondrial genomes SO BMC GENOMICS LA English DT Article ID TETRAHYMENA-PYRIFORMIS MITOCHONDRIA; COMPARATIVE SEQUENCE-ANALYSIS; PHENYLALANINE TRANSFER-RNA; SECONDARY STRUCTURE MODEL; NUCLEOTIDE-SEQUENCE; GREEN-ALGAE; RIBONUCLEIC-ACID; DNA SEQUENCE; DISCONTINUOUS MITOCHONDRIAL; CHLAMYDOMONAS-REINHARDTII AB Background: Discontinuous genes have been observed in bacteria, archaea, and eukaryotic nuclei, mitochondria and chloroplasts. Gene discontinuity occurs in multiple forms: the two most frequent forms result from introns that are spliced out of the RNA and the resulting exons are spliced together to form a single transcript, and fragmented gene transcripts that are not covalently attached post-transcriptionally. Within the past few years, fragmented ribosomal RNA (rRNA) genes have been discovered in bilateral metazoan mitochondria, all within a group of related oysters. Results: In this study, we have characterized this fragmentation with comparative analysis and experimentation. We present secondary structures, modeled using comparative sequence analysis of the discontinuous mitochondrial large subunit rRNA genes of the cupped oysters C. virginica, C. gigas, and C. hongkongensis. Comparative structure models for the large subunit rRNA in each of the three oyster species are generally similar to those for other bilateral metazoans. We also used RT-PCR and analyzed ESTs to determine if the two fragmented LSU rRNAs are spliced together. The two segments are transcribed separately, and not spliced together although they still form functional rRNAs and ribosomes. Conclusions: Although many examples of discontinuous ribosomal genes have been documented in bacteria and archaea, as well as the nuclei, chloroplasts, and mitochondria of eukaryotes, oysters are some of the first characterized examples of fragmented bilateral animal mitochondrial rRNA genes. The secondary structures of the oyster LSU rRNA fragments have been predicted on the basis of previous comparative metazoan mitochondrial LSU rRNA structure models. C1 [Milbury, Coren A.; Gaffney, Patrick M.] Univ Delaware, Coll Earth Ocean & Environm, Lewes, DE 19958 USA. [Lee, Jung C.; Cannone, Jamie J.; Gutell, Robin R.] Univ Texas Austin, Inst Cellular & Mol Biol, Ctr Computat Biol & Bioinformat, Austin, TX 78712 USA. [Milbury, Coren A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Milbury, CA (reprint author), Univ Delaware, Coll Earth Ocean & Environm, Lewes, DE 19958 USA. EM coren_milbury@dfci.harvard.edu FU National Institutes of Health [GM067317]; Welch Foundation [F-1427] FX We would like to thank the reviewers for their comments and critiques. We thank Barbara Hidalgo-Sotelo for her work on the initial rRNA alignments. This work was supported by the National Institutes of Health (GM067317 to R.R.G.) and the Welch Foundation (F-1427 to R.R.G.). NR 87 TC 9 Z9 9 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD SEP 2 PY 2010 VL 11 AR 485 DI 10.1186/1471-2164-11-485 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 662EN UT WOS:000282790200002 PM 20813041 ER PT J AU Galarce, EM McDannald, MA Holland, PC AF Galarce, Ezequiel M. McDannald, Michael A. Holland, Peter C. TI The basolateral amygdala mediates the effects of cues associated with meal interruption on feeding behavior SO BRAIN RESEARCH LA English DT Article DE Amygdala; Conditioning; Cue-potentiated feeding; Scarcity; Bingeing ID PAVLOVIAN-INSTRUMENTAL TRANSFER; CONDITIONED INHIBITION; EFFERENT PROJECTIONS; UNRESTRAINED EATERS; DOUBLE DISSOCIATION; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; FOOD RESTRICTION; LEARNED CUES; SATED RATS AB Considerable evidence shows that environmental cues that signal food delivery when rats are food-deprived can substantially potentiate feeding later when rats are food-sated. Similarly, cues associated with meal interruption, food removal or impending food scarcity may also induce increased eating. For example, after learning the association between a discrete "interruption" stimulus and the unexpected termination of food trials, sated rats show enhanced food consumption when exposed to that stimulus. In Experiment 1, unlike sham-lesioned controls, rats with bilateral excitotoxic lesions of the basolateral amygdala (BLA) failed to display such cue-potentiated feeding. In Experiment 2, potentiation of feeding by an interruption signal was found to be food-specific. That is, a stimulus that signaled interruption of trials with one food but not trials with a second food later only facilitated consumption of the first food. These studies extend our knowledge of the psychological and neural processes underlying cue-induced feeding. Understanding these mechanisms may contribute our understanding of the etiology and treatment of binge eating disorders. (C) 2010 Elsevier B.V. All rights reserved. C1 [Galarce, Ezequiel M.; McDannald, Michael A.; Holland, Peter C.] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Galarce, EM (reprint author), Dana Farber Canc Inst, 44 Binney St,LW 601, Boston, MA 02115 USA. EM ezequiel_galarce@dfci.harvard.edu; mmcda001@umaryland.edu; pch@jhu.edu FU NIMH [MH53667, MH65879] FX This research was supported by NIMH grants MH53667 and MH65879. NR 52 TC 7 Z9 7 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 2 PY 2010 VL 1350 SI SI BP 112 EP 122 DI 10.1016/j.brainres.2010.02.042 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 653EA UT WOS:000282069500013 PM 20171956 ER PT J AU Altshuler, DM Gibbs, RA Peltonen, L Dermitzakis, E Schaffner, SF Yu, FL Bonnen, PE de Bakker, PIW Deloukas, P Gabriel, SB Gwilliam, R Hunt, S Inouye, M Jia, XM Palotie, A Parkin, M Whittaker, P Chang, K Hawes, A Lewis, LR Ren, YR Wheeler, D Muzny, DM Barnes, C Darvishi, K Hurles, M Korn, JM Kristiansson, K Lee, C McCarroll, SA Nemesh, J Keinan, A Montgomery, SB Pollack, S Price, AL Soranzo, N Gonzaga-Jauregui, C Anttila, V Brodeur, W Daly, MJ Leslie, S McVean, G Moutsianas, L Nguyen, H Zhang, QR Ghori, MJR McGinnis, R McLaren, W Takeuchi, F Grossman, SR Shlyakhter, I Hostetter, EB Sabeti, PC Adebamowo, CA Foster, MW Gordon, DR Licinio, J Manca, MC Marshall, PA Matsuda, I Ngare, D Wang, VO Reddy, D Rotimi, CN Royal, CD Sharp, RR Zeng, CQ Brooks, LD McEwen, JE AF Altshuler, David M. Gibbs, Richard A. Peltonen, Leena Dermitzakis, Emmanouil Schaffner, Stephen F. Yu, Fuli Bonnen, Penelope E. de Bakker, Paul I. W. Deloukas, Panos Gabriel, Stacey B. Gwilliam, Rhian Hunt, Sarah Inouye, Michael Jia, Xiaoming Palotie, Aarno Parkin, Melissa Whittaker, Pamela Chang, Kyle Hawes, Alicia Lewis, Lora R. Ren, Yanru Wheeler, David Muzny, Donna Marie Barnes, Chris Darvishi, Katayoon Hurles, Matthew Korn, Joshua M. Kristiansson, Kati Lee, Charles McCarroll, Steven A. Nemesh, James Keinan, Alon Montgomery, Stephen B. Pollack, Samuela Price, Alkes L. Soranzo, Nicole Gonzaga-Jauregui, Claudia Anttila, Verneri Brodeur, Wendy Daly, Mark J. Leslie, Stephen McVean, Gil Moutsianas, Loukas Nguyen, Huy Zhang, Qingrun Ghori, Mohammed J. R. McGinnis, Ralph McLaren, William Takeuchi, Fumihiko Grossman, Sharon R. Shlyakhter, Ilya Hostetter, Elizabeth B. Sabeti, Pardis C. Adebamowo, Clement A. Foster, Morris W. Gordon, Deborah R. Licinio, Julio Manca, Maria Cristina Marshall, Patricia A. Matsuda, Ichiro Ngare, Duncan Wang, Vivian Ota Reddy, Deepa Rotimi, Charles N. Royal, Charmaine D. Sharp, Richard R. Zeng, Changqing Brooks, Lisa D. McEwen, Jean E. CA Int HapMap 3 Consortium TI Integrating common and rare genetic variation in diverse human populations SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; COPY NUMBER VARIATION; POSITIVE SELECTION; HAPLOTYPE MAP; VARIANTS; DISEASES; SIGNALS; REGIONS; SNPS AB Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of <= 5%, and demonstrated the feasibility of imputing newly discovered CNPs and SNPs. This expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation. C1 [Altshuler, David M.; Schaffner, Stephen F.; de Bakker, Paul I. W.; Gabriel, Stacey B.; Jia, Xiaoming; Parkin, Melissa; Korn, Joshua M.; McCarroll, Steven A.; Pollack, Samuela; Brodeur, Wendy; Nguyen, Huy; Shlyakhter, Ilya] Broad Inst, Cambridge, MA 02138 USA. [Gibbs, Richard A.; Yu, Fuli; Bonnen, Penelope E.; Chang, Kyle; Hawes, Alicia; Lewis, Lora R.; Ren, Yanru; Wheeler, David; Muzny, Donna Marie; Gonzaga-Jauregui, Claudia] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA. [Dermitzakis, Emmanouil; Montgomery, Stephen B.] Univ Geneva, Sch Med, Dept Genet Med & Dev, Fac Med, CH-1211 Geneva, Switzerland. [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Genet, Boston, MA 02115 USA. [Deloukas, Panos; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Palotie, Aarno; Whittaker, Pamela; Barnes, Chris; Hurles, Matthew; Kristiansson, Kati; Soranzo, Nicole; Anttila, Verneri; Zhang, Qingrun; Ghori, Mohammed J. R.; McGinnis, Ralph; McLaren, William; Takeuchi, Fumihiko] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge CB10 1HH, England. [Palotie, Aarno; Anttila, Verneri] Univ Helsinki, Inst Mol Med Finland, FIN-00290 Helsinki, Finland. [Palotie, Aarno; Anttila, Verneri] Univ Helsinki, Dept Med Genet, FIN-00290 Helsinki, Finland. [Palotie, Aarno; Anttila, Verneri] Univ Cent Hosp, Helsinki 00290, Finland. [Darvishi, Katayoon; Lee, Charles] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Keinan, Alon] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Simches Res Ctr, Boston, MA 02114 USA. [Leslie, Stephen; McVean, Gil; Moutsianas, Loukas] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Grossman, Sharon R.; Hostetter, Elizabeth B.; Sabeti, Pardis C.] Harvard Univ, Dept Organism & Evolutionary Biol, Ctr Syst Biol, Cambridge, MA 02215 USA. [Adebamowo, Clement A.] Univ Maryland, Sch Med, Dept Epidemiol & Preventat Med, Inst Human Virol N406, Baltimore, MD 21201 USA. [Foster, Morris W.] Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA. [Gordon, Deborah R.] Univ Calif San Francisco, Dept Anthropol Hist & Social Med, San Francisco, CA 94143 USA. [Licinio, Julio] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2603, Australia. [Manca, Maria Cristina] Inst Oncol Study & Prevent, I-50139 Florence, Italy. [Marshall, Patricia A.] Case Western Reserve Univ, Dept Bioeth, Sch Med TA200, Cleveland, OH 44106 USA. [Matsuda, Ichiro] Hlth Sci Univ Hokkaido, Tobetsu, Hokkaido 0610293, Japan. [Ngare, Duncan] Moi Univ, Dept Populat & Family Hlth, Eldoret 30100, Kenya. [Wang, Vivian Ota; Brooks, Lisa D.; McEwen, Jean E.] NHGRI, NIH, Bethesda, MD 20892 USA. [Reddy, Deepa] Univ Houston Clear Lake City, Dept Anthropol, Houston, TX 77058 USA. [Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Royal, Charmaine D.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA. [Sharp, Richard R.] Cleveland Clin, Dept Bioeth, Cleveland, OH 44124 USA. [Zeng, Changqing] Chinese Acad Sci, Beijing Inst Genom, Beijing 101300, Peoples R China. RP Altshuler, DM (reprint author), Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02138 USA. EM altshuler@molbio.mgh.harvard.edu; agibbs@bcm.edu RI Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011; Deloukas, Panos/B-2922-2013; Dermitzakis, Emmanouil/B-7687-2013; Licinio, Julio/L-4244-2013; de Bakker, Paul/B-8730-2009; OI Gonzaga-Jauregui, Claudia/0000-0002-4667-3679; Altshuler, David/0000-0002-7250-4107; Deloukas, Panos/0000-0001-9251-070X; Licinio, Julio/0000-0001-6905-5884; de Bakker, Paul/0000-0001-7735-7858; Anttila, Verneri/0000-0002-0073-4675; Soranzo, Nicole/0000-0003-1095-3852; Kristiansson, Kati/0000-0003-4688-107X; Adebamowo, Clement/0000-0002-6571-2880; Hunt, Sarah/0000-0002-8350-1235; Barnes, Chris/0000-0002-9459-1395; McLaren, William/0000-0001-6218-1116 FU USA National Institutes of Health; National Human Genome Research Institute; National Institute on Deafness and Other Communication Disorders; Wellcome Trust [068545/Z/02, 076113]; Louis-Jeantet Foundation; NCCR 'Frontiers in Genetics' (Swiss National Science Foundation); UK Medical Research Council [G0000934] FX We dedicate this work to Leena Peltonen for her vital leadership role in this study, and in memory of a valued friend and colleague. We thank E. Boerwinkle and R. Durbin for critical reading of the manuscript. We thank the USA National Institutes of Health, the National Human Genome Research Institute, the National Institute on Deafness and Other Communication Disorders and the Wellcome Trust for supporting the majority of this work. Funding was also provided by the Louis-Jeantet Foundation and the NCCR 'Frontiers in Genetics' (Swiss National Science Foundation). We thank the people from the following communities who were generous in donating their blood samples to be studied in this project: the Yoruba in Ibadan, Nigeria; the Maasai in Kinyawa, Kenya; the Luhya in Webuye, Kenya; the Han Chinese in Beijing, China; the Japanese in Tokyo, Japan; the Chinese in metropolitan Denver, Colorado; the Gujarati Indians in Houston, Texas; the Toscani in Italia; the community of African ancestry in the southwestern USA; and the community of Mexican ancestry in Los Angeles, California. We also thank the people in the Utah Centre d'Etude du Polymorphisme Humain community who allowed the samples they donated earlier to be used for the project. The authors acknowledge use of DNA from the 1958 British birth cohort collection, funded by the UK Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. The Illumina 550K genotype data for the 1958 British birth cohort samples were made available by the Sanger Institute. For the 1958 British birth cohort Affymetrix 500K genotype data, we thank the Wellcome Trust Case Control Consortium (http://www.wtccc.org.uk), which was funded by Wellcome Trust award 076113. NR 27 TC 1087 Z9 1100 U1 9 U2 104 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 2 PY 2010 VL 467 IS 7311 BP 52 EP 58 DI 10.1038/nature09298 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 645MB UT WOS:000281461200033 ER PT J AU Fisher, DE James, WD AF Fisher, David E. James, William D. TI Indoor Tanning - Science, Behavior, and Policy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MELANOMA C1 [Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Fisher, David E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Fisher, David E.] Harvard Univ, Sch Med, Boston, MA USA. [James, William D.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR043369] NR 5 TC 48 Z9 49 U1 1 U2 5 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 2 PY 2010 VL 363 IS 10 BP 901 EP 903 DI 10.1056/NEJMp1005999 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 645GW UT WOS:000281441500003 PM 20818900 ER PT J AU Follett, K Weaver, F Stern, M AF Follett, Kenneth Weaver, Frances Stern, Matthew TI Deep-Brain Stimulation for Parkinson's Disease REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Follett, Kenneth] Iowa City Vet Affairs Med Ctr, Iowa City, IA USA. [Weaver, Frances] Hines Vet Affairs Hosp, Hines, IL USA. [Stern, Matthew] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Follett, K (reprint author), Iowa City Vet Affairs Med Ctr, Iowa City, IA USA. EM frances.weaver@va.gov NR 1 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 2 PY 2010 VL 363 IS 10 BP 988 EP 988 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 645GW UT WOS:000281441500018 ER PT J AU Al Gadban, MM Smith, KJ Soodavar, F Piansay, C Chassereau, C Twal, WO Klein, RL Virella, G Lopes-Virella, MF Hammad, SM AF Al Gadban, Mohammed M. Smith, Kent J. Soodavar, Farzan Piansay, Christabelle Chassereau, Charlyne Twal, Waleed O. Klein, Richard L. Virella, Gabriel Lopes-Virella, Maria F. Hammad, Samar M. TI Differential Trafficking of Oxidized LDL and Oxidized LDL Immune Complexes in Macrophages: Impact on Oxidative Stress SO PLOS ONE LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; SCAVENGER RECEPTORS; ANTIPHOSPHOLIPID SYNDROME; HEAT-SHOCK; CELLS; ATHEROSCLEROSIS; ANTIBODIES; OXLDL; ATHEROGENESIS AB Background: Oxidized low-density lipoproteins (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) contribute to formation of lipid-laden macrophages (foam cells). It has been shown that oxLDL-IC are considerably more efficient than oxLDL in induction of foam cell formation, inflammatory cytokines secretion, and cell survival promotion. Whereas oxLDL is taken up by several scavenger receptors, oxLDL-IC are predominantly internalized through the FCc receptor I (FCc RI). This study examined differences in intracellular trafficking of lipid and apolipoprotein moieties of oxLDL and oxLDL-IC and the impact on oxidative stress. Methodology/Findings: Fluorescently labeled lipid and protein moieties of oxLDL co-localized within endosomal and lysosomal compartments in U937 human monocytic cells. In contrast, the lipid moiety of oxLDL-IC was detected in the endosomal compartment, whereas its apolipoprotein moiety advanced to the lysosomal compartment. Cells treated with oxLDL-IC prior to oxLDL demonstrated co-localization of internalized lipid moieties from both oxLDL and oxLDL-IC in the endosomal compartment. This sequential treatment likely inhibited oxLDL lipid moieties from trafficking to the lysosomal compartment. In RAW 264.7 macrophages, oxLDL-IC but not oxLDL induced GFP-tagged heat shock protein 70 (HSP70) and HSP70B', which co-localized with the lipid moiety of oxLDL-IC in the endosomal compartment. This suggests that HSP70 family members might prevent the degradation of the internalized lipid moiety of oxLDL-IC by delaying its advancement to the lysosome. The data also showed that mitochondrial membrane potential was decreased and generation of reactive oxygen and nitrogen species was increased in U937 cell treated with oxLDL compared to oxLDL-IC. Conclusions/Significance: Findings suggest that lipid and apolipoprotein moieties of oxLDL-IC traffic to separate cellular compartments, and that HSP70/70B' might sequester the lipid moiety of oxLDL-IC in the endosomal compartment. This mechanism could ultimately influence macrophage function and survival. Furthermore, oxLDL-IC might regulate the intracellular trafficking of free oxLDL possibly through the induction of HSP70/70B'. C1 [Al Gadban, Mohammed M.; Smith, Kent J.; Soodavar, Farzan; Twal, Waleed O.; Hammad, Samar M.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Piansay, Christabelle] Med Univ S Carolina, Summer Undergrad Res Program, Coll Grad Studies, Charleston, SC 29425 USA. [Chassereau, Charlyne; Klein, Richard L.; Lopes-Virella, Maria F.] Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. [Klein, Richard L.; Lopes-Virella, Maria F.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Al Gadban, MM (reprint author), Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. EM hammadsm@musc.edu FU National Institutes of Health (NIH) [HL079274]; NIH (ARRA) [R01 HL079274-04S1]; NCRR [P20 RR17677]; NIH [P01 HL55782, R01 DK081352, R01 DK081352-02S1]; Department of Veterans Affairs FX This work was supported by the National Institutes of Health (NIH) grant HL079274, NIH (ARRA) grant R01 HL079274-04S1, and the South Carolina COBRE in Lipidomics and Pathobiology (P20 RR17677 from NCRR) to SMH, and NIH grants P01 HL55782, R01 DK081352 and R01 DK081352-02S1 (ARRA) to MLV, and funding from the Department of Veterans Affairs to MLV and RLK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 9 Z9 9 U1 0 U2 3 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 2 PY 2010 VL 5 IS 9 AR e12534 DI 10.1371/journal.pone.0012534 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 645RB UT WOS:000281480900017 ER PT J AU Ullrich, C Dussel, V Hilden, J Sheaffer, J Lehmann, L Wolfe, J AF Ullrich, Christina Dussel, Veronica Hilden, Joanne Sheaffer, Jan Lehmann, Leslie Wolfe, Joanne TI End-of-Life Experience of Children Undergoing Hematopoietic Stem Cell Transplantation for Malignancy: Parent and Provider Perspectives and Patterns of Care SO JOURNAL OF PALLIATIVE CARE LA English DT Meeting Abstract C1 [Ullrich, Christina; Dussel, Veronica; Lehmann, Leslie; Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hilden, Joanne] Peyton Manning Childrens Hosp St Vincent, Indianapolis, IN USA. [Sheaffer, Jan] Childrens Hosp & Clin Minnesota, St Paul, MN USA. [Sheaffer, Jan] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL PI MONTREAL PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD FAL PY 2010 VL 26 IS 3 BP 221 EP 221 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 802BE UT WOS:000293483500058 ER PT J AU Levy, C Pointer, L AF Levy, Cari Pointer, Lauren TI Identifying Hospice Eligible Nursing Home Residents SO JOURNAL OF PALLIATIVE CARE LA English DT Meeting Abstract C1 [Levy, Cari; Pointer, Lauren] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL PI MONTREAL PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD FAL PY 2010 VL 26 IS 3 BP 244 EP 244 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 802BE UT WOS:000293483500148 ER PT J AU Schulman-Green, D Bradley, E Digiovanna, M Knobf, M Prigerson, H Mccorkle, R AF Schulman-Green, Dena Bradley, Elizabeth Digiovanna, Michael Knobf, Mary Prigerson, Holly Mccorkle, Ruth TI Self-Management and Transitions in Palliative Care SO JOURNAL OF PALLIATIVE CARE LA English DT Meeting Abstract C1 [Schulman-Green, Dena; Knobf, Mary; Mccorkle, Ruth] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Bradley, Elizabeth] Yale Univ, Sch Publ Hlth, New Haven, CT 06536 USA. [Digiovanna, Michael] Yale Univ, Sch Med, New Haven, CT 06536 USA. [Prigerson, Holly] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL PI MONTREAL PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD FAL PY 2010 VL 26 IS 3 BP 251 EP 251 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 802BE UT WOS:000293483500177 ER PT J AU Mc Glothlin, D De Marco, T Yeh, DD Foreman, AJ Miller, DP Farber, HW AF Mc Glothlin, D. De Marco, T. Yeh, D. De Faria Foreman, A. J. Miller, D. P. Farber, H. W. TI Predictors of renal insufficiency in patients with pulmonary arterial hypertension: insights from the REVEAL registry SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Mc Glothlin, D.; De Marco, T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yeh, D. De Faria] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Foreman, A. J.; Miller, D. P.] ICON Clin Res, San Francisco, CA USA. [Farber, H. W.] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2010 VL 31 SU 1 BP 21 EP 21 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531900072 ER PT J AU James, S Roe, MT Cannon, CP Raev, D Horrow, J Husted, S Kontny, F Storey, RF Wallentin, L Harrington, R AF James, S. Roe, M. T. Cannon, C. P. Raev, D. Horrow, J. Husted, S. Kontny, F. Storey, R. F. Wallentin, L. Harrington, R. TI Ticagrelor versus clopidogrel in patients with Acute Coronary Syndromes intended for a non-invasive management in the PLATO trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [James, S.; Wallentin, L.] Univ Uppsala Hosp, Uppsala Clin Res Ctr UCR, Uppsala, Sweden. [Roe, M. T.; Harrington, R.] Duke Clin Res Inst, Durham, NC USA. [Cannon, C. P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Raev, D.] Minist Interior, Inst Med, Sofia, Bulgaria. [Horrow, J.] Astra Zeneca Res & Dev, Wilmington, DE USA. [Husted, S.] Aarhus Univ Hosp, Dept Cardiol, DK-8000 Aarhus, Denmark. [Kontny, F.] Volvat Med Ctr, Oslo, Norway. [Storey, R. F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. NR 0 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2010 VL 31 SU 1 BP 203 EP 203 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531901283 ER PT J AU Rodriguez, A Hlatky, M Grinfeld, L Mieres, J Rodriguez-Granillo, MA Berrocal, D Boothroyd, D Fernandez-Pereira, C Palacios, IP Oneill, W AF Rodriguez, A. Hlatky, M. Grinfeld, L. Mieres, J. Rodriguez-Granillo, M. A. Berrocal, D. Boothroyd, D. Fernandez-Pereira, C. Palacios, I. P. Oneill, W. TI Results in long term outcome of patients with multiple vessel disease treated with drug eluting,bare metal stents and coronary bypass surgery: insights from five years follow up of ERACI III study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Rodriguez, A.; Mieres, J.; Rodriguez-Granillo, M. A.; Fernandez-Pereira, C.] Sanatorium Otamendi, Buenos Aires, DF, Argentina. [Hlatky, M.; Boothroyd, D.] Stanford Univ, Med Ctr, Div Cardiovasc Med, Stanford, CA 94305 USA. [Grinfeld, L.; Berrocal, D.] Italian Hosp, Buenos Aires, DF, Argentina. [Palacios, I. P.; Oneill, W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2010 VL 31 SU 1 BP 219 EP 219 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531901342 ER PT J AU Corsini, A Raab, S Zhang, X Wang, J Xiao, R Huang, P Sebokova, E AF Corsini, A. Raab, S. Zhang, X. Wang, J. Xiao, R. Huang, P. Sebokova, E. TI Effect of aleglitazar, a balanced dual PPARalpha/gamma agonist, on pro-inflammatory biomarkers of atherothrombotic vascular disease and HDL functionality in non-human primates with metabolic syndrome SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Corsini, A.] Univ Milan, Lab Cellular Pharmacol Atherosclerosis, Milan, Italy. [Raab, S.; Sebokova, E.] F Hoffmann La Roche & Cie AG, Basel, Switzerland. [Zhang, X.; Wang, J.; Xiao, R.] Peking Univ, Primate Res Ctr, Beijing 100871, Peoples R China. [Huang, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2010 VL 31 SU 1 BP 251 EP 251 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531901472 ER PT J AU Cheng, S Xanthakis, V Sullivan, L Lieb, W Aragam, J Benjamin, E Vasan, R AF Cheng, S. Xanthakis, V. Sullivan, L. Lieb, W. Aragam, J. Benjamin, E. Vasan, R. TI Correlates of cardiac remodeling over the life course SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Cheng, S.; Aragam, J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Xanthakis, V.; Sullivan, L.; Lieb, W.; Benjamin, E.; Vasan, R.] Boston Univ, Boston, MA 02215 USA. [Aragam, J.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2010 VL 31 SU 1 BP 546 EP 546 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531903387 ER PT J AU Bersohn, M Shapiro, S Miller, DP Turner, MP Traiger, G Frost, AE AF Bersohn, M. Shapiro, S. Miller, D. P. Turner, M. P. Traiger, G. Frost, A. E. TI Prognostic value of heart rate and systemic systolic blood pressure in pulmonary arterial hypertension in the REVEAL registry SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Bersohn, M.; Shapiro, S.; Traiger, G.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare, Los Angeles, CA USA. [Miller, D. P.; Turner, M. P.] ICON Clin Res, San Francisco, CA USA. [Frost, A. E.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2010 VL 31 SU 1 BP 756 EP 756 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531905083 ER PT J AU Shah, A Lam, CS Cheng, S Verma, A Oparil, S Pitt, B Zile, MR Aurigemma, GP Solomon, SD AF Shah, A. Lam, C. S. Cheng, S. Verma, A. Oparil, S. Pitt, B. Zile, M. R. Aurigemma, G. P. Solomon, S. D. TI Albuminuria is associated with increased systolic ventricular-arterial stiffness in asymptomatic hypertensive subjects with diastolic dysfunction SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Shah, A.; Lam, C. S.; Cheng, S.; Verma, A.; Solomon, S. D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Oparil, S.] Univ Alabama, Birmingham, AL USA. [Pitt, B.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Zile, M. R.] Med Univ S Carolina, Charleston, SC USA. [Zile, M. R.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Aurigemma, G. P.] Univ Massachusetts, Worcester, MA 01605 USA. RI Solomon, Scott/I-5789-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2010 VL 31 SU 1 BP 911 EP 911 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531906135 ER PT J AU Fernandez, SM Januzzi, J Gonzalez, JCB Esparza, CM Perez, FJP Garcia, MB Oton, MDA Casas, T Valdes, M Pascual-Figal, DA AF Manzano Fernandez, S. Januzzi, J. Bonaque Gonzalez, J. C. Munoz Esparza, C. Pastor Perez, F. J. Boronat Garcia, M. Albaladejo Oton, M. D. Casas, T. Valdes, M. Pascual-Figal, D. A. TI Beta trace protein, cystatin C and prognosis in acutely destabilized heart failure SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Manzano Fernandez, S.; Bonaque Gonzalez, J. C.; Munoz Esparza, C.; Pastor Perez, F. J.; Boronat Garcia, M.; Albaladejo Oton, M. D.; Casas, T.; Valdes, M.; Pascual-Figal, D. A.] Univ Hosp Virgen De La Arrixaca, Murcia, Spain. [Januzzi, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2010 VL 31 SU 1 BP 1052 EP 1052 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531906680 ER PT J AU Kelly, JF Dow, SJ Westerhoff, C AF Kelly, John F. Dow, Sarah J. Westerhoff, Cara TI DOES OUR CHOICE OF SUBSTANCE-RELATED TERMS INFLUENCE PERCEPTIONS OF TREATMENT NEED? AN EMPIRICAL INVESTIGATION WITH TWO COMMONLY USED TERMS SO JOURNAL OF DRUG ISSUES LA English DT Article ID ALCOHOL; DISEASE AB Substance-related terminology is often a contentious topic because certain terms may convey meanings that have stigmatizing consequences and present a barrier to treatment. Chief among these are the labels, "abuse" and "abuser" While intense rhetoric has persisted on this topic, little empirical information exists to inform this debate. We tested whether referring to an individual as "a substance abuser (SA)" versus "having a substance use disorder" (SUD) evokes different judgments about treatment need, punishment, social threat, problem etiology, and self-regulation. Participants (N = 314, 76% female, 81% White, M age 38) from an urban setting completed an online 35-item assessment comparing two individuals labeled with these terms. Dependent t-tests were used to examine subscale differences. Compared to the SUD individual, the SA was perceived as engaging in wilful misconduct, a greater social threat, and more deserving of punishment. The "abuser" label may perpetuate stigmatizing attitudes and serve as a barrier to help-seeking. C1 [Kelly, John F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Kelly, John F.] Massachusetts Gen Hosp, ARMS, Boston, MA 02114 USA. [Dow, Sarah J.; Westerhoff, Cara] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA USA. RP Kelly, JF (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 22 TC 9 Z9 9 U1 0 U2 4 PU J DRUG ISSUES INC PI TALLAHASSEE PA FLORIDA STATE UNIV, SCHOOL CRIMINOLOGY CRIMINAL JUSTICE, PO BOX 66696, TALLAHASSEE, FL 32313-6696 USA SN 0022-0426 J9 J DRUG ISSUES JI J. Drug Issues PD FAL PY 2010 VL 40 IS 4 BP 805 EP 818 PG 14 WC Substance Abuse SC Substance Abuse GA 716VI UT WOS:000287001200004 ER PT J AU Schwartzman, A AF Schwartzman, Armin TI Correlated z-Values and the Accuracy of Large-Scale Statistical Estimates Comment SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Editorial Material ID DISTRIBUTIONS; HYPOTHESIS; INFERENCE; NULL C1 [Schwartzman, Armin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Schwartzman, Armin] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schwartzman, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM armins@hsph.harvard.edu OI Schwartzman, Armin/0000-0001-5335-1611 FU NCI NIH HHS [P01 CA134294-02, P01 CA134294] NR 8 TC 4 Z9 4 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2010 VL 105 IS 491 BP 1059 EP 1063 DI 10.1198/jasa.2010.tm10237 PG 5 WC Statistics & Probability SC Mathematics GA 673WQ UT WOS:000283695300019 PM 22021943 ER PT J AU Tsai, CL Magid, DJ Sullivan, AF Gordon, JA Kaushal, R Ho, PM Peterson, PN Blumenthal, D Camargo, CA AF Tsai, Chu-Lin Magid, David J. Sullivan, Ashley F. Gordon, James A. Kaushal, Rainu Ho, P. Michael Peterson, Pamela N. Blumenthal, David Camargo, Carlos A., Jr. TI Quality of Care for Acute Myocardial Infarction in 58 US Emergency Departments SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE acute myocardial infarction; emergency department; guidelines; quality of care ID ACUTE CORONARY SYNDROMES; TO-BALLOON TIME; ASSOCIATION TASK-FORCE; PRACTICE GUIDELINES COMMITTEE; AMERICAN-HEART-ASSOCIATION; 2007 FOCUSED UPDATE; ACC/AHA GUIDELINES; NATIONAL REGISTRY; HOSPITAL QUALITY; REPERFUSION AB P>Objectives: The objectives of this study were to determine concordance of emergency department (ED) management of acute myocardial infarction (AMI) with guideline recommendations and to identify ED and patient characteristics predictive of higher guideline concordance. Methods: The authors conducted a chart review study of ED AMI care as part of the National Emergency Department Safety Study (NEDSS). Using a primary hospital discharge diagnosis of AMI (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM], codes 410.XX), a random sample of ED visits for AMI in 58 urban EDs across 20 U.S. states between 2003 and 2006 were identified. Concordance with American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations was evaluated using five individual quality measures and a composite concordance score. Concordance scores were calculated as the percentage of eligible patients who received guidelines-recommended care. These percentage scores were rescaled from 0 to 100, with 100 indicating perfect concordance. Results: The cohort consisted of 3,819 subjects; their median age was 65 years, and 62% were men. The mean (+/- standard deviation [SD]) ED composite concordance score was 61 +/- 8), with a broad range of values (42 to 84). Except for aspirin use (mean concordance, 82), ED concordance scores were low (beta-blocker use, 56; timely electrocardiogram [ECG], 41; timely fibrinolytic therapy, 26; timely ED disposition for primary percutaneous coronary intervention [PCI] candidates, 43). In multivariable analyses, older age (beta-coefficient per 10-year increase, -1.5; 95% confidence interval [CI] = -2.4 to -0.5) and southern EDs (beta-coefficient, -5.2; 95% CI = -9.6 to -0.9) were associated with lower guideline concordance, whereas ST-segment elevation on initial ED ECG was associated with higher guideline concordance (beta-coefficient, 3.6; 95% CI = 1.5 to 5.7). Conclusions: Overall ED concordance with guideline-recommended processes of care was low to moderate. Emergency physicians should continue to work with other stakeholders in AMI care, such as emergency medical services (EMS) and cardiologists, to develop strategies to improve care processes. C1 [Tsai, Chu-Lin; Sullivan, Ashley F.; Gordon, James A.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Blumenthal, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Magid, David J.; Peterson, Pamela N.] Univ Colorado, Inst Hlth Res, Kaiser Permanente Colorado, Denver, CO 80202 USA. [Magid, David J.] Univ Colorado, Dept Emergency Med & Prevent Med, Denver, CO 80202 USA. [Magid, David J.] Univ Colorado, Dept Biometr, Denver, CO 80202 USA. [Ho, P. Michael] Univ Colorado, Denver VA Med Ctr, Denver, CO 80202 USA. [Peterson, Pamela N.] Univ Colorado, Denver Hlth Med Ctr, Denver, CO 80202 USA. [Kaushal, Rainu] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Kaushal, Rainu] New York Presbyterian Hosp, New York, NY USA. RP Tsai, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Agency for Healthcare Research and Quality (Rockville, MD) [R01 HS013099] FX This study was supported by grant number R01 HS013099 from the Agency for Healthcare Research and Quality (Rockville, MD). NR 56 TC 7 Z9 7 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD SEP PY 2010 VL 17 IS 9 BP 940 EP 950 DI 10.1111/j.1553-2712.2010.00832.x PG 11 WC Emergency Medicine SC Emergency Medicine GA 647PV UT WOS:000281632000005 PM 20836774 ER PT J AU Senecal, EL Thomas, SH Beeson, MS AF Senecal, Emily L. Thomas, Stephen H. Beeson, Michael S. TI With No Shelf Exam Available, SAEM Online Clerkship Testing Tool Best Option - In Reply SO ACADEMIC EMERGENCY MEDICINE LA English DT Letter C1 [Senecal, Emily L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp, Boston, MA 02163 USA. [Thomas, Stephen H.] Univ Oklahoma, Dept Emergency Med, Sch Community Med, Tulsa, OK USA. [Beeson, Michael S.] Northeastern Ohio Univ Coll Med & Pharm, Dept Emergency Med, Coll Med, Chicago, IL USA. RP Senecal, EL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp, Boston, MA 02163 USA. EM ESenecal@Partners.org 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 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD SEP PY 2010 VL 17 IS 9 BP 1029 EP 1029 DI 10.1111/j.1553-2712.2010.00859.x PG 1 WC Emergency Medicine SC Emergency Medicine GA 647PV UT WOS:000281632000022 ER PT J AU Crenshaw, K Curry, W Salanitro, AH Safford, MM Houston, TK Allison, JJ Estrada, CA AF Crenshaw, Katie Curry, William Salanitro, Amanda H. Safford, Monika M. Houston, Thomas K. Allison, Jeroan J. Estrada, Carlos A. TI Is Physician Engagement With Web-Based CME Associated With Patients' Baseline Hemoglobin A1c Levels? The Rural Diabetes Online Care Study SO ACADEMIC MEDICINE LA English DT Article ID CONTINUING MEDICAL-EDUCATION; RANDOMIZED CONTROLLED-TRIAL; ACHIEVABLE BENCHMARKS; POISSON REGRESSION; SPACED EDUCATION; COUNT DATA; FEEDBACK; STUDENTS; QUALITY; HEALTH AB Purpose To investigate the association between physician participants' levels of engagement in a Web-based educational intervention and their patients' baseline diabetes measures. Method The authors conducted a randomized trial of online CME activities designed to improve diabetes care provided by family, general, and internal medicine physicians in rural areas of 11 southeastern states between September 2006 and July 2008. Using incidence rate ratios derived from negative binomial models, the relationship between physicians' engagement with the study Web site and baseline proportion of their patients having controlled diabetes (hemoglobin A1c <= 7%) was explored. Results One hundred thirty-three participants (intervention = 64; control = 69) provided information for 1,637 patients with diabetes. In the intervention group, physicians in practices in the worst quartiles of A1c control were least engaged with the study Web site in nearly all dimensions. Total number of pages viewed decreased as quartile of A1c control worsened (137, 73, 68, 57; P = .007); similarly, for a given 10% increase in proportion of patients with controlled A1c, participants viewed 1.13 times more pages (95% CI: 1.02-1.26, P = .02). In the control group, engagement was neither correlated with A1c control nor different across quartiles of A1c control. Conclusions Engagement in Web-based interventions is measurable and has important implications for research and education. Because physicians of patients with the greatest need for improvement in A1c control may not use online educational resources as intensely as others, other strategies may be necessary to engage these physicians in professional development activities. C1 [Crenshaw, Katie] Univ Alabama, Div Continuing Med Educ, Birmingham, AL 35294 USA. [Curry, William; Salanitro, Amanda H.; Estrada, Carlos A.] Univ Alabama, Div Gen Internal Med, Birmingham, AL 35294 USA. [Salanitro, Amanda H.; Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA. [Safford, Monika M.] Univ Alabama, Div Prevent Med, Birmingham, AL 35294 USA. [Houston, Thomas K.] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Houston, Thomas K.] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, Worcester, MA USA. [Allison, Jeroan J.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness, REAP Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. RP Crenshaw, K (reprint author), Univ Alabama, Div Continuing Med Educ, 1670 Univ Blvd,VH Box 603, Birmingham, AL 35294 USA. EM kcrenshaw@uab.edu RI Houston, Thomas/F-2469-2013; OI Allison, Jeroan/0000-0003-4472-2112 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [5R18DK065001]; Veterans Affairs Quality Scholars fellowship FX This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 5R18DK065001 to Dr. Allison. Dr. Salanitro was supported by a Veterans Affairs Quality Scholars fellowship. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. NR 32 TC 8 Z9 8 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 2010 VL 85 IS 9 BP 1511 EP 1517 DI 10.1097/ACM.0b013e3181eac036 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 647IH UT WOS:000281611300025 PM 20736679 ER PT J AU Gadomski, A Wissow, LS Slade, E Jenkins, P AF Gadomski, Anne Wissow, Lawrence S. Slade, Eric Jenkins, Paul TI Training Clinicians in Mental Health Communication Skills: Impact on Primary Care Utilization SO ACADEMIC PEDIATRICS LA English DT Article DE child mental health; primary care utilization; Strengths and Difficulties Questionnaire ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PEDIATRIC PRIMARY-CARE; DIFFICULTIES QUESTIONNAIRE; PSYCHOMETRIC PROPERTIES; PSYCHIATRIC-DISORDERS; MEDICAL-CARE; CHILDREN; STRENGTHS; PHYSICIANS; SERVICES AB OBJECTIVE: Although it is known that children with mental health problems utilize primary care services more than most other children, it is unknown how addressing mental health problems in primary care affects children's subsequent services utilization. This study measures primary care utilization in the context of a randomized trial of a communication skills training program for primary care clinicians that had a positive impact on child mental health outcomes. METHODS: From 2002 to 2005, 48 pediatric primary care clinicians at 13 sites in rural upstate New York, urban Maryland, and Washington, DC, were randomized to in-office training or to a control group. Consecutive primary care patients between the ages of 5 and 16 years were screened for mental health problems, as indicated by a possible or probable score on the Strengths and Difficulties Questionnaire (SDQ). For 397 screened children, primary care visits during the next 6 months were identified using chart review and administrative databases. Using generalized estimating equation regression to account for clustering at the clinician level, primary care utilization was compared by study group and SDQ status. RESULTS: The number of primary care visits to the trained clinicians did not differ significantly from those made to control clinicians (2.5 for both groups; P =.63). Children with possible or probable SDQ scores made, on average, 0.38 or 0.65 more visits on a per child basis, respectively, during the 6-month follow-up period than SDQ unlikely children (P =.0002). CONCLUSIONS: Seeing a trained clinician did not increase subsequent primary care utilization. However, primary care utilization was greater among children with mental health problems as measured by the SDQ. Addressing children's mental health in primary care does not increase the primary care visit burden. Research on overall health services utilization is needed. C1 [Gadomski, Anne; Jenkins, Paul] Bassett Healthcare, Res Inst, Ctr Comp, Cooperstown, NY 13326 USA. [Wissow, Lawrence S.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Slade, Eric] US Dept Vet Affairs, Mental Illness Res & Educ Clin Ctr VISN5, Baltimore, MD USA. RP Gadomski, A (reprint author), Bassett Healthcare, Res Inst, Ctr Comp, 1 Atwell Rd, Cooperstown, NY 13326 USA. EM anne.gadomski@bassett.org FU National Institute of Mental Health [R01-MH62469] FX We thank the families, clinicians, and research assistants who took part in the study. The study was funded by grant R01-MH62469 to Dr Lawrence S. Wissow by the National Institute of Mental Health. NR 37 TC 3 Z9 3 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD SEP-OCT PY 2010 VL 10 IS 5 BP 346 EP 352 PG 7 WC Pediatrics SC Pediatrics GA 653PS UT WOS:000282109700012 PM 20685190 ER PT J AU Jakupcak, M Tull, MT McDermott, MJ Kaysen, D Hunt, S Simpson, T AF Jakupcak, Matthew Tull, Matthew T. McDermott, Michael J. Kaysen, Debra Hunt, Stephen Simpson, Tracy TI PTSD symptom clusters in relationship to alcohol misuse among Iraq and Afghanistan war veterans seeking post-deployment VA health care SO ADDICTIVE BEHAVIORS LA English DT Article DE Iraq and Afghanistan War Veterans; Alcohol misuse; PTSD; Depression ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSIS; DUTY MILITARY PERSONNEL; SUBSTANCE-ABUSE; COMBAT VETERANS; DRINKING; DIMENSIONALITY; SOLDIERS; BEHAVIOR; TRENDS AB Demographic factors, characteristics of military service, PTSD, and depression were examined as predictors of alcohol misuse in Iraq and Afghanistan War Veterans (N = 287) presenting for post-deployment Veteran Affairs (VA) health care. Results indicated that alcohol misuse was more common among younger male Veterans who served in the Army or Marine Corps. Accounting for demographic factors and characteristics of service, Veterans who screened positive for PTSD or depression were two times more likely to report alcohol misuse relative to Veterans who did not screen positive for these disorders. The examination of specific PTSD symptom clusters suggested that emotional numbing symptoms were most strongly associated with alcohol misuse. The implications for interventions for alcohol misuse in returning Veterans are discussed. Published by Elsevier Ltd. C1 [Jakupcak, Matthew; Simpson, Tracy] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA 98108 USA. [Jakupcak, Matthew; Kaysen, Debra; Simpson, Tracy] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Tull, Matthew T.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. [McDermott, Michael J.] Univ Mississippi, Dept Psychol, Oxford, MS USA. RP Jakupcak, M (reprint author), VA Puget Sound Hlth Care Syst, MIRECC, S-116,1660 S Columbian Way, Seattle, WA 98108 USA. EM matthew.jakupcak@va.gov FU VA Puget Sound Health Care System, Seattle, Washington FX This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington. NR 31 TC 76 Z9 76 U1 2 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD SEP PY 2010 VL 35 IS 9 BP 840 EP 843 DI 10.1016/j.addbeh.2010.03.023 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 627HL UT WOS:000280030000006 PM 20471180 ER PT J AU Roy, JE Hunt, JL AF Roy, Jennifer E. Hunt, Jennifer L. TI Detection and Classification of Diagnostic Discrepancies (Errors) in Surgical Pathology SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE error; diagnostic discrepancy; amended reports ID FROZEN-SECTION CONSULTATION; MANDATORY 2ND OPINION; ANATOMIC PATHOLOGY; Q-PROBES; AMENDED REPORTS; BIOPSY INTERPRETATION; MALPRACTICE CLAIMS; PATIENT SAFETY; LABORATORIES; MANAGEMENT AB Detecting and classifying error in a surgical pathology (SP) practice is an important part of a comprehensive quality assurance program. There are a number of mechanisms to detect error, including secondary review, examination of amended reports, correlation studies (cytology-histology and frozen-final diagnosis correlation). These different detection methods are reviewed in this paper. Additionally, the most common methods for error classification are also reviewed, along with the benefits and limitations of each. Although there is presently no gold standard for detecting or classifying errors in SP, based on this review of the literature, it is clearly good practice to consistently apply a standard method. Most importantly, these data should be incorporated into quality assurance and quality improvement activities, such that departments strive to reduce errors, and to help improve overall quality in SP. C1 [Roy, Jennifer E.; Hunt, Jennifer L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hunt, JL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 202,55 Fruit St, Boston, MA 02114 USA. EM jhunt5@partners.org NR 54 TC 18 Z9 18 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD SEP PY 2010 VL 17 IS 5 BP 359 EP 365 DI 10.1097/PAP.0b013e3181ece0db PG 7 WC Pathology SC Pathology GA 642CY UT WOS:000281182300004 PM 20733354 ER PT J AU Lee, HY Tong, YP Xing, S Cooke, CE AF Lee, Helen Y. Tong, Yvette P. Xing, Shan Cooke, Catherine E. TI Total costs and atrial fibrillation ablation success or failure in medicare-aged patients in the United States SO ADVANCES IN THERAPY LA English DT Article DE aspirin; cardiovascular disease; medication therapy management; women ID RANDOMIZED CONTROLLED-TRIALS; SERVICES TASK-FORCE; LOW-DOSE ASPIRIN; PRIMARY PREVENTION; CARDIOVASCULAR-DISEASE; COLLABORATIVE METAANALYSIS; SECONDARY PREVENTION; RISK; WOMEN; CARE AB Introduction: Cardiovascular disease is the largest single cause of death among women in the US. The American Heart Association guidelines recommend aspirin use in women >= 65 years of age if blood pressure is controlled and the benefits of cardiovascular risk reduction likely outweigh the risk of bleeding. The objective of this study is to determine the prevalence of aspirin use in elderly women and factors associated with use. Methods: This retrospective study evaluated aspirin use in women aged >= 65 years based on cardiovascular and gastrointestinal bleeding risk using a medication therapy management database within a large mid-Atlantic managed care organization. Logistic regression was used to analyze patient-related variables associated with aspirin use. Variables included clinical coronary heart disease (CHD), number of CHD risk factors, diabetes diagnosis, number of chronic medications and presence of contraindications to aspirin. Results: Aspirin use was reported in 50% of patients: 68.0% in the secondary prevention group and 46.3% in the primary prevention group. The percentage of patients using aspirin or with relative aspirin contraindications increased to 84% for the secondary prevention group and 65.9% for the primary prevention group. Patients with clinical CHD and those with diabetes and without clinical CHD were 5.88 (P=0.008) and 7.54 (P=0.012) times more likely to utilize aspirin, respectively, than patients with only one CHD risk factor of age. Patients with relative contraindications to aspirin were less likely to use aspirin (P<0.001). Conclusion: The high use of aspirin in patients at higher CHD risk supports national recommendations. Clinical practitioners need to carefully assess the value of aspirin in patients at low CHD risk and those 80 years of age and beyond where evidence of benefit should be weighed against risk. C1 [Cooke, Catherine E.] PosiHealth Inc, Ellicott City, MD 21043 USA. [Lee, Helen Y.] CareFirst BlueCross BlueShield, Baltimore, MD USA. [Tong, Yvette P.] Denver VA Med Ctr, Denver, CO USA. [Xing, Shan] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. RP Cooke, CE (reprint author), PosiHealth Inc, 5106 Bonnie Branch Rd, Ellicott City, MD 21043 USA. EM cCooke@PosiHealth.com NR 24 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0741-238X J9 ADV THER JI Adv. Ther. PD SEP PY 2010 VL 27 IS 9 BP 613 EP 622 DI 10.1007/s12325-010-0060-3 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 642UP UT WOS:000281246600004 PM 20607467 ER PT J AU Clements, K Schumacher, JA AF Clements, Kahni Schumacher, Julie A. TI Perceptual biases in social cognition as potential moderators of the relationship between alcohol and intimate partner violence: A review SO AGGRESSION AND VIOLENT BEHAVIOR LA English DT Review DE Intimate partner violence; Alcohol use disorders; Alcohol; Couples; Perceptual biases; Hostile attribution bias; Family violence; Social information processing; Social skills deficits; Marriage; Domestic violence; Aggression; Alcoholism ID EMOTIONAL FACIAL EXPRESSION; ARTICULATED THOUGHTS; MARITALLY VIOLENT; PHYSICAL AGGRESSION; NONVIOLENT MEN; ANGER AROUSAL; TRAIT ANGER; PERSONALITY-DISORDER; RISK-FACTORS; HOSTILITY AB Heavy drinking and alcohol use disorders are well-established risk factors for the perpetration of intimate partner violence (IPV). Yet, there is considerable debate over the functional role of alcohol in IPV. Psychopharmacological effects of alcohol intoxication may escalate the risk of violence directly by impairing cognitive function and facilitating aggressogenic processes by distorting perceptions of social cues and lowering inhibitions. Additionally, alcohol limits the capacity to attend to social cues and, in conflict situations, may thereby increase the salience of provocative cues. Importantly, research on stable personality characteristics of partner-violent men has identified social cognitive processing biases that may heighten the risk for IPV, especially during alcohol intoxication. This review examines social perceptual deficits as possible moderators of the effect of alcohol on IPV within the context of the multiple threshold model. Specifically, we examine maladaptive or deficient social perceptual processes that have been identified as risk factors for IPV and have also been implicated as moderators of the association between alcohol and general aggression: empathic accuracy, facial affect recognition, and anger/hostile attribution biases. Despite the interrelations among cognitive processes related to IPV and risk markers for alcohol-related aggression, many of these constructs continue to be examined in separate literatures. Published by Elsevier Ltd. C1 [Clements, Kahni] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Clements, Kahni; Schumacher, Julie A.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. RP Clements, K (reprint author), Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, 940 Belmont St 116B1, Brockton, MA 02301 USA. EM kahni_clements@hms.harvard.edu; jschumacher@psychiatry.umsmed.edu NR 98 TC 21 Z9 21 U1 6 U2 40 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-1789 J9 AGGRESS VIOLENT BEH JI Aggress. Violent Behav. PD SEP-OCT PY 2010 VL 15 IS 5 BP 357 EP 368 DI 10.1016/j.avb.2010.06.004 PG 12 WC Criminology & Penology; Psychology, Multidisciplinary SC Criminology & Penology; Psychology GA 660VS UT WOS:000282675200005 ER PT J AU Pinto, LA Sullivan, EL Rosenbaum, A Wyngarden, N Umhau, JC Miller, MW Taft, CT AF Pinto, Lavinia A. Sullivan, Eric L. Rosenbaum, Alan Wyngarden, Nicole Umhau, John C. Miller, Mark W. Taft, Casey T. TI Biological correlates of intimate partner violence perpetration SO AGGRESSION AND VIOLENT BEHAVIOR LA English DT Article DE Intimate partner violence; Biological factors; Neuropsychology; Psychophysiology; Neurochemistry; Genetics ID MONOAMINE-OXIDASE-A; PHYSICAL HEALTH CONSEQUENCES; YOUNG-ADULT PRISONERS; HEART-RATE REACTIVITY; AL. 1995 TYPOLOGY; DOMESTIC VIOLENCE; AGGRESSIVE-BEHAVIOR; INTERGENERATIONAL TRANSMISSION; CONFLICT-TACTICS; FUNCTIONAL POLYMORPHISM AB An extensive literature documents biological correlates of general aggression, but there has been less focus on biological correlates of intimate partner violence (IPV). The purpose of this review is to summarize the research literature to date that has reported on biological factors in IPV perpetration. We review the existing literature on four domains of biological processes that have been examined with respect to IPV perpetration, including: head injury and neuropsychology; psychophysiology; neurochemistry, metabolism and endocrinology; and genetics. We critique the literature, discuss the clinical relevance of research findings, and provide some recommendations for future biologically-oriented IPV research. Published by Elsevier Ltd. C1 [Pinto, Lavinia A.; Miller, Mark W.; Taft, Casey T.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Sullivan, Eric L.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Rosenbaum, Alan; Wyngarden, Nicole] No Illinois Univ, Dept Psychol, De Kalb, IL 60115 USA. [Umhau, John C.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Miller, Mark W.; Taft, Casey T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. EM Casey.Taft@va.gov FU NIMH NIH HHS [R01 MH079806] NR 111 TC 27 Z9 27 U1 9 U2 30 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-1789 J9 AGGRESS VIOLENT BEH JI Aggress. Violent Behav. PD SEP-OCT PY 2010 VL 15 IS 5 BP 387 EP 398 DI 10.1016/j.avb.2010.07.001 PG 12 WC Criminology & Penology; Psychology, Multidisciplinary SC Criminology & Penology; Psychology GA 660VS UT WOS:000282675200008 PM 23393423 ER PT J AU Ling, M Long, AA AF Ling, Morris Long, Aidan A. TI Pet dander and difficult-to-control asthma: Therapeutic options SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID DOUBLE-BLIND PLACEBO; FEL-D-I; STANDARDIZED CAT EXTRACT; DUST MITE ALLERGENS; SUBLINGUAL IMMUNOTHERAPY; CONTROLLED TRIAL; DOG ALLERGEN; INTERNATIONAL WORKSHOP; COCKROACH ALLERGENS; DOMESTIC ALLERGENS AB The prevalence of sensitization to cat and dog allergens is high in the general population and poses a challenge to the physician managing allergic asthma. Adequate allergen avoidance is difficult to achieve because of the physical characteristics of airborne animal allergens and patient noncompliance. Allergen-specific high-dose subcutaneous immunotherapy has shown benefit in cat-allergic patients with asthma and rhinoconjunctivitis, whereas the data for dog-allergic patients are not as convincing. Alternative immunotherapy approaches including the sublingual route or allergen-derived peptide-based immunotherapy remain experimental. Pharmacotherapy of pet-allergic asthmatic patients requires a stepwise approach following established asthma management guidelines. In addition to short-acting beta-agonists and inhaled corticosteroids, prophylactic antihistamines before anticipated pet exposure, the use of intranasal steroids, and the use of leukotriene antagonists may also be considered as adjunctive therapy in pet-allergic patients with asthma and/or allergic rhinitis. Omalizumab appears to have particular efficacy in pet allergen induced asthma. Novel therapies such as Fcgamma-Fel d 1 chimeric proteins still have to be evaluated in the human setting. C1 [Ling, Morris; Long, Aidan A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Long, AA (reprint author), Harvard Univ, DRAI, COX 201,55 Fruit St, Boston, MA 02114 USA. EM aalong@partners.org OI Ling, Morris/0000-0002-9657-8960 NR 58 TC 10 Z9 11 U1 0 U2 2 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 2010 VL 31 IS 5 BP 385 EP 391 DI 10.2500/aap.2010.31.3390 PG 7 WC Allergy SC Allergy GA 664ZK UT WOS:000283002600005 PM 20929605 ER PT J AU Lumry, WR Castaldo, AJ Vernon, MK Blaustein, MB Wilson, DA Horn, PT AF Lumry, William R. Castaldo, Anthony J. Vernon, Margaret K. Blaustein, Marc B. Wilson, David A. Horn, Patrick T. TI The humanistic burden of hereditary angioedema: Impact on health-related quality of life, productivity, and depression SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID C1 INHIBITOR DEFICIENCY; ACTIVITY IMPAIRMENT; WORK PRODUCTIVITY; MANAGEMENT; DIAGNOSIS; SYMPTOMS; THERAPY; ANGIODEMA; VALIDITY; ATTACKS AB Hereditary angioedema (HAE) is a rare, autosomal dominant disorder characterized by recurrent acute attacks of swelling of the larynx, abdomen, and periphery. This study was designed to assess the humanistic burden of illness associated with HAE. HAE burden was assessed via a web-based survey of patients that solicited information on attack characterization, treatment, side effects, pain, and functional and emotional burden of disease management. In addition to HAE-specific sections, the survey used three standardized instruments to compare HAE patient data to normative (healthy) and chronic disease populations: the 12-Item Short Form (SF-12) Health Survey, the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire, and the Hamilton Depression Inventory-Short Form (HDI-SF). A total of 457 HAE patients responded to the survey (response rate, similar to 19%). Patients reported significantly poorer health-related quality of life versus population norms, based on the SF-12 Physical Component Summary (mean, 43.7 versus 49.6; p < 0.001) and Mental Component Summary (mean, 42.6 versus 49.4; p < 0.001). HAE patients also had higher mean HDI-SF scores than population norms (8.1 +/- 6.5 versus 3.1 +/- 3.0; p < 0.001), with 42.5% of HAE patients scoring >8.5, indicative of depressive symptomatology. Productivity was also markedly impaired in all WPAI-GH categories, including 34% overall work impairment. Because of their most recent HAE attack, workers lost a mean of 3.3 days; students lost a mean of 1.9 days. HAE results in considerable humanistic burden to patients across physical and mental health domains; negatively impacts education, career, and work productivity; and compounds the substantial economic burdens that are reported separately. C1 [Blaustein, Marc B.; Horn, Patrick T.] Dyax Corp, Cambridge, MA 02139 USA. [Lumry, William R.] AARA Res Ctr, Dallas, TX USA. [Castaldo, Anthony J.] US Hereditary Angioedema Assoc, Honolulu, HI USA. [Vernon, Margaret K.] United BioSource Corp, Ctr Hlth Outcomes Res, Bethesda, MD USA. [Wilson, David A.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Horn, PT (reprint author), Dyax Corp, 300 Technol Sq, Cambridge, MA 02139 USA. EM phorn@dyax.com FU Dyax Corp.; Lev/Viropharma; Jerini/Shire FX Financial support provided by Dyax Corp.; W. Lumry has received research support from Dyax Corp., Lev/Viropharma, Jerini/Shire, and speaker fees from Lev/Viropharma; M. Vernon and D. Wilson are both paid consultants to Dyax Corp.; M. Blaustein is a former full-time employee of Dyax Corp. and P. Horn is a full-time employee of Dyax Corp.; A. Castaldo had no conflicts of interest with this research NR 33 TC 108 Z9 109 U1 0 U2 6 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 2010 VL 31 IS 5 BP 407 EP 414 DI 10.2500/aap.2010.31.3394 PG 8 WC Allergy SC Allergy GA 664ZK UT WOS:000283002600008 PM 20929608 ER PT J AU Mittelman, M Alperson, SY Arcari, PM Donnelly, GF Ford, LC Koithan, M Kreitzer, MJ AF Mittelman, Michele Alperson, Sunny Yim Arcari, Patricia Martin Donnelly, Gloria Ferraro Ford, Loretta C. Koithan, Mary Kreitzer, Mary Jo TI NURSING AND INTEGRATIVE HEALTH CARE SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE LA English DT Editorial Material C1 [Alperson, Sunny Yim] NINR, Washington, DC USA. [Alperson, Sunny Yim] NIH, Ctr Clin, Washington, DC USA. [Arcari, Patricia Martin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arcari, Patricia Martin] Benson Henry Inst Mind Body Med, Mind Body Program Mothers, Boston, MA USA. [Donnelly, Gloria Ferraro] Drexel Univ, Coll Nursing & Hlth Profess, Philadelphia, PA 19104 USA. [Ford, Loretta C.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Koithan, Mary] Univ Arizona, Coll Nursing, Tucson, AZ 85721 USA. [Kreitzer, Mary Jo] Univ Minnesota, Ctr Spiritual & Healing, Minneapolis, MN USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1078-6791 J9 ALTERN THER HEALTH M JI Altern. Ther. Health Med. PD SEP-OCT PY 2010 VL 16 IS 5 BP 74 EP 84 PG 11 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA V28TS UT WOS:000208703700014 PM 20882736 ER PT J AU Bendlin, BB Ries, ML Canu, E Sodhi, A Lazar, M Alexander, AL Carlsson, CM Sager, MA Asthana, S Johnson, SC AF Bendlin, Barbara B. Ries, Michele L. Canu, Elisa Sodhi, Aparna Lazar, Mariana Alexander, Andrew L. Carlsson, Cynthia M. Sager, Mark A. Asthana, Sanjay Johnson, Sterling C. TI White matter is altered with parental family history of Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Family history; APOE epsilon 4;; Diffusion tensor imaging; MRI; White matter ID MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E EPSILON-4; BRAIN GLUCOSE-METABOLISM; DIFFUSION-TENSOR MRI; MYELIN BREAKDOWN; NEUROPSYCHOLOGICAL ASSESSMENT; FRONTOTEMPORAL DEMENTIA; POSTERIOR CINGULATE; RECOGNITION MEMORY; CORPUS-CALLOSUM AB Background: Brain alterations in structure and function have been identified in people with risk factors for sporadic type Alzheimer's disease (AD), suggesting that alterations can be detected decades before AD diagnosis. Although the effect of apolipoprotein E (APOE) epsilon 4 on the brain is well-studied, less is known about the effect of family history of AD. We examined the main effects of family history and APOE epsilon 4 on brain integrity, in addition to assessing possible additive effects of these two risk factors. Methods: Diffusion tensor imaging was performed in 136 middle-aged asymptomatic participants stratified on family history and APOE epsilon 4. Mean diffusivity and fractional anisotropy (FA) were entered in factorial analyses to test the effect of AD risk on microstructural brain integrity. We performed a post hoc analysis of the three principal diffusivities (lambda 1, lambda 2, lambda 3) to provide potential additional insight on underlying tissue differences. Results: Parental family history of AD was associated with lower FA in regions of the brain known to be affected by AD, including cingulum, corpus callosum, tapetum, uncinate fasciculus, hippocampus, and adjacent white matter. Contrary to previous reports, there was no main effect of APOE epsilon 4; however, there was an additive effect of family history and APOE epsilon 4 in which family history positive participants who were also APOE epsilon 4 carriers had the lowest FA compared with the other groups. Conclusions: The data indicate that unknown risk factors contained in family history are associated with changes in microstructural brain integrity in areas of the brain known to be affected by AD. Importantly, the results provide further evidence that AD pathology might be detected before cognitive changes, perhaps decades before disease onset. (c) 2010 The Alzheimer's Association. All rights reserved. C1 [Bendlin, Barbara B.; Canu, Elisa; Sodhi, Aparna; Carlsson, Cynthia M.; Sager, Mark A.; Asthana, Sanjay; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Bendlin, Barbara B.; Ries, Michele L.; Canu, Elisa; Sodhi, Aparna; Carlsson, Cynthia M.; Sager, Mark A.; Asthana, Sanjay; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Lazar, Mariana] NYU, Sch Med, Dept Radiol, New York, NY USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Psychiat, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Alexander, Andrew L.] Waisman Lab Brain Imaging & Behav, Madison, WI USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. EM scj@medicine.wisc.edu RI Canu, Elisa/K-1423-2016 OI Lazar, Mariana/0000-0001-9285-8124; Bendlin, Barbara/0000-0002-0580-9875; Canu, Elisa/0000-0001-5804-3378 FU National Institutes of Health [AG021155, MH62015, R01 AG27161]; Department of Veterans Affairs FX The authors gratefully acknowledge the assistance of Donald McLaren, Brent Thiel, Britta Jabbar, Michele Fitzgerald, and Erik Kastman. In addition, we would like to acknowledge the support of researchers and staff at the Waisman Center, University of Wisconsin-Madison, where MR imaging took place. Finally, we thank our volunteers for their participation in this research. This work was supported by the National Institutes of Health (AG021155 to S.C.J., MH62015 to A.L.A., and R01 AG27161 to M.A.S); a Merit Review Grant from the Department of Veterans Affairs (to S.C.J.), and by the facilities and resources at the William S. Middleton Memorial Veterans Hospital (GRECC manuscript number 2009-09). NR 89 TC 43 Z9 46 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD SEP PY 2010 VL 6 IS 5 BP 394 EP 403 DI 10.1016/j.jalz.2009.11.003 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 654HF UT WOS:000282158400004 PM 20713315 ER PT J AU Yan, RT Fernandes, V Yan, AT Cushman, M Redheuil, A Tracy, R Vogel-Claussen, J Bahrami, H Nasir, K Bluemke, DA Lima, JAC AF Yan, Raymond T. Fernandes, Veronica Yan, Andrew T. Cushman, Mary Redheuil, Alban Tracy, Russell Vogel-Claussen, Jens Bahrami, Hossein Nasir, Khurram Bluemke, David A. Lima, Joao A. C. TI Fibrinogen and left ventricular myocardial systolic function: The Multi-Ethnic Study of Atherosclerosis (MESA) SO AMERICAN HEART JOURNAL LA English DT Article ID INDIVIDUAL PARTICIPANT METAANALYSIS; INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ASYMPTOMATIC INDIVIDUALS; HARP MRI; ARTERY; INFLAMMATION AB Background Increasing evidence suggests that elevated plasma fibrinogen is associated with incident heart failure. However, the underlying pathophysiological mechanisms have not been well elucidated. Methods We examined the relationship between plasma fibrinogen level and peak systolic midwall circumferential strain (Ecc) at the base, mid cavity, and apex of the left ventricle measured by magnetic resonance imaging myocardial tagging in 1096 participants without clinical cardiovascular disease enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Results After adjustment for demographics, established risk factors and body mass index, elevated fibrinogen was independently associated with reductions in absolute Ecc indicative of impaired systolic function in all regions (all P <= .015). The relationships were consistently significant upon further adjustment for measures of atherosclerosis (all P < .024) and were modestly attenuated with regional heterogeneity after additional adjustment for other inflammatory biomarker and N-terminal pro-brain natriuretic peptide. In this fully-adjusted model, every 1-SD (74 mg/dL) increment in plasma fibrinogen was independently associated with a reduction in left ventricular absolute Ecc of 0.29% (95% CI 0.03%-0.59%, P = .048) at the base, 0.22% (95% CI 0.006%-0.43%, P = .044) at mid cavity, 0.20% (95% CI = -0.035% to 0.43%, P = .097) at the apex, and 0.24% (95% CI = 0.05%-0.43%, P = .015) overall. Conclusions Among asymptomatic individuals without clinical cardiovascular disease, elevated fibrinogen is independently associated with impaired myocardial systolic function. These findings support roles of inflammation, procoagulation, and hyperviscosity underlying hyperfibrinogenemia in the pathogenesis of incipient myocardial dysfunction. (Am Heart J 2010;160:479-86.) C1 [Yan, Raymond T.; Redheuil, Alban; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA. [Fernandes, Veronica] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Yan, Andrew T.] Univ Toronto, St Michaels Hosp, Div Cardiol, Toronto, ON M5B 1W8, Canada. [Cushman, Mary; Tracy, Russell] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Vogel-Claussen, Jens] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA. [Bahrami, Hossein] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Nasir, Khurram] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, Blalock 524,600 N Wolfe St, Baltimore, MD 21287 USA. EM jlima@jhmi.edu OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [RO1-HL66075-01]; Multi-Ethnic Study of Atherosclerosis study [NO1-HC-95162, NO1-HC-95168, NO1-HC-95169]; Canadian Institutes of Health Research; Royal College of Physicians and Surgeons of Canada FX This study was supported by the National Heart, Lung, and Blood Institute grant (RO1-HL66075-01) and the Multi-Ethnic Study of Atherosclerosis study contracts (NO1-HC-95162, NO1-HC-95168 and NO1-HC-95169). Dr Raymond Yan was supported by fellowship awards from the Canadian Institutes of Health Research and the Royal College of Physicians and Surgeons of Canada. NR 45 TC 12 Z9 14 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2010 VL 160 IS 3 BP 479 EP 486 DI 10.1016/j.ahj.2010.06.001 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647YH UT WOS:000281656300015 PM 20826256 ER PT J AU Cheng, S Larson, MG Keyes, MJ McCabe, EL Newton-Cheh, C Levy, D Benjamin, EJ Vasan, RS Wang, TJ AF Cheng, Susan Larson, Martin G. Keyes, Michelle J. McCabe, Elizabeth L. Newton-Cheh, Christopher Levy, Daniel Benjamin, Emelia J. Vasan, Ramachandran S. Wang, Thomas J. TI Relation of QRS Width in Healthy Persons to Risk of Future Permanent Pacemaker Implantation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BUNDLE-BRANCH-BLOCK; COMPLETE ATRIOVENTRICULAR-BLOCK; MYOCARDIAL-INFARCTION; INTRAVENTRICULAR-CONDUCTION; ELDERLY PATIENTS; VALVE SURGERY; HEART-DISEASE; PATHOLOGY; DURATION; LOCATIONS AB In the setting of acute myocardial infarction, prolongation of the QRS interval on electrocardiography identifies patients at risk for needing permanent pacemaker implantation. However, the implications of prolonged QRS intervals in healthy subjects are unclear, especially given that the QRS prolongation encountered in this setting is typically mild. The aim of this study was to assess the relation between QRS duration and incident pacemaker implantation in a community-based cohort of 8,311 subjects (mean age 54 years, 55% women) who attended 17,731 routine examinations with resting 12-lead electrocardiography. QRS duration was analyzed as a continuous and a categorical variable (<100, 100 to <120, and >= 120 ms). During up to 35 years of follow-up, 157 participants (56 women) developed need for permanent pacemakers. In multivariable Cox regression models adjusting for cardiovascular risk factors and previous myocardial infarction or heart failure, mild QRS prolongation was associated with a threefold risk for pacemaker implantation (adjusted hazard ratio 2.90, 95% confidence interval 1.81 to 4.66, p < 0.0001), and bundle branch block was associated with a fourfold risk for pacemaker implantation (hazard ratio 4.43, 95% confidence interval 2.94 to 6.68, p < 0.0001). Each standard deviation increment in QRS duration (11 ms) was associated with an adjusted hazard ratio of 1.14 (95% confidence interval 1.11 to 1.18, p < 0.0001) for pacemaker placement. This association remained significant after excluding subjects with QRS durations >= 120 ms. In conclusion, subjects with prolonged QRS durations, even without bundle branch block, are at increased risk for future pacemaker implantation. Such individuals may warrant monitoring for progressive conduction disease. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 20102010;106:668-672) C1 [Cheng, Susan; Larson, Martin G.; Keyes, Michelle J.; McCabe, Elizabeth L.; Newton-Cheh, Christopher; Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Cheng, Susan; McCabe, Elizabeth L.; Newton-Cheh, Christopher; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Larson, Martin G.; Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Cardiovasc Med, Boston, MA 02115 USA. [Keyes, Michelle J.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Newton-Cheh, Christopher] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Wang, TJ (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA USA. OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Framingham Heart Study of the National Heart, Lung, and Blood Institute, Bethesda, Maryland [N01-HC-25195] FX This work was supported by the Framingham Heart Study of the National Heart, Lung, and Blood Institute, Bethesda, Maryland (Contract Number N01-HC-25195) NR 22 TC 11 Z9 12 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 2010 VL 106 IS 5 BP 668 EP 672 DI 10.1016/j.amjcard.2010.04.021 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647JW UT WOS:000281615800012 PM 20723643 ER PT J AU Ross, JS Torres-Mora, J Wagle, N Jennings, TA Jones, DM AF Ross, Jeffrey S. Torres-Mora, Jorge Wagle, Nikhil Jennings, Timothy A. Jones, David M. TI Biomarker-Based Prediction of Response to Therapy for Colorectal Cancer Current Perspective SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Colorectal cancer; CRC; Biomarkers; Molecular classification; Pharmacogenomics; Pharmacogenetics; Review ID GROWTH-FACTOR RECEPTOR; OXALIPLATIN-BASED CHEMOTHERAPY; CETUXIMAB PLUS IRINOTECAN; MTHFR GENE POLYMORPHISMS; RESECTED COLON-CANCER; CELL LUNG-CANCER; S-TRANSFERASE-PI; MONOCLONAL-ANTIBODIES; THYMIDYLATE SYNTHASE; 1ST-LINE TREATMENT AB The diagnosis and management of colorectal cancer (CRC) has been impacted by the discovery and validation of a wide variety of biomarkers designed to facilitate a personalized approach for the treatment of the disease. Recently, CRC has been reclassified based on molecular analyses of various genes and proteins capable of separating morphologic types of tumors into molecular categories. At the same time, a number of new prognostic and predictive single genes and proteins have been discovered that are designed to reflect sensitivity and/or resistance to existing therapies. Multigene predictors have also been developed to predict the risk of relapse for intermediate-stage CRC after completion of surgical extirpation. More recently, a number of biomarkers tested by a variety of methods have been proposed as specific predictors of chemotherapy and radiotherapy response. Other markers have been successfully used to predict toxic effects of standard therapies. In this review, a series of novel biomarkers are considered and compared with standard-of-care markers for their potential use as pharmacogenomic and pharmacogenetic predictors of disease outcome. C1 [Ross, Jeffrey S.; Torres-Mora, Jorge; Jennings, Timothy A.; Jones, David M.] Albany Med Coll, Dept Pathol & Lab Med, Albany, NY 12208 USA. [Ross, Jeffrey S.] Fdn Med, Cambridge, MA USA. [Wagle, Nikhil] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wagle, Nikhil] Harvard Univ, Sch Med, Boston, MA USA. RP Ross, JS (reprint author), Albany Med Coll, Dept Pathol, Mail Code 81,47 New Scotland Ave, Albany, NY 12208 USA. FU NCI NIH HHS [T32 CA009172] NR 115 TC 39 Z9 41 U1 0 U2 5 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2010 VL 134 IS 3 BP 478 EP 490 DI 10.1309/AJCP2Y8KTDPOAORH PG 13 WC Pathology SC Pathology GA 640KL UT WOS:000281050000018 PM 20716806 ER PT J AU Klepeis, VE Sohani, AR AF Klepeis, Veronica E. Sohani, Aliyah R. TI Pathologist Review as a Strategy to Improve the Diagnostic Accuracy of Body Fluid Analysis in the Hematology Laboratory SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the Academy-of-Clinical-Laboratory-Physicians-Scientists CY JUN 03-05, 2010 CL Nashville, TN SP Acad Clin Lab Phys Sci C1 [Klepeis, Veronica E.; Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2010 VL 134 IS 3 MA 78 BP 510 EP 510 PG 1 WC Pathology SC Pathology GA 640KL UT WOS:000281050000069 ER PT J AU Tsai, CL Clark, S Camargo, CA AF Tsai, Chu-Lin Clark, Sunday Camargo, Carlos A., Jr. TI Risk stratification for hospitalization in acute asthma: the CHOP classification tree SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID CLINICAL-PREDICTION RULES; EMERGENCY-DEPARTMENT; METHODOLOGICAL STANDARDS; PROSPECTIVE MULTICENTER; ADULTS; NEED; MORTALITY; ADMISSION; CHILDREN; MODELS AB Objective: Simple risk stratification rules are limited in acute asthma. We developed and externally validated a classification tree for asthma hospitalization. Methods: Data were obtained from 2 large, multicenter studies on acute asthma, the National Emergency Department Safety Study and the Multicenter Airway Research Collaboration cohorts. Both studies involved emergency department (ED) patients aged 18 to 54 years presenting to the ED with acute asthma. Clinical information was obtained from medical record review. The Classification and Regression Tree method was used to generate a simple decision tree. The tree was derived in the National Emergency Department Safety Study cohort and then was validated in the Multicenter Airway Research Collaboration cohort. Results: There were 1825 patients in the derivation cohort and 1335 in the validation cohort. Admission rates were 18% and 21% in the derivation and validation cohorts, respectively. The Classification and Regression Tree method identified 4 important variables (CHOP): change [C] in peak expiratory flow severity category, ever hospitalization [H] for asthma, oxygen [O] saturation on room air, and initial peak expiratory flow [P]. In a simple 3-step process, the decision rule risk-stratified patients into 7 groups, with a risk of admission ranging from 9% to 48%. The classification tree performed satisfactorily on discrimination in both the derivation and validation cohorts, with an area under the receiver operating characteristic curve of 0.72 and 0.65, respectively. Conclusions: We developed and externally validated a novel classification tree for hospitalization among ED patients with acute asthma. Use of this explicit risk stratification rule may aid decision making in the emergency care of acute asthma. (C) 2010 Elsevier Inc. All rights reserved. C1 [Tsai, Chu-Lin; Camargo, Carlos A., Jr.] Harvard Univ, Dept Emergency Med, EMNet Coordinating Ctr, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15213 USA. RP Tsai, CL (reprint author), Harvard Univ, Dept Emergency Med, EMNet Coordinating Ctr, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 FU GlaxoSmithKline (Research Triangle Park, NC); Agency for Healthcare Research and Quality (Rockville, MD) [R01 HS-13099]; [R01 HL-84401] FX The two underlying studies were supported by unrestricted grants from GlaxoSmithKline (Research Triangle Park, NC) and grant R01 HS-13099 from the Agency for Healthcare Research and Quality (Rockville, MD), respectively. Doctor Camargo also was funded by grant R01 HL-84401 (Bethesda, MD). NR 28 TC 8 Z9 8 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD SEP PY 2010 VL 28 IS 7 BP 803 EP 808 DI 10.1016/j.ajem.2009.04.009 PG 6 WC Emergency Medicine SC Emergency Medicine GA 654DX UT WOS:000282149800009 PM 20837258 ER PT J AU Iles-Shih, L Collins, JF Holub, JL Lieberman, DA AF Iles-Shih, LuLu Collins, Judy F. Holub, Jennifer L. Lieberman, David A. TI Prevalence of Significant Neoplasia in FOBT-Positive Patients on Warfarin Compared With Those Not on Warfarin SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID FECAL OCCULT BLOOD; LOW-DOSE ASPIRIN; ACUTE GASTROINTESTINAL HEMORRHAGE; AMERICAN-CANCER-SOCIETY; COLORECTAL-CANCER; ANTICOAGULANT-THERAPY; ATRIAL-FIBRILLATION; TASK-FORCE; SURVEILLANCE; POLYPS AB OBJECTIVES: The fecal occult blood test (FOBT) is widely used for colorectal cancer screening. However, the impact of warfarin use on FOBT sensitivity and specificity remains unclear. This study compares the relative risk of neoplasia in FOBT-positive patients stratified by warfarin use. METHODS: The Clinical Outcomes Research Initiative database was used to identify patients with positive FOBT as the only indication for colonoscopy during 2005-2006. Patients were categorized on the basis of documented warfarin status within a 30-day period before FOBT. We compared the demographics and prevalence of significant colon findings (defined as polyp > 9 mm or suspected malignant tumor) among the two groups. After adjusting for confounding variables, logistic regression was used to estimate the odds ratio of significant findings in warfarin-positive vs. warfarin-negative patients. RESULTS: Of 10,266 patients with positive FOBT, 372 used warfarin, 9,265 did not use warfarin, and 629 were excluded because of missing warfarin status. Warfarin-positive patients were more likely male (65 vs. 50%; P < 0.0001), Caucasian (88 vs. 80%; P < 0.0001), and veterans (53 vs. 33%; P < 0.0001). The prevalence of a significant finding was greater in the warfarin group, 16 vs. 11.4% (P < 0.01). After adjusting for age and sex, the relative risk of significant colon findings among warfarin-positive patients was not significantly different from warfarin-negative patients (odds ratio 1.1, 95% confidence interval: 0.81-1.44). CONCLUSIONS: No increased risk for significant colonic findings among FOBT-positive patients according to warfarin use was identified. These findings suggest that continuing warfarin before FOBT will not affect the positive predictive value of this screening test. C1 [Iles-Shih, LuLu; Collins, Judy F.; Holub, Jennifer L.; Lieberman, David A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Collins, Judy F.; Lieberman, David A.] Portland VA Med Ctr, Portland, OR USA. RP Collins, JF (reprint author), VAMC, Dept Internal Med, Div Gastroenterol, P3-GI ,3710 SW Vet Hosp Rd, Portland, OR 97239 USA. EM collinsj@ohsu.edu FU NIDDK NIH HHS [U01 DK057132, R33 DK061778] NR 33 TC 11 Z9 12 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2010 VL 105 IS 9 BP 2030 EP 2034 DI 10.1038/ajg.2010.264 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 646SM UT WOS:000281563100018 PM 20683445 ER PT J AU Jutabha, R Jensen, DM Chavalitdhamrong, D AF Jutabha, Rome Jensen, Dennis M. Chavalitdhamrong, Disaya TI Hepatitis B Vaccine Administered by Intradermal Route in Patients With Celiac Disease Unresponsive to the Intramuscular Vaccination Schedule: A Pilot Study Response SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID LIGATION C1 [Jutabha, Rome] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. [Jutabha, Rome; Jensen, Dennis M.; Chavalitdhamrong, Disaya] Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA 90095 USA. RP Jutabha, R (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. EM rjutabha@mednet.ucla.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2010 VL 105 IS 9 BP 2119 EP 2119 DI 10.1038/ajg.2010.176 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 646SM UT WOS:000281563100041 PM 20818369 ER PT J AU Kasckow, J Fellows, I Golshan, S Solorzano, E Meeks, T Zisook, S AF Kasckow, John Fellows, Ian Golshan, Shahrokh Solorzano, Ellen Meeks, Thomas Zisook, Sidney TI Treatment of Subsyndromal Depressive Symptoms in Middle-Age and Older Patients With Schizophrenia: Effect of Age on Response SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Schizophrenia; age differences; citalopram; depression; psychopathology; quality of life ID SCALE AB Objective: The authors hypothesized that age would moderate the response of patients with schizophrenia and subsyndromal depression (SSD) treated citalopram with depressive symptoms and other outcomes. Also, older patients would exhibit more side effects with citalopram. Methods: Participants of 40 years or older had schizophrenia or schizoaffective disorder with SSD. Patients randomly received flexible dosing of citalopram or placebo augmentation of their antipsychotic medication. Linear regression determined whether age had any moderating effect on depressive symptoms, global psychopathology, negative symptoms, mental functioning, and quality of life. Age-related side effects were examined. Results: There were no significant drug group by age interaction in depressive or psychotic symptoms, mental Short Form-12, or quality of life scores. Similarly, there were few age-related side effect differences. Conclusion: Symptoms in younger and older patients with schizophrenia and SSD treated with citalopram seem to respond similarly. Adverse events do not seem to differ with age. (Am J Geriatr Psychiatry 2010; 18:853-857) C1 [Kasckow, John] VA Pittsburgh Hlth Care Syst, MIRECC & Behav Hlth Serv, Pittsburgh, PA 15206 USA. [Kasckow, John] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. [Fellows, Ian; Golshan, Shahrokh; Solorzano, Ellen; Meeks, Thomas; Zisook, Sidney] Univ Calif San Diego, VA San Diego Hlth Care Syst, Dept Psychiat, San Diego, CA 92103 USA. RP Kasckow, J (reprint author), VA Pittsburgh Hlth Care Syst, MIRECC & Behav Hlth Serv, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM kasckowjw@upmc.edu FU Cincinnati VA Medical Center; University of Cincinnati College Of Medicine; VISN 4; VISN 22 MIRECC; University of California, San Diego, CA.; Center for Community-based Research in Older People with Psychoses; Aspect Medical; PamLab; Forest; Astra Zeneca; Bristol Meyers Squibb; Pfizer; Johnson and Johnson; Solvay; Eli Lilly; [MH6398] FX The authors thank the Cincinnati VA Medical Center and the University of Cincinnati College Of Medicine for their support.; This work was supported by MH6398 (to SZ, JWK), the VISN 4 and VISN 22 MIRECC, and the University of California, San Diego, CA., Center for Community-based Research in Older People with Psychoses. Research support from Aspect Medical and PamLab and speaker's honoraria from Forest Pharmaceuticals, Inc. and GlaxoSmithKline (to SZ). Grant support as well as honoraria for speaking and consultation from Forest, Astra Zeneca, Bristol Meyers Squibb, Pfizer, Johnson and Johnson, Solvay and Eli Lilly (to JK). NR 10 TC 5 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SEP PY 2010 VL 18 IS 9 BP 853 EP 857 DI 10.1097/JGP.0b013e3181dba12f PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 647HV UT WOS:000281610000010 PM 20808103 ER PT J AU Ramanadhan, S Wiecha, JL Gortmaker, SL Emmons, KM Viswanath, K AF Ramanadhan, Shoba Wiecha, Jean L. Gortmaker, Steven L. Emmons, Karen M. Viswanath, Kasisomayajula TI Informal Training in Staff Networks to Support Dissemination of Health Promotion Programs SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Information Dissemination; Implementation; Health Promotion; Afterschool; Social Networks ID PUBLIC-HEALTH; DIFFUSION; KNOWLEDGE AB Purpose. To study informal skill transfer via staff networks as a complement to formal training among afterschool childcare providers implementing a health promotion program. Design. Gross-sectional, sociometric network analysis. Setting. Boston Young Men's Christian Association (YMCA) afterschool programs implementing the iPLAY program. Participants. All 91 staff members at 20 sites were eligible; 80 completed the survey (88% response rate). Measures. At the network level, network density measured system-level connectedness. At the staff level, the independent variable was out degree, the number of individuals to whom respondents noted a program-related connection. The dependent variable was skill gains, the number of key implementation skills gained from the network. Analysis. We mapped the staff program-related social network. We utilized multiple linear regression to estimate the relationship between out degree and skill gains, and we adjusted for clustering of staff in sites. Results. Most staff (77%) reported gaining at least one skill from the network, but only 2% of potential network connections were established. The regression model showed that out degree (i.e., number of program-related contacts) was significantly associated with skill gains (beta = .48, p < .01) independent of other variables. Conclusion. Informal skill transfer in staff networks may be a useful complement to formal training for implementation of health promotion programs, but informal skill transfer was likely underutilized in this network. Future research employing longitudinal and/or multisite data should examine these findings in greater detail. (Am J Health Promot 2010;25111:12-18.) C1 [Ramanadhan, Shoba; Wiecha, Jean L.; Gortmaker, Steven L.; Emmons, Karen M.; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Ramanadhan, S (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,Mail Stop LW 703, Boston, MA 02115 USA. EM shoba_ramanadhan@dfci.harvard.edu FU NCI NIH HHS [5 R25 CA057711-14, R25 CA057711, R25 CA057711-09] NR 43 TC 4 Z9 5 U1 2 U2 7 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD SEP-OCT PY 2010 VL 25 IS 1 BP 12 EP 18 DI 10.4278/ajhp.080826-QUAN-163 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 646YD UT WOS:000281580700004 PM 20809826 ER PT J AU Ghobrial, IM Xie, WL Padmanabhan, S Badros, A Rourke, M Leduc, R Chuma, S Kunsman, J Warren, D Poon, T Harris, B Sam, A Anderson, KC Richardson, PG Treon, SP Weller, D Matous, J AF Ghobrial, Irene M. Xie, Wanling Padmanabhan, Swaminathan Badros, Ashraf Rourke, Meghan Leduc, Renee Chuma, Stacey Kunsman, Janet Warren, Diane Poon, Tiffany Harris, Brianna Sam, Amy Anderson, Kenneth C. Richardson, Paul G. Treon, Steven P. Weller, Die Matous, Jeffrey TI Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenstrom Macroglobulinemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; CLINICAL-TRIAL; THERAPY; MANAGEMENT; SURVIVAL AB This study aimed to determine the activity and safety of weekly bortezomib and rituximab in patients with untreated Waldenstrom Macroglobulinemia (WM). Patients with no prior therapy and symptomatic disease were eligible. Patients received bortezomib IV weekly at 1.6 mg/m(2) on days 1, 8, 15, q 28 days x 6 cycles, and rituximab 375 mg/m(2) weekly on cycles 1 and 4. Primary endpoint was the percent of patients with at least a minor response (MR). Twenty-six patients were treated. At least MR was observed in 23/26 patients (88%) (95% Cl: 70-98%) with 1 complete response (4%), 1 near-complete response (4%), 15 partial remission (58%), and 6 MR (23%). Using IgM response evaluated by nephlometry, all 26 patients (100%) achieved at least MR or better. The median time to progression has not been reached, with an estimated 1-year event free rate of 79% (95% Cl: 53, 91%). Common grade 3 and 4 therapy related adverse events included reversible neutropenia in 12%, anemia in 8%, and thrombocytopenia in 8%. No grade 3 or 4 neuropathy occurred. The combination of weekly bortezomib and rituximab exhibited significant activity and minimal neurological toxicity in patients with untreated WM. Am. J. Hematol. 85:670-674, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Ghobrial, Irene M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Padmanabhan, Swaminathan] Roswell Pk Canc Ctr, Buffalo, NY USA. [Badros, Ashraf] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Matous, Jeffrey] Rocky Mt Canc Ctr, Denver, CO USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu OI Harris, Brianna/0000-0001-6229-9907 FU Takeda/Millennium Inc; Michelle and Steven Kirsch lab for Waldenstrom Macroglobulinemia; Heje Fellowship for Waldenstrom; Millennium FX Contract grant sponsors: Takeda/Millennium Inc, Michelle and Steven Kirsch lab for Waldenstrom Macroglobulinemia, Heje Fellowship for Waldenstrom.; Authors' Contributions and Conflict of Interest: Irene M.Ghobrial: Prinicipal Investigator, conducted study and analyzed data. Former speaker bureau of Millennium, Celgene, and Novartis. Research support: Millennium. Wan ling Xie: Statistical analysis. No COI. Swaminathan Padmanabhan: enrolled patients. No COI. Ashraf Badros: Enrolled patients. No COI. Meghan Rourke: Clinical research coordinator/monitor/study manager. No COI. Renee Leduc: Clinical research coordinator. No COI. Stacey Chuma: Research nurse. No COI. Janet Kunsman: Enrolled patients. No COI. Diane Warren: Project manager. No COI. Tiffany Poon: Clinical research coordinator. No COI. Brianna Harris: Clinical research coordinator. No COI. Amy Sam: Clinical research coordinator. No COI. Kenneth C. Anderson: Analyzed and reviewed data and manuscript. Former speaker bureau of Millennium and Celgene. Research support: Millennium. Paul G. Richardson: Analyzed and reviewed data and manuscript. Former speaker bureau and Advisory Board for Millennium, Celgene and Gentium. Steven P. Treon: Analyzed and reviewed data and manuscript. Former speaker bureau of Millennium and Celgene and Genenetech. Research support: Millennium. Edie Weller: Staticial analysis. No COI. Jeffrey Matous: Enrolled patients and reviewed final data and manuscript. NR 22 TC 44 Z9 46 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2010 VL 85 IS 9 BP 670 EP 674 DI 10.1002/ajh.21788 PG 5 WC Hematology SC Hematology GA 647EZ UT WOS:000281601900007 PM 20652865 ER PT J AU Hammond, SP Marty, FM Bryar, JM DeAngelo, DJ Baden, LR AF Hammond, Sarah P. Marty, Francisco M. Bryar, Julie M. DeAngelo, Daniel J. Baden, Lindsey R. TI Invasive fungal disease in patients treated for newly diagnosed acute leukemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTS; HEMATOLOGIC MALIGNANCIES; FLUCONAZOLE PROPHYLAXIS; ANTIFUNGAL PROPHYLAXIS; CANCER-PATIENTS; BREAKTHROUGH ZYGOMYCOSIS; POSACONAZOLE PROPHYLAXIS; NEUTROPENIC PATIENTS AB Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in patients undergoing treatment for acute leukemia (AL). Antifungal prophylactic strategies are associated with significant toxicities and cost. We performed a retrospective study of the incidence and risk factors for IFD among patients newly diagnosed with and treated for AL between January 1, 2004 and July 1, 2006. Patient follow up concluded January 1, 2007. Among 231 patients with newly diagnosed AL, 31(13.4%) developed IFD by the end of follow up, 24 (10.4%) of whom developed IFD within the first 100 days after diagnosis of AL. The cumulative probability of developing IFD was 5.9% by 30 days and 11.1% at 100 days after AL diagnosis. Patients who had persistent leukemia after an initial course of induction chemotherapy were significantly more likely to develop IFD than those who did not have evidence of persistent leukemia (14/65 (21.5%) vs. 15/148 (10.1%), P = 0.03). In a time-dependent Cox model, the adjusted hazard ratio for developing IFD within the first 100 days of AL diagnosis based on the number of days of neutropenia in that period was 4.85 (95% confidence interval: 1.52, 15.4). Those patients with more days of neutropenia in the first 100 days after AL diagnosis, such as those who did not achieve remission after a first course of induction chemotherapy, were more likely to develop IFD. Am. J. Hematol. 85:695-699, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Hammond, Sarah P.; Marty, Francisco M.; Bryar, Julie M.; Baden, Lindsey R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Hammond, Sarah P.; Marty, Francisco M.; DeAngelo, Daniel J.; Baden, Lindsey R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hammond, Sarah P.; Marty, Francisco M.; DeAngelo, Daniel J.; Baden, Lindsey R.] Harvard Univ, Sch Med, Boston, MA USA. [Bryar, Julie M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Hammond, SP (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB A4, Boston, MA 02115 USA. EM shammond2@partners.org NR 26 TC 16 Z9 18 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2010 VL 85 IS 9 BP 695 EP 699 DI 10.1002/ajh.21776 PG 5 WC Hematology SC Hematology GA 647EZ UT WOS:000281601900011 PM 20652970 ER PT J AU Fromme, EK Smith, AK Hughes, MT Brokaw, FC Rosenfeld, KE Arnold, RM AF Fromme, Erik K. Smith, Alexander K. Hughes, Mark T. Brokaw, Frances C. Rosenfeld, Kenneth E. Arnold, Robert M. TI Update in Palliative Medicine SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Editorial Material ID CARE CONSULTATION; CANCER; DEPRESSION; OUTCOMES; PAIN C1 [Fromme, Erik K.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Smith, Alexander K.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Hughes, Mark T.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA. [Brokaw, Frances C.] Dartmouth Hitchcock Med Ctr, Div Gen Internal Med, Lebanon, NH 03766 USA. [Rosenfeld, Kenneth E.] VA Greater Los Angeles Healthcare Syst, Div Gen Med, Palliat Care Sect, Los Angeles, CA USA. [Arnold, Robert M.] Univ Pittsburgh, Div Gen Internal Med, Sect Palliat Care & Med Eth, Pittsburgh, PA USA. RP Fromme, EK (reprint author), Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, L586,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM frommee@ohsu.edu FU NCI NIH HHS [K07CA109511] NR 16 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD SEP PY 2010 VL 27 IS 6 BP 420 EP 427 DI 10.1177/1049909110370745 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 636DD UT WOS:000280707500010 PM 20555038 ER PT J AU Grota, PG Stone, PW Jordan, S Pogorzelska, M Larson, E AF Grota, Patti G. Stone, Patricia W. Jordan, Sarah Pogorzelska, Monika Larson, Elaine TI Electronic surveillance systems in infection prevention: Organizational support, program characteristics, and user satisfaction SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Surveillance; infection prevention programs; organizational support ID CARE-ASSOCIATED INFECTIONS; AUTOMATED SURVEILLANCE; HEALTH; TECHNOLOGY; EPIDEMIOLOGY AB Background: The use of electronic surveillance systems (ESSs) is gradually increasing in infection prevention and control programs. Little is known about the characteristics of hospitals that have a ESS, user satisfaction with ESSs, and organizational support for implementation of ESSs. Methods: A total of 350 acute care hospitals in California were invited to participate in a Web-based survey; 207 hospitals (59%) agreed to participate. The survey included a description of infection prevention and control department staff, where and how they spent their time, a measure of organizational support for infection prevention and control, and reported experience with ESSs. Results: Only 23% (44/192) of responding infection prevention and control departments had an ESS. No statistically significant difference was seen in how and where infection preventionists (IPs) who used an ESS and those who did not spend their time. The 2 significant predictors of whether an ESS was present were score on the Organizational Support Scale (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02-1.18) and hospital bed size (OR, 1.004; 95% CI, 1.00-1.007). Organizational support also was positively correlated with IP satisfaction with the ESS, as measured on the Computer Usability Scale (P = .02). Conclusion: Despite evidence that such systems may improve efficiency of data collection and potentially improve patient outcomes, ESSs remain relatively uncommon in infection prevention and control programs. Based on our findings, organizational support appears to be a major predictor of the presence, use, and satisfaction with ESSs in infection prevention and control programs. Key Words: Surveillance; infection prevention programs; organizational support. C1 [Stone, Patricia W.; Jordan, Sarah; Pogorzelska, Monika; Larson, Elaine] Columbia Univ, Sch Nursing, New York, NY 10035 USA. [Grota, Patti G.] Univ Texas Hlth Sci Ctr San Antonio, Infect Prevent Adm, S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. RP Larson, E (reprint author), Columbia Univ, Sch Nursing, 617 W 168th St, New York, NY 10035 USA. EM ell23@columbia.edu FU Blue Shield of California Foundation [BSCAFND 2490932] FX The authors thank all of the participating California hospitals. This study was funded by the Blue Shield of California Foundation (Grant BSCAFND 2490932) and conducted in collaboration with APIC. NR 23 TC 15 Z9 16 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD SEP PY 2010 VL 38 IS 7 SI SI BP 509 EP 514 DI 10.1016/j.ajic.2009.10.007 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 641SK UT WOS:000281149800002 PM 20176411 ER PT J AU Kim, KH Fonda, JR Lawler, EV Gagnon, D Kaufman, JS AF Kim, Kyung-Ho Fonda, Jennifer R. Lawler, Elizabeth V. Gagnon, David Kaufman, James S. TI Change in Use of Gadolinium-Enhanced Magnetic Resonance Studies in Kidney Disease Patients After US Food and Drug Administration Warnings: A Cross-sectional Study of Veterans Affairs Health Care System Data From 2005-2008 SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Gadolinium; nephrogenic systemic fibrosis; US Food and Drug Administration; magnetic resonance; glomerular filtration rate; chronic kidney disease ID NEPHROGENIC FIBROSING DERMOPATHY; CONTRAST-MEDIA AB Background: Exposure to gadolinium in patients with kidney disease has been linked to risk of developing nephrogenic systemic fibrosis. The US Food and Drug Administration (FDA) has issued warnings against the use of gadolinium in this population. We studied the impact of these warnings on the use of gadolinium-enhanced magnetic resonance (GE-MR) studies in patients with decreased estimated glomerular filtration rate (eGFR) and the practice of measuring serum creatinine before gadolinium exposure. Study Design: Cross-sectional study of patients who had undergone MR studies from October 2002 to September 2008. Setting & Participants: Patients receiving medical care in the US Department of Veterans Affairs Health Care System. Predictor: Date of MR imaging, serum creatinine level, and eGFR using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Outcomes & Measurements: The rate of MR studies performed with and without gadolinium from July 2005 to September 2008 in patients with different stages of kidney disease, defined using eGFR. The proportion of GE-MR studies with a screening serum creatinine level. Results: There was a 71% decrease in the rate of GE-MR use in patients with GFR <30 mL/min/1.73 m(2) 2 years after the release of the first public health advisory, although studies continued to be performed in patients with stages 4 and 5 chronic kidney disease. The proportion of GE-MR studies with serum creatinine measured within 1 month before the study increased by 99%. Limitations: Data available up to September 30, 2008. Indications for the GE-MR studies were not assessed. The accuracy of Current Procedural Terminology and International Classification of Diseases, Ninth Revision coding was not assessed. Conclusion: There was a large decrease in the use of GE-MR studies in patients with GFR <30 mL/min/1.73 m(2) and a large but not universal increase in the practice of measuring serum creatinine before GE-MR after the release of the FDA warnings. Am J Kidney Dis 56: 458-467. (C) 2010 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Kim, Kyung-Ho] SUNY Stony Brook, Renal Sect, Stony Brook, NY 11794 USA. [Fonda, Jennifer R.; Lawler, Elizabeth V.; Gagnon, David] VA Boston Healthcare System, Dept Vet Affairs Cooperat Study Program, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA. [Lawler, Elizabeth V.] Harvard Univ, Sch Med, Boston, MA USA. [Gagnon, David] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Kaufman, James S.] VA Boston Healthcare Syst, Renal Sect, Boston, MA USA. [Kaufman, James S.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Kim, KH (reprint author), SUNY Stony Brook, Renal Sect, Stony Brook, NY 11794 USA. EM kykkim@notes.cc.sunysb.edu OI Gagnon, David/0000-0002-6367-3179 FU Office of Research and Development; VA; Department of Veterans Affairs FX This study was conducted with support from the Office of Research and Development, VA Cooperative Studies Program, Department of Veterans Affairs and using the facilities and infrastructure of the VA Boston Healthcare System. NR 24 TC 11 Z9 12 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2010 VL 56 IS 3 BP 458 EP 467 DI 10.1053/j.ajkd.2010.03.027 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 642IH UT WOS:000281203200008 PM 20580477 ER PT J AU Sambamoorthi, U Bean-Mayberry, B Findley, PA Yano, EM Banerjea, R AF Sambamoorthi, Usha Bean-Mayberry, Bevanne Findley, Patricia A. Yano, Elizabeth M. Banerjea, Ranjana TI Organization of Care and Diagnosed Depression Among Women Veterans SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID AFFAIRS PRIMARY-CARE; MENTAL-HEALTH-CARE; MEDICAL HOME; CLINICS; DISORDERS; ILLNESS; MANAGEMENT; INNOVATION; DELIVERY; QUALITY AB Objective: To analyze the association between the organizational features of integration of physical and mental healthcare in women's health clinics and the diagnosis of depression among women veterans with or at risk for cardiovascular conditions (ie, diabetes mellitus, heart disease, or hypertension). Study Design: Retrospective and observational secondary data analyses. Methods: We studied 27,972 women veterans from 118 facilities with diagnosed cardiovascular conditions in fiscal year 2001 (FY2001) using merged Medicare claims and Veterans Health Administration (VHA) data merged with the 1999 VHA Survey of Primary Care Practices and the 2001 VHA Survey of Women Veterans Health Programs and Practices. The dependent variable was a binary indicator for diagnosed depression during FY2001 at the individual level. We used a multilevel logistic regression model to control for clustering of women veterans within facilities. Individual-level independent variables included demographics, socioeconomic characteristics, and chronic physical conditions. Results: Overall, 27% of women veterans using the VHA were diagnosed as having depression in FY2001. Across facilities, rates of diagnosed depression varied from 13% to 41%. After controlling for individual-level and facility-level independent variables, women veterans who were served in separate women's health clinics with integrated physical and mental healthcare were more likely to have diagnosed depression. The adjusted odds ratio was 1.12 (95% confidence interval, 1.01-1.25). Conclusions: Existing women-specific VHA organizational features with integration of primary care and mental health seem effective in diagnosing depression. Emerging patient-centered medical home models may facilitate diagnosis and treatment of mental health issues among women with complex chronic conditions. (Am J Manag Care. 2010; 16(9): 657-665) C1 [Findley, Patricia A.] Rutgers State Univ, Sch Social Work, New Brunswick, NJ 08901 USA. [Sambamoorthi, Usha] W Virginia Univ, Dept Pharmaceut Syst & Policy, Morgantown, WV 26506 USA. [Sambamoorthi, Usha; Findley, Patricia A.; Banerjea, Ranjana] Dept Vet Affairs New Jersey Hlth Care Syst, HSR&D Ctr Healthcare Knowledge Management, E Orange, NJ USA. [Sambamoorthi, Usha] Morehouse Sch Med, Dept Community Hlth & Prevent Med, Atlanta, GA 30310 USA. [Bean-Mayberry, Bevanne; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Excellence, Sepulveda, CA USA. [Bean-Mayberry, Bevanne] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. RP Findley, PA (reprint author), Rutgers State Univ, Sch Social Work, 536 George St, New Brunswick, NJ 08901 USA. EM pfindley@ssw.rutgers.edu OI Sambamoorthi, Usha/0000-0001-8311-1360 FU Department of Veterans Affairs-Health Services Research and Development Service [IAE-05-255, IIR-05-016] FX This research was supported by grants IAE-05-255, IIR-05-016, and the Diabetes Epidemiology Cohort II from the Department of Veterans Affairs-Health Services Research and Development Service. NR 35 TC 6 Z9 6 U1 1 U2 5 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD SEP PY 2010 VL 16 IS 9 BP 657 EP 665 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 660EA UT WOS:000282621400003 PM 20873953 ER PT J AU Singh, JA Sloan, JA Atherton, PJ Smith, T Hack, TF Huschka, MM Rummans, TA Clark, MM Diekmann, B Degner, LF AF Singh, Jasvinder A. Sloan, Jeff A. Atherton, Pamela J. Smith, Tenbroeck Hack, Thomas F. Huschka, Mashele M. Rummans, Teresa A. Clark, Matthew M. Diekmann, Brent Degner, Lesley F. TI Preferred Roles in Treatment Decision Making Among Patients With Cancer: A Pooled Analysis of Studies Using the Control Preferences Scale SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID BREAST-CANCER; URINARY-INCONTINENCE; CONTROLLED-TRIAL; UNITED-STATES; TREATMENT CONSULTATIONS; PROVIDING AUDIOTAPES; INVOLVEMENT; WOMEN; CARE; PARTICIPATION AB Objectives: To collect normative data, assess differences between demographic groups, and indirectly compare US and Canadian medical systems relative to patient expectations of involvement in cancer treatment decision making. Study Design: Meta-analysis. Methods: Individual patient data were compiled across 6 clinical studies among 3491 patients with cancer who completed the 2-item Control Preferences Scale indicating the roles they preferred versus actually experienced in treatment decision making. Results: The roles in treatment decision making that patients preferred were 26% active, 49% collaborative, and 25% passive. The roles that patients reported actually experiencing were 30% active, 34% collaborative, and 36% passive. Roughly 61% of patients reported having their preferred role; only 6% experienced extreme discordance between their preferred versus actual roles. More men than women (66% vs 60%, P = .001) and more US patients than Canadian patients (84% vs 54%, P < .001) reported concordance between their preferred versus actual roles. More Canadian patients than US patients preferred and actually experienced (42% vs 18%, P < .001) passive roles. More women than men reported taking a passive role (40% vs 24%, P < .001). Older patients preferred and were more likely than younger patients to assume a passive role. Conclusions: Roughly half of the studied patients with cancer indicated that they preferred to have a collaborative relationship with physicians. Although most patients had the decision-making role they preferred, about 40% experienced discordance. This highlights the need for incorporation of individualized patient communication styles into treatment plans. (Am J Manag Care. 2010; 16(9): 688--696) C1 [Singh, Jasvinder A.; Sloan, Jeff A.; Atherton, Pamela J.; Huschka, Mashele M.; Rummans, Teresa A.; Clark, Matthew M.; Diekmann, Brent] Mayo Clin, Rochester, MN USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL USA. [Smith, Tenbroeck] Amer Canc Soc, Atlanta, GA 30329 USA. [Hack, Thomas F.; Degner, Lesley F.] Univ Manitoba, Winnipeg, MB, Canada. [Hack, Thomas F.; Degner, Lesley F.] St Boniface Gen Hosp, Res Ctr, Winnipeg, MB R2H 2A6, Canada. RP Singh, JA (reprint author), Minneapolis Vet Affairs Ctr, 1 Vet Dr 111R, Minneapolis, MN 55417 USA. EM jasvinder.md@gmail.com RI Hack, Thomas/C-5174-2012; OI Hack, Thomas/0000-0002-6913-8732; singh, jasvinder/0000-0003-3485-0006 FU National Institutes of Health [1 KL2 RR024151-01] FX Supported by clinical and translational science award 1 KL2 RR024151-01 from the National Institutes of Health (to the Mayo Clinic Center for Clinical and Translational Research). NR 42 TC 50 Z9 54 U1 3 U2 12 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD SEP PY 2010 VL 16 IS 9 BP 688 EP 696 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 660EA UT WOS:000282621400006 PM 20873956 ER PT J AU Wu, AHB Lewandrowski, K Gronowski, AM Grenache, DG Sokoll, LJ Magnani, B AF Wu, Alan H. B. Lewandrowski, Kent Gronowski, Ann M. Grenache, David G. Sokoll, Lori J. Magnani, Barbarajean TI Antiquated Tests Within the Clinical Pathology Laboratory SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID ERYTHROCYTE SEDIMENTATION-RATE; FETAL LUNG MATURITY; RESPIRATORY-DISTRESS-SYNDROME; C-REACTIVE PROTEIN; LAMELLAR BODY COUNT; MYOCARDIAL-INFARCTION; BLEEDING-TIME; ACID-PHOSPHATASE; CARDIAC TROPONIN; LECITHIN/SPHINGOMYELIN RATIO AB Objective: To provide evidence supporting the discontinuation of laboratory tests that do not have clinical utility today. Study Design: We selected 10 representative tests considered antiquated by most experts in the clinical laboratory medicine field: creatine kinase-MB, myoglobin, serum folate and red blood cell folate, amylase, lecithin/sphingomyelin ratio, qualitative serum human chorionic gonadotropin, prostatic acid phosphatase, bleeding time, and erythrocyte sedimentation rate. Methods: Published literature was reviewed to provide evidence of the poor performance and/or limited clinical utility of these tests. When available, subscriptions to the Proficiency Testing Program of the College of American Pathologists were tracked from 1993 to 2008 as supporting evidence. Finally, when appropriate, alternative testing was suggested. Results: The data show clearly that there is a national trend toward reduction or elimination of these 10 tests. Conclusion: Together with their clinical colleagues, clinical laboratorians should review their menu of tests and consider removing tests that do not provide clinical benefit. In most cases, alternative tests are already in clinical use. (Am J Manag Care. 2010; 16(9): e220-e227) C1 [Wu, Alan H. B.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94110 USA. [Lewandrowski, Kent] Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. [Gronowski, Ann M.] Washington Univ, Div Lab & Genom Med, St Louis, MO USA. [Grenache, David G.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Sokoll, Lori J.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Magnani, Barbarajean] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA USA. RP Wu, AHB (reprint author), Univ Calif San Francisco, Dept Lab Med, 1001 Potreor Ave,Rm 2M27, San Francisco, CA 94110 USA. EM wualan@labmed2.ucsf.edu NR 59 TC 11 Z9 11 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD SEP PY 2010 VL 16 IS 9 BP E220 EP E227 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 660EA UT WOS:000282621400008 PM 21250398 ER PT J AU Rogers, RS Pronovost, P Isaac, T Schoenfeld, A Leape, L Iezzoni, LI Blumenthal, D AF Rogers, Robert S. Pronovost, Peter Isaac, Thomas Schoenfeld, Amy Leape, Lucian Iezzoni, Lisa I. Blumenthal, David TI Systematically Seeking Clinicians' Insights to Identify New Safety Measures for Intensive Care Units and General Surgery Services SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE safety measures; clinician insight; ICU services; general surgery services ID SURGICAL CARE AB Comprehensive measures to benchmark or track safety performance do not yet exist. The authors aimed to develop and validate a process to identify comprehensive, clinically meaningful sets of safety measures that would draw on the clinical experiences and perceptions of active practitioners. They pilot tested this process for safety measure development for 2 hospital departments (ie, intensive care units and general surgery services) by holding 7 brainstorming sessions with physicians and nurses in major academic and community teaching hospitals in Boston, Massachusetts, and Baltimore, Maryland. Participants identified lists of patient harms that they considered to be among the 20 most frequent and the 20 most severe in their respective units. The authors generated a master list of patient harms, which participants then ranked by both frequency and severity via E-mail voting. This process produced safety measures with inherent credibility with clinicians on the front lines of care. C1 [Rogers, Robert S.; Schoenfeld, Amy; Iezzoni, Lisa I.; Blumenthal, David] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Pronovost, Peter] Johns Hopkins Univ, Baltimore, MD USA. [Isaac, Thomas] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Leape, Lucian] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM liezzoni@partners.org FU The Commonwealth Fund [20070334] FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: This work was supported by Grant No. 20070334 from The Commonwealth Fund. NR 10 TC 2 Z9 2 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD SEP-OCT PY 2010 VL 25 IS 5 BP 359 EP 364 DI 10.1177/1062860610367678 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 686LA UT WOS:000284696600006 PM 20445132 ER PT J AU Borrero, S Moore, CG Creinin, MD Ibrahim, SA AF Borrero, Sonya Moore, Charity G. Creinin, Mitchell D. Ibrahim, Said A. TI Low Rates of Vasectomy Among Minorities: A Result of Differential Receipt of Counseling? SO AMERICAN JOURNAL OF MENS HEALTH LA English DT Article DE sterilization; vasectomy; disparities; health services; contraception ID HEALTH-SERVICES; UNITED-STATES; YOUNG MEN; STERILIZATION AB Male sterilization is a highly effective contraceptive method that is underused especially among minorities. This analysis examined the association between race/ethnicity and receipt of sterilization counseling. This study used data collected by the 2002 National Survey of Family Growth. The analysis included men 15 to 44 years old who had not undergone sterilization. The outcome was receipt of sterilization counseling in the 12 months prior to interview, and the primary predictor was race/ethnicity. Sociodemographic characteristics, history of fathering an unintended birth, intention for more children, and access to health care were examined as confounders. Sixty-one (1.7%) men reported receiving sterilization counseling. Although counseling was reported more commonly by Black and Hispanic men compared with White men, the rates were not significantly different (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 0.8-7.1 and OR = 1.9, 95% CI = 0.9-4.1, respectively). In this nationally representative sample of men aged 15 to 44 years, there were exceedingly low rates of sterilization counseling for all men regardless of race/ethnicity. C1 [Borrero, Sonya; Moore, Charity G.; Ibrahim, Said A.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Borrero, Sonya; Ibrahim, Said A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Creinin, Mitchell D.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Biol, Pittsburgh, PA USA. [Creinin, Mitchell D.] Magee Womens Res Inst, Pittsburgh, PA USA. [Creinin, Mitchell D.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Borrero, S (reprint author), Univ Pittsburgh, Sch Med, Div Gen Internal Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu OI Moore, Charity/0000-0002-0060-0124 FU NCATS NIH HHS [KL2 TR000146]; NCRR NIH HHS [KL2 RR024154-016500, 1KL2 RR02415403, KL2 RR024154] NR 19 TC 4 Z9 4 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1557-9883 J9 AM J MENS HEALTH JI Am. J. Mens Health PD SEP PY 2010 VL 4 IS 3 BP 243 EP 249 DI 10.1177/1557988309337619 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 638WY UT WOS:000280930400008 PM 19706674 ER PT J AU Baker, AM Haeri, S Klein, RL Boggess, K AF Baker, Arthur M. Haeri, Sina Klein, Richard L. Boggess, Klim TI Association of midgestation paraoxonase 1 activity and pregnancies complicated by preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med, Univ Texas Med Branch, Dept Obstetrics & Gynecology DE oxidative stress; paraoxonase 1; preterm birth ID DEPENDENT DIABETES-MELLITUS; CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; DELIVERY; RISK; POLYMORPHISMS; LIPOPROTEINS; MORTALITY; COHORT AB OBJECTIVE: The objective of the study was to determine whether an association exists between low paraoxonase 1 activity and dyslipidemia at midgestation and preterm birth. STUDY DESIGN: We conducted a case-control study of 30 women with preterm birth and 90 women with uncomplicated term deliveries. Maternal serum collected at 15-20 weeks was used to measure lipid concentrations and paraoxonase 1 activity using 2 substrates: paraoxon and phenylacetate (arylesterase activity). RESULTS: The groups did not differ with respect to maternal demographics. Paraoxonase 1 activity (paraoxon) was significantly lower in women delivering preterm compared with controls (12.9 +/- 6.1 vs 16.6 +/- 7.7 dA/min; P = .02). Arylesterase activity and serum lipid concentrations were similar between women with preterm birth and controls. CONCLUSION: Midgestation paraoxonase 1 activity is lower in women who later experience spontaneous preterm birth compared with women who have term deliveries. Prospective studies are needed to determine the significance of paraoxonase 1 in the pathogenesis of preterm birth. C1 [Baker, Arthur M.; Haeri, Sina; Boggess, Klim] Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chapel Hill, NC 27599 USA. [Klein, Richard L.] Med Univ S Carolina, Dept Med, Div Endocrinol Metab & Med Genet, Charleston, SC 29425 USA. [Klein, Richard L.] Vet Affairs Med Ctr, Res Serv, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Baker, AM (reprint author), Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, 3010 Old Clin Bldg,CB 7516, Chapel Hill, NC 27599 USA. EM abaker2@med.unc.edu NR 24 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2010 VL 203 IS 3 AR 246.e1 DI 10.1016/j.ajog.2010.04.048 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 647FH UT WOS:000281602700025 PM 20541733 ER PT J AU Moore, RG Jabre-Raughley, M Brown, AK Robison, KM Miller, MC Allard, WJ Kurman, RJ Bast, RC Skates, SJ AF Moore, Richard G. Jabre-Raughley, Moune Brown, Amy K. Robison, Katina M. Miller, M. Craig Allard, W. Jeffery Kurman, Robert J. Bast, Robert C. Skates, Steven J. TI Comparison of a novel multiple marker assay vs the Risk of Malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Society-of-Gynecologic-Oncologists CY FEB 05-08, 2009 CL San Antonio, TX SP Soc Gynecol Oncol DE CA125; HE4; ovarian cancer; pelvic mass; ROMA ID SURVIVAL; CARCINOMA; SURGERY; IMPACT; CARE AB OBJECTIVE: We sought to compare the Risk of Malignancy Index (RMI) to the Risk of Ovarian Malignancy Algorithm (ROMA) to predict epithelial ovarian cancer (EOC) in women with a pelvic mass. STUDY DESIGN: In all, 457 women with imaging results from ultrasound, computed tomography, magnetic resonance imaging, and serum HE4 and CA125 determined prior to surgery for pelvic mass were evaluable. RMI values were determined using CA125, imaging score, and menopausal status. ROMA values were determined using HE4, CA125, and menopausal status. RESULTS: At a set specificity of 75%, ROMA had a sensitivity of 94.3% and RMI had a sensitivity of 84.6% for distinguishing benign status from EOC (P = .0029). In patients with stage I and II disease, ROMA achieved a sensitivity of 85.3% compared with 64.7% for RMI (P < .0001). CONCLUSION: The dual marker algorithm utilizing HE4 and CA125 to calculate a ROMA value achieves a significantly higher sensitivity for identifying women with EOC than does RMI. C1 [Moore, Richard G.; Jabre-Raughley, Moune; Robison, Katina M.] Brown Univ, Women & Infants Hosp Rhode Isl, Dept Obstet & Gynecol, Program Womens Oncol,Warren Alpert Med Sch, Providence, RI 02905 USA. [Brown, Amy K.] Hartford Hosp, Dept Obstet & Gynecol, Hartford, CT 06115 USA. [Miller, M. Craig; Allard, W. Jeffery] Medivice Consulting, New Durham, NH USA. [Kurman, Robert J.] Johns Hopkins Med Sch, Dept Pathol, Baltimore, MD USA. [Bast, Robert C.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Skates, Steven J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Moore, RG (reprint author), Brown Univ, Women & Infants Hosp Rhode Isl, Dept Obstet & Gynecol, Program Womens Oncol,Alpert Med Sch, 101 Dudley St, Providence, RI 02905 USA. EM rmoore@wihri.org RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 FU NCI NIH HHS [CA086381, CA105009, P50 CA083639, P50 CA105009, U01 CA086381] NR 21 TC 30 Z9 35 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2010 VL 203 IS 3 AR 228.e1 DI 10.1016/j.ajog.2010.03.043 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 647FH UT WOS:000281602700017 PM 20471625 ER PT J AU Landeck, L Schalock, PC Baden, LA Gonzalez, E AF Landeck, Lilla Schalock, Peter C. Baden, Lynn A. Gonzalez, Ernesto TI Periorbital Contact Sensitization SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EYELID DERMATITIS; ALLERGY; NICKEL AB PURPOSE: To identify frequency and pattern of contact sensitization among patients with periorbital dermatitis. DESIGN: Cross-sectional retrospective investigation of 1247 patients referred for patch testing over a 17-year period. METHODS: Data were collected for patients undergoing patch testing to the standard and customized trays between January 1990 and December 2006 at the Massachusetts General Hospital, Contact Dermatitis Clinic. Our study group consisted of 266 patients affected by periorbital dermatitis. Findings were compared to 981 referrals without periorbital dermatitis (controls). Patch test results were read after 48 and 72 hours and classified as allergic, questionable, irritant, or negative. Statistical analyses were carried out by using chi(2) test and Fisher exact test. RESULTS: General epidemiologic data among periorbital dermatitis patients showed significant predominance of female gender (87.6%) and of individuals aged 40 to 59 years (45.9%). Nickel (16.5%) and fragrance mix (13.2%) were the top-ranking sensitizers. Ingredients of topical ophthalmologic products did not result in significant sensitization. Comparison of the periorbital dermatitis group to the controls did not reveal significant differences in sensitization pattern. Patch testing confirmed the likelihood of allergic contact dermatitis in 50.8% of the periorbital dermatitis patients tested. CONCLUSIONS: Allergic contact dermatitis is a common cause of periorbital dermatitis. Patch testing should be considered in all patients with periorbital dermatitis when suspecting contact allergy in order to identify and avoid offending allergens. (Am J Ophthalmol 2010;150: 366-370. (C) 2010 by Elsevier Inc. All rights reserved.) C1 [Landeck, Lilla; Schalock, Peter C.; Gonzalez, Ernesto] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Baden, Lynn A.] Ctr Dermatol & Aesthet Med, Newton, MA USA. RP Gonzalez, E (reprint author), Massachusetts Gen Hosp, Dept Dermatol BAR 610, 55 Fruit St, Boston, MA 02114 USA. EM egonzalezl@partners.org OI Schalock, Peter/0000-0001-8953-4639 NR 21 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2010 VL 150 IS 3 BP 366 EP 370 DI 10.1016/j.ajo.2010.03.026 PG 5 WC Ophthalmology SC Ophthalmology GA 649ON UT WOS:000281781800011 PM 20541737 ER PT J AU Stacy, RC Jakobiec, FA Schoenfield, L Singh, AD AF Stacy, Rebecca C. Jakobiec, Frederick A. Schoenfield, Lynn Singh, Arun D. TI Unifocal and Multifocal Reactive Lymphoid Hyperplasia vs Follicular Lymphoma of the Ocular Adnexa SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID IGG4-RELATED SCLEROSING DISEASE; PRIMARY ORBITAL LYMPHOMA; B-CELL LYMPHOMA; CASTLEMANS-DISEASE; LYMPHOPROLIFERATIVE LESIONS; MALIGNANT-LYMPHOMA; CLINICAL-FEATURES; JAPANESE PATIENTS; TUMORS; RADIOTHERAPY AB PURPOSE: To characterize the differentiating histopathologic and immunophenotypic features of reactive lymphoid hyperplasia (RLH) and follicular lymphoma of the ocular adnexa. DESIGN: Retrospective case study with clinical follow-up and review of the literature. METHODS: Clinical records of 9 cases of RLH and 6 cases of follicular lymphoma from 2 institutions were reviewed. Light microscopic evaluation and immunohistochemical stains including CD20, CD3, CD5, CD21, CD23, BCL-2, BCL-6, CD10, kappa, lambda, and Ki67 were used to distinguish the 2 categories. RESULTS: RLH preferentially involved the conjunctiva, whereas follicular lymphoma had a propensity to involve the lacrimal gland. Microscopic analysis with immunohistochemical staining distinguished RLH from follicular lymphoma. BCL-2 was positive in follicular centers of follicular lymphoma but not in RLH. CD10 identified follicular center cells and Ki67 quantified cells in S-phase. CD21 and CD23 detected denclritic cell scaffoldings of indistinct germinal centers. None of the patients with RLH developed lymphoma during their clinical courses (up to 18 years). However, 3 patients with orbital, but not conjunctival, RLH developed immunohistochemically proven multifocal nonophthalmic supradiaphragmatic adnexal RLH (sites included lung, parotid, axillary nodes, and uvea). All 6 patients with follicular lymphoma had disseminated disease. CONCLUSIONS: A correct diagnosis of RLH vs follicular lymphoma can be reliably established employing immunohistochemical methods. A heretofore undescribed "multifocal RLH" syndrome must be distinguished from follicular lymphoma. Conjunctival RLH can usually be managed surgically without radiotherapy, but "multifocal RLH" required systemic treatment in 2 of 3 patients. Follicular lymphoma requires systemic chemotherapy if discovered beyond stage 1E. (Am J Ophthalmol 2010;150:412-426. (C) 2010 by Elsevier Inc. All rights reserved.) C1 [Stacy, Rebecca C.; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Stacy, Rebecca C.; Jakobiec, Frederick A.] Harvard Univ, Sch Med, Boston, MA USA. [Schoenfield, Lynn] Cleveland Clin Fdn, Dept Anat Pathol, Cole Eye Inst, Cleveland, OH 44195 USA. [Singh, Arun D.] Cleveland Clin Fdn, Dept Ophthalm Oncol, Cole Eye Inst, Cleveland, OH 44195 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, 243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu RI Schoenfield, Lynn/J-6183-2013 FU HEED FOUNDATION, CLEVELAND, OHIO FX REBECCA STACY IS SUPPORTED IN PART BY THE HEED FOUNDATION, CLEVELAND, OHIO. THE AUTHORS INDICATE NO financial conflict of interest. Involved in design of study (R.S., F.A.J.); conduct of study (R.S., F.A.J., L.S., A.S.); collection, management, analysis, and interpretation of the data (R.S., F.A.J., L.S., A.S.); and preparation, review, and approval of the manuscript (R.S., F.A.J., L.S., A.S.). The above study was conducted in compliance with the Institutional Review Boards of the Massachusetts Eye and Ear Infirmary and the Cleveland Clinic. Health Insurance Portability and Accountability Act compliance was maintained. Care of the patients in this study was in accordance with the Declaration of Helsinki and all federal and state laws. NR 69 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2010 VL 150 IS 3 BP 412 EP 426 DI 10.1016/j.ajo.2010.04.007 PG 15 WC Ophthalmology SC Ophthalmology GA 649ON UT WOS:000281781800019 PM 20599186 ER PT J AU Quesnel, AM Lindsay, RW Hadlock, TA AF Quesnel, Alicia M. Lindsay, Robin W. Hadlock, Tessa A. TI When the bell tolls on Bell's palsy: finding occult malignancy in acute-onset facial paralysis SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID NERVE PARALYSIS; MANAGEMENT; DIAGNOSIS AB Purpose: This study reports 4 cases of occult parotid malignancy presenting with sudden-onset facial paralysis to demonstrate that failure to regain tone 6 months after onset distinguishes these patients from Bell's palsy patients with delayed recovery and to propose a diagnostic algorithm for this subset of patients. Materials and methods: A case series of 4 patients with occult parotid malignancies presenting with acute-onset unilateral facial paralysis is reported. Results: Initial imaging on all 4 patients did not demonstrate a parotid mass. Diagnostic delays ranged from 7 to 36 months from time of onset of facial paralysis to time of diagnosis of parotid malignancy. Additional physical examination findings, especially failure to regain tone, as well as properly protocolled radiologic studies reviewed with dedicated head and neck radiologists, were helpful in arriving at the diagnosis. Conclusion: An algorithm to minimize diagnostic delays in this subset of acute facial paralysis patients is presented. Careful attention to facial tone, in addition to movement, is important in the diagnostic evaluation of acute-onset facial paralysis. (C) 2010 Elsevier Inc. All rights reserved. C1 [Quesnel, Alicia M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Quesnel, AM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM alicia_quesnel@meei.harvard.edu NR 13 TC 9 Z9 10 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 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD SEP-OCT PY 2010 VL 31 IS 5 BP 339 EP 342 DI 10.1016/j.amjoto.2009.04.003 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 648SY UT WOS:000281715600006 PM 20015776 ER PT J AU Romeo, S Duim, RAJ Bridge, JA Mertens, F de Jong, D Dal Cin, P Wijers-Koster, PM Debiec-Rychter, M Sciot, R Rosenberg, AE Szuhai, K Hogendoorn, PCW AF Romeo, Salvatore Duim, Ronald A. J. Bridge, Julia A. Mertens, Fredrik de Jong, Danielle Dal Cin, Paola Wijers-Koster, Pauline M. Debiec-Rychter, Maria Sciot, Raf Rosenberg, Andrew E. Szuhai, Karoly Hogendoorn, Pancras C. W. TI Heterogeneous and Complex Rearrangements of Chromosome Arm 6q in Chondromyxoid Fibroma Delineation of Breakpoints and Analysis of Candidate Target Genes SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CENTRAL CHONDROSARCOMA; CARTILAGINOUS TUMORS; BENIGN; DIFFERENTIATION; CHONDROBLASTOMA; ABERRATIONS; MOLECULES; KARYOTYPE; BONE AB Chondromyxoid fibroma (CMF) is an uncommon benign cartilaginous minor of bone usually occurring during the second decade of life. CMF is associated with recurrent rearrangements of chromosome bands 6p23-25, 6q12-15, and 6q23-27. To delineate further the role and frequency of the involvement of three candidate regions (6q13, 6q23.3 and 6q24) in the pathogenesis of CMF, we studied a group of 43 cases wing a molecular cytogenetic approach. Fluorescence in sit:, hybridization with probe sets bracketing the putative breakpoint regions was performed in 30 cases. The expression level of nearby candidate genes was studied by immunohistochemistry and quantitative RT-PCR in 24 and 23 cases, respectively. Whole-genome copy number screening was performed by array comparative genomic hybridization in 16 cases. Balanced and unbalanced rearrangements of 6q13 and 6q23.3 occurred in six and five cases, respectivel, and a hemizygous deletion in 6q24 was found in five cases. Two known tumor suppressor genes map to the latter region: PLAGL1 and UTRN However, neither of these two genes nor BCLAF1 and COL12A1, respectively located in 6q23.3 and 6q13, showed altered expression. Therefore, although rearrangements of chromosomal regions 6q13, 6q23.3, and 6q24 are common in CMF, the complexity of the changes precludes the use of a single fluorescence in situ hybridization probe set as an adjunct diagnostic tool. These data indicate that the genetic alterations in CM.F are heterogeneous and are likely a result of a cryptic rearrangement beyond the resolution level of combined binary ratio fluorescence hi situ hybridization or a point mutation. (Am J Pathol 2010, 177.1365-1376; DOI: 10.2353/ajpath.2010.091277) C1 [Romeo, Salvatore; Duim, Ronald A. J.; Wijers-Koster, Pauline M.; Hogendoorn, Pancras C. W.] Leiden Univ, Dept Pathol, Med Ctr, NL-2300 RC Leiden, Netherlands. [de Jong, Danielle; Szuhai, Karoly] Leiden Univ, Dept Mol Cell Biol, Med Ctr, NL-2300 RC Leiden, Netherlands. [Bridge, Julia A.] Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE USA. [Bridge, Julia A.] Univ Nebraska, Med Ctr, Dept Pediat, Omaha, NE USA. [Bridge, Julia A.] Univ Nebraska, Med Ctr, Dept Orthopaed Surg, Omaha, NE USA. [Mertens, Fredrik] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden. [Dal Cin, Paola] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Debiec-Rychter, Maria] Catholic Univ Louvain, Dept Human Genet, B-3000 Louvain, Belgium. [Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hogendoorn, PCW (reprint author), Leiden Univ, Dept Pathol, Med Ctr, POB 2300, NL-2300 RC Leiden, Netherlands. RI Szuhai, Karoly/A-1100-2008; Hogendoorn, Pancras/H-5859-2015; OI Szuhai, Karoly/0000-0002-1228-4245; Hogendoorn, Pancras/0000-0002-1513-8104; Mertens, Fredrik/0000-0002-6278-5232 FU EuroBoNeT; European Community [LSHC-CT-2006-018814] FX Supported by EuroBoNeT, a European Community granted network of excellence for studying the pathology and genetics of bone tumors (grant LSHC-CT-2006-018814) SR, R A J D, FM, DJ, P M W K, M D R, R S, K S. and P C W H are partners within EuroBoNeT NR 28 TC 9 Z9 9 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2010 VL 177 IS 3 BP 1365 EP 1376 DI 10.2353/ajpath.2010.091277 PG 12 WC Pathology SC Pathology GA 648TR UT WOS:000281717700032 PM 20696777 ER PT J AU Lennerz, JKM Kim, SH Oates, EL Huh, WJ Doherty, JM Tian, X Bredemeyer, AJ Goldenring, JR Lauwers, GY Shin, YK Mills, JC AF Lennerz, Jochen K. M. Kim, Seok-Hyung Oates, Edward L. Huh, Won Jae Doherty, Jason M. Tian, Xiaolin Bredemeyer, Andrew J. Goldenring, James R. Lauwers, Gregory Y. Shin, Young-Kee Mills, Jason C. TI The Transcription Factor MIST1 Is a Novel Human Gastric Chief Cell Marker Whose Expression Is Lost in Metaplasia, Dysplasia, and Carcinoma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID INTESTINAL METAPLASIA; SPASMOLYTIC POLYPEPTIDE; HELICOBACTER-PYLORI; PARIETAL-CELL; HUMAN STOMACH; BARRETT-ESOPHAGUS; TRANSGENIC MICE; OXYNTIC ATROPHY; SONIC HEDGEHOG; STEM-CELLS AB The lack of reliable molecular markers for normal differentiated epithelial cells limits understanding of human gastric carcinogenesis. Recognized precursor lesions for gastric adenocarcinoma are intestinal metaplasia and spasmolytic polypeptide expressing metaplasia (SPEM), defined here by ectopic CDX2 and TFE2 expression, respectively. In mice, expression of the bHLH transcription factor MIST1, normally restricted to mature chief cells, is down-regulated as chief cells undergo experimentally induced metaplasia. Here, we show MIST1 expression is also a specific marker of human chief cells. SPEM, with and without MIST1, is present in human lesions and, akin to murine data, likely represents transitional (TFF2(+)/MIST1(+) = "hybrid"-SPEM) and established (TIT2(+)/ MIST1(-) = SPEM) stages. Co-visualization of MIST1 and CDX2 shows similar progressive loss of MIST1 with a transitional, CDX2(+)/MIST1(-) hybrid-intestinal metaplasia stage. Interinstitutional analysis and comparison of findings in tissue microarrays, resection specimens, and biopsies (is > 400 samples), comprising the entire spectrum of recognized stages of gastric carcinogenesis, confirm MIST1 expression is restricted to the chief cell compartment in normal oxyntic mucosa, rare in established metaplastic lesions, and lost in intraepithelial neoplasia/dysplasia and carcinoma of various types with the exception of rare chief cell carcinoma (similar to 1%). Our findings implicate MIST1 as a reliable marker of mature, healthy chief cells, and we provide the first evidence that metaplasia in humans arises at least in part from the chief cell lineage. (Am J Pathol 2010, 177-1514-1533; DOI: 10.2353/ajpath.2010.100328) C1 [Lennerz, Jochen K. M.; Oates, Edward L.; Huh, Won Jae; Doherty, Jason M.; Tian, Xiaolin; Bredemeyer, Andrew J.; Mills, Jason C.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Oates, Edward L.; Huh, Won Jae; Tian, Xiaolin; Bredemeyer, Andrew J.; Mills, Jason C.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Mol Cell Biol Program, St Louis, MO 63110 USA. [Lennerz, Jochen K. M.; Lauwers, Gregory Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Sungkyunkwan Univ, Samsung Med Ctr, Dept Pathol, Seoul, South Korea. Louisiana State Univ, Neurosci Ctr Excellence, Hlth Sci Ctr, New Orleans, LA USA. [Bredemeyer, Andrew J.] Partners HealthCare Syst, Boston, MA USA. [Goldenring, James R.] Vanderbilt Univ, Sch Med, Dept Surg & Dev Biol, Epithehal Biol Ctr, Nashville, TN 37212 USA. Vanderbilt Ingram Canc Ctr Nashville, Dept Vet Affairs, Med Ctr, Nashville, TN USA. [Shin, Young-Kee] Seoul Natl Univ, Dept Pharm, Seoul, South Korea. RP Mills, JC (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, Box 8118,660 S Euclid Ave, St Louis, MO 63110 USA. RI Shin, Young Kee/C-8929-2011 FU Cancer Washington University Digestive Diseases Research Core Center, Bio-Bank and Clinical Data Core [P30 DK52574] FX Supported by J C M (R01 DK-079798-01, ACS DDC-115769), X T (T32-A1007172). A J B (T32-CA009547). and J R G (Department of Veterans Affairs Merit Review Award. RO1 DK071590) J C M and J R G were recipients of the AGA Funderburg Award in Gastric Biology Related to Cancer Washington University Digestive Diseases Research Core Center, Bio-Bank and Clinical Data Core was supported by grant #P30 DK52574 NR 111 TC 38 Z9 39 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2010 VL 177 IS 3 BP 1514 EP 1533 DI 10.2353/ajpath.2010.100328 PG 20 WC Pathology SC Pathology GA 648TR UT WOS:000281717700045 PM 20709804 ER PT J AU Panchenko, MP Siddiquee, Z Dombkowski, DM Alekseyev, YO Lenburg, ME Walker, JD MacGillivray, TE Preffer, FI Stone, JR AF Panchenko, Mikhail P. Siddiquee, Zakir Dombkowski, David M. Alekseyev, Yuriy O. Lenburg, Marc E. Walker, Jennifer D. MacGillivray, Thomas E. Preffer, Frederic I. Stone, James R. TI Protein Kinase CK1 alpha LS Promotes Vascular Cell Proliferation and Intimal Hyperplasia SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NUCLEAR RIBONUCLEOPROTEIN C1/C2; COLONY-STIMULATING FACTOR; MESSENGER-RNA; HYDROGEN-PEROXIDE; I FAMILY; HNRNP-C; GM-CSF; EXPRESSION; PHOSPHORYLATION; TRANSLATION AB Protein kinase CK1 alpha regulates several fundamental cellular processes including proliferation and differentiation. Up to four forms of this kinase are expressed in vertebrates resulting from alternative splicing of exons; these exons encode either the L-insert located within the catalytic domain or the S-insert located at the C terminus of the protein. Whereas the L-insert is known to target the kinase to the nucleus, the functional significance of nuclear CK1 alpha LS has been unclear. Here we demonstrate that selective L-insert-targeted short hairpin small interfering RNA-mediated knockdown of CK1 alpha LS in human vascular endothelial cells and vascular smooth muscle cells impairs proliferation and abolishes hydrogen peroxide-stimulated proliferation of vascular smooth muscle cells, with the cells accumulating in G(0)/G(1). In addition, selective knockdown of CK1 alpha LS in cultured human arteries inhibits vascular activation, preventing smooth muscle cell proliferation, intimal hyperplasia, and proteoglycan deposition. Knockdown of CK1 alpha LS results in the harmonious down-regulation of its target substrate heterogeneous nuclear ribonucleoprotein C and results in the altered expression or alternative splicing of key genes involved in cellular activation including CXCR4, MMP3, CSF2, and SMURF1. Our results indicate that the nuclear form of CK1 alpha in humans, CK1 alpha LS, plays a critical role in vascular cell proliferation, cellular activation, and hydrogen peroxide-mediated mitogenic signal transduction. (Am Pathol 2010, 177:1562-1572: DOI: 10.2353/ajpath.2010.100327) C1 [Panchenko, Mikhail P.; Siddiquee, Zakir; Stone, James R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Panchenko, Mikhail P.; Siddiquee, Zakir; Dombkowski, David M.; Preffer, Frederic I.; Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Walker, Jennifer D.; MacGillivray, Thomas E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Walker, Jennifer D.] Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Sirrches Res Bldg Room 8236,185 Cambridge St, Boston, MA 02114 USA. RI Lenburg, Marc/B-8027-2008; OI Lenburg, Marc/0000-0002-5760-4708; Alekseyev, Yuriy/0000-0001-6105-8861 FU Massachusetts General Hospital FX Supported by the Massachusetts General Hospital NR 52 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2010 VL 177 IS 3 BP 1562 EP 1572 DI 10.2353/ajpath.2010.100327 PG 11 WC Pathology SC Pathology GA 648TR UT WOS:000281717700048 PM 20696773 ER PT J AU Hsu, PT Chung, HY Wang, JL Lew, HL AF Hsu, Pei-Te Chung, Hsin-Yeh Wang, Jue-Long Lew, Henry L. TI Successful Conservative Treatment of Chronic Atlantoaxial Rotatory Fixation in a Child with Torticollis SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Torticollis; Atlantoaxial Rotatory Fixation; Children; Conservative Management ID SUBLUXATION AB A 7-yr-old girl was diagnosed with atlantoaxial rotatory fixation, a serious but treatable cause of acquired torticollis in children and not well known by clinical physicians. Two and a half years after conservative treatment, she had recovered completely. This case report suggests that if the patient has no previous adequate rehabilitation treatment, then conservative treatments are effective for chronic but stable atlantoaxial rotatory fixation. C1 [Hsu, Pei-Te; Chung, Hsin-Yeh; Wang, Jue-Long] Kaohsiung Vet Gen Hosp, Dept Phys Med & Rehabil, Kaohsiung 813, Taiwan. [Lew, Henry L.] Harvard Univ, Sch Med, Dept PM&R, Boston, MA USA. [Lew, Henry L.] VA Boston Healthcare Syst, Traumat Brain Injury Ctr Excellence, Boston, MA USA. RP Hsu, PT (reprint author), Kaohsiung Vet Gen Hosp, Dept Phys Med & Rehabil, 386 Dajhong 1st Rd, Kaohsiung 813, Taiwan. FU Department of Physical Medicine & Rehabilitation, Kaohsiung Veterans General Hospital FX Supported by the Department of Physical Medicine & Rehabilitation, Kaohsiung Veterans General Hospital. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. NR 5 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD SEP PY 2010 VL 89 IS 9 BP 776 EP 778 DI 10.1097/PHM.0b013e3181e29cad PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 641SL UT WOS:000281149900012 PM 20531156 ER PT J AU Cowart, LA AF Cowart, L. Ashley TI A novel role for sphingolipid metabolism in oxidant-mediated skeletal muscle fatigue. Focus on "Sphingomyelinase stimulates oxidant signaling to weaken skeletal muscle and promote fatigue" SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article ID PROTEIN-KINASE-C; NEUTRAL SPHINGOMYELINASES; SPHINGOSINE INHIBITION; HUMAN-PLATELETS; CERAMIDE; DIFFERENTIATION; APOPTOSIS; EXERCISE; BASES C1 [Cowart, L. Ashley] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Cowart, L. Ashley] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Cowart, LA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM cowartl@musc.edu NR 26 TC 2 Z9 2 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 2010 VL 299 IS 3 BP C549 EP C551 DI 10.1152/ajpcell.00236.2010 PG 3 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 644OR UT WOS:000281389100002 PM 20573998 ER PT J AU Ceppa, E Cattaruzza, F Lyo, V Amadesi, S Pelayo, JC Poole, DP Vaksman, N Liedtke, W Cohen, DM Grady, EF Bunnett, NW Kirkwood, KS AF Ceppa, Eugene Cattaruzza, Fiore Lyo, Victoria Amadesi, Silvia Pelayo, Juan-Carlos Poole, Daniel P. Vaksman, Natalya Liedtke, Wolfgang Cohen, David M. Grady, Eileen F. Bunnett, Nigel W. Kirkwood, Kimberly S. TI Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE neurogenic inflammation; TRP channels ID INDUCED NEUROGENIC INFLAMMATION; GENE-RELATED PEPTIDE; CAPSAICIN RECEPTOR; SENSORY NEURONS; ACTIVATED RECEPTOR-2; TRPV4 CHANNELS; RAT PANCREAS; MOUSE MODEL; TRPA1; HYPERALGESIA AB Ceppa E, Cattaruzza F, Lyo V, Amadesi S, Pelayo J, Poole DP, Vaksman N, Liedtke W, Cohen DM, Grady EF, Bunnett NW, Kirkwood KS. Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice. Am J Physiol Gastrointest Liver Physiol 299: G556-G571, 2010. First published June 10, 2010; doi: 10.1152/ajpgi.00433.2009.-The mechanisms of pancreatic pain, a cardinal symptom of pancreatitis, are unknown. Proinflammatory agents that activate transient receptor potential (TRP) channels in nociceptive neurons can cause neurogenic inflammation and pain. We report a major role for TRPV4, which detects osmotic pressure and arachidonic acid metabolites, and TRPA1, which responds to 4-hydroxynonenal and cyclopentenone prostaglandins, in pancreatic inflammation and pain in mice. Immunoreactive TRPV4 and TRPA1 were detected in pancreatic nerve fibers and in dorsal root ganglia neurons innervating the pancreas, which were identified by retrograde tracing. Agonists of TRPV4 and TRPA1 increased intracellular Ca2+ concentration ([Ca2+](i)) in these neurons in culture, and neurons also responded to the TRPV1 agonist capsaicin and are thus nociceptors. Intraductal injection of TRPV4 and TRPA1 agonists increased c-Fos expression in spinal neurons, indicative of nociceptor activation, and intraductal TRPA1 agonists also caused pancreatic inflammation. The effects of TRPV4 and TRPA1 agonists on [Ca2+](i), pain and inflammation were markedly diminished or abolished in trpv4 and trpa1 knockout mice. The secretagogue cerulein induced pancreatitis, c-Fos expression in spinal neurons, and pain behavior in wild-type mice. Deletion of trpv4 or trpa1 suppressed c-Fos expression and pain behavior, and deletion of trpa1 attenuated pancreatitis. Thus TRPV4 and TRPA1 contribute to pancreatic pain, and TRPA1 also mediates pancreatic inflammation. Our results provide new information about the contributions of TRPV4 and TRPA1 to inflammatory pain and suggest that channel antagonists are an effective therapy for pancreatitis, when multiple proinflammatory agents are generated that can activate and sensitize these channels. C1 [Ceppa, Eugene; Cattaruzza, Fiore; Lyo, Victoria; Amadesi, Silvia; Pelayo, Juan-Carlos; Poole, Daniel P.; Vaksman, Natalya; Grady, Eileen F.; Bunnett, Nigel W.; Kirkwood, Kimberly S.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Bunnett, Nigel W.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. [Liedtke, Wolfgang] Duke Univ Med Ctr, Dept Med & Neurobiol, Durham, NC USA. [Cohen, David M.] Portland VA Med Ctr, Portland, OR USA. RP Bunnett, NW (reprint author), Univ Calif San Francisco, Dept Surg, 513 Parnassus Ave,Rm S1268, San Francisco, CA 94143 USA. EM nigel.bunnett@ucsf.edu RI Liedtke, Wolfgang/G-4633-2011 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK46285, DK57840, DK43207, DK39957, T32 DK07573]; Crohn's and Colitis Foundation [1730] FX This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK46285 (K. S. Kirkwood, N. W. Bunnett), DK57840 (N. W. Bunnett), DK43207 (N. W. Bunnett), DK39957 (N. W. Bunnett), and T32 DK07573 (E. Ceppa, N. W. Bunnett), and Crohn's and Colitis Foundation 1730 (E. F. Grady). NR 57 TC 44 Z9 45 U1 1 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD SEP PY 2010 VL 299 IS 3 BP G556 EP G571 DI 10.1152/ajpgi.00433.2009 PG 16 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 644MV UT WOS:000281382600002 PM 20539005 ER PT J AU Cheng, F McLaughlin, PJ Banks, WA Zagon, IS AF Cheng, Fan McLaughlin, Patricia J. Banks, William A. Zagon, Ian S. TI Internalization of the opioid growth factor, [Met(5)]-enkephalin, is dependent on clathrin-mediated endocytosis for downregulation of cell proliferation SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE human mesenchymal stem cells; active transport; DNA synthase; nucleocytoplasmic transport; siRNA ID FACTOR RECEPTOR OGFR; AXIS; PEPTIDES; BIOLOGY; CANCER; LOCALIZATION; CAVEOLIN-1; BRAIN; HEAD AB Cheng F, McLaughlin PJ, Banks WA, Zagon IS. Internalization of the opioid growth factor, [Met(5)]-enkephalin, is dependent on clathrin-mediated endocytosis for downregulation of cell proliferation. Am J Physiol Regul Integr Comp Physiol 299: R774-R785, 2010. First published June 30, 2010; doi:10.1152/ajpregu.00318.2010.-The opioid growth factor (OGF; [Met(5)]-enkephalin), a constitutively expressed and tonically active inhibitory peptide, interacts with the OGF receptor (OGFr) to form an endogenous growth-regulating pathway in homeostasis. Amplification of OGF-OGFr interfacing in animal and clinical studies depresses development, neoplasia, angiogenesis, and immunity. Disruption of the OGF-OGFr axis accelerates cell proliferation and has been particularly important in wound repair. To investigate how OGF enters cells, OGF was labeled with 5,6-tetramethylrhodamine OGF (RhoOGF) to study its uptake in live cells. African green monkey kidney cells (COS-7) incubated with RhoOGF exhibited a temperature-dependent course of entry, being internalized at 37 C but not at 4 C. RhoOGF was detected in the cytoplasm 15 min after initial exposure, observed in both cytoplasm and nucleus within 30 min, and remained in the cells for as long as 5 h. A 100-fold excess of OGF or the opioid antagonist naltrexone, but not other opioid ligands (some selective for classic opioid receptors), markedly reduced entry of RhoOGF into cells. RhoOGF was functional because DNA synthesis in cells incubated with RhoOGF (10(-5) to 10(-8) M) was decreased 24-36%, and was comparable to cells treated with unlabeled OGF (reductions of 26-39%). OGF internalization was dependent on clathrin-mediated endocytosis, with addition of clathrin siRNA diminishing the uptake of RhoOGF and upregulating DNA synthesis. RhoOGF clathrin-mediated endocytosis was unrelated to endosomal or Golgi pathways. Taken together, these results suggest that OGF enters cells by active transport in a saturable manner that requires clathrin-mediated endocytosis. C1 [Cheng, Fan; McLaughlin, Patricia J.; Zagon, Ian S.] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA. [Banks, William A.] Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Zagon, IS (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Neural & Behav Sci, H109,500 Univ Dr,Rm C3729, Hershey, PA 17033 USA. EM isz1@psu.edu FU Paul K. and Anna E. Shockey Family Foundation; Zagon/Kostel families; Veterans Affairs Merit Review FX This study was supported, in part, by the Paul K. and Anna E. Shockey Family Foundation and the Zagon/Kostel families and a Veterans Affairs Merit Review (to W. A. Banks). NR 31 TC 8 Z9 8 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 2010 VL 299 IS 3 BP R774 EP R785 DI 10.1152/ajpregu.00318.2010 PG 12 WC Physiology SC Physiology GA 646KA UT WOS:000281537500007 PM 20592180 ER PT J AU Martinez, CO McHale, MJ Wells, JT Ochoa, O Michalek, JE McManus, LM Shireman, PK AF Martinez, Carlo O. McHale, Matthew J. Wells, Jason T. Ochoa, Oscar Michalek, Joel E. McManus, Linda M. Shireman, Paula K. TI Regulation of skeletal muscle regeneration by CCR2-activating chemokines is directly related to macrophage recruitment SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE monocyte/macrophage; angiogenesis; CC chemokine receptor 2; MCP-1/CCL2; MCP-5/CCL12 ID STEM-CELLS; IN-VIVO; ALTERED INFLAMMATION; CC-CHEMOKINE; BONE-MARROW; CCR2-/-MICE; EXPRESSION; MCP-1; ACTIVATION; MONOCYTES AB Martinez CO, McHale MJ, Wells JT, Ochoa O, Michalek JE, McManus LM, Shireman PK. Regulation of skeletal muscle regeneration by CCR2-activating chemokines is directly related to macrophage recruitment. Am J Physiol Regul Integr Comp Physiol 299: R832-R842, 2010. First published July 14, 2010; doi:10.1152/ajpregu.00797.2009.-Muscle regeneration requires CC chemokine receptor 2 (CCR2) expression on bone marrow-derived cells; macrophages are a prominent CCR2-expressing cell in this process. CCR2-/- mice have severe impairments in angiogenesis, macrophage recruitment, and skeletal muscle regeneration following cardiotoxin (CTX)-induced injury. However, multiple chemokines activate CCR2, including monocyte chemotactic proteins (MCP)-1, -3, and -5. We hypothesized that MCP-1 is the chemokine ligand that mediates the impairments present in CCR2-/- mice. We examined muscle regeneration, capillary density, and cellular recruitment in MCP-1-/- and CCR2-/- mice following injury. Muscle regeneration and adipocyte accumulation, but not capillary density, were significantly impaired in MCP-1-/- compared with wild-type (WT) mice; however, muscle regeneration and adipocyte accumulation impairments were not as severe as observed in CCR2-/- mice. Although tissue levels of MCP-5 were elevated in MCP-1-/- mice compared with WT, the administration of MCP-5 neutralizing antibody did not alter muscle regeneration in MCP-1-/- mice. While neutrophil accumulation after injury was similar in all three mouse strains, macrophage recruitment was highest in WT mice, intermediate in MCP-1-/- mice, and severely impaired in CCR2-/- mice. In conclusion, while the absence of MCP-1 resulted in impaired macrophage recruitment and muscle regeneration, MCP-1-/- mice exhibit an intermediate phenotype compared with CCR2-/- mice. Intermediate macrophage recruitment in MCP-1-/- mice was associated with similar capillary density to WT, suggesting that fewer macrophages may be needed to restore angiogenesis vs. muscle regeneration. Finally, other chemokines, in addition to MCP-1 and MCP-5, may activate CCR2-dependent regenerative processes resulting in an intermediate phenotype in MCP-1-/- mice. C1 [Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Div Vasc Surg, Dept Surg, San Antonio, TX 78229 USA. [Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Michalek, Joel E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Shireman, Paula K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Shireman, PK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Vasc Surg, Dept Surg, 7703 Floyd Curl Dr MSC 7741, San Antonio, TX 78229 USA. EM shireman@uthscsa.edu FU Veterans Administration; National Heart, Lung, and Blood Institute [HL-070158, HL-074236]; University of Texas Health Science Center San Antonio; National Cancer Institute, Cancer Therapy & Research Center [P30-CA-054174] FX This work was supported, in part, by a Veterans Administration Merit Review grant and the National Heart, Lung, and Blood Institute Grants HL-070158 and HL-074236. Data was generated in the Core Flow Cytometry Facility, which is supported by the University of Texas Health Science Center San Antonio and National Cancer Institute Grant P30-CA-054174 (Cancer Therapy & Research Center). NR 38 TC 45 Z9 46 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 2010 VL 299 IS 3 BP R832 EP R842 DI 10.1152/ajpregu.00797.2009 PG 11 WC Physiology SC Physiology GA 646KA UT WOS:000281537500013 PM 20631294 ER PT J AU Melhorn, SJ Krause, EG Scott, KA Mooney, MR Johnson, JD Woods, SC Sakai, RR AF Melhorn, Susan J. Krause, Eric G. Scott, Karen A. Mooney, Marie R. Johnson, Jeffrey D. Woods, Stephen C. Sakai, Randall R. TI Meal patterns and hypothalamic NPY expression during chronic social stress and recovery SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE adiposity; meal size; body composition; food intake ID CORTICOTROPIN-RELEASING HORMONE; VISIBLE BURROW SYSTEM; PITUITARY-ADRENAL AXIS; FOOD-INTAKE; BODY-WEIGHT; GENE-EXPRESSION; NEUROPEPTIDE-Y; EATING BEHAVIOR; FEMALE RATS; SUBORDINATION STRESS AB Melhorn SJ, Krause EG, Scott KA, Mooney MR, Johnson JD, Woods SC, Sakai RR. Meal patterns and hypothalamic NPY expression during chronic social stress and recovery. Am J Physiol Regul Integr Comp Physiol 299: R813-R822, 2010. First published July 7, 2010; doi:10.1152/ajpregu.00820.2009.-In the present study, we examined meal patterns during and after exposure to the visible burrow system (VBS), a rodent model of chronic social stress, to determine how the microstructure of food intake relates to the metabolic consequences of social subordination. Male Long-Evans rats were housed in mixed-sex VBS colonies (4 male, 2 female) for 2 wk, during which time a dominance hierarchy formed [1 dominant male (DOM) and 3 subordinate males (SUB)], and then male rats were individually housed for a 3-wk recovery period. Controls were individually housed with females during the 2-wk VBS period and had no changes in ingestive behavior compared with a habituation period. During the hierarchy-formation phase of VBS housing, DOM and SUB had a reduced meal frequency, whereas SUB also had a reduced meal size. However, during the hierarchy-maintenance phase of VBS housing, DOM meal patterns did not differ from controls, whereas SUB continued to display a reduced food intake via less frequent meals. During recovery, DOM had comparable meal patterns to controls, whereas SUB had an increased meal size. Hypothalamic neuropeptide Y (NPY) mRNA levels were not different between these groups during the experimental period. Together, the results suggest that exposure to chronic social stress alters ingestive behavior both acutely and in the long term, which may influence the metabolic changes that accompany bouts of stress and recovery; however, these differences in meal patterns do not appear to be mediated by hypothalamic NPY. C1 [Melhorn, Susan J.; Krause, Eric G.; Scott, Karen A.; Woods, Stephen C.; Sakai, Randall R.] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. [Melhorn, Susan J.; Scott, Karen A.] Univ Cincinnati, Coll Med, Program Neurosci, Cincinnati, OH USA. [Mooney, Marie R.; Johnson, Jeffrey D.] Univ Cincinnati, Coll Med, Dept Biomed Engn, Cincinnati, OH USA. RP Melhorn, SJ (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,151 Metab, Seattle, WA 98108 USA. EM smelhorn@u.washington.edu FU National Institute of Diabetes, Digestive and Kidney Diseases [RO1 DK066596-06] FX These studies were supported by the National Institute of Diabetes, Digestive and Kidney Diseases Grant RO1 DK066596-06 (to R. R. Sakai). NR 57 TC 21 Z9 22 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 2010 VL 299 IS 3 BP R813 EP R822 DI 10.1152/ajpregu.00820.2009 PG 10 WC Physiology SC Physiology GA 646KA UT WOS:000281537500011 PM 20610828 ER PT J AU Cronin, CG Harisinghani, MG Catalano, O Blake, MA AF Cronin, Carmel G. Harisinghani, Mukesh G. Catalano, Onofrio Blake, Michael A. TI Multitechnique Imaging Findings of Prolene Plug Hernia Repair SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE inguinal hernia; polypropylene; Prolene plug repair system; Prolene plugs ID INGUINAL-HERNIA; SYSTEM; COMPLICATIONS; APPEARANCE AB OBJECTIVE. The objective of this article is to illustrate the spectrum of imaging findings of polypropylene (Prolene) plug hernia repair. CONCLUSION. Knowledge of patient history and awareness of postsurgical imaging appearances are of importance because Prolene plugs are often incidentally encountered and if misdiagnosed may lead to erroneous patient disease staging and management. C1 [Cronin, Carmel G.; Harisinghani, Mukesh G.; Catalano, Onofrio; Blake, Michael A.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. [Cronin, Carmel G.; Harisinghani, Mukesh G.; Catalano, Onofrio; Blake, Michael A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cronin, CG (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2010 VL 195 IS 3 BP 701 EP 706 DI 10.2214/AJR.09.4142 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 642CI UT WOS:000281180500024 PM 20729449 ER PT J AU Boland, GWL Halpern, EF Gazelle, GS AF Boland, Giles W. L. Halpern, Elkan F. Gazelle, G. Scott TI Radiologist Report Turnaround Time: Impact of Pay-for-PerformanceMeasures SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE pay-for-performance; radiologist reporting; report turnaround time ID PRIMARY-CARE; QUALITY; ENGLAND AB OBJECTIVE. Expedited finalized radiologist report turnaround times (RTAT) are considered an important quality care metric in medicine. This study was performed to evaluate the impact of a radiologist pay-for-performance (PFP) program on reducing RTAT. MATERIALS AND METHODS. A radiologist PFP program was used to assess its impact on RTAT for all departmental reports from 11 subspecialty divisions. Study periods were 3 months before (baseline period) and immediately after (immediate period) the introduction of the program and 2 years later after the program had terminated (post period). Three RTAT components were evaluated for individual radiologists and for each radiology division: examination completion (C) to final signature (F), C to preliminary signature (P), and P to F. RESULTS. Eighty-one radiologists met the inclusion criterion for the study and performed a final signature on 99,959 reports during the baseline period, 104,673 reports during the immediate period, and 91,379 reports during the post period. Mean C-F, C-P, and P-F for all reports decreased significantly from baseline to immediate to post period (p < 0.0001), with the largest effect on the P-F component. Similarly, divisional C-F, C-P, and P-F also significantly decreased (p < 0.0001) for all divisions except the C-F for nuclear and neurovascular radiology from baseline to immediate period and the C-P component from baseline to post period for cardiac radiology. CONCLUSION. A radiologist PFP program appears to have a marked effect on expediting final report turnaround times, which continues after its termination. C1 [Boland, Giles W. L.; Halpern, Elkan F.; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Boland, Giles W. L.; Halpern, Elkan F.; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, White Bldg 270C,55 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org NR 25 TC 15 Z9 15 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2010 VL 195 IS 3 BP 707 EP 711 DI 10.2214/AJR.09.4164 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 642CI UT WOS:000281180500025 PM 20729450 ER PT J AU Nishino, M Jackman, DM Hatabu, H Yeap, BY Cioffredi, LA Yap, JT Janne, PA Johnson, BE Van den Abbeele, AD AF Nishino, Mizuki Jackman, David M. Hatabu, Hiroto Yeap, Beow Y. Cioffredi, Leigh-Anne Yap, Jeffrey T. Janne, Pasi A. Johnson, Bruce E. Van den Abbeele, Annick D. TI New Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines for Advanced Non-Small Cell Lung Cancer: Comparison With Original RECIST and Impact on Assessment of Tumor Response to Targeted Therapy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; lung cancer; PET/CT; Response Evaluation Criteria in Solid Tumors (RECIST); tumor measurement ID GEFITINIB; MUTATIONS; VARIABILITY; RESISTANCE; AGREEMENT; ERLOTINIB; LESIONS AB OBJECTIVE. The purpose of this article is to compare the recently published revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1) to the original guidelines (RECIST 1.0) for advanced non-small cell lung cancer (NSCLC) after erlotinib therapy and to evaluate the impact of the new CT tumor measurement guideline on response assessment. MATERIALS AND METHODS. Forty-three chemotherapy-naive patients with advanced NSCLC treated with erlotinib in a single-arm phase 2 multicenter open-label clinical trial were retrospectively studied. CT tumor measurement records using RECIST 1.0 that were generated as part of the prospective clinical trial were reviewed. A second set of CT tumor measurements was generated from the records to meet RECIST 1.1 guidelines. The number of target lesions, best response, and time to progression were compared between RECIST 1.1 and RECIST 1.0. RESULTS. The number of target lesions according to RECIST 1.1 decreased in 22 patients (51%) and did not change in 21 patients (49%) compared with the number according to RECIST 1.0 (p < 0.0001, paired Student's t test). Almost perfect agreement was observed between best responses using RECIST 1.1 and RECIST 1.0 (weighted kappa = 0.905). Two patients with stable disease according to RECIST 1.0 had progressive disease according to RECIST 1.1 criteria because of new lesions found on PET/CT. There was no significant difference in time to progression between RECIST 1.1 and RECIST 1.0 (p = 1.000, sign test). CONCLUSION. RECIST 1.1 provided almost perfect agreement in response assessment after erlotinib therapy compared with RECIST 1.0. Assessment with PET/CT was a major factor that influenced the difference in best response assessment between RECIST 1.1 and RECIST 1.0. C1 [Nishino, Mizuki; Yap, Jeffrey T.; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02116 USA. [Jackman, David M.; Cioffredi, Leigh-Anne; Janne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02116 USA. [Hatabu, Hiroto] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Nishino, M (reprint author), Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02116 USA. EM Mizuki_Nishino@dfci.harvard.edu FU Agfa HealthCare; National Institutes of Health [5R21CA11627-02, 1R0-1CA114465-01]; National Cancer Institute [2P50CA090578-06]; Genentech, Inc.; Doris and William Krupp Research Fund FX The authors received support from Agfa HealthCare (2009-2010 RSNA Research Scholar Grant to M. Nishino); the National Institutes of Health (grant 5R21CA11627-02 to H. Hatabu and grant 1R0-1CA114465-01 to B. Y. Yeap, P. A. Janne, and B. E. Johnson); the National Cancer Institute Specialized Program of Research Excellence in Lung Cancer (grant 2P50CA090578-06 to B. Y. Yeap, P. A. Janne, and B. E. Johnson); Genentech, Inc.; and the Doris and William Krupp Research Fund in Thoracic Oncology. NR 19 TC 64 Z9 74 U1 2 U2 6 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2010 VL 195 IS 3 BP W221 EP W228 DI 10.2214/AJR.09.3928 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 642CI UT WOS:000281180500045 PM 20729419 ER PT J AU Oei, TN Jagannathan, JP Ramaiya, N Ros, PR AF Oei, Tamara N. Jagannathan, Jyothi P. Ramaiya, Nikhil Ros, Pablo R. TI Peritoneal Sarcomatosis Versus Peritoneal Carcinomatosis: Imaging Findings at MDCT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE oncology; peritoneal carcinomatosis; peritoneal sarcomatosis; sarcoma ID CLEAR-CELL SARCOMA; INTERGROUP RHABDOMYOSARCOMA; CT FINDINGS; TUMORS; FEATURES; LIPOSARCOMA; MANAGEMENT; CONSENSUS AB OBJECTIVE. Peritoneal sarcomatosis is an entity analogous to the better known peritoneal carcinomatosis. The purpose of this article is to discuss the imaging findings of peritoneal sarcomatosis versus peritoneal carcinomatosis. CONCLUSION. Sarcomatosis is most commonly seen in gastrointestinal stromal tumor, liposarcoma, and leiomyosarcoma. A few distinguishing features of peritoneal sarcomatosis include heterogeneous bulky masses, hypervascularity with or without hemoperitoneum, and variable presence of ascites. C1 [Oei, Tamara N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Mellins Lib, Boston, MA 02115 USA. [Jagannathan, Jyothi P.; Ramaiya, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Ros, Pablo R.] Case Western Reserve Univ, Dept Radiol, Cleveland, OH 44106 USA. RP Oei, TN (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Mellins Lib, 75 Francis St, Boston, MA 02115 USA. EM toei@partners.org NR 24 TC 12 Z9 14 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2010 VL 195 IS 3 BP W229 EP W235 DI 10.2214/AJR.09.3907 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 642CI UT WOS:000281180500046 PM 20729420 ER PT J AU Bafford, A Gadd, M Gu, XM Lipsitz, S Golshan, M AF Bafford, Andrea Gadd, Michele Gu, Xiangmei Lipsitz, Stuart Golshan, Mehra TI Diminishing morbidity with the increased use of sentinel node biopsy in breast carcinoma SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Breast cancer; Sentinel node biopsy; complications ID ROUTINE AXILLARY DISSECTION; CANCER PATIENTS; TRIAL; COMPLICATIONS; MULTICENTER; IMMEDIATE; OUTCOMES AB BACKGROUND: Sentinel lymph node biopsy has largely replaced axillary node dissection in the staging of women with clinically negative axillas. The aim of this study was to compare the morbidity of sentinel node biopsy only, sentinel node biopsy followed by axillary dissection, and axillary node dissection only. METHODS: Retrospective review of a prospectively maintained database of patients who underwent sentinel lymph node biopsy, axillary lymph node dissection, or both between June 1996 and August 2008 was performed. The incidence of postoperative complications, including arm cellulitis, diminished shoulder range of motion, axillary hematoma, intercostal brachial nerve injury, pulmonary embolus or deep-vein thrombosis, lymphocele requiring aspiration, wound dehiscence, and wound infection, was compared among the 3 groups using Fisher's exact test. RESULTS: Of the 6,847 axillary operations performed, 2,745 (40%) were sentinel node biopsy only, 1,825 (27%) were sentinel lymph node biopsy followed by completion axillary dissection, and 2,277 (33%) were axillary dissection only. The mean node retrieval was 2 for sentinel node biopsy, 13 for sentinel node biopsy and completion axillary dissection, and 14 for axillary dissection. The mean age was 58 years. The overall complication rate was higher during the first half of the study period than during the second half (9.9% vs 3.9%, P < .0001). Axillary dissection had the highest overall complication rate (11.1%), followed by sentinel node biopsy and completion axillary dissection (7.3%), followed by sentinel node biopsy alone (2.6%) (P < .0001). Significantly less shoulder range of motion limitation, axillary hematoma, and lymphocele requiring aspiration were seen after sentinel node biopsy alone than after sentinel node biopsy plus completion axillary dissection or axillary dissection alone (P < .0001). Wound infection was also significantly less common after sentinel node biopsy than after axillary dissection (P = .02). No difference was seen in incidence of postoperative pulmonary embolus or deep-vein thrombosis, arm cellulitis, intercostal brachial nerve injury, or wound dehiscence. CONCLUSIONS: Sentinel lymph node biopsy is less morbid than sentinel node biopsy followed by completion axillary dissection and axillary node dissection alone. The morbidity of axillary surgery has decreased over time. (C) 2010 Elsevier Inc. All rights reserved. C1 [Bafford, Andrea; Gu, Xiangmei; Lipsitz, Stuart; Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Bafford, Andrea; Gu, Xiangmei; Lipsitz, Stuart; Golshan, Mehra] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gadd, Michele] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 19 TC 15 Z9 15 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD SEP PY 2010 VL 200 IS 3 BP 374 EP 377 DI 10.1016/j.amjsurg.2009.10.012 PG 4 WC Surgery SC Surgery GA 653IT UT WOS:000282083500011 PM 20409517 ER PT J AU Demicco, EG Rosenberg, AE Bjornsson, J Rybak, LD Unni, KK Nielsen, GP AF Demicco, Elizabeth G. Rosenberg, Andrew E. Bjornsson, Johannes Rybak, Leon D. Unni, K. Krishnan Nielsen, G. Petur TI Primary Rosai-Dorfman Disease of Bone A Clinicopathologic Study of 15 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Rosai-Dorfman disease; sinus histiocytosis; bone; extranodal ID NEEDLE-ASPIRATION-CYTOLOGY; SPINAL-CORD COMPRESSION; MASSIVE LYMPHADENOPATHY; SINUS HISTIOCYTOSIS; OSSEOUS LOCALIZATION; SOLE MANIFESTATION; SOLITARY LESION; INVOLVEMENT; PSEUDOTUMOR; ENTITY AB Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder of unknown etiology. Most patients present with lymph node involvement manifesting as adenopathy; however, RDD may arise primarily in a variety of extranodal sites, including bone. We report herein our experience with 15 cases of primary intraosseous RDD. The patients include 8 females and 7 males, who ranged in age from 3 to 56 (mean 27) years. The lesions arose in a variety of anatomical locations, including the tibia, femur, clavicle, skull, maxilla, calcaneus, phalanx, metacarpal, and sacrum. Radiographically, the lesions were lytic with well defined and usually sclerotic margins. Histologically, the lesions demonstrated the classic features of RDD and consisted of a mixed inflammatory infiltrate with numerous large histiocytes with abundant eosinophilic cytoplasm which exhibited emperipolesis. Some cases also contained numerous neutrophils. Immunohistochemical stains showed that the large histiocytes were S-100 positive. Follow-up information was available for 12 patients. Five patients eventually developed additional extraosseous manifestations, including testicular, lymph node, and subcutaneous lesions. One of these 5 also developed a new bony lesion within the sternum. One patient developed additional lesions within multiple bones of the hand and wrist, without extraosseous disease. One patient had stable bony lesions, whereas 5 remained disease free after treatment. C1 [Demicco, Elizabeth G.; Rosenberg, Andrew E.; Nielsen, G. Petur] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Bjornsson, Johannes; Unni, K. Krishnan] Mayo Clin, Dept Pathol, Rochester, MN USA. [Rybak, Leon D.] NYU, Dept Radiol, Hosp Joint Dis, New York, NY 10016 USA. RP Nielsen, GP (reprint author), Massachusetts Gen Hosp, Dept Pathol Warren 2, 55 Fruit St, Boston, MA 02114 USA. EM gnielsen@partners.org NR 31 TC 22 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2010 VL 34 IS 9 BP 1324 EP 1333 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 646XW UT WOS:000281579800012 PM 20679880 ER PT J AU Sangoi, AR Beck, AH Amin, MB Cheng, L Epstein, JI Hansel, DE Iczkowski, KA Lopez-Beltran, A Oliva, E Paner, GP Reuter, VE Ro, JY Shah, RB Shen, SS Tamboli, P McKenney, JK AF Sangoi, Ankur R. Beck, Andrew H. Amin, Mahul B. Cheng, Liang Epstein, Jonathan I. Hansel, Donna E. Iczkowski, Kenneth A. Lopez-Beltran, Antonio Oliva, Esther Paner, Gladell P. Reuter, Victor E. Ro, Jae Y. Shah, Rajal B. Shen, Steven S. Tamboli, Pheroze McKenney, Jesse K. TI Interobserver Reproducibility in the Diagnosis of Invasive Micropapillary Carcinoma of the Urinary Tract Among Urologic Pathologists SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE micropapillary; reproducibility; urothelial carcinoma; stromal retraction; urinary bladder ID TRANSITIONAL-CELL CARCINOMA; UROTHELIAL CARCINOMA; BLADDER-CANCER; RETRACTION ARTIFACT; CLINICAL-SIGNIFICANCE; BREAST-CARCINOMA; RENAL PELVIS; VARIANT; PATTERN; DIFFERENTIATION AB Invasive micropapillary carcinoma (IMPC) of the urinary tract is a well-described variant of the urothelial carcinoma with aggressive clinical behavior. Recent studies have proposed that patients with IMPC on transurethral resection should be treated with radical cystectomy regardless of the pathologic stage. Despite the potentially important therapeutic implications of this diagnosis, interobserver variation in the diagnosis of IMPC has not been studied. Sixty digital images, each from hematoxylin and eosin-stained slides, representing 30 invasive urothelial carcinomas (2 images per case), were distributed to 14 genitourinary subspecialists and each pathologist was requested to classify cases as IMPC or not. These cases included "classic" IMPC (n = 10) and urothelial carcinoma with retraction and variably sized nests that might potentially be regarded as IMPC (n = 20). The following 13 morphologic features were recorded as positive/negative for all cases independent of the reviewers' diagnoses: columnar cells, elongate nests or processes, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial ring forms, intracytoplasmic vacuolization, multiple nests within the same lacunar space, back-to-back lacunar spaces, epithelial nest anastomosis/confluence, marked nuclear pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, and tumor nest size. In addition, a mean tumor nest size was calculated for each image based on the number of nuclei spanning the width of the nests. Interobserver reproducibility was assessed and the morphologic features were correlated with the classic IMPC and nonclassic/potential IMPC groups. In addition, the relationships between morphologic features, pathologists' interpretations, and case type (classic IMPC vs. nonclassic/potential IMPC) were evaluated using unsupervised hierarchical clustering analysis. Interobserver reproducibility for a diagnosis of IMPC in the 30 study cases was moderate (kappa: 0.54). Although classification as IMPC among the 10 "classic" IMPC cases was relatively uniform (93% agreement), the classification in the subset of 20 invasive urothelial carcinomas with extensive retraction and varying sized tumor nests was more variable. Multiple nests within the same lacunar space had the highest association with a diagnosis of classic IMPC. These findings suggest that more study of IMPC is needed to identify the individual pathologic features that might potentially correlate with an aggressive outcome and response to intravesical therapy. C1 [Sangoi, Ankur R.] El Camino Hosp, Dept Pathol, Mountain View, CA 94040 USA. [Sangoi, Ankur R.; Beck, Andrew H.; McKenney, Jesse K.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Cheng, Liang] Indiana Univ, Sch Med, Indianapolis, IN USA. [Amin, Mahul B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Epstein, Jonathan I.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Hansel, Donna E.] Cleveland Clin, Cleveland, OH 44106 USA. [Iczkowski, Kenneth A.] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Lopez-Beltran, Antonio] Univ Cordoba, Fac Med, Anat Pathol Unit, E-14071 Cordoba, Spain. [Oliva, Esther] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Paner, Gladell P.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Reuter, Victor E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ro, Jae Y.; Shen, Steven S.] Methodist Hosp, Houston, TX 77030 USA. [Tamboli, Pheroze] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Shah, Rajal B.] Caris Diagnost, Irving, TX USA. RP Sangoi, AR (reprint author), El Camino Hosp, Dept Pathol, GC-33, Mountain View, CA 94040 USA. EM asangoi2@yahoo.com NR 43 TC 39 Z9 40 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2010 VL 34 IS 9 BP 1367 EP 1376 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 646XW UT WOS:000281579800017 PM 20717002 ER PT J AU Shapiro, R Halloran, PF Delmonico, FL Bromberg, JS AF Shapiro, R. Halloran, P. F. Delmonico, F. L. Bromberg, J. S. TI The 'Two, One, Zero' Decision: What to Do with Suboptimal Deceased Donor Kidneys SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material C1 [Shapiro, R.] Univ Pittsburgh, Div Transplantat, Starzl Transplantat Inst, Pittsburgh, PA 15260 USA. [Halloran, P. F.] Univ Alberta, Dept Med, Alberta Transplant Appl Genom Ctr, Div Nephrol & Immunol, Edmonton, AB, Canada. [Delmonico, F. L.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Bromberg, J. S.] Mt Sinai Sch Med, Dept Surg, New York, NY USA. [Bromberg, J. S.] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY USA. [Bromberg, J. S.] Mt Sinai Sch Med, Inst Immunol, New York, NY USA. [Bromberg, J. S.] Mt Sinai Sch Med, Recanati Miller Transplantat Inst, New York, NY USA. RP Shapiro, R (reprint author), Univ Pittsburgh, Div Transplantat, Starzl Transplantat Inst, Pittsburgh, PA 15260 USA. EM shapiror@upmc.edu RI Halloran, Philip/J-1390-2012 OI Halloran, Philip/0000-0003-1371-1947 NR 3 TC 20 Z9 20 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2010 VL 10 IS 9 BP 1959 EP 1960 DI 10.1111/j.1600-6143.2010.03204.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 643PD UT WOS:000281309400003 PM 20645944 ER PT J AU Coviello, DM Cornish, JW Lynch, KG Alterman, AI O'Brien, CP AF Coviello, Donna M. Cornish, James W. Lynch, Kevin G. Alterman, Arthur I. O'Brien, Charles P. TI A Randomized Trial of Oral Naltrexone for Treating Opioid-Dependent Offenders SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID HEALTH-CARE PROFESSIONALS; ADDICTION SEVERITY INDEX; CLINICAL-EXPERIENCE; HEROIN-ADDICTION; FOLLOW-UP; NARCOTIC-ANTAGONIST; MATCHING ALCOHOLICS; METHADONE PATIENTS; MAINTENANCE; PHARMACOTHERAPY AB Offenders with a history of opioid dependence are a particularly difficult group to treat. A large proportion of offenders typically relapse shortly after release from prison, commit drug-related crimes, and then are arrested and eventually re-incarcerated. Previous research demonstrated that oral naltrexone was effective in reducing opioid use and preventing recidivism among offenders under federal supervision. The 111 opioid-dependent offenders in this study were under various levels of supervision that included county and federal probation/parole, a treatment court, an alternative disposition program, and an intermediate punishment program. Subjects were randomly assigned to receive 6 months of either 300 mg per week of oral naltrexone plus standard psychosocial treatment as usual (n = 56) or standard psychosocial treatment as usual (TAU) without naltrexone (n = 55). While the TAU subjects who remained in treatment used more opioids than the naltrexone subjects who remained, the high dropout rate for both groups made it difficult to assess the effectiveness of naltrexone. The study provides limited support for the use of oral naltrexone for offenders who are not closely monitored by the criminal justice system. (Am J Addict 2010;00:1-11). C1 [Coviello, Donna M.; Cornish, James W.; Lynch, Kevin G.; Alterman, Arthur I.; O'Brien, Charles P.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Cornish, James W.; O'Brien, Charles P.] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Coviello, DM (reprint author), Treatment Res Ctr, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. EM coviello_d@mail.trc.upenn.edu FU NIDA NIH HHS [R01 DA012268, R01 DA012268-01A2, R01-DA-012268] NR 47 TC 20 Z9 20 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2010 VL 19 IS 5 BP 422 EP 432 DI 10.1111/j.1521-0391.2010.00070.x PG 11 WC Substance Abuse SC Substance Abuse GA 640NT UT WOS:000281059000006 PM 20716305 ER PT J AU Chakravorty, S Kuna, ST Zaharakis, N O'Brien, CP Kampman, KM Oslin, D AF Chakravorty, Subhajit Kuna, Samuel T. Zaharakis, Nikola O'Brien, Charles P. Kampman, Kyle M. Oslin, David TI Covariates of Craving in Actively Drinking Alcoholics SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PSYCHOMETRIC PROPERTIES; SOCIAL SUPPORT; NICOTINE DEPENDENCE; DOPAMINE SYNTHESIS; CUE REACTIVITY; MOOD STATES; DSM-IV; RELAPSE; NALTREXONE AB The goal of this cross-sectional study was to assess the relationship of alcohol craving with biopsychosocial and addiction factors that are clinically pertinent to alcoholism treatment. Alcohol craving was assessed in 315 treatment-seeking, alcohol dependent subjects using the Penn Alcohol Craving Scale questionnaire. Standard validated questionnaires were used to evaluate a variety of biological, addiction, psychological, psychiatric, and social factors. Individual covariates of craving included age, race, problematic consequences of drinking, heavy drinking, motivation for change, mood disturbance, sleep problems, and social supports. In a multivariate analysis (R2 = .34), alcohol craving was positively associated with mood disturbance, heavy drinking, readiness for change, and negatively associated with age. The results from this study suggest that alcohol craving is a complex phenomenon influenced by multiple factors. (Am J Addict 2010;00:1-8). C1 [Chakravorty, Subhajit; O'Brien, Charles P.; Oslin, David] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Vet Integrated Serv Network, Philadelphia, PA 19104 USA. [Chakravorty, Subhajit; Kuna, Samuel T.] Univ Penn, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. [Chakravorty, Subhajit; O'Brien, Charles P.; Kampman, Kyle M.; Oslin, David] Univ Penn, Treatment Res Ctr, Ctr Study Addict, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Philadelphia VA Med Ctr, Pulm Crit Care & Sleep Sect, Philadelphia, PA 19104 USA. [Zaharakis, Nikola] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Oslin, David] Univ Penn, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. RP Chakravorty, S (reprint author), Philadelphia VA Med Ctr, MIRECC VISN 4, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM Subhajit.Chakravorty@uphs.upenn.edu FU NIAAA NIH HHS [5R01AA014851, R01 AA014851-04, R01 AA014851-01, R01 AA014851-02, R01 AA014851, R01 AA014851-05, R01 AA014851-03] NR 62 TC 14 Z9 18 U1 6 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2010 VL 19 IS 5 BP 450 EP 457 DI 10.1111/j.1521-0391.2010.00067.x PG 8 WC Substance Abuse SC Substance Abuse GA 640NT UT WOS:000281059000009 PM 20716308 ER PT J AU Warshaw, AL AF Warshaw, Andrew L. TI Invited Commentary Four Decades Fighting Pancreatic Cancer SO AMERICAN SURGEON LA English DT Article C1 [Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Warshaw, Andrew L.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WHT506, Boston, MA 02114 USA. EM awarshaw@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD SEP PY 2010 VL 76 IS 9 BP 921 EP 924 PG 4 WC Surgery SC Surgery GA 643LD UT WOS:000281297000001 PM 20836335 ER PT J AU Ko, JY Leffert, LR AF Ko, James Y. Leffert, Lisa R. TI Paramedian Approach for Neuroaxial Anesthesia in Parturients with Scoliosis Response SO ANESTHESIA AND ANALGESIA LA English DT Letter C1 [Ko, James Y.; Leffert, Lisa R.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Div Obstetr Anesthesia, Boston, MA 02114 USA. RP Ko, JY (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Div Obstetr Anesthesia, Boston, MA 02114 USA. EM jyko@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 2010 VL 111 IS 3 BP 822 EP 822 DI 10.1213/ANE.0b013e3181e638b0 PG 1 WC Anesthesiology SC Anesthesiology GA 641SN UT WOS:000281150100042 ER PT J AU Badgett, RG Lawrence, VA Cohn, SL AF Badgett, Robert G. Lawrence, Valerie A. Cohn, Steven L. TI Variations in Pharmacology of beta-Blockers May Contribute to Heterogeneous Results in Trials of Perioperative beta-Blockade SO ANESTHESIOLOGY LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; HIGH-RISK PATIENTS; NONCARDIAC SURGERY; MYOCARDIAL-INFARCTION; RECEPTOR GENOTYPE; MULTICENTER TRIAL; VASCULAR-SURGERY; HEART-FAILURE; METOPROLOL; MORTALITY AB Background: Randomized controlled trials and meta-analyses provide conflicting guidance on the role of beta-adrenergic receptor blockers (beta-blockers) in reducing perioperative complications. We hypothesize that variability in trial results may be due in part to heterogeneous properties of beta-blockers. First, we propose that the extent of beta-blocker metabolism by cytochrome P-450 and the time available to titrate the dosage before surgery (titration time) may interact; dependence on P-450 may be most harmful when titration time is short. Second, beta-blockers vary in their selectivity for the beta-1 receptor and reduced selectivity may contribute to cerebral ischemia. Methods: We used meta-analysis and meta-regression of existing trials to explore the role of these pharmacological properties. Results: We found that both of these pharmacological factors are significantly associated with reduced efficacy of beta-blockers. Conclusions: Pharmacological properties of beta-blockers may contribute to heterogeneous trial results. Many trials have used metoprolol, which is extensively metabolized by cytochrome P450 and is less selective for the beta-1 receptor. For these two reasons, the efficacy of metoprolol to prevent perioperative cardiac complications should be compared with the efficacy of other beta-blockers. C1 [Badgett, Robert G.; Lawrence, Valerie A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Badgett, Robert G.; Lawrence, Valerie A.] Audie L Murphy Mem Vet Affairs Hosp, San Antonio, TX USA. [Cohn, Steven L.] SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA. RP Badgett, RG (reprint author), Univ Kansas, Sch Med Wichita, Dept Med, 1010 N Kansas St, Wichita, KS 67214 USA. EM rbadgett@kumc.edu OI Badgett, Robert/0000-0003-2888-3303 NR 44 TC 29 Z9 31 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2010 VL 113 IS 3 BP 585 EP 592 DI 10.1097/ALN.0b013e3181e73eea PG 8 WC Anesthesiology SC Anesthesiology GA 642WL UT WOS:000281251600012 PM 20693881 ER PT J AU Yuki, K Astrof, NS Bracken, C Soriano, SG Shimaoka, M AF Yuki, Koichi Astrof, Nathan S. Bracken, Clay Soriano, Sulpicio G. Shimaoka, Motomu TI Sevoflurane Binds and Allosterically Blocks Integrin Lymphocyte Function-associated Antigen-1 SO ANESTHESIOLOGY LA English DT Article ID I-DOMAIN; VOLATILE ANESTHETICS; STRUCTURAL BASIS; CONFORMATIONAL REGULATION; GENERAL-ANESTHETICS; HIGH-AFFINITY; LUNG INJURY; LFA-1; ISOFLURANE; PROTEIN AB Background: Volatile anesthetics have been shown to modify immune cell functions via several mechanisms, some of which have been only partially elucidated. We demonstrated that isoflurane inhibits primary leukocyte integrin lymphocyte function-associated antigen-1 (LFA-1) by binding to the allosteric cavity critical for conformational activation to its high-affinity form. It remains to be determined whether the allosteric inhibition of LFA-1 by isoflurane can be generalized to other anesthetics such as sevoflurane. Methods: The effects of sevoflurane on the ability of LFA-1 to bind to its counter-ligand, intercellular adhesion molecule-1, was studied in leukocytes by flow cytometry. To examine whether sevoflurane acts directly on LFA-1, we measured ligand-binding using beads coated with purified LFA-1 protein. To distinguish between competitive versus allosteric inhibition, we analyzed the effects of sevoflurane on both wild-type and mutant-locked high-affinity LFA-1. One-way analysis of variance was employed for statistical analysis of the data. Nuclear magnetic resonance spectroscopy was used to identify sevoflurane binding site(s). Results: Sevoflurane at clinically relevant concentrations inhibited the ligand-binding function of LFA-1 in leukocytes as well as in cell-free assays (P < 0.05). Sevoflurane blocked wild-type but not locked high-affinity LFA-1, thereby demonstrating an allosteric mode of inhibition. Nuclear magnetic resonance spectroscopy revealed that sevoflurane bound to the allosteric cavity, to which LFA-1 allosteric antagonists and isoflurane also bind. Conclusions: This study suggests that sevoflurane also blocks the activation-dependent conformational changes of LFA-1 to the high-affinity form. The allosteric mode of action exemplified by sevoflurane and isoflurane via LFA-1 might represent one of the underlying mechanisms of anesthetic-mediated immunomodulation. C1 [Shimaoka, Motomu] Childrens Hosp Boston, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yuki, Koichi; Soriano, Sulpicio G.] Childrens Hosp Boston, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Yuki, Koichi; Soriano, Sulpicio G.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Astrof, Nathan S.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Bracken, Clay] Cornell Univ, Weil Med Coll, Dept Biochem, New York, NY 10021 USA. RP Shimaoka, M (reprint author), Childrens Hosp Boston, Immune Dis Inst, Program Cellular & Mol Med, 3 Blackfan Cir,Room 3041, Boston, MA 02115 USA. EM shimaoka@idi.harvard.edu FU National Institutes of Health, Bethesda, Maryland [AI063421, HL048675, CA139444] FX Received from the Department of Anesthesiology, Perioperative and Pain Medicine, Children's Hospital Boston, Boston, Massachusetts, and the Immune Disease Institute, Boston, Massachusetts. Submitted for publication December 11, 2009. Accepted for publication May 10, 2010. Supported by grants AI063421, HL048675, and CA139444 (to Dr. Shimaoka) from the National Institutes of Health, Bethesda, Maryland. NR 58 TC 23 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2010 VL 113 IS 3 BP 600 EP 609 DI 10.1097/ALN.0b013e3181e89a77 PG 10 WC Anesthesiology SC Anesthesiology GA 642WL UT WOS:000281251600014 PM 20693879 ER PT J AU Li, HH Su, XL Yan, XB Wasserloos, K Chao, W Kaynar, AM Liu, ZQ Leikauf, GD Pitt, BR Zhang, LM AF Li, Huihua Su, Xiaoli Yan, Xuebin Wasserloos, Karla Chao, Wei Kaynar, A. Murat Liu, Zhao-Qian Leikauf, George D. Pitt, Bruce R. Zhang, Li-Ming TI Toll-like Receptor 4-Myeloid Differentiation Factor 88 Signaling Contributes to Ventilator-induced Lung Injury in Mice SO ANESTHESIOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; TIDAL VOLUME VENTILATION; NF-KAPPA-B; MECHANICAL VENTILATION; OXIDIZED PHOSPHOLIPIDS; INFLAMMATORY RESPONSE; ENDOGENOUS LIGANDS; INNATE IMMUNITY; REPERFUSION INJURY; INTERFERON-BETA AB Background: The mechanisms of ventilator-induced lung injury, an iatrogenic inflammatory condition induced by mechanical ventilation, are not completely understood. Toll-like receptor 4 (TLR4) signaling via the adaptor protein myeloid differentiation factor 88 (MyD88) is proinflammatory and plays a critical role in host immune response to invading pathogen and noninfectious tissue injury. The role of TLR4-MyD88 signaling in ventilator-induced lung injury remains incompletely understood. Methods: Mice were ventilated with low or high tidal volume (HTV), 7 or 20 ml/kg, after tracheotomy for 4 h. Con-trol mice were tracheotomized without ventilation. Lung injury was assessed by: alveolar capillary permeability to Evans blue albumin, wet/dry ratio, bronchoalveolar lavage analysis for cell counts, total proteins and cytokines, results of histopathological examination of the lung, and plasma cytokine levels. Results: Wild-type mice subjected to HTV had increased pulmonary permeability, inflammatory cell infiltration/lung edema, and interleukin-6/macrophage-inflammatory protein-2 in the lavage compared with control mice. In HTV, levels of inhibitor of kappa B alpha decreased, whereas phosphorylated extracellular signal-regulated kinases increased. TLR4 mutant and MyD88(-/-) mice showed markedly attenuated response to HTV, including less lung inflammation, pulmonary edema, cell number, protein content, and the cytokines in the lavage. Furthermore, compared with wild-type mice, both TLR4 mutant and MyD88(-/-) mice had significantly higher levels of inhibitor of kappa B alpha and reduced extracellular signal-regulated kinase phosphorylation after HTV. Conclusions: TLR4-MyD88 signaling plays an important role in the development of ventilator-induced lung injury in mice, possibly through mechanisms involving nuclear factor-kappa B and mitogen-activated protein kinase pathways. C1 [Zhang, Li-Ming] Univ Pittsburgh, Med Ctr, Dept Anesthesiol, Sch Med, Pittsburgh, PA 15213 USA. [Li, Huihua; Liu, Zhao-Qian] Cent S Univ, Inst Clin Pharmacol, Changsha, Hunan, Peoples R China. [Wasserloos, Karla; Leikauf, George D.; Pitt, Bruce R.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Chao, Wei] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Chao, Wei] Harvard Univ, Sch Med, Boston, MA USA. [Kaynar, A. Murat] Univ Pittsburgh, Dept Crit Care Med, Sch Med, Pittsburgh, PA 15213 USA. RP Zhang, LM (reprint author), Univ Pittsburgh, Med Ctr, Dept Anesthesiol, Sch Med, 200 Lothrop St,MUH N463, Pittsburgh, PA 15213 USA. EM zhangl1@anes.upmc.edu RI Li, Huihua/B-8795-2012; OI Leikauf, George/0000-0002-4514-7060; Kaynar, Ata Murat/0000-0001-8847-0450 FU National Institutes of Health (Bethesda, Maryland) [HL79456, HL077763, ES015675, HL65697]; National Heart, Lung, and Blood Institute (Bethesda, Maryland); Department of Anesthesiology, University of Pittsburgh Medical Center FX Received from the Department of Anesthesiology, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Submitted for publication January 22, 2010. Accepted for publication April 20, 2010. Supported in part by grants HL79456 (to Dr. Zhang), HL077763, ES015675 (to Dr. Leikauf), and HL65697 (to Dr. Pitt) from the National Institutes of Health (Bethesda, Maryland) and National Heart, Lung, and Blood Institute (Bethesda, Maryland), and a Seed grant from the Department of Anesthesiology, University of Pittsburgh Medical Center. Presented in part at the Annual Meeting of the American Society of Anesthesiologists, New Orleans, Louisiana, October 20, 2009. NR 59 TC 20 Z9 29 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2010 VL 113 IS 3 BP 619 EP 629 DI 10.1097/ALN.0b013e3181e89ab2 PG 11 WC Anesthesiology SC Anesthesiology GA 642WL UT WOS:000281251600016 PM 20683250 ER PT J AU Baker, K AF Baker, Keith TI Clinical Teaching Improves with Resident Evaluation and Feedback SO ANESTHESIOLOGY LA English DT Article ID ATTENDING PHYSICIANS; STUDENT-EVALUATIONS; SURGICAL FACULTY; SELF-ASSESSMENT; PERFORMANCE; RATINGS; TEACHERS; VALIDITY; MEDICINE; INSTRUCTION AB Background: The literature is mixed on whether evaluation and feedback to clinical teachers improves clinical teaching. This study sought to determine whether resident-provided numerical evaluation and written feedback to clinical teachers improved clinical teaching scores. Methods: Anesthesia residents anonymously provided numerical scores and narrative comments to faculty members who provided clinical teaching. Residents returned 19,306 evaluations between December 2000 and May 2006. Faculty members received a quantitative summary report and all narrative comments every 6 months. Residents also filled out annual residency program evaluations in which they listed the best and worst teachers in the department. Results: The average teaching score for the entire faculty rose over time and reached a plateau with a time constant of approximately 1 yr. At first, individual faculty members had average teaching scores that were numerically diverse. Over time, the average scores became more homogeneous. Faculty members ranked highest by teaching scores were also most frequently named as the best teachers. Faculty members ranked lowest by teaching scores were most frequently named as the worst teachers. Analysis of ranks, differential improvement in scores, and a decrease in score diversity effectively ruled out simple score inflation as the cause for increased scores. An increase in teaching scores was most likely due to improved teaching. Conclusions: A combination of evaluation and feedback, including comments on areas for improvement, was related to a substantial improvement in teaching scores. Clinical teachers are able to improve by using feedback from residents. C1 [Baker, Keith] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Baker, Keith] Harvard Univ, Sch Med, Boston, MA USA. RP Baker, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM khbaker@partners.org NR 34 TC 22 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2010 VL 113 IS 3 BP 693 EP 703 DI 10.1097/ALN.0b013e3181eaacf4 PG 11 WC Anesthesiology SC Anesthesiology GA 642WL UT WOS:000281251600026 PM 20693873 ER PT J AU Eikermann, M Chamberlin, NL AF Eikermann, Matthias Chamberlin, Nancy L. TI Anesthetics and Circadian Regulation: "Hands" or "Gears" of the Clock? SO ANESTHESIOLOGY LA English DT Letter ID PROPOFOL ANESTHESIA; RATS; TEMPERATURE C1 [Eikermann, Matthias] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA USA. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM meikermann@partners.org NR 5 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2010 VL 113 IS 3 BP 755 EP 756 DI 10.1097/ALN.0b013e3181eaa5ab PG 3 WC Anesthesiology SC Anesthesiology GA 642WL UT WOS:000281251600039 PM 20733397 ER PT J AU Wang, TT Kwon, HS Dai, GP Wang, RP Mijailovich, SM Moss, RL So, PTC Wedeen, VJ Gilbert, RJ AF Wang, Teresa T. Kwon, Hyuk Sang Dai, Guangping Wang, Ruopeng Mijailovich, Srboljub M. Moss, Richard L. So, Peter T. C. Wedeen, Van J. Gilbert, Richard J. TI Resolving Myoarchitectural Disarray in the Mouse Ventricular Wall with Diffusion Spectrum Magnetic Resonance Imaging SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Cardiac fiber organization; Myofilament; Diffusion spectrum MRI; Cardiomyopathy ID BINDING-PROTEIN-C; SPIN ECHOES; HYPERTROPHIC CARDIOMYOPATHY; FIELD GRADIENT; MYOCARDIUM; KNOCKOUT; ABLATION; MRI; EPICARDIUM; MECHANICS AB The myoarchitecture of the ventricular wall provides a structural template dictating tissue-scale patterns of mechanical function. We studied whether myofiber tract imaging performed with MR diffusion spectrum imaging (DSI) tractography has the capacity to resolve abnormalities of ventricular myoarchitecture in a model of congenital hypertrophic cardiomyopathy (HCM) associated with the ablation of myosin binding protein-C (MyBP-C). Homozygous MyBP-C knockout mice were generated by deletion of exons 3-10 from the endogenous MyBP-C gene. Fiber alignment in the left ventricular wall of wild type mice was depicted through DSI tractography (and confirmed by multi-slice two-photon microscopy) as a set of helical structures whose angles display a continuous transition from negative in the subepicardium to positive in the subendocardium. In contrast, the hearts obtained from the MyBP-C knockouts displayed substantial myoarchitectural disarray, characterized by a loss of voxel-to-voxel orientational coherence for fibers principally located in the mid-myocardium-subendocardium and impairment of the transmural progression of helix angles. These results substantiate the use of DSI tractography in determining myoarchitectural disarray in models of cardiomyopathy and suggest a biological association between myofilament expression, cardiac fiber alignment, and torsional rotation in the setting of congenital HCM. C1 [Gilbert, Richard J.] Caritas St Elizabeths Med Ctr, Dept Med, Boston, MA 02135 USA. [Wang, Teresa T.; Kwon, Hyuk Sang; So, Peter T. C.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Dai, Guangping; Wang, Ruopeng; Wedeen, Van J.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Mijailovich, Srboljub M.] Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. [Moss, Richard L.] Univ Wisconsin, Dept Physiol, Madison, WI 53706 USA. RP Gilbert, RJ (reprint author), Caritas St Elizabeths Med Ctr, Dept Med, 736 Cambridge St, Boston, MA 02135 USA. EM richard.gilbert@caritaschristi.org OI Mijailovich, Srboljub/0000-0003-1498-308X FU NIEHS NIH HHS [P30 ES002109] NR 43 TC 10 Z9 10 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD SEP PY 2010 VL 38 IS 9 BP 2841 EP 2850 DI 10.1007/s10439-010-0031-5 PG 10 WC Engineering, Biomedical SC Engineering GA 634PB UT WOS:000280594300005 PM 20461466 ER PT J AU Isaacson, BM Stinstra, JG MacLeod, RS Pasquina, PF Bloebaum, RD AF Isaacson, Brad M. Stinstra, Jeroen G. MacLeod, Rob S. Pasquina, Paul F. Bloebaum, Roy D. TI Developing a Quantitative Measurement System for Assessing Heterotopic Ossification and Monitoring the Bioelectric Metrics from Electrically Induced Osseointegration in the Residual Limb of Service Members SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Electrical stimulation; Finite element analysis; Heterotopic ossification; Osseointegration; Residual limb; Service members ID TOTAL HIP-ARTHROPLASTY; HEAD-INJURED ADULTS; BONE-FORMATION; TRAUMATIC AMPUTEE; RISK-FACTORS; STIMULATION; FRACTURES; FIELD; FIBROBLASTS; PROSTHESES AB Poor prosthetic fit is often the result of heterotopic ossification (HO), a frequent problem following blast injuries for returning service members. Osseointegration technology offers an advantage for individuals with significant HO and poor socket tolerance by using direct skeletal attachment of a prosthesis to the distal residual limb, but remains limited due to prolonged post-operative rehabilitation regimens. Therefore, electrical stimulation has been proposed as a catalyst for expediting skeletal attachment and the bioelectric effects of HO were evaluated using finite element analysis in 11 servicemen with transfemoral amputations. Retrospective computed tomography (CT) scans provided accurate reconstructions, and volume conductor models demonstrated the variability in residual limb anatomy and necessity for patient-specific modeling to characterize electrical field variance if patients were to undergo a theoretical osseointegration of a prosthesis. In this investigation, the volume of HO was statistically significant when selecting the optimal potential difference for enhanced skeletal fixation, since higher HO volumes required increased voltages at the periprosthetic bone (p = 0.024, r = 0.670). Results from Spearman's rho correlations also indicated that the age of the subject and volume of HO were statistically significant and inversely proportional, in which younger service members had a higher frequency of HO (p = 0.041, r = -0.622). This study demonstrates that the volume of HO and age may affect the voltage threshold necessary to improve current osseointegration procedures. C1 [Isaacson, Brad M.; Bloebaum, Roy D.] US Dept Vet Affairs, Bone & Joint Res Lab, Salt Lake City, UT 84148 USA. [Pasquina, Paul F.] Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA. [Isaacson, Brad M.; MacLeod, Rob S.; Bloebaum, Roy D.] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. [Bloebaum, Roy D.] Univ Utah, Dept Orthopaed, Salt Lake City, UT USA. [Bloebaum, Roy D.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. [Stinstra, Jeroen G.; MacLeod, Rob S.] Univ Utah, Sci Comp & Imagining Inst, Salt Lake City, UT USA. RP Bloebaum, RD (reprint author), US Dept Vet Affairs, Bone & Joint Res Lab 151F, Salt Lake City, UT 84148 USA. EM roy.bloebaum@hsc.utah.edu FU Veterans Affairs Office of Research and Development, Rehabilitation R&D Service, DVA SLC Health Care System, Salt Lake City, UT; Albert & Margaret Hofmann Chair and the Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, UT; Technology Commercialization Office, University of Utah, Salt Lake City, UT FX Gratitude is expressed to Gregory Stoddard for assistance and interpretation of statistical analysis, Darrell Swenson for support with image visualizations, and Gwenevere Shaw and Sharon Weeks for support with manuscript preparation. Grant & Financial Support: This material is based on study supported by the Veterans Affairs Office of Research and Development, Rehabilitation R&D Service, DVA SLC Health Care System, Salt Lake City, UT; the Albert & Margaret Hofmann Chair and the Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, UT; the Technology Commercialization Office, University of Utah, Salt Lake City, UT. Technical support for the simulations was provided by the Center for Integrative Biomedical Computing of Scientific Computing and Imaging Institute, and was made possible in part by software from the NIH/NCRR Center for Integrative Biomedical Computing, P41-RR12553-07. NR 56 TC 7 Z9 7 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD SEP PY 2010 VL 38 IS 9 BP 2968 EP 2978 DI 10.1007/s10439-010-0050-2 PG 11 WC Engineering, Biomedical SC Engineering GA 634PB UT WOS:000280594300016 PM 20458630 ER PT J AU Broder, JS Hamedani, AG Liu, SW Emerman, CL AF Broder, J. S. Hamedani, A. G. Liu, S. W. Emerman, C. L. TI Emergency Department Contrast Practices for Abdominal/Pelvic CT: A National Survey SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Duke Univ, Med Ctr, Durham, NC USA. Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Metrohlth Med Ctr, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S17 EP S17 PG 1 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000050 ER PT J AU Delgado, M Berg, L Montoy, J Ginde, AA Camargo, CA AF Delgado, M. Berg, L. Montoy, J. Ginde, A. A. Camargo, C. A., Jr. TI Availability of Routine HIV Screening in US Emergency Departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Stanford Kaiser Emergency Med Residency, Palo Alto, CA USA. Univ Colorado, Denver Sch Med, Aurora, CO USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S145 EP S146 PG 2 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000451 ER PT J AU Edwardsen, EA Dichter, ME Horwitz, SH Cerulli, C AF Edwardsen, E. A. Dichter, M. E. Horwitz, S. H. Cerulli, C. TI Instructional Curriculum Improves Medical Staff Understanding of the Importance for Routine Inquiry About Partner Violence and Appropriate Service Referral SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Univ Rochester, Rochester, NY USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S39 EP S40 PG 2 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000119 ER PT J AU Elmer, J Pallin, DJ Liu, S Pearson, C Chang, Y Greenberg, SM Rosand, J Goldstein, J AF Elmer, J. Pallin, D. J. Liu, S. Pearson, C. Chang, Y. Greenberg, S. M. Rosand, J. Goldstein, J. TI Prolonged Emergency Department Length of Stay Is Not Associated With Worse Neurologic Outcomes In Patients With Intracerebral Hemorrhage SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S8 EP S9 PG 2 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000024 ER PT J AU Hamedani, AG Liu, SW Brown, DF Asplin, BR Camargo, CA AF Hamedani, A. G. Liu, S. W. Brown, D. F. Asplin, B. R. Camargo, Jr C. A. TI Vertical Patient Flow, an Innovative Approach to Crowding In US Academic Emergency Departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin, Coll Med, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S60 EP S60 PG 1 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000181 ER PT J AU Helland, L Westfall, JM Camargo, CA Rogers, J Ginde, AA AF Helland, L. Westfall, J. M. Camargo, Jr C. A. Rogers, J. Ginde, A. A. TI Motivations and Barriers for Recruitment of New Emergency Medicine Residency Graduates to Rural Emergency Departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Univ Colorado, Sch Med, Aurora, CO USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Monroe Cty Hosp, Forsyth, GA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S154 EP S155 PG 2 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000480 ER PT J AU Henneman, PL Marquard, JL Fisher, DL Bleil, J Walsh, B Henneman, JP Blank, FS Higgins, A Nathanson, BH Henneman, EA AF Henneman, P. L. Marquard, J. L. Fisher, D. L. Bleil, J. Walsh, B. Henneman, J. P. Blank, F. S. Higgins, A. Nathanson, B. H. Henneman, E. A. TI Bar-Code Scanning May Reduce but Not Eliminate Medication and Patient Identification Errors In Clinical Simulation SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Tufts Baystate Med Ctr, Springfield, MA USA. Univ Massachusetts, Amherst, MA 01003 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Baystate Med Ctr, Springfield, MA USA. OptiStatim LLC, Longmeadow, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S66 EP S66 PG 1 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000199 ER PT J AU Hsia, RY Asch, SM Weiss, RE Zingmond, DS Liang, L McCreath, H Sun, BC AF Hsia, R. Y. Asch, S. M. Weiss, R. E. Zingmond, D. S. Liang, L. McCreath, H. Sun, B. C. TI County and Hospital Determinants of Ambulance Diversion SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Greater Los Angeles VA Hlth Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S93 EP S93 PG 1 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000283 ER PT J AU LeMaster, C Hoffart, N Benzer, T Chafe, T Pallin, D Schreiber, H Wang, R Schuur, J AF LeMaster, C. Hoffart, N. Benzer, T. Chafe, T. Pallin, D. Schreiber, H. Wang, R. Schuur, J. TI Implementation of the Central Venous Catheter Observer and Checklist Bundle In Emergency Departments: A Qualitative Study SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Cambridge, MA 02138 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S155 EP S155 PG 1 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000481 ER PT J AU Peacock, W Baumann, B Borczuk, P Cannon, C Chandra, A Diercks, D Kaminski, B Levy, P Nowak, R Schrock, J Varon, J AF Peacock, W. Baumann, B. Borczuk, P. Cannon, C. Chandra, A. Diercks, D. Kaminski, B. Levy, P. Nowak, R. Schrock, J. Varon, J. TI CLUE: A Comparative Effectiveness Trial of Nicardipine Versus Labetalol Use In the Emergency Department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Cleveland Clin, Cleveland, OH 44106 USA. Cooper Univ Hosp, Camden, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Kansas, Kansas City, KS USA. Duke Univ, Durham, NC USA. Univ Calif, Sacramento, CA USA. Toledo Hosp, Toledo, OH USA. Wayne State Univ, Detroit, MI USA. Henry Ford Hosp, Detroit, MI 48202 USA. Metrohlth Med Ctr, Cleveland, OH USA. St Lukes Episcopal Hosp, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S34 EP S35 PG 2 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000105 ER PT J AU Shah, S Dalal, A Smith, R Dyer, GS AF Shah, S. Dalal, A. Smith, R. Dyer, G. S. CA Partners Hlth Haiti St Marc Hosp G TI Successes and Challenges of Trauma Care During the Haitian Earthquake SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Rhode Isl Hosp, Providence, RI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S135 EP S135 PG 1 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000421 ER PT J AU Singer, A Diercks, D Hollander, JE Thode, HC Nagurney, J Peacock, W AF Singer, A. Diercks, D. Hollander, J. E. Thode, H. C., Jr. Nagurney, J. Peacock, W. TI The Association Between Self-Reported Physical Fitness and Exercise Frequency With ACS In Emergency Department Chest Pain Patients SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin, Cleveland, OH 44106 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S33 EP S33 PG 1 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000100 ER PT J AU Steptoe, AP Sullivan, AF Rogers, J Ginde, AA Camargo, CA AF Steptoe, A. P. Sullivan, A. F. Rogers, J. Ginde, A. A. Camargo, C. A., Jr. TI Factors In Recruiting and Retaining Emergency Physicians to Rural Emergency Departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Monroe Cty Hosp, Forsyth, GA USA. Univ Colorado Denver, Denver Sch Med, Aurora, CO 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S72 EP S72 PG 1 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000219 ER PT J AU Sullivan, AF Steptoe, AP Ginde, AA Camargo, CA AF Sullivan, A. F. Steptoe, A. P. Ginde, A. A. Camargo, C. A., Jr. TI A Profile of Emergency Medicine Board-Certified Physicians: 2001-2007 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Conference on American-College-of-Emergency-Physicians-Research-Forum CY SEP 28-29, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys Res Forum C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Colorado Denver, Sch Med, Aurora, CO 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2010 VL 56 IS 3 SU S BP S71 EP S71 PG 1 WC Emergency Medicine SC Emergency Medicine GA 645FY UT WOS:000281438000215 ER PT J AU Parchman, ML Zeber, JE Palmer, RF AF Parchman, Michael L. Zeber, John E. Palmer, Raymond F. TI Participatory Decision Making, Patient Activation, Medication Adherence, and Intermediate Clinical Outcomes in Type 2 Diabetes: A STARNet Study SO ANNALS OF FAMILY MEDICINE LA English DT Article DE Patient-centered care; physician-patient relations; diabetes mellitus, type 2 ID SELF-MANAGEMENT; PRIMARY-CARE; PHYSICIAN; COMMUNICATION; INERTIA; HEMOGLOBIN; PREDICTORS; ALLIANCE; MELLITUS; QUALITY AB PURPOSE Participatory decision making (PDM) is associated with improved diabetes control. We examine a causal model linking PDM to improved clinical outcomes that included patient activation and medication adherence. METHODS This observational study was conducted in 5 family physician offices. Diabetic patients were recruited by mail and by completing a study interest card at the conclusion of their office visit. Two survey questionnaires, administered 12 months apart, elicited patients' ratings of their physician's PDM style at baseline and their level of activation and medication adherence both at baseline and at follow-up. Measures of glycated hemoglobin (hemoglobin A(1c)), systolic blood pressure, and low-density lipoprotein (LDL) cholesterol were abstracted from the medical record starting 12 months before the baseline survey to 12 months after the follow-up survey. A path analysis using a structural equation model was used to test hypotheses. RESULTS We mailed questionnaires to 236 participants; 166 (70%) returned the baseline questionnaire, and 141 (80%) returned the follow-up questionnaire. Hemoglobin A(1c) levels, systolic blood pressure, and LDL cholesterol values all declined significantly, and patient activation and medication adherence improved. PDM at baseline was associated with patient activation at follow-up. Patient activation at follow-up was associated with medication adherence at follow-up, and medication adherence at follow-up was associated with change in hemoglobin A(1c) levels and LDL cholesterol values but not with systolic blood pressure. CONCLUSIONS Participatory decision making during primary care encounters by patients with type 2 diabetes resulted in improvements in hemoglobin A(1c) levels and LDL cholesterol values by improving patient activation, which in turn improved medication adherence. C1 [Parchman, Michael L.; Zeber, John E.] S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Program, San Antonio, TX 78229 USA. [Parchman, Michael L.; Palmer, Raymond F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Zeber, John E.] Scott & White Healthcare, Ctr Appl Hlth Res, Temple, TX USA. [Zeber, John E.] Cent Texan Vet Hlth Care Syst, Temple, TX USA. RP Parchman, ML (reprint author), S Texas Vet Hlth Care Syst, VERDICT 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM parchman@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU National Institutes of Health, National Institute for Diabetes, Digestive and Kidney Disorders [DK067300-02]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FX This research was supported by the National Institutes of Health, National Institute for Diabetes, Digestive and Kidney Disorders (DK067300-02); and the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service. NR 40 TC 73 Z9 75 U1 4 U2 19 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD SEP-OCT PY 2010 VL 8 IS 5 BP 410 EP 417 DI 10.1370/afm.1161 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 662JT UT WOS:000282804300005 PM 20843882 ER PT J AU Tyler, KL AF Tyler, Kenneth L. TI Progressive Multifocal Leukoencephalopathy: Can We Reduce Risk in Patients Receiving Biological Immunomodulatory Therapies? SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID JC VIRUS-DNA; MULTIPLE-SCLEROSIS; NATALIZUMAB; BRAIN; INFECTION; PROTEINS; LATENCY C1 [Tyler, Kenneth L.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80202 USA. [Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80202 USA. OI Tyler, Kenneth/0000-0003-3294-5888 NR 20 TC 21 Z9 21 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2010 VL 68 IS 3 BP 271 EP 274 DI 10.1002/ana.22185 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 644ZX UT WOS:000281421800004 PM 20818784 ER PT J AU Feinberg, S Lopez-Guerra, G Zeitels, SM AF Feinberg, Steven Lopez-Guerra, Gerardo Zeitels, Steven M. TI Hypopharyngeal Extrusion of 2.5 Feet (76 cm) of Polytetrafluoroethylene (Gore-Tex): Initial Laser-Assisted Office-Based Removal and Micropharyngeal Completion SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the American-Broncho-Esophagological-Association CY MAY 28-29, 2009 CL Phoenix, AZ SP Amer Broncho Esophagol Assoc DE Gore-Tex; KTP laser; laryngoplasty; larynx; laser; polytetrafluoroethylene; vocal cord; vocal cord paralysis; vocal fold ID MEDIALIZATION LARYNGOPLASTY; FIBER AB Extrusion of an implant after medialization laryngoplasty is unusual and warrants removal. Most commonly, it extrudes through the laryngeal introitus, but rarely, it extrudes through the pyriform sinus. A case report in which 2.5 feet (76 cm) of polytetrafluoroethylene (Gore-Tex) was removed from an 80-year-old female patient is presented to evaluate factors that led to this surgical complication and strategies that solved the problem. Because of the patient's multiple medical problems, initial removal of the foreign body was attempted in the office with topical anesthesia. When the Gore-Tex was noted to be lodged in the laryngeal parenchyma, it was severed at the edge of the pyriform sinus to stabilize the airway. Subsequently, microlaryngoscopic-controlled completion removal was done in the operating room with general anesthesia. The patient healed uneventfully with no further sequelae. Analysis of this case illustrates a number of factors leading to a rare iatrogenic foreign body complication. Office-based removal of the Gore-Tex implant evolved into a unique scenario in which the rapid use of a fiber-based laser to divide the foreign body facilitated stabilizing the airway to allow for elective completion removal in a controlled fashion. C1 [Feinberg, Steven; Lopez-Guerra, Gerardo; Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Lopez-Guerra, Gerardo; Zeitels, Steven M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 2010 VL 119 IS 9 BP 573 EP 577 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 648TA UT WOS:000281715800001 PM 21033022 ER PT J AU Stepp, CE Heaton, JT Jette, ME Burns, JA Hillman, RE AF Stepp, Cara E. Heaton, James T. Jette, Marie E. Burns, James A. Hillman, Robert E. TI Neck Surface Electromyography as a Measure of Vocal Hyperfunction Before and After Injection Laryngoplasty SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE electromyography; injection laryngoplasty; speech acoustics; vocal hyperfunction ID MUSCLE TENSION DYSPHONIA; PARKINSON-DISEASE; THYROID-SURGERY; VOICE DISORDERS; COMPRESSION; PROTOCOL; OUTCOMES; ONSET; EMG AB Objectives: The goal of this preliminary study was to determine whether neck surface electromyography (sEMG) is sensitive to possible changes in vocal hyperfunction associated with injection laryngoplasty, particularly with respect to alterations in the degree of vocal hyperfunction. Methods: Thirteen individuals undergoing office-based injection laryngoplasty for glottal phonatory insufficiency were prospectively studied with a battery of acoustic, aerodynamic, endoscopic, and anterior neck sEMG assessments before the procedure and approximately 1 week afterward. Results: Anterior neck sEMG values were not significantly reduced (p < 0.05) after the procedure; however, perceptual ratings of strain and false vocal fold compression were both significantly reduced, reflecting a decrease in vocal hyperfunction. Conclusions: The results do not support the use of anterior neck sEMG measures to assess vocal hyperfunction, and place into question the use of some other measures (estimates of anterior-posterior supraglottic compression, quantitative measures of anterior-posterior and false vocal fold supraglottic compression, and acoustic vowel rise times) that have been considered reflective of vocal hyperfunction. C1 [Stepp, Cara E.; Heaton, James T.; Jette, Marie E.; Burns, James A.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Heaton, James T.; Burns, James A.; Hillman, Robert E.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Stepp, Cara E.; Hillman, Robert E.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA. RP Stepp, CE (reprint author), Univ Washington, Comp Sci & Engn Box 352350, Seattle, WA 98195 USA. OI Jette, Marie/0000-0003-4705-1289 FU National Institute on Deafness and Other Communication Disorders [5T32DC000038-17] FX From the Center for Laryngeal Surgery and Voice Rehabilitation, Massachusetts General Hospital (all authors), and the Department of Surgery, Harvard Medical School (Heaton, Burns, Hillman), Boston, and the Division of Health Science and Technology, Harvard-Massachusetts Institute of Technology, Cambridge (Stepp, Hillman), Massachusetts. This work was supported in part by grant 5T32DC000038-17 from the National Institute on Deafness and Other Communication Disorders. NR 26 TC 6 Z9 7 U1 1 U2 5 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 2010 VL 119 IS 9 BP 594 EP 601 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 648TA UT WOS:000281715800005 PM 21033026 ER PT J AU Wasif, N Ko, CY Farrell, J Wainberg, Z Hines, OJ Reber, H Tomlinson, JS AF Wasif, Nabil Ko, Clifford Y. Farrell, James Wainberg, Zev Hines, Oscar J. Reber, Howard Tomlinson, James S. TI Impact of Tumor Grade on Prognosis in Pancreatic Cancer: Should We Include Grade in AJCC Staging? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID SINGLE-INSTITUTION EXPERIENCE; LONG-TERM SURVIVAL; DUCTAL ADENOCARCINOMA; RESECTION; DATABASE; CHEMOTHERAPY; VALIDATION; NOMOGRAM; TRIAL AB Background. AJCC staging of pancreatic cancer (PAC) is used to determine prognosis, yet survival within each stage shows wide variation and remains unpredictable. We hypothesized that tumor grade might be responsible for some of this variation and that the addition of grade to current AJCC staging would provide improved prognostication. Methods. The Surveillance, Epidemiology, and End Results (SEER) database (1991-2005) was used to identify 8082 patients with resected PAC. The impact of grade on overall and stage-specific survival was assessed using Cox regression analysis. Variables in the model were age, sex, tumor size, lymph node status, and tumor grade. Results. For each AJCC stage, survival was significantly worse for high-grade versus low-grade tumors. On multivariate analysis, high tumor grade was an independent predictor of survival for the entire cohort (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.31-1.48) as well as for stage I (HR 1.28, 95% CI 1.07-1.54), stage IIA (HR 1.43, 95% CI 1.26-1.61), stage IIB (HR 1.38, 95% CI 1.27-1.50), stage III (HR 1.28, 95% CI 1.02-1.59), and stage IV (HR 1.58, 95% CI 1.21-2.05) patients. The addition of grade to staging results in a statistically significant survival discrimination between all stages. Conclusions. Tumor grade is an important prognostic variable of survival in PAC. We propose a novel staging system incorporating grade into current AJCC staging for pancreas cancer. The improved prognostication is more reflective of tumor biology and may impact therapy decisions and stratification of future clinical trials. C1 [Ko, Clifford Y.; Hines, Oscar J.; Reber, Howard; Tomlinson, James S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Wasif, Nabil] St Johns Hlth Ctr, John Wayne Canc Inst, Santa Monica, CA USA. [Ko, Clifford Y.; Tomlinson, James S.] Greater Los Angeles VA Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Farrell, James] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Wainberg, Zev] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol, Los Angeles, CA 90095 USA. RP Tomlinson, JS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. EM james.tomlinson@va.gov FU Gonda (Goldschmied) Research Laboratories of the John Wayne Cancer Institute at Saint John's Health Center; QVC; Fashion Footwear Association of New York Charitable Foundation (New York, NY); Margie and Robert E. Petersen Foundation (Los Angeles, CA); Los Angeles, CA; Associates for Breast and Prostate Cancer Studies (Santa Monica, CA); Family of Robert Novick (Los Angeles, CA); Ruth and Martin H. Weil Fund (Los Angeles, CA); Wrather Family Foundation (Los Alamos, CA) FX Supported by grants from the Gonda (Goldschmied) Research Laboratories of the John Wayne Cancer Institute at Saint John's Health Center. Supported by funding from QVC and the Fashion Footwear Association of New York Charitable Foundation (New York, NY), the Margie and Robert E. Petersen Foundation (Los Angeles, CA), Mrs. Lois Rosen (Los Angeles, CA), and the Associates for Breast and Prostate Cancer Studies (Santa Monica, CA). Supported by funding from the Family of Robert Novick (Los Angeles, CA), Ruth and Martin H. Weil Fund (Los Angeles, CA), and the Wrather Family Foundation (Los Alamos, CA). NR 28 TC 46 Z9 46 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD SEP PY 2010 VL 17 IS 9 BP 2312 EP 2320 DI 10.1245/s10434-010-1071-7 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 650OJ UT WOS:000281858600009 PM 20422460 ER PT J AU Stevens, LM Agnihotri, AK Khairy, P Torchiana, DF AF Stevens, Louis-Mathieu Agnihotri, Arvind K. Khairy, Paul Torchiana, David F. TI Financial Consequences of Implementing a Partner-in-Care in Cardiac Surgery SO ANNALS OF THORACIC SURGERY LA English DT Article ID CORONARY REVASCULARIZATION; MEDICARE BENEFICIARIES; CERTIFICATE; DATABASE; OUTCOMES; VOLUME; TRENDS; IMPACT AB Background. In 2003, a satellite cardiac surgery program (SAT) was implemented at an affiliated community hospital located in an area historically served by an academic medical center (AMC). This study assessed the financial consequences and the changes in case-mix that occurred at the AMC after SAT implementation. Methods. From June 2002 through December 2005, 4593 adult patients underwent cardiac operations at the AMC. Excluded were 400 patients operated on during the 4-month transition period after SAT implementation and 1210 patients living more than 35 miles from the AMC. Multivariable regression was used to compare changes in case-mix and propensity-score adjusted costs for AMC patients referred from SAT area (N(before/after) (=) 328/291) vs other patients (N(before/after =) 897/1467). Results. The SAT area referral rate decreased by 55%. Compared with other patients, AMC patients referred from the SAT area showed a greater increase in age in the second period (p = 0.013). The nursing workload and adjusted mean costs increased more for patients from the SAT area (p = 0.015 and 0.014, respectively). The hospital margin decreased in the second period for both referral areas (p < 0.001). For the patient subgroup undergoing coronary artery bypass grafting, this hospital margin decrease was greater for SAT area patients (p = 0.017). Conclusions. After implementation of SAT program, fewer patients of lower complexity came to the AMC from the SAT area, and there was a significant increase in nursing workload and costs. During this interval, hospital margin for cardiac operations decreased from both referral areas but decreased significantly more for coronary artery bypass graft patients from the SAT area. (Ann Thorac Surg 2010; 90: 805-12) (C) 2010 by The Society of Thoracic Surgeons C1 Ctr Hosp Univ Montreal, Div Cardiac Surg, Montreal, PQ, Canada. Montreal Heart Inst, Div Cardiol, Montreal, PQ H1T 1C8, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA USA. RP Torchiana, DF (reprint author), Massachusetts Gen Phys Org, 55 Fruit St,BUL 2-208, Boston, MA 02114 USA. EM dtorchiana@partners.org RI Stevens, Louis-Mathieu/E-6453-2016 OI Stevens, Louis-Mathieu/0000-0003-3372-3419 FU Canadian Institutes of Health Research's Clinical Research Initiative; Massachusetts General Hospital, Boston, Massachusetts FX We are grateful for the research assistance provided by Karen E. Lynch and the financial expertise from Benjamin S. Parson and Robert Seger. Salary support to Dr Stevens was provided by a fellowship award from the Canadian Institutes of Health Research's Clinical Research Initiative and the Rossetti Fund (Massachusetts General Hospital, Boston, Massachusetts). NR 19 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2010 VL 90 IS 3 BP 805 EP 812 DI 10.1016/j.athoracsur.2010.04.009 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 641PX UT WOS:000281142600018 PM 20732500 ER PT J AU Kozower, BD Sheng, SB O'Brien, SM Liptay, MJ Lau, CL Jones, DR Shahian, DM Wright, CD AF Kozower, Benjamin D. Sheng, Shubin O'Brien, Sean M. Liptay, Michael J. Lau, Christine L. Jones, David R. Shahian, David M. Wright, Cameron D. TI STS Database Risk Models: Predictors of Mortality and Major Morbidity for Lung Cancer Resection SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 24-27, 2010 CL Ft Lauderdale, FL SP Soc Thorac Surg ID THORACIC-SURGERY DATABASE; LENGTH-OF-STAY; MULTIPLE IMPUTATION; PULMONARY RESECTION; INDUCTION THERAPY; ADJUSTMENT MODEL; SOCIETY; THORACOTOMY; CESSATION; COMPLICATIONS AB Background. The aim of this study is to create models for perioperative risk of lung cancer resection using the STS GTDB (Society of Thoracic Surgeons General Thoracic Database). Methods. The STS GTDB was queried for all patients treated with resection for primary lung cancer between January 1, 2002 and June 30, 2008. Three separate multivariable risk models were constructed (mortality, major morbidity, and composite mortality or major morbidity). Results. There were 18,800 lung cancer resections performed at 111 participating centers. Perioperative mortality was 413 of 18,800 (2.2%). Composite major morbidity or mortality occurred in 1,612 patients (8.6%). Predictors of mortality include the following: pneumonectomy (p < 0.001), bilobectomy (p < 0.001), American Society of Anesthesiology rating (p < 0.018), Zubrod performance status (p < 0.001), renal dysfunction (p = 0.001), induction chemoradiation therapy (p = 0.01), steroids (p = 0.002), age (p < 0.001), urgent procedures (p = 0.015), male gender (p = 0.013), forced expiratory volume in one second (p < 0.001), and body mass index (p = 0.015). Conclusions. Thoracic surgeons participating in the STS GTDB perform lung cancer resections with a low mortality and morbidity. The risk-adjustment models created have excellent performance characteristics and identify important predictors of mortality and major morbidity for lung cancer resections. These models may be used to inform clinical decisions and to compare risk-adjusted outcomes for quality improvement purposes. (Ann Thorac Surg 2010;90:875-83) (C) 2010 by The Society of Thoracic Surgeons C1 [Kozower, Benjamin D.] Univ Virginia Hlth Syst, Dept Surg, Charlottesville, VA 22908 USA. Univ Virginia Hlth Syst, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. Duke Univ, Duke Clin Res Inst, Durham, NC USA. Rush Univ, Dept Cardiovasc & Thorac Surg, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. RP Kozower, BD (reprint author), Univ Virginia Hlth Syst, Dept Surg, POB 800679, Charlottesville, VA 22908 USA. EM bdk8g@virginia.edu RI O'Brien, Sean/H-6268-2013 FU AHRQ HHS [K08-HS18049] NR 32 TC 116 Z9 118 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2010 VL 90 IS 3 BP 875 EP 881 DI 10.1016/j.athoracsur.2010.03.115 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 641PX UT WOS:000281142600030 PM 20732512 ER PT J AU Shapiro, M Swanson, SJ Wright, CD Chin, C Sheng, SB Wisnivesky, J Weiser, TS AF Shapiro, Mark Swanson, Scott J. Wright, Cameron D. Chin, Cynthia Sheng, Shubin Wisnivesky, Juan Weiser, Todd S. TI Predictors of Major Morbidity and Mortality After Pneumonectomy Utilizing The Society for Thoracic Surgeons General Thoracic Surgery Database SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 24-27, 2010 CL Ft Lauderdale, FL SP Soc Thorac Surg ID CELL LUNG-CANCER; 30-DAY OPERATIVE MORTALITY; RISK-ADJUSTMENT MODEL; INDUCTION CHEMOTHERAPY; ELECTIVE PNEUMONECTOMY; COMPLICATIONS; RESECTION; DISEASE; MANAGEMENT; THERAPY AB Background. Pneumonectomy is associated with a significant incidence of perioperative morbidity and mortality. The purpose of this study is to identify the risk factors responsible for adverse outcomes in patients after pneumonectomy utilizing The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTDB). Methods. All patients who had undergone pneumonectomy between January 2002 and December 2007 were identified in the STS GTDB. Among 80 participating centers, 1,267 patients were selected. Logistic regression analysis was performed on preoperative variables for major adverse outcomes. Results. The rate of major adverse perioperative events was 30.4%, including 71 patients who died (5.6%). Major morbidity was defined as pneumonia, adult respiratory distress syndrome, empyema, sepsis, bronchopleural fistula, pulmonary embolism, ventilatory support beyond 48 hours, reintubation, tracheostomy, atrial or ventricular arrhythmias requiring treatment, myocardial infarct, reoperation for bleeding, and central neurologic event. Patients with major morbidity had a longer mean length of stay compared with patients without major morbidity (13.3 versus 6.1 days, p < 0.001). Independent predictors of major adverse outcomes were age 65 years or older (p < 0.001), male sex (p = 0.026), congestive heart failure (p = 0.04), forced expiratory volume in 1 second less than 60% of predicted (p = 0.01), benign lung disease (p = 0.006), and requiring extrapleural pneumonectomy (p = 0.018). Among patients with lung carcinoma, those receiving neoadjuvant chemoradiotherapy were more at risk for major morbidity than patients without induction therapy (p = 0.049). Conclusions. The mortality rate after pneumonectomy by thoracic surgeons participating in the STS database compares favorably to that in previously published studies. We identified risk factors for major adverse outcomes in patients undergoing pneumonectomy. C1 Mt Sinai Med Ctr, Dept Surg, New York, NY 10029 USA. Mt Sinai Med Ctr, Div Thorac Surg, New York, NY 10029 USA. Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. RP Weiser, TS (reprint author), Mt Sinai Med Ctr, Dept Cardiothorac Surg, 1190 5th Ave,Box 1028, New York, NY 10029 USA. EM todd.weiser@mountsinai.org NR 33 TC 70 Z9 71 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2010 VL 90 IS 3 BP 927 EP 934 DI 10.1016/j.athoracsur.2010.05.041 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 641PX UT WOS:000281142600041 PM 20732520 ER PT J AU Huang, L Huang, YY Mroz, P Tegos, GP Zhiyentayev, T Sharma, SK Lu, Z Balasubramanian, T Krayer, M Ruzie, C Yang, E Kee, HL Kirmaier, C Diers, JR Bocian, DF Holten, D Lindsey, JS Hamblin, MR AF Huang, Liyi Huang, Ying-Ying Mroz, Pawel Tegos, George P. Zhiyentayev, Timur Sharma, Sulbha K. Lu, Zongshun Balasubramanian, Thiagarajan Krayer, Michael Ruzie, Christian Yang, Eunkyung Kee, Hooi Ling Kirmaier, Christine Diers, James R. Bocian, David F. Holten, Dewey Lindsey, Jonathan S. Hamblin, Michael R. TI Stable Synthetic Cationic Bacteriochlorins as Selective Antimicrobial Photosensitizers SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID TARGETED PHOTODYNAMIC THERAPY; GRAM-NEGATIVE BACTERIA; CANDIDA-ALBICANS; IN-VITRO; PHOTOINACTIVATION; INACTIVATION; INFECTIONS; PORPHYRINS; CANCER; PHTHALOCYANINE AB Photodynamic inactivation is a rapidly developing antimicrobial treatment that employs a nontoxic photo-activatable dye or photosensitizer in combination with harmless visible light to generate reactive oxygen species that are toxic to cells. Tetrapyrroles (e. g., porphyrins, chlorins, bacteriochlorins) are a class of photosensitizers that exhibit promising characteristics to serve as broad-spectrum antimicrobials. In order to bind to and efficiently penetrate into all classes of microbial cells, tetrapyrroles should have structures that contain (i) one or more cationic charge(s) or (ii) a basic group. In this report, we investigate the use of new stable synthetic bacteriochlorins that have a strong absorption band in the range 720 to 740 nm, which is in the near-infrared spectral region. Four bacteriochlorins with 2, 4, or 6 quaternized ammonium groups or 2 basic amine groups were compared for light-mediated killing against a Gram-positive bacterium (Staphylococcus aureus), a Gram-negative bacterium (Escherichia coli), and a dimorphic fungal yeast (Candida albicans). Selectivity was assessed by determining phototoxicity against human HeLa cancer cells under the same conditions. All four compounds were highly active (6 logs of killing at 1 mu M or less) against S. aureus and showed selectivity for bacteria over human cells. Increasing the cationic charge increased activity against E. coli. Only the compound with basic groups was highly active against C. albicans. Supporting photochemical and theoretical characterization studies indicate that (i) the four bacteriochlorins have comparable photophysical features in homogeneous solution and (ii) the anticipated redox characteristics do not correlate with cell-killing ability. These results support the interpretation that the disparate biological activities observed stem from cellular binding and localization effects rather than intrinsic electronic properties. These findings further establish cationic bacteriochlorins as extremely active and selective near-infrared activated antimicrobial photosensitizers, and the results provide fundamental information on structure-activity relationships for antimicrobial photosensitizers. C1 [Huang, Liyi; Huang, Ying-Ying; Mroz, Pawel; Tegos, George P.; Zhiyentayev, Timur; Sharma, Sulbha K.; Lu, Zongshun; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Liyi; Huang, Ying-Ying; Mroz, Pawel; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning, Peoples R China. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Zhiyentayev, Timur] MIT, Dept Chem, Cambridge, MA 02139 USA. [Lu, Zongshun] Tianjin Med Univ, Gen Hosp, Dept Gastroenterol, Tianjin, Peoples R China. [Balasubramanian, Thiagarajan] NIRvana Pharmaceut Inc, Raleigh, NC USA. [Krayer, Michael; Ruzie, Christian; Lindsey, Jonathan S.] N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. [Yang, Eunkyung; Kee, Hooi Ling; Kirmaier, Christine; Holten, Dewey] Washington Univ, Dept Chem, St Louis, MO 63130 USA. [Diers, James R.; Bocian, David F.] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; Lindsey, Jonathan/J-7761-2012; Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875, R01GM36238]; Burroughs-Wellcome fellowship; JimmyV NCSU Cancer Therapeutics Training Program; National Institute of Allergy and Infectious Diseases [R41AI072854]; Genzyme-Partners Translational Research Grant; Massachusetts Technology Transfer Center; Division of Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences of the U.S. Department of Energy [DE-FG02-05ER15660, DE-FG02-05ER15661] FX This work was supported by grants from the NIH (R01AI050875 to M. R. H. and R01GM36238 to J.S.L.), a Burroughs-Wellcome fellowship (to M. K.), and the JimmyV NCSU Cancer Therapeutics Training Program. L. H., Y.-Y.H. and T. B. were supported by a grant (R41AI072854) from the National Institute of Allergy and Infectious Diseases to NIRvana Pharmaceuticals, Inc. P. M. was partly supported by a Genzyme-Partners Translational Research Grant. G. P. T was partly supported by a Massachusetts Technology Transfer Center Award. Characterization of the photophysical and redox properties of the bacteriochlorins described herein was initially motivated by solar-energy studies and supported by grants from the Division of Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences of the U.S. Department of Energy, to D. F. B. (DE-FG02-05ER15660) and D. H. (DE-FG02-05ER15661). NR 58 TC 67 Z9 68 U1 2 U2 30 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2010 VL 54 IS 9 BP 3834 EP 3841 DI 10.1128/AAC.00125-10 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 639WC UT WOS:000281005900044 PM 20625146 ER PT J AU Bray, D Henstrom, DK Cheney, ML Hadlock, TA AF Bray, Dominic Henstrom, Douglas K. Cheney, Mack L. Hadlock, Tessa A. TI Assessing Outcomes in Facial Reanimation: Evaluation and Validation of the SMILE System for Measuring Lip Excursion During Smiling SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Letter ID NERVE FUNCTION; QUANTIFICATION; MOVEMENT; MOTION; VIDEO C1 [Henstrom, Douglas K.; Cheney, Mack L.; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Facial Nerve Ctr, Boston, MA 02114 USA. [Bray, Dominic] Guys Hosp, Dept Otolaryngol Head & Neck Surg, London SE1 9RT, England. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Facial Nerve Ctr, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 10 TC 27 Z9 27 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD SEP-OCT PY 2010 VL 12 IS 5 BP 352 EP 354 PG 3 WC Surgery SC Surgery GA 652KP UT WOS:000282005600015 PM 20855780 ER PT J AU Khoury, SJ Healy, BC Kivisakk, P Viglietta, V Egorova, S Guttmann, CRG Wedgwood, JF Hafler, DA Weiner, HL Buckle, G Cook, S Reddy, S AF Khoury, Samia J. Healy, Brian C. Kivisakk, Pia Viglietta, Vissia Egorova, Svetlana Guttmann, Charles R. G. Wedgwood, Josiah F. Hafler, David A. Weiner, Howard L. Buckle, Guy Cook, Sandra Reddy, Susheel TI A Randomized Controlled Double-Masked Trial of Albuterol Add-on Therapy in Patients With Multiple Sclerosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GLATIRAMER ACETATE; T-CELLS; NEUROTROPHIC FACTOR; LONGITUDINAL DATA; BRAIN; INTERLEUKIN-12; DISEASE; MECHANISMS; RESPONSES AB Background:Interleukin 12 (IL-12), a cytokine that promotes generation of helper T cells subtype 1, is increased in multiple sclerosis. Albuterol sulfate, a beta 2-adrenergic agonist, reduces IL-12 expression, so we tested the effect of albuterol as an add-on treatment to glatiramer acetate therapy. Objectives: To investigate the clinical and immunologic effects of albuterol treatment as an add-on therapy in patients starting glatiramer acetate treatment. Design: Single-center double-masked clinical trial. Setting: Academic research. Patients: Subjects with relapsing-remitting multiple sclerosis. Main Outcome Measures: In this single-center double-masked clinical trial, subjects with relapsing-remitting multiple sclerosis were randomized to receive a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of placebo daily for 2 years or a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of albuterol daily for 2 years. The primary clinical efficacy measurement was the change in Multiple Sclerosis Functional Composite at 2 years, and the primary immunologic end point was the change in expression of IL-13 and interferon gamma at each study time point. The clas-sification level of evidence from this trial is C for each question, as this is the first class II clinical trial addressing the efficacy of glatiramer acetate plus albuterol. Results: Forty-four subjects were randomized to receive glatiramer acetate plus albuterol or glatiramer acetate plus placebo, and 39 subjects contributed to the analysis. Improvement in the Multiple Sclerosis Functional Composite was observed in the glatiramer acetate plus albuterol group at the 6-month (P=.005) and 12-month (P=.04) time points but not at the 24-month time point. A delay in the time to first relapse was also observed in the glatiramer acetate plus albuterol group (P=.03). Immunologically, IL-13 and interferon-gamma production decreased in both treatment groups, and a treatment effect on IL-13 production was observed at the 12-month time point (P<.05). Adverse events were generally mild, and only 3 moderate or severe events were considered related to the treatment. Conclusion: Treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis. C1 [Khoury, Samia J.; Kivisakk, Pia; Viglietta, Vissia; Hafler, David A.; Weiner, Howard L.; Buckle, Guy; Cook, Sandra] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ctr Neurol Dis, Boston, MA 02115 USA. [Egorova, Svetlana; Guttmann, Charles R. G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Ctr Neurol Imaging, Boston, MA 02115 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Wedgwood, Josiah F.] NIAID, NIH, Bethesda, MD 20892 USA. [Reddy, Susheel] Rho Inc, Chapel Hill, NC USA. RP Khoury, SJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ctr Neurol Dis, Room 710,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM skhoury@rics.bwh.harvard.edu OI khoury, samia/0000-0003-3198-6063 FU National Institute of Allergy and Infectious Diseases [U19A1046130]; EpiVax; LifeCycle Pharmaceutical; PDL; BioPharma; Repligen; Wyeth Pharmaceuticals; Allozyne, Inc; EISAI Research Institute; Xceed Molecular Corporation; Actelion; AutoImmune; Biogen Idec; EMD Serono; Enzo; Gen-. entech; Teva Neuroscience; Vascular Biogenics; Millennium Pharmaceuticals; Bayer; Pfizer FX This study was supported in part by Autoimmunity Center of Excellence Study grant U19A1046130 from the National Institute of Allergy and Infectious Diseases (Dr Khoury).; Dr Khoury has received consulting or lecture fees from EpiVax, LifeCycle Pharmaceutical, PDL, BioPharma, Repligen, and Wyeth Pharmaceuticals. Dr Hafler has received consulting or lecture fees from Allozyne, Inc, EISAI Research Institute, Xceed Molecular Corporation, and Actelion. Dr Weiner has received consulting or lecture fees from AutoImmune, Biogen Idec, EMD Serono, Enzo, Gen-. entech, Teva Neuroscience, and Vascular Biogenics and has received grant support from Millennium Pharmaceuticals. Dr Buckle has received consulting or lecture fees from Bayer, Biogen Idec, EMD Serono, Pfizer, and Teva Neuroscience. NR 32 TC 20 Z9 21 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 2010 VL 67 IS 9 BP 1055 EP 1061 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 653OW UT WOS:000282102800002 PM 20837847 ER PT J AU Wecht, JM Rosado-Rivera, D Handrakis, JP Radulovic, M Bauman, WA AF Wecht, Jill M. Rosado-Rivera, Dwindally Handrakis, John P. Radulovic, Miroslav Bauman, William A. TI Effects of Midodrine Hydrochloride on Blood Pressure and Cerebral Blood Flow During Orthostasis in Persons With Chronic Tetraplegia SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Congress of Spinal Cord Medicine and Rehabilitation CY SEP 24, 2009 CL Dallas, TX DE Hypotension, orthostatic; Midodrine; Rehabilitation; Spinal cord injuries; Tilt-table test ID SPINAL-CORD-INJURY; COGNITIVE PERFORMANCE; TRANSCRANIAL DOPPLER; ESSENTIAL HYPOTENSION; DOUBLE-BLIND; MEN; EJACULATION; PLACEBO; STIMULATION; ENHANCEMENT AB Wecht JM, Rosado-Rivera D, Handrakis JP, Radulovic M. Bauman WA. Effects of midodrine hydrochloride on blood pressure and cerebral blood flow during orthostasis in persons with chronic tetraplegia. Arch Phys Med Rehabil 2010;91:1429-35. Objective: To determine the mean arterial pressure (MAP) and middle cerebral artery mean blood flow velocity (MFV) responses to 5 and 10mg midodrine during head-up tilt (HUT) in persons with tetraplegia. Design: Prospective dose-response trial. Setting: James J. Peters Veterans Administration Medical Center. Participants: Persons (N=10) with chronic tetraplegia (duration of injury = 23 +/- 11y). Intervention: A dose titration study was performed over 3 testing days: control (no drug), 5mg midodrine (5mg), or 10mg midodrine (10mg) during 30 minutes of baseline (predrug/no drug), 30 minutes of supine rest postdrug/no drug, 15 minutes of progressive HUT (5 minutes at 15 degrees, 25 degrees, 35 degrees), and 45 minutes of 45 degrees HUT. Main Outcome Measures: MAP and MFV response to midodrine supine and during HUT. Results: Ten milligrams of midodrine significantly increased MAP while supine and during the HUT maneuver. Of note, the mean increase in MAP during HUT with 10mg was a result of a robust effect in 2 persons, with minimal change in the remaining 8 study subjects. The reduction in cerebral MFV during HUT was attenuated with 10mg. Conclusions: These findings suggest that midodrine 10mg may be efficacious for treatment of hypotension and orthostatic hypotension in select persons with tetraplegia. Although midodrine is routinely prescribed to treat orthostatic hypotension, the results of our work suggests limited efficacy of this agent, but additional studies in a larger sample of subjects with spinal cord injury should be performed. C1 [Wecht, Jill M.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Wecht, Jill M.; Rosado-Rivera, Dwindally; Handrakis, John P.; Radulovic, Miroslav; Bauman, William A.] Mt Sinai Sch Med, Ctr Excellence, New York, NY USA. [Wecht, Jill M.; Radulovic, Miroslav; Bauman, William A.] Mt Sinai Sch Med, Med Serv, New York, NY USA. [Wecht, Jill M.; Radulovic, Miroslav; Bauman, William A.] NYIT, Dept Med, Old Westbury, NY USA. [Wecht, Jill M.; Radulovic, Miroslav; Bauman, William A.] NYIT, Dept Rehabil Med, Old Westbury, NY USA. [Handrakis, John P.] NYIT, Sch Hlth Profess, Old Westbury, NY USA. RP Wecht, JM (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM JM.WECHT@VA.GOV NR 43 TC 14 Z9 14 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 2010 VL 91 IS 9 BP 1429 EP 1435 DI 10.1016/j.apmr.2010.06.017 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 651IM UT WOS:000281921400018 PM 20801263 ER PT J AU Ingraham, AM Cohen, ME Bilimoria, KY Ko, CY Hall, BL Russell, TR Nathens, AB AF Ingraham, Angela M. Cohen, Mark E. Bilimoria, Karl Y. Ko, Clifford Y. Hall, Bruce L. Russell, Thomas R. Nathens, Avery B. TI Effect of Delay to Operation on Outcomes in Adults With Acute Appendicitis SO ARCHIVES OF SURGERY LA English DT Article ID SURGICAL CARE; APPENDECTOMY; SURGERY; QUALITY; TRIAL; NIGHT; NSQIP; RISK AB Objective: To examine the effect of delay from surgical admission to induction of anesthesia on outcomes after appendectomy for acute appendicitis in adults. Design: Retrospective cohort study with the principal exposure being time to operation. Regression models yielded probabilities of outcomes adjusted for patient and operative risk factors. Setting: Data were submitted to the American College of Surgeons National Surgical Quality Improvement Program database from January 1, 2005, through December 31, 2008. Patients: Patients with acute appendicitis who underwent an appendectomy. Main Outcome Measures: Thirty-day overall morbidity and serious morbidity/mortality. Results: Of 32 782 patients, 24 647 (75.2%) underwent operations within 6 hours of surgical admission, 4934(15.1%) underwent operations more than 6 through 12 hours, and 3201 (9.8%) underwent operations more than 12 hours after surgical admission. Differences in operative duration (51, 50, and 55 minutes, respectively; P<.001) were statistically significant but not clinically meaningful. The length of postoperative stay (2.2 days for the >12-hour group vs 1.8 days for the remaining groups; P<.001) was statistically significant but not clinically meaningful. No significant differences were found in adjusted overall morbidity (5.5%, 5.4%, and 6.1%, respectively; P=.33) or serious morbidity/mortality (3.0%, 3.6%, and 3.0%, respectively; P=.17). Duration from surgical admission to induction of anesthesia was not predictive in regression models for overall morbidity or serious morbidity/mortality. Conclusions: In this retrospective study, delay of appendectomy for acute appendicitis in adults does not appear to adversely affect 30-day outcomes. This information can guide the use of potentially limited operative and professional resources allocated for emergency care. C1 [Ingraham, Angela M.; Cohen, Mark E.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Ingraham, Angela M.] Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hall, Bruce L.] Washington Univ, Sch Med, Dept Surg, John Cochran Vet Affairs Med Ctr, St Louis, MO 63110 USA. [Hall, Bruce L.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO 63110 USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO 63110 USA. [Russell, Thomas R.] Univ Calif San Francisco, Div Surg, San Francisco, CA 94143 USA. [Nathens, Avery B.] St Michaels Hosp, Div Surg & Trauma, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. 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 FU American College of Surgeons; Northwestern University; Canada Research Chair in Systems of Trauma Care; Center for Health Policy, Washington University in St Louis FX Dr Ingraham is supported by the Clinical Scholar in Residence Program at the American College of Surgeons. Dr Bilimoria is supported by a Priority Grant from Northwestern University. Dr Nathens is supported by a Canada Research Chair in Systems of Trauma Care. Dr Hall is supported by the Center for Health Policy, Washington University in St Louis. NR 23 TC 47 Z9 49 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD SEP PY 2010 VL 145 IS 9 BP 886 EP 892 PG 7 WC Surgery SC Surgery GA 649JH UT WOS:000281764400020 PM 20855760 ER PT J AU Liao, S Padera, TP Jain, RK AF Liao, Shan Padera, Timothy P. Jain, Rakesh K. TI Notch Leads Lymphatics and Links Them to Blood Vessels SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Editorial Material DE Notch; lymphatic; blood vessel; embryogenesis ID ENDOTHELIAL-CELLS; LYMPHANGIOGENESIS; PLASTICITY; EXPRESSION C1 [Liao, Shan; Padera, Timothy P.; Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,EL Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,EL Steele Lab Tumor Biol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI Padera, Timothy/0000-0002-3453-9384 FU NCI NIH HHS [R01 CA085140-10, K99 CA137167, K99 CA137167-02, K99-CA137167, P01 CA080124, P01 CA080124-10, P01-CA080124, R00 CA137167, R01 CA085140, R01 CA115767, R01 CA115767-05, R01 CA126642, R01 CA126642-04, R01-CA085140, R01-CA115767, R01-CA126642] NR 15 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 2010 VL 30 IS 9 BP 1682 EP 1683 DI 10.1161/ATVBAHA.110.210633 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 641NX UT WOS:000281135900002 PM 20720193 ER PT J AU Feng, J Damrauer, SM Lee, M Sellke, FW Ferran, C Abid, MR AF Feng, Jun Damrauer, Scott M. Lee, Monica Sellke, Frank W. Ferran, Christiane Abid, Md Ruhul TI Endothelium-Dependent Coronary Vasodilatation Requires NADPH Oxidase-Derived Reactive Oxygen Species SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE coronary artery disease; endothelial function; nitric oxide; reactive oxygen species; signal transduction; NADPH oxidase ID SMOOTH-MUSCLE-CELLS; VASCULAR-PERMEABILITY FACTOR; GROWTH-FACTOR; NITRIC-OXIDE; ANGIOTENSIN-II; S-NITROSYLATION; SIGNALING PATHWAYS; CRITICAL COMPONENT; NAD(P)H OXIDASE; ARTERY-DISEASE AB Objective-To determine the functional significance of physiological reactive oxygen species (ROS) levels in endothelium-dependent nitric oxide (NO)-mediated coronary vasodilatation. Methods and Results-Endothelium-derived NO is important in regulating coronary vascular tone. Excess ROS have been shown to reduce NO bioavailability, resulting in endothelial dysfunction and coronary diseases. NADPH oxidase is a major source of ROS in endothelial cells (ECs). By using lucigenin-based superoxide production and dichlorfluorescein diacetate (DCFH-DA) fluorescence-activated cell sorter assays, we found that mouse heart ECs from NADPH oxidase-knockdown (p47(phox-/-)) animals have reduced NADPH oxidase activity (>40%) and ROS levels (>30%) compared with wild-type mouse heart ECs. Surprisingly, a reduction in ROS did not improve coronary vasomotion; rather, endothelium-dependent vascular endothelial growth factor-mediated coronary vasodilatation was reduced by greater than 50% in p47(phox-/-) animals. Western blots and L-citrulline assays showed a significant reduction in Akt/protein kinase B (PKB) and endothelial NO synthase phosphorylation and NO synthesis, respectively, in p47(phox-/-) coronary vessels and mouse heart ECs. Adenoviral expression of constitutively active endothelial NO synthase restored vascular endothelial growth factor-mediated coronary vasodilatation in p47(phox-/-) animals. Conclusion-Endothelium-dependent vascular endothelial growth factor regulation of coronary vascular tone may require NADPH oxidase-derived ROS to activate phosphatidylinositol 3-kinase-Akt-endothelial NO synthase axis. (Arterioscler Thromb Vasc Biol. 2010; 30: 1703-1710.) C1 [Lee, Monica; Abid, Md Ruhul] Beth Israel Deaconess Med Ctr, Dept Med, Vasc Biol Res Ctr, Boston, MA 02215 USA. [Feng, Jun; Damrauer, Scott M.; Sellke, Frank W.; Ferran, Christiane] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Feng, Jun; Sellke, Frank W.] Brown Univ, Alpert Sch Med, Providence, RI 02912 USA. [Damrauer, Scott M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Abid, Md Ruhul] Harvard Univ, Sch Med, Boston, MA USA. RP Abid, MR (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Vasc Biol Res Ctr, RN-232,330 Brookline Ave, Boston, MA 02215 USA. EM rabid@bidmc.harvard.edu FU American Heart Association [SDG 0453284N, 10GRNT3640011]; National Institutes of Health [5T32HL007734-14, HL-46716, HL-69024, HL080130] FX This study was supported by grants SDG 0453284N and 10GRNT3640011 from the American Heart Association (Dr Abid); and also in part by grants 5T32HL007734-14 (Dr Damrauer), HL-46716 and HL-69024 (Dr Sellke), and HL080130 (Dr Ferran) from the National Institutes of Health. NR 69 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 2010 VL 30 IS 9 BP 1703 EP U74 DI 10.1161/ATVBAHA.110.209726 PG 13 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 641NX UT WOS:000281135900006 PM 20702812 ER PT J AU Lieb, W Gona, P Larson, MG Massaro, JM Lipinska, I Keaney, JF Rong, JA Corey, D Hoffmann, U Fox, CS Vasan, RS Benjamin, EJ O'Donnell, CJ Kathiresan, S AF Lieb, Wolfgang Gona, Philimon Larson, Martin G. Massaro, Joseph M. Lipinska, Izabella Keaney, John F., Jr. Rong, Jian Corey, Diane Hoffmann, Udo Fox, Caroline S. Vasan, Ramachandran S. Benjamin, Emelia J. O'Donnell, Christopher J. Kathiresan, Sekar TI Biomarkers of the Osteoprotegerin Pathway Clinical Correlates, Subclinical Disease, Incident Cardiovascular Disease, and Mortality SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE coronary heart disease; vascular biology; osteoprotegerin; receptor activator of nuclear factor-kappa B ligand ID SERUM OSTEOPROTEGERIN; CORONARY-ARTERY; VASCULAR CALCIFICATION; RECEPTOR ACTIVATOR; DEFICIENT MICE; BONE-DENSITY; RANKL; LIGAND; RISK; OSTEOPOROSIS AB Objective-Experimental evidence identified the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL) pathway as a candidate system modulating vascular remodeling and cardiovascular disease (CVD). Methods and Results-Serum concentrations of OPG and RANKL were measured in 3250 Framingham Study participants (54% women, 61 +/- 9 years). During a mean follow-up of 4.6 years, 143 (of 3084 free of CVD at baseline) participants developed a first CVD event, and 235 died. In multivariable models, OPG was associated with increased hazards for incident CVD and mortality (hazard ratio, 1.27; 95% CI, 1.04 to 1.54; and hazard ratio, 1.25; 95% CI, 1.07 to 1.47, per 1-SD increment in log-OPG, respectively). Log-OPG was positively related to multiple CVD risk factors, including age, smoking, diabetes, systolic blood pressure, and prevalent CVD. In a subsample (n=1264), the prevalence of coronary artery calcification, measured by computed tomography, increased nonsignificantly with OPG quartiles. RANKL concentrations displayed inverse associations with multiple CVD risk factors, including smoking, diabetes, and antihypertensive treatment, and were not related to coronary artery calcification or incident CVD or mortality. Conclusion-Our prospective data reinforce OPG as marker for CVD risk factor burden and predictor for CVD and mortality in the community. (Arterioscler Thromb Vasc Biol. 2010; 30: 1849-1854.) C1 [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lieb, Wolfgang; Gona, Philimon; Larson, Martin G.; Massaro, Joseph M.; Rong, Jian; Corey, Diane; Fox, Caroline S.; Vasan, Ramachandran S.; Benjamin, Emelia J.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol, Boston, MA 02115 USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Gona, Philimon; Larson, Martin G.; Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Prevent Med & Epidemiol Sect, Boston, MA 02215 USA. [Lipinska, Izabella; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [O'Donnell, Christopher J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA. EM skathiresan@partners.org RI Lieb, Wolfgang/C-1990-2012; OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; Doris Duke Charitable Foundation; [R01-HL076784]; [1R01-AG028321]; [R01-HL064753] FX This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195) and by R01-HL076784, 1R01-AG028321, and R01-HL064753 (to E.J.B.). Dr Kathiresan was funded by a Clinical Scientist Development Award from the Doris Duke Charitable Foundation and by a Mentored Patient-Oriented Research Career Development Award from the National Heart, Lung, and Blood Institute. NR 27 TC 70 Z9 76 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 2010 VL 30 IS 9 BP 1849 EP U386 DI 10.1161/ATVBAHA.109.199661 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 641NX UT WOS:000281135900025 PM 20448212 ER PT J AU Dhingra, R Gona, P Wang, TJ Fox, CS D'Agostino, RB Vasan, RS AF Dhingra, Ravi Gona, Philimon Wang, Thomas J. Fox, Caroline S. D'Agostino, Ralph B., Sr. Vasan, Ramachandran S. TI Serum gamma-Glutamyl Transferase and Risk of Heart Failure in the Community SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE epidemiology; heart failure; risk factors; oxidative stress; gamma-glutamyl transferase ID CORONARY MICROVASCULAR FUNCTION; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; GENERAL-POPULATION; METABOLIC SYNDROME; OXIDATIVE STRESS; PROGNOSTIC VALUE; BLOOD-PRESSURE; TRANSPEPTIDASE AB Objective-To examine the association of serum gamma-glutamyltransferase (GGT) with incident heart failure. Methods and Results-We related serum GGT to the incidence of heart failure in 3544 (mean age, 44.5 years; 1833 women and 1711 men) Framingham Study participants who were free of heart failure and myocardial infarction. On follow-up (mean, 23.6 years), 188 participants (77 women) developed new-onset heart failure. In multivariable Cox proportional hazards regression models adjusting for standard risk factors and alcohol consumption as time-varying covariates (updated every 4 years), each SD increase in log-GGT was associated with a 1.39-fold risk of heart failure (95% CI, 1.20 to 1.62). The linearity of the association was confirmed by multivariable-adjusted splines, and the relations remained robust on additional adjustment for hepatic aminotransferases and C-reactive protein. Participants with a serum GGT level at the median or greater had a 1.71-fold risk of heart failure (95% CI, 1.21 to 2.41) compared with individuals with GGT concentrations less than the median. GGT marginally increased the model C-statistic from 0.85 to 0.86 but improved the risk reclassification modestly (net reclassification index, 5.7%; P = 0.01). Conclusion-In this prospective study of a large community-based sample, higher serum GGT concentrations within the "normal" range were associated with greater risk of heart failure and incrementally improved prediction of heart failure risk. (Arterioscler Thromb Vasc Biol. 2010;30:1855-1860.) C1 [Dhingra, Ravi; Wang, Thomas J.; Fox, Caroline S.; D'Agostino, Ralph B., Sr.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Dhingra, Ravi] Dartmouth Hitchcock Med Ctr, Div Cardiol, Lebanon, NH 03766 USA. [Dhingra, Ravi] Harvard Univ, Sch Publ Hlth, Masters Publ Hlth Program, Boston, MA 02115 USA. [Gona, Philimon; D'Agostino, Ralph B., Sr.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Fox, Caroline S.] NHLBI, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Max, Mad/E-5238-2010; OI Max, Mad/0000-0001-6966-6829; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [N01-HC-25195, N01HV28178, R01HL71039, R01HL67288] FX This study was supported by contracts N01-HC-25195, N01HV28178 (Dr Vasan), R01HL71039 (Dr Vasan), and R01HL67288 (Dr Vasan) from the National Heart, Lung, and Blood Institute's Framingham Heart Study. NR 40 TC 30 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 2010 VL 30 IS 9 BP 1855 EP 1860 DI 10.1161/ATVBAHA.110.207340 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 641NX UT WOS:000281135900026 PM 20539015 ER PT J AU Ike, R Arnold, E Arnold, W Craig-Muller, J Kaeley, G McAlindon, T Nazarian, L Reginato, A AF Ike, Robert Arnold, Erin Arnold, William Craig-Muller, Jurgen Kaeley, Gurjit McAlindon, Timothy Nazarian, Levon Reginato, Antonio CA Amer Coll Rheumatology TI Ultrasound in American Rheumatology Practice: Report of the American College of Rheumatology Musculoskeletal Ultrasound Task Force SO ARTHRITIS CARE & RESEARCH LA English DT Article ID POWER DOPPLER SONOGRAPHY; INTRAARTICULAR STEROID INJECTION; JUVENILE IDIOPATHIC ARTHRITIS; AAPM/RSNA PHYSICS TUTORIAL; CLINICAL EXAMINATION; GREY-SCALE; FOLLOW-UP; ULTRASONOGRAPHIC ASSESSMENT; METACARPOPHALANGEAL JOINTS; CONVENTIONAL RADIOGRAPHY C1 [Ike, Robert] Univ Michigan Hlth Syst, Dept Internal Med, Div Rheumatol, Ann Arbor, MI 48109 USA. [Arnold, Erin; Arnold, William] Illinois Bone & Joint Inst, Morton Grove, IL USA. [Craig-Muller, Jurgen] CentraCare Clin, St Cloud, MN USA. [Kaeley, Gurjit] Univ Florida, Gainesville, FL USA. [McAlindon, Timothy] Tufts Med Ctr, Boston, MA USA. [Nazarian, Levon] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Reginato, Antonio] Brown Univ, Boston, MA USA. [Reginato, Antonio] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ike, R (reprint author), Univ Michigan Hlth Syst, Dept Internal Med, Div Rheumatol, 1500 E Med Ctr Dr,3918 Taubman Ctr, Ann Arbor, MI 48109 USA. EM rike@umich.edu FU Biosound Esaote and Sonosite; Robert Wood Johnson Foundation; UCB; URL Pharma; Centocor; Genzyme; Takeda FX Dr. Ike has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Genzyme. Dr. Craig-Muller is employed by CentraCare Rheumatology. Dr. Kaeley's work was supported by an unrestricted equipment loan from Biosound Esaote and Sonosite. Dr. Reginato's work was supported by a grant from the Robert Wood Johnson Foundation and he has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from UCB, Takeda, URL Pharma, and Centocor. NR 159 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2010 VL 62 IS 9 BP 1206 EP 1219 DI 10.1002/acr.20241 PG 14 WC Rheumatology SC Rheumatology GA 651FY UT WOS:000281913400002 ER PT J AU Stefanik, JJ Zhu, Y Zumwalt, AC Gross, KD Clancy, M Lynch, JA Law, LAF Lewis, CE Roemer, FW Powers, CM Guermazi, A Felson, DT AF Stefanik, J. J. Zhu, Y. Zumwalt, A. C. Gross, K. D. Clancy, M. Lynch, J. A. Law, L. A. Frey Lewis, C. E. Roemer, F. W. Powers, C. M. Guermazi, A. Felson, D. T. TI Association Between Patella Alta and the Prevalence and Worsening of Structural Features of Patellofemoral Joint Osteoarthritis: The Multicenter Osteoarthritis Study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID VARUS-VALGUS ALIGNMENT; BONE-MARROW LESIONS; KNEE OSTEOARTHRITIS; RADIOGRAPHIC OSTEOARTHRITIS; CHONDROMALACIA PATELLAE; KINEMATIC MRI; UNITED-STATES; PAIN; PROGRESSION; INSTABILITY AB Objective. To examine the relationship between patella alta and the prevalence and worsening at followup of structural features of patellofemoral joint (PFJ) osteoarthritis (OA) on magnetic resonance imaging (MRI). Methods. The Multicenter Osteoarthritis Study is a cohort study of persons ages 50-79 years with or at risk for knee OA. Patella alta was measured using the Insall-Salvati ratio (ISR) on the baseline lateral radiograph, and cartilage damage, bone marrow lesions (BMLs), and subchondral bone attrition (SBA) were graded on MRI at baseline and at 30 months of followup in the PFJ. We examined the association of the ISR with the prevalence and worsening of cartilage damage, BMLs, and SBA in the PFJ using logistic regression. Results. A total of 907 knees were studied (mean age 62 years, body mass index 30 kg/m(2), ISR 1.10), 63% from female subjects. Compared with knees in the lowest ISR quartile at baseline, those in the highest quartile had 2.4 (95% confidence interval [95% CI] 1.7-3.3), 2.9 (95% CI 2.0-4.3), and 3.5 (95% CI 2.3-5.5) times the odds of having lateral PFJ cartilage damage, BMLs, and SBA, respectively, and 1.5 (95% CI 1.1-2.0), 1.3 (95% CI 0.9-1.8), and 2.2 (95% CI 1.4-3.4) times the odds of having medial PFJ cartilage damage, BMLs, and SBA, respectively. Similarly, those with high ISRs were also at risk for worsening of cartilage damage and BMLs over time than those with low ISRs. Conclusion. A high ISR, indicative of patella alta, is associated with structural features of OA in the PFJ. Additionally, the same knees have an increased risk of worsening of these same features over time. C1 [Stefanik, J. J.; Zhu, Y.; Zumwalt, A. C.; Clancy, M.; Roemer, F. W.; Guermazi, A.; Felson, D. T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gross, K. D.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gross, K. D.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Lynch, J. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Law, L. A. Frey] Univ Iowa, Iowa City, IA USA. [Lewis, C. E.] Univ Alabama, Birmingham, AL USA. [Roemer, F. W.] Klinikum Augsburg, Augsburg, Germany. [Powers, C. M.] Univ So Calif, Los Angeles, CA USA. RP Stefanik, JJ (reprint author), Boston Univ, Sch Med, 650 Albany St,Suite 200, Boston, MA 02118 USA. EM stefanik@bu.edu RI Zhu, Yanyan/C-7833-2011; Lynch, John/F-8209-2012; Powers, Christopher/J-2662-2014; OI Felson, David/0000-0002-2668-2447 FU NIH [U01-AG18820, U01-AG18832, U01-AG18947, U01-AG19069, AR-47785]; Arthritis Foundation FX The Multicenter Osteoarthritis Study was supported by the NIH (grants U01-AG18820, U01-AG18832, U01-AG18947, U01-AG19069, and AR-47785). Mr. Stefanik's work was supported by a doctoral dissertation award from the Arthritis Foundation. NR 36 TC 29 Z9 31 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2010 VL 62 IS 9 BP 1258 EP 1265 DI 10.1002/acr.20214 PG 8 WC Rheumatology SC Rheumatology GA 651FY UT WOS:000281913400008 PM 20506169 ER PT J AU Singh, JA Alpert, MD Kerr, G AF Singh, Jasvinder A. Alpert, Michael D. Kerr, Gail TI A National Survey of Veterans Affairs Rheumatologists for Relevance of Quality of Care Indicators for Gout Management SO ARTHRITIS CARE & RESEARCH LA English DT Article ID HYPERURICEMIA; ALLOPURINOL; ADHERENCE AB Objective. To determine the relevance of current gout quality indicators (QIs). Methods. Members of the Veterans Affairs (VA) Rheumatology Consortium were invited to participate in an online survey and provide opinions (rank 0-10) regarding existing gout QIs. Opinions sought on each QI were 1) relevance to US veterans, 2) likelihood to improve gout care, and 3) ease of electronic capture. Participants were also asked to rank their top 3 gout QIs. Results. Participating VA rheumatologists were mainly men, with a mean age of 51.3 years, and experienced in the management of gout. All 10 gout QIs were considered relevant, with a score of 8.2 or higher. The initiation of urate-lowering therapy, monitoring of urate levels after initiation of urate-lowering therapy, and treatment of acute gout with antiinflammatory agents scored the highest with regard to likelihood of improving gout care, with the first 2 QIs also thought to be the most relevant. Adjustment of initial allopurinol dosing in patients with renal impairment and in those receiving concurrent azathioprine/6-mercaptopurine were perceived as the QIs most amenable to electronic capture. The top-ranked QIs were initiation of urate-lowering therapy with frequent gout attacks, serum urate monitoring after initiation of urate-lowering therapy, and adjustment of initial allopurinol dose to renal function. Conclusion. In a national survey of VA rheumatologists, most gout QIs were thought to be highly relevant. QIs related to initiation of urate-lowering therapy, serum urate monitoring, and initial dosing of allopurinol were ranked the most important for veterans with gout. C1 [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Rochester, MN USA. [Alpert, Michael D.] Yale Univ, Sch Med, New Haven, CT USA. [Alpert, Michael D.; Kerr, Gail] Howard Univ Hosp, Washington, DC USA. RP Singh, JA (reprint author), Univ Alabama, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU NIH [1-KL2-RR024151-01]; Abbott; Amgen; Centocor; Savient; URL Pharmaceuticals; Allergan; Takeda; Wyeth; Bristol-Myers Squibb FX Supported by the NIH Clinical and Translational Science Award (1-KL2-RR024151-01) to the Mayo Clinic Center for Clinical and Translational Research. The VA Rheumatology Consortium has received unrestricted educational grants from Abbott, Amgen, Centocor, and Savient.; Dr. Singh has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott, Savient, and URL Pharmaceuticals, and has received research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen. Dr. Kerr has received speaking fees and/or honoraria (less than $10,000 each) from Abbott, Amgen, and Bristol-Myers Squibb, and has received research grants from Abbott, Amgen, and Savient. NR 15 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2010 VL 62 IS 9 BP 1306 EP 1311 DI 10.1002/acr.20192 PG 6 WC Rheumatology SC Rheumatology GA 651FY UT WOS:000281913400015 PM 20235197 ER PT J AU Dahlgren, M Khosroshahi, A Nielsen, GP Deshpande, V Stone, JH AF Dahlgren, Mollie Khosroshahi, Arezou Nielsen, G. Petur Deshpande, Vikram Stone, John H. TI Riedel's Thyroiditis and Multifocal Fibrosclerosis Are Part of the IgG4-Related Systemic Disease Spectrum SO ARTHRITIS CARE & RESEARCH LA English DT Article ID CHRONIC SCLEROSING SIALADENITIS; AUTOIMMUNE PANCREATITIS; RETROPERITONEAL FIBROSIS; INFLAMMATORY PSEUDOTUMOR; MEDIASTINAL FIBROSIS; CHOLANGITIS; TAMOXIFEN; DIAGNOSIS; STRUMA; IGG4 AB Objective. Riedel's thyroiditis is a chronic fibrosing disorder of unknown etiology often associated with "multifocal fibrosclerosis." IgG4-related systemic disease is characterized by IgG4+ plasma cell infiltration and fibrosis throughout many organs. We hypothesized that Riedel's thyroiditis is part of the IgG4-related systemic disease spectrum. Methods. We searched our institution's pathology database using the terms "Riedel's," "struma," "thyroid," and "fibrosis," and identified 3 cases of Riedel's thyroiditis. Riedel's thyroiditis was diagnosed if there was a fibroinflammatory process involving all or a portion of the thyroid gland, with evidence of extension of the process into surrounding tissues. Immunohistochemical stains for IgG4 and IgG were performed. The histopathologic and immunohistochemical features of each involved organ were evaluated. The clinical features of one patient with multiple organ system disease were described. Results. All 3 thyroidectomy samples stained positively for IgG4-bearing plasma cells. One patient had extensive extrathyroidal involvement diagnostic of IgG4-related systemic disease, including cholangitis, pseudotumors of both the lung and lacrimal gland, and a lymph node contiguous to the thyroid that stained intensely for IgG4+ plasma cells. The histologic features of all organs involved were consistent with IgG4-related systemic disease. Patient 3 had 10 IgG4+ plasma cells per high-power field initially, but rebiopsy 2 years later demonstrated no IgG4+ plasma cells. That patient's second biopsy, characterized by fibrosis and minimal residual inflammation, further solidifies the link between IgG4-bearing plasma cells in tissue and the histologic evolution to Riedel's thyroiditis. Conclusion. Riedel's thyroiditis is part of the IgG4-related systemic disease spectrum. In many cases, multifocal fibrosclerosis and IgG4-related systemic disease are probably the same entity. C1 [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Dahlgren, Mollie; Khosroshahi, Arezou; Nielsen, G. Petur; Deshpande, Vikram; Stone, John H.] Harvard Univ, Sch Med, Boston, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2-55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org NR 37 TC 117 Z9 126 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2010 VL 62 IS 9 BP 1312 EP 1318 DI 10.1002/acr.20215 PG 7 WC Rheumatology SC Rheumatology GA 651FY UT WOS:000281913400016 PM 20506114 ER PT J AU Yang, R Ma, YX Chen, LF Zhou, Y Yang, ZP Zhu, Y Du, XL Shi, JD Ma, HS Zhang, J AF Yang, Rui Ma, Yu-Xia Chen, Lin-Feng Zhou, Ying Yang, Zhan-Po Zhu, Yan Du, Xiao-Ling Shi, Jian-Dang Ma, Hong-Shun Zhang, Ju TI Antagonism of estrogen-mediated cell proliferation by raloxifene in prevention of ageing-related prostatic hyperplasia SO ASIAN JOURNAL OF ANDROLOGY LA English DT Article DE estrogen; prostatic hyperplasia; raloxifene; rats ID SMOOTH-MUSCLE-CELLS; STROMAL CELLS; RECEPTOR MODULATORS; EPITHELIAL-CELLS; BREAST-CANCER; APOPTOSIS; ANDROGEN; ESTRADIOL; AGONIST/ANTAGONIST; THERAPY AB Estrogen has important roles in the initiation and development of benign prostatic hyperplasia (BPH). Regulators of the estrogen receptor (ER) are tissue- and cell-specific. We evaluated the effect of estrogen antagonist, raloxifene (Ral), on the prevention and treatment of BPH by investigating its effect on the proliferation of two different prostate cell lines: a stromal cell line, WPMY-1, and a benign prostatic hyperplasia epithelial cell line, BPH-1. We additionally evaluated its effect on prostatic hyperplasia induced by estrogen and androgen in a rat model. The effect of Ral on the prevention of prostatic hyperplasia was analyzed by haematoxylin and eosin staining and quantitative immunohistochemistry (IHC) for proliferating cell nuclear antigen and alpha-smooth muscle actin. In vitro and in vivo, tamoxifen (Tam), another anti-estrogen drug, and finasteride (Fin), a drug for the clinical treatment of BPH, served as efficacy controls. The in vitro data showed that neither Ral nor Tam alone affected the proliferation of WPMY-1 and BPH-1, but both antagonized the effect of oestradiol in promoting the proliferation of the two cells. Results from the IHC staining of the rat prostates indicated that, similar to Tam and Fin, Ral inhibited the proliferation of stromal cells in vivo. Interestingly, in contrast to Tam, both Ral and Fin inhibited the proliferation of epithelial cells. Furthemore, Ral treatment much strongly decreased the number of prostatic acini and the surrounding layers of smooth muscle cells than Fin (P < 0.05). Our data showed for the first time that Ral may have a role in the response of the rat prostate to selective ER modulators. C1 [Yang, Rui; Ma, Yu-Xia; Zhou, Ying; Du, Xiao-Ling; Shi, Jian-Dang; Zhang, Ju] Nankai Univ, Bioact Mat Key Lab, Minist Educ, Dept Biochem & Mol Biol,Coll Life Sci, Tianjin 300071, Peoples R China. [Chen, Lin-Feng] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02445 USA. [Yang, Zhan-Po; Ma, Hong-Shun] Tianjin First Cent Hosp, Dept Urol, Tianjin 300192, Peoples R China. [Zhu, Yan] Tufts Univ, Sch Med, Tufts Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. RP Zhang, J (reprint author), Nankai Univ, Bioact Mat Key Lab, Minist Educ, Dept Biochem & Mol Biol,Coll Life Sci, Tianjin 300071, Peoples R China. EM shijd@nankai.edu.cn; zhangju@nankai.edu.cn FU National Basic Research Programs, China (973 Programs) [2009CB918904, 2010CB945003]; National Natural Science Foundation of China [30872592]; Joint Research Fund for Overseas Chinese Scholars and Scholars in Hong Kong and Macao, China [30928027]; Tianjin Municipal Science and Technology Commission, China [09ZCKFSF00800] FX This research was funded by the following grants: the National Basic Research Programs, China (973 Programs, No. 2009CB918904, No. 2010CB945003), the National Natural Science Foundation of China (No. 30872592), Joint Research Fund for Overseas Chinese Scholars and Scholars in Hong Kong and Macao, China (No. 30928027), and the key research project of Tianjin Municipal Science and Technology Commission, China (No. 09ZCKFSF00800). NR 25 TC 8 Z9 12 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1008-682X J9 ASIAN J ANDROL JI Asian J. Androl. PD SEP PY 2010 VL 12 IS 5 BP 735 EP 743 DI 10.1038/aja.2010.24 PG 9 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 647FC UT WOS:000281602200015 PM 20473319 ER PT J AU Sheth, RA Maricevich, M Mahmood, U AF Sheth, Rahul A. Maricevich, Marco Mahmood, Umar TI In vivo optical molecular imaging of matrix metalloproteinase activity in abdominal aortic aneurysms correlates with treatment effects on growth rate SO ATHEROSCLEROSIS LA English DT Article DE Molecular imaging; Abdominal aortic aneurysm; Optical imaging; Pre-clinical; Endovascular imaging; Matrix metalloproteinase ID DOXYCYCLINE; INFLAMMATION; INHIBITION; ATHEROSCLEROSIS; DEGENERATION; GELATINASE; MICE AB Objectives: We present a method to quantify the inflammatory processes that drive abdominal aortic aneurysm (AAA) development that may help predict the rate of growth and thus guide medical and surgical management. We use an in vivo optical molecular imaging approach to quantify protease activity within the walls of AAAs in a rodent model. Methods: AAAs were generated in mice by topical application of calcium chloride, followed by the administration of the MMP inhibitor doxycycline for 3 months. After this time period, an enzyme-activatable optical molecular imaging agent sensitive to MMP activity was administered, and MMP proteolytic activity was measured in vivo. Histology and in situ zymography were performed for validation. AAAs were also generated in rats, and MMP activity within the walls of AAAs was also quantified endovascularly. Results: A dose-dependent response of AAA growth rate to doxycycline administration was demonstrated, with high doses of the drug resulting in nearly complete suppression of aneurysm formation. There was a direct relationship between the rate of aneurysmal growth and measured MMP activity, with a linear best-fit well approximating the relationship. We additionally performed endovascular imaging of AAAs in rats and demonstrated a similar suppression of intramural MMP activity following doxycycline administration. Conclusions: We present an in vivo evaluation of MMP activity within the walls of AAAs in rodents and show a direct, linear relationship between proteolytic activity and aneurysmal growth. We also illustrate that this functional imaging method can be performed endovascularly, demonstrating potential pre-clinical and clinical applications. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Sheth, Rahul A.; Maricevich, Marco; Mahmood, Umar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,White 427, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu FU NIH [RO1-EB001872] FX This research was supported in part by NIH grant RO1-EB001872. NR 30 TC 30 Z9 31 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 2010 VL 212 IS 1 BP 181 EP 187 DI 10.1016/j.atherosclerosis.2010.05.012 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 645LS UT WOS:000281459900029 PM 20542274 ER PT J AU DeLisi, LE AF DeLisi, Lynn E. TI STRUCTURAL CHANGE OVER TIME IN PEOPLE WITH SCHIZOPHRENIA AND THE AGING PROCESS SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 [DeLisi, Lynn E.] VA Boston Healthcare Syst, Boston, MA USA. [DeLisi, Lynn E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD SEP PY 2010 VL 44 SU 1 BP A7 EP A8 PG 2 WC Psychiatry SC Psychiatry GA 664IX UT WOS:000282954700013 ER PT J AU Souberbielle, JC Body, JJ Lappe, JM Plebani, M Shoenfeld, Y Wang, TJ Bischoff-Ferrari, HA Cavalier, E Ebeling, PR Fardellone, P Gandini, S Gruson, D Guerin, AP Heickendorff, L Hollis, BW Ish-Shalom, S Jean, G von Landenberg, P Largura, A Olsson, T Pierrot-Deseilligny, C Pilz, S Tincani, A Valcour, A Zittermann, A AF Souberbielle, Jean-Claude Body, Jean-Jacques Lappe, Joan M. Plebani, Mario Shoenfeld, Yehuda Wang, Thomas J. Bischoff-Ferrari, Heike A. Cavalier, Etienne Ebeling, Peter R. Fardellone, Patrice Gandini, Sara Gruson, Damien Guerin, Alain P. Heickendorff, Lene Hollis, Bruce W. Ish-Shalom, Sofia Jean, Guillaume von Landenberg, Philipp Largura, Alvaro Olsson, Tomas Pierrot-Deseilligny, Charles Pilz, Stefan Tincani, Angela Valcour, Andre Zittermann, Armin TI Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice SO AUTOIMMUNITY REVIEWS LA English DT Review DE Vitamin D; Supplementation; 25(OH)D; Testing; Recommendations ID RANDOMIZED-CONTROLLED-TRIALS; PLACEBO-CONTROLLED TRIAL; CHRONIC KIDNEY-DISEASE; D SUPPLEMENTATION; BREAST-CANCER; D DEFICIENCY; SERUM 25-HYDROXYVITAMIN-D; BLOOD-PRESSURE; CALCIUM SUPPLEMENTATION; VASCULAR CALCIFICATION AB Background: There is increasing evidence that, in addition to the well-known effects on musculoskeletal health, vitamin D status may be related to a number of non-skeletal diseases. An international expert panel formulated recommendations on vitamin D for clinical practice, taking into consideration the best evidence available based on published literature today. In addition, where data were limited to smaller clinical trials or epidemiologic studies, the panel made expert-opinion based recommendations. Methods: Twenty-five experts from various disciplines (classical clinical applications, cardiology, auto-immunity, and cancer) established draft recommendations during a 2-day meeting. Thereafter, representatives of all disciplines refined the recommendations and related texts, subsequently reviewed by all panelists. For all recommendations, panelists expressed the extent of agreement using a 5-point scale. Results and conclusion: Recommendations were restricted to clinical practice and concern adult patients with or at risk for fractures, falls, cardiovascular or autoimmune diseases, and cancer. The panel reached substantial agreement about the need for vitamin D supplementation in specific groups of patients in these clinical areas and the need for assessing their 25-hydroxyvitamin D (25(OH)D) serum levels for optimal clinical care. A target range of at least 30 to 40 ng/mL was recommended. As response to treatment varies by environmental factors and starting levels of 25(OH)D, testing may be warranted after at least 3 months of supplementation. An assay measuring both 25(OH)D(2) and 25(OH)D(3) is recommended. Dark-skinned or veiled individuals not exposed much to the sun, elderly and institutionalized individuals may be supplemented (800 IU/day) without baseline testing. (C) 2010 Elsevier B.V. All rights reserved. C1 [Souberbielle, Jean-Claude] CHU Necker, Physiol Lab, F-75015 Paris, France. [Body, Jean-Jacques] Univ Libre Bruxelles, CHU Brugmann, Dept Med, Brussels, Belgium. [Lappe, Joan M.] Creighton Univ, Omaha, NE 68178 USA. [Plebani, Mario] Univ Padua, Lab Med, Leonardo Fdn, Abano Terme Gen Hosp, I-35100 Padua, Italy. [Shoenfeld, Yehuda] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel. [Shoenfeld, Yehuda] Chaim Sheba Med Ctr, Zabludowizc Ctr Autoimmune Dis, Dept Med B, IL-52621 Tel Hashomer, Israel. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Bischoff-Ferrari, Heike A.] Univ Zurich, Ctr Aging & Mobil, Zurich, Switzerland. [Bischoff-Ferrari, Heike A.] Univ Zurich Hosp, Dept Rheumatol, CH-8091 Zurich, Switzerland. [Bischoff-Ferrari, Heike A.] Univ Zurich Hosp, Inst Med Phys, CH-8091 Zurich, Switzerland. [Cavalier, Etienne] Univ Liege, CHU Liege, Dept Clin Chem, Liege, Belgium. [Ebeling, Peter R.] Univ Melbourne, Med RMH WH, Footscray, Vic 3011, Australia. [Fardellone, Patrice] CHU Amiens, INSERM, ERI 12, Amiens, France. [Gandini, Sara] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy. [Gruson, Damien] Clin Univ St Luc, Dept Lab Med, B-1200 Brussels, Belgium. [Guerin, Alain P.] Ctr Hosp Manhes, Fleury Merogis, France. [Heickendorff, Lene] Aarhus Univ Hosp, Dept Clin Chem, DK-8000 Aarhus, Denmark. [Hollis, Bruce W.] Med Univ S Carolina, Charleston, SC 29425 USA. [Ish-Shalom, Sofia] Technion Israel Inst Technol, Fac Med, Bone & Mineral Metab Unit, Haifa, Israel. [Jean, Guillaume] Ctr Rein Artificiel, Tassin La Demi Lune, France. [von Landenberg, Philipp] IFLM, Solothurner Spitaler AG, Olten, Switzerland. [Largura, Alvaro] Alvaro Ctr Anal & Clin Res DASA, Cascavel, Brazil. [Olsson, Tomas] Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, Neuroimmunol Unit, Stockholm, Sweden. [Pierrot-Deseilligny, Charles] Hop La Pitie Salpetriere, Serv Neurol 1, Paris, France. [Pilz, Stefan] Med Univ Graz, Div Endocrinol & Nucl Med, Dept Internal Med, Graz, Austria. [Tincani, Angela] Univ Brescia, Brescia, Italy. [Valcour, Andre] Spedali Civil Brescia, I-25125 Brescia, Italy. [Zittermann, Armin] Lab Corp Amer, Ctr Esoter Testing, Burlington, NC USA. [Zittermann, Armin] Heart Ctr N Rhine Westphalia, Clin Thorac & Cardiovasc Surg, Bad Oeynhausen, Germany. RP Souberbielle, JC (reprint author), CHU Necker, Physiol Lab, 149 Rue Sevres, F-75015 Paris, France. EM jean-claude.souberbielle@nck.aphp.fr RI Cavalier, Etienne/E-8661-2011; Tincani, Angela/E-7608-2010; Ebeling, Peter/A-9129-2012; 刘, 李陆/H-8469-2015; OI Gandini, Sara/0000-0002-1348-4548 FU DiaSorin S.p.A. FX The authors are grateful to Ismar Healthcare for their assistance in editing of the manuscript. The Vitamin D Summit Meeting was financially supported by DiaSorin S.p.A. NR 66 TC 227 Z9 236 U1 5 U2 44 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9972 J9 AUTOIMMUN REV JI Autoimmun. Rev. PD SEP PY 2010 VL 9 IS 11 BP 709 EP 715 DI 10.1016/j.autrev.2010.06.009 PG 7 WC Immunology SC Immunology GA 657LR UT WOS:000282414700001 PM 20601202 ER PT J AU Gros, DF Simms, LJ Antony, MM AF Gros, Daniel F. Simms, Leonard J. Antony, Martin M. TI Psychometric Properties of the State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA) in Friendship Dyads SO BEHAVIOR THERAPY LA English DT Article ID SELF-OTHER AGREEMENT; SOCIAL PHOBIA INVENTORY; BELIEFS SCALE; QUESTIONNAIRE; THOUGHTS; PERSONALITY; SIMILARITY; MATRIX; SAMPLE AB Recently, Gros, Antony, Simms, and McCabe (2007) demonstrated support for the psychometric properties of a new measure of state and trait anxiety, the State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA). In the present study, we further investigated the STICSA-Trait Version in 127 friendship dyads with a self-report from one participant (target) and an other-report of the target from a friend (informant). Consistent with previous research, confirmatory factor analyses supported the 2-factor structure of the STICSA-Trait in the target and informant reports. Moreover, the STICSA-Trait Cognitive and Somatic Anxiety subscales showed acceptable convergent and discriminant validity with related measures of anxiety. In addition, the STICSA-Trait subscales demonstrated adequate internal consistency and self-other agreement across the target and informant reports. Together, these findings provide additional support for the STICSA-Trait subscales as reliable and valid measures of cognitive and somatic anxiety. C1 [Gros, Daniel F.] Ralph H Johnson Vet Adm Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Gros, Daniel F.] Med Univ S Carolina, Charleston, SC 29425 USA. [Simms, Leonard J.] SUNY Buffalo, Buffalo, NY 14260 USA. [Antony, Martin M.] Ryerson Univ, Toronto, ON, Canada. RP Gros, DF (reprint author), Ralph H Johnson Vet Adm Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu RI Antony, Martin/K-1991-2012 OI Antony, Martin/0000-0002-3508-377X FU NIMH NIH HHS [R01 MH080086] NR 33 TC 18 Z9 18 U1 13 U2 21 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD SEP PY 2010 VL 41 IS 3 BP 277 EP 284 PG 8 WC Psychology, Clinical SC Psychology GA 612JA UT WOS:000278892500002 PM 20569777 ER PT J AU Reese, HE McNally, RJ Wilhelm, S AF Reese, Hannah E. McNally, Richard J. Wilhelm, Sabine TI Facial asymmetry detection in patients with body dysmorphic disorder SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Body dysmorphic disorder; Aestheticality; Symmetry; Facial perception ID OBSESSIVE-COMPULSIVE SCALE; BEHAVIORAL-MODEL; SYMMETRY; RELIABILITY; VALIDITY; BEAUTY; ART AB Cognitive-behavioral models of body dysmorphic disorder (BDD) propose that individuals with BDD may possess a better or more developed sense of aestheticality than do individuals without BDD. Evidence for this proposition, however, is limited. One perceptual process that could contribute to heightened aestheticality is the ability to detect differences in symmetry. In this experiment we tested whether individuals with BDD (n = 20), relative to individuals with obsessive compulsive disorder (OCD; n = 20) and healthy controls (n = 20), show an enhanced ability to detect differences in the symmetry of others' faces, symmetry of dot arrays, and/or show a greater preference for symmetrical faces. Individuals with BDD were not significantly more accurate in detecting differences in facial symmetry or dot arrays relative to individuals with OCD and healthy controls. Individuals with OCD took longer to make facial symmetry judgments than did individuals in the other two groups. All participants, regardless of diagnostic group, preferred more symmetrical faces than nonsymmetrical ones. Taken together, our results do not support a heightened perceptual ability or evaluative preference for symmetry among individuals with BDD. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Reese, Hannah E.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Reese, Hannah E.; Wilhelm, Sabine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Reese, HE (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM hreese@fas.harvard.edu NR 25 TC 15 Z9 15 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD SEP PY 2010 VL 48 IS 9 BP 936 EP 940 DI 10.1016/j.brat.2010.05.021 PG 5 WC Psychology, Clinical SC Psychology GA 643NO UT WOS:000281303600015 PM 20619825 ER PT J AU Kaplan, GB Vasterling, JJ Vedak, PC AF Kaplan, Gary B. Vasterling, Jennifer J. Vedak, Priyanka C. TI Brain-derived neurotrophic factor in traumatic brain injury, post-traumatic stress disorder, and their comorbid conditions: role in pathogenesis and treatment SO BEHAVIOURAL PHARMACOLOGY LA English DT Review DE brain-derived neurotrophic factor; D-cycloserine; hippocampus; histone deacetylase inhibitors; neurogenesis; plasticity; prefrontal cortex; post-traumatic stress disorder; traumatic brain injury ID BDNF MESSENGER-RNA; PERSISTENT POSTCONCUSSIVE SYMPTOMS; HISTONE DEACETYLASE INHIBITOR; MESENCHYMAL STEM-CELLS; ADULT-RAT BRAIN; HIPPOCAMPAL VOLUME; VIETNAM VETERANS; DENTATE GYRUS; WAR VETERANS; PREFRONTAL CORTEX AB As US military service members return from the wars in Iraq and Afghanistan with elevated rates of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), attention has been increasingly focused on TBI/PTSD comorbidity, its neurobiological mechanisms, and novel and effective treatment approaches. TBI and PTSD, and their comorbid conditions, present with a spectrum of common clinical features such as sleep disturbance, depression, anxiety, irritability, difficulty in concentrating, fatigue, suicidality, chronic pain, and alterations in arousal. These TBI and PTSD disorders are also thought to be characterized by overlapping neural mechanisms. Both conditions are associated with changes in hippocampal, prefrontal cortical, and limbic region function because of alterations in synaptogenesis, dendritic remodeling, and neurogenesis. Neural changes in TBI and PTSD result from pathophysiological disturbances in metabolic, cytotoxic, inflammatory, and apoptic processes, amongst other mechanisms. Neurotrophins have well-established actions in regulating cell growth and survival, differentiation, apoptosis, and cytoskeleton restructuring. A body of research indicates that dysregulation of neural brain-derived neurotrophic factor (BDNF) is found in conditions of TBI and PTSD. Induction of BDNF and activation of its intracellular receptors can produce neural regeneration, reconnection, and dendritic sprouting, and can improve synaptic efficacy. In this review, we consider treatment approaches that enhance BDNF-related signaling and have the potential to restore neural connectivity. Such treatment approaches could facilitate neuroplastic changes that lead to adaptive neural repair and reverse cognitive and emotional deficits in both TBI and PTSD. Behavioural Pharmacology 21:427-437 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Kaplan, Gary B.] VA Boston Healthcare Syst, Mental Hlth & Psychiat Serv, Boston, MA USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA USA. [Vedak, Priyanka C.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Kaplan, Gary B.; Vasterling, Jennifer J.; Vedak, Priyanka C.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Kaplan, GB (reprint author), VA Boston, 150 S Huntington Ave, Boston, MA 02130 USA. EM gary.kaplan@va.gov FU Department of Veterans Affairs; Department of Defense FX This research was supported by Grants from the Department of Veterans Affairs (G. B. K. and J.J.V.) and by the Department of Defense (G. B. K.). Kaplan, Vasterling, and Vedak, contributed to and have approved the final study. NR 117 TC 64 Z9 69 U1 6 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2010 VL 21 IS 5-6 BP 427 EP 437 DI 10.1097/FBP.0b013e32833d8bc9 PG 11 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 641IS UT WOS:000281119000006 PM 20679891 ER PT J AU Flaherty, KT Puzanov, I AF Flaherty, Keith T. Puzanov, Igor TI Building on a foundation of VEGF and mTOR targeted agents in renal cell carcinoma SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE Renal cell carcinoma; VHL; HIF; VEGF; Angiogenesis ID ENDOTHELIAL-GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ADVANCED SOLID TUMORS; LINDAU GENE STATUS; PHASE-III TRIAL; ANTITUMOR-ACTIVITY; IN-VIVO; ANGIOGENESIS INHIBITOR; MULTIKINASE INHIBITOR AB Since late 2005 six new drugs have been approved by the Food and Drug Administration (FDA) for the treatment of metastatic renal cell carcinoma (RCC). However, the similarity of these agents with regard to mechanism of action makes it unclear if each agent has unique clinical utility. This flurry of drug development activity stems from the understanding of the central role that loss of von Hippel Lindau (VHL) gene function plays in the pathophysiology of clear cell RCC. The first agent to establish the therapeutic value of targeting the downstream consequences of VHL loss of function was a vascular endothelial growth factor (VEGF) directed monoclonal antibody, bevacizumab. Following the initial observations with bevacizumab, three VEGF receptor (VEGFR) tyrosine kinase inhibitors, with varied spectra beyond VEGFR, have been successfully developed clinically. Unanticipated clinical activity was observed with inhibitors of mTOR, a central component of the nutrient-sensing PI3 kinase pathway, in RCC. Subsequent work identified that mTOR also regulates the expression of hypoxia inducible factor (HIF), which is regulated by VHL outside of the setting of inactivating mutations or deletions. This appears to tie all of the six approved therapies to the direct consequences of loss of VHL function in clear cell RCC. It remains poorly understood to what extent these therapies differ from one another. Although the outcome of patients with metastatic RCC has been substantially altered with administration of the currently available therapies, the proper selection of currently available therapy, rational development of agents with novel mechanism of action and development of predictive biomarkers of response remains a challenge. (C) 2010 Elsevier Inc. All rights reserved. C1 [Flaherty, Keith T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Puzanov, Igor] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RP Flaherty, KT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM kflaherty@partners.org NR 112 TC 17 Z9 18 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 2010 VL 80 IS 5 SI SI BP 638 EP 646 DI 10.1016/j.bcp.2010.04.005 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 627FL UT WOS:000280024800011 PM 20382128 ER PT J AU Sharma, SV Settleman, J AF Sharma, Sreenath V. Settleman, Jeff TI Exploiting the balance between life and death: Targeted cancer therapy and "oncogenic shock" SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE Cancer; Oncogene addiction; Therapeutics; Kinases; Drug targets ID PROTEIN-KINASE-C; APOPTOTIC CELL-DEATH; SYNTHETIC LETHAL INTERACTIONS; ANAPLASTIC LYMPHOMA KINASE; GROWTH-FACTOR DEPRIVATION; MYELOID-LEUKEMIA CELLS; BCR-ABL; IN-VIVO; POLY(ADP-RIBOSE) POLYMERASE; PROAPOPTOTIC FUNCTION AB Rational approaches to targeted cancer therapy have begun to predominate the pipelines of oncology drug development. Our rapidly increasing understanding of the "wiring" of tumor cells and the vulnerabilities of such cells that can potentially be exploited through targeted treatments has opened up enormous opportunities for improved therapies. Accumulating evidence suggests that many of these vulnerabilities reflect states of dependency or "addiction" that are unique to cancer cells (versus normal cells). Such addiction can arise due to a strict dependency on a single activated oncogene, a cell lineage-specific factor, or even to a non-oncogene, and identifying these "Achilles' heels" within individual tumors remains an important challenge to the development of targeted therapies. Recent technology advances that facilitate high-throughput genomic analysis of tumor specimens and genome-wide RNA interference screening in cancer cell lines are key among the newly developed tools that are beginning to reveal novel context-dependent therapeutic targets, and the rapidly increasing application of these technologies by a large number of laboratories will undoubtedly lead to more effective cancer therapies in the near future. Here, we review the various forms of cancer cell addiction and their relevance to the discovery of novel therapeutic targets. (C) 2010 Elsevier Inc. All rights reserved. C1 [Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu NR 109 TC 31 Z9 31 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 2010 VL 80 IS 5 SI SI BP 666 EP 673 DI 10.1016/j.bcp.2010.03.001 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 627FL UT WOS:000280024800014 PM 20211150 ER PT J AU Michowski, W Ferretti, R Wisniewska, MB Ambrozkiewicz, M Beresewicz, M Fusella, F Skibinska-Kijek, A Zablocka, B Brancaccio, M Tarone, G Kuznicki, J AF Michowski, Wojciech Ferretti, Roberta Wisniewska, Marta B. Ambrozkiewicz, Mateusz Beresewicz, Malgorzata Fusella, Federica Skibinska-Kijek, Anna Zablocka, Barbara Brancaccio, Mara Tarone, Guido Kuznicki, Jacek TI Morgana/CHP-1 is a novel chaperone able to protect cells from stress SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Morgana/CHP-1; CHORD; Co-chaperone; Heat shock protein; HSP90; stress ID GERBIL HIPPOCAMPUS; PRESSURE-OVERLOAD; CEREBRAL-ISCHEMIA; HEAT-SHOCK; MELUSIN; KINASE; HSP90; CHORD; IMMUNOREACTIVITY; COMPLEXES AB Morgana/CHP-1 (CHORD containing protein-1) has been recently shown to be necessary for proper cell divisions. However, the presence of the protein in postmitotic tissues such as brain and striated muscle suggests that morgana/CHP-1 has additional cellular functions. Here we show that morgana/CHP-1 behaves like an HSP90 co-chaperone and possesses an independent molecular chaperone activity towards denatured proteins. The expression time profile of morgana/Chp-1 in NIH3T3 cells in response to heat stress is similar to that of Hsp70, a classical effector of Heat Shock Factor-1 mediated stress response. Moreover, overexpression of morgana/CHP-1 in NIH3T3 cells leads to the increased stress resistance of the cells. Interestingly, morgana/Chp-1 upregulation in response to transient global brain ischemia lasts longer in ischemia-resistant regions of the gerbil hippocampus than in vulnerable ones, suggesting the involvement of morgana/CHP-1 in natural protective mechanisms in vivo. (C) 2010 Elsevier B.V. All rights reserved. C1 [Michowski, Wojciech; Wisniewska, Marta B.; Ambrozkiewicz, Mateusz; Skibinska-Kijek, Anna; Kuznicki, Jacek] Int Inst Mol & Cell Biol, PL-02109 Warsaw, Poland. [Michowski, Wojciech; Kuznicki, Jacek] M Nencki Inst Expt Biol, PL-02093 Warsaw, Poland. [Ferretti, Roberta; Fusella, Federica; Brancaccio, Mara; Tarone, Guido] Univ Turin, Dipartimento Genet Biol & Biochim, I-10126 Turin, Italy. [Beresewicz, Malgorzata; Zablocka, Barbara] Polish Acad Sci, Mol Biol Unit, Mossakowski Med Res Ctr, PL-02106 Warsaw, Poland. RP Michowski, W (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM Wojciech_Michowski@dfci.harvard.edu RI Wisniewska, Marta/A-6691-2009; OI Wisniewska, Marta/0000-0002-1593-0361; Tarone, Guido/0000-0003-4805-086X FU Polish-German [S001/P-N/2007/01, 01G20713]; Statutory Donation for the International Institute of Molecular and Cell Biology-Decision [1789/E-529/S/2009]; Foundation for Polish Science; Progetto di Ricerca Sanitaria Finalizzata; AIRC FX This work was supported by the Polish-German Grant (#S001/P-N/2007/01; #01G20713) and Statutory Donation for the International Institute of Molecular and Cell Biology-Decision No. 1789/E-529/S/2009 to J.K; Foundation for Polish Science to J.K and W.M.; Progetto di Ricerca Sanitaria Finalizzata 2007 and 2008 to MB and AIRC 2008 to MB. NR 27 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD SEP PY 2010 VL 1803 IS 9 BP 1043 EP 1049 DI 10.1016/j.bbamcr.2010.05.005 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 638VM UT WOS:000280925600007 PM 20493909 ER PT J AU Naamati, G Askenazi, M Linial, M AF Naamati, Guy Askenazi, Manor Linial, Michal TI A predictor for toxin-like proteins exposes cell modulator candidates within viral genomes SO BIOINFORMATICS LA English DT Article; Proceedings Paper CT 9th European Conference on Computational Biology CY SEP 26-29, 2010 CL Ghent, BELGIUM SP Int Conf Ctr, IBM, FWO, Flanders, FNRS ID EVOLUTION; SYSTEM; HOST; COEVOLUTION; SEQUENCES; PEPTIDES AB Motivation: Animal toxins operate by binding to receptors and ion channels. These proteins are short and vary in sequence, structure and function. Sporadic discoveries have also revealed endogenous toxin-like proteins in non-venomous organisms. Viral proteins are the largest group of quickly evolving proteomes. We tested the hypothesis that toxin-like proteins exist in viruses and that they act to modulate functions of their hosts. Results: We updated and improved a classifier for compact proteins resembling short animal toxins that is based on a machine-learning method. We applied it in a large-scale setting to identify toxin-like proteins among short viral proteins. Among the similar to 26 000 representatives of such short proteins, 510 sequences were positively identified. We focused on the 19 highest scoring proteins. Among them, we identified conotoxin-like proteins, growth factors receptor-like proteins and anti-bacterial peptides. Our predictor was shown to enhance annotation inference for many 'uncharacterized' proteins. We conclude that our protocol can expose toxin-like proteins in unexplored niches including metagenomics data and enhance the systematic discovery of novel cell modulators for drug development. C1 [Askenazi, Manor; Linial, Michal] Hebrew Univ Jerusalem, Dept Biol Chem, Sudarsky Ctr Computat Biol, IL-91905 Jerusalem, Israel. [Naamati, Guy] Hebrew Univ Jerusalem, Sch Comp Sci & Engn, IL-91905 Jerusalem, Israel. [Askenazi, Manor] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. RP Linial, M (reprint author), Hebrew Univ Jerusalem, Dept Biol Chem, Sudarsky Ctr Computat Biol, IL-91905 Jerusalem, Israel. EM michall@cc.huji.ac.il OI Naamati, Guy/0000-0002-0523-4071 NR 26 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD SEP PY 2010 VL 26 IS 18 BP i482 EP i488 DI 10.1093/bioinformatics/btq375 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 648SK UT WOS:000281714100012 PM 20823311 ER PT J AU Hoganson, DM O'Doherty, EM Owens, GE Harilal, DO Goldman, SM Bowley, CM Neville, CM Kronengold, RT Vacanti, JP AF Hoganson, David M. O'Doherty, Elisabeth M. Owens, Gwen E. Harilal, Dina O. Goldman, Scott M. Bowley, Chris M. Neville, Craig M. Kronengold, Russell T. Vacanti, Joseph P. TI The retention of extracellular matrix proteins and angiogenic and mitogenic cytokines in a decellularized porcine dermis SO BIOMATERIALS LA English DT Article DE ECM; Cytokine; Surgical mesh; Cell culture ID SMALL-INTESTINAL SUBMUCOSA; ACELLULAR DERMIS; GROWTH; CELLS; RECONSTRUCTION; IDENTIFICATION; ADHESION; REPAIR AB Decellularized dermis materials demonstrate considerable utility in surgical procedures including hernia repair and breast reconstruction. A new decellularized porcine dermis material has been developed that retains many native extracellular matrix (ECM) proteins and cytokines. This material has substantial mechanical strength with maximum tensile strength of 141.7 +/- 85.4 (N/cm) and suture pull through strength of 47.0 +/- 14.0 (N). After processing, many ECM proteins remained in the material including collagen III, collagen IV, collagen VII, laminin and fibronectin. Glycosaminoglycans, including hyaluronic acid, were also preserved. Among several cytokines whose levels were quantified, more vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) were retained within this material than in comparable decellularized dermis materials. The retention of bioactivity was demonstrated in a cell culture assay. Because this decellularized porcine dermis material both retains significant strength and has substantial biological activity, it may promote rapid integration and repair in clinical applications. (C) 2010 Published by Elsevier Ltd. C1 [Vacanti, Joseph P.] Massachusetts Gen Hosp Children, Dept Pediat Surg, Boston, MA 02114 USA. [Hoganson, David M.; O'Doherty, Elisabeth M.; Owens, Gwen E.; Neville, Craig M.; Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, Boston, MA 02114 USA. [Harilal, Dina O.; Goldman, Scott M.; Bowley, Chris M.; Kronengold, Russell T.] Kensey Nash Corp, Exton, PA 19341 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp Children, Dept Pediat Surg, 55 Fruit St,Warren 1151, Boston, MA 02114 USA. EM jvacanti@partners.org OI Hoganson, David/0000-0002-8141-7793 FU NIH [F32 DK076349-01] FX This study was funded in part by a generous gift from Kensey Nash Corporation. The authors gratefully acknowledge support from the NIH (F32 DK076349-01, DMH). The authors also acknowledge expert assistance with the immunofluorescent staining from Dennis Brown and Margaret McLaughlin from the Massachusetts General Hospital Program in Membrane Biology. NR 26 TC 34 Z9 34 U1 1 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2010 VL 31 IS 26 BP 6730 EP 6737 DI 10.1016/j.biomaterials.2010.05.019 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 635XZ UT WOS:000280692500008 PM 20576289 ER PT J AU Hoganson, DM Owens, GE O'Doherty, EM Bowley, CM Goldman, SM Harilal, DO Neville, CM Kronengold, RT Vacanti, JR AF Hoganson, David M. Owens, Gwen E. O'Doherty, Elisabeth M. Bowley, Chris M. Goldman, Scott M. Harilal, Dina O. Neville, Craig M. Kronengold, Russell T. Vacanti, Joseph R. TI Preserved extracellular matrix components and retained biological activity in decellularized porcine mesothelium SO BIOMATERIALS LA English DT Article DE ECM; Cytokine; Surgical mesh; Cell culture ID SMALL-INTESTINAL SUBMUCOSA; ENDOTHELIAL-CELL ADHERENCE; GROWTH-FACTOR; BASEMENT-MEMBRANE; ACELLULAR DERMIS; IN-VITRO; RECONSTRUCTION; COLLAGEN; VIVO; IDENTIFICATION AB Mesothelium tissues such as peritoneum and pleura have a thin and strong layer of extracellular matrix that supports mesothelial cells capable of rapid healing. Decellularized porcine mesothelium was characterized for strength, composition of the matrix and biological activity. The tensile strength of the material was 40.65 +/- 21.65 N/cm. Extracellular matrix proteins collagen IV, fibronectin, and laminin as well as glycosaminoglycans were present in the material. Cytokines inherent in the extracellular matrix were preserved. Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and transforming growth factor beta (TGF-beta) were retained and the levels of VEGF and TGF-beta in the decellularized mesothelium were higher than those found in decellularized small intestinal submucosa (SIS). The decellularized mesothelium also stimulated human fibroblasts to produce more VEGF than fibroblasts grown on tissue culture plastic. Decellularized mesothelium is a sheet material with a combination of strength and biological activity that may have many potential applications in surgical repair and regenerative medicine. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Vacanti, Joseph R.] Massachusetts Gen Hosp Children, Dept Pediat Surg, Boston, MA 02114 USA. [Hoganson, David M.; Owens, Gwen E.; O'Doherty, Elisabeth M.; Neville, Craig M.; Vacanti, Joseph R.] Massachusetts Gen Hosp, Ctr Regenerat Med, Dept Surg, Boston, MA 02114 USA. [Bowley, Chris M.; Goldman, Scott M.; Harilal, Dina O.; Kronengold, Russell T.] Kensey Nash Corp, Exton, PA 19341 USA. RP Vacanti, JR (reprint author), Massachusetts Gen Hosp Children, Dept Pediat Surg, 55 Fruit St,Warren 1151, Boston, MA 02114 USA. EM jvacanti@partners.org OI Hoganson, David/0000-0002-8141-7793 FU Kensey Nash Corporation; NIH [F32 DK076349-01] FX This study was funded in part by a generous gift from Kensey Nash Corporation. The authors gratefully acknowledge support from the NIH (F32 DK076349-01, DMH). The authors also acknowledge expert assistance with the immunofluorescent staining from Dennis Brown and Margaret McLaughlin from the Massachusetts General Hospital Program in Membrane Biology and would like to thank Kevin Graham for assistance with material preparation and testing. NR 42 TC 26 Z9 27 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2010 VL 31 IS 27 BP 6934 EP 6940 DI 10.1016/j.biomaterials.2010.05.026 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 634WJ UT WOS:000280616300005 PM 20584548 ER PT J AU Oral, E Ghali, BW Rowell, SL Micheli, BR Lozynsky, AJ Muratoglu, OK AF Oral, Ebru Ghali, Bassem W. Rowell, Shannon L. Micheli, Brad R. Lozynsky, Andrew J. Muratoglu, Orhun K. TI A surface crosslinked UHMWPE stabilized by vitamin E with low wear and high fatigue strength SO BIOMATERIALS LA English DT Article DE Vitamin E; Arthroplasty; Delamination; Interface; Biomaterial; Implant ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL HIP-ARTHROPLASTY; ALPHA-TOCOPHEROL; PROPAGATION RESISTANCE; ACETABULAR COMPONENTS; MECHANICAL-PROPERTIES; LINKING; IRRADIATION; OXIDATION; REPLACEMENT AB Wear particle-induced periprosthetic osteolysis has been a clinical problem driving the development of wear resistant ultrahigh molecular weight polyethylene (UHMWPE) for total joint replacement. Radiation crosslinking has been used to decrease wear through decreased plastic deformation; but crosslinking also reduces mechanical properties including fatigue resistance, a major factor limiting the longevity of joint implants. Reducing UHMWPE wear with minimal detriment to mechanical properties is an unaddressed need for articular bearing surface development. Here we report a novel approach to achieve this by limiting crosslinking to the articular surface. The antioxidant vitamin E reduces crosslinking efficiency in UHMWPE during irradiation with increasing concentration, thus we propose to spatially control the crosslink density distribution by controlling the vitamin E concentration profile. Surface crosslinking UHMWPE prepared using this approach had high wear resistance and decreased crosslinking in the bulk resulting in high fatigue crack propagation resistance. The interface region did not represent a weakness in the material due to the gradual change in the crosslink density. Such an implant has the potential of decreasing risk of fatigue fracture of total joint implants as well as expanding the use of UHMWPE to younger and more active patients. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Oral, Ebru; Ghali, Bassem W.; Rowell, Shannon L.; Micheli, Brad R.; Lozynsky, Andrew J.; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Oral, E (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM eoral@partners.org FU Zimmer, Inc. FX This work was funded by laboratory funds and a research grant from Zimmer, Inc. Dr. Muratoglu received royalties from Biomet, Inc. and Zimmer, Inc. Dr. Oral received royalties from Zimmer, Inc. NR 42 TC 34 Z9 38 U1 8 U2 46 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2010 VL 31 IS 27 BP 7051 EP 7060 DI 10.1016/j.biomaterials.2010.05.041 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 634WJ UT WOS:000280616300017 PM 20579730 ER PT J AU Rivkin, I Cohen, K Koffler, J Melikhov, D Peer, D Margalit, R AF Rivkin, Ilia Cohen, Keren Koffler, Jacob Melikhov, Dina Peer, Dan Margalit, Rimona TI Paclitaxel-clusters coated with hyaluronan as selective tumor-targeted nanovectors SO BIOMATERIALS LA English DT Article DE Paclitaxel; Drug delivery; Tumor targeting; Hyaluronan; Abraxane ID CONTAINING LIPOSOMES; HYPERSENSITIVITY REACTIONS; MOLECULAR-INTERACTIONS; PHOSPHOLIPID-BILAYERS; ANTITUMOR-ACTIVITY; SIRNA DELIVERY; IN-VIVO; CD44; TAXOL; FORMULATIONS AB Paclitaxel (PTX) is a widely used anti-tumor agent in the treatment of solid tumors. Lack of selective strategies to target FIX into tumor cells together with poor solubility necessitating detergent, are severe clinical limitations. To address these hurdles, we devised a strategy that utilized PTX insolubility, mixing it with lipids that self-assemble into nanoparticle-like clusters. These clusters were then coated with hyaluronan, a glycosaminoglycan (GAG), and termed PTX-GAGs. These particles, delivered PTX selectively into tumor cells in a CD44-dependent manner. Injected systemically to mice bearing solid tumors, the PTX-GAGs showed high safety profile and tumor accumulation. Tumor progression was exponential upon treatment with free PTX or PTX in albumin nanoparticles (the FDA-approved Taxol (R) and Abraxane (R), respectively). Under the same conditions, PTX-GAGs induced tumor arrest and were as potent as a 4-fold higher Taxol (R) dose. Our findings suggest GAGs merit further investigation as vehicles for taxanes, and may be applicable as carriers in other therapeutic settings. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Peer, Dan] Tel Aviv Univ, Lab Nanomed, Dept Cell Res & Immunol, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel. [Margalit, Rimona] Tel Aviv Univ, Dept Biochem & Mol Biol, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel. [Cohen, Keren; Peer, Dan; Margalit, Rimona] Tel Aviv Univ, Ctr Nanosci & Nanotechnol, IL-69978 Tel Aviv, Israel. [Peer, Dan] Harvard Univ, Immune Dis Inst, Sch Med, Boston, MA 02115 USA. RP Peer, D (reprint author), Tel Aviv Univ, Lab Nanomed, Dept Cell Res & Immunol, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel. EM peer@post.tau.ac.il; rimona@post.tau.ac.il RI Peer, Dan/A-1785-2011; Koffler, Yacov/K-7329-2012 OI Peer, Dan/0000-0001-8238-0673; FU Alon Foundation; European Union; Lewis family-trust for cancer research FX We declare no conflict of interests. This work was supported by grants from the Alon Foundation, the Marie Curie IRG-FP7 of the European Union, and the Lewis family-trust for cancer research to Dan Peer. NR 50 TC 89 Z9 94 U1 6 U2 58 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2010 VL 31 IS 27 BP 7106 EP 7114 DI 10.1016/j.biomaterials.2010.05.067 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 634WJ UT WOS:000280616300023 PM 20619792 ER PT J AU Carp, SA Dai, GP Boas, DA Franceschini, MA Kim, YR AF Carp, S. A. Dai, G. P. Boas, D. A. Franceschini, M. A. Kim, Y. R. TI Validation of diffuse correlation spectroscopy measurements of rodent cerebral blood flow with simultaneous arterial spin labeling MRI; towards MRI-optical continuous cerebral metabolic monitoring SO BIOMEDICAL OPTICS EXPRESS LA English DT Article AB Cerebral blood flow (CBF) during stepped hypercapnia was measured simultaneously in the rat brain using near-infrared diffuse correlation spectroscopy (DCS) and arterial spin labeling MRI (ASL). DCS and ASL CBF values agree very well, with high correlation (R = 0.86, p < 10(-9)), even when physiological instability perturbed the vascular response. A partial volume effect was evident in the smaller magnitude of the optical CBF response compared to the MRI values (averaged over the cortical area), primarily due to the inclusion of white matter in the optically sampled volume. The 8.2 and 11.7 mm mid-separation channels of the multi-distance optical probe had the lowest partial volume impact, reflecting similar to 75 % of the MR signal change. Using a multiplicative correction factor, the ASL CBF could be predicted with no more than 10% relative error, affording an opportunity for real-time relative cerebral metabolism monitoring in conjunction with MR measurement of cerebral blood volume using super paramagnetic contrast agents. (C) 2010 Optical Society of America C1 [Carp, S. A.; Dai, G. P.; Boas, D. A.; Franceschini, M. A.; Kim, Y. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Carp, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM carp@nmr.mgh.harvard.edu FU National Institute of Health (NIH) [R01EB006385, R01NS057476, R01EB001954, R01HD42908, P41RR014075, R01EB002066] FX Funding from National Institute of Health (NIH) grants R01EB006385, R01NS057476, R01EB001954, R01HD42908, P41RR014075, and R01EB002066. NR 46 TC 46 Z9 46 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD SEP 1 PY 2010 VL 1 IS 2 BP 553 EP 565 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA V21LN UT WOS:000208209200021 PM 21258489 ER PT J AU Hariri, LP Bouma, BE Waxman, S Shishkov, M Vakoc, BJ Suter, MJ Freilich, MI Oh, WY Rosenberg, M Tearney, GJ AF Hariri, Lida P. Bouma, Brett E. Waxman, Sergio Shishkov, Milen Vakoc, Benjamin J. Suter, Melissa J. Freilich, Mark I. Oh, Wang-Yul Rosenberg, Mireille Tearney, Guillermo J. TI An automatic image processing algorithm for initiating and terminating intracoronary OFDI pullback SO BIOMEDICAL OPTICS EXPRESS LA English DT Article AB Intracoronary optical frequency domain imaging (OFDI) provides high resolution, three-dimensional views of coronary artery microstructure, but requires a non-occlusive saline/contrast purge to displace blood for clear artery views. Recent studies utilized manual pullback initiation/termination based on real-time image observation. Automated pullback initiation/termination by real-time OFDI signal analysis would enable more efficient data acquisition. We evaluate the use of simple imaging parameters to automatically and robustly differentiate between diagnostic-quality clear artery wall (CAW) versus blood-obstructed fields (BOF). Algorithms are tested using intracoronary OCT human data retrospectively and intracoronary OFDI swine and human data prospectively. In prospective analysis of OFDI swine data, the sensitivity and specificity of the ratio of second and first moments (contrast parameter) were 99.6% and 97.2%, respectively. In prospective analysis of OFDI clinical data, the contrast parameter yielded 96.0% sensitivity and 94.5% specificity. Accuracy improved further by analyzing sequential frames. These results indicate the algorithm may be utilized with intracoronary OFDI for initiating and terminating automated pullback and digital data recording. (C) 2010 Optical Society of America C1 [Hariri, Lida P.; Bouma, Brett E.; Shishkov, Milen; Vakoc, Benjamin J.; Suter, Melissa J.; Oh, Wang-Yul; Rosenberg, Mireille; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hariri, Lida P.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bouma, Brett E.; Shishkov, Milen; Vakoc, Benjamin J.; Suter, Melissa J.; Oh, Wang-Yul] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Waxman, Sergio; Freilich, Mark I.] Lahey Clin Fdn, Dept Cardiol, Burlington, MA 01803 USA. [Bouma, Brett E.; Vakoc, Benjamin J.; Tearney, Guillermo J.] MIT Harvard Div Hlth Sci & Technol, Cambridge, MA USA. RP Hariri, LP (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM lhariri@partners.org FU National Institutes of Health [R01HL076398 (NHLBI)]; Terumo Corporation FX This work was supported in part by the National Institutes of Health under Grant R01HL076398 (NHLBI). Terumo Corporation sponsors non-clinical OFDI research in the laboratory of Drs. Tearney and Bouma and has a technology-licensing arrangement with Massachusetts General Hospital. Drs. Tearney and Bouma have the right to receive licensing income from Terumo Corporation. NR 19 TC 2 Z9 2 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD SEP 1 PY 2010 VL 1 IS 2 BP 566 EP 573 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA V21LN UT WOS:000208209200022 PM 21258490 ER PT J AU Finkelstein, DM Wang, R Ficociello, LH Schoenfeld, DA AF Finkelstein, Dianne M. Wang, Rui Ficociello, Linda H. Schoenfeld, David A. TI A Score Test for Association of a Longitudinal Marker and an Event with Missing Data SO BIOMETRICS LA English DT Article DE EM algorithm; Conditional expected score test (CEST); Interval-censored failure time data; Pooling repeated observations (PRO) logistic model; Random effects model ID PROPORTIONAL HAZARDS MODEL; FAILURE TIME DATA; MICROALBUMINURIA; REGRESSION; COVARIATE AB Often clinical studies periodically record information on disease progression as well as results from laboratory studies that are believed to reflect the progressing stages of the disease. A primary aim of such a study is to determine the relationship between the lab measurements and a disease progression. If there were no missing or censored data, these analyses would be straightforward. However, often patients miss visits, and return after their disease has progressed. In this case, not only is their progression time interval censored, but their lab test series is also incomplete. In this article, we propose a simple test for the association between a longitudinal marker and an event time from incomplete data. We derive the test using a very intuitive technique of calculating the expected complete data score conditional on the observed incomplete data (conditional expected score test, CEST). The problem was motivated by data from an observational study of patients with diabetes. C1 [Finkelstein, Dianne M.; Wang, Rui; Schoenfeld, David A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Finkelstein, Dianne M.; Wang, Rui; Schoenfeld, David A.] Harvard Univ, Biostat Unit, Boston, MA 02114 USA. [Ficociello, Linda H.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA. EM dfinkelstein@partners.org FU NIH [HD05520, CA 74302, CA075971, DK-41526] FX We wish to thank Drs Adrienne Cupples and Andrzej Krolewski for assistance with the diabetes data analysis, and Manor Ashkenazi and Peter Lazar for programming assistance. This work was partially funded by grants from the NIH: HD05520, CA 74302, CA075971, and DK-41526. NR 17 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2010 VL 66 IS 3 BP 726 EP 732 DI 10.1111/j.1541-0420.2009.01326.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 651TM UT WOS:000281950000007 PM 19754923 ER PT J AU Cook, AJ Li, Y Arterburn, D Tiwari, RC AF Cook, Andrea J. Li, Yi Arterburn, David Tiwari, Ram C. TI Spatial Cluster Detection for Weighted Outcomes Using Cumulative Geographic Residuals SO BIOMETRICS LA English DT Article DE Body mass index; Cumulative residuals; Generalized estimating equations; Socioeconomic status; Spatial cluster detection; Weighted linear regression ID LINEAR MIXED MODELS; NEIGHBORHOOD ENVIRONMENT; OBJECTIVE MEASURES; PHYSICAL-ACTIVITY AB P>Spatial cluster detection is an important methodology for identifying regions with excessive numbers of adverse health events without making strong model assumptions on the underlying spatial dependence structure. Previous work has focused on point or individual-level outcome data and few advances have been made when the outcome data are reported at an aggregated level, for example, at the county- or census-tract level. This article proposes a new class of spatial cluster detection methods for point or aggregate data, comprising of continuous, binary, and count data. Compared with the existing spatial cluster detection methods it has the following advantages. First, it readily incorporates region-specific weights, for example, based on a region's population or a region's outcome variance, which is the key for aggregate data. Second, the established general framework allows for area-level and individual-level covariate adjustment. A simulation study is conducted to evaluate the performance of the method. The proposed method is then applied to assess spatial clustering of high Body Mass Index in a health maintenance organization population in the Seattle, Washington, USA area. C1 [Cook, Andrea J.; Arterburn, David] Grp Hlth Res Inst, Biostat Unit, Seattle, WA 98101 USA. [Cook, Andrea J.] Univ Washington, Dept Biostat, Seattle, WA 98105 USA. [Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tiwari, Ram C.] US FDA, Off Biostat, CDR, Silver Spring, MD 20993 USA. RP Cook, AJ (reprint author), Grp Hlth Res Inst, Biostat Unit, Seattle, WA 98101 USA. EM cook.aj@ghc.org FU NIH [5P20RR020774, RO1 CA95747] FX The authors would like to thank the associate editor and reviewers for their helpful feedback. This work was supported for by NIH Roadmap 5P20RR020774 (AJC) and NIH RO1 CA95747(YL). NR 23 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2010 VL 66 IS 3 BP 783 EP 792 DI 10.1111/j.1541-0420.2009.01323.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 651TM UT WOS:000281950000013 PM 19751250 ER PT J AU Katz, MS Carroll, PR Cowan, JE Chan, JM D'Amico, AV AF Katz, Matthew S. Carroll, Peter R. Cowan, Janet E. Chan, June M. D'Amico, Anthony V. TI Association of statin and nonsteroidal anti-inflammatory drug use with prostate cancer outcomes: results from CaPSURE SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; statin; NSAID; all-cause mortality; prostatectomy; radiotherapy ID MYOCARDIAL-INFARCTION; RISK; METAANALYSIS; INHIBITORS; THERAPY; COHORT; DEATH; MEN AB OBJECTIVE To determine whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with the risk of prostate cancer and improved survival in men with prostate cancer. PATIENTS AND METHODS We retrospectively examined the association between NSAID and statin use among 7042 men who underwent radical prostatectomy (RP, 4611) or radiotherapy (RT, 2431) for prostate cancer between 1990 and 2003 identified in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a primarily community-based national prostate cancer registry. We compared clinical and sociodemographic variables by statin and NSAID use, using chi-square tests and multinomial logistic regression. We examined associations between medications and comorbid illness with mortality using unadjusted and adjusted Cox proportional hazard models. RESULTS The median (range) follow-up from treatment was 4 (0-16) years. In multivariate survival analysis, statin 'ever-use' was associated with a reduced risk of all-cause mortality (ACM) after RP (hazard ratio, HR, 0.35, 95% confidence interval, CI, 0.21-0.58) and RT (0.59, 0.37-0.94). NSAID ever-use was also associated with a reduced risk of ACM after RP (HR 0.47, 95% CI 0.30-0.75) and RT (0.39, 0.25-0.59). CONCLUSIONS In a population of men with prostate cancer, statin and NSAID ever-use were associated with a reduced risk of ACM. Our study highlights the importance of multidisciplinary survivorship care for men with prostate cancer. C1 [Katz, Matthew S.] Radiat Oncol Associates, Dept Radiat Oncol, St Med Ctr, Lowell, MA 01852 USA. [Katz, Matthew S.] Radiat Oncol Associates PA, Manchester, NH USA. [Katz, Matthew S.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Carroll, Peter R.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Chan, June M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Katz, MS (reprint author), Radiat Oncol Associates, Dept Radiat Oncol, St Med Ctr, 1 Hosp Dr, Lowell, MA 01852 USA. EM matt@roa-ne.com FU CaPSURE; TAP Pharmaceutical Products, Inc FX CaPSURE is grateful to our generous founding sponsor, TAP Pharmaceutical Products, Inc. Currently, CaPSURE is not using any NIH grant funding or funding from TAP Pharmaceutical Products, Inc. NR 26 TC 22 Z9 24 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD SEP PY 2010 VL 106 IS 5 BP 627 EP 632 DI 10.1111/j.1464-410X.2010.09232.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 639QP UT WOS:000280989600007 PM 20151961 ER PT J AU Choueiri, TK Regan, MM Rosenberg, JE Oh, WK Clement, J Amato, AM McDermott, D Cho, DC Atkins, MB Signoretti, S AF Choueiri, Toni K. Regan, Meredith M. Rosenberg, Jonathan E. Oh, William K. Clement, Jessica Amato, Angela M. McDermott, David Cho, Daniel C. Atkins, Michael B. Signoretti, Sabina TI Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy SO BJU INTERNATIONAL LA English DT Article DE renal cell cancer; vascular endothelial growth factor; carbonic anhydrase IX; pathological features ID INTERFERON-ALPHA; EXPRESSION; SURVIVAL; CANCER AB OBJECTIVE To investigate the utility of tumour carbonic anhydrase IX (CAIX) expression and histological features for predicting the outcome in patients with metastatic clear-cell renal cell carcinoma (mRCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy. PATIENTS AND METHODS We identified 118 patients with mRCC initiating first-line VEGF-targeted therapy, including 94 with clinical and histological data, and available tissue. The primary endpoint was to detect an interaction between sorafenib vs sunitinib treatment and CAIX status on tumour shrinkage. Other treatment outcomes were also assessed. RESULTS There was heterogeneity in tumour responsiveness to sunitinib or sorafenib according to CAIX status; the mean shrinkage was -17% vs -25% for sunitinib-treated patients with high vs low tumour CAIX expression, compared to -13% vs +9% for sorafenib-treated patients (P interaction, 0.05). A higher tumour clear-cell component was independently associated with greater tumour shrinkage (P = 0.02), response (P = 0.02) and treatment duration (P = 0.02). CONCLUSIONS Although CAIX expression had no prognostic value in patients with clear-cell mRCC treated with VEGF-targeted therapy, it might be a predictive biomarker for response to sorafenib treatment. Patients with a higher clear-cell component in their tumours are likely to have a superior clinical benefit from VEGF-targeted therapy. C1 [Choueiri, Toni K.; Regan, Meredith M.; Rosenberg, Jonathan E.; Oh, William K.; Clement, Jessica; Amato, Angela M.; McDermott, David; Cho, Daniel C.; Atkins, Michael B.; Signoretti, Sabina] Dana Farber Harvard Canc Ctr, Renal Canc Program, Boston, MA USA. RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Lank Ctr Genitourinary Onco, 44 Binney St, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu; ssignoretti@partners.org RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU Dana-Farber/Harvard Cancer Center Kidney SPORE NCI [P50CA101942] FX Supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE NCI P50CA101942. The authors acknowledge Ashley Brick and Miranda Rogers from Dana-Farber Cancer Institute, and Christabel Kwabi, Karishma Shah and Andrew Percy from Beth Israel Deaconess Medical Center, for their assistance in collecting renal cancer specimens and their help in creating the database. NR 20 TC 52 Z9 56 U1 3 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD SEP PY 2010 VL 106 IS 6 BP 772 EP 778 DI 10.1111/j.1464-410X.2010.09218.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 643HK UT WOS:000281286000008 PM 20230385 ER PT J AU Blashill, AJ AF Blashill, Aaron J. TI Elements of male body image: Prediction of depression, eating pathology and social sensitivity among gay men SO BODY IMAGE LA English DT Article DE Body image dissatisfaction; Body fat; Muscularity; Height; Depression; Eating pathology; Social sensitivity; Gay men ID NEGATIVE-EVALUATION-SCALE; BRIEF VERSION; DISORDERS; MUSCULARITY; DRIVE; FEAR; DISSATISFACTION; OBJECTIFICATION; EXTENSION; ANXIETY AB The aim of the current study was to assess the relative uniqueness of three components of male body image (i.e., muscle, body fat, and height dissatisfaction) in the prediction of indices of psychological distress (i.e., depression, eating restraint, eating concerns, and social sensitivity) among a community sample of 228 gay men. Results indicated that body fat dissatisfaction was predictive of all four criterion variables (controlling for muscle dissatisfaction). Conversely, muscle dissatisfaction was only associated with social sensitivity, while height dissatisfaction failed to significantly predict any of the criterion variables. These findings highlight the relative importance of body fat dissatisfaction among gay men and suggest that researchers and clinicians working with this population should utilize measures which include assessment of both muscularity and body fat. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Blashill, Aaron J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Blashill, Aaron J.] St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. RP Blashill, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org NR 37 TC 20 Z9 22 U1 3 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1740-1445 J9 BODY IMAGE JI Body Image PD SEP PY 2010 VL 7 IS 4 BP 310 EP 316 DI 10.1016/j.bodyim.2010.07.006 PG 7 WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary SC Psychology; Psychiatry GA 681VI UT WOS:000284348500007 PM 20813600 ER PT J AU Rosenblatt, J Bissonnette, A Ahmad, R Wu, Z Vasir, B Stevenson, K Zarwan, C Keefe, W Glotzbecker, B Mills, H Joyce, R Levine, JD Tzachanis, D Boussiotis, V Kufe, D Avigan, D AF Rosenblatt, J. Bissonnette, A. Ahmad, R. Wu, Z. Vasir, B. Stevenson, K. Zarwan, C. Keefe, W. Glotzbecker, B. Mills, H. Joyce, R. Levine, J. D. Tzachanis, D. Boussiotis, V. Kufe, D. Avigan, D. TI Immunomodulatory effects of vitamin D: implications for GVHD SO BONE MARROW TRANSPLANTATION LA English DT Article DE vitamin D; GVHD; DC ID VERSUS-HOST-DISEASE; NF-KAPPA-B; DENDRITIC CELLS; 1,25-DIHYDROXYVITAMIN D-3; T-CELLS; DIFFERENTIATION; MATURATION; STAT1; TRANSPLANTATION; INHIBITION AB GVHD remains a major source of morbidity and mortality after allogeneic BMT. GVHD is mediated by alloreactive T cells derived from the hematopoietic graft that target host tissues. Pre-clinical models have shown that presentation of alloantigens by host DCs results in the activation of donor-derived T cells that mediate GVHD. Strategies that interfere with the Ag-presenting capacity of DCs after allogeneic transplantation may decrease the risk of developing GVHD. Vitamin D is a hormone essential for calcium metabolism that shows immunomodulatory properties. We showed that correction of vitamin D deficiency appeared to mitigate manifestations of GVHD. In preclinical studies, we have shown that vitamin D inhibits DC maturation, polarizes T-cell populations toward the expression of Th2 as compared with Th1 cytokines, and blunts allogeneic T-cell proliferation in response to DC stimulation. Exposure to vitamin D resulted in increased expression of IDO, an enzyme responsible for tryptophan metabolism that is upregulated in tolerizing DCs. These data suggest that exposure to vitamin D results in immature DC populations that bias toward tolerizing rather than stimulatory T-cell populations. Vitamin D may therefore have a role in the prevention of GVHD. Bone Marrow Transplantation (2010) 45, 1463-1468; doi:10.1038/bmt.2009.366; published online 18 January 2010 C1 [Rosenblatt, J.; Zarwan, C.; Glotzbecker, B.; Mills, H.; Joyce, R.; Levine, J. D.; Tzachanis, D.; Boussiotis, V.; Avigan, D.] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Bissonnette, A.; Ahmad, R.; Wu, Z.; Vasir, B.; Stevenson, K.; Keefe, W.; Kufe, D.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Rosenblatt, J (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, East Campus,330 Brookline Ave,KS 136, Boston, MA 02215 USA. EM jrosenb1@bidmc.harvard.edu NR 23 TC 16 Z9 18 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD SEP PY 2010 VL 45 IS 9 BP 1463 EP 1468 DI 10.1038/bmt.2009.366 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 648CS UT WOS:000281668600013 PM 20081878 ER PT J AU Csercsa, R Dombovari, B Fabo, D Wittner, L Eross, L Entz, L Solyom, A Rasonyi, G Szucs, A Kelemen, A Jakus, R Juhos, V Grand, L Magony, A Halasz, P Freund, TF Magloczky, Z Cash, SS Papp, L Karmos, G Halgren, E Ulbert, I AF Csercsa, Richard Dombovari, Balazs Fabo, Daniel Wittner, Lucia Eross, Lorand Entz, Laszlo Solyom, Andras Rasonyi, Gyoergy Szucs, Anna Kelemen, Anna Jakus, Rita Juhos, Vera Grand, Laszlo Magony, Andor Halasz, Peter Freund, Tamas F. Magloczky, Zsofia Cash, Sydney S. Papp, Laszlo Karmos, Gyoergy Halgren, Eric Ulbert, Istvan TI Laminar analysis of slow wave activity in humans SO BRAIN LA English DT Article DE current source density; unit activity; laminar recording; slow wave activity; sleep ID HIGH-FREQUENCY OSCILLATIONS; CURRENT SOURCE-DENSITY; INTERICTAL SPIKE GENERATION; ACTIVITY IN-VIVO; PREFRONTAL CORTEX; TEMPORAL-LOBE; NEURONAL OSCILLATIONS; NEOCORTICAL NEURONS; SYNAPTIC CONNECTIONS; ENTORHINAL CORTEX AB Brain electrical activity is largely composed of oscillations at characteristic frequencies. These rhythms are hierarchically organized and are thought to perform important pathological and physiological functions. The slow wave is a fundamental cortical rhythm that emerges in deep non-rapid eye movement sleep. In animals, the slow wave modulates delta, theta, spindle, alpha, beta, gamma and ripple oscillations, thus orchestrating brain electrical rhythms in sleep. While slow wave activity can enhance epileptic manifestations, it is also thought to underlie essential restorative processes and facilitate the consolidation of declarative memories. Animal studies show that slow wave activity is composed of rhythmically recurring phases of widespread, increased cortical cellular and synaptic activity, referred to as active- or up-state, followed by cellular and synaptic inactivation, referred to as silent- or down-state. However, its neural mechanisms in humans are poorly understood, since the traditional intracellular techniques used in animals are inappropriate for investigating the cellular and synaptic/transmembrane events in humans. To elucidate the intracortical neuronal mechanisms of slow wave activity in humans, novel, laminar multichannel microelectrodes were chronically implanted into the cortex of patients with drug-resistant focal epilepsy undergoing cortical mapping for seizure focus localization. Intracortical laminar local field potential gradient, multiple-unit and single-unit activities were recorded during slow wave sleep, related to simultaneous electrocorticography, and analysed with current source density and spectral methods. We found that slow wave activity in humans reflects a rhythmic oscillation between widespread cortical activation and silence. Cortical activation was demonstrated as increased wideband (0.3-200 Hz) spectral power including virtually all bands of cortical oscillations, increased multiple- and single-unit activity and powerful inward transmembrane currents, mainly localized to the supragranular layers. Neuronal firing in the up-state was sparse and the average discharge rate of single cells was less than expected from animal studies. Action potentials at up-state onset were synchronized within +/- 10 ms across all cortical layers, suggesting that any layer could initiate firing at up-state onset. These findings provide strong direct experimental evidence that slow wave activity in humans is characterized by hyperpolarizing currents associated with suppressed cell firing, alternating with high levels of oscillatory synaptic/transmembrane activity associated with increased cell firing. Our results emphasize the major involvement of supragranular layers in the genesis of slow wave activity. C1 [Csercsa, Richard; Dombovari, Balazs; Fabo, Daniel; Wittner, Lucia; Entz, Laszlo; Grand, Laszlo; Magony, Andor; Karmos, Gyoergy; Ulbert, Istvan] Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. [Dombovari, Balazs; Grand, Laszlo; Halasz, Peter; Karmos, Gyoergy; Ulbert, Istvan] Pazmany Peter Catholic Univ, Fac Informat Technol, Budapest, Hungary. [Fabo, Daniel; Wittner, Lucia; Eross, Lorand; Entz, Laszlo; Solyom, Andras; Rasonyi, Gyoergy; Szucs, Anna; Kelemen, Anna; Jakus, Rita; Ulbert, Istvan] Natl Inst Neurosci, Budapest, Hungary. [Wittner, Lucia; Freund, Tamas F.; Magloczky, Zsofia] Hungarian Acad Sci, Inst Expt Med, Budapest, Hungary. [Juhos, Vera] Szent Istvan Hosp, Dept Neurol, Budapest, Hungary. [Magony, Andor] Univ Birmingham, Sch Clin & Expt Med, Birmingham, W Midlands, England. [Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Papp, Laszlo] Neuronelektrod Kft, Budapest, Hungary. [Halgren, Eric] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Halgren, Eric] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Halgren, Eric] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. RP Ulbert, I (reprint author), MTA PKI, Szondi U 83-85, H-1068 Budapest, Hungary. EM ulbert@cogpsyphy.hu RI Ulbert, Istvan/F-2213-2010; Wittner, Lucia/C-9386-2013; OI Wittner, Lucia/0000-0001-6800-0953; Eross, Lorand/0000-0002-5796-5546 FU NeuroProbes [IST-027017]; Epicure [LSH-CT-2006-037315]; OTKA [PD-77864, K-81357]; NKTH-ANR Neurogen [EB9282, NS18741] FX NeuroProbes IST-027017, Epicure LSH-CT-2006-037315, OTKA PD-77864, OTKA K-81357, NKTH-ANR Neurogen, EB9282, NS18741. NR 96 TC 89 Z9 90 U1 1 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2010 VL 133 BP 2814 EP 2829 DI 10.1093/brain/awq169 PN 9 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 646HE UT WOS:000281529000030 PM 20656697 ER PT J AU Hedley-Whyte, ET Stein, TD Cros, D AF Hedley-Whyte, E. T. Stein, T. D. Cros, D. TI Neuropathology of facial onset sensory and motor neuronopathy (fosmn syndrome) SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 17th International Congress of Neuropathology (ICN 2010) CY SEP 11-15, 2010 CL Salzburg, AUSTRIA C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 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 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2010 VL 20 SU 1 BP 31 EP 32 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 649TZ UT WOS:000281798100111 ER PT J AU Lain, AH Lieberman, A Pfannl, R Hedley-Whyte, ET AF Lain, A. H. Lieberman, A. Pfannl, R. Hedley-Whyte, E. T. TI Nodular bilateral amygdala degeneration in dementing disorders SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 17th International Congress of Neuropathology (ICN 2010) CY SEP 11-15, 2010 CL Salzburg, AUSTRIA C1 [Lain, A. H.; Hedley-Whyte, E. T.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA USA. [Lain, A. H.] Hosp Univ 12 Octubre, Dept Pathol Neuropathol, Madrid, Spain. [Lieberman, A.] Univ Michigan, Dept Pathol Neuropathol, Ann Arbor, MI 48109 USA. [Pfannl, R.] Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 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 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2010 VL 20 SU 1 BP 42 EP 42 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 649TZ UT WOS:000281798100148 ER PT J AU Horbinski, C Kofler, J Yeaney, G Camelo-Piragua, S Venneti, S Louis, DN Murdoch, G Nikiforova, M AF Horbinski, C. Kofler, J. Yeaney, G. Camelo-Piragua, S. Venneti, S. Louis, D. N. Murdoch, G. Nikiforova, M. TI Isocitrate dehydrogenase 1 mutations are adverse prognostic markers in gangliogliomas SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 17th International Congress of Neuropathology (ICN 2010) CY SEP 11-15, 2010 CL Salzburg, AUSTRIA C1 [Horbinski, C.] Univ Kentucky, Lexington, KY USA. [Kofler, J.; Venneti, S.; Murdoch, G.; Nikiforova, M.] Univ Pittsburgh, Pittsburgh, PA USA. [Yeaney, G.] Univ Rochester, Rochester, NY USA. [Camelo-Piragua, S.; Louis, D. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2010 VL 20 SU 1 BP 47 EP 47 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 649TZ UT WOS:000281798100166 ER PT J AU Ahlfors, SP Han, J Belliveau, JW Hamalainen, MS AF Ahlfors, Seppo P. Han, Jooman Belliveau, John W. Haemaelaeinen, Matti S. TI Sensitivity of MEG and EEG to Source Orientation SO BRAIN TOPOGRAPHY LA English DT Article DE Magnetoencephalography; Electroencephalography; Suppression ratio; Current dipole; Radial source current ID SURFACE-BASED ANALYSIS; TO-NOISE-RATIOS; LOCALIZATION ACCURACY; HEAD MODEL; SIMULATION; BRAIN; MAGNETOENCEPHALOGRAPHY; ELECTROENCEPHALOGRAPHY; RECONSTRUCTION; ANISOTROPY AB An important difference between magnetoencephalography (MEG) and electroencephalography (EEG) is that MEG is insensitive to radially oriented sources. We quantified computationally the dependency of MEG and EEG on the source orientation using a forward model with realistic tissue boundaries. Similar to the simpler case of a spherical head model, in which MEG cannot see radial sources at all, for most cortical locations there was a source orientation to which MEG was insensitive. The median value for the ratio of the signal magnitude for the source orientation of the lowest and the highest sensitivity was 0.06 for MEG and 0.63 for EEG. The difference in the sensitivity to the source orientation is expected to contribute to systematic differences in the signal-to-noise ratio between MEG and EEG. C1 [Ahlfors, Seppo P.; Han, Jooman; Belliveau, John W.; Haemaelaeinen, Matti S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HST Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Ahlfors, Seppo P.; Belliveau, John W.; Haemaelaeinen, Matti S.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02135 USA. RP Ahlfors, SP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH HST Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Rm 2301, Boston, MA 02129 USA. EM seppo@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013; Ahlfors, Seppo/P-3644-2016 FU NIH [NS057500, NS037462, HD040712]; National Center for Research Resources [P41RR14075]; MIND Research Network FX This work was supported by NIH grants NS057500, NS037462, and HD040712. This work was supported in part by The National Center for Research Resources (P41RR14075) and the MIND Research Network. We thank Drs. David Cohen and Maria Mody for valuable discussions and comments on the manuscript. NR 37 TC 67 Z9 67 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0896-0267 J9 BRAIN TOPOGR JI Brain Topogr. PD SEP PY 2010 VL 23 IS 3 BP 227 EP 232 DI 10.1007/s10548-010-0154-x PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 634XK UT WOS:000280619300001 PM 20640882 ER PT J AU Butterly, A Bittner, EA George, E Sandberg, WS Eikermann, M Schmidt, U AF Butterly, A. Bittner, E. A. George, E. Sandberg, W. S. Eikermann, M. Schmidt, U. TI Postoperative residual curarization from intermediate-acting neuromuscular blocking agents delays recovery room discharge SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE muscle skeletal; neuromuscular block; recovery; relaxation ID POSTANESTHESIA CARE-UNIT; MUSCLE-RELAXANT; PARALYSIS; BLOCKADE; COMPLICATIONS; ROCURONIUM; PANCURONIUM; PHARYNGEAL; ANESTHESIA; VECURONIUM AB Background. Postoperative residual curarization (PORC) [train-of-four ratio (T4/T1) <0.9] is associated with increased morbidity and may delay postoperative recovery room (PACU) discharge. We tested the hypothesis that postoperative T4/T1 <0.9 increases PACU length of stay. Methods. At admission to the PACU, neuromuscular transmission was assessed by acceleromyography (stimulation current: 30 mA) in 246 consecutive patients. The potential consequences of PORC-induced increases in PACU length of stay on PACU throughput were estimated by application of a validated queuing model taking into account the rate of PACU admissions and mean length of stay in the joint system of the PACU plus patients recovering in operation theatre waiting for PACU beds. Results. PACU length of stay was significantly longer in patients with T4/T1 <0.9 (323 min), compared with patients with adequate recovery of neuromuscular transmission (243 min). Age (P=0.021) and diagnosis of T4/T1 <0.9 (P=0.027), but not the type of neuromuscular blocking agent, were independently associated with PACU length of stay. The incidence of T4/T1 <0.9 was higher in patients receiving vecuronium. Delayed discharge significantly increases the chances of patients having to wait to enter the PACU. The presence of PORC is estimated to be associated with significant delays in recovery room admission. Conclusions. PORC is associated with a delayed PACU discharge. The magnitude of the effect is clinically significant. In our system, PORC increases the chances of patients having to wait to enter the PACU. C1 [Butterly, A.; Bittner, E. A.; George, E.; Eikermann, M.; Schmidt, U.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Sandberg, W. S.] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA. [Eikermann, M.] Univ Klinikum Essen, Essen, Germany. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM meikermann@rics.bwh.harvard.edu FU Department of Anesthesia, Critical Care, and Pain Medicine of the Massachusetts General Hospital FX This study was supported by the Department of Anesthesia, Critical Care, and Pain Medicine of the Massachusetts General Hospital. NR 24 TC 57 Z9 65 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD SEP PY 2010 VL 105 IS 3 BP 304 EP 309 DI 10.1093/bja/aeq157 PG 6 WC Anesthesiology SC Anesthesiology GA 653FQ UT WOS:000282074300009 PM 20576632 ER PT J AU Reddy, VB Lerner, EA AF Reddy, V. B. Lerner, E. A. TI Plant cysteine proteases that evoke itch activate protease-activated receptors SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE cysteine protease; itch; protease-activated receptor; pruritus ID PRURITUS AB P>Background Bromelain, ficin and papain are cysteine proteases from plants that produce itch upon injection into skin. Their mechanism of action has not been considered previously. Objectives To determine the mechanism by which these proteases function. Methods The ability of these proteases to activate protease-activated receptors was determined by ratiometric calcium imaging. Results We show here that bromelain, ficin and papain activate protease-activated receptors 2 and 4. Conclusions Bromelain, ficin and papain function as signalling molecules and activate protease-activated receptors. Activation of these receptors is the likely mechanism by which these proteases evoke itch. C1 [Reddy, V. B.; Lerner, E. A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Lerner, EA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM elerner@partners.org RI Silva, Mariana/B-9530-2012 FU Massachusetts General Hospital; Shiseido Co., Ltd. FX This study was supported by an agreement between Massachusetts General Hospital and the Shiseido Co., Ltd. NR 12 TC 14 Z9 14 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD SEP PY 2010 VL 163 IS 3 BP 532 EP 535 DI 10.1111/j.1365-2133.2010.09862.x PG 4 WC Dermatology SC Dermatology GA 641NW UT WOS:000281135800016 PM 20491769 ER PT J AU Prabhu, SL Molinari, V Bowers, T Lomax, J AF Prabhu, Sheila Lobo Molinari, Victor Bowers, Theron Lomax, James TI Role of the family in suicide prevention: An attachment and family systems perspective SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article ID COMMUNITY RESILIENCE; PROTECTIVE FACTORS; CONTROLLED-TRIAL; THERAPY; RISK; ADOLESCENTS; STRATEGIES; DISORDER; IDEATION; BEHAVIOR AB Suicide can be an act of despair, anger, or escape from intolerable pain associated with prior bonding disturbances within the family system, interpersonal loss, and current perceived lack of social support. Using a variety of online databases, the authors examined the research on the family's role in preventing suicide from an attachment and family systems perspective. They found relevant articles describing how to make use of family support in suicide prevention. From a study of the literature, the authors outline three new family concepts in suicide prevention: family cohesion, family adhesion, and formation of a new family. Therapists should use every familial resource to avoid premature closure and to expand perception of support options. The authors suggest specific practice recommendations to successfully involve families in suicide prevention based on the outlined family conceptual framework, and they recommend research investigation to determine empirical validation of these tentative formulations. (Bulletin of the Menninger Clinic, 74[4], 301-327) C1 [Prabhu, Sheila Lobo; Bowers, Theron; Lomax, James] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Prabhu, Sheila Lobo; Bowers, Theron] Baylor Coll Med, Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Prabhu, SL (reprint author), Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, 6655 Travis, Houston, TX 77030 USA. EM SheilaM.Loboprabhu@med.va.gov NR 59 TC 9 Z9 9 U1 3 U2 9 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD FAL PY 2010 VL 74 IS 4 BP 301 EP 327 DI 10.1521/bumc.2010.74.4.301 PG 27 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 699MX UT WOS:000285668600003 ER PT J AU Ajani, JA Winter, KA Gunderson, LL Pedersen, J Benson, AB Thomas, CR Mayer, RJ Haddock, MG Rich, TA Willett, CG AF Ajani, Jaffer A. Winter, Kathryn A. Gunderson, Leonard L. Pedersen, John Benson, Al B., III Thomas, Charles R., Jr. Mayer, Robert J. Haddock, Michael G. Rich, Tyvin A. Willett, Christopher G. TI Prognostic Factors Derived from A Prospective Database Dictate Clinical Biology of Anal Cancer The Intergroup Trial (RTOG 98-11) SO CANCER LA English DT Article DE anal cancer; clinical biology; prognostic factors; prospective database; survival ID SQUAMOUS-CELL CARCINOMA; EPIDERMOID CARCINOMA; RANDOMIZED-TRIAL; RADIOTHERAPY; CHEMOTHERAPY; MANAGEMENT; RADIATION; MITOMYCIN; THERAPY; CHEMORADIATION AB BACKGROUND: Only 4 prospective randomized phase 3 trials have been reported for anal cancer. A prognostic factor analysis for anal cancer from a prospective database has been published from only 1 study (N = 110). To confirm and uncover new prognostic factors, we analyzed the prospective database of intergroup RTOG 98-11. METHODS: Univariate and multivariate analyses of the baseline characteristics for 5-year overall survival (OS) and disease-free survival (DFS) were carried out. Various combinations of tumor diameter and clinically positive nodes (N+) were analyzed to identify subgroups. RESULTS: A total of 644 were assessable and analyzed. Tumor diameter >5 cm was associated with poorer 5-year DFS (P = .0003) and poorer 5-year OS (P = .0031), and N+ was associated with poorer 5-year DFS (P <= .0001) and poorer 5-year OS (P = <= .0001) in the multivariate analysis. In stratified analyses, N+ had more adverse influence on DFS and OS than did tumor diameter. Patients with >5-cm tumor and N+ had the worst DFS (only 30% at 3 years compared with 74% for the best group; <5 cm primary and NO) and OS (only 48% at 4 years compared with 81% for the best group; <5 cm primary and NO). Men had worse DFS (P = .02) and OS (P = .016). These factors maintained their influence in each treatment arm. CONCLUSIONS: This prospective prognostic factor analysis establishes tumor diameter as an independent prognosticator of poorer 5-year DFS and OS and confirms N+ and male sex as poor prognostic factors. This analysis also uncovers novel subgroups (derived from combining prognostic factors) with incremental worsening of DFS and OS. Cancer 2010;116:4007-13. (C) 2010 American Cancer Society. C1 [Ajani, Jaffer A.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Winter, Kathryn A.] Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Gunderson, Leonard L.] Mayo Clin, Scottsdale, AZ USA. [Benson, Al B., III] Northwestern Univ, Chicago, IL USA. [Thomas, Charles R., Jr.] Knight Canc Inst, Portland, OR USA. [Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Portland, OR USA. [Mayer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Haddock, Michael G.] Mayo Clin, Rochester, MN USA. [Rich, Tyvin A.] Univ Virginia, Charlottesville, VA USA. [Willett, Christopher G.] Duke Univ, Durham, NC USA. RP Ajani, JA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, 1515 Holcombe Blvd,Mail Stop 426, Houston, TX 77030 USA. EM jajani@mdanderson.org FU National Cancer Institute, Bethesda, Maryland [U10 CA21661, U10 CA37422, U10 CA32115] FX Supported by RTOG U10 CA21661, CCOP U10 CA37422, and Star U10 CA32115 from the National Cancer Institute, Bethesda, Maryland. Registration number: NCT00003596 (www.clinicaltrials.gov). NR 25 TC 39 Z9 39 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2010 VL 116 IS 17 BP 4007 EP 4013 DI 10.1002/cncr.25188 PG 7 WC Oncology SC Oncology GA 640CS UT WOS:000281026000007 PM 20564111 ER PT J AU Yin, L Ahmad, R Kosugi, M Kawano, T Avigan, D Stone, R Kharbanda, S Kufe, D AF Yin, Li Ahmad, Rehan Kosugi, Michio Kawano, Takeshi Avigan, David Stone, Richard Kharbanda, Surender Kufe, Donald TI Terminal differentiation of chronic myelogenous leukemia cells is induced by targeting of the MUC1-C oncoprotein SO CANCER BIOLOGY & THERAPY LA English DT Article DE MUC1; CML; Bcr-Abl; myeloid differentiation; targeted therapy ID CHRONIC MYELOID-LEUKEMIA; CARCINOMA-ASSOCIATED ANTIGEN; BCR-ABL; BETA-CATENIN; STEM-CELLS; CANCER; THERAPY; KINASE; CML; HEAT-SHOCK-PROTEIN-90 AB Chronic myelogenous leukemia (CML) is caused by expression of the Bcr-Abl fusion protein in hematopoietic stem cells. The MUC1-C oncoprotein is expressed in CML blasts and stabilizes Bcr-Abl. The present studies demonstrate that treatment of KU812 and K562 CML cells with GO-201, a cell-penetrating peptide inhibitor of MUC1-C oligomerization, downregulates Bcr-Abl expression and inhibits cell growth. In concert with decreases in Bcr-Abl levels, KU812 and K562 cells responded to GO-201 with induction of a differentiated myeloid phenotype as evidenced by increased expression of CD11b, CD11c and CD14. The results also show that the GO-201-treated cells undergo a late apoptotic/necrotic response, consistent with induction of terminal differentiation. Primary CML blasts expressing MUC1 similarly responded to GO-201 with induction of a more differentiated phenotype and late apoptosis/necrosis. In addition, treatment of KU812 xenografts in nude mice was associated with upregulation of CD11 and tumor regression. These findings indicate that CML blasts respond to targeting of the MUC1-C oncoprotein with induction of terminal differentiation. C1 [Yin, Li; Ahmad, Rehan; Kosugi, Michio; Kawano, Takeshi; Stone, Richard; Kharbanda, Surender; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Avigan, David] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Donald_Kufe@dfci.harvard.edu FU National Cancer Institute [CA42802]; Multiple Myeloma Research Foundation; Leukemia Lymphoma Society; Genus Oncology [GO-201, CP-1] FX This work was supported by grants from the National Cancer Institute (CA42802), the Multiple Myeloma Research Foundation and the Leukemia Lymphoma Society. GO-201 and CP-1 were provided by Genus Oncology. NR 30 TC 10 Z9 11 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD SEP 1 PY 2010 VL 10 IS 5 DI 10.4161/cbt.10.5.12584 PG 9 WC Oncology SC Oncology GA 651EZ UT WOS:000281909400011 PM 20592495 ER PT J AU Allen, JD Othus, MKD Hart, A Tom, L Li, Y Berry, D Bowen, D AF Allen, Jennifer D. Othus, Megan K. D. Hart, Alton, Jr. Tom, Laura Li, Yi Berry, Donna Bowen, Deborah TI A Randomized Trial of a Computer-Tailored Decision Aid to Improve Prostate Cancer Screening Decisions: Results from the Take the Wheel Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AFRICAN-AMERICAN MEN; PATIENT EDUCATION; ANTIGEN TEST; KNOWLEDGE; INTERVENTIONS; INFORMATION; HEALTH; MORTALITY; PROGRAMS; BENEFITS AB Objective: To evaluate a decision aid (DA) designed to promote informed decision making for prostate cancer screening. Methods: Twelve work sites were randomly assigned to an intervention or nonintervention comparison condition. Intervention sites received access to a computer-tailored DA at the workplace. Male employees age 45 years and above (n = 625) completed surveys at baseline and at 3-month follow-up, documenting aspects of informed decision making. Results: Using an intention-to-treat analysis, men in the intervention group were significantly more likely to have made a screening decision and to have improved knowledge without increased decisional conflict, relative to men in the comparison group. These changes were observed despite the fact that only 30% of men in intervention sites used the DA. Among DA users, similar improvements were observed, although the magnitudes of changes were substantially greater, and significant improvements in decision self-efficacy were observed. Conclusions: A DA offered in the workplace promoted decision making, improved knowledge, and increased decision self-efficacy among users, without increasing decisional conflict. However, participation was suboptimal, suggesting that better methods for engaging men in workplace interventions are needed. Impact Statement: This trial shows the efficacy of a computer-tailored DA in promoting informed decisions about prostate cancer screening. The DA was delivered through work sites, thereby providing access to resources required to participate in informed decision making without requiring a medical appointment. However, participation rates were suboptimal, and additional strategies for engaging men are needed. Cancer Epidemiol Biomarkers Prev; 19(9); 2172-86. (C) 2010 AACR. C1 [Allen, Jennifer D.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Allen, Jennifer D.] Harvard Univ, Sch Med, Boston, MA USA. [Othus, Megan K. D.; Li, Yi; Berry, Donna] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bowen, Deborah] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Hart, Alton, Jr.] Virginia Commonwealth Univ, Richmond, VA USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. EM jennifer_allen@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015 FU Centers for Disease Control and Prevention [3U48DP000064-01S1, SIP 21-04] FX Centers for Disease Control and Prevention (Grant 3U48DP000064-01S1, SIP 21-04 Community Intervention to Increase IDM for Prostate Cancer). NR 52 TC 21 Z9 21 U1 5 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2010 VL 19 IS 9 BP 2172 EP 2186 DI 10.1158/1055-9965.EPI-09-0410 PG 15 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 648HS UT WOS:000281683800007 PM 20716619 ER PT J AU Allen, JD Othus, MKD Shelton, RC Li, Y Norman, N Tom, L del Carmen, MG AF Allen, Jennifer D. Othus, Megan K. D. Shelton, Rachel C. Li, Yi Norman, Nancy Tom, Laura del Carmen, Marcela G. TI Parental Decision Making about the HPV Vaccine SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN-PAPILLOMAVIRUS VACCINATION; CERVICAL-CANCER; YOUNG-WOMEN; ACCEPTABILITY; ACCEPTANCE; INFORMATION; ATTITUDES; PREDICTORS; DAUGHTERS; KNOWLEDGE AB Background: Prophylactic human papillomavirus (HPV) vaccines are available, but uptake is suboptimal. Information on factors influencing parental decisions regarding vaccination will facilitate the development of successful interventions. Methods: Parents of girls ages 9 to 17 years (n = 476; cooperation rate = 67%) from a panel of U. S. households completed online surveys between September 2007 and January 2008, documenting vaccine knowledge, attitudes, and intentions. Results: Among those aware of the vaccine, 19% had already vaccinated their daughter(s), 34% intended to, 24% were undecided, and 24% had decided against vaccination. Awareness of HPV was high but knowledge levels were suboptimal (mean 72%, SEM 0.8%). Black and Hispanic parents were significantly less likely to be aware of the vaccine compared with White parents. In multivariate analyses, compared with parents who opposed vaccination, those who had already vaccinated their daughter(s) or who intended to do so had more positive attitudes, reported fewer barriers, and were more likely to perceive that family and friends would endorse vaccination. They also reported higher levels of trust in pharmaceutical companies that produce the vaccine. Conclusions: Despite limited knowledge, most parents had decided to vaccinate their daughter(s). Given evidence of diminished access to information among Black and Hispanic parents, programs should focus on reaching these groups. Interventions should address parental concerns about behavioral consequences, reduce structural barriers, and promote the perception that vaccination is endorsed by significant others. Moreover, interventions may need to address mistrust of pharmaceutical companies. Impact Statement: This study documents factors associated with parental decisions about HPV vaccination for their daughter(s) and provides direction for intervention development. Cancer Epidemiol Biomarkers Prev; 19 (9); 2187-98. (C) 2010 AACR. C1 [Allen, Jennifer D.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Allen, Jennifer D.; Li, Yi; del Carmen, Marcela G.] Harvard Univ, Sch Med, Boston, MA USA. [Norman, Nancy] Boston Publ Hlth Commiss, Boston, MA USA. [del Carmen, Marcela G.] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. [Othus, Megan K. D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Shelton, Rachel C.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave, Boston, MA 02115 USA. EM Jennifer_Allen@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015 FU Dana-Farber/Harvard Cancer Center FX Dana-Farber/Harvard Cancer Center Nodal Point Award. NR 42 TC 87 Z9 87 U1 3 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2010 VL 19 IS 9 BP 2187 EP 2198 DI 10.1158/1055-9965.EPI-10-0217 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 648HS UT WOS:000281683800008 PM 20826829 ER PT J AU Creaney, J Olsen, NJ Brims, F Dick, IM Musk, AW de Klerk, NH Skates, SJ Robinson, BWS AF Creaney, Jenette Olsen, Nola J. Brims, Fraser Dick, Ian M. Musk, Arthur W. de Klerk, Nicholas H. Skates, Steven J. Robinson, Bruce W. S. TI Serum Mesothelin for Early Detection of Asbestos-Induced Cancer Malignant Mesothelioma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PLEURAL MESOTHELIOMA; SOLUBLE MESOTHELIN; WESTERN-AUSTRALIA; BLUE ASBESTOS; VITAMIN-A; WITTENOOM; PREVENTION; MORTALITY; DIAGNOSIS; DISEASES AB Background: Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, primarily caused by exposure to asbestos. Since the recent discovery that serum mesothelin is a sensitive and highly specific biomarker for mesothelioma, one of the key issues raised is whether mesothelin levels represent a useful screening test for asbestos-exposed at-risk individuals. In this study, soluble mesothelin was determined in sequential serum samples collected from asbestos-exposed individuals before the development of mesothelioma. Methods: Archival serum samples from 106 individuals who developed mesothelioma, 99 asbestos-exposed individuals from the Wittenoom Cancer Surveillance Program, and 109 non-asbestos-exposed individuals from the Busselton Health Survey were identified. Serum mesothelin concentrations were determined using the MESOMARK assay. Results: Longitudinal mesothelin levels determined in healthy asbestos-exposed individuals over a period of 4 years were stable (Pearson's r = 0.96; P < 0.0001). There was no correlation between mesothelin concentration and cumulative asbestos exposure. Mesothelin concentrations were greater than the threshold value of 2.5 nmol/L in the penultimate serum sample before the diagnosis of mesothelioma in 17 of 106 people. Using an increase above the 95% confidence interval of the mean of a given individual's longitudinal mesothelin results, 33 of 82 individuals had increasing mesothelin levels before diagnosis. Conclusion: In a population with a high pretest probability of developing mesothelioma, the serum biomarker mesothelin is elevated in absolute terms in 15% and in relative terms in 40% of the group. Impact: Future studies examining a combination of biomarkers could improve sensitivity of screening. Cancer Epidemiol Biomarkers Prev; 19(9); 2238-46. (C) 2010 AACR. C1 [Creaney, Jenette; Dick, Ian M.; Robinson, Bruce W. S.] Univ Western Australia, Sch Med & Pharmacol, QEII Med Ctr, Nedlands, WA 6009, Australia. [Olsen, Nola J.; Brims, Fraser; Musk, Arthur W.; Robinson, Bruce W. S.] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia. [Olsen, Nola J.; Musk, Arthur W.; de Klerk, Nicholas H.] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia. [Creaney, Jenette; Dick, Ian M.; Musk, Arthur W.; de Klerk, Nicholas H.; Robinson, Bruce W. S.] Sir Charles Gairdner Hosp, Natl Res Ctr Asbestos Related Dis, Nedlands, WA 6009, Australia. [de Klerk, Nicholas H.] Telethon Inst Child Hlth Res, Biostat & Epidemiol Unit, Subiaco, WA, Australia. [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Creaney, J (reprint author), Univ Western Australia, Natl Res Ctr Asbestos Related Dis, Sch Med & Pharmacol M503, Sir Charles Gardiner Hosp, 4th Floor,G Block,Verdun Ave, Nedlands, WA 6009, Australia. EM creaneyj@cyllene.uwa.edu.au RI Robinson, Bruce/N-1900-2014; de Klerk, Nicholas/D-8388-2016; OI de Klerk, Nicholas/0000-0001-9223-0767; Brims, Fraser/0000-0002-6725-7535 FU Fujirebio Diagnostics, Inc.; National Health and Medical Research Council of Australia; Insurance Commission of Western Australia FX B. Robinson: commercial research grant, Fujirebio Diagnostics, Inc.; consultant/advisory board, Fujirebio Diagnostics, Inc. J. Creaney: consultant/advisory board, Fujirebio Diagnostics, Inc.; National Health and Medical Research Council of Australia and the Insurance Commission of Western Australia. NR 39 TC 30 Z9 30 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2010 VL 19 IS 9 BP 2238 EP 2246 DI 10.1158/1055-9965.EPI-10-0346 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 648HS UT WOS:000281683800013 PM 20651076 ER PT J AU Grandi, P Fernandez, J Szentirmai, O Carter, R Gianni, D Sena-Esteves, M Breakefield, XO AF Grandi, P. Fernandez, J. Szentirmai, O. Carter, R. Gianni, D. Sena-Esteves, M. Breakefield, X. O. TI Targeting HSV-1 virions for specific binding to epidermal growth factor receptor-vIII-bearing tumor cells SO CANCER GENE THERAPY LA English DT Article DE EGFR; oncolytic; HSV; glioma; tropism; glycoprotein C; mouse tumor model; HSV vector retargeting ID HERPES-SIMPLEX-VIRUS; ONCOLYTIC VIRUSES; CANCER-THERAPY; REPLICATION-COMPETENT; AMPLICON VECTORS; TYPE-1 INFECTION; MALIGNANT GLIOMA; HEPARAN-SULFATE; GLYCOPROTEIN-C; GENE-TRANSFER AB Oncolytic herpes simplex virus (HSV) vectors have been used in early phase human clinical trials as a therapy for recurrent malignant glioblastoma. This treatment proved safe but limited improvements in patient survival were observed. The potency of these vectors might be enhanced by targeting vector infectivity to tumor cells. Glioma tumors often express a mutant form (vIII) of the epidermal growth factor receptor (EGFR) resulting in the presence of a novel epitope on the cell surface. This epitope is specifically recognized by a single-chain antibody designated MR1-1. HSV-1 infection involves initial binding to heparan sulfate (HS) on the cell surface mediated primarily by the viral envelope, glycoprotein C (gC). Here we joined the MR1-1 single-chain antibody (scFv) to the gC sequence deleted for the HS-binding domain as a means of targeting viral attachment to EGFRvIII on glial tumor cells. Virions bearing MR1-1-modified gC had fivefold increased infectivity for EGFRvIII-bearing human glioma U87 cells compared to mutant receptor-deficient cells. Further, MR1-1/EGFRvIII-mediated infection was more efficient for EGFRvIII-positive cells than was wild-type virus for either positive or negative cells. Sustained infection of EGFRvIII+ glioma cells by MR1-1-modified gC-bearing oncolytic virus, as compared to wild-type gC oncolytic virus, was also shown in subcutaneous tumors in vivo using firefly luciferase as a reporter of infection. These data show that HSV tropism can be manipulated so that virions recognize a cell-specific binding site with increased infectivity for the target cell. The retargeting of HSV infection to tumor cells should enhance vector specificity, tumor cell killing and vector safety. Cancer Gene Therapy (2010) 17, 655-663; doi:10.1038/cgt.2010.22; published online 28 May 2010 C1 [Grandi, P.; Fernandez, J.; Gianni, D.; Sena-Esteves, M.; Breakefield, X. O.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Grandi, P.; Fernandez, J.; Gianni, D.; Sena-Esteves, M.; Breakefield, X. O.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Szentirmai, O.; Carter, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Szentirmai, O.; Carter, R.] Harvard Univ, Sch Med, Neurosci Program, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Grandi, P (reprint author), UPMC Presbyterian, Dept Neurol Surg, Suite B-400,200 Lothrop St, Pittsburgh, PA 15213 USA. EM pag24@mgb.pitt.edu FU NCI [CA69246, CA92782, CA119298]; NINDS [NS 40923] FX We thank Dr Bigner for his kind gift of the MR1-1 and MRB constructs. We also thank Ms Deborah Schuback for advice on virion purification and western blots, Ms Suzanne McDavitt for skilled editorial assistance and the Center for Molecular Imaging Research at Massachusetts General Hospital for help and facilities to assess bioluminescence. This work was supported by NCI Grants CA69246, CA92782 and CA119298, and by NINDS NS 40923. NR 51 TC 10 Z9 11 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD SEP PY 2010 VL 17 IS 9 BP 655 EP 663 DI 10.1038/cgt.2010.22 PG 9 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 639YF UT WOS:000281012400006 PM 20508670 ER PT J AU Campbell, TC Carey, EC Jackson, VA Saraiya, B Yang, HB Back, AL Arnold, RM AF Campbell, Toby C. Carey, Elise C. Jackson, Vicki A. Saraiya, Biren Yang, Holly B. Back, Anthony L. Arnold, Robert M. TI Discussing Prognosis Balancing Hope and Realism SO CANCER JOURNAL LA English DT Review DE Cancer prognosis; hope; realism ID BREAKING BAD-NEWS; ILL CANCER-PATIENTS; PHYSICIAN COMMUNICATION; PATIENTS PREFERENCES; LIFE; INFORMATION; DISCLOSURE; ONCOLOGISTS; END; PERCEPTIONS AB "How much time do I have?" A patient's question about his/her life expectancy is among the most difficult of conversation topics. Oncologists, often with very little training in communication, routinely handle these requests for sensitive information. Oncologists are aware of the emotional weight surrounding a prognosis discussion: answering a prognosis question poorly can damage both a patient's sense of hope and the relationship with his/her physician. Conversely, when handled well, the discussion can affirm the relationship, build trust, and leave the patient feeling hopeful. Our review presents clinicians with a practical approach to handling prognosis discussions by dealing with 4 critical issues. First, we review what information should be conveyed about a patient's prognosis. Next, we provide tools to help the oncologist deal with a patient's emotional reaction. Then, we provide a framework for the discussion that helps preserve a patient's hope despite a poor prognosis. Finally, we address the impact on the physician and provide some suggestions for dealing with our own emotional reactions. C1 [Carey, Elise C.] May Clin, Rochester, NY USA. [Jackson, Vicki A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Saraiya, Biren] Robert Wood Johnson Univ Hosp, New Brunswick, NJ USA. [Yang, Holly B.] San Diego Hosp, San Diego, CA USA. [Back, Anthony L.] Univ Washington, Seattle, WA 98195 USA. [Arnold, Robert M.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Campbell, TC (reprint author), Univ Wisconsin, Hlth Sci Learning Ctr, Sch Med & Publ Hlth, 750 Highland Ave, Madison, WI 53705 USA. EM tcc@medicine.wisc.edu NR 39 TC 19 Z9 19 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD SEP-OCT PY 2010 VL 16 IS 5 SI SI BP 461 EP 466 DI 10.1097/PPO.0b013e3181f30e07 PG 6 WC Oncology SC Oncology GA 656TG UT WOS:000282359100007 PM 20890141 ER PT J AU Engelman, JA Cantley, LC AF Engelman, Jeffrey A. Cantley, Lewis C. TI Chemoprevention Meets Glucose Control SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID MAMMALIAN TARGET; CELL-GROWTH; RAPAMYCIN; CANCER; ACTIVATION; INHIBITION; METFORMIN; KINASE; PHOSPHORYLATION; TUMORIGENESIS AB The report by Memmott et al. (beginning on page 1066 in this issue of the journal) assessing the efficacy of the antidiabetes drug metformin in a mouse model of lung carcinogenesis suggests protective effects via two possible avenues: Decreased circulating insulin and insulin-like growth factor levels and energy stress leading to inhibition of mammalian target of rapamycin signaling. These potential mechanisms are discussed in this perspective, as are their implications for cancer prevention and therapy. Cancer Prev Res; 3(9); 1049-52. (C) 2010 AACR. C1 [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Engelman, Jeffrey A.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St,Room 7408, Charlestown, MA 02129 USA. EM jengelman@partners.org RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 30 TC 34 Z9 36 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD SEP PY 2010 VL 3 IS 9 BP 1049 EP 1052 DI 10.1158/1940-6207.CAPR-10-0178 PG 4 WC Oncology SC Oncology GA 646KH UT WOS:000281538400001 PM 20810671 ER PT J AU Karoor, V Le, M Merrick, D Dempsey, EC Miller, YE AF Karoor, Vijaya Le, Mysan Merrick, Daniel Dempsey, Edward C. Miller, York E. TI Vascular Endothelial Growth Factor Receptor 2-Targeted Chemoprevention of Murine Lung Tumors SO CANCER PREVENTION RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; TRANSGENIC MICE; CANCER; ANGIOGENESIS; INHIBITION; EXPRESSION; RISK; ADENOCARCINOMAS; OVEREXPRESSION; INDUCTION AB No clinically effective chemoprevention for lung cancer has been found. Angiogenesis is an early feature of both adenocarcinoma and squamous cell lung cancer. We investigated the effects of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) inhibition on lung carcinogenesis in a murine model of adenocarcinoma. The VEGFR-2 tyrosine kinase inhibitor, vandetanib, was given to FVB/N mice in chow for 7 days at varying doses to show pharmacologic activity by inhibition of VEGF-mediated VEFGR-2 and ERK phosphorylation. Plasma levels corroborated adequate dosage. For chemoprevention experiments, mice were injected i.p. with 1 mg/g of urethane, a carcinogen found in tobacco smoke. Chow containing vandetanib, 75 mg/kg/d, or control chow was given to mice, starting 7 days after urethane administration. Sixteen weeks after urethane injection, mice were sacrificed, tumors enumerated and measured. Vandetanib resulted in reductions in tumor multiplicity (6.5 +/- 0.86 versus 1.0 +/- 0.30, P = 0.001) and average tumor volume (0.85 +/- 0.10 versus 0.15 +/- 0.09 mm(3), P = 0.001), but not incidence (71% versus 100%, P = ns), compared with control. As vandetanib has other activities besides VEGFR-2 tyrosine kinase inhibition, we gave the anti-VEGFR-2 monoclonal antibody, DC101, for weeks 11 to 15 of a urethane carcinogenesis protocol with an arrest in tumor volume increase, but no change in multiplicity or incidence. Further investigation of the chemopreventive effect of vandetanib and other VEGF signaling inhibitors is needed. Cancer Prev Res; 3(9); 1141-7. (C) 2010 AACR. C1 [Miller, York E.] Univ Colorado, Denver Vet Affairs Med Ctr, Ctr Canc, Denver, CO 80220 USA. [Karoor, Vijaya; Dempsey, Edward C.; Miller, York E.] Univ Colorado, Dept Med, Denver, CO 80220 USA. [Merrick, Daniel] Univ Colorado, Dept Pathol, Denver, CO 80220 USA. [Le, Mysan; Merrick, Daniel; Dempsey, Edward C.; Miller, York E.] Dept Vet Affairs Med Ctr, Denver, CO USA. RP Miller, YE (reprint author), Univ Colorado, Denver Vet Affairs Med Ctr, Ctr Canc, Pulm 111A,1055 Clermont St, Denver, CO 80220 USA. EM york.miller@ucdenver.edu FU Department of Veterans Affairs; NCI [P50 CA58187]; NHLBI [RO1 HL078929]; PPG [HL14985] FX Department of Veterans Affairs Merit Review and NCI P50 CA58187 (Y.E. Miller), NHLBI RO1 HL078929, and PPG HL14985 (V. Karoor and E. C. Dempsey). NR 30 TC 8 Z9 8 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD SEP PY 2010 VL 3 IS 9 BP 1141 EP 1147 DI 10.1158/1940-6207.CAPR-10-0005 PG 7 WC Oncology SC Oncology GA 646KH UT WOS:000281538400013 PM 20647338 ER PT J AU Meyer, MS Penney, KL Stark, JR Schumacher, FR Sesso, HD Loda, M Fiorentino, M Finn, S Flavin, RJ Kurth, T Price, AL Giovannucci, EL Fall, K Stampfer, MJ Ma, J Mucci, LA AF Meyer, Mara S. Penney, Kathryn L. Stark, Jennifer R. Schumacher, Fredrick R. Sesso, Howard D. Loda, Massimo Fiorentino, Michelangelo Finn, Stephen Flavin, Richard J. Kurth, Tobias Price, Alkes L. Giovannucci, Edward L. Fall, Katja Stampfer, Meir J. Ma, Jing Mucci, Lorelei A. TI Genetic variation in RNASEL associated with prostate cancer risk and progression SO CARCINOGENESIS LA English DT Article ID C-REACTIVE PROTEIN; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCUS; COLORECTAL-CANCER; VARIANTS; MEN; INTERLEUKIN-6; MSR1; CARCINOGENESIS; POLYMORPHISMS AB Variation in genes contributing to the host immune response may mediate the relationship between inflammation and prostate carcinogenesis. RNASEL at chromosome 1q25 encodes ribonuclease L, part of the interferon-mediated immune response to viral infection. We therefore investigated the association between variation in RNASEL and prostate cancer risk and progression in a study of 1286 cases and 1264 controls nested within the prospective Physicians' Health Study. Eleven single-nucleotide polymorphisms (SNPs) were selected using the web-based 'Tagger' in the HapMap CEPH panel (Utah residents of Northern and Western European Ancestry). Unconditional logistic regression models assessed the relationship between each SNP and incident advanced stage (T(3)/T(4), T(0)-T(4)/M(1) and lethal disease) and high Gleason grade (>= 7) prostate cancer. Further analyses were stratified by calendar year of diagnosis. Cox proportional hazards models examined the relationship between genotype and prostate cancer-specific survival. We also explored associations between genotype and serum inflammatory biomarkers interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor-alpha receptor 2 using linear regression. Individuals homozygous for the variant allele of rs12757998 had an increased risk of prostate cancer [AA versus GG; odds ratio (OR): 1.63, 95% confidence interval (CI): 1.18-2.25), and more specifically, high-grade tumors (OR: 1.90, 95% CI: 1.25-2.89). The same genotype was associated with increased CRP (P = 0.02) and IL-6 (P = 0.05) levels. Missense mutations R462Q and D541E were associated with an increased risk of advanced stage disease only in the pre-prostate-specific antigen era. There were no significant associations with survival. The results of this study support a link between RNASEL and prostate cancer and suggest that the association may be mediated through inflammation. These novel findings warrant replication in future studies. C1 [Meyer, Mara S.; Penney, Kathryn L.; Stark, Jennifer R.; Kurth, Tobias; Price, Alkes L.; Giovannucci, Edward L.; Fall, Katja; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Sesso, Howard D.; Kurth, Tobias] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. [Loda, Massimo; Fiorentino, Michelangelo; Finn, Stephen; Flavin, Richard J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fall, Katja] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden. [Stampfer, Meir J.; Ma, Jing; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Stampfer, Meir J.; Ma, Jing; Mucci, Lorelei A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Meyer, MS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM mameyer@hsph.harvard.edu RI Rider, Jennifer/A-5371-2011; Fall, Katja/A-9186-2012; Kurth, Tobias/A-9243-2012; OI Kurth, Tobias/0000-0001-7169-2620; Rider, Jennifer/0000-0002-2637-6036; Finn, Stephen/0000-0002-8628-5814; Fall, Katja/0000-0002-3649-2639 FU French National Research Agency; National Institutes of Health; Merck; Migraine Research Foundation; Restless Legs Syndrome Foundation; National Cancer Institute [CA-058684, CA-34944, CA-40360, CA-097193]; National Institutes of Health [T32 CA-09001]; Harvard University Franklin Reynolds Fund; National Heart, Lung, and Blood Institute, Bethesda, MD [HL-26490, HL-34595] FX Conflict of Interest Statement: Dr Kurth has received within the last 2 years investigator-initiated research funding from the French National Research Agency, the National Institutes of Health, Merck and the Migraine Research Foundation. Furthermore, he is a consultant to i3 Drug Safety and World Health Information Science Consultants, LLC; he has received honoraria from Genzyme, Merck and Pfizer for educational lectures; he has received travel funds from the Restless Legs Syndrome Foundation. The other authors report no conflicts of interest.; National Cancer Institute (CA-058684 to M. J. S.); the National Research Service Award Training Program in Cancer Epidemiology from the National Institutes of Health (T32 CA-09001 to J. R. S. and K. L. P.); the Harvard University Franklin Reynolds Fund (to M. S. M.); L. A. M. is a Milken Scholar, Prostate Cancer Foundation. The Physicians' Health Study is supported by the National Cancer Institute (CA-34944, CA-40360, CA-097193); the National Heart, Lung, and Blood Institute (HL-26490, HL-34595), Bethesda, MD. NR 38 TC 23 Z9 26 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2010 VL 31 IS 9 BP 1597 EP 1603 DI 10.1093/carcin/bgq132 PG 7 WC Oncology SC Oncology GA 646HP UT WOS:000281530400013 PM 20576793 ER PT J AU Orea-Tejeda, A Orozco-Gutierrez, JJ Castillo-Martinez, L Keirns-Davies, C Montano-Hernandez, P Vazquez-Diaz, O Valdespino-Trejo, A Infante, O Martinez-Memije, R AF Orea-Tejeda, Arturo Jose Orozco-Gutierrez, Juan Castillo-Martinez, Lilia Keirns-Davies, Candace Montano-Hernandez, Patricia Vazquez-Diaz, Oscar Valdespino-Trejo, Adrian Infante, Oscar Martinez-Memije, Raul TI The effect of L-arginine and citrulline on endothelial function in patients in heart failure with preserved ejection fraction SO CARDIOLOGY JOURNAL LA English DT Article DE L-arginine; citrulline; heart failure; endothelial function ID NITRIC-OXIDE PRODUCTION; DILATION; DYSFUNCTION; AMPLITUDE; SYNTHASE AB Background To evaluate the effect of the amino acids L-arginine and citrulline on endothelial function in patients in stable diastolic and right heart failure using photoplethysmography Methods Thirty patients from the Heart Failure Clinic of the Instituto Nacional de Ciencias Medicas y Nutricion "Salvador Zubiran" underwent photoplethysmography using the hyperemia technique Index finger flow was assessed at baseline and after ischemia every 30 s by maximum amplitude time (MAT), total time of the curve (TT) and the index of the two (MAT/TT < 30 = normal) before and after the administration of L-arginine (8 g/day in two doses, n = 15) or citrulline (3 g/day in one dose, n = 15) for 60 days in addition to optimal pharmacological treatment Results There were no statistically significant differences between the two groups at baseline After the intervention, the MAT/TT index of all patients normalized in each evaluation period with statistically significant differences Basal L-arginine group = 38 75 +/- 11 52, final 23 32 +/- 6 08, p = 0 007 and basal citrulline group = 41 4 +/- 13 47, final 23 65 +/- 6 74, p = 0 007 at 60-90 s Post-ischemia basal L-arginine 36 60 +/- 11 51, final 18 81 +/- 15 13, p = 0 004 and basal citrulline = 49 51 +/- 15 1 7, final 27 13 +/- 7 87, p = 0 003 Conclusions The administration of L-arginine and citrulline has a beneficial effect on endothelial function as shown by the normalized MAT/TT index It probably improves systemic and pulmonary hemodynamics, which could help in the treatment of diastolic heart failure (Cardiol J 2010, 17, 5 464-470) C1 [Orea-Tejeda, Arturo; Keirns-Davies, Candace] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Cardiol, Mexico City 03100, DF, Mexico. [Orea-Tejeda, Arturo; Jose Orozco-Gutierrez, Juan; Castillo-Martinez, Lilia; Montano-Hernandez, Patricia; Vazquez-Diaz, Oscar; Valdespino-Trejo, Adrian] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Heart Failure Clin, Mexico City 03100, DF, Mexico. [Infante, Oscar; Martinez-Memije, Raul] Inst Nacl Cardiol ICh, Instrumentat Dept, Mexico City, DF, Mexico. [Keirns-Davies, Candace] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Castillo-Martinez, L (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Cardiol, Prov 1218-A 402 Col Valle, Mexico City 03100, DF, Mexico. RI Castillo-Martinez, Lilia/H-3750-2013 NR 29 TC 7 Z9 9 U1 1 U2 4 PU VIA MEDICA PI GDANSK PA UL SWIETOKRZYSKA 73, 80-180 GDANSK, POLAND SN 1897-5593 J9 CARDIOL J JI Cardiol. J. PD SEP PY 2010 VL 17 IS 5 BP 464 EP 470 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 681TI UT WOS:000284341800006 PM 20865676 ER PT J AU Haas, MS Alicot, EM Schuerpf, F Chiu, I Li, JN Moore, FD Carroll, MC AF Haas, Michael S. Alicot, Elisabeth M. Schuerpf, Franziska Chiu, Isaac Li, Jinan Moore, Francis D. Carroll, Michael C. TI Blockade of self-reactive IgM significantly reduces injury in a murine model of acute myocardial infarction SO CARDIOVASCULAR RESEARCH LA English DT Article DE Myocardial infarction; Peptides; Lymphocytes; Antibodies; Reperfusion ID ISCHEMIA-REPERFUSION INJURY; COMPLEMENT RECEPTOR TYPE-1; MANNOSE-BINDING LECTIN; SKELETAL-MUSCLE; ISCHEMIA/REPERFUSION INJURY; NATURAL IGM; MAST-CELLS; MONOCLONAL-ANTIBODY; HEART-DISEASE; IDENTIFICATION AB Coronary artery occlusion resulting in ischaemia/reperfusion (I/R) injury is a major cause of mortality in the western world. Circulating natural IgM has been shown to play a significant role in reperfusion injury, leading to the notion of a pathogenic response against self by the innate immune system. A specific self-antigen (non-muscle myosin heavy chain II) was recently identified as the major target of pathogenic natural IgM. Therefore, we hypothesized that a synthetic peptide mimetope (N2) or monoclonal antibodies directed against the self-antigen would prevent specific IgM binding to the self-antigen and reduce reperfusion injury in the heart. We find that treatment with N2 peptide reduces infarct size by 47% and serum cardiac troponin-I levels by 69% following 1 h ischaemia and 24 h reperfusion. N2 peptide or an anti-N2 F(ab')(2) (21G6) is also effective at preventing IgM and complement deposition. Additionally, N2 peptide treatment significantly reduces monocyte and neutrophil infiltration at 24 h and collagen deposition at 5 days. Finally, we show that human IgM (hIgM) also includes specificity for the highly conserved self-antigen and that myocardial injury in antibody-deficient mice reconstituted with hIgM is blocked by treatment with N2 peptide or 21G6 F(ab')(2). The findings in this study identify potential therapeutics [i.e. N2 peptide or 21G6 F(ab')(2)] that prevent specific IgM binding to ischaemic antigens in the heart, resulting in a significant reduction in cardiac I/R injury. C1 [Alicot, Elisabeth M.; Chiu, Isaac; Carroll, Michael C.] Harvard Univ, Dept Pediat, Childrens Hosp Boston, Sch Med, Boston, MA 02115 USA. [Haas, Michael S.; Alicot, Elisabeth M.; Schuerpf, Franziska] DecImmune Therapeut Inc, Boston, MA USA. [Chiu, Isaac; Carroll, Michael C.] Harvard Univ, Childrens Hosp Boston, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Sch Med, Boston, MA 02115 USA. [Li, Jinan] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden. [Moore, Francis D.] Harvard Univ, Dept Surg, Sch Med, Boston, MA 02115 USA. [Moore, Francis D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Harvard Univ, Dept Pediat, Childrens Hosp Boston, Sch Med, Boston, MA 02115 USA. EM carroll@idi.harvard.edu FU National Institutes of Health [GM52585, HL084821]; DecImmune Therapeutics, Inc. FX This work was partly funded by grants from the National Institutes of Health (GM52585 for M. C. C. and F. D. M.; HL084821 for E. M. A.) as well as support from DecImmune Therapeutics, Inc. NR 45 TC 32 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD SEP PY 2010 VL 87 IS 4 BP 618 EP 627 DI 10.1093/cvr/cvq141 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 638OR UT WOS:000280904700008 PM 20462867 ER PT J AU Nedeltchev, K Pattynama, PM Biaminoo, G Diehm, N Jaff, MR Hopkins, LN Ramee, S van Sambeek, M Talen, A Vermassen, F Cremonesi, A AF Nedeltchev, Krassen Pattynama, Peter M. Biaminoo, Giancarlo Diehm, Nicolas Jaff, Michael R. Hopkins, L. Nelson Ramee, Stephen van Sambeek, Marc Talen, Aly Vermassen, Frank Cremonesi, Alberto TI Standardized Definitions and Clinical Endpoints in Carotid Artery and Supra-Aortic Trunk Revascularization Trials SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE carotid artery; supra-aortic arteries; endovascular treatment; stents; endpoint definitions; clinical trials ID TRANSIENT ISCHEMIC ATTACK; RANDOMIZED CONTROLLED-TRIAL; HIGH-RISK PATIENTS; QUALITY-OF-LIFE; SYMPTOMATIC PATIENTS; ARCH CALCIFICATION; VERTEBRAL ARTERY; SUBCLAVIAN STEAL; STRING SIGN; BLOOD-FLOW AB Background: Endovascular therapy has emerged as a promising alternative to open surgery for stroke prevention in patients with obstructive disease of the supra-aortic arteries. Although most previous studies have used similar safety and efficacy endpoints, differences in definitions, timing of assessments, and standards of reporting have hampered direct comparisons across various trials. Methods and results: The DEFINE group, an informal collaboration of multidisciplinary physicians, involved in the therapy of patients with obstructive disease of the supra-aortic arteries in Europe and the United States reviewed the current literature and, after extensive correspondence and meetings, proposed the definitions outlined in the present manuscript. Three meetings including all authors of the manuscript, along with representatives of the United States Food and Drug Administration (FDA) and commercial device manufacturers were held in Barcelona, Spain, in May 2008, in Munich, Germany, in July 2008, and in New York in November 2008. The proposed definitions encompass baseline clinical and anatomic characteristics, clinical and radiologic outcomes, complications, standards of reporting, and timing of assessment. Conclusions: Considering the broad consensus between the multidisciplinary scientific members and the regulatory authorities, the proposed definitions are expected to find adoption in future clinical investigations. These definitions can be applied to both endovascular and open surgery trials and will allow reliable comparisons between these two revascularization methods. (C) 2010 Wiley-Liss, Inc C1 [Nedeltchev, Krassen] Triemli Hosp, Dept Neurol, CH-8063 Zurich, Switzerland. [Pattynama, Peter M.] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Biaminoo, Giancarlo; Cremonesi, Alberto] Villa Maria Cecilia Hosp, Grp Villa Maria Endovasc, Cotignola, Italy. [Diehm, Nicolas] Univ Bern, Inselspital, Swiss Cardiovasc Ctr, Div Clin & Intervent Angiol, CH-3012 Bern, Switzerland. [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vasc Ctr, Boston, MA USA. [Hopkins, L. Nelson] Sch Med & Biomed Sci, Dept Neurosurg, Buffalo, NY USA. [Ramee, Stephen] Ochsner Heart & Vasc Inst, New Orleans, LA USA. [van Sambeek, Marc] Catharina Hosp, Dept Surg, Eindhoven, Netherlands. [Talen, Aly] Genae Associates Nv, Antwerp, Belgium. [Vermassen, Frank] Ghent Univ Hosp, Dept Vasc Surg, B-9000 Ghent, Belgium. RP Nedeltchev, K (reprint author), Triemli Hosp, Dept Neurol, CH-8063 Zurich, Switzerland. NR 58 TC 7 Z9 7 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP 1 PY 2010 VL 76 IS 3 BP 333 EP 344 DI 10.1002/ccd.22560 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647CE UT WOS:000281592600004 PM 20506555 ER PT J AU Wu, PC Wang, Q Dong, ZM Chu, E Roberson, RS Ivanova, IC Wu, DY AF Wu, P. C. Wang, Q. Dong, Z. M. Chu, E. Roberson, R. S. Ivanova, I. C. Wu, D. Y. TI Expression of coxsackie and adenovirus receptor distinguishes transitional cancer states in therapy-induced cellular senescence SO CELL DEATH & DISEASE LA English DT Article DE cellular senescence; coxsackie and adenovirus receptor; transition state; biomarker ID MEDIATED GENE-TRANSFER; HUMAN TUMOR-CELLS; REPLICATIVE SENESCENCE; BARRETTS-ESOPHAGUS; FUNCTIONAL P53; GROWTH ARREST; HUMAN LUNG; P16(INK4A); FIBROBLASTS; SUPPRESSION AB Therapy-induced cellular senescence describes the phenomenon of cell cycle arrest that can be invoked in cancer cells in response to chemotherapy. Sustained proliferative arrest is often overcome as a contingent of senescent tumor cells can bypass this cell cycle restriction. The mechanism regulating cell cycle re-entry of senescent cancer cells remains poorly understood. This is the first report of the isolation and characterization of two distinct transitional states in chemotherapy-induced senescent cells that share indistinguishable morphological senescence phenotypes and are functionally classified by their ability to escape cell cycle arrest. It has been observed that cell surface expression of coxsackie and adenovirus receptor (CAR) is downregulated in cancer cells treated with chemotherapy. We show the novel use of surface CAR expression and adenoviral transduction to differentiate senescent states and also show in vivo evidence of CAR downregulation in colorectal cancer patients treated with neoadjuvant chemoradiation. This study suggests that CAR is a candidate biomarker for senescence response to antitumor therapy, and CAR expression can be used to distinguish transitional states in early senescence to study fundamental regulatory events in therapy-induced senescence. Cell Death and Disease (2010) 1, e70; doi:10.1038/cddis.2010.47; published online 2 September 2010 C1 [Wu, P. C.] Univ Washington, Dept Surg, Seattle, WA 98108 USA. [Wu, P. C.; Chu, E.] VA Puget Sound Hlth Care Syst, Dept Surg, Seattle, WA USA. [Wang, Q.; Roberson, R. S.; Ivanova, I. C.; Wu, D. Y.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Dong, Z. M.] VA Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA USA. [Wu, D. Y.] Univ Washington, Div Oncol, Dept Med, Seattle, WA 98108 USA. [Wu, D. Y.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Wu, PC (reprint author), Univ Washington, Dept Surg, 1660 S Columbian Way S-112, Seattle, WA 98108 USA. EM pcwu@u.washington.edu FU Veteran Affairs Office of Research & Development Medical Research Service; National Cancer Institute [R01-CA113892-01] FX This material is based on work supported by the Veteran Affairs Office of Research & Development Medical Research Service (Biomedical Laboratory R&D Career Development Award-2 to PCW) and National Cancer Institute (R01-CA113892-01 to DYW). We thank Dr. Liu Yang for his critical reading of our manuscript and his insightful suggestions. NR 38 TC 9 Z9 10 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD SEP PY 2010 VL 1 AR e70 DI 10.1038/cddis.2010.47 PG 10 WC Cell Biology SC Cell Biology GA 656UA UT WOS:000282361700002 PM 21364674 ER PT J AU Chen, LY Wang, DK Wu, ZT Ma, LP Daley, GQ AF Chen, Lingyi Wang, Dekun Wu, Zhaoting Ma, Liping Daley, George Q. TI Molecular basis of the first cell fate determination in mouse embryogenesis SO CELL RESEARCH LA English DT Review DE inner cell mass; trophectoderm; embryogenesis ID EMBRYONIC STEM-CELLS; X-CHROMOSOME INACTIVATION; ZYGOTIC PATERNAL GENOME; PREIMPLANTATION DEVELOPMENT; MAMMALIAN DEVELOPMENT; DNA METHYLATION; TROPHOBLAST DEVELOPMENT; TRANSCRIPTION FACTOR; REGULATES PLURIPOTENCY; DOSAGE COMPENSATION AB Through proliferation and differentiation, a single cell, the zygote, can give rise to a complex organism composed of many types of cells. Up to the eight-cell embryo stage, the blastomeres are morphologically identical and distributed symmetrically in the mammalian embryo. Functionally, in some species, they are all totipotent. However, due to the compaction of blastomeres and the asymmetrical cell division at the late phase of the eight-cell embryo, the blastomeres of the morula are no longer identical. During the transition from morula to blastocyst, blastomeres differentiate, resulting in the first cell fate decision in embryogenesis, namely, the segregation of the inner cell mass and the trophectoderm. In this review, we will discuss the regulatory mechanisms essential for the cell fate choice during blastocyst development, including transcriptional regulation, epigenetic regulation, microRNAs, and signal transduction. C1 [Chen, Lingyi; Wang, Dekun; Wu, Zhaoting; Ma, Liping] Nankai Univ, Coll Life Sci, Minist Educ, Key Lab Bioact Mat, Tianjin 300071, Peoples R China. [Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Harvard Stem Cell Inst, Boston, MA USA. [Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Chen, LY (reprint author), Nankai Univ, Coll Life Sci, Minist Educ, Key Lab Bioact Mat, 94 Weijin Rd, Tianjin 300071, Peoples R China. EM lingyichen@nankai.edu.cn; george.daley@childrens.harvard.edu RI Chen, Lingyi/G-6309-2013 FU National Institutes of Health; NIH Roadmap for Medical Research; Children's Hospital; Burroughs Wellcome Fund; Leukemia and Lymphoma Society; National Natural Science Foundation of China [90919009]; National Key Basic Research and Development Program of China [2009CB941000, 2010CB833603]; Ministry of Agriculture of China [2009ZX08006-010B, 2009ZX08006-011B] FX GQD was supported by grants from the National Institutes of Health, the NIH Director's Pioneer Award of the NIH Roadmap for Medical Research, and private funds contributed to the Harvard Stem Cell Institute and the Children's Hospital Stem Cell Program, USA. GQD is a recipient of Clinical Scientist Awards in Translational Research from the Burroughs Wellcome Fund and the Leukemia and Lymphoma Society, and is an Investigator at the Howard Hughes Medical Institute. LC was supported by the National Natural Science Foundation of China (Grant no. 90919009), the National Key Basic Research and Development Program of China (Grant no. 2009CB941000 and 2010CB833603), and the Ministry of Agriculture of China (Grant no. 2009ZX08006-010B and 2009ZX08006-011B). NR 116 TC 27 Z9 28 U1 1 U2 8 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD SEP PY 2010 VL 20 IS 9 BP 982 EP 993 DI 10.1038/cr.2010.106 PG 12 WC Cell Biology SC Cell Biology GA 645RZ UT WOS:000281483800005 PM 20628366 ER PT J AU Teodorescu, M Polomis, DA Hall, SV Teodorescu, MC Gangnon, RE Peterson, AG Xie, AL Sorkness, CA Jarjour, NN AF Teodorescu, Mihaela Polomis, David A. Hall, Stephanie V. Teodorescu, Mihai C. Gangnon, Ronald E. Peterson, Andrea G. Xie, Ailiang Sorkness, Christine A. Jarjour, Nizar N. TI Association of Obstructive Sleep Apnea Risk With Asthma Control in Adults SO CHEST LA English DT Article ID POSITIVE AIRWAY PRESSURE; BODY-MASS INDEX; TO-TREAT ASTHMA; CONTROL QUESTIONNAIRE; NOCTURNAL ASTHMA; HYPOXIA SUPPRESSES; BREATH CONDENSATE; INFLAMMATION; OBESITY; POPULATION AB Background: Unrecognized obstructive sleep apnea (OSA) may lead to poor asthma control despite optimal therapy. Our objective was to evaluate the relationship between OSA risk and asthma control in adults. Methods: Patients with asthma seen routinely at tertiary-care clinic visits completed the validated Sleep Apnea Scale of the Sleep Disorders Questionnaire (SA-SDQ) and Asthma Control Questionnaire (ACQ). An ACQ score of >= 1.5 defined not-well-controlled asthma, and an SA-SDQ score of >= 36 for men and >= 32 for women defined high OSA risk. Logistic regression was used to model associations of high OSA risk with not-well-controlled asthma (ACQ full version and short versions). Results: Among 472 subjects with asthma, the mean +/- SD ACQ (full version) score was 0.87 +/- 0.90, and 80 (17%) subjects were not well controlled. Mean SA-SDQ score was 27 +/- 7, and 109 (23%) subjects met the definition of high OSA risk. High OSA risk was associated, on average, with 2.87-times higher odds for not-well-controlled asthma (ACQ full version) (95% CI, 1.54-5.32; P = .0009) after adjusting for obesity and other factors known to worsen asthma control. Similar independent associations were seen when using the short ACQ versions. Conclusions: High OSA risk is significantly associated with not-well-controlled asthma independent of known asthma aggravators and regardless of the ACQ version used. Patients who have difficulty achieving adequate asthma control should be screened for OSA. CHEST 2010; 138(3):543-550 C1 [Teodorescu, Mihaela; Polomis, David A.; Hall, Stephanie V.; Peterson, Andrea G.; Xie, Ailiang; Sorkness, Christine A.; Jarjour, Nizar N.] Univ Wisconsin, Sch Med & Publ Hlth, Sect Allergy Pulm & Crit Care Med, Madison, WI 53792 USA. [Teodorescu, Mihaela; Teodorescu, Mihai C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Sleep Inst, Madison, WI 53792 USA. [Teodorescu, Mihai C.] Univ Wisconsin, Sch Med & Publ Hlth, Sect Geriatr & Gerontol, Madison, WI 53792 USA. [Gangnon, Ronald E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat & Populat Hlth Sci, Madison, WI 53792 USA. [Sorkness, Christine A.] Univ Wisconsin, Sch Pharm, Madison, WI 53792 USA. [Teodorescu, Mihaela; Teodorescu, Mihai C.] William S Middleton Mem Vet Adm Med Ctr, Med Serv, Madison, WI USA. RP Teodorescu, M (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Sect Allergy Pulm & Crit Care Med, K4-910 CSC 9988,600 Highland Ave, Madison, WI 53792 USA. EM mt3@medicine.wisc.edu FU University of Wisconsin School of Medicine and Public Health, Department of Medicine, and Medical Education and Research Committee-New Investigator [1UL1RR025011]; National Center for Research Resources, National Institutes of Health; Novartis; Merck; Asthmatx; National Institutes of Health; GlaxoSmith Kline; Medimmune; Genentech FX Funding/Support: This work was performed at the University of Wisconsin-Madison and was funded by the University of Wisconsin School of Medicine and Public Health, Department of Medicine, and Medical Education and Research Committee-New Investigator Award; 1UL1RR025011 from the Clinical and Translational Science Award program of the National Center for Research Resources, National Institutes of Health; and additional resources from the William S. Middleton Memorial Veterans Hospital, Madison, WI (to Dr M. Teodorescu).; Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Sorkness is on the advisory board for GlaxoSmithKline (<$10,000). Dr Jarjour is on the advisory board for GlaxoSmithKline and received speaker honoraria (each <$10,000) from Novartis and Merck and consulting fees (> $10,000) from Asthmatx. He received funding support from the National Institutes of Health, GlaxoSmith Kline, Medimmune, and Genentech. Drs M. Teodorescu, Polomis, M. C. Teodorescu, Gangnon, and Xie and Mss Hall and Peterson have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 50 TC 43 Z9 46 U1 3 U2 8 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2010 VL 138 IS 3 BP 543 EP 550 DI 10.1378/chest.09-3066 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 659IZ UT WOS:000282561500017 PM 20495105 ER PT J AU Sheu, CC Gong, MN Zhai, RH Chen, F Bajwa, EK Clardy, PF Gallagher, DC Thompson, BT Christiani, DC AF Sheu, Chau-Chyun Gong, Michelle N. Zhai, Rihong Chen, Feng Bajwa, Ednan K. Clardy, Peter F. Gallagher, Diana C. Thompson, B. Taylor Christiani, David C. TI Clinical Characteristics and Outcomes of Sepsis-Related vs Non-Sepsis-Related ARDS SO CHEST LA English DT Article ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; ADMISSION PLASMA-GLUCOSE; TIDAL VOLUME VENTILATION; INDEPENDENT RISK-FACTOR; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; ACTIVATED PROTEIN-C; SEPTIC SHOCK; HOSPITAL MORTALITY AB Background: ARDS may occur after either septic or nonseptie injuries. Sepsis is the major cause of ARDS, but little is known about the differences between sepsis-related and non-sepsis-related ARDS. Methods: A total of 2,786 patients with ARDS-predisposing conditions were enrolled consecutively into a prospective cohort, of which 736 patients developed ARDS. We defined sepsis-related ARDS as ARDS developing in patients with sepsis and non-sepsis-related ARDS as ARDS developing after nonseptie injuries, such as trauma, aspiration, and multiple transfusions. Patients with both septic and nonseptic risks were excluded from analysis. Results: Compared with patients with non-sepsis-related ARDS (n = 62), patients with sepsis-related ARDS (n = 524) were more likely to be women and to have diabetes, less likely to have preceding surgery, and had longer pre-ICU hospital stays and higher APACHE III (Acute Physiology and Chronic Health Evaluation III) scores (median, 78 vs 65, P < .0001). There were no differences in lung injury score, blood pH, Pao(2)/Flo(2) ratio, and Paco(2) on ARDS diagnosis. However, patients with sepsis-related ARDS had significantly lower Pao(2)/Flo(2) ratios than patients with nonsepsis-related ARDS patients on ARDS day 3 (P = .018), day 7 (P = .004), and day 14 (P = .004) (repeated-measures analysis, P = .011). Compared with patients with non-sepsis-related ARDS, those with sepsis-related had a higher 60-day mortality (38.2% vs 22.6%; P = .016), a lower successful extubation rate (53.6% vs 72.6%; P = .005), and fewer ICU-free days (P = .0001) and ventilator-free days (P = .003). In multivariate analysis, age, APACHE III score, liver cirrhosis, metastatic cancer, admission serum bilirubin and glucose levels, and treatment with activated protein C were independently associated with 60-day ARDS mortality. After adjustment, sepsis-related ARDS was no longer associated with higher 60-day mortality (hazard ratio, 1.26; 95% CI, 0.71-2.22). Conclusion: Sepsis-related ARDS has a higher overall disease severity, poorer recovery from lung injury, lower successful extubation rate, and higher mortality than non-sepsis-related ARDS. Worse clinical outcomes in sepsis-related ARDS appear to be driven by disease severity and comorbidities. CHEST 2010; 138(3):559-567 C1 [Sheu, Chau-Chyun; Zhai, Rihong; Chen, Feng; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Bajwa, Ednan K.; Thompson, B. Taylor; Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Pulm & Crit Care Unit, Boston, MA 02115 USA. [Clardy, Peter F.; Gallagher, Diana C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA 02115 USA. [Gong, Michelle N.] Albert Einstein Coll Med, Montefiore Med Ctr, Div Crit Care Med, Bronx, NY USA. [Gong, Michelle N.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY USA. [Sheu, Chau-Chyun] Kaohsiung Med Univ Hosp, Div Pulm & Crit Care Med, Kaohsiung, Taiwan. [Sheu, Chau-Chyun] Kaohsiung Med Univ, Coll Med, Fac Resp Therapy, Kaohsiung, Taiwan. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Room I-1401, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Institutes of Health [ES00002, HL60710, HL087934]; Eli Lilly FX Funding/Support: The work was supported by National Institutes of Health [Grants ES00002, HL60710, and HL087934].; Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Thompson reports financial support from Eli Lilly for his role as the co-principal investigator of the PROWESS-SHOCK study, a randomized trial of activated protein C vs placebo for septic shock. Drs Sheu, Gong, Zinn, Chen, Bajwa, Clardy, Gallagher, and Christiani have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 50 TC 63 Z9 72 U1 1 U2 7 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2010 VL 138 IS 3 BP 559 EP 567 DI 10.1378/chest.09-2933 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 659IZ UT WOS:000282561500019 PM 20507948 ER PT J AU Slatore, CG Cecere, LM Reinke, LF Ganzini, L Udris, EM Moss, BR Bryson, CL Curtis, JR Au, DH AF Slatore, Christopher G. Cecere, Laura M. Reinke, Lynn F. Ganzini, Linda Udris, Edmunds M. Moss, Brianna R. Bryson, Chris L. Curtis, J. Randall Au, David H. TI Patient-Clinician Communication Associations With Important Health Outcomes Among Veterans With COPD SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; PRIMARY-CARE PHYSICIANS; QUALITY-OF-LIFE; SINGLE-ITEM; QUESTIONNAIRE; MANAGEMENT; RECOMMENDATIONS; PREDICTION; MORTALITY; IMPROVE AB Background: High quality patient-clinician communication is widely advocated, but little is known about which health outcomes are associated with communication for patients with COPD. Methods: Using a cross-sectional study of 342 veterans enrolled in a randomized controlled trial, we evaluated the association of communication, measured with the quality of communication (QOC) instrument, with subject-reported quality of clinician care, breathing problem confidence, and general self-rated health. We measured these associations using general estimating equations and adjusted odds ratios (OR) of patient-reported outcomes associated with one-point changes in QOC scores. Results: Nearly one-half of the subjects reported receiving the best imaginable care (47%), whereas fewer reported being confident with their breathing problems all the time (29%) or in very good or excellent health (15%). General communication was associated with best-imagined quality of care (OR, 4.29; 95% CI, 2.84-6.48; P <.001) and confidence in dealing with breathing problems all the time (OR, 1.74; 95% CI, 1.34-2.25; P <.001) but not general self-rated health (OR, 1.19; 95% CI, 0.92-1.55; P =.19). Specific clinician behaviors with larger associations with higher quality care included listening, caring, and attentiveness. The associations between general communication and quality care increased over time (P for interaction .03). Conclusions: Communication between patients and clinicians is associated with quality of care and confidence in dealing with breathing problems, and this association may change over time. Attention to specific communication strategies may lead to improvements in the care of patients with COPD. CHEST 2010; 138(3):628-634 C1 [Slatore, Christopher G.; Ganzini, Linda] Portland VA Med Ctr, Hlth Serv Res & Dev, Portland, OR 97239 USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Cecere, Laura M.; Reinke, Lynn F.; Udris, Edmunds M.; Moss, Brianna R.; Bryson, Chris L.; Au, David H.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Cecere, Laura M.; Bryson, Chris L.; Curtis, J. Randall; Au, David H.] Univ Washington, Dept Med, Seattle, WA USA. RP Slatore, CG (reprint author), Portland VA Med Ctr, Hlth Serv Res & Dev, 3710 SW US Vet Hosp Rd,R&D 66, Portland, OR 97239 USA. EM slatore@ohsu.edu OI Slatore, Christopher/0000-0003-0958-8122 FU Health Services Research and Development, Department of Veterans Affairs [IIR 02-292]; National Institute of Health [CA130328]; National Institutes of Health-National Heart, Lung, and Blood Institute; Department of Veterans Affairs; American Lung Association; Gilead Science, Inc. FX This work was supported by the Health Services Research and Development, Department of Veterans Affairs [IIR 02-292), and Dr Slatore was supported by funding from the National Institute of Health [CA130328].; The authors have reported to CHEST the following conflicts of interest: Dr Au has received research funding from the National Institutes of Health-National Heart, Lung, and Blood Institute, the Department of Veterans Affairs, the American Lung Association, and Gilead Science, Inc. Drs Slatore, Cecere; Reinke, Ganzini, Bryson, Curtis, and Au; Mr Udris; and Ms Moss have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 37 TC 24 Z9 25 U1 0 U2 10 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2010 VL 138 IS 3 BP 628 EP 634 DI 10.1378/chest.09-2328 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 659IZ UT WOS:000282561500027 PM 20299633 ER PT J AU Castriotta, RJ Eldadah, BA Foster, WM Halter, JB Hazzard, WR Kiley, JP King, TE Horne, FM Nayfield, SG Reynolds, HY Schmader, KE Toews, GB High, KP AF Castriotta, Richard J. Eldadah, Basil A. Foster, W. Michael Halter, Jeffrey B. Hazzard, William R. Kiley, James P. King, Talmadge E., Jr. Horne, Frances McFarland Nayfield, Susan G. Reynolds, Herbert Y. Schmader, Kenneth E. Toews, Galen B. High, Kevin P. TI Workshop on Idiopathic Pulmonary Fibrosis in Older Adults SO CHEST LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; INTERSTITIAL LUNG-DISEASE; ALVEOLAR EPITHELIAL-CELLS; GASTROESOPHAGEAL-REFLUX DISEASE; GENE-EXPRESSION PROFILES; PLACEBO-CONTROLLED TRIAL; MESENCHYMAL STEM-CELLS; ARTERIAL-HYPERTENSION; ACUTE EXACERBATIONS; DIABETES-MELLITUS AB Idiopathic pulmonary fibrosis (IPF), a heterogeneous disease with respect to clinical presentation and rates of progression, disproportionately affects older adults. The diagnosis of IPF is descriptive, based on clinical, radiologic, and histopathologic examination, and definitive diagnosis is hampered by poor interobserver agreement and lack of a consensus definition. There are no effective treatments. Cellular, molecular, genetic, and environmental risk factors have been identified for IPF, but the initiating event and the characteristics of preclinical stages are not known. IPF is predominantly a disease of older adults, and the processes underlying normal aging might significantly influence the development of IPF. Yet, the biology of aging and the principles of medical care for this population have been typically ignored in basic, translational, or clinical IPF research. In August 2009, the Association of Specialty Professors, in collaboration with the American College of Chest Physicians, the American Geriatrics Society, the National Institute on Aging, and the National Heart, Lung, and Blood Institute, held a workshop, summarized herein, to review what is known, to identify research gaps at the interface of aging and IPF, and to suggest priority areas for future research. Efforts to answer the questions identified will require the integration of geriatrics, gerontology, and pulmonary, research, but these efforts have great potential to improve care for patients with IPF. CHEST 2010; 138(3):693-703 C1 [High, Kevin P.] Wake Forest Univ, Bowman Gray Sch Med, Infect Dis Sect, Winston Salem, NC 27157 USA. [Castriotta, Richard J.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Eldadah, Basil A.] NIA, Bethesda, MD 20892 USA. [Foster, W. Michael] Duke Univ, Sch Med, Durham, NC USA. [Halter, Jeffrey B.; Toews, Galen B.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Hazzard, William R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Kiley, James P.; Reynolds, Herbert Y.] NHLBI, Bethesda, MD 20892 USA. [King, Talmadge E., Jr.] Univ Calif San Francisco, San Francisco Sch Med, San Francisco, CA USA. [Horne, Frances McFarland] Assoc Specialty Prof, Washington, DC USA. [Nayfield, Susan G.] Univ Florida, Sch Med, Gainesville, FL USA. [Schmader, Kenneth E.] Duke Univ, Med Ctr, Durham, NC USA. [Schmader, Kenneth E.] GRECC Durham VA Med Ctr, Durham, NC USA. RP High, KP (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Infect Dis Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM khigh@wfubmc.edu OI Castriotta, Richard/0000-0003-3502-4558 FU John A. Hartford Foundation [2006-0239]; Cephalon, Inc.; Merck; Wyeth; Pfizer; Optimer; Chimerix; Afexa Life Sciences FX This workshop was supported by a grant from the John A. Hartford Foundation to the Association of Specialty Professors [Grant 2006-0239].; The authors have reported to CHEST the following conflicts of interest: Dr Castriotta is a consultant for Blue Cross and Blue Shield of Texas and has received past research support from Cephalon, Inc. Dr Eldadah is a federal employee with the National Institutes of Health. Dr King serves as a consultant to the following pharmaceutical or medical device companies: Actelion, AstraZeneca, Boehringer Ingelheim, Centocor, Chronoger, CV Therapeutics, Domantis Limited, FibroGen, Genzyme, Human Genome Sciences, Huya Bioscience, InterMune, Millennium Pharmaceuticals, Merck, GlaxoSmithKline, Gilead, Novartis, Hoffman-La Roche, Inc., and Serono. He also serves on the advisory committees for Actelion and InterMune and on the data safety monitoring boards for Centocor and GlaxoSmithKline. Dr Nayfield is a federal employee with the National Institutes of Health. Dr Reynolds is a federal employee with the National Institutes of Health. Dr Schmader has received grant support from Merck and Wyeth and serves as a consultant for Merck and GlaxoSmithKline. Dr High has received grant support from Merck, Pfizer, Optimer, Chimerix, and Afexa Life Sciences, and serves as a consultant for Optimer and GlaxoSmithKline. Drs Foster, Halter, Hazzard, Kiley, McFarland Home, and Toews have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 106 TC 25 Z9 25 U1 1 U2 9 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2010 VL 138 IS 3 BP 693 EP 703 DI 10.1378/chest.09-3006 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 659IZ UT WOS:000282561500035 PM 20822991 ER PT J AU Fox, CS Massaro, JM Schlett, CL Lehman, SJ Meigs, JB O'Donnell, CJ Hoffmann, U Murabito, JM AF Fox, Caroline S. Massaro, Joseph M. Schlett, Christopher L. Lehman, Sam J. Meigs, James B. O'Donnell, Christopher J. Hoffmann, Udo Murabito, Joanne M. TI Periaortic Fat Deposition Is Associated With Peripheral Arterial Disease The Framingham Heart Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE obesity; atherosclerosis; peripheral vascular diseases ID NUTRITION EXAMINATION SURVEY; ANKLE-BRACHIAL INDEX; ADIPOSE-TISSUE; RISK-FACTORS; INTERMITTENT CLAUDICATION; METABOLIC SYNDROME; PERIVASCULAR FAT; NATIONAL-HEALTH; OBESITY; PREVALENCE AB Background-Central obesity is associated with peripheral arterial disease, suggesting that ectopic fat depots may be associated with localized diseases of the aorta and lower-extremity arteries. We hypothesized that persons with greater amounts of periaortic fat are more likely to have clinical PAD and a low ankle-brachial index. Methods and Results-We quantified periaortic fat surrounding the thoracic aorta using a novel volumetric quantitative approach in 1205 participants from the Framingham Heart Study Offspring cohort (mean age, 65.9 years; women, 54%); visceral abdominal fat also was measured. Clinical peripheral arterial disease was defined as a history of intermittent claudication, and ankle-brachial index was dichotomized as low (<= 0.9) or lower-extremity revascularization versus normal (>0.9 to <1.4). Regression models were created to examine the association between periaortic fat and intermittent claudication or low ankle-brachial index (n = 66). In multivariable logistic regression, per 1 SD increase in periaortic fat, the odds ratio for the combined end point was 1.52 (P = 0.004); these results were strengthened with additional adjustment for body mass index (odds ratio, 1.69; P = 0.002) or visceral abdominal fat (odds ratio, 1.67; P = 0.009), whereas no association was observed for visceral abdominal fat (P = 0.16). Similarly, per SD increase in body mass index or waist circumference, no association was observed after accounting for visceral abdominal fat (body mass index, P = 0.35; waist circumference, P = 0.49). Conclusions-Periaortic fat is associated with low ABI and intermittent claudication. (Circ Cardiovasc Imaging. 2010;3:515-519.) C1 [Fox, Caroline S.; O'Donnell, Christopher J.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. [Fox, Caroline S.; O'Donnell, Christopher J.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Schlett, Christopher L.; Lehman, Sam J.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Cardiac MR PET CT, Boston, MA 02114 USA. [Massaro, Joseph M.] Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA. [Fox, Caroline S.; Schlett, Christopher L.; Lehman, Sam J.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Lehman, Sam J.] Flinders Univ S Australia, Dept Cardiol, Adelaide, SA 5001, Australia. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Murabito, Joanne/0000-0002-0192-7516; Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; General Clinical Research Centers Program [M01-RR-01066]; American Diabetes Association; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140]; GlaxoSmithKline; Sanofi-Aventis FX This work was supported by the National Heart, Lung, and Blood Institute Framingham Heart Study (N01-HC-25195), the General Clinical Research Centers Program (grant number M01-RR-01066), and a Career Development Award from the American Diabetes Association and National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK080140) to Dr Massaro.; Dr Massaro currently has research grants from GlaxoSmithKline and Sanofi-Aventis, and has consulting agreements with Eli Lilly and Interleukin Genetics. The other authors report no conflicts. NR 24 TC 35 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD SEP PY 2010 VL 3 IS 5 BP 515 EP 519 DI 10.1161/CIRCIMAGING.110.958884 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 649RH UT WOS:000281790000006 PM 20639302 ER PT J AU Thanassoulis, G Massaro, JM Hoffmann, U Mahabadi, AA Vasan, RS O'Donnell, CJ Fox, CS AF Thanassoulis, George Massaro, Joseph M. Hoffmann, Udo Mahabadi, Amir A. Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Prevalence, Distribution, and Risk Factor Correlates of High Pericardial and Intrathoracic Fat Depots in the Framingham Heart Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE pericardial fat; obesity; epidemiology ID EPICARDIAL ADIPOSE-TISSUE; VISCERAL ABDOMINAL FAT; METABOLIC SYNDROME; OBESE SUBJECTS; DISEASE; MEN; ASSOCIATION; COMMUNITY AB Background-Pericardial and intrathoracic fat depots may represent novel risk factors for obesity-related cardiovascular disease. We sought to determine the prevalence, distribution, and risk factor correlates of high pericardial and intrathoracic fat deposits. Methods and Results-Participants from the Framingham Heart Study (n = 3312; mean age, 52 years; 48% women) underwent multidetector CT imaging in 2002 to 2005; high pericardial and high intrathoracic fat were defined on the basis of the sex-specific 90th percentile for these fat depots in a healthy reference sample. For men and women, the prevalence of high pericardial fat was 29.3% and 26.3%, respectively, and high intrathoracic fat was 31.4% and 35.3%, respectively. Overall, 22.1% of the sample was discordant for pericardial and intrathoracic fat depots: 8.3% had high pericardial but normal intrathoracic fat and 13.8% had high intrathoracic but normal pericardial fat. Higher body mass index, higher waist circumference, and increased prevalence of metabolic syndrome were more prevalent in participants with high intrathoracic fat depots than with high pericardial fat (P < 0.05 for all comparisons). High abdominal visceral adipose tissue was more frequent in participants with high intrathoracic adipose tissue compared with those with high pericardial fat (P < 0.001). Intrathoracic fat but not waist circumference was more highly correlated with visceral adipose tissue (r = 0.76 and 0.78 in men and women, respectively; P < 0.0001) than with subcutaneous adipose tissue (SAT) (r = 0.46 and 0.54 in men and women, respectively; P < 0.0001). Conclusions-Although prevalence of pericardial fat and intrathoracic fat were comparable at 30%, intrathoracic fat correlated more closely with metabolic risk and visceral fat. Intrathoracic fat may be a potential marker of metabolic risk and visceral fat on thoracic imaging. (Circ Cardiovasc Imaging. 2010;3:559-566.) C1 [Thanassoulis, George; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, NIH, Framingham Heart Study, Framingham, MA 01702 USA. [Thanassoulis, George] Boston Univ, Sch Med, Boston, MA 02118 USA. [Massaro, Joseph M.; Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Hoffmann, Udo; Mahabadi, Amir A.; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Div Endocrinol, Boston, MA USA. [O'Donnell, Christopher J.] NIH, Div Intramural Res, Bethesda, MD USA. [Fox, Caroline S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, NIH, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI 王, 强/F-4212-2011; OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU Canadian Institute of Health Research; Fonds de Recherche en Sante du Quebec; National Institutes of Health [N01-HC-25195]; [R01-DK-080739] FX Dr Thanassoulis is supported by a Research Fellowship from the Canadian Institute of Health Research and the Fonds de Recherche en Sante du Quebec. The Framingham Heart Study is supported by National Institutes of Health Contract No. N01-HC-25195. Dr Vasan was supported in part by grant R01-DK-080739. NR 21 TC 32 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD SEP PY 2010 VL 3 IS 5 BP 559 EP U85 DI 10.1161/CIRCIMAGING.110.956706 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 649RH UT WOS:000281790000012 PM 20525769 ER PT J AU Magid, DJ Shetterly, SM Margolis, KL Tavel, HM O'Connor, PJ Selby, JV Ho, PM AF Magid, David J. Shetterly, Susan M. Margolis, Karen L. Tavel, Heather M. O'Connor, Patrick J. Selby, Joe V. Ho, P. Michael TI Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors Versus beta-Blockers as Second-Line Therapy for Hypertension SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE hypertension; comparative effectiveness; diuretics; cardiovascular diseases ID JOINT NATIONAL COMMITTEE; HIGH BLOOD-PRESSURE; CARDIOVASCULAR EVENTS; RANDOMIZED-TRIALS; PROPENSITY SCORE; 7TH REPORT; OUTCOMES; RISK; AMLODIPINE; PREVENTION AB Background-Trials comparing hypertension monotherapies have found either no difference or modest differences in blood pressure (BP) and cardiovascular events. However, no trial has assessed the comparative effectiveness of 2nd-line therapy in patients whose BP was not controlled with a thiazide diuretic. Methods and Results-This was an observational study conducted with a hypertension registry of adults enrolled in 3 large integrated health care delivery systems from 2002 to 2007. Patients newly started on thiazide monotherapy whose BP remained uncontrolled were observed after addition of either an angiotensin-converting enzyme (ACE) inhibitor or beta-blocker for subsequent BP control and cardiovascular events. Patients for whom either add-on drug was indicated or contraindicated were excluded. After adjustment for patient characteristics and study year, BP control during the subsequent 6 to 18 months was comparable for the 2 agents (70.5% ACE, 69.0% beta-blockers; P=0.09). Rates of incident myocardial infarction (hazard ratio, 1.05; 95% confidence interval, 0.69 to 1.58) and stroke (hazard ratio, 1.01; 95% confidence interval, 0.68 to 1.52) were also similar for the ACE inhibitor and beta-blocker groups during an average of 2.3 years of follow-up. There were also no differences in heart failure or renal function. Conclusions-ACE inhibitors and beta-blockers are equally effective in lowering BP and preventing cardiovascular events for patients whose BP is not controlled with a thiazide diuretic alone and who have no compelling indication for a specific 2nd-line agent. (Circ Cardiovasc Qual Outcomes. 2010; 3:453-458.) C1 [Magid, David J.; Shetterly, Susan M.; Tavel, Heather M.; Ho, P. Michael] Kaiser Permanente, Inst Hlth Res, Denver, CO USA. [Magid, David J.; Ho, P. Michael] Univ Colorado, Denver, CO 80202 USA. [Margolis, Karen L.; O'Connor, Patrick J.] Hlth Partners Res Fdn, Minneapolis, MN USA. [Selby, Joe V.] Kaiser Permanente No Calif, Oakland, CA USA. [Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. RP Magid, DJ (reprint author), KPCO IHR, 10065 E Harvard Ave,Suite 300, Denver, CO 80231 USA. EM David.J.Magid@kp.org FU Agency for Healthcare Research and Quality, US Department of Health and Human Services [290-2005-0033] FX This project was funded under Contract No. 290-2005-0033 from the Agency for Healthcare Research and Quality, US Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the US Department of Health and Human Services. NR 25 TC 6 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2010 VL 3 IS 5 BP 453 EP 458 DI 10.1161/CIRCOUTCOMES.110.940874 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680UW UT WOS:000284262100005 PM 20716714 ER PT J AU Bernheim, SM Grady, JN Lin, ZQ Wang, Y Wang, YF Savage, SV Bhat, KR Ross, JS Desai, MM Merrill, AR Han, LF Rapp, MT Drye, EE Normand, SLT Krumholz, HM AF Bernheim, Susannah M. Grady, Jacqueline N. Lin, Zhenqiu Wang, Yun Wang, Yongfei Savage, Shantal V. Bhat, Kanchana R. Ross, Joseph S. Desai, Mayur M. Merrill, Angela R. Han, Lein F. Rapp, Michael T. Drye, Elizabeth E. Normand, Sharon-Lise T. Krumholz, Harlan M. TI National Patterns of Risk-Standardized Mortality and Readmission for Acute Myocardial Infarction and Heart Failure Update on Publicly Reported Outcomes Measures Based on the 2010 Release SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE mortality; myocardial infarction; heart failure; performance measurement; readmission ID PROFILING HOSPITAL PERFORMANCE; RATES; TRIAL; CARE AB Background-Patient outcomes provide a critical perspective on quality of care. The Centers for Medicare and Medicaid Services (CMS) is publicly reporting hospital 30-day risk-standardized mortality rates (RSMRs) and risk-standardized readmission rates (RSRRs) for patients hospitalized with acute myocardial infarction (AMI) and heart failure (HF). We provide a national perspective on hospital performance for the 2010 release of these measures. Methods and Results-The hospital RSMRs and RSRRs are calculated from Medicare claims data for fee-for-service Medicare beneficiaries, 65 years or older, hospitalized with AMI or HF between July 1, 2006, and June 30, 2009. The rates are calculated using hierarchical logistic modeling to account for patient clustering, and are risk-adjusted for age, sex, and patient comorbidities. The median RSMR for AMI was 16.0% and for HF was 10.8%. Both measures had a wide range of hospital performance with an absolute 5.2% difference between hospitals in the 5th versus 95th percentile for AMI and 5.0% for HF. The median RSRR for AMI was 19.9% and for HF was 24.5% (3.9% range for 5th to 95th percentile for AMI, 6.7% for HF). Distinct regional patterns were evident for both measures and both conditions. Conclusions-High RSRRs persist for AMI and HF and clinically meaningful variation exists for RSMRs and RSRRs for both conditions. Our results suggest continued opportunities for improvement in patient outcomes for HF and AMI. (Circ Cardiovasc Qual Outcomes. 2010; 3:459-467.) C1 [Bernheim, Susannah M.; Grady, Jacqueline N.; Lin, Zhenqiu; Wang, Yun; Wang, Yongfei; Savage, Shantal V.; Bhat, Kanchana R.; Desai, Mayur M.; Drye, Elizabeth E.; Krumholz, Harlan M.] Yale New Haven Hlth Serv Corp, Ctr Outcomes Res & Evaluat, New Haven, CT USA. [Desai, Mayur M.] Yale Univ, Sch Publ Hlth, Sect Chron Dis Epidemiol, New Haven, CT USA. [Wang, Yun; Wang, Yongfei; Drye, Elizabeth E.; Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA. [Krumholz, Harlan M.] Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr, New York, NY USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Adult Dev & Med, New York, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, HSR&D Targeted Res Enhancement Program, Bronx, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Merrill, Angela R.] Math Policy Res Inc, Cambridge, MA USA. [Han, Lein F.; Rapp, Michael T.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Rapp, Michael T.] George Washington Univ, Sch Med & Hlth Sci, Sect Emergency Med, Washington, DC 20052 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Bernheim, SM (reprint author), Yale YNHH Ctr Outcomes Res & Evaluat, 1 Church St,Suite 200, New Haven, CT 06510 USA. EM susannah.bernheim@yale.edu FU CMS, Department of Health and Human Services [HHSM-500-2008-0025I (0001), HHSM-500-2008-00020I (0001)]; National Institute on Aging [K08 AG032886]; American Federation of Aging Research; CMS FX The analyses on which this publication is based were performed under Contract No. HHSM-500-2008-0025I (0001), entitled "Measure and Instrument Development and Support (MIDS)-Development and Re-evaluation of the CMS Hospital Outcomes and Efficiency Measures," and HHSM-500-2008-00020I (0001), entitled " Production and Implementation of Hospital Outcome and Efficiency Measures" funded by the CMS, Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services. The authors assume full responsibility for the accuracy and completeness of the ideas presented. Dr Ross is currently supported by the National Institute on Aging (K08 AG032886) and by the American Federation of Aging Research through the Paul B. Beeson Career Development Award.; Dr Bernheim, Jacqueline Grady, Zhenqiu Lin, Yun Wang, Yongfei Wang, Shantal V. Savage, Kanchana R. Bhat, Elizabeth Drye, and Harlan Krumholz all work under contract with CMS to develop and maintain performance measures. Dr Merrill works under contract with CMS to produce and implement the outcomes measures. Dr Han and Dr Rapp are employed by CMS. NR 17 TC 98 Z9 99 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2010 VL 3 IS 5 BP 459 EP 467 DI 10.1161/CIRCOUTCOMES.110.957613 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 680UW UT WOS:000284262100006 PM 20736442 ER PT J AU Beeri, R Chaput, M Guerrero, JL Kawase, Y Yosefy, C Abedat, S Karakikes, I Morel, C Tisosky, A Sullivan, S Handschumacher, MD Gilon, D Vlahakes, GJ Hajjar, RJ Levine, RA AF Beeri, Ronen Chaput, Miguel Guerrero, J. Luis Kawase, Yoshiaki Yosefy, Chaim Abedat, Suzan Karakikes, Ioannis Morel, Charlotte Tisosky, Ashley Sullivan, Suzanne Handschumacher, Mark D. Gilon, Dan Vlahakes, Gus J. Hajjar, Roger J. Levine, Robert A. TI Gene Delivery of Sarcoplasmic Reticulum Calcium ATPase Inhibits Ventricular Remodeling in Ischemic Mitral Regurgitation SO CIRCULATION-HEART FAILURE LA English DT Article DE mitral regurgitation; valvular heart disease; echocardiography; remodeling ID HEART-FAILURE; RAT HEARTS; IN-VIVO; 3-DIMENSIONAL ECHOCARDIOGRAPHY; MYOCARDIAL-INFARCTION; CLINICAL-IMPLICATIONS; CARDIAC-HYPERTROPHY; DIASTOLIC FUNCTION; VOLUME OVERLOAD; NA/CA EXCHANGE AB Background-Mitral regurgitation (MR) doubles mortality after myocardial infarction (MI). We have demonstrated that MR worsens remodeling after MI and that early correction reverses remodeling. Sarcoplasmic reticulum Ca+2-ATPase (SERCA2a) is downregulated in this process. We hypothesized that upregulating SERCA2a might inhibit remodeling in a surgical model of apical MI (no intrinsic MR) with independent MR-type flow. Methods and Results-In 12 sheep, percutaneous gene delivery was performed by using a validated protocol to perfuse both the left anterior descending and circumflex coronary arteries with occlusion of venous drainage. We administered adeno-associated virus 6 (AAV6) carrying SERCA2a under a Cytomegalovirus promoter control in 6 sheep and a reporter gene in 6 controls. After 2 weeks, a standardized apical MI was created, and a shunt was implanted between the left ventricle and left atrium, producing regurgitant fractions of approximate to 30%. Animals were compared at baseline and 1 and 3 months by 3D echocardiography, Millar hemodynamics, and biopsies. The SERCA2a group had a well-maintained preload-recruitable stroke work at 3 months (decrease by 8 +/- 10% vs 42 +/- 12% with reporter gene controls; P<0.001). Left ventricular dP/dt followed the same pattern (no change vs 55% decrease; P<0.001). Left ventricular end-systolic volume was lower with SERCA2a (82.6 +/- 9.6 vs 99.4 +/- 9.7 mL; P=0.03); left ventricular end-diastolic volume, reflecting volume overload, was not significantly different (127.8 +/- 6.2 vs 134.3 +/- 9.4 mL). SERCA2a sheep showed a 15% rise in antiapoptotic pAkt versus a 30% reduction with the reporter gene (P<0.001). Prohypertrophic activated STAT3 was also 41% higher with SERCA2a than in controls (P<0.001). Proapoptotic activated caspase-3 rose >5-fold during 1 month in both SERCA2a and control animals (P=NS) and decreased by 19% at 3 months, remaining elevated in both groups. Conclusions-In this controlled model, upregulating SERCA2a induced better function and lesser remodeling, with improved contractility, smaller volume, and activation of prohypertrophic/antiapoptotic pathways. Although caspase-3 remained activated in both groups, SERCA2a sheep had increased molecular antiremodeling "tone." We therefore conclude that upregulating SERCA2a inhibits MR-induced post-MI remodeling in this model and thus may constitute a useful approach to reduce the vicious circle of remodeling in ischemic MR. (Circ Heart Fail. 2010;3:627-634.) C1 [Beeri, Ronen; Chaput, Miguel; Guerrero, J. Luis; Kawase, Yoshiaki; Yosefy, Chaim; Sullivan, Suzanne; Handschumacher, Mark D.; Vlahakes, Gus J.; Levine, Robert A.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Ctr Heart, Boston, MA 02114 USA. [Beeri, Ronen; Chaput, Miguel; Guerrero, J. Luis; Kawase, Yoshiaki; Yosefy, Chaim; Sullivan, Suzanne; Handschumacher, Mark D.; Vlahakes, Gus J.; Levine, Robert A.] Massachusetts Gen Hosp, Dept Cardiac Surg, Ctr Heart, Boston, MA 02114 USA. [Beeri, Ronen; Abedat, Suzan; Gilon, Dan] Hadassah Hebrew Univ Med Ctr, Inst Heart, Cardiovasc Res Ctr, Jerusalem, Israel. [Morel, Charlotte; Tisosky, Ashley; Hajjar, Roger J.] Mt Sinai Sch Med, Cardiovasc Inst, Cardiovasc Res Ctr, New York, NY USA. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Ctr Heart, YAW5,55 Fruit St, Boston, MA 02114 USA. EM rlevine@partners.org RI Beeri, Ronen/A-4035-2009 OI Beeri, Ronen/0000-0002-8014-0702 FU National Institutes of Health/National Heart, Lung, and Blood Institute [R01 HL72265, R01 HL078731, R01 HL080498, R01 HL083156, K24 HL67434]; USA/Israel Binational Science Foundation [2005250]; Transatlantic MITRAL Network, Leducq Foundation, Paris, France [07CVD04] FX This study was supported in part by grants R01 HL72265, R01 HL078731, R01 HL080498, R01 HL083156, and K24 HL67434 from National Institutes of Health/National Heart, Lung, and Blood Institute, and grant 2005250 from the USA/Israel Binational Science Foundation. Dr Levine was also supported by grant 07CVD04 for the Transatlantic MITRAL Network, Leducq Foundation, Paris, France. NR 50 TC 34 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2010 VL 3 IS 5 BP 627 EP 634 DI 10.1161/CIRCHEARTFAILURE.109.891184 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 650OF UT WOS:000281858200010 PM 20634484 ER PT J AU Castelino, FV Seiders, J Bain, G King, C Swaney, JS Lorrain, DS Chun, J Luster, AD Tager, AM AF Castelino, F., V Seiders, J. Bain, G. King, C. Swaney, J. S. Lorrain, D. S. Chun, J. Luster, A. D. Tager, A. M. TI Genetic deletion or pharmacologic antagonism of LPA(1) ameliorates dermal fibrosis in a mouse model of systemic sclerosis SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Castelino, F., V; Luster, A. D.; Tager, A. M.] Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Castelino, F., V; Luster, A. D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Seiders, J.; Bain, G.; King, C.; Swaney, J. S.; Lorrain, D. S.] Amira Pharmaceut, San Diego, CA 92121 USA. [Chun, J.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Tager, A. M.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD SEP-OCT PY 2010 VL 28 IS 5 SU 62 BP S57 EP S57 PG 1 WC Rheumatology SC Rheumatology GA 677XJ UT WOS:000284028600013 ER PT J AU Gerstel-Thompson, JL Wilkey, JF Baptiste, JC Navas, JS Pai, SY Pass, KA Eaton, RB Comeau, AM AF Gerstel-Thompson, Jacalyn L. Wilkey, Jonathan F. Baptiste, Jennifer C. Navas, Jennifer S. Pai, Sung-Yun Pass, Kenneth A. Eaton, Roger B. Comeau, Anne Marie TI High-Throughput Multiplexed T-Cell-Receptor Excision Circle Quantitative PCR Assay with Internal Controls for Detection of Severe Combined Immunodeficiency in Population-Based Newborn Screening SO CLINICAL CHEMISTRY LA English DT Article ID LYMPHOCYTES; DEFECTS; AGE AB BACKGROUND: Real-time quantitative PCR (qPCR) targeting a specific marker of functional T cells, the Tcell-receptor excision circle (TREC), detects the absence of functional T cells and has a demonstrated clinical validity for detecting severe combined immunodeficiency (SCID) in infants. There is need for a qPCR TREC assay with an internal control to monitor DNA quality and the relative cellular content of the particular dried blood spot punch sampled in each reaction. The utility of the qPCR TREC assay would also be far improved if more tests could be performed on the same newborn screening sample. METHODS: We approached the multiplexing of qPCR for TREC by attenuating the reaction for the reference gene, with focus on maintaining tight quality assurance for reproducible slopes and for prevention of sample-to-sample cross contamination. Statewide newborn screening for SCID using the multiplexed assay was implemented, and quality-assurance data were recorded. RESULTS: The multiplex qPCR TREC assay showed nearly 100% amplification efficiency for each of the TREC and reference sequences, clinical validity for multiple forms of SCID, and an analytic limit of detection consistent with prevention of contamination. The eluate and residual ghost from a 3.2-mm dried blood spot could be used as source material for multiplexed immunoassays and multiplexed DNA tests (Multiplex Plus), with no disruption to the multiplex TREC qPCR. CONCLUSIONS: Population-based SCID newborn screening programs should consider multiplexing for quality assurance purposes. Potential benefits of using Multiplex Plus include the ability to perform multianalyte profiling. (C) 2010 American Association for Clinical Chemistry C1 [Gerstel-Thompson, Jacalyn L.; Wilkey, Jonathan F.; Baptiste, Jennifer C.; Navas, Jennifer S.; Eaton, Roger B.; Comeau, Anne Marie] Univ Massachusetts, New England Newborn Screening Program, Sch Med, Jamaica Plain, MA 02130 USA. [Pai, Sung-Yun] Harvard Univ, Sch Med,Childrens Hosp Boston, Dana Farber Canc Inst, Dept Pediat Oncol,Div Hematol Oncol, Boston, MA 02115 USA. [Pass, Kenneth A.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Eaton, Roger B.; Comeau, Anne Marie] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. RP Comeau, AM (reprint author), Univ Massachusetts, New England Newborn Screening Program, Sch Med, 305 South St, Jamaica Plain, MA 02130 USA. EM anne.comeau@umassmed.edu FU CDC [1U01EH000362] FX CDC grant 1U01EH000362. NR 15 TC 37 Z9 38 U1 1 U2 7 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2010 VL 56 IS 9 BP 1466 EP 1474 DI 10.1373/clinchem.2010.144915 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 644SP UT WOS:000281400600017 PM 20660142 ER PT J AU Saokar, A Islam, T Jantsch, M Saksena, MA Hahn, PF Harisinghani, MG AF Saokar, Anuradha Islam, Tina Jantsch, Marion Saksena, Mansi A. Hahn, Peter F. Harisinghani, Mukesh G. TI Detection of lymph nodes in pelvic malignancies with computed tomography and magnetic resonance imaging SO CLINICAL IMAGING LA English DT Article DE Lymph node metastasis; Computed tomography; Magnetic resonance imaging; Lymphotropic nanoparticle-enhanced MRI ID POSITRON-EMISSION-TOMOGRAPHY; PROSTATE-CANCER; RECTAL-CANCER; METASTASES; CARCINOMA; CT AB Thirty patients with prostate or bladder cancer underwent CT and MRI for nodal staging. CT detected 189 nodes, and MRI detected 271 nodes. This difference was statistically significant in the external iliac (CT/MRI=73/87 nodes), obturator (CT/MRI=48/75 nodes), and internal iliac (CT/MRI=24/46 nodes) nodal chains. Based on size, the number of nodes detected by CT and MRI were as follows: 1-5 mm, CT/MRI=91/166; 6-10 mm, CT/MRI=91/98; >10 mm, CT/MRI=7/7 nodes. MRI detected significantly more lymph nodes in the size range of 1-5 mm. (C) 2010 Elsevier Inc. All rights reserved. C1 [Saokar, Anuradha; Islam, Tina; Jantsch, Marion; Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Saokar, Anuradha; Islam, Tina; Jantsch, Marion; Saksena, Mansi A.; Hahn, Peter F.; Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dis Abdominal Imaging & Intervent,Dept Radiol, Boston, MA 02114 USA. RP Islam, T (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging, Dept Radiol, Boston, MA 02114 USA. EM islam.tina@mgh.harvard.edu NR 14 TC 25 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD SEP-OCT PY 2010 VL 34 IS 5 BP 361 EP 366 DI 10.1016/j.clinimag.2009.07.004 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 651GT UT WOS:000281916400008 PM 20813300 ER PT J AU Hermos, J AF Hermos, John TI Comment on Edlund et al "Trends in Use of Opioids for Chronic Noncancer Pain Among Individuals With Mental Health and Substance Abuse Disorders: The TROUP Study'' SO CLINICAL JOURNAL OF PAIN LA English DT Letter ID VETERAN PATIENTS; PRESCRIPTIONS C1 VA Boston Healthcare Syst 151MAV, VA Cooperat Studies Program, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Hermos, J (reprint author), VA Boston Healthcare Syst 151MAV, VA Cooperat Studies Program, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD SEP PY 2010 VL 26 IS 7 BP 645 EP 645 DI 10.1097/AJP.0b013e3181d92d35 PG 1 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 641HJ UT WOS:000281115100014 PM 20716971 ER PT J AU Williams, ME Lacson, E Wang, WL Lazarus, JM Hakim, R AF Williams, Mark E. Lacson, Eduardo, Jr. Wang, Weiling Lazarus, J. Michael Hakim, Raymond TI Glycemic Control and Extended Hemodialysis Survival in Patients with Diabetes Mellitus: Comparative Results of Traditional and Time-Dependent Cox Model Analyses SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; BLOOD-GLUCOSE CONTROL; MAINTENANCE HEMODIALYSIS; GLYCATED ALBUMIN; AMERICAN-COLLEGE; OLDER PATIENTS; RISK; COMPLICATIONS; HEMOGLOBIN; HOSPITALIZATION AB Background and objectives: The benefits and risks of aggressive glycemic control in diabetes mellitus complicated by end-stage kidney failure remain uncertain but have importance because of the large patient population with inferior overall prognosis. Recent large observational studies with differing methodologies reached somewhat contrasting conclusions regarding the association of hemoglobin A1c with survival in diabetic chronic hemodialysis patients. Design, setting, participants, & measurements: This study supplements the authors' previous analysis (which found no correlation) by extending the follow-up period to 3 years and using time-dependent survival models with repeated measures. Among 24,875 nationally distributed study patients, 94.5% had type 2 diabetes, allowing additional analysis in the subset with type 1 diabetes. Data were collected at baseline and every quarter to a maximum of 3 years' follow-up. Results: Adjusted standard and time-dependent Cox models indicated that only extremes of glycemia were associated with inferior survival. There was no effect modification by serum albumin levels, a marker of protein nutrition status, and no trend associated with random glucose measurements in a post hoc analysis. In type 1 diabetic patients, upper extreme hemoglobin A1c values indicated lower survival risk. Conclusions: Sustained extremes of glycemia were only variably and weakly associated with decreased survival in this population. In the absence of randomized, controlled trials, these results suggest that aggressive glycemic control cannot be routinely recommended for all diabetic hemodialysis patients on the basis of reducing mortality risk. Physicians are encouraged to individualize glycemic targets based on potential risks and benefits in diabetic ESRD patients. Clin J Am Soc Nephrol 5: 1595-1601, 2010. doi: 10.2215/CJN.09301209 C1 [Williams, Mark E.] Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. [Lacson, Eduardo, Jr.; Wang, Weiling; Lazarus, J. Michael; Hakim, Raymond] Fresenius Med Care N Amer, Lexington, MA USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 37 TC 44 Z9 44 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2010 VL 5 IS 9 BP 1595 EP 1601 DI 10.2215/CJN.09301209 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 648II UT WOS:000281685600010 PM 20671217 ER PT J AU Awan, SN Roy, N Jette, ME Meltzner, GS Hillman, RE AF Awan, Shaheen N. Roy, Nelson Jette, Marie E. Meltzner, Geoffrey S. Hillman, Robert E. TI Quantifying dysphonia severity using a spectral/cepstral-based acoustic index: Comparisons with auditory-perceptual judgements from the CAPE-V SO CLINICAL LINGUISTICS & PHONETICS LA English DT Article DE cepstrum; cepstral analysis; spectral analysis; continuous speech analysis; dysphonia severity ID CEPSTRAL PEAK PROMINENCE; CONTINUOUS SPEECH; VOICE QUALITY; PATHOLOGICAL VOICE; CONNECTED SPEECH; VOCAL QUALITY; CLASSIFICATION; PREDICTION; BREATHY; MODEL AB This study investigated the relationship between acoustic spectral/cepstral measures and listener severity ratings in normal and disordered voice samples. CAPE-V sentence samples and the vowel/alpha/were elicited from eight normal speakers and 24 patients with varying degrees of dysphonia severity. Samples were analysed for measures of the cepstral peak prominence (CPP), the ratio of low-to-high spectral energy, and their respective standard deviations. Perceptual ratings of overall severity were also obtained for all samples. Results showed that all acoustic variables combined in a four-factor model which correlated with perceived severity with R = 0.81 (R(2) = 0.65). For the vowel/alpha/, a five-factor model incorporating all acoustic variables and gender correlated with perceived severity with R = 0.96 (R(2) = 0.91). Results indicate that a strong relationship between perceptual and acoustic estimates of dysphonia severity can be achieved in both continuous speech and vowel contexts using a model incorporating spectral/cepstral measures. C1 [Awan, Shaheen N.] Bloomsburg Univ Penn, Dept Speech Pathol & Audiol, Bloomsburg, PA 17815 USA. [Roy, Nelson] Univ Utah, Dept Commun Sci & Disorders, Salt Lake City, UT USA. [Jette, Marie E.] Univ Wisconsin Madison, Wisconsin Inst Med Res, Madison, WI USA. [Meltzner, Geoffrey S.] BAE Syst Inc, Burlington, MA USA. [Hillman, Robert E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA USA. RP Awan, SN (reprint author), Bloomsburg Univ Penn, Dept Speech Pathol & Audiol, Centennial Hall,400 E 2nd St, Bloomsburg, PA 17815 USA. EM sawan@bloomu.edu OI Jette, Marie/0000-0003-4705-1289 NR 33 TC 53 Z9 55 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9206 J9 CLIN LINGUIST PHONET JI Clin. Linguist. Phon. PD SEP PY 2010 VL 24 IS 9 BP 742 EP 758 DI 10.3109/02699206.2010.492446 PG 17 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 651XG UT WOS:000281960300005 PM 20687828 ER PT J AU Naunheim, MR Nahed, BV Walcott, BP Kahle, KT Soupir, CP Cahill, DP Borges, LF AF Naunheim, Matthew R. Nahed, Brian V. Walcott, Brian P. Kahle, Kristopher T. Soupir, Chad P. Cahill, Daniel P. Borges, Lawrence F. TI Diagnosis of acute lymphoblastic leukemia from intracerebral hemorrhage and blast crisis. A case report and review of the literature SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Review DE Acute leukemia; ALL; Blast crisis; Intracerebral hemorrhage; Leukocytosis ID FATAL INTRACRANIAL HEMORRHAGE; CEREBRAL-HEMORRHAGE; SURGERY; ASSOCIATION; MORTALITY; HEMATOMA; GROWTH; CANCER; TRIAL AB Intracerebral hemorrhage (ICH) contributes significantly to the morbidity and mortality of patients suffering from acute leukemia. While ICH is often identified in autopsy studies of leukemic patients, it is rare for ICH to be the presenting sign that ultimately leads to the diagnosis of leukemia. We report a patient with previously undiagnosed acute precursor B-cell lymphoblastic leukemia (ALL) who presented with diffuse encephalopathy due to ICH in the setting of an acute blast crisis. The diagnosis of ALL was initially suspected, because of the hyperleukocytosis observed on presentation, then confirmed with a bone marrow biopsy and flow cytometry study of the peripheral blood. Furthermore, detection of the BCR/ABL Philadelphia translocation t(9:22)(q34:q11) in this leukemic patient by fluorescent in situ hybridization permitted targeted therapy of the blast crisis with imatinib (Gleevec). Understanding the underlying etiology of ICH is pivotal in its management. This case demonstrates that the presence of hyperleukocytosis in a patient with intracerebral hemorrhage should raise clinical suspicion for acute leukemia as the cause of the ICH. (C) 2010 Elsevier B.V. All rights reserved. C1 [Naunheim, Matthew R.; Nahed, Brian V.; Walcott, Brian P.; Kahle, Kristopher T.; Cahill, Daniel P.; Borges, Lawrence F.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Soupir, Chad P.] Massachusetts Gen Hosp, Dept Hematopathol, Boston, MA 02114 USA. [Naunheim, Matthew R.; Nahed, Brian V.; Walcott, Brian P.; Kahle, Kristopher T.; Soupir, Chad P.; Cahill, Daniel P.; Borges, Lawrence F.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Borges, LF (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St, Boston, MA 02114 USA. EM lborges@partners.org OI Cahill, Daniel/0000-0003-2552-6546 NR 25 TC 4 Z9 6 U1 0 U2 4 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 SEP PY 2010 VL 112 IS 7 BP 575 EP 577 DI 10.1016/j.clineuro.2010.04.001 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 636YF UT WOS:000280779900006 PM 20493628 ER PT J AU Handforth, A Bordelon, Y Frucht, SJ Quesada, A AF Handforth, Adrian Bordelon, Yvette Frucht, Steven J. Quesada, Arnulfo TI A Pilot Efficacy and Tolerability Trial of Memantine for Essential Tremor SO CLINICAL NEUROPHARMACOLOGY LA English DT Article DE essential tremor; memantine; clinical trial ID HARMALINE-INDUCED TREMOR; AMINO-ACIDS; ACTIVATION; EXPRESSION; RECEPTORS; BRAIN; BLIND; NMDA; RATS; MICE AB Objective: We studied the potential efficacy and tolerance of memantine for essential tremor in an open-treatment trial. Methods: Participants with upper-limb tremor were titrated to no more than 40 mg/d memantine, as monotherapy or as adjunct to stable antitremor medication, followed by a 12-week extension phase. Tremor was assessed in study 1 with accelerometry and in study 2 by blinded ratings of videotaped Washington Heights Inwood Genetic Essential Tremor (WHIGET) rating scale items. Subjects also rated their tremor treatment response and tremor-associated impairment on the Functional Disabilities scale. Results: In study 1, average accelerometry-measured tremor at last titration visit (average dose, 30.3 mg/d) did not change from baseline, but 2 of 9 subjects, taking 40 mg/d, had greater than 70% accelerometry tremor reduction. In study 2, 13 of 16 provided evaluable data. Average blinded rater-evaluated WHIGET scores were significantly different from baseline scores among those taking 20 mg/d (-12.7%; P<0.05), but not at last titration visit (-8.4%; average dose, 30.4 mg/d), 40 mg/d (-14.1%), or at end-of-extension visit (-18.2%). Raters judged WHIGET scores as greater than 30% improved in 2 subjects. Unblinded subjects rated Functional Disabilities significantly improved at 30 to 40 but not at 10 to 20 mg/d, and tremor treatment response was positive at all doses. Adverse events were more common at higher doses and included dizziness, somnolence, and poor energy. Conclusions: These pilot results with small samples indicate that the average effect of memantine on tremor is mild or not significant. However, in a small subset of patients, memantine may confer meaningful tremor benefit. C1 [Handforth, Adrian] Univ Calif Los Angeles, Dept Neurol, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [Bordelon, Yvette] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Frucht, Steven J.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Quesada, Arnulfo] Univ Calif Los Angeles, Res Serv, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [Quesada, Arnulfo] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90024 USA. RP Handforth, A (reprint author), VA Greater Los Angeles, Neurol Serv W127, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM charles.handforth@va.gov FU Forest Laboratories; Veterans Affairs FX Supported by Forest Laboratories and by Veterans Affairs. NR 27 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD SEP-OCT PY 2010 VL 33 IS 5 BP 223 EP 226 DI 10.1097/WNF.0b013e3181ebd109 PG 4 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 653YL UT WOS:000282134400002 PM 20838216 ER PT J AU Bozic, KJ Pui, CM Ludeman, MJ Vail, TP Silverstein, MD AF Bozic, Kevin J. Pui, Christine M. Ludeman, Matthew J. Vail, Thomas P. Silverstein, Marc D. TI Do the Potential Benefits of Metal-on-Metal Hip Resurfacing Justify the Increased Cost and Risk of Complications? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL KNEE ARTHROPLASTY; QUALITY-OF-LIFE; 1ST 10 YEARS; SURFACE REPLACEMENT; UNITED-STATES; FOLLOW-UP; OUTCOMES; MORTALITY; REVISION; OSTEOARTHRITIS AB Metal-on-metal hip resurfacing arthroplasty (MoM HRA) may offer potential advantages over total hip arthroplasty (THA) for certain patients with advanced osteoarthritis of the hip. However, the cost effectiveness of MoM HRA compared with THA is unclear. The purpose of this study was to compare the clinical effectiveness and cost-effectiveness of MoM HRA to THA. A Markov decision model was constructed to compare the quality-adjusted life-years (QALYs) and costs associated with HRA versus THA from the healthcare system perspective over a 30-year time horizon. We performed sensitivity analyses to evaluate the impact of patient characteristics, clinical outcome probabilities, quality of life and costs on the discounted incremental costs, incremental clinical effectiveness, and the incremental cost-effectiveness ratio (ICER) of HRA compared to THA. MoM HRA was associated with modest improvements in QALYs at a small incremental cost, and had an ICER less than $50,000 per QALY gained for men younger than 65 and for women younger than 55. MoM HRA and THA failure rates, device costs, and the difference in quality of life after conversion from HRA to THA compared to primary THA had the largest impact on costs and quality of life. MoM HRA could be clinically advantageous and cost-effective in younger men and women. Further research on the comparative effectiveness of MoM HRA versus THA should include assessments of the quality of life and resource use in addition to the clinical outcomes associated with both procedures. Level I, economic and decision analysis. See Guidelines for Authors for a complete description of levels of evidence. C1 [Bozic, Kevin J.; Pui, Christine M.; Ludeman, Matthew J.; Vail, Thomas P.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Bozic, Kevin J.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Silverstein, Marc D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Boston, MA 02114 USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA. EM kevin.bozic@ucsf.edu FU Orthopaedic Research and Education Foundation FX One or more of the authors (KJB) have received funding from the Orthopaedic Research and Education Foundation. NR 52 TC 19 Z9 19 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2010 VL 468 IS 9 BP 2301 EP 2312 DI 10.1007/s11999-010-1301-0 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 634PA UT WOS:000280594200002 PM 20232182 ER PT J AU Bozic, KJ Ong, K Lau, E Kurtz, SM Vail, TP Rubash, HE Berry, DJ AF Bozic, Kevin J. Ong, Kevin Lau, Edmund Kurtz, Steven M. Vail, Thomas P. Rubash, Harry E. Berry, Daniel J. TI Risk of Complication and Revision Total Hip Arthroplasty Among Medicare Patients with Different Bearing Surfaces SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PATIENTS YOUNGER; UNITED-STATES; FOLLOW-UP; WEAR; REPLACEMENTS; EPIDEMIOLOGY; SURVIVORSHIP; POLYETHYLENE; INFECTION; INDEX AB To address the long-term problems of bearing surface wear and osteolysis associated with conventional metal-polyethylene (M-PE) total hip arthroplasty (THA), metal-metal (M-M), and ceramic-ceramic (C-C) bearings have been introduced. These bearing surfaces are associated with unique risks and benefits and higher costs. However the relative risks of these three bearings in an older population is unknown. We compared the short-term risk of complication and revision THA among Medicare patients having a primary THA with metal-polyethylene (M-PE), metal-metal (M-M), and ceramic-ceramic (C-C) bearings. We used the 2005 to 2007 100% Medicare inpatient claim files to perform a matched cohort analysis in three separate cohorts of THA patients (M-PE, M-M, and C-C) who were matched by age, gender, and US census region. Multivariate Cox proportional-hazards models were constructed to compare complication and revision THA risk among cohorts, adjusting for medical comorbidities, race, socioeconomic status, and hospital factors. After adjusting for patient and hospital factors, M-M bearings were associated with a higher risk of periprosthetic joint infection (hazard ratio, 3.03; confidence interval, 1.02-9.09) when compared with C-C bearings (0.59% versus 0.32%, respectively). There were no other differences among bearing cohorts in the adjusted risk of revision THA or any other complication. The risk of short-term complication (including dislocation) and revision THA were similar among appropriately matched Medicare THA patients regardless of bearing surface. Hard-on-hard THA bearings are of questionable value in Medicare patients, given the higher cost associated with their use and uncertain long-term benefits in older patients. Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Bozic, Kevin J.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Bozic, Kevin J.; Vail, Thomas P.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Ong, Kevin; Kurtz, Steven M.] Exponent Inc, Philadelphia, PA USA. [Lau, Edmund] Exponent Inc, Menlo Pk, CA USA. [Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Berry, Daniel J.] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA. EM kevin.bozic@ucsf.edu FU Orthopaedic Research and Education Foundation FX Financial support was received from the Orthopaedic Research and Education Foundation. One or more of the authors (SMK, KO, EL) are employees of Exponent, Inc. One or more of the authors (DJB, TPV) receive consulting income and royalties from DePuy, Inc. One author (HER) receives royalties from Zimmer, Inc. NR 29 TC 55 Z9 58 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2010 VL 468 IS 9 BP 2357 EP 2362 DI 10.1007/s11999-010-1262-3 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 634PA UT WOS:000280594200009 PM 20165935 ER PT J AU Blais, MA Jacobo, MC Smith, SR AF Blais, Mark A. Jacobo, Michelle C. Smith, Steven R. TI Exploring Therapeutic Alliance in Brief Inpatient Psychotherapy: A Preliminary Study SO CLINICAL PSYCHOLOGY & PSYCHOTHERAPY LA English DT Article DE Psychotherapy; Inpatient Psychotherapy Research; Alliance Ratings; Treatment Outcome ID PSYCHOLOGICAL-ASSESSMENT; HELPING ALLIANCE; PHASE MODEL; THERAPIST; CLIENT; SCALE; CARE AB Background: Therapeutic alliance is one of the most widely investigated variables in psychotherapy research but few studies have explored its role in inpatient psychotherapy. Many factors likely contribute to the lack of inpatient alliance research including the short length of hospital stays, complexity of patient psychopathology and the burdensome quality of most alliance scales. This paper reports on the development and initial application of two comparable brief scales designed to capture patient and therapist alliance ratings. Method: Participants were 20 patients receiving supportive-expressive inpatient psychotherapy. The patients were predominantly depressed women. Baseline measures of distress, symptom severity and functioning were obtained at the first and third sessions. Measures of alliance were obtained at the second session. Results: The brief alliance scales demonstrated adequate internal consistency and the individual items had good adjusted item-to-scale correlations. Consistent with the broad alliance literature, we found that patients rated alliance higher than therapists, patient and therapist alliance ratings were not significantly correlated, and level of functioning was significantly associated with both patients and therapists' alliance ratings. The perceived depth of psychotherapy was also significantly associated with alliance. Unexpectedly, alliance ratings were also negatively associated with improvement during hospitalization. Conclusions: Overall, the study demonstrates both the feasibility and potential benefit of conducting inpatient psychotherapy research. Copyright (C) 2009 John Wiley & Sons, Ltd. Key Practitioner Message: This paper shows that inpatient psychotherapy can be studied and potentially improved through the application of brief targeted instruments. C1 [Blais, Mark A.; Jacobo, Michelle C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blais, Mark A.; Jacobo, Michelle C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Smith, Steven R.] Univ Calif Santa Barbara, Grad Sch Educ, Santa Barbara, CA 93106 USA. RP Blais, MA (reprint author), Psychol Assessment Ctr, 1 Bowdoin Sq,702, Boston, MA 02114 USA. EM Mblais@partners.org NR 26 TC 4 Z9 4 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1063-3995 J9 CLIN PSYCHOL PSYCHOT JI Clin. Psychol. Psychother. PD SEP-OCT PY 2010 VL 17 IS 5 BP 386 EP 394 DI 10.1002/cpp.666 PG 9 WC Psychology, Clinical SC Psychology GA 654IA UT WOS:000282160500004 PM 20013757 ER PT J AU O'Glasser, AY Scott, DL Corless, CL Zaman, A Sasaki, A Gopal, DV Rayhill, SC Orloff, SL Ham, JM Rabkin, JM Flora, K Davies, CH Broberg, CS Schwartz, JM AF O'Glasser, Avital Y. Scott, David L. Corless, Christopher L. Zaman, Atif Sasaki, Anna Gopal, Deepak V. Rayhill, Stephen C. Orloff, Susan L. Ham, John M. Rabkin, John M. Flora, Ken Davies, Crispin H. Broberg, Craig S. Schwartz, Jonathan M. TI Hepatic and cardiac iron overload among patients with end-stage liver disease referred for liver transplantation SO CLINICAL TRANSPLANTATION LA English DT Article DE hemochromatosis; hemosiderosis; liver transplantation ID HEREDITARY HEMOCHROMATOSIS; HEPCIDIN TRANSCRIPTION; SURVIVAL; PATHOGENESIS; EXPRESSION; LEVEL; METABOLISM; CIRRHOSIS; REGISTRY; FAILURE AB Background: Iron overload is associated with fatal cardiovascular events following liver transplantation. Myocardial iron deposits were observed post-mortem in patients who died of cardiac events after transplantation at our institution. This observation prompted testing to exclude cardiac iron in subsequent transplant candidates. Aims: To assess the results of testing for iron overload in liver transplant candidates at our institution. Methods: Ferritin, TIBC, and serum iron were measured in cirrhotics referred for transplantation. Patients with transferrin saturation >= 50% and ferritin >= 250 ng/mL underwent liver biopsy graded for iron. Patients with 3-4+ hepatic iron deposits underwent HFE mutation analysis and endomyocardial biopsy with iron staining. Results: Eight hundred and fifty-six patients were evaluated for liver transplantation between January 1997 and March 2005. Two hundred and eighty-seven patients (34%) had transferrin saturation >= 50% and ferritin >= 250 ng/mL. Patients with markers of iron overload had more advanced liver disease than those with normal iron indices. One hundred and fifty-three patients underwent liver biopsy. Twenty-six patients (17%) had 3-4+ hepatic iron staining. One patient was a C282Y heterozygote. Endomyocardial biopsy was performed in 14 patients of whom nine had cardiac iron deposition. Conclusions: Non-HFE-related cardiac iron overload can occur in advanced liver disease We therefore recommend screening for cardiac iron prior to liver transplantation. C1 [O'Glasser, Avital Y.; Zaman, Atif; Sasaki, Anna; Schwartz, Jonathan M.] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Dept Med, Portland, OR 97219 USA. [O'Glasser, Avital Y.; Zaman, Atif; Sasaki, Anna; Rayhill, Stephen C.; Orloff, Susan L.; Ham, John M.; Schwartz, Jonathan M.] Portland VA Med Ctr, Portland, OR 97219 USA. [Rayhill, Stephen C.; Orloff, Susan L.; Ham, John M.] Oregon Hlth & Sci Univ, Div Liver Pancreas Transplantat, Dept Surg, Portland, OR 97219 USA. [Corless, Christopher L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97219 USA. [Gopal, Deepak V.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Sect Gastroenterol & Hepatol, Madison, WI USA. [Rabkin, John M.] Calif Pacific Med Ctr, San Francisco, CA USA. [Flora, Ken] Oregon Clin, Portland, OR USA. [Davies, Crispin H.; Broberg, Craig S.] Oregon Hlth & Sci Univ, Div Cardiol, Dept Med, Portland, OR 97219 USA. RP Schwartz, JM (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Dept Med, 3181 Sam Jackson Pk Rd,L461, Portland, OR 97219 USA. EM schwajon@ohsu.edu NR 39 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD SEP-OCT PY 2010 VL 24 IS 5 BP 643 EP 651 DI 10.1111/j.1399-0012.2009.01136.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 659MJ UT WOS:000282570300023 PM 19925473 ER PT J AU Caughey, AB Kaimal, AJ Odibo, AO AF Caughey, Aaron B. Kaimal, Anjali J. Odibo, Anthony O. TI Cost-Effectiveness of Down Syndrome Screening Paradigms SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Cost-benefit analysis; Cost-effectiveness analysis; Economics; Prenatal diagnosis; Down syndrome ID PRENATAL-DIAGNOSIS; BENEFIT-ANALYSIS; HEALTH; 1ST-TRIMESTER; STRATEGIES; PREFERENCES; GYNECOLOGY; OBSTETRICS; MEDICINE; GUIDE AB Methodologic and ethical concerns in the area of prenatal diagnosis include whether the effects of such testing on individuals other than patients are considered, what assumptions are made regarding termination of pregnancy following a diagnosis, whether the redundancy of screening and diagnostic methods is considered, and how the impact of positive or negative screening results on patient experience and anxiety can be quantified. Several studies have examined the cost-effectiveness of screening for Down syndrome (DS). Given the current test characteristics, screening for DS is cost-effective across a wide variety of clinical situations. In fact, contingent screening is potentially a dominant strategy (costs less and leads to better outcomes). Understanding the methodology and salient issues of cost-effectiveness analysis is critical for researchers, editors, and clinicians to accurately interpret results of the growing body of cost-effectiveness studies in prenatal diagnosis. C1 [Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97239 USA. [Kaimal, Anjali J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. [Odibo, Anthony O.] Washington Univ, Div Maternal Fetal Med, Dept Obstet & Gynecol, St Louis, MO USA. RP Caughey, AB (reprint author), Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, L466,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM abcmd@berkeley.edu NR 35 TC 10 Z9 10 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 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 2010 VL 30 IS 3 BP 629 EP + DI 10.1016/j.cll.2010.04.007 PG 16 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 636LB UT WOS:000280735700011 PM 20638577 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI Depression: There Is No Upside SO CNS SPECTRUMS LA English DT Editorial Material C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Boston, MA 02138 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Boston, MA 02138 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD SEP PY 2010 VL 15 IS 9 BP 552 EP 553 DI 10.1017/S1092852900000511 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA V36CE UT WOS:000209190200001 ER PT J AU Misra, M Le Clair, M Mendes, N Miller, KK Lawson, E Meenaghan, E Weigel, T Ebrahimi, S Herzog, DB Klibanski, A AF Misra, Madhusmita Le Clair, Marie Mendes, Nara Miller, Karen K. Lawson, Elizabeth Meenaghan, Erinne Weigel, Thomas Ebrahimi, Seda Herzog, David B. Klibanski, Anne TI Use of SSRIs May Impact Bone Density in Adolescent and Young Women With Anorexia Nervosa SO CNS SPECTRUMS LA English DT Article AB Objectives: Alterations in serotonin impact bone metabolism in animal models, and selective serotonin reuptake inhibitors (SSRIs) have been associated with increased fracture risk in older adults. SSRIs are commonly used in anorexia nervosa (AN), a condition that predisposes to low bone mineral density (BMD). Our objective was to determine whether SSRI use is associated with low BMD in AN. Methods: We examined Z-scores for spine, hip, and whole body (WB) BMD, spine bone mineral apparent density, and WB bone mineral content/height (BMC/Ht) in females 12-21 years of age with AN who had never been on SSRIs, had been on SSRIs for <6 months (<6M), or had been on SSRIs for >6 months (>6M). Results: Subjects on SSRIs for >6M had lower spine, femoral-neck, and WBBMD Z-scores than those on SSRIs for <6M. Hip BMD and WBBMC/ Ht Z-scores were lowest in subjects on SSRIs for >6M. Duration of SSRI use, duration since AN diagnosis and duration of amenorrhea inversely predicted BMD, whereas BMI was a positive predictor. In a regression model, duration of SSRI use remained an independent negative predictor of BMD. Discussion: Duration of SSRI use >6M is associated with low BMD in AN. Conclusion: It may be necessary to monitor BMD more rigorously when duration of SSRI use exceeds 6M. C1 [Misra, Madhusmita; Le Clair, Marie; Mendes, Nara; Miller, Karen K.; Lawson, Elizabeth; Meenaghan, Erinne; Weigel, Thomas; Herzog, David B.; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA USA. [Ebrahimi, Seda] Cambridge Eating Disorders Ctr, Cambridge, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU National Institutes of Health [1 UL1 RR025758-01, DK 062249, K23 RR018851] FX Funding for this study was provided in part by National Institutes of Health grants 1 UL1 RR025758-01, DK 062249 and K23 RR018851. The study was performed in the Neuroendocrine Unit of Massachusetts General Hospital. NR 43 TC 8 Z9 8 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD SEP PY 2010 VL 15 IS 9 BP 579 EP 586 DI 10.1017/S1092852900000559 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA V36CE UT WOS:000209190200005 PM 24790401 ER PT J AU Lee, JT AF Lee, Jeannie T. TI The X as Model for RNA's Niche in Epigenomic Regulation SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; CHROMOSOME INACTIVATION; XIST GENE; NONCODING RNAS; DOSAGE COMPENSATION; ANTISENSE TRANSCRIPTION; TSIX TRANSCRIPTION; HISTONE H3; CHROMATIN-STRUCTURE; DNA METHYLATION AB The X-linked region now known as the "X-inactivation center" (Xic) was once dominated by protein-coding genes but, with the rise of Eutherian mammals some 150-200 million years ago, became infiltrated by genes that produce long noncoding RNA (ncRNA). Some of the noncoding genes have been shown to play crucial roles during X-chromosome inactivation (XCI), including the targeting of chromatin modifiers to the X. The rapid establishment of ncRNA hints at a possible preference for long transcripts in some aspects of epigenetic regulation. This article discusses the role of RNA in XCI and considers the advantages RNA offers in delivering allelic, cis-limited, and locus-specific control. Unlike proteins and small RNAs, long ncRNAs are tethered to the site of transcription and effectively tag the allele of origin. Furthermore, long ncRNAs are drawn from larger sequence space than proteins and can mark a unique region in a complex genome. Thus, like their small RNA cousins, long ncRNAs may emerge as versatile and powerful regulators of the epigenome. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol,Massachusetts Gen Hosp,Dept Genet, Boston, MA 02115 USA. RP Lee, JT (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol,Massachusetts Gen Hosp,Dept Genet, Boston, MA 02115 USA. EM lee@molbio.mgh.harvard.edu FU National Institutes of Health [RO1-GM58839]; HHMI FX I am greatly indebted to all members of my lab for their invaluable discussions, insights, and inspiration. Work described in this article has been sponsored by either the National Institutes of Health. (RO1-GM58839) or by the HHMI, where JTL is an investigator. NR 124 TC 40 Z9 46 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD SEP PY 2010 VL 2 IS 9 AR a003749 DI 10.1101/cshperspect.a003749 PG 12 WC Cell Biology SC Cell Biology GA 646WS UT WOS:000281575800011 PM 20739414 ER PT J AU Schrum, JP Zhu, TF Szostak, JW AF Schrum, Jason P. Zhu, Ting F. Szostak, Jack W. TI The Origins of Cellular Life SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID TEMPLATE-DIRECTED SYNTHESIS; FATTY-ACID VESICLES; MURCHISON CARBONACEOUS CHONDRITE; SELF-REPRODUCING VESICLES; RNA-POLYMERASE MODEL; PRIMER EXTENSION; GROWTH; OLIGOMERIZATION; POLYMERIZATION; PROTOCELL AB Understanding the origin of cellular life on Earth requires the discovery of plausible pathways for the transition from complex prebiotic chemistry to simple biology, defined as the emergence of chemical assemblies capable of Darwinian evolution. We have proposed that a simple primitive cell, or protocell, would consist of two key components: a protocell membrane that defines a spatially localized compartment, and an informational polymer that allows for the replication and inheritance of functional information. Recent studies of vesicles composed of fatty-acid membranes have shed considerable light on pathways for protocell growth and division, as well as means by which protocells could take up nutrients from their environment. Additional work with genetic polymers has provided insight into the potential for chemical genome replication and compatibility with membrane encapsulation. The integration of a dynamic fatty-acid compartment with robust, generalized genetic polymer replication would yield a laboratory model of a protocell with the potential for classical Darwinian biological evolution, and may help to evaluate potential pathways for the emergence of life on the early Earth. Here we discuss efforts to devise such an integrated protocell model. C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute NR 62 TC 47 Z9 49 U1 9 U2 63 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD SEP PY 2010 VL 2 IS 9 AR a002212 DI 10.1101/cshperspect.a002212 PG 15 WC Cell Biology SC Cell Biology GA 646WS UT WOS:000281575800007 PM 20484387 ER PT J AU Kelley, JM Kaptchuk, TJ AF Kelley, John M. Kaptchuk, Ted J. TI Group analysis versus individual response: The inferential limits of randomized controlled trials SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Randomized controlled trial; Clinical trial; Placebo effect; Treatment responder ID PERSONALIZED MEDICINE; CLINICAL-TRIALS; THERAPY AB The randomized controlled trial (RCT) is the gold standard for assessing the efficacy of medical treatments. Over the past 50 years, RCT methodology has proven to be quite successful in identifying effective treatments and weeding out ineffective ones, thus transforming medicine from an intuitive art into an empirical science. However, the enormous success of the RCT has inadvertently contributed to a common inferential error that is insufficiently appreciated by some clinicians and researchers. Although RCTs can effectively distinguish between placebo and active treatment effects at the level of the group, contrary to intuition, this same disentanglement is much more difficult to achieve at the level of the individual. For individual patients it is surprisingly difficult to determine who is a treatment responder and who is not. Using data from a recent RCT, we illustrate the problem and detail its negative effects for research and clinical practice. Finally, we suggest strategies for minimizing these negative effects. (C) 2010 Elsevier Inc. All rights reserved. C1 [Kelley, John M.] Endicott Coll, Dept Psychol, Beverly, MA 01915 USA. [Kelley, John M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Kaptchuk, Ted J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Kelley, JM (reprint author), Endicott Coll, Dept Psychol, 376 Hale St, Beverly, MA 01915 USA. EM JohnKelley@Post.Harvard.Edu FU National Center for Complementary and Alternative Medicine (NCCAM) [1R01 AT001414-01, 1R21 AT002564, 1K24 AT004095]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) FX This study was supported by National Institutes of Health (NIH) grant no. 1R01 AT001414-01 from the National Center for Complementary and Alternative Medicine (NCCAM) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); and grant nos. 1R21 AT002564 and 1K24 AT004095 from NCCAM. The contents of this article do not necessarily represent the official views of NCCAM, NIDDK, or the NIH. NR 17 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2010 VL 31 IS 5 BP 423 EP 428 DI 10.1016/j.cct.2010.07.003 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 657CX UT WOS:000282391000010 PM 20624483 ER PT J AU Weisbord, SD Shields, AM Mor, MK Sevick, MA Homer, M Peternel, J Porter, P Rollman, BL Palevsky, PM Arnold, RM Fine, MJ AF Weisbord, Steven D. Shields, Anne Marie Mor, Maria K. Sevick, Mary Ann Homer, Marcia Peternel, Janet Porter, Patricia Rollman, Bruce L. Palevsky, Paul M. Arnold, Robert M. Fine, Michael J. TI Methodology of a randomized clinical trial of symptom management strategies in patients receiving chronic hemodialysis: The SMILE study SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Symptoms; Hemodialysis; Pain; Sexual dysfunction; Erectile dysfunction; Depression ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; MAINTENANCE HEMODIALYSIS; ERECTILE DYSFUNCTION; DEPRESSED-PATIENTS; DIALYSIS PATIENTS; SEXUAL FUNCTION; MINI-COG; PAIN; PREVALENCE AB Despite the high prevalence of pain, sexual dysfunction, and depression in patients on chronic hemodialysis, these symptoms are often unrecognized and under-treated by renal providers. This report describes the rationale and methodology of the SMILE study (Symptom Management Involving End-Stage Renal Disease), a multi-center, randomized clinical trial comparing the effectiveness of two strategies for implementing treatment for these symptoms in patients receiving chronic hemodialysis. Approximately 250 patients from nine outpatient dialysis units will participate. Over a 2-12 month observational phase, participants complete monthly surveys characterizing their pain, sexual dysfunction, and depression. Following this observational period, subjects are randomized to one of two study arms to receive a 12-month intervention. In one study arm (feedback intervention), patients continue to complete the same three symptom surveys, and the presence and severity of the symptoms reported on these surveys is mailed to the patient's renal provider along with evidence-based algorithms outlining treatment options for these symptoms. Decisions on treatment are left at the discretion of the provider. Patients randomized to the other study arm (management intervention) also continue to complete the same monthly symptom surveys and are evaluated by a symptom management nurse trained in the management of these symptoms. This nurse then discusses the patient's symptoms with the renal provider, provides specific recommendations for treatment, and facilitates the implementation of treatment. The primary endpoints are changes in scores on pain, erectile dysfunction, and depression surveys. This report describes the rationale and methodology of this clinical trial. Published by Elsevier Inc. C1 [Weisbord, Steven D.; Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Med Specialty Serv Line, Renal Sect, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Shields, Anne Marie; Mor, Maria K.; Sevick, Mary Ann; Homer, Marcia; Peternel, Janet; Porter, Patricia; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann; Rollman, Bruce L.; Arnold, Robert M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Sch Med, Div Palliat Care, Pittsburgh, PA USA. [Sevick, Mary Ann] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Med Specialty Serv Line, Renal Sect, 7E Room 120,111F-U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU Department of Veterans Affairs Health Services Research and Development [IIR 07-190] FX This work was supported by a Department of Veterans Affairs Health Services Research and Development Merit Review award (IIR 07-190). 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 42 TC 20 Z9 20 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2010 VL 31 IS 5 BP 491 EP 497 DI 10.1016/j.cct.2010.06.005 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 657CX UT WOS:000282391000019 PM 20601163 ER PT J AU Tanhehco, T Colby, K AF Tanhehco, Tasha Colby, Kathryn TI The Clinical Experience of Acanthamoeba Keratitis at a Tertiary Care Eye Hospital SO CORNEA LA English DT Article DE Acanthamoeba keratitis; contact lenses wear; infectious keratitis epidemiology; corneal transplant ID CONFOCAL MICROSCOPY; CASTELLANII CYSTS; DIAGNOSIS; EPIDEMIOLOGY; MANAGEMENT; EFFICACY; SYSTEMS AB Purpose: In recent years, outbreaks of Acanthamoeba keratitis (AK) have been reported worldwide. The purpose of this study was to examine the clinical experience of AK at the Massachusetts Eye and Ear Infirmary. Methods: A retrospective case review was completed on patients with infectious keratitis whose corneal cultures were positive for Acanthamoeba between January 2000 and December 2008. The clinical characteristics and visual outcomes were examined in those patients with a follow-up period greater than 6 months. Results: Four cases were identified between January 2000 and December 2003, whereas 26 cases were identified between January 2004 and December 2008. Charts before 2004 were unavailable for review. A total of 15 cases between 2004 and 2008 had a follow-up period of greater than 6 months. In these cases, possible risk factors associated with AK included soft contact lens wear (12 of 15 cases), exposure to freshwater or saltwater sources (8 of 15 cases), chronic ocular surface disease (6 of 15 cases), ocular trauma (3 of 15 cases), and concomitant infectious keratitis (2 of 15 cases). Four cases were associated with the use of Advanced Medical Optics Complete MoisturePlus Multi-Purpose Solution. Many cases were recalcitrant to medical therapy alone, necessitating therapeutic penetrating keratoplasty in 8 of 15 cases. Conclusions: The number of AK cases at the Massachusetts Eye and Ear Infirmary has increased since 2004. Contact lens wear and exposure to contaminated water sources were potential risk factors for AK. Clinicians should maintain a high clinical suspicion for AK in cases of atypical keratitis with known risk factors for AK. C1 [Tanhehco, Tasha; Colby, Kathryn] Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. [Tanhehco, Tasha; Colby, Kathryn] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Colby, K (reprint author), Massachusetts Eye & Ear Infirm, Cornea Serv, 243 Charles St,Suite 727, Boston, MA 02114 USA. EM kacolby@meei.harvard.edu NR 31 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD SEP PY 2010 VL 29 IS 9 BP 1005 EP 1010 DI 10.1097/ICO.0b013e3181cf9949 PG 6 WC Ophthalmology SC Ophthalmology GA 641UO UT WOS:000281155500009 PM 20539211 ER PT J AU Kanoff, JM Colby, K AF Kanoff, Justin M. Colby, Kathryn TI Pigmented Deposits on a Boston Keratoprosthesis From Topical Ibopamine SO CORNEA LA English DT Article DE ibopamine; keratoprosthesis; contact lens; adrenochrome ID EPINEPHRINE AB Purpose: To report a case of pigmented deposits on a type I Boston keratoprosthesis (KPro) associated with the use of topical ibopamine as a treatment for hypotony. Methods: Case report and literature review. Results: The dopamine-like agent ibopamine caused black deposits on the bandage lens and on the front plate of the Boston KPro that resulted in reduced visual acuity. Change to a daily disposable contact lens and regular cleaning of the KPro front plate with diluted baby shampoo eliminated this problem. Conclusion: This is the first report of this complication with topical ibopamine use and should be considered when ibopamine is used chronically for hypotony. C1 [Kanoff, Justin M.; Colby, Kathryn] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Colby, K (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St,Suite 727, Boston, MA 02114 USA. EM kacolby@meei.harvard.edu NR 8 TC 1 Z9 1 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 SEP PY 2010 VL 29 IS 9 BP 1069 EP 1071 DI 10.1097/ICO.0b013e3181d07567 PG 3 WC Ophthalmology SC Ophthalmology GA 641UO UT WOS:000281155500021 PM 20567201 ER PT J AU King, DR Velmahos, GC AF King, David R. Velmahos, George C. TI Difficulties in managing the surgical patient who is morbidly obese SO CRITICAL CARE MEDICINE LA English DT Article DE morbid obesity; overweight; volume of distribution; obese; pickwickian ID VENA-CAVA FILTERS; BARIATRIC SURGERY PATIENTS; INTENSIVE-CARE-UNIT; BODY-MASS INDEX; LAPAROSCOPIC GASTRIC BYPASS; TARGET-CONTROLLED INFUSION; MOLECULAR-WEIGHT HEPARIN; CRITICALLY-ILL PATIENTS; PULMONARY-EMBOLISM; WOUND-INFECTION AB Managing patients who are morbidly obese in the intensive care unit is associated with a variety of problems uncommonly experienced with the those who are not morbidly obese. Clinicians experience a myriad of unique problems and circumstances, from the need for special beds and lifts to unusual and unknown volumes of distribution resulting in unclear drug dosing. This review examines several issues including sedation, invasive monitoring, venous thromboembolism prophylaxis, surgical infections, nutritional support, and other complications that may be of particular importance to the critically ill patient who is morbidly obese. In many cases, care is altered based on the complicating issues surrounding morbid obesity. In other cases, the presence of obesity suggests no alterations in our routine critical care delivery. A comprehensive review of the literature is undertaken, data are critically considered, and overall opinion is rendered based on the available peer-reviewed literature. In many cases, data are not available that address the specific patient population in question, so related papers (like gastric bypass data) are considered. Many issues do not have definitive answers based on randomized controlled trials, and much is left to treating clinician opinion and local practice patterns. Where good data exist, however, one should consider carefully and individually deviation from the evidence-based approach. (Crit Care Med 2010; 38[Suppl.]:S478-S482) C1 [King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. OI King, David/0000-0003-1028-1478 NR 87 TC 10 Z9 10 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2010 VL 38 IS 9 SU S BP S478 EP S482 DI 10.1097/CCM.0b013e3181ec54f6 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 647FB UT WOS:000281602100009 PM 20724881 ER PT J AU Yeh, SI Han, KY Sabri, A Rosenblatt, MI Azar, DT Jain, S Chang, JH AF Yeh, Shu-I Han, Kyu-Yeon Sabri, Abdellah Rosenblatt, Mark I. Azar, Dimitri T. Jain, Sandeep Chang, Jin-Hong TI MMP-7 Knock-In Corneal Fibroblast Cell Lines Secrete MMP-7 with Proteolytic Activity towards Collagen XVIII SO CURRENT EYE RESEARCH LA English DT Article DE Cornea; Gene transfer; Matrilysin; Matrix metalloproteinases; MMP-7 ID MATRIX-METALLOPROTEINASE MATRILYSIN; KERATOCYTE PHENOTYPE; BOVINE KERATOCYTES; GENE-EXPRESSION; CLEAVAGE; NEOVASCULARIZATION; DIFFERENTIATION; OVEREXPRESSION; MIGRATION; GROWTH AB Purpose: To determine whether matrix metalloproteinase-7 (MMP-7) that is stably overexpressed by mouse corneal fibroblast cell lines exhibits proteolytic activity against the NC1 fragment of collagen XVIII. Methods: Corneal fibroblasts isolated from MMP-7 knockout (7ko) mice were subjected to SV40 T-antigen immortalization and stably transfected with a bicistronic retroviral vector encoding green fluorescence protein and active MMP-7. The resulting MMP-7 knock-in fibroblasts (7ko-MMP-7 cells) were isolated and enriched by fluorescence activated cell sorting (FACS). Culture media samples from 7ko and 7ko-MMP-7 cells were then incubated with the recombinant NC1 fragment of collagen XVIII, and NC1 degradation was monitored by immunoblotting. Results: Immunoblot analysis revealed that MMP-7 was present in lysates and culture media from 7ko-MMP-7 fibroblasts, but not media from immortalized 7ko fibroblasts. Importantly, lower amounts of the NC1 fragment were present in in vitro enzymatic reaction mixtures containing concentrated 7ko-MMP-7 media than in those containing concentrated 7ko media. Conclusion: Immortalized fibroblasts stably transfected with MMP-7 secrete active MMP-7 with proteolytic activity towards the NC1 fragment of collagen XVIII. C1 [Han, Kyu-Yeon; Sabri, Abdellah; Azar, Dimitri T.; Jain, Sandeep; Chang, Jin-Hong] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. [Yeh, Shu-I; Rosenblatt, Mark I.; Azar, Dimitri T.; Jain, Sandeep; Chang, Jin-Hong] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Yeh, Shu-I; Rosenblatt, Mark I.; Azar, Dimitri T.; Chang, Jin-Hong] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Chang, JH (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM changr@uic.edu FU National Institutes of Health [EY001792, EY10101, EY14048]; MEEI-Schepens FX Supported by National Institutes of Health Grant EY001792, EY10101 (DTA), EY14048 (JHC), MEEI-Schepens Joint Center for Clinical Research Fellowship (MIR). NR 26 TC 3 Z9 3 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD SEP PY 2010 VL 35 IS 9 BP 799 EP 805 DI 10.3109/02713683.2010.494239 PG 7 WC Ophthalmology SC Ophthalmology GA 664KL UT WOS:000282958700004 PM 20795861 ER PT J AU Garibyan, L Fisher, DE AF Garibyan, Lilit Fisher, David E. TI How Sunlight Causes Melanoma SO CURRENT ONCOLOGY REPORTS LA English DT Article DE Ultraviolet; Melanoma; Tanning; Carcinogenesis; Immunosuppression ID CYCLOBUTANE PYRIMIDINE DIMERS; PLATELET-ACTIVATING-FACTOR; SKIN-CANCER; MALIGNANT-MELANOMA; ULTRAVIOLET-RADIATION; MOLECULAR-MECHANISMS; CUTANEOUS MELANOMA; BRAF MUTATIONS; SUN EXPOSURE; UV AB The incidence of melanoma has continued to rise dramatically over the past few decades, especially in young females. Due to the deadly nature of this disease, melanoma has become an important public health problem. It is generally accepted that ultraviolet light radiation (UVR) from sunlight is a major risk factor for melanoma skin cancer development. However, the mechanistic details of how sunlight via UVR causes melanoma are still being elucidated. Currently, it is thought that carcinogenic, inflammatory, and immunosuppressive properties of UVR all contribute to initiation, progression, and metastasis of primary melanoma. We review current findings on how sunlight-generated UVR generates DNA damage, inflammation, and immune suppression, thus leading to melanoma. C1 [Garibyan, Lilit; Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp Boston, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA 02114 USA. [Garibyan, Lilit; Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp Boston, Melanoma Program, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp Boston, Cutaneous Biol Res Ctr,Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. EM dfisher3@partners.org FU NIAMS NIH HHS [R01 AR043369] NR 58 TC 40 Z9 41 U1 2 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD SEP PY 2010 VL 12 IS 5 BP 319 EP 326 DI 10.1007/s11912-010-0119-y PG 8 WC Oncology SC Oncology GA 723IW UT WOS:000287501100007 PM 20623386 ER PT J AU Swales, HH Wang, TJ AF Swales, Heather H. Wang, Thomas J. TI Vitamin D and cardiovascular disease risk: emerging evidence SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE blood pressure; cardiovascular disease; diabetes mellitus; metabolic syndrome; supplementation; vitamin D ID 25-HYDROXYVITAMIN D LEVELS; SMOOTH-MUSCLE-CELLS; ALL-CAUSE MORTALITY; NUTRITION EXAMINATION SURVEY; RENIN-ANGIOTENSIN SYSTEM; PLACEBO-CONTROLLED TRIAL; BODY-MASS INDEX; BLOOD-PRESSURE; D DEFICIENCY; 1,25-DIHYDROXYVITAMIN D-3 AB Purpose of review Vitamin D deficiency is common throughout the world, with a particularly high prevalence in northern latitudes and colder climates. Although the best known sequelae of vitamin D deficiency involve the musculoskeletal system, a growing body of evidence suggests that vitamin D status may influence cardiovascular health as well. This review focuses on recent studies linking vitamin D and cardiovascular disease risk, emphasizing the potential relevance to primary prevention. Recent findings There is strong experimental evidence that vitamin D status may influence cardiovascular structure and function. The number of clinical studies has steadily grown in recent years, with the largest number comprising observational studies showing associations between low vitamin D status, the presence of various cardiovascular risk factors, and adverse cardiovascular outcomes. A few small, randomized, controlled studies have been published, but these have been largely inconclusive. Summary Despite substantial clinical evidence linking vitamin D deficiency with increased cardiovascular risk, it remains to be established whether this represents a causal association. Further study is needed with prospective, randomized controlled trials before vitamin D supplementation can be routinely recommended for the primary or secondary prevention of cardiovascular disease. C1 [Wang, Thomas J.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Swales, Heather H.] Univ Massachusetts, Sch Med, Div Cardiol, Worcester, MA USA. RP Wang, TJ (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org FU National Institutes of Health [R01-HL-086875, R01-HL-083197, R01-HL-098283, R01-DK-081572]; American Heart Association FX Dr Wang was supported by grants from the National Institutes of Health (R01-HL-086875, R01-HL-083197, R01-HL-098283, and R01-DK-081572) and the American Heart Association. NR 66 TC 14 Z9 14 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD SEP PY 2010 VL 25 IS 5 BP 513 EP 517 DI 10.1097/HCO.0b013e32833cd491 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 634BE UT WOS:000280553100014 PM 20616710 ER PT J AU Weiss, JW Thorp, ML O'Hare, AM AF Weiss, Jessica W. Thorp, Micah L. O'Hare, Ann M. TI Renin-angiotensin system blockade in older adults with chronic kidney disease: a review of the literature SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE aging; angiotensin-converting enzyme inhibitor; angiotensin receptor blocker; chronic kidney disease; elderly ID CONVERTING-ENZYME-INHIBITION; RANDOMIZED CONTROLLED-TRIAL; CORONARY-ARTERY-DISEASE; HIGH-RISK PATIENTS; CARDIOVASCULAR EVENTS; BLOOD-PRESSURE; RENAL OUTCOMES; HYPERTENSIVE PATIENTS; MORTALITY RISK; DOUBLE-BLIND AB Purpose of review We have reviewed the literature examining the benefits and harms of renin-angiotensin system (RAS) blockade in older adults, using studies which included patients with chronic kidney disease (CKD) as well as those which included a broader patient population. Recent findings We review the results of key trials which evaluate the impact of RAS blockade on renal outcomes, and those which address the impact of RAS blockade on more global outcomes (cardiovascular events and mortality). Many trials examining renal outcomes of RAS blockade excluded older patients or did not present age-stratified results, whereas trials which examined global outcomes often excluded patients with CKD. Most older patients with CKD have nonproteinuric nondiabetic CKD, thus differing from participants in trials which examined renal outcomes, which often included only patients with diabetes or proteinuria. Most studies did not address alternate outcomes which may carry greatest import for older patients, such as worsening comorbid illness or changes in functional status. Summary The role of RAS inhibition for older patients with CKD remains unclear. Information on age-specific effects of RAS blockade on a range of different outcomes among older patients with CKD would improve our ability to assess the benefits and harms of RAS inhibition in this population. C1 [Weiss, Jessica W.] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, Portland, OR 97239 USA. [Thorp, Micah L.] Kaiser Permanente NW, Dept Nephrol, Lake Rd Nephrol Ctr, Milwaukie, OR USA. [O'Hare, Ann M.] Univ Washington, Dept Med, Div Nephrol, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. RP Weiss, JW (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, 3314 SW US Vet Hosp Rd Mail Code PP 262, Portland, OR 97239 USA. EM weinstje@ohsu.edu FU AHRQ [HS017582]; National Institute on Aging FX J.W.W. was supported by a AHRQ T32 training grant HS017582. A.M.O'H. was supported by a Beeson Career Development Award from the National Institute on Aging. She receives royalties from UpToDate. NR 40 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 EI 1473-6543 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 2010 VL 19 IS 5 BP 413 EP 419 DI 10.1097/MNH.0b013e32833b8d6b PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 640YW UT WOS:000281091300001 PM 20539228 ER PT J AU Lauritzen, HPMM Galbo, H Toyoda, T Goodyear, LJ AF Lauritzen, Hans P. M. M. Galbo, Henrik Toyoda, Taro Goodyear, Laurie J. TI Kinetics of Contraction-Induced GLUT4 Translocation in Skeletal Muscle Fibers From Living Mice SO DIABETES LA English DT Article ID GREEN-FLUORESCENT PROTEIN; INDUCED GLUCOSE-TRANSPORT; TRANSVERSE TUBULES; T-TUBULES; INSULIN STIMULATION; INTRACELLULAR POOL; VACUOLE FORMATION; VESICLE DYNAMICS; IN-VIVO; RAT AB OBJECTIVE-Exercise is an important strategy for the treatment of type 2 diabetes. This is due in part to an increase in glucose transport that occurs in the working skeletal muscles. Glucose transport is regulated by GLUT4 translocation in muscle, but the molecular machinery mediating this process is poorly understood. The purpose of this study was to 1) use a novel imaging system to elucidate the kinetics of contraction-induced GLUT4 translocation in skeletal muscle and 2) determine the function of AMP-activated protein kinase alpha 2 (AMPK alpha 2) in this process. RESEARCH DESIGN AND METHODS-Confocal imaging was used to visualize GLUT4-enhanced green fluorescent protein (EGFP) in transfected quadriceps muscle fibers in living mice subjected to contractions or the AMPK-activator AICAR. RESULTS-Contraction increased GLUT4-EGFP translocation from intracellular vesicle depots to both the sarcolemma and t-tubules with similar kinetics, although translocation was greater with contractions elicited by higher voltage. Re-internalization of GLUT4 did not begin until 10 mm after contractions ceased and was not complete until 130 min after contractions. AICAR increased GLUT4-EGFP translocation to both sarcolemma and t-tubules with similar kinetics. Ablation of AMPK alpha 2 activity in AMPK alpha 2 inactive transgenic mice did not change GLUT4-EGFP's basal localization, contraction-stimulated intracellular GLUT4-EGFP vesicle depletion, translocation, or re-internalization, but diminished AICAR-induced translocation. CONCLUSIONS-We have developed a novel imaging system to study contraction-stimulated GLUT4 translocation in living mice. Contractions increase GLUT4 translocation to the sarcolemma and t-tubules with similar kinetics and do not require AMPK alpha 2 activity. Diabetes 59:2134-2144, 2010 C1 [Lauritzen, Hans P. M. M.; Toyoda, Taro; Goodyear, Laurie J.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Lauritzen, Hans P. M. M.; Toyoda, Taro; Goodyear, Laurie J.] Harvard Univ, Sch Med, Boston, MA USA. [Galbo, Henrik] Copenhagen Univ Hosp, Rigshosp, Dept Rheumatol, Copenhagen, Denmark. [Galbo, Henrik] Copenhagen Univ Hosp, Rigshosp, Inst Inflammat Res, Copenhagen, Denmark. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu FU National Institutes of Health [R01AR45670, R01DK68626]; Diabetes and Endocrinology Research Center at the Joslin Diabetes Center [P30DK036836]; Weimann Foundation; Beckett Foundation; Danish National Research Foundation; American Diabetes Association FX This project was supported by grants from the National Institutes of Health (R01AR45670 and R01DK68626) (L.J.G.) and the Diabetes and Endocrinology Research Center at the Joslin Diabetes Center (P30DK036836). H.P.M.M.L. was supported by the Weimann Foundation, the Beckett Foundation, and the Danish National Research Foundation. T.T. was supported by an American Diabetes Association mentor-based fellowship (L.J.G.). NR 45 TC 32 Z9 32 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2010 VL 59 IS 9 BP 2134 EP 2144 DI 10.2337/db10-0233 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647IN UT WOS:000281612000008 PM 20622170 ER PT J AU Tong, J Prigeon, RL Davis, HW Bidlingmaier, M Kahn, SE Cummings, DE Tschop, MH D'Alessio, D AF Tong, Jenny Prigeon, Ronald L. Davis, Harold W. Bidlingmaier, Martin Kahn, Steven E. Cummings, David E. Tschoep, Matthias H. D'Alessio, David TI Ghrelin Suppresses Glucose-Stimulated Insulin Secretion and Deteriorates Glucose Tolerance in Healthy Humans SO DIABETES LA English DT Article ID GROWTH-HORMONE; RAT ISLETS; BETA-CELLS; GLUCAGON-SECRETION; PANCREATIC-ISLETS; RELEASE; RESISTANCE; ENDOCRINE; RECEPTOR; HOMEOSTASIS AB OBJECTIVE-The orexigenic gut hormone ghrelin and its receptor are present in pancreatic islets. Although ghrelin reduces insulin secretion in rodents, its effect on insulin secretion in humans has not been established. The goal of this study was to test the hypothesis that circulating ghrelin suppresses glucose-stimulated insulin secretion in healthy subjects. RESEARCH DESIGN AND METHODS-Ghrelin (0.3, 0.9 and 1.5 nmol/kg/h) or saline was infused for more than 65 min in 12 healthy patients (8 male/4 female) on 4 separate occasions in a counterbalanced fashion. An intravenous glucose tolerance test was performed during steady state plasma ghrelin levels. The acute insulin response to intravenous glucose (AIRg) was calculated from plasma insulin concentrations between 2 and 10 min after the glucose bolus. Intravenous glucose tolerance was measured as the glucose disappearance constant (Kg) from 10 to 30 min. RESULTS-The three ghrelin infusions raised plasma total ghrelin concentrations to 4-, 15-, and 23-fold above the fasting level, respectively. Ghrelin infusion did not alter fasting plasma insulin or glucose, but compared with saline, the 0.3, 0.9, and 1.5 nmol/kg/h doses decreased AIRg (2,152 +/- 448 vs. 1,478 +/- 2,889, 1,419 +/- 275, and 1,120 +/- 174 pmol/l) and Kg (0.3 and 1.5 nmol/kg/h doses only) significantly (P < 0.05 for all). Ghrelin infusion raised plasma growth hormone and serum cortisol concentrations significantly (P < 0.001 for both), but had no effect on glucagon, epinephrine, or norepinephrine levels (P = 0.44, 0.74, and 0.48, respectively). CONCLUSIONS-This is a robust proof-of-concept study showing that exogenous ghrelin reduces glucose-stimulated insulin secretion and glucose disappearance in healthy humans. Our findings raise the possibility that endogenous ghrelin has a role in physiologic insulin secretion, and that ghrelin antagonists could improve beta-cell function. Diabetes 59:2145-2151, 2010 C1 [Tong, Jenny; Davis, Harold W.; Tschoep, Matthias H.; D'Alessio, David] Univ Cincinnati, Dept Med, Div Endocrinol Diabet & Metab, Cincinnati, OH 45221 USA. [Prigeon, Ronald L.] Univ Maryland, Sch Med, Vet Affairs Med Ctr, Baltimore, MD 21201 USA. [Bidlingmaier, Martin] Univ Munich, Med Klin Innenstadt, D-8000 Munich, Germany. [Kahn, Steven E.; Cummings, David E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.; Cummings, David E.] Univ Washington, Seattle, WA 98195 USA. [D'Alessio, David] Cincinnati VA Med Ctr, Cincinnati, OH USA. RP Tong, J (reprint author), Univ Cincinnati, Dept Med, Div Endocrinol Diabet & Metab, Cincinnati, OH 45221 USA. EM jenny.tong@uc.edu RI Tschoep, Matthias/I-5443-2014; OI Bidlingmaier, Martin/0000-0002-4681-6668; Kahn, Steven/0000-0001-7307-9002; Tschoep, Matthias/0000-0002-4744-371X FU NIH/NIDDK [5K23DK-80081, R0157900]; Department of Veterans Affairs FX Funding for this research was provided by NIH/NIDDK (5K23DK-80081 to J.T. and R0157900 to D.D.) and the Department of Veterans Affairs. M.H.T. is a scientific advisory board member and stockholder of Marcadia Biotech, Acylin Pharmaceutical, and Ambrx Inc. NR 49 TC 135 Z9 138 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2010 VL 59 IS 9 BP 2145 EP 2151 DI 10.2337/db10-0504 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647IN UT WOS:000281612000009 PM 20584998 ER PT J AU Vergani, A D'Addio, F Jurewicz, M Petrelli, A Watanabe, T Liu, KF Law, K Schuetz, C Carvello, M Orsenigo, E Deng, SP Rodig, SJ Ansari, JM Staudacher, C Abdi, R Williams, J Markmann, J Atkinson, M Sayegh, MH Fiorina, P AF Vergani, Andrea D'Addio, Francesca Jurewicz, Mollie Petrelli, Alessandra Watanabe, Toshihiko Liu, Kaifeng Law, Kenneth Schuetz, Christian Carvello, Michele Orsenigo, Elena Deng, Shaoping Rodig, Scott J. Ansari, Javeed M. Staudacher, Carlo Abdi, Reza Williams, John Markmann, James Atkinson, Mark Sayegh, Mohamed H. Fiorina, Paolo TI A Novel Clinically Relevant Strategy to Abrogate Autoimmunity and Regulate Alloimmunity in NOD Mice SO DIABETES LA English DT Article ID ISLET ALLOGRAFT SURVIVAL; MEMORY T-CELLS; HOMEOSTATIC PROLIFERATION; ANTITHYMOCYTE GLOBULIN; RENAL-TRANSPLANTATION; RHEUMATOID-ARTHRITIS; THYMOCYTE GLOBULIN; CUTTING EDGE; ABATACEPT; RESPONSES AB OBJECTIVE-To investigate a new clinically relevant immunoregulatory strategy based on treatment with murine Thymoglobulin mATG Genzyme and CTLA4-Ig in NOD mice to prevent allo- and autoimmune activation using a stringent model of islet transplantation and diabetes reversal. RESEARCH DESIGN AND METHODS-Using allogeneic islet transplantation models as well as NOD mice with recent onset type 1 diabetes, we addressed the therapeutic efficacy and immunomodulatory mechanisms associated with a new immunoregulatory protocol based on prolonged low-dose mATG plus CTLA4-Ig. RESULTS-BALB/c islets transplanted into hyperglycemic NOD mice under prolonged mATG+CTLA4-Ig treatment showed a pronounced delay in allograft rejection compared with untreated mice (mean survival time: 54 vs. 8 days, P < 0.0001). Immunologic analysis of mice receiving transplants revealed a complete abrogation of autoimmune responses and severe downregulation of alloimmunity in response to treatment. The striking effect on autoimmunity was confirmed by 100% diabetes reversal in newly hyperglycemic NOD mice and 100% indefinite survival of syngeneic islet transplantation (NOD.SCID into NOD mice). CONCLUSIONS-The capacity to regulate alloimmunity and to abrogate the autoimmune response in NOD mice in different settings confirmed that prolonged mATG+CTLA4-Ig treatment is a clinically relevant strategy to translate to humans with type 1 diabetes. Diabetes 59:2253-2264, 2010 C1 [Vergani, Andrea; D'Addio, Francesca; Jurewicz, Mollie; Petrelli, Alessandra; Watanabe, Toshihiko; Carvello, Michele; Ansari, Javeed M.; Abdi, Reza; Sayegh, Mohamed H.; Fiorina, Paolo] Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Vergani, Andrea; D'Addio, Francesca; Jurewicz, Mollie; Petrelli, Alessandra; Watanabe, Toshihiko; Carvello, Michele; Ansari, Javeed M.; Abdi, Reza; Sayegh, Mohamed H.; Fiorina, Paolo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Vergani, Andrea; Petrelli, Alessandra; Carvello, Michele; Orsenigo, Elena; Staudacher, Carlo; Fiorina, Paolo] Ist Sci San Raffaele, Dept Med & Surg, I-20132 Milan, Italy. [Liu, Kaifeng] Harvard Univ, Sch Med, Div Pulm Med, Childrens Hosp Boston, Boston, MA USA. [Law, Kenneth; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Div Hematopathol, Boston, MA 02115 USA. [Schuetz, Christian; Deng, Shaoping; Markmann, James] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Williams, John] Genzyme, Cambridge, MA USA. [Atkinson, Mark] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. RP Fiorina, P (reprint author), Childrens Hosp, Transplantat Res Ctr, 300 Longwood Ave, Boston, MA 02115 USA. EM paolo.fiorina@childrens.harvard.edu RI Petrelli, Alessandra/B-7972-2011; Petrelli, Alessandra/M-7004-2015; Schuetz, Christian/K-5234-2013; D'Addio, Francesca/F-3417-2017 OI Petrelli, Alessandra/0000-0002-5639-9415; Schuetz, Christian/0000-0002-6828-4543; D'Addio, Francesca/0000-0002-0345-0694 FU American Society of Transplantation Juvenile Diabetes Research Foundation (AST-JDRF); Juvenile Diabetes Research Foundation (JDRF); American Society of Nephrology (ASN); Boston Area Diabetes Endocrinology Research Center [5P30DK57521] FX P.F. is the recipient of an American Society of Transplantation Juvenile Diabetes Research Foundation (AST-JDRF) Faculty Grant and a Juvenile Diabetes Research Foundation (JDRF)-Career Development Award and American Society of Nephrology (ASN)-Career Development Award. A.V. is the recipient of an Amercian Society of Transplantation-Juvenile Diabetes Research Foundation (AST-JDRF)-fellowship grant. P.F. acknowledges support from a Pilot and Feasibility Award from the Boston Area Diabetes Endocrinology Research Center (5P30DK57521). NR 36 TC 40 Z9 44 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2010 VL 59 IS 9 BP 2253 EP 2264 DI 10.2337/db09-1264 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647IN UT WOS:000281612000022 PM 20805386 ER PT J AU Klingensmith, GJ Pyle, L Arslanian, S Copeland, KC Cuttler, L Kaufman, F Laffel, L Marcovina, S Tollefsen, SE Weinstock, RS Linder, B AF Klingensmith, Georgeanna J. Pyle, Laura Arslanian, Silva Copeland, Kenneth C. Cuttler, Leona Kaufman, Francine Laffel, Lori Marcovina, Santica Tollefsen, Sherida E. Weinstock, Ruth S. Linder, Barbara CA TODAY Study Grp TI The Presence of GAD and IA-2 Antibodies in Youth With a Type 2 Diabetes Phenotype Results from the TODAY study SO DIABETES CARE LA English DT Article ID CHILDREN; ADOLESCENTS; AUTOIMMUNITY; MELLITUS; EUROPE; TRENDS; ONSET AB OBJECTIVE - To determine the frequency of islet cell autoimmunity in youth clinically diagnosed with type 2 diabetes and describe associated clinical and laboratory findings. RESEARCH DESIGN AND METHODS - Children (10-17 years) diagnosed with type 2 diabetes were screened for participation in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Measurements included GAD-65 and insulinoma-associated protein 2 autoantibodies using the new National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health (NIDDK/NIH) standardized assays, a physical examination, and fasting lipid, C-peptide, and A1C determinations. RESULTS - Of the 1,206 subjects screened and considered clinically to have type 2 diabetes, 118 (9.8%) were antibody positive; of these, 71 (5.9%) were positive for a single antibody, and 47 were positive (3.9%) for both antibodies. Diabetes autoantibody (DAA) positivity was significantly associated with race (P < 0.0001), with positive subjects more likely to be white (40.7 vs. 19%) (P < 0.0001) and male (51.7 vs. 35.7%) (P = 0.0007). BMI, BMI z score, C-peptide, A1C, triglycerides, HDL cholesterol, and blood pressure were significantly different by antibody status. The antibody-positive subjects were less likely to display characteristics clinically associated with type 2 diabetes and a metabolic syndrome phenotype, although the range for BMI z score, blood pressure, fasting C-peptide, and serum lipids overlapped between antibody-positive and antibody-negative subjects. CONCLUSIONS - Obese youth with a clinical diagnosis of type 2 diabetes may have evidence of islet autoimmunity contributing to insulin deficiency. As a group, patients with DAA have clinical characteristics significantly different from those without DAA. However, without islet autoantibody analysis, these characteristics cannot reliably distinguish between obese young individuals with type 2 diabetes and those with autoimmune diabetes. C1 [Klingensmith, Georgeanna J.] Univ Colorado Denver, Barbara Davis Ctr, Aurora, CO 80202 USA. [Klingensmith, Georgeanna J.] Univ Colorado Denver, Childrens Hosp, Aurora, CO USA. [Pyle, Laura] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Arslanian, Silva] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Copeland, Kenneth C.] Univ Oklahoma, Coll Med, Oklahoma City, OK 73190 USA. [Cuttler, Leona] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Kaufman, Francine] Univ So Calif, Los Angeles, CA USA. [Kaufman, Francine] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. [Laffel, Lori] Harvard Univ, Sch Med, Boston, MA USA. [Marcovina, Santica] Univ Washington, Dept Med, Seattle, WA USA. [Tollefsen, Sherida E.] St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Syracuse, NY USA. [Weinstock, Ruth S.] Dept Vet Affairs Med Ctr, Syracuse, NY USA. [Linder, Barbara] NIDDKD, NIH, Bethesda, MD 20892 USA. RP Klingensmith, GJ (reprint author), Univ Colorado Denver, Barbara Davis Ctr, Aurora, CO 80202 USA. EM georgeanna.klingensmith@ucdenver.edu FU NIDDK, NIH [U01-DK-61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, U01-DK-61254]; National Center for Research Resources General Clinical Research Centers [M01-RR-00036, M01-RR-00043-45, M01-RR-00069, M01-RR-00084, M01-RR-01066, M01-RR-00125, M01-RR14467] FX This work was completed with funding from NIDDK, NIH (grants U01-DK-61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, and U01-DK-61254) and from the National Center for Research Resources General Clinical Research Centers Program (grant M01-RR-00036 [Washington University in St. Louis School of Medicine], M01-RR-00043-45 [Children's Hospital Los Angeles], M01-RR-00069 [University of Colorado Health Sciences Center], M01-RR-00084 [Children's Hospital of Pittsburgh], M01-RR-01066 [Massachusetts General Hospital], M01-RR-00125 [Yale University], and M01-RR14467 [University of Oklahoma Health Sciences Center]). NR 19 TC 46 Z9 50 U1 0 U2 0 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 SEP PY 2010 VL 33 IS 9 BP 1970 EP 1975 DI 10.2337/dc10-0373 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 659IN UT WOS:000282560300014 PM 20519658 ER PT J AU van Melle, JP Bot, M De Jonge, P De Boer, RA van Veldhuisen, DJ Whooley, MA AF van Melle, Joost P. Bot, Marisica De Jonge, Peter De Boer, Rudolf A. van Veldhuisen, Dirk J. Whooley, Mary A. TI Diabetes, Glycemic Control, and New-Onset Heart Failure in Patients With Stable Coronary Artery Disease Data from the Heart and Soul Study SO DIABETES CARE LA English DT Article ID GLUCOSE-LEVELS; NATRIURETIC PEPTIDE; EUROPEAN-SOCIETY; OF-CARDIOLOGY; RISK-FACTOR; TASK-FORCE; ASSOCIATION; GUIDELINES; DIAGNOSIS; ADULTS AB OBJECTIVE- Diabetes is a predictor of both coronary artery disease (CAD) and heart failure. It is unknown to what extent the association between diabetes and heart failure is influenced by other risk factors for heart failure. RESEARCH DESIGN AND METHODS- We evaluated the association of diabetes and A1C with incident heart failure in outpatients with stable CAD and no history of heart failure (average follow-up 4.1 years). RESULTS- Of 839 participants, 200 had diabetes (23.8%). Compared with patients who did not have diabetes, those with diabetes had an increased risk of heart failure (hazard ratio [HR] 2.17 [95% CI 1.37-3.44]). Adjustment for risk factors for CAD (age, sex, race, smoking, physical inactivity, obesity, blood pressure, and LDL cholesterol), interim myocardial infarction, and myocardial ischemia did not alter the strength of the association between diabetes and heart failure. After inclusion also of other risk factors for heart failure (left ventricular ejection fraction, diastolic dysfunction, and C-reactive protein) and medication use, diabetes remained an independent predictor of heart failure (HR 3.34 [95% Cl 1.65-6.76]; P = 0.001). Each 1% increase in A1C concentration was associated with a 36% increased HR of heart failure hospitalization (HR 1.36 [95% Cl 1.17-1.58]). CONCLUSIONS- In patients with stable CAD who are free from heart failure at baseline, diabetes and glycemic control are independent risk factors for new-onset heart failure. The mechanisms by which diabetes and hyperglycemia lead to heart failure deserve further study, as the association is independent of baseline functional assessment of ischemia, systolic and diastolic function, and interim myocardial infarction. C1 [van Melle, Joost P.; De Boer, Rudolf A.; van Veldhuisen, Dirk J.] Univ Groningen, Dept Cardiol, Thoraxcenter, Univ Med Ctr Groningen, Groningen, Netherlands. [Bot, Marisica; De Jonge, Peter] Tilburg Univ, Dept Med Psychol, Ctr Res Psychol Somat Dis, NL-5000 LE Tilburg, Netherlands. [De Jonge, Peter] Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. [Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP van Melle, JP (reprint author), Univ Groningen, Dept Cardiol, Thoraxcenter, Univ Med Ctr Groningen, Groningen, Netherlands. EM j.p.van.melle@thorax.umcg.nl RI Max, Mad/E-5238-2010; de Jonge, peter/L-6395-2013; van Veldhuisen, Dirk Jan/E-8967-2014 OI Max, Mad/0000-0001-6966-6829; de Jonge, peter/0000-0002-0866-6929; NR 26 TC 19 Z9 19 U1 0 U2 7 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 SEP PY 2010 VL 33 IS 9 BP 2084 EP 2089 DI 10.2337/dc10-0286 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 659IN UT WOS:000282560300037 PM 20805280 ER PT J AU Hirsch, IB Gilliam, LK Fitzpatrick, K Khakpour, D Weinzimer, SA Tamborlane, WV Ives, B Bosson-Heenan, J Wolpert, H Shetty, G Atakov-Castillo, A Giusti, J O'Donnell, S Ghiloni, S Bode, BW O'Neil, K Tolbert, L Wysocki, T Fox, LA Mauras, N Englert, K Permuy, J Buckingham, B Wilson, DM Block, J Benassi, K Tsalikian, E Tansey, M Kucera, D Coffey, J Cabbage, J Laffel, L Milaszewski, K Pratt, K Bismuth, E Keady, J Lawlor, M Chase, HP Fiallo-Scharer, R Wadwa, P Messer, L Gage, V Burdick, P Lawrence, JM Clemons, R Maeva, M Sattler, B Beck, RW Ruedy, KJ Kollman, C Xing, DY Sibayan, J Steffes, M Bucksa, JM Nowicki, ML Van Hale, C Makky, V O'Grady, M Huang, E Basu, A Meltzer, DO Zhao, L Lee, J Kowalski, AJ Laffel, L Tamborlane, WV Beck, RW Kowalski, AJ Ruedy, KJ Weinstock, RS Anderson, BJ Kruger, D LaVange, L Rodriguez, H Cheng, J AF Hirsch, Irl B. Gilliam, Lisa K. Fitzpatrick, Kathy Khakpour, Dori Weinzimer, Stuart A. Tamborlane, William V. Ives, Brett Bosson-Heenan, Joan Wolpert, Howard Shetty, Greeshma Atakov-Castillo, Astrid Giusti, Judith O'Donnell, Stacey Ghiloni, Suzanne Bode, Bruce W. O'Neil, Kelli Tolbert, Lisa Wysocki, Tim Fox, Larry A. Mauras, Nelly Englert, Kimberly Permuy, Joe Buckingham, Bruce Wilson, Darrell M. Block, Jennifer Benassi, Kari Tsalikian, Eva Tansey, Michael Kucera, Debra Coffey, Julie Cabbage, Joanne Laffel, Lori Milaszewski, Kerry Pratt, Katherine Bismuth, Elise Keady, Joyce Lawlor, Margie Chase, H. Peter Fiallo-Scharer, Rosanna Wadwa, Paul Messer, Laurel Gage, Victoria Burdick, Patricia Lawrence, Jean M. Clemons, Robert Maeva, Michelle Sattler, Bonnie Beck, Roy W. Ruedy, Katrina J. Kollman, Craig Xing, Dongyuan Sibayan, Judy Steffes, Michael Bucksa, Jean M. Nowicki, Maren L. Van Hale, Carol Makky, Vicky O'Grady, Michael Huang, Elbert Basu, Anirban Meltzer, David O. Zhao, Lan Lee, Joyce Kowalski, Aaron J. Laffel, Lori Tamborlane, William V. Beck, Roy W. Kowalski, Aaron J. Ruedy, Katrina J. Weinstock, Ruth S. Anderson, Barbara J. Kruger, Davida LaVange, Lisa Rodriguez, Henry Cheng, Jing CA Juvenile Diabet Res Fdn Continuous TI Validation of Measures of Satisfaction with and Impact of Continuous and Conventional Glucose Monitoring SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID CHILDREN; SYSTEM; MANAGEMENT; ACCURACY; TRIAL AB Background: The evaluation of patient-reported outcomes (e. g. impact, satisfaction) is important in trials of continuous glucose monitoring (CGM). We evaluated psychometric properties of the CGM Satisfaction Scale (CGM-SAT) and the Glucose Monitoring Survey (GMS). Methods: CGM-SAT is a 44-item scale on which patients (n -224) or parents (n 102) rated their experience with CGM over the prior 6 months. GMS is a 22-item scale on which patients (n 447) or parents (n 221) rated the blood glucose monitoring system they were using (home glucose meter with or without CGM) at baseline and 6 months. Results: The alpha coefficient for the CGM-SAT was >= 0.94 for all respondents and for the GMS was >= 0.84 for all respondents at baseline and 6 months. Parent-youth agreement was 0.52 for the CGM-SAT at 6 months and 0.24 and 0.20 for the GMS at baseline and 6 months for the Standard Care Group, respectively. Test-retest reliability of the GMS at 6 months for controls was r = 0.76 for adult patients, 0.63 for pediatric patients, and 0.43 for parents. Factor analysis isolated measurement factors for the CGM-SAT labeled Benefits of CGM and Hassles of CGM, accounting for 33% and 9% of score variance, respectively. For the GMS, two factors emerged: Glucose Control and Social Complications, accounting for 28% and 9% of variance, respectively. Significant correlations of CGM-SAT with frequency of CGM use between 6 months and baseline and GMS with frequency of conventional daily self-monitoring of blood glucose at baseline support their convergent validity. Conclusions: The CGM-SAT and GMS are reliable and valid measures of patient-reported CGM outcomes. C1 [Hirsch, Irl B.; Gilliam, Lisa K.; Fitzpatrick, Kathy; Khakpour, Dori] Univ Washington, Diabet Care Ctr, Seattle, WA 98195 USA. [Weinzimer, Stuart A.; Tamborlane, William V.; Ives, Brett; Bosson-Heenan, Joan] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Wolpert, Howard; Shetty, Greeshma; Atakov-Castillo, Astrid; Giusti, Judith; O'Donnell, Stacey; Ghiloni, Suzanne] Joslin Diabet Ctr, Adult Sect, Boston, MA 02215 USA. [Bode, Bruce W.; O'Neil, Kelli; Tolbert, Lisa] Atlanta Diabet Associates, Atlanta, GA USA. [Wysocki, Tim; Fox, Larry A.; Mauras, Nelly; Englert, Kimberly; Permuy, Joe] Nemours Childrens Clin, Jacksonville, FL USA. [Buckingham, Bruce; Wilson, Darrell M.; Block, Jennifer; Benassi, Kari] Stanford Univ, Div Pediat Endocrinol & Diabet, Stanford, CA 94305 USA. [Tsalikian, Eva; Tansey, Michael; Kucera, Debra; Coffey, Julie; Cabbage, Joanne] Univ Iowa Carver Coll Med, Dept Pediat, Iowa City, IA USA. [Laffel, Lori; Milaszewski, Kerry; Pratt, Katherine; Bismuth, Elise; Keady, Joyce; Lawlor, Margie] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Chase, H. Peter; Fiallo-Scharer, Rosanna; Wadwa, Paul; Messer, Laurel; Gage, Victoria; Burdick, Patricia] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Denver, CO 80202 USA. [Lawrence, Jean M.; Clemons, Robert; Maeva, Michelle; Sattler, Bonnie] Kaiser Permanente, Dept Pediat Endocrinol & Res & Evaluat, Pasadena, CA USA. [Lawrence, Jean M.; Clemons, Robert; Maeva, Michelle; Sattler, Bonnie] Kaiser Permanente, Dept Pediat Endocrinol & Res & Evaluat, San Diego, CA USA. [Wysocki, Tim; Beck, Roy W.; Ruedy, Katrina J.; Kollman, Craig; Xing, Dongyuan; Sibayan, Judy] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Steffes, Michael; Bucksa, Jean M.; Nowicki, Maren L.; Van Hale, Carol; Makky, Vicky] Univ Minnesota, Cent Lab, Minneapolis, MN USA. [O'Grady, Michael; Huang, Elbert; Basu, Anirban; Meltzer, David O.; Zhao, Lan] Univ Chicago, Natl Opin Res Ctr, Chicago, IL 60637 USA. [Lee, Joyce] Univ Michigan, Ann Arbor, MI 48109 USA. [Kowalski, Aaron J.] Juvenile Diabet Res Fdn Inc, New York, NY USA. RP Wysocki, T (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM jdrfapp@jaeb.org RI Meltzer, David/C-2926-2009 OI Meltzer, David/0000-0003-2790-7393 NR 15 TC 24 Z9 24 U1 0 U2 1 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 SEP PY 2010 VL 12 IS 9 BP 679 EP 684 DI 10.1089/dia.2010.0015 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 638HB UT WOS:000280883100001 ER PT J AU Ritholz, MD Atakov-Castillo, A Beste, M Beverly, EA Leighton, A Weinger, K Wolpert, H AF Ritholz, M. D. Atakov-Castillo, A. Beste, M. Beverly, E. A. Leighton, A. Weinger, K. Wolpert, H. TI Psychosocial factors associated with use of continuous glucose monitoring SO DIABETIC MEDICINE LA English DT Article DE continuous glucose monitoring; psychosocial; qualitative study; semi-structured interview ID QUALITY-OF-LIFE; TYPE-1; PUMP; ADHERENCE; REGIMEN; BENEFIT; ADULTS; IMPACT AB P>Aims To identify psychosocial factors associated with the use of continuous glucose monitoring by adults with Type 1 diabetes. Methods Twenty adult patients (aged 45 +/- 15 years, diabetes duration 25 +/- 19 years, 50% female) followed at our site in the multi-centre Juvenile Diabetes Research Foundation continuous glucose monitoring trial were divided into three groups: Glycated haemoglobin (HbA(1c)) Responders who demonstrated an improvement in glycaemic control with continuous glucose monitoring (baseline HbA(1c) >= 7.0%, HbA(1c) reduction greater than or equal to 0.5%), Hypoglycaemia Responders (baseline HbA(1c) < 7.0%) who demonstrated decreased time < 3.9 mmol/l while remaining within target HbA(1c), and HbA(1c) Non-Responders (baseline HbA(1c) >= 7.0%, HbA(1c) reduction less than 0.5%). Subjects participated in semi-structured interviews focusing on their psychosocial experiences with continuous glucose monitoring. Results Three major themes were identified that differentiated Responders (including both the HbA(1c) and Hypoglycaemia groups) from Non-Responders: (i) coping with frustrations-Responders used self-controlled rather than emotions-based coping when faced with continuous glucose monitoring frustrations; (ii) use of information-Responders used retrospective pattern analysis, not just minute-by-minute data analysis, in glycaemic management; (iii) 'significant other'/spousal involvement-Responders endorsed interest, encouragement and participation by their loved ones. Both Responders and Non-Responders expressed body image concerns when wearing continuous glucose monitoring devices. Conclusions This qualitative study points to the importance of coping skills, retrospective review of data, and 'significant other' involvement in the effective use of continuous glucose monitoring. These findings will inform clinical initiatives to improve patient selection and training in the use of this new technology and have served as the basis for development of quantitative surveys to be used in clinical practice. C1 [Ritholz, M. D.; Atakov-Castillo, A.; Beste, M.; Beverly, E. A.; Leighton, A.; Weinger, K.; Wolpert, H.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ritholz, M. D.; Beverly, E. A.; Weinger, K.; Wolpert, H.] Harvard Univ, Sch Med, Boston, MA USA. [Ritholz, M. D.] Childrens Hosp, Boston, MA 02115 USA. [Wolpert, H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Ritholz, MD (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Marilyn.Ritholz@joslin.harvard.edu FU Holtsinger Foundation FX The authors would like to thank the devoted patients who participated in this study. This work was supported by a grant from the Holtsinger Foundation. NR 26 TC 15 Z9 15 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD SEP PY 2010 VL 27 IS 9 BP 1060 EP 1065 DI 10.1111/j.1464-5491.2010.03061.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 640PD UT WOS:000281062900014 PM 20722681 ER PT J AU Home, PD Kahn, SE Jones, NP Noronha, D Beck-Nielsen, H Viberti, G AF Home, P. D. Kahn, S. E. Jones, N. P. Noronha, D. Beck-Nielsen, H. Viberti, G. CA ADOPT Study Grp RECORD Steering Comm TI Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials SO DIABETOLOGIA LA English DT Article DE Cancer; Diabetes mellitus; Metformin; Rosiglitazone; Sulfonylureas; Thiazolidinediones ID METFORMIN; CANCER; RISK; COMPLICATIONS; INSULIN AB Aims/hypothesis Observational and mechanistic studies have suggested a possible relationship between treatment with metformin and decreased incidence of cancer in participants with type 2 diabetes. We extracted data for malignancies from the ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) randomised controlled clinical trials, in which the efficacy and/or safety of metformin was assessed in comparison with sulfonylureas and rosiglitazone. Methods Neoplasm occurrences were collected as adverse events in these studies. We reviewed and re-analysed the individual participant data in both studies for serious adverse events, malignancies reported as adverse events and related neoplasms of special interest. Results In ADOPT, 50 participants (3.4%) on metformin and 55 (3.8%) on each of rosiglitazone and glibenclamide (known as glyburide in the USA and Canada) developed serious adverse event malignancies (excluding non-melanoma skin cancers). This corresponds to 1.03, 1.12 and 1.31 per 100 person-years, giving hazard ratios for metformin of 0.92 (95% CI 0.63-1.35) vs rosiglitazone and 0.78 (0.53-1.14) vs glibenclamide. In RECORD, on a background of sulfonylurea, 69 (6.1%) participants developed malignant neoplasms in the metformin group, compared with 56 (5.1%) in the rosiglitazone group (HR 1.22 [0.86-1.74]). On a background of metformin, 74 (6.7%) participants in the sulfonylurea group developed malignant neoplasms, compared with 57 (5.1%) in the rosiglitazone group (HR 1.33 [0.94-1.88]). Conclusions/interpretation The malignancy rates in these two randomised controlled clinical trials do not support a view that metformin offers any particular protection against malignancy compared with rosiglitazone. However, they do not refute the possibility of a difference compared with sulfonylureas. C1 [Home, P. D.] Newcastle Univ, Sch Med, ICM Diabet, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Kahn, S. E.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, S. E.] Univ Washington, Seattle, WA 98195 USA. [Jones, N. P.] GlaxoSmithKline Res & Dev Ltd, Harlow, Essex, England. [Noronha, D.] GlaxoSmithKline Res & Dev Ltd, Greenford, Middx, England. [Beck-Nielsen, H.] Univ So Denmark, Endocrinol Res Unit, Odense, Denmark. [Viberti, G.] Kings Coll London, Metab Med Unit, Sch Med, London WC2R 2LS, England. RP Home, PD (reprint author), Newcastle Univ, Sch Med, ICM Diabet, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. EM philip.home@newcastle.ac.uk FU GlaxoSmithKline (GSK) FX The authors or institutions connected with them have received funding from GlaxoSmithKline (GSK) and other oral glucose-lowering drug manufacturers in connection with advisory, educational and research activities, including those relating to rosiglitazone. N. P. Jones and D. Noronha are employees of GSK. NR 15 TC 66 Z9 71 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 IS 9 BP 1838 EP 1845 DI 10.1007/s00125-010-1804-y PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 639YD UT WOS:000281012200006 PM 20532476 ER PT J AU Gao, Y Shao, S Xie, B Nishimura, W Sharma, A Li, G AF Gao, Y. Shao, S. Xie, B. Nishimura, W. Sharma, A. Li, G. TI MafA promotes maturation of mouse embryonic progenitor-derived insulin-producing cells SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Gao, Y.; Shao, S.; Xie, B.; Li, G.] Natl Univ Singapore, Natl Univ Med Inst, Singapore, Singapore. [Nishimura, W.; Sharma, A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 466 BP S192 EP S192 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689700467 ER PT J AU Mather, KJ Christophi, CA Jablonski, KA Knowler, WC Goldberg, RB Kahn, SE Pi-Sunyer, FX Pollin, TI Florez, JC Franks, PW AF Mather, K. J. Christophi, C. A. Jablonski, K. A. Knowler, W. C. Goldberg, R. B. Kahn, S. E. Pi-Sunyer, F. X. Pollin, T. I. Florez, J. C. Franks, P. W. CA Diabet Prevention Program Res Grp TI Associations of common variants of ADIPOQ, ADIPOR1 and ADIPOR2 with adiponectin concentration and diabetes incidence in the Diabetes Prevention Program SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Mather, K. J.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Christophi, C. A.; Jablonski, K. A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Knowler, W. C.] NIDDKD, Phoenix, AZ USA. [Goldberg, R. B.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Kahn, S. E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Pi-Sunyer, F. X.] St Lukes Roosevelt Hosp, New York, NY 10025 USA. [Pollin, T. I.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Franks, P. W.] Umea Univ Hosp, S-90185 Umea, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 303 BP S130 EP S131 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689700304 ER PT J AU Shungin, D Renstrom, F Johansson, I Florez, JC Hallmans, G Hu, FB Franks, PW AF Shungin, D. Renstrom, F. Johansson, I. Florez, J. C. Hallmans, G. Hu, F. B. Franks, P. W. CA MAGIC Investigators TI Genetic predisposition to long-term deterioration in glucose homeostasis: 10-yr follow-up of the GLACIER Study SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Shungin, D.; Renstrom, F.; Franks, P. W.] GECRG, Dept Publ Hlth & Clin Med, Umea, Sweden. [Shungin, D.; Johansson, I.] Umea Univ, Dept Odontol, S-90187 Umea, Sweden. [Renstrom, F.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Florez, J. C.; Hu, F. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hallmans, G.] Dept Publ Hlth & Clin Med, Sect Nutr Res, Umea, Sweden. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 283 BP S123 EP S123 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689700284 ER PT J AU Ampudia-Blasco, FJ Nauck, M Andjelkovic, M Horton, E Boldrin, M Balena, R AF Ampudia-Blasco, F. J. Nauck, M. Andjelkovic, M. Horton, E. Boldrin, M. Balena, R. TI Taspoglutide added to metformin provides comparable glycaemic control as insulin glargine with superior weight loss and less hypoglycaemia in type 2 diabetes: The T-emerge 5 Trial SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Ampudia-Blasco, F. J.] Clin Univ Hosp, Valencia, Spain. [Nauck, M.] Diabet Zentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany. [Andjelkovic, M.; Balena, R.] F Hoffmann La Roche, Basel, Switzerland. [Horton, E.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Boldrin, M.] Roche Pharmaceut, Nutley, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 864 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701306 ER PT J AU Bacci, S Powers, C Pacilli, A Facciorusso, A Hauser, TH De Cosmo, SA Zhang, YY Gervino, EV Di Stolfo, G Mangiacotti, D Xu, R Copetti, M Prudente, S Doria, A Trischitta, V AF Bacci, S. Powers, C. Pacilli, A. Facciorusso, A. Hauser, T. H. De Cosmo, S. A. Zhang, Y. -Y. Gervino, E. V. Di Stolfo, G. Mangiacotti, D. Xu, R. Copetti, M. Prudente, S. Doria, A. Trischitta, V. TI The ENPP1 K121Q polymorphism predicts accelerated cardiovascular events in obese patients with type 2 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Bacci, S.; Pacilli, A.; De Cosmo, S. A.] IRCCS, Endocrinol Unit, San Giovanni Rotondo, Italy. [Powers, C.; Zhang, Y. -Y.; Xu, R.; Doria, A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Facciorusso, A.; Di Stolfo, G.] IRCCS, Cardiol Unit, San Giovanni Rotondo, Italy. [Hauser, T. H.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Gervino, E. V.] Beth Israel Deaconess, Div Cardiovasc, Boston, MA USA. [Mangiacotti, D.] IRCCS, Lab Diabetol, San Giovanni Rotondo, Italy. [Copetti, M.] IRCCS, Biostat Unit, San Giovanni Rotondo, Italy. [Prudente, S.] IRCCS, Genet Lab, Rome, Italy. [Trischitta, V.] IRCCS, Diabet Lab, San Giovanni Rotondo, Italy. [Trischitta, V.] Univ Roma La Sapienza, Rome, Italy. RI Prudente, Sabrina/H-2886-2016; De Cosmo, Salvatore/J-7420-2016; Trischitta, Vincenzo/K-1487-2016 OI Prudente, Sabrina/0000-0001-9220-8981; De Cosmo, Salvatore/0000-0001-8787-8286; Trischitta, Vincenzo/0000-0003-1174-127X NR 0 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 1240 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701679 ER PT J AU Borg, R Jensen, AC Carstensen, B Kuenen, J Heine, RJ Zheng, H Nathan, DM Witte, DR AF Borg, R. Jensen, A. C. Carstensen, B. Kuenen, J. Heine, R. J. Zheng, H. Nathan, D. M. Witte, D. R. TI Can we identify typical glycaemic patterns around meals for individuals with or without diabetes? The ADAG Study SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Borg, R.; Jensen, A. C.; Carstensen, B.; Witte, D. R.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Kuenen, J.; Heine, R. J.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Zheng, H.; Nathan, D. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Biostat Dept, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 679 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701122 ER PT J AU Cyganek, K Hebda-Szydlo, A Katra, B Janas, I Borodako, A Kaim, I Skupien, J Reron, A Sieradzki, J Malecki, MT AF Cyganek, K. Hebda-Szydlo, A. Katra, B. Janas, I. Borodako, A. Kaim, I. Skupien, J. Reron, A. Sieradzki, J. Malecki, M. T. TI Pregnancy outcomes in women with type 1 and type 2 diabetes in a polish population SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Cyganek, K.; Hebda-Szydlo, A.; Katra, B.; Janas, I.; Borodako, A.; Sieradzki, J.; Malecki, M. T.] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. [Kaim, I.; Reron, A.] Jagiellonian Univ, Coll Med, Dept Obstet & Perinatol, Krakow, Poland. [Skupien, J.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 1071 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701511 ER PT J AU Garvey, WT Troupin, B Day, WW AF Garvey, W. T. Troupin, B. Day, W. W. TI Once-daily, low-dose, controlled-release phentermine/topiramate results in significant clinical improvements in overweight/obese patients with type 2 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Garvey, W. T.] Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA. [Troupin, B.; Day, W. W.] VIVUS Inc, Mountain View, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 774 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701217 ER PT J AU Goedecke, JH Adams, K Hayes, P Evans, J Dave, J Levitt, NS Lambert, EV Kahn, SE Olsson, T AF Goedecke, J. H. Adams, K. Hayes, P. Evans, J. Dave, J. Levitt, N. S. Lambert, E. V. Kahn, S. E. Olsson, T. TI Defects in glutaeal adipogenesis are associated with obesity-related insulin resistance in black South African women SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Goedecke, J. H.] S African MRC, Cape Town, South Africa. [Goedecke, J. H.; Evans, J.; Lambert, E. V.] Univ Cape Town, Dept Human Biol, ZA-7700 Rondebosch, South Africa. [Adams, K.; Hayes, P.; Dave, J.; Levitt, N. S.] Univ Cape Town, Dept Med, ZA-7700 Rondebosch, South Africa. [Kahn, S. E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. [Kahn, S. E.] Univ Washington, Seattle, WA 98195 USA. [Olsson, T.] Umea Univ, Dept Med, S-90187 Umea, Sweden. RI Goedecke, Julia/J-8628-2013; Goedecke, Julia/E-1820-2016 OI Goedecke, Julia/0000-0001-6795-4771; Goedecke, Julia/0000-0001-6795-4771 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 603 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701046 ER PT J AU Schiotz, ML Strandberg-Larsen, M Frolich, A Krasnik, A Bellows, J Kristensen, JK Vedsted, P Eskildsen, P Beck-Nielsen, H Hsu, J AF Schiotz, M. L. Strandberg-Larsen, M. Frolich, A. Krasnik, A. Bellows, J. Kristensen, J. K. Vedsted, P. Eskildsen, P. Beck-Nielsen, H. Hsu, J. TI Self-management support - a comparison of current practices for diabetes care in the Danish Healthcare System and Kaiser Permanente SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Schiotz, M. L.] Steno Diabet Ctr, Steno Hlth Promot Ctr, DK-2820 Gentofte, Denmark. [Strandberg-Larsen, M.; Krasnik, A.] Inst Publ Hlth, Sect Hlth Serv Res, Copenhagen, Denmark. [Frolich, A.] Bispebjerg Hosp, Copenhagen Hosp Corp, DK-2400 Copenhagen, Denmark. [Bellows, J.] Care Management Inst, Oakland, CA USA. [Kristensen, J. K.; Vedsted, P.] Res Unit Gen Practice, Aarhus, Denmark. [Beck-Nielsen, H.] Odense Univ Hosp, Odense, Denmark. [Hsu, J.] Massachusetts Gen Hosp, Clin Econ & Policy Anal Program, Dept Hlth Care Policy, Boston, MA 02114 USA. RI Vedsted, Peter/C-2583-2008 OI Vedsted, Peter/0000-0003-2113-5599 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 1038 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701479 ER PT J AU Solnica, B Kusnierz-Cabala, B Slowinska-Solnica, K Skupien, J Witek, P Cempa, A Malecki, MT AF Solnica, B. Kusnierz-Cabala, B. Slowinska-Solnica, K. Skupien, J. Witek, P. Cempa, A. Malecki, M. T. TI The effect of haematocrit on the results of measurements using glucose meters based on different techniques SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Solnica, B.; Kusnierz-Cabala, B.; Slowinska-Solnica, K.] Jagiellonian Univ, Coll Med, Dept Diagnost, Krakow, Poland. [Skupien, J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. [Witek, P.; Cempa, A.; Malecki, M. T.] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 1022 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701463 ER PT J AU Van Gaal, LF Garvey, WT Troupin, B Day, WW AF Van Gaal, L. F. Garvey, W. T. Troupin, B. Day, W. W. TI Phentermine/topiramate combination therapy significantly improves glucose impairment in overweight/obese patients SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Van Gaal, L. F.] Univ Antwerp Hosp, Antwerp, Belgium. [Garvey, W. T.] Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA. [Troupin, B.; Day, W. W.] VIVUS Inc, Mountain View, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 773 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701216 ER PT J AU Irahara, N Baba, Y Nosho, K Shima, K Yan, LY Dias-Santagata, D Iafrate, AJ Fuchs, CS Haigis, KM Ogino, S AF Irahara, Natsumi Baba, Yoshifumi Nosho, Katsuhiko Shima, Kaori Yan, Liying Dias-Santagata, Dora Iafrate, Anthony John Fuchs, Charles S. Haigis, Kevin M. Ogino, Shuji TI NRAS Mutations Are Rare in Colorectal Cancer SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE NRAS; colon cancer; clinical outcome; sequencing; signal transduction ID ISLAND METHYLATOR PHENOTYPE; POPULATION-BASED SAMPLE; COLON-CANCER; MICROSATELLITE INSTABILITY; TUMOR PROGRESSION; N-RAS; PIK3CA MUTATION; BRAF MUTATIONS; CYCLIN D1; CIMP-LOW AB Activating mutations in members of the RAS oncogene family (KRAS, HRAS, and NRAS) have been found in a variety of human malignancies, suggesting a dominant role in carcinogenesis. In colon cancers, KRAS mutations are common and clearly contribute to malignant progression. The frequency of NRAS mutations and their relationship with clinical, pathologic, and molecular features remains uncertain. We developed and validated a Pyroseqencing assay to detect NRAS mutations at codons 12, 13, and 61. Using a collection of 225 colorectal cancers from 2 prospective cohort studies, we examined the relationship between NRAS mutations, clinical outcome, and other molecular features, including mutation of KRAS, BRAF, and PIK3CA, microsatellite instability, and the CpG island methylator phenotype. Finally, we examined whether NRAS mutation was associated with patient survival or prognosis. NRAS mutations were detected in 5 (2.2%) of the 225 colorectal cancers and tended to occur in left-sided cancers arising in women, but did not seem to be associated with any of the molecular features that were examined. C1 [Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Irahara, Natsumi; Baba, Yoshifumi; Nosho, Katsuhiko; Shima, Kaori; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dias-Santagata, Dora; Iafrate, Anthony John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Fuchs, Charles S.] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Dept Med,Sch Med, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Yan, Liying] EpigenDx, Worcester, MA USA. RP Haigis, KM (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 149 13th St,6-010, Charlestown, MA 02129 USA. EM khaigis@partners.org FU US National Institute of Health [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826, K01 CA118425]; Bennett Family Fund; Entertainment Industry Foundation National Colorectal Cancer Research Alliance; Japan Society for Promotion of Science FX This work was supported by the US National Institute of Health (P01 CA87969 to S. Hankinson, P01 CA55075 to W. Willett, P50 CA127003 to C. S. F., K07 CA122826 to S.O., K01 CA118425 to K. M. H.); the Bennett Family Fund; the Entertainment Industry Foundation National Colorectal Cancer Research Alliance. Katsuhiko Nosho 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. Funding agencies did not have any role in the design of the study; the collection, analysis, or interpretation of the data; the decision to submit the manuscript for publication; or the writing of the manuscript. NR 52 TC 63 Z9 64 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD SEP PY 2010 VL 19 IS 3 BP 157 EP 163 DI 10.1097/PDM.0b013e3181c93fd1 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 643OY UT WOS:000281308500005 PM 20736745 ER PT J AU Mendez-Navarro, J Chirino, RA Corey, KE Gorospe, EC Zheng, H Moran, S Chung, RT Dehesa-Violante, M AF Mendez-Navarro, Jorge Chirino, Ruby A. Corey, Kathleen E. Gorospe, Emmanuel C. Zheng, Hui Moran, Segundo 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 SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Chronic hepatitis C; Amantadine; Latino; Peginterferon; Sustained virological response ID PLACEBO-CONTROLLED TRIAL; TREATMENT-NAIVE PATIENTS; PEGINTERFERON ALPHA-2A; PLUS RIBAVIRIN; INITIAL TREATMENT; VIRUS-INFECTION; ION-CHANNEL; INTERFERON; HCV; MONOTHERAPY AB With only a third of Latinos achieving sustained virologic response (SVR), there is a need for enhanced HCV treatment. Amantadine has been proposed to improve response rates in addition to standard therapy with peginterferon alpha and ribavirin. Our objective is to evaluate whether triple therapy with amantadine improves SVR rates in this special population. Treatment-na < ve Latino subjects with HCV genotype 1 infection were randomized to receive peginterferon alpha-2a plus weight-based ribavirin for 48 weeks (double therapy) or the same regimen plus amantadine 200 mg daily (triple therapy). The primary endpoint was SVR. Predictors of liver fibrosis using APRI and Forns indices were also evaluated. We enrolled 124 patients with chronic hepatitis C genotype 1. Sixty-three received conventional therapy and 61 patients had triple therapy with amantadine. SVR at week 72 was achieved in 25 patients (39.7%) vs. 26 patients (42.6%) in the double and triple regimen, respectively (p = 0.561). After multivariate analysis, advanced fibrosis, obesity, and low pretreatment ALT levels were associated with non-response in both groups (p = 0.0234, p = 0.0012, p = 0.0249, respectively). APRI values delimited an area under the ROC curve (AUROC) of 0.724 and Forns index with AUROC of 0.733. There was no difference between both indices in predicting significant fibrosis (Knodell index: F3-F4). Our study demonstrates that the addition of amantadine to standard treatment of chronic HCV does not improve SVR rates in Latino patients with genotype 1. Further research to improve response rates in this special population is needed. C1 [Mendez-Navarro, Jorge; Chirino, Ruby A.; Moran, Segundo; Dehesa-Violante, Margarita] Hosp Especialidades Ctr Med La Raza, Dept Gastroenterol, Ctr Med Nacl Siglo 21, IMSS, Mexico City 06725, DF, Mexico. [Mendez-Navarro, Jorge; Corey, Kathleen E.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 02114 USA. RP Mendez-Navarro, J (reprint author), Hosp Especialidades Ctr Med La Raza, Dept Gastroenterol, Ctr Med Nacl Siglo 21, IMSS, Av Cuauhtemoc 330, Mexico City 06725, DF, Mexico. EM jmndoc@yahoo.com; rtchung@partners.org OI Moran, Segundo/0000-0001-6833-2392 FU Roche-Syntex SA. de CV, Mexico FX This study was performed in part with unrestricted support by Roche-Syntex SA. de CV, Mexico. We appreciate the great help of Nurse Leticia Casillas in the patients' management advocacy and her work in the database. We value the full participation of Dr. Jesus A. Juarez in this project. NR 39 TC 6 Z9 6 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 SEP PY 2010 VL 55 IS 9 BP 2629 EP 2635 DI 10.1007/s10620-009-1062-3 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 634PN UT WOS:000280595500028 PM 19960257 ER PT J AU Papachristou, GI Muddana, V Papachristou, DJ Stello, K Whitcomb, DC AF Papachristou, Georgios I. Muddana, Venkata Papachristou, Dionysios J. Stello, Kim Whitcomb, David C. TI Epidermal Growth Factor Serum Levels and the 61 G/A Polymorphism in Patients with Acute Pancreatitis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE EGF; Acute pancreatitis; Polymorphism; Serum; Severity ID CERULEIN-INDUCED PANCREATITIS; EGF GENE; FUNCTIONAL POLYMORPHISM; BINDING; RELEASE; DISEASE; FAMILY; DAMAGE; RATS AB Epidermal growth factor (EGF) binds to pancreatic acinar cells and facilitates recovery from acute pancreatitis (AP). In animal models, EGF protects against pancreatic injury and prevents septic complications. The role of EGF in human AP is unknown. The aim of this study was to assess EGF serum levels in AP patients and whether the EGF +61 G/A single nucleotide polymorphism (SNP) affects susceptibility and/or severity of AP. Hospitalized AP patients were prospectively enrolled. Demographics, clinical features, DNA and early serum samples were collected when available. Patients were classified into mild (79%) and severe AP (21%) based on organ failure for a parts per thousand yen48 h. Early serum samples were quantitatively assayed for EGF levels. The EGF +61 G/A SNP was evaluated by restriction fragment length polymorphism analysis. There were 179 patients ascertained with AP. EGF levels were measured in a subgroup of 60 patients with early serum samples (17 severe) and in serum from 58 healthy controls. Serum EGF levels within 48 h from the onset of pain were significantly lower in AP patients (mean 13.5 pg/ml) compared to controls (25.2 pg/ml; P = 0.015). Furthermore, EGF levels were significantly lower in severe patients when compared to mild (7.8 vs. 14.3 pg/ml; P = 0.026). DNA from all 179 patients and 189 healthy controls was sequenced. The EGF +61 G/A SNP did not affect susceptibility to or severity of AP. EGF serum levels are decreased early in the course of AP and are further suppressed in severe AP. The EGF +61 G/A polymorphism has no effect on AP. C1 [Papachristou, Georgios I.; Muddana, Venkata; Stello, Kim; Whitcomb, David C.] Univ Pittsburgh, Med Ctr, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Papachristou, Georgios I.] Vet Affairs Pittsburgh Hlth Syst, Div Gastroenterol, Pittsburgh, PA USA. [Papachristou, Dionysios J.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. [Whitcomb, David C.] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Whitcomb, David C.] Univ Pittsburgh, Sch Med, Dept Human Genet, Pittsburgh, PA 15213 USA. RP Papachristou, GI (reprint author), Univ Pittsburgh, Med Ctr, Dept Med, Div Gastroenterol Hepatol & Nutr, M2 C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. EM papachri@pitt.edu FU VA Stars; Stripes Healthcare Network 2007 Competitive Pilot Project Fund FX Georgios Papachristou, MD was supported by the VA Stars and Stripes Healthcare Network 2007 Competitive Pilot Project Fund. NR 28 TC 0 Z9 0 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 SEP PY 2010 VL 55 IS 9 BP 2676 EP 2680 DI 10.1007/s10620-010-1129-1 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 634PN UT WOS:000280595500035 PM 20127414 ER PT J AU McMains, VC Myre, M Kreppel, L Kimmel, AR AF McMains, Vanessa C. Myre, Michael Kreppel, Lisa Kimmel, Alan R. TI Dictyostelium possesses highly diverged presenilin/gamma-secretase that regulates growth and cell-fate specification and can accurately process human APP: a system for functional studies of the presenilin/gamma-secretase complex SO DISEASE MODELS & MECHANISMS LA English DT Article ID AMYLOID PRECURSOR PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; C-TERMINAL FRAGMENT; GAMMA-SECRETASE; INTRAMEMBRANE PROTEOLYSIS; BETA-CATENIN; TRANSMEMBRANE ASPARTATES; INTRACELLULAR DOMAIN; LINKED MUTATIONS; DISCOIDEUM AB Presenilin (PS) is the catalytic moiety of the gamma-secretase complex. PS and other gamma-secretase components are well conserved among metazoa, but their presence and function in more-distant species are not resolved. Because inappropriate gamma-secretase processing of amyloid precursor protein (APP) in humans is associated with familial Alzheimer's disease, understanding essential elements within each gamma-secretase component is crucial to functional studies. Diverged proteins have been identified in primitive plants but experiments have failed to demonstrate gamma-secretase activity. We have identified highly diverged orthologs for each gamma-secretase component in the ancient eukaryote Dictyostelium, which lacks equivalents of APP, Notch and other characterized PS/gamma-secretase substrates. We show that wild-type (WT) Dictyostelium is capable of amyloidogenic processing of ectopically expressed human APP to generate amyloid-beta peptides A beta(40) and A beta(42); strains deficient in gamma-secretase cannot produce A beta peptides but accumulate processed intermediates of APP that co-migrate with the C-terminal fragments alpha-and beta-CTF of APP that are found in mammalian cells. We further demonstrate that Dictyostelium requires PS for phagocytosis and cell-fate specification in a cell-autonomous manner, and show that regulation of phagocytosis requires an active gamma-secretase, a pathway suggested, but not proven, to occur in mammalian and Drosophila cells. Our results indicate that PS signaling is an ancient process that arose prior to metazoan radiation, perhaps independently of Notch. Dictyostelium might serve to identify novel PS/gamma-secretase signaling targets and provide a unique system for high-throughput screening of small-molecule libraries to select new therapeutic targets for diseases associated with this pathway. C1 [McMains, Vanessa C.; Kreppel, Lisa; Kimmel, Alan R.] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [McMains, Vanessa C.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Myre, Michael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Richard B Simches Res Ctr, Boston, MA 02114 USA. RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM ark1@helix.nih.gov FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Xiuli Huang, Xin-Hua Liao, Collette Young, Marielle Young, Jonathan Buggey, Joseph Brzostowski and Taruna Khurana for insightful discussions and expert technical advice. We also thank Konstantin Chumakov for guidance on phylogenic analyses, and appreciate the generosity of Wilma Wasco. This research was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. Deposited in PMC for release after 12 months. NR 66 TC 20 Z9 20 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD SEP-OCT PY 2010 VL 3 IS 9-10 BP 581 EP 594 DI 10.1242/dmm.004457 PG 14 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 678FR UT WOS:000284060000014 PM 20699477 ER PT J AU Malandraki, GA Sutton, BP Perlman, AL Karampinos, DC AF Malandraki, Georgia A. Sutton, Bradley P. Perlman, Adrienne L. Karampinos, Dimitrios C. TI Age-Related Differences in Laterality of Cortical Activations in Swallowing SO DYSPHAGIA LA English DT Article DE Neuroimaging; Swallowing; fMRI; Lateralization; Neurophysiology; Aging; Deglutition; Deglutition disorders ID PRIMARY SOMATOSENSORY CORTEX; TONGUE MOVEMENT; FUNCTIONAL MRI; INTERINDIVIDUAL VARIABILITY; HEMISPHERIC ACTIVATION; LESION LOCALIZATION; STROKE PATIENTS; MOTOR FUNCTION; AREAS 3A; FMRI AB The present study examined age differences in neural lateralization patterns during swallowing and three related tasks, using functional magnetic resonance imaging (fMRI). Ten healthy right-handed young adults (mean age = 21.7 years, SD = 2.1 years) and nine healthy elders (mean age = 70.2 years, SD = 3.9 years) were scanned in a 3-T MRI head scanner. Participants were visually cued to "prepare to swallow," "swallow," "tap your tongue," and "clear your throat" in randomized order. Laterality preference for each task was examined within and between groups using region-of-interest (ROI) analyses in seven areas of the left and right primary sensorimotor and premotor cortices. Results of the within-group comparisons verified a more active role of the left premotor cortex in motor-cognitive planning of deglutition in both young and older adults and a more active role of selected areas of the right hemisphere during swallowing in young adults. Greater variability was seen during tongue tapping and throat clearing in both groups. Finally, as people age the cortical hemispheric control of swallowing seems to start becoming more symmetrical/bilateral, which may indicate neural compensatory mechanisms of the aging brain commonly seen for other motor and cognitive functions. C1 [Malandraki, Georgia A.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. [Malandraki, Georgia A.] Univ Wisconsin, Dept Med, Madison, WI USA. [Sutton, Bradley P.] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Perlman, Adrienne L.] Univ Illinois, Dept Speech & Hearing Sci, Champaign, IL 61820 USA. [Karampinos, Dimitrios C.] Univ Illinois, Dept Mech Sci & Engn, Urbana, IL 61801 USA. RP Malandraki, GA (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, 2500 Overlook Terrace,11G, Madison, WI 53705 USA. EM gmaland@medicine.wisc.edu RI Karampinos, Dimitrios/A-5994-2011; Sutton, Bradley/A-4801-2008 OI Karampinos, Dimitrios/0000-0003-4922-3662; Sutton, Bradley/0000-0002-8443-0408 FU College of Applied Health Sciences; Campus Research Board of the University of Illinois at Urbana-Champaign FX This work was performed at the Biomedical Imaging Center of the Beckman Institute at the University of Illinois at Urbana-Champaign. This work was partially supported by the Mary Jane Neer Research Fund Award of the College of Applied Health Sciences and by the Campus Research Board of the University of Illinois at Urbana-Champaign. NR 47 TC 15 Z9 18 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD SEP PY 2010 VL 25 IS 3 BP 238 EP 249 DI 10.1007/s00455-009-9250-z PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA 644RB UT WOS:000281396100010 PM 19760457 ER PT J AU Delinsky, SS St Germain, SA Thomas, JJ Craigen, KE Fagley, WH Weigel, TJ Levendusky, P Becker, AE AF Delinsky, S. S. St Germain, S. A. Thomas, J. J. Craigen, K. Ellison Fagley, W. H. Weigel, T. J. Levendusky, P. Becker, A. E. TI Naturalistic study of course, effectiveness, and predictors of outcome among female adolescents in residential treatment for eating disorders SO EATING AND WEIGHT DISORDERS-STUDIES ON ANOREXIA BULIMIA AND OBESITY LA English DT Article DE Eating disorders; outcome; naturalistic residential treatment; adolescents ID ANOREXIA-NERVOSA; PSYCHIATRIC-INPATIENTS; BULIMIA-NERVOSA; QUESTIONNAIRE; HOSPITALIZATION; READINESS; INTERVIEW AB Few empirical data address naturalistic outcomes of residential eating disorder (ED) treatment. Study aims were to evaluate course, effectiveness, and predictors of outcome in a residential treatment program. We evaluated 80 consecutively admitted female adolescents with the SCID-IV. Primary outcomes were treatment completion, subsequent readmission, clinical global impressions, and changes in body weight. Mean length of stay was 51 days, and 80% of patients were discharged according to treatment plans. Mean expected body weight (EBW) for AN patients increased from 80% to 91%. Patients reported significant improvements in ED symptoms, depression, and quality of life. Low admission %EBW and previous psychiatric hospitalizations were associated with premature termination. Overall, findings support that residential treatment is largely acceptable to patients, and that residential care may provide an opportunity for substantive therapeutic gains. (Eating Weight Disord. 15:e127-e135,2010). (C) 2010, Editrice Kurds C1 [Delinsky, S. S.; St Germain, S. A.; Thomas, J. J.; Craigen, K. Ellison; Fagley, W. H.; Weigel, T. J.; Levendusky, P.] McLean Hosp, Klarman Eating Disorders Ctr, Belmont, MA 02478 USA. [Delinsky, S. S.; Thomas, J. J.; Becker, A. E.] Massachusetts Gen Hosp, Dept Psychiat, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Delinsky, S. S.; Thomas, J. J.; Weigel, T. J.; Levendusky, P.; Becker, A. E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [St Germain, S. A.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Craigen, K. Ellison] Fairleigh Dickinson Univ, Dept Psychol, Teaneck, NJ USA. [Fagley, W. H.] Germaine Lawrence Sch, Arlington, MA USA. [Becker, A. E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. RP Delinsky, SS (reprint author), McLean Hosp, Klarman Eating Disorders Ctr, 115 Mill St, Belmont, MA 02478 USA. EM sdelinsky@gmail.com FU Klarman Family Foundation; Harvard Medical School FX This research was funded by the Klarman Family Foundation, Mr. And Mrs. Samuel Martini, and Harvard Medical School's Livingston Fellowship. We would also like to thank Stephen A. Wonderlich, Ph.D. for his invaluable critical review of a previous version of this manuscript. NR 30 TC 4 Z9 4 U1 1 U2 3 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1124-4909 J9 EAT WEIGHT DISORD-ST JI Eat. Weight Disord.-Stud. Anorex. PD SEP PY 2010 VL 15 IS 3 BP E127 EP E135 PG 9 WC Psychiatry SC Psychiatry GA 704BW UT WOS:000286027100002 PM 21150248 ER PT J AU Randolph, GW Pearce, EN AF Randolph, Gregory W. Pearce, Elizabeth N. TI SURGERY OF WELL-DIFFERENTIATED THYROID CARCINOMA: THE PENDULUM SWINGS BACK IN THE CENTRAL NECK SO ENDOCRINE PRACTICE LA English DT Editorial Material ID LYMPH-NODE DISSECTION; CENTRAL COMPARTMENT; CLINICAL-SIGNIFICANCE; PROGNOSTIC-FACTORS; PAPILLARY; CANCER; METASTASIS; RECURRENCE; MANAGEMENT; SURVIVAL C1 [Randolph, Gregory W.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Div Thyroid & Parathyroid, Boston, MA 02114 USA. [Pearce, Elizabeth N.] Boston Univ, Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. RP Randolph, GW (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Div Thyroid & Parathyroid, 243 Charles St, Boston, MA 02114 USA. EM Gregory_randolph@meei.harvard.edu NR 35 TC 0 Z9 0 U1 1 U2 4 PU AMER ASSOC CLIN ENDOCRINOL PI JACKSONVILLE PA 1000 RIVERSIDE AVE, STE 205, JACKSONVILLE, FL 32204 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD SEP-OCT PY 2010 VL 16 IS 5 BP 913 EP 917 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 672FZ UT WOS:000283569700024 PM 21356639 ER PT J AU Lodish, MB Adams, KT Huynh, TT Prodanov, T Ling, A Chen, C Shusterman, S Jimenez, C Merino, M Hughes, M Cradic, KW Milosevic, D Singh, RJ Stratakis, CA Pacak, K AF Lodish, Maya B. Adams, Karen T. Huynh, Thanh T. Prodanov, Tamara Ling, Alex Chen, Clara Shusterman, Suzanne Jimenez, Camilo Merino, Maria Hughes, Marybeth Cradic, Kendall W. Milosevic, Dragana Singh, Ravinder J. Stratakis, Constantine A. Pacak, Karel TI Succinate dehydrogenase gene mutations are strongly associated with paraganglioma of the organ of Zuckerkandl SO ENDOCRINE-RELATED CANCER LA English DT Article ID MALIGNANT PHEOCHROMOCYTOMAS; FUNCTIONAL PARAGANGLIOMA; FAMILIAL PARAGANGLIOMA; GERMLINE MUTATIONS; SUBUNIT-B; SDHB; SUSCEPTIBILITY; PENETRANCE; NEOPLASIA; DISTINCT AB Organ of Zuckerkandl paragangliomas (PGLs) are rare neuroendocrine tumors that are derived from chromaffin cells located around the origin of the inferior mesenteric artery extending to the level of the aortic bifurcation. Mutations in the genes encoding succinate dehydrogenase subunits (SDH) B, C, and D (SDHx) have been associated with PGLs, but their contribution to PGLs of the organ of Zuckerkandl PGLs is not known. We aimed to describe the clinical presentation of patients with PGLs of the organ of Zuckerkandl and investigate the prevalence of SDHx mutations and other genetic defects among them. The clinical characteristics of 14 patients with PGL of the organ of Zuckerkandl were analyzed retrospectively; their DNA was tested for SDHx mutations and deletions. Eleven out of 14 (79%) patients with PGLs of the organ of Zuckerkandl were found to have mutations in the SDHB (9) or SDHD (2) genes; one patient was found to have the Carney-Stratakis syndrome (CSS), and his PGL was discovered during surgery for gastrointestinal stromal tumor. Our results show that SDHx mutations are prevalent in pediatric and adult PGLs of the organ of Zuckerkandl. Patients with PGLs of the organ of Zuckerkandl should be screened for SDHx mutations and the CSS; in addition, asymptomatic carriers of an SDHx mutation among the relatives of affected patients may benefit from tumor screening for early PGL detection. Endocrine-Related Cancer (2010) 17 581-588 C1 [Lodish, Maya B.; Stratakis, Constantine A.] Natl Inst Child Hlth & Human Dev NICHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH,CRC, Bethesda, MD 20892 USA. [Pacak, Karel] NICHD, Sect Med Neuroendocrinol, Reprod Biol & Adult Endocrinol Program, NIH,CRC, Bethesda, MD 20892 USA. [Ling, Alex; Chen, Clara] NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Shusterman, Suzanne] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Jimenez, Camilo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Merino, Maria] NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. [Hughes, Marybeth] NCI, Dept Surg, NIH, Bethesda, MD 20892 USA. [Cradic, Kendall W.; Milosevic, Dragana; Singh, Ravinder J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, Reprod Biol & Adult Endocrinol Program, NIH,CRC, Bldg 10,Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health FX This work was supported by the Intramural Research funding of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. NR 37 TC 14 Z9 15 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD SEP PY 2010 VL 17 IS 3 BP 581 EP 588 DI 10.1677/ERC-10-0004 PG 8 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 657VE UT WOS:000282445100009 PM 20418362 ER PT J AU Leung, YK Lam, HM Wu, SL Song, D Levin, L Cheng, LA Wu, CL Ho, SM AF Leung, Yuet-Kin Lam, Hung-Ming Wu, Shulin Song, Dan Levin, Linda Cheng, Liang Wu, Chin-Lee Ho, Shuk-Mei TI Estrogen receptor beta 2 and beta 5 are associated with poor prognosis in prostate cancer, and promote cancer cell migration and invasion SO ENDOCRINE-RELATED CANCER LA English DT Article ID ER-BETA; ANDROGEN-RECEPTOR; DIFFERENTIAL EXPRESSION; BREAST-CANCER; REPRODUCTIVE PHENOTYPES; METASTATIC CARCINOMA; SPLICE VARIANT; ALPHA; LOCALIZATION; ISOFORMS AB Estrogens play a pivotal role in the development and progression of prostate cancer (PCa). Their actions are mediated by estrogen receptors (ERs), particularly ER beta in the prostate epithelium. With the discovery of ER beta isoforms, data from previous studies that focused principally on the wild-type ER beta (ER beta 1) may not be adequate in explaining the still controversial role of ER beta(s) in prostate carcinogenesis. In this study, using newly generated isoform-specific antibodies, immunohistochemistry (IHC) was performed on a tumor microarray comprised of 144 specimens. IHC results were correlated with pathological and clinical follow-up data to delineate the distinct roles of ER beta 1, ER beta 2, and ER beta 5 in PCa. ER beta 2 was commonly found in the cytoplasm and was the most abundant isoform followed by ER beta 1 localized predominantly in the nucleus, and ER beta 5 was primarily located in the cytoplasm. Logistic regression analyses demonstrated that nuclear ER beta 2 (nER beta 2) is an independent prognostic marker for prostate specific antigen (PSA) failure and post operative metastasis (POM). In a Kaplan-Meier analysis, the combined expression of both nER beta 2 and cytoplasmic ER beta 5 identified a group of patients with the shortest POM-free survival. Cox proportional hazard models revealed that nER beta 2 predicted shorter time to POM. In concordance with IHC data, stable, ectopic expression of ER beta 2 or ER beta 5 enhanced PCa cell invasiveness but only PCa cells expressing ER beta 5 exhibited augmented cell migration. This is the first study to uncover a metastasis-promoting role of ER beta 2 and ER beta 5 in PCa, and show that the two isoforms, singularly and conjointly, have prognostic values for PCa progression. These findings may aid future clinical management of PCa. Endocrine-Related Cancer (2010) 17 675-689 C1 [Leung, Yuet-Kin; Lam, Hung-Ming; Song, Dan; Ho, Shuk-Mei] Univ Cincinnati, Med Ctr, Div Environm Genet & Mol Toxicol, Dept Environm Hlth,Coll Med, Cincinnati, OH 45267 USA. [Levin, Linda] Univ Cincinnati, Med Ctr, Div Epidemiol & Biostat, Dept Environm Hlth,Coll Med, Cincinnati, OH 45267 USA. [Leung, Yuet-Kin; Ho, Shuk-Mei] Univ Cincinnati, Med Ctr, Ctr Canc, Coll Med, Cincinnati, OH 45267 USA. [Wu, Shulin; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wu, Shulin; Wu, Chin-Lee] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Levin, Linda] Indiana Univ, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. RP Ho, SM (reprint author), Univ Cincinnati, Med Ctr, Div Environm Genet & Mol Toxicol, Dept Environm Hlth,Coll Med, Cincinnati, OH 45267 USA. EM shuk-mei.ho@uc.edu FU NIH [ES006096, CA15776, CA112532]; Bertucci Foundation of Prostate Cancer Research; US Army Prostate Cancer Program [81XWH-04-1-0165]; University of Cincinnati Medical Center FX This work was supported by grants from NIH (ES006096, CA15776, and CA112532 to S-M Ho), the Bertucci Foundation of Prostate Cancer Research (to C-L Wu), and the US Army Prostate Cancer Program (81XWH-04-1-0165 to S-M Ho), and an internal funding source from the University of Cincinnati Medical Center. NR 62 TC 66 Z9 69 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD SEP PY 2010 VL 17 IS 3 BP 675 EP 689 DI 10.1677/ERC-09-0294 PG 15 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 657VE UT WOS:000282445100017 PM 20501637 ER PT J AU Baskin, DG Kim, F Gelling, RW Russell, BJ Schwartz, MW Morton, GJ Simhan, HN Moralejo, DH Blevins, JE AF Baskin, Denis G. Kim, Francis Gelling, Richard W. Russell, Brian J. Schwartz, Michael W. Morton, Gregory J. Simhan, Hyagriv N. Moralejo, Daniel H. Blevins, James E. TI A New Oxytocin-Saporin Cytotoxin for Lesioning Oxytocin-Receptive Neurons in the Rat Hindbrain SO ENDOCRINOLOGY LA English DT Article ID BRAIN-STEM NUCLEI; FOOD-INTAKE; CHOLECYSTOKININ; INHIBITION; EXPRESSION; LEPTIN AB Evidence suggests that release of oxytocin in the nucleus tractus solitarius (NTS) of the hindbrain from descending projections that originate in the paraventricular nucleus can inhibit food intake by amplifying the satiety response to cholecystokinin (CCK). To further evaluate this mechanism in rats, we used a novel cytotoxin, saporin conjugated to oxytocin (OXY-SAP), a compound designed to destroy cells that express oxytocin receptors (OXYr). OXY-SAP was injected directly into the NTS to lesion neurons that express OXYr and that are implicated in potentiating CCK's satiety effects. The control consisted of injection of saporin conjugated to a nonsense peptide. We found that OXY-SAP was cytotoxic to human uterine smooth muscle cells in vitro, demonstrating that OXY-SAP can lesion cells that express OXYr. Using laser capture microdissection and real-time quantitative PCR, we demonstrated that OXYr mRNA levels were reduced in the NTS after OXY-SAP administration. Moreover, we found that OXY-SAP attenuated the efficacy of CCK-8 to reduce food intake and blocked the actions of an OXYr antagonist to stimulate food intake. The findings suggest that OXY-SAP is an effective neurotoxin for in vivo elimination of cells that express OXYr and is potentially useful for studies to analyze central nervous system mechanisms that involve the action of oxytocin on food intake and other physiological processes. (Endocrinology 151: 4207-4213, 2010) C1 [Baskin, Denis G.; Blevins, James E.] Dept Vet Affairs Med Ctr, Vet Affairs Puget Sound Hlth Care Syst, Off Res & Dev, Med Res Serv, Seattle, WA 98108 USA. [Baskin, Denis G.; Schwartz, Michael W.; Morton, Gregory J.; Blevins, James E.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Kim, Francis] Univ Washington, Sch Med, Div Cardiol, Dept Med, Seattle, WA 98195 USA. [Baskin, Denis G.] Univ Washington, Sch Med, Dept Biol Struct, Seattle, WA 98195 USA. [Moralejo, Daniel H.] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA. [Russell, Brian J.] Adv Targeting Syst, San Diego, CA 92121 USA. [Gelling, Richard W.] Lilly Singapore Ctr Drug Discovery, Singapore 138648, Singapore. [Simhan, Hyagriv N.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. RP Blevins, JE (reprint author), Vet Adm Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jeblevin@u.washington.edu RI Schwartz, Michael/H-9950-2012 FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs; Department of Veterans Affairs; National Institutes of Health (NIH) Diabetes Endocrinology Research Center; NIH Clinical Nutrition Research Unit at the University of Washington; University of Washington NIH Clinical Nutrition Research Unit; NIH [DK17047, P30 DK035816, P30 DK017047, PO1 DK068384] FX This work was supported by resources from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, including the Department of Veterans Affairs Career Development Program, Merit Review Research Program, and the Career Scientist Program. D. G. B. is the recipient of a Department of Veterans Affairs Senior Research Career Scientist Award at the Veterans Affairs Puget Sound Health Care System. The research was also supported by the biomedical research core programs, particularly the Cellular and Molecular Imagine Core of the National Institutes of Health (NIH) Diabetes Endocrinology Research Center and the NIH Clinical Nutrition Research Unit at the University of Washington. The research in our laboratory has been supported by a Pilot and Feasibility grant from the University of Washington NIH Clinical Nutrition Research Unit, NIH Grants DK17047, P30 DK035816, P30 DK017047, and PO1 DK068384. NR 22 TC 35 Z9 36 U1 0 U2 4 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 SEP PY 2010 VL 151 IS 9 BP 4207 EP 4213 DI 10.1210/en.2010-0295 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 642WP UT WOS:000281252000017 PM 20610562 ER PT J AU Stengel, A Coskun, T Goebel, M Wang, LX Craft, L Alsina-Fernandez, J Rivier, J Tache, Y AF Stengel, Andreas Coskun, Tamer Goebel, Miriam Wang, Lixin Craft, Libbey Alsina-Fernandez, Jorge Rivier, Jean Tache, Yvette TI Central Injection of the Stable Somatostatin Analog ODT8-SST Induces a Somatostatin(2) Receptor-Mediated Orexigenic Effect: Role of Neuropeptide Y and Opioid Signaling Pathways in Rats SO ENDOCRINOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MELANIN-CONCENTRATING HORMONE; FOOD-INTAKE; ENERGY-EXPENDITURE; GROWTH-HORMONE; DIURNAL-VARIATIONS; FEEDING-BEHAVIOR; BARREL ROTATION; ARCUATE NUCLEUS; MEAL PATTERNS AB Somatostatin and octreotide injected into the brain have been reported to modulate food intake. However, little is known regarding the underlying mechanisms. The stable oligosomatostatin analog, des-AA(1,2,4,5,12,13)-[DTrp(8)]-somatostatin (ODT8-SST), like somatostatin, binds to all five somatostatin receptors (sst(1-5)). We characterized the effects of ODT8-SST injected intracerebroventricularly (icv) on food consumption and related mechanisms of action in freely fed rats. ODT8-SST (0.3 and 1 mu g per rat, icv) injected during the light or dark phase induced an early onset (within 1 h) and long-lasting (4 h) increase in food intake in nonfasted rats. By contrast, ip injection (0.3-3 mg/kg) or icv injection of selective sst(1) or sst(4) agonists (1 mu g per rat) had no effect. The 2 h food intake response during the light phase was blocked by icv injection of a sst(2) antagonist, the neuropeptide Y (NPY)Y-1 receptor antagonist, BIBP-3226, and ip injection of the mu-opioid receptor antagonist, naloxone, and not associated with changes in plasma ghrelin levels. ODT8-SST (1 mu g per rat, icv) stimulated gastric emptying of a solid meal which was also blocked by naloxone. The increased food intake was accompanied by a sustained increase in respiratory quotient, energy expenditure, and drinking as well as mu-opioid receptor-independent grooming behavior and hyperthermia, while ambulatory movements were not altered after ODT8-SST (1 mu g per rat, icv). These data show that ODT8-SST acts primarily through brain sst(2) receptors to induce a long-lasting orexigenic effect that involves the activation of Y-1 and opiate-receptors, accompanied by enhanced gastric transit and energy expenditure suggesting a modulation of NPYergic and opioidergic orexigenic systems by brain sst(2) receptors. (Endocrinology 151: 4224-4235, 2010) C1 [Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, Ctr Neurobiol Stress, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Ulcer Res & Educ, Ctr Neurobiol Stress, Dept Med,Digest Dis Res Ctr,Digest Dis Div, Los Angeles, CA 90073 USA. [Coskun, Tamer; Craft, Libbey; Alsina-Fernandez, Jorge] Eli Lilly & Co, Biotechnol Discovery Res, Indianapolis, IN 46285 USA. [Rivier, Jean] Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA 92037 USA. RP Tache, Y (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, Ctr Neurobiol Stress, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU German Research Foundation [STE 1765/1-1, GO 1718/1-1]; National Institutes of Health (NIH) [R01 DK-33061]; NIH Center [DK-41301]; Veterans Affairs Research Career Scientist award FX This work was supported by German Research Foundation Grants STE 1765/1-1 (to A. S.) and GO 1718/1-1 (to M.G.), National Institutes of Health (NIH) Grant R01 DK-33061, NIH Center Grant DK-41301 (Animal Core), and Veterans Affairs Research Career Scientist award (to Y.T.). J.R. is the Dr. Frederik Paulsen Chair in Neurosciences Professor. NR 81 TC 18 Z9 18 U1 0 U2 0 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 SEP PY 2010 VL 151 IS 9 BP 4224 EP 4235 DI 10.1210/en.2010-0195 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 642WP UT WOS:000281252000019 PM 20610566 ER PT J AU Ramaswamy, S Seminara, SB Ali, B Ciofi, P Amin, NA Plant, TM AF Ramaswamy, Suresh Seminara, Stephanie B. Ali, Barkat Ciofi, Philippe Amin, Nisar A. Plant, Tony M. TI Neurokinin B Stimulates GnRH Release in the Male Monkey (Macaca mulatta) and Is Colocalized with Kisspeptin in the Arcuate Nucleus SO ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE SECRETION; HYPOGONADOTROPIC HYPOGONADISM; NEUROPEPTIDE-Y; DYNORPHIN-A; GONADOTROPIN; NEURONS; RECEPTORS; HYPOTHALAMUS; GPR54; GENE AB Humangenetics indicate that kisspeptin and neurokinin B (NKB) signaling are necessary for generating pulsatile LH release and therefore for initiation of puberty and maintaining gonadal function. In the present study, male monkeys were employed to examine 1) whether activation of the NKB receptor (NK3R) is associated with GnRH release, and 2) hypothalamic localization of these peptides using immunofluorescence histochemistry. Agonadal juveniles, in which pituitary responsiveness to GnRH was heightened by GnRH priming, were employed to indirectly examine GnRH-releasing actions of NK3R and kisspeptin receptor agonists by tracking LH after their iv injection. Castrated adults were used for immunohistochemistry. Single iv injections of NKB or senktide (an NK3R agonist) elicited robust LH discharges that were abolished by GnRH receptor antagonism (acyline) confirming the ligands' hypothalamic action. Intermittent infusion of senktide (1-min pulse every hour for 4 h), in contrast to that of kisspeptin, failed to sustain pulsatile GnRH release. Repetitive senktide injections did not compromise the GnRH-releasing action of kisspeptin. NKB and kisspeptin were colocalized in perikarya of the arcuate nucleus and in axonal projections to the median eminence, confirming earlier findings in sheep. These results are consistent with the human genetics, and indicate that although brief activation of NK3R stimulates GnRH release, repetitive stimulation of this pathway, in contrast to that of kisspeptin receptor, fails to sustain pulsatile GnRH release. In addition, the data provide a platform for future elucidation of the interactions between NKB and kisspeptin that are required for generating pulsatile GnRH release in primates. (Endocrinology 151: 4494-4503, 2010) C1 [Ramaswamy, Suresh; Ali, Barkat; Amin, Nisar A.; Plant, Tony M.] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Seminara, Stephanie B.] Massachusetts Gen Hosp, Reprod Endocrinol Unit, Boston, MA 02114 USA. [Ciofi, Philippe] Inst Francois Magendie, INSERM, U862, Neuroctr, F-33077 Bordeaux, France. [Ciofi, Philippe] Univ Bordeaux, F-33077 Bordeaux, France. RP Plant, TM (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Magee Womens Res Inst B331, Pittsburgh, PA 15213 USA. EM plant1@pitt.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U54 HD08610, U54 HD028138]; National Institutes of Health [R01 HD13254]; Institut National de la Sante et de la Recherche Medicale; University of Bordeaux FX The work in Pittsburgh and at Massachusetts General Hospital was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through cooperative agreement U54 HD08610 and U54 HD028138 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research and National Institutes of Health Grant R01 HD13254 ( to T. M. P.). P. C. was supported by Institut National de la Sante et de la Recherche Medicale and the University of Bordeaux. NR 31 TC 118 Z9 122 U1 4 U2 11 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 SEP PY 2010 VL 151 IS 9 BP 4494 EP 4503 DI 10.1210/en.2010-0223 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 642WP UT WOS:000281252000045 PM 20573725 ER PT J AU Hall, JA Ribich, S Christoffolete, MA Simovic, G Correa-Medina, M Patti, ME Bianco, AC AF Hall, Jessica A. Ribich, Scott Christoffolete, Marcelo A. Simovic, Gordana Correa-Medina, Mayrin Patti, Mary Elizabeth Bianco, Antonio C. TI Absence of Thyroid Hormone Activation during Development Underlies a Permanent Defect in Adaptive Thermogenesis SO ENDOCRINOLOGY LA English DT Article ID BROWN ADIPOSE-TISSUE; TYPE-2 IODOTHYRONINE DEIODINASE; OXIDATIVE STRESS; GENE-EXPRESSION; ADIPOCYTE DIFFERENTIATION; MITOCHONDRIAL BIOGENESIS; TRANSCRIPTIONAL CONTROL; TARGETED DISRUPTION; INSULIN-RESISTANCE; NUCLEAR RECEPTORS AB Type 2 deiodinase (D2), which is highly expressed in brown adipose tissue (BAT), is an enzyme that amplifies thyroid hormone signaling in individual cells. Mice with inactivation of the D2 pathway (D2KO) exhibit dramatically impaired thermogenesis in BAT, leading to hypothermia during cold exposure and a greater susceptibility to diet-induced obesity. This was interpreted as a result of defective acute activation of BAT D2. Here we report that the adult D2KO BAT has a permanent thermogenic defect that stems from impaired embryonic BAT development. D2KO embryos have normal serum T3 but due to lack of D2-generated T3 in BAT, this tissue exhibits decreased expression of genes defining BAT identity [i.e. UCP1, PGC-1 alpha and Dio2 (nonfunctional)], which results in impaired differentiation and oxidative capacity. Coinciding with a reduction of these T3-responsive genes, there is oxidative stress that in a cell model of brown adipogenesis can be linked to decreased insulin signaling and decreased adipogenesis. This discovery highlights the importance of deiodinase-controlled thyroid hormone signaling in BAT development, where it has important metabolic repercussions for energy homeostasis in adulthood. (Endocrinology 151: 4573-4582, 2010) C1 [Simovic, Gordana; Correa-Medina, Mayrin; Bianco, Antonio C.] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA. [Hall, Jessica A.; Bianco, Antonio C.] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA 02115 USA. [Ribich, Scott; Christoffolete, Marcelo A.] Harvard Univ, Sch Med, Div Endocrinol Diabet & Hypertens, Brigham & Womens Hosp, Boston, MA 02115 USA. [Patti, Mary Elizabeth] Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Bianco, AC (reprint author), Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, 1400 NW 10th St,Dominion Towers Suite 816, Miami, FL 33136 USA. EM abianco@deiodinase.org RI Bianco, Antonio/A-4965-2008 OI Bianco, Antonio/0000-0001-7737-6813 FU National Institutes of Health [DK65055]; Dana-Farber Microarray Core Facility FX This work was supported in part by National Institutes of Health Grant DK65055 and by Dana-Farber Microarray Core Facility. NR 38 TC 46 Z9 48 U1 0 U2 3 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 SEP PY 2010 VL 151 IS 9 BP 4573 EP 4582 DI 10.1210/en.2010-0511 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 642WP UT WOS:000281252000053 PM 20660060 ER PT J AU Mehta, SN Wolfsdorf, JI AF Mehta, Sanjeev N. Wolfsdorf, Joseph I. TI Contemporary Management of Patients with Type 1 Diabetes SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article DE Diabetes; Management; Intensive therapy; Outcomes ID SUBCUTANEOUS INSULIN INFUSION; MEDICAL NUTRITION THERAPY; MULTIPLE DAILY INJECTIONS; BLOOD-GLUCOSE CONTROL; HVIDORE STUDY-GROUP; GLYCEMIC CONTROL; PUMP THERAPY; SEVERE HYPOGLYCEMIA; INTENSIVE THERAPY; COMPLICATIONS TRIAL AB The current standard of care for patients with type 1 diabetes (T1D) employs a system of intensive diabetes management aimed at near-normal glycemia, which reduces the risk of micro- and macrovascular complications. Optimal management is an ongoing process based on a patient-centered collaboration with a primary care clinician and a multidisciplinary diabetes team that provides diabetes management, including education and psychosocial support. Intensive diabetes therapy attempts to mimic physiologic insulin replacement. Over the past 15 years, there has been widespread use of multiple-dose insulin regimens using a variety of insulin analogs, administered either by injection or insulin pump therapy, together with medical nutrition therapy, frequent self-monitoring of blood glucose and, more recently, continuous logo glucose monitoring. It is now possible to achieve previously unattainable levels of glycemic control with less risk of severe hypoglycemia, and yet only a minority of patients achieves target hemoglobin A1c values. This review discusses contemporary management of T1D with a focus on health outcomes. C1 [Wolfsdorf, Joseph I.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Mehta, Sanjeev N.; Wolfsdorf, Joseph I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mehta, Sanjeev N.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Mehta, Sanjeev N.] Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. RP Wolfsdorf, JI (reprint author), Childrens Hosp, Div Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA. EM Joseph.Wolfsdorf@childrens.harvard.edu FU National Institutes of Health Training Grant in Pediatric Endocrinology [K12 DK639605] FX This work was supported by a National Institutes of Health Training Grant in Pediatric Endocrinology (K12 DK639605). NR 114 TC 12 Z9 13 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 2010 VL 39 IS 3 BP 573 EP + DI 10.1016/j.ecl.2010.05.002 PG 23 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 654CM UT WOS:000282146100009 PM 20723821 ER PT J AU Kar, S Krishnaswamy, A Shishehbor, MH Cam, A Tuzcu, EM Bhatt, DL Bajzer, C Kapadia, SR AF Kar, Subrata Krishnaswamy, Amar Shishehbor, Mehdi H. Cam, Akin Tuzcu, E. Murat Bhatt, Deepak L. Bajzer, Christopher Kapadia, Samir R. TI Safety and efficacy of carotid stenting in individuals with concomitant severe carotid and aortic stenosis SO EUROINTERVENTION LA English DT Article DE Aortic stenosis; carotid stenosis; carotid artery stenting; high risk carotid endarterectomy ID CORONARY-ARTERY-BYPASS; HIGH-RISK PATIENTS; CARDIAC-SURGERY; ENDARTERECTOMY; DISEASE; REVASCULARIZATION; ANGIOPLASTY; ASSOCIATION; PROGRESSION; STROKE AB Aims: Carotid artery stenting (CAS) prior to open-heart surgery may be a useful approach to minimise the risk of neurologic events in patients undergoing aortic valve replacement (AVR). Methods and results: All patients referred for carotid intervention at our institution between 1998 and 2005 with concomitant severe aortic stenosis (AS) (aortic valve area < 1.0 cm(2)) were included. Data were obtained prospectively and confirmed by chart review. The primary endpoint was all-cause mortality at 30-days after CAS or AVR. Secondary endpoints included incidence of stroke, transient ischaemic attack (TIA), and myocardial infarction (MI) at 30-days after CAS or AVR. Patients were followed-up at 30-days, six months, and annually thereafter. Of the 829 patients who underwent CAS, 52 had severe AS. Carotid stenting in 28 (54%) of the patients was attempted using embolic protection devices. Three patients (6%) died < 30 days after carotid stenting, and two (4%) died > 30 days after carotid stenting but prior to aortic valve replacement. At one year after CAS, a total of nine patients had died. There were a total of 19 deaths (37%) over a median follow-up of 3.8 years. One patient (2%) suffered a TIA during carotid stenting; at 30-days and 1-year there were no strokes in the CAS group. There were no MI's. AVR was performed in 29 patients (56%), and at 30-days and 1-year there were no strokes or deaths noted in those patients. Conclusions: In patients with severe AS, CAS can be accomplished effectively and with a low rate of stroke, MI, and death. C1 [Kar, Subrata; Kapadia, Samir R.] Cleveland Clin, Dept Internal Med, Cleveland, OH 44195 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Dept Cardiol, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kapadia, SR (reprint author), Cleveland Clin, Dept Internal Med, 9500 Euclid Ave,Desk J2-3, Cleveland, OH 44195 USA. EM kapadis@ccf.org FU AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Heartscape; Sanofi-Aventis; Medicines Company FX Dr Bhatt has received research grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi-Aventis, and The Medicines Company. The other authors have no conflicts of interest to declare. NR 32 TC 4 Z9 4 U1 0 U2 0 PU EUROPA EDITION PI TOULOUSE CEDEX 6 PA 5, RUE SAINT-PANTALEON, BP 61508, TOULOUSE CEDEX 6, 31015, FRANCE SN 1774-024X J9 EUROINTERVENTION JI EuroIntervention PD SEP PY 2010 VL 6 IS 4 BP 492 EP 497 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 810OO UT WOS:000294134900011 PM 20884437 ER PT J AU Ehrlich, S Franke, L Scherag, S Burghardt, R Schott, R Schneider, N Brockhaus, S Hein, J Uebelhack, R Lehmkuhl, U AF Ehrlich, Stefan Franke, Leonora Scherag, Susann Burghardt, Roland Schott, Regina Schneider, Nora Brockhaus, Simone Hein, Jakob Uebelhack, Ralf Lehmkuhl, Ulrike TI The 5-HTTLPR polymorphism, platelet serotonin transporter activity and platelet serotonin content in underweight and weight-recovered females with anorexia nervosa SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE Anorexia nervosa; Serotonin transporter; Platelet; 5-HTTLPR deletion/insertion polymorphism; Leptin ID EATING-DISORDERS; MAJOR DEPRESSION; RECEPTOR-BINDING; HEALTHY-SUBJECTS; UPTAKE SITE; IMIPRAMINE BINDING; GENE POLYMORPHISMS; PLASMA TRYPTOPHAN; FOOD RESTRICTION; BULIMIA-NERVOSA AB Serotonin (5-HT) pathways play an important role in the pathophysiology of anorexia nervosa (AN). In this study, we investigated functional characteristics of the platelet 5-HT transporter and platelet 5-HT content in AN patients at various stages of their illness in comparison to healthy control woman (HCW) controlling for the 5-HTTLPR deletion/insertion polymorphism and other confounding variables. Fasting blood samples of 58 acutely underweight AN patients (acAN, BMI = 15.2 +/- A 1.4), 26 AN patients of the initial acAN sample after short-term/partial weight restoration (BMI = 17.3 +/- A 0.9), 36 weight-recovered AN patients (recAN, BMI = 20.7 +/- A 2.2) and 58 HCW (BMI = 21.6 +/- A 2.0) were assessed for kinetic characteristics of platelet 5-HT uptake (V (max), K (m)) and platelet 5-HT content. Plasma leptin served as an indicator of malnutrition. Mean V (max) and K (m) values were significantly higher in recAN subjects in comparison to HCW (2.05 +/- A 0.62 vs. 1.66 +/- A 0.40 nmol 5-HT/10(9) platelets min and 432 +/- A 215 vs. 315 +/- A 136 nmol, respectively) but there were no differences in platelet 5-HT content (464.8 +/- A 210.6 vs. 472.0 +/- A 162.2 ng 5-HT/10(9) platelets). 5-HT parameters in acAN patients and HCW were similar. 5-HTTLPR variants were not related to 5-HT platelet variables. In the longitudinal part of the study we found significantly increased 5-HT content but unchanged 5-HT uptake in AN patients after short-term/partial weight restoration. Our results highlight the importance of malnutrition for the interpretation of abnormalities in neurotransmitter systems in AN. Changes in platelet 5-HT transporter activity were related to the stage of the illness but not to 5-HTTLPR genotype. Increased V (max) and K (m) in recovered AN patients might mirror adaptive modulations of the 5-HT system. C1 [Ehrlich, Stefan] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Sch Med,Dept Psychiat, Charlestown, MA 02129 USA. [Ehrlich, Stefan; Burghardt, Roland; Schott, Regina; Schneider, Nora; Brockhaus, Simone; Lehmkuhl, Ulrike] Charite, Dept Child & Adolescent Psychiat, CVK, D-13353 Berlin, Germany. [Ehrlich, Stefan; Franke, Leonora; Hein, Jakob; Uebelhack, Ralf] Charite, Dept Psychiat & Psychotherapy, CCM, D-13353 Berlin, Germany. [Scherag, Susann] Univ Duisburg Essen, Dept Child & Adolescent Psychiat, Essen, Germany. RP Ehrlich, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Sch Med,Dept Psychiat, CNY Bldg 120,Suite 100, Charlestown, MA 02129 USA. EM stefan@nmr.mgh.harvard.edu OI Ehrlich, Stefan/0000-0003-2132-4445 FU Charite Research Fund; German Research Fund (DFG) FX The authors would like to thank I. Kamenzky for excellent technical assistance, D. Weiss, M. D. for help with the biochemical assessments and J.V. Merle as well as A. Oskamp for help with the patient recruitment. Funding for this study was provided by the Charite Research Fund and the German Research Fund (DFG, personal grant to SE). NR 58 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0940-1334 EI 1433-8491 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD SEP PY 2010 VL 260 IS 6 BP 483 EP 490 DI 10.1007/s00406-009-0092-3 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 651SI UT WOS:000281947000006 PM 19957188 ER PT J AU Kwon, DS Kaufmann, DE AF Kwon, Douglas S. Kaufmann, Daniel E. TI Protective and detrimental roles of IL-10 in HIV pathogenesis SO EUROPEAN CYTOKINE NETWORK LA English DT Article DE interleukin-10 (IL-10); antigen-presenting cell; CD4 T cell; CD8 T cell; regulatory T cell; HIV; T cell exhaustion; immune activation ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; CHRONIC VIRAL-INFECTION; CHRONIC HEPATITIS-C; INTERLEUKIN-10 PROMOTER POLYMORPHISM; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; CYTOKINE EXPRESSION; IMMUNE FUNCTION; HUMAN MONOCYTES AB Successful pathogen clearance depends on a finely orchestrated equilibrium between inflammatory immune responses and immunoregulatory mechanisms that limit collateral tissue damage. The cytokine interleukin 10 (IL-10) has been shown to play a critical role in this balance in numerous infectious diseases. Studies in animal models have revealed that IL-10 gene-knockout or signaling blockade can enhance resistance to pathogens, and substantially facilitate viral clearance. These same interventions in other infections however, result in more severe disease due to the inability of the immune system to adequately contain the pathogen load, and to control immune-mediate damage. This IL-10-regulated balance is also apparent in human infectious diseases. This review summarizes evidence that IL-10 impacts many aspects of HIV pathogenesis, including the regulation of HIV-specific CD4 and CD8 T cell functions, as well as modulation of HIV-replication in PBMC subsets. Genetic polymorphisms in the IL-10 gene promoter that lead to decreased IL-10 expression have been associated with more rapid disease progression in late stages of HIV infection, suggesting that the anti-inflammatory effects of IL-10 may be protective in the setting of chronic immune activation. We conclude with a discussion of important questions remaining, and the potential for therapeutic intervention based on manipulation of the IL-10 pathway. C1 [Kwon, Douglas S.; Kaufmann, Daniel E.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Kwon, Douglas S.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Kwon, Douglas S.; Kaufmann, Daniel E.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Kaufmann, DE (reprint author), Massachusetts Gen Hosp E, Ragon Inst MGH MIT & Harvard, Room 5239,149 13th St, Charlestown, MA 02129 USA. EM dkaufmann@partners.org NR 69 TC 14 Z9 15 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 2010 VL 21 IS 3 BP 208 EP 214 DI 10.1684/ecn.2010.0201 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 651XX UT WOS:000281962000009 PM 20732847 ER PT J AU Morrow, DA Antman, EM Fox, KAA White, HD Giugliano, R Murphy, SA McCabe, CH Braunwald, E AF Morrow, David A. Antman, Elliott M. Fox, Keith A. A. White, Harvey D. Giugliano, Robert Murphy, Sabina A. McCabe, Carolyn H. Braunwald, Eugene CA ExTRACT-TIMI 25 Investigators TI One-year outcomes after a strategy using enoxaparin vs. unfractionated heparin in patients undergoing fibrinolysis for ST-segment elevation myocardial infarction: 1-year results of the ExTRACT-TIMI 25 Trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Enoxaparin; Heparin; Anti-thrombin; Myocardial infarction; Fibrinolysis ID ACUTE CORONARY SYNDROMES; RANDOMIZED CONTROLLED-TRIAL; MOLECULAR-WEIGHT HEPARIN; ANTITHROMBIN THERAPY; THROMBOLYSIS; ASPIRIN; MORTALITY; REPERFUSION; COMBINATION; SAFETY AB To determine the impact of a strategy using enoxaparin for up to 8 days compared with unfractionated heparin (UFH) for 48 h as an adjunct to fibrinolysis for ST-segment elevation myocardial infarction (STEMI) on 1-year clinical outcomes. Follow-up at 1 year (n = 20 275) was conducted by telephone in the ExTRACT-TIMI 25 trial to ascertain the endpoints of death, MI, and disabling stroke. The primary endpoint of death or non-fatal MI occurred in 1614 (15.8%) and 1732 (17.0%) of patients allocated to enoxaparin and UFH, respectively [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.86-0.98, P = 0.01]. The enoxaparin strategy significantly reduced non-fatal MI at 1 year (5.7 vs. 6.8%, HR 0.82, 95% CI 0.73-0.92, P < 0.001). The risks of death (10.5 vs. 10.6%, HR 0.98, 95% CI 0.91-1.07) and disabling stroke (1.1 vs. 1.2%, HR 0.97, 95% CI 0.75-1.26) were not reduced. The composite of death, MI, or disabling stroke favoured enoxaparin (HR 0.91, 95% CI 0.85-0.98, P = 0.007). Compared with UFH for 48 h, a strategy using enoxaparin as an adjunct to fibrinolysis resulted in a sustained reduction in death or MI at 1 year with no additional benefit after 30 days. Mortality was not reduced at 1 year with the enoxaparin strategy. The study was registered at ClinicalTrials.gov, NCT00077792. C1 [Morrow, David A.; Antman, Elliott M.; Giugliano, Robert; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [White, Harvey D.] Auckland City Hosp, Auckland, New Zealand. RP Morrow, DA (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org FU Sanofi-aventis, Bridgewater, NJ, USA; Accumetrics; AstraZeneca; Bayer Healthcare; Beckman Coulter; Biosite; Bristol-Myers Squibb; CV Therapeutics; Daiichi Sankyo Ltd; Eli Lilly and Co; GlaxoSmithKline; Integrated Therapeutics; Merck and Company; Millennium Pharmaceuticals; Novartis Pharmaceuticals; Nuvelo; Ortho-Clinical Diagnostics; Pfizer; Roche Diagnostics; Sanofi-aventis; Sanofi-Synthelabo; Schering-Plough; Amgen FX ExTRACT-TIMI 25 was funded by sanofi-aventis, Bridgewater, NJ, USA.; The TIMI Study Group has received significant research grant support from Accumetrics, Amgen, AstraZeneca, Bayer Healthcare, Beckman Coulter, Biosite, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo Ltd, Eli Lilly and Co, GlaxoSmithKline, Integrated Therapeutics, Merck and Company, Millennium Pharmaceuticals, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, sanofi-aventis, Sanofi-Synthelabo, and Schering-Plough. D. A. M. has received honoraria for educational presentations from Eli Lilly and sanofi-aventis. He has served as a consultant for AstraZeneca, CV Therapeutics, GlaxoSmithKline, sanofi-aventis, Schering-Plough, and Genentech. K. A. A. F. has received grant support from sanofi-aventis, Bristol-Myers Squibb, and GlaxoSmithKline and honoraria for speaking from sanofi-aventis, and GlaxoSmithKline. H. D. W. has received research grant support from and has served as an advisor to sanofi-aventis. S. A. M. and C. H. M. have no additional relationships to report. E. M. A. and E. B. have received honoraria for educational presentations and have served as consultants to sanofi-aventis. NR 28 TC 5 Z9 7 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2010 VL 31 IS 17 BP 2097 EP 2102 DI 10.1093/eurheartj/ehq098 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646HZ UT WOS:000281531500011 PM 20400762 ER PT J AU Giugliano, RP Giraldez, RR Morrow, DA Antman, EM Gibson, CM Mohanavelu, S Murphy, SA McCabe, CH Braunwald, E AF Giugliano, Robert P. Giraldez, Roberto R. Morrow, David A. Antman, Elliott M. Gibson, C. Michael Mohanavelu, Satishkumar Murphy, Sabina A. McCabe, Carolyn H. Braunwald, Eugene TI Relations between bleeding and outcomes in patients with ST-elevation myocardial infarction in the ExTRACT-TIMI 25 trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Bleeding; Mortality; Myocardial infarction; Anticoagulant; Outcomes ID ACUTE CORONARY SYNDROMES; CLINICAL-OUTCOMES; UNFRACTIONATED HEPARIN; BLOOD-TRANSFUSION; THERAPY; PREDICTORS; ENOXAPARIN; MORTALITY; IMPACT; RISK AB To evaluate the association of bleeding with mortality in ST-elevation myocardial infarction (STEMI). We studied 20 323 patients with STEMI receiving fibrinolytic therapy and an antithrombin in ExTRACT-TIMI 25. Relationships between in-hospital bleeding, patient characteristics, treatments, and in-hospital cardiovascular complications with mortality were evaluated using Cox models. Likelihood ratios estimated each variable's model contribution. High 30-day mortality after major bleeding (n = 309, 37.6% mortality) was driven by the poor prognosis of intracranial haemorrhage (ICH; n = 143, 65.4% mortality, model contribution 7.8%). The adjusted hazard ratios (HRs) for 30-day death for any major bleeding and for ICH were 2.9 [2.4-3.6] and 10.3 [8.2-12.8], respectively. Neither non-ICH major nor minor bleeding was associated with 30-day death after adjustment. Cardiogenic shock (HR 13.5, 61% contribution) and age (HR 1.6/decade, 17% contribution) were most strongly correlated with 30-day death. Among 30-day survivors, age (HR 1.6/decade, contribution 43%) and heart rate (HR 1.2 per 10 b.p.m., contribution 18%) were most strongly associated with mortality between Days 31 and 365. Cardiogenic shock, age, and ICH were important independent correlates of 30-day and 1-year mortality in STEMI patients receiving fibrinolytic therapy. In-hospital non-ICH major and minor bleeding were not independently associated with increased mortality at 30 days or 1 year. C1 [Giugliano, Robert P.; Giraldez, Roberto R.; Morrow, David A.; Antman, Elliott M.; Gibson, C. Michael; Mohanavelu, Satishkumar; Murphy, Sabina A.; McCabe, Carolyn H.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org FU Sanofi-Aventis; Bristol-Myers Squibb FX The ExTRACT-TIMI 25 trial was supported by a research grant from Sanofi-Aventis to the TIMI Study Group. However, no funding or other support was provided for this manuscript. All co-authors are/were members of the TIMI Study Group.; D. A. M., E. M. A., C. M. G. and E. B. report having received research grant support from Sanofi-Aventis. R. P. G., D. A. M., E. M. A., C. M. G. and E. B. have received lecture fees and/or have served on paid advisory boards for Sanofi-Aventis and Bristol-Myers Squibb. C. H. M. and S. A. M. have received research grant support from Sanofi-Aventis. R. R. G. and S. M. report no conflicts of interest relevant to this article. NR 24 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2010 VL 31 IS 17 BP 2103 EP 2110 DI 10.1093/eurheartj/ehq100 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646HZ UT WOS:000281531500012 PM 20413397 ER PT J AU Sultan, I Casanova, M Al-Jumaily, U Meazza, C Rodriguez-Galindo, C Ferrari, A AF Sultan, Iyad Casanova, Michela Al-Jumaily, Usama Meazza, Cristina Rodriguez-Galindo, Carlos Ferrari, Andrea TI Soft tissue sarcomas in the first year of life SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Sarcoma; Rhabdomyosarcoma; Fibrosarcoma; Haemangiopericytoma; SEER; Prognosis ID INFANTILE FIBROSARCOMA; ONCOLOGY-GROUP; RHABDOMYOSARCOMA; EXPERIENCE; TUMORS; AGE; HEMANGIOPERICYTOMA; CHEMOTHERAPY; COMMITTEE; YOUNGER AB Background: Soft tissue sarcomas (STS) occurring in the first year of life represent a rare entity. Challenges in delivering optimal therapy may affect the outcome in this very young population. Methods: We searched the SEER database for records of infants less than 1 year of age, with a reported diagnosis of STS who were diagnosed from 1973 to 2006. We analysed their clinical features and survival. These patients were also compared to older patients (1-18 years old) in order to understand the differences between the two groups. Results: The incidence rate of STS in the first year of life was 16.0 per million. As an entity, they represented 7.3% of malignancies reported in the first year of life. One fifth of these tumours (20.9%) were reported to be metastatic at diagnosis. The most common histologies were rhabdomyosarcoma (n = 99, 32.8%), fibrosarcoma (n = 74, 24.5%), malignant rhabdoid tumours (n = 43, 14.2%) and haemangiopericytoma (n = 12, 4.0%); except for rhabdomyosarcoma, the other 3 entities were very rare in older children. The 5-year survival of STS in children less than 1 year of age (62 +/- 3.0%) was significantly worse than that of older children (71 +/- 0.9%, P = 0.0002). In a multivariate model, histologic types other than fibrosarcoma and haemangiopericytoma (HR, 5.7; 95% CI, 2.28-14.20) as well as advanced stage (HR, 5.15; 95% CI, 3.28-8.10) were found to be significant adverse prognostic factors. Significantly less use of radiation was reported in infants when compared to older children (P < 0.0001). Conclusion: As a group, infantile STS are associated with worse survival than STS in older children. Outcome, however, is significantly associated with histologic subtype, with infantile fibrosarcoma and infantile haemangiopericytoma having better outcomes. Avoidance of radiotherapy in this young age may contribute to worse outcomes. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Sultan, Iyad; Al-Jumaily, Usama] King Hussein Canc Ctr, Dept Pediat Oncol, Amman 11941, Jordan. [Casanova, Michela; Ferrari, Andrea] Ist Nazl Tumori, Pediat Oncol Unit, I-20133 Milan, Italy. [Rodriguez-Galindo, Carlos] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA USA. [Rodriguez-Galindo, Carlos] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. RP Sultan, I (reprint author), King Hussein Canc Ctr, Dept Pediat Oncol, Queen Rania Al Abdullah St,POB 1269, Amman 11941, Jordan. EM isultan@khcc.jo RI Casanova, Michela/K-8436-2016; Meazza, Cristina/E-8191-2017; OI Casanova, Michela/0000-0003-0368-7883; Meazza, Cristina/0000-0002-1875-9563; Ferrari, Andrea/0000-0002-4724-0517 NR 24 TC 18 Z9 19 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2010 VL 46 IS 13 BP 2449 EP 2456 DI 10.1016/j.ejca.2010.05.002 PG 8 WC Oncology SC Oncology GA 652HJ UT WOS:000281994100017 PM 20538453 ER PT J AU Bosso, JA Mauldin, PD Salgado, CD AF Bosso, J. A. Mauldin, P. D. Salgado, C. D. TI The association between antibiotic use and resistance: the role of secondary antibiotics SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID LACTAMASE-PRODUCING ENTEROBACTERIACEAE; PSEUDOMONAS-AERUGINOSA; FLUOROQUINOLONE USE; SUSCEPTIBILITY; HOSPITALS; ANTIMICROBIALS; SURVEILLANCE; KLEBSIELLA; PATHOGENS; HEALTH AB Using susceptibility rates of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae over time as markers, we assessed the significance of the change of susceptibility rates to imipenem, ceftriaxone, cefepime, piperacillin/tazobactam, and ciprofloxacin over time and the relationship to antibiotic use for the period 2000-2006. Antibiotic use-susceptibility relationships were assessed using longitudinal regression analysis. The variables "time" and define daily doses (DDD)/1,000 patient days for the specific drug related to the susceptibility rates of that particular model's dependent variable were considered as the main effects, with significance determined at the 0.05 level. Decreases in susceptibility of the target organisms were common over the period of observation. Decreasing susceptibility trends over time were not statistically associated with the primary drug (e.g., organism susceptibility rate to imipenem with imipenem usage). However, secondary drug use was associated with susceptibility rates (e.g., susceptibility of E. cloacae to cefepime with piperacillin/tazobactam usage). These results suggest that antibiotic use-resistance relationships are influenced by the use of secondary antibiotics. Thus, a resistance problem may not be adequately addressed by simply altering the utilization of the primary antibiotic. C1 [Bosso, J. A.; Mauldin, P. D.] S Carolina Coll Pharm, Dept Clin Pharm & Outcome Sci, Charleston, SC 29425 USA. [Mauldin, P. D.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Bosso, J. A.; Salgado, C. D.] Med Univ S Carolina, Coll Med, Dept Med, Div Infect Dis, Charleston, SC 29425 USA. RP Bosso, JA (reprint author), S Carolina Coll Pharm, Dept Clin Pharm & Outcome Sci, MUSC Campus,280 Calhoun St,MSC 140, Charleston, SC 29425 USA. EM bossoja@musc.edu FU AstraZeneca Pharmaceuticals FX This work was supported, in part, by an investigator-initiated research grant from AstraZeneca Pharmaceuticals. NR 18 TC 8 Z9 9 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD SEP PY 2010 VL 29 IS 9 BP 1125 EP 1129 DI 10.1007/s10096-010-0972-5 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 637UP UT WOS:000280844500011 PM 20535624 ER PT J AU Turan, S Akin, L Akcay, T Adal, E Sarikaya, S Bastepe, M Juppner, H AF Turan, Serap Akin, Leyla Akcay, Teoman Adal, Erdal Sarikaya, Sevil Bastepe, Murat Jueppner, Harald TI Recessive versus imprinted disorder: consanguinity can impede establishing the diagnosis of autosomal dominant pseudohypoparathyroidism type Ib SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID FAMILIAL ISOLATED HYPOPARATHYROIDISM; ALBRIGHTS HEREDITARY OSTEODYSTROPHY; PARATHYROID-HORMONE RESISTANCE; GNAS LOCUS; CONTROL ELEMENT; SIGNAL PEPTIDE; URIC-ACID; GENE; MUTATIONS; FEATURES AB Hypocalcemia and hyperphosphatemia with low/normal parathyroid hormone (PTH) levels can be observed in hypoparathyroidism (HP), a disorder that may follow an autosomal dominant (AD) or autosomal recessive (AR) mode of inheritance. Similar biochemical changes are also observed in pseudohypoparathyroidism (PHP) type Ia and Ib, but affected patients usually show elevated PTH levels indicative of hormonal resistance. Features of Albright's hereditary osteodystrophy (AHO) are typically not observed in patients affected by familial forms of PHP-Ib, which are most frequently caused by maternally inherited, heterozygous microdeletions within STX16 and are associated with isolated loss of methylation at GNAS exon A/B. We established the molecular defect in two children of consanguineous Turkish parents, who presented with hypocalcemia, hyperphosphatemia, and low 25-OH vitamin D levels, but initially normal or only mildly elevated PTH levels, i.e. findings that do not readily exclude HP. After normalizing serum magnesium levels, hypocalcemia and hyperphosphatemia persisted, and PTH levels increased, suggesting PTH resistance rather than PTH deficiency. Because of the absence of AHO and parental consanguinity, an AR form of PHP-Ib appeared plausible, which had previously been suggested for sporadic cases. However, loss of GNAS methylation was restricted to exon A/B, which led to the identification of the 3-kb STX16 microdeletion. The same mutation was also detected in the healthy mother, who did not show any GNAS methylation abnormality, indicating that her deletion resides on the paternal allele. Our findings emphasize the importance of considering a parentally imprinted, AD disorder even if consanguinity suggests an AR mode of inheritance. C1 [Turan, Serap; Bastepe, Murat; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Akin, Leyla; Akcay, Teoman; Adal, Erdal; Sarikaya, Sevil] Bakirkoy Childhood & Matern Educ Hosp, Minist Hlth, Istanbul, Turkey. RP Turan, S (reprint author), Marmara Univ, Dept Pediat Endocrinol, Tophanelioglu Cad, Istanbul, Turkey. EM serap.turan@marmara.edu.tr FU Fulbright Scholarship; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK073911, R37 DK46718] FX S Turan was recipient of a grant from Fulbright Scholarship Program. This study was supported by research grants from National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK073911 to M Bastepe and R37 DK46718 to H Juppner). NR 26 TC 2 Z9 2 U1 0 U2 2 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD SEP PY 2010 VL 163 IS 3 BP 489 EP 493 DI 10.1530/EJE-10-0348 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 639OG UT WOS:000280983500017 PM 20538864 ER PT J AU Kinkel, RP Simon, J O'Connor, PW Foulds, P You, X Pace, A Hyde, R AF Kinkel, R. P. Simon, J. O'Connor, P. W. Foulds, P. You, X. Pace, A. Hyde, R. CA CHAMPIONS Study Grp TI Early MRI activity on IM IFN beta-1a predicts disease activity at 10 years SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 14th Congress of European-Federation-of-Neurological-Societies CY SEP, 2010 CL Geneva, SWITZERLAND SP European Federat Neurol Soc C1 [Kinkel, R. P.] Beth Israel Deaconess Med Ctr, Multiple Sclerosis Ctr, Boston, MA 02215 USA. [Simon, J.] Portland VA Med Ctr, Portland, OR USA. [O'Connor, P. W.] St Michaels Hosp, Div Neurol, Toronto, ON M5B 1W8, Canada. [Foulds, P.; You, X.; Pace, A.; Hyde, R.] Biogen Idec Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2010 VL 17 SU 3 SI SI BP 221 EP 221 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 800BD UT WOS:000293331100423 ER PT J AU Ahn, YJ Hwang, SK Han, S Moskowitz, MA Liao, JK Kim, HH AF Ahn, Y. -J. Hwang, S. -K. Han, S. Moskowitz, M. A. Liao, J. K. Kim, H. -H. TI Metformin prevents focal cerebral ischemic injury via AMPK/mTOR/S6 signalling pathways in a mouse model SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 14th Congress of European-Federation-of-Neurological-Societies CY SEP, 2010 CL Geneva, SWITZERLAND SP European Federat Neurol Soc C1 [Ahn, Y. -J.; Hwang, S. -K.; Liao, J. K.; Kim, H. -H.] Brigham & Womens Hosp, Cambridge, MA USA. [Ahn, Y. -J.; Hwang, S. -K.; Liao, J. K.; Kim, H. -H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Han, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Han, S.] Harvard Univ, Sch Med, Boston, MA USA. [Moskowitz, M. A.] Massachusetts Gen Hosp, Charlestown, MA USA. [Moskowitz, M. A.] Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2010 VL 17 SU 3 SI SI BP 419 EP 419 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 800BD UT WOS:000293331101137 ER PT J AU Atri, A AF Atri, A. TI Long-term effects of Alzheimer's disease treatment SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 14th Congress of European-Federation-of-Neurological-Societies CY SEP, 2010 CL Geneva, SWITZERLAND SP European Federat Neurol Soc C1 [Atri, A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Atri, A.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Atri, A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2010 VL 17 SU 3 SI SI BP 661 EP 661 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 800BD UT WOS:000293331101597 ER PT J AU Ducharme, N Banks, WA Morley, JE Robinson, SM Niehoff, ML Mattern, C AF Ducharme, Nicole Banks, William A. Morley, John E. Robinson, Sandra M. Niehoff, Michael L. Mattern, Claudia TI Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Intranasal; Neurosteroid; Pregnenolone; Progesterone; Memory; Anxiety ID RECEPTOR ISOFORMS EXPRESSION; FEMALE MICE; RAT-BRAIN; NEUROSTEROIDS; SULFATE; METABOLISM; INFUSION; STEROIDS; HORMONES AB Neurosteroids hold great promise for the treatment of diseases of the central nervous system (CNS). We compared the uptake by 11 brain regions and appearance in blood of tritium-labeled pregnenolone and progesterone after intranasal and intravenous (IV) injection. Both neurosteroids appeared in blood and brain after either method of administration, but with important differences in uptake. Bioavailability based on appearance in arterial serum showed that about 23% and 14% of the intranasal administered doses of pregnenolone and progesterone, respectively, entered the blood. Brain levels were about two fold lower after intranasal administration for the two neurosteroids. With intranasal administration, brain levels of the two steroids did not vary over time (2-120 min), whereas brain levels were higher early (10 min or less) after i.v. administration. With iv. administration, uptake by brain regions did not vary, whereas the olfactory bulb, hippocampus, and hypothalamus had high uptake rates after intranasal administration. Intranasal administration of prenenolone improved memory, whereas progesterone decreased anxiety, thus demonstrating that therapeutic levels of neurosteroids can be delivered to the brain by intranasal administration. The neurosteroids were rapidly degraded after i.v. or intranasal delivery, but pregnenolone was more resistant to degradation in the brain after intranasal administration and in serum after iv. administration. These results show that either the iv. or intranasal routes of administration can deliver neurosteroids to blood and brain, but that the two routes have significant differences with intranasal administration favoring some brain regions. Published by Elsevier B.V. C1 [Ducharme, Nicole; Morley, John E.; Robinson, Sandra M.; Niehoff, Michael L.] Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO USA. [Ducharme, Nicole; Banks, William A.; Morley, John E.; Robinson, Sandra M.; Niehoff, Michael L.] St Louis Univ, Sch Med, Dept Internal Med, Div Geriatr, St Louis, MO USA. [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Mattern, Claudia] M&P Pharma AG, CH-6370 Stans, Switzerland. RP Banks, WA (reprint author), WAB, Bldg 1,Rm 810A,1600 Columbian Way, Seattle, WA USA. EM wabanks1@uw.edu RI morley, john/F-9177-2011 OI morley, john/0000-0001-6444-2965 FU Mattern Pharmaceutical [NSR01 051334] FX Supported by Mattern Pharmaceutical and NSR01 051334. NR 33 TC 15 Z9 15 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD SEP 1 PY 2010 VL 641 IS 2-3 BP 128 EP 134 DI 10.1016/j.ejphar.2010.05.033 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 625OU UT WOS:000279905500009 PM 20570588 ER PT J AU Norgren, L Hiatt, WR Dormandy, JA Hirsch, AT Jaff, MR Diehm, C Baumgartner, I Belch, JJF AF Norgren, L. Hiatt, W. R. Dormandy, J. A. Hirsch, A. T. Jaff, M. R. Diehm, C. Baumgartner, I. Belch, J. J. F. TI The Next 10 years in the Management of Peripheral Artery Disease: Perspectives from The 'PAD 2009' Conference SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE Peripheral artery disease; Information; Research; Guidelines ID RANDOMIZED CONTROLLED-TRIAL; INTERMITTENT CLAUDICATION; COST-EFFECTIVENESS; LOWER-EXTREMITY; CELL THERAPY; HEALTH-CARE; REVASCULARIZATION; EXERCISE; AWARENESS; ISCHEMIA AB Objectives: To briefly inform on the conclusions from a conference on the next 10 years in the management of peripheral artery disease (PAD). Design of the Conference: International participation, invited presentations and open discussion were based on the following issues: Why is PAD under-recognised? Health economic impact of PAD; funding of PAD research; changes of treatment options? Aspects on clinical trials and regulatory views; and the role of guidelines. Results and Conclusions: A relative lack of knowledge about cardiovascular risk and optimal management of PAD patients exists not only among the public, but also in parts of the health-care system. Specialists are required to act for improved information. More specific PAD research is needed for risk management and to apply the best possible evaluation of evidence for treatment strategies. Better strategies for funding are required based on, for example, public/private initiatives. The proportion of endovascular treatments is steadily increasing, more frequently based on observational studies than on randomised controlled trials. The role of guidelines is therefore important to guide the profession in the assessment of most relevant treatment. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. C1 [Norgren, L.] Univ Hosp, Dept Surg, S-70185 Orebro, Sweden. [Hiatt, W. R.] Univ Colorado, Denver Sch Med, Denver, CO 80202 USA. [Dormandy, J. A.] St George Hosp, Dept Clin Vasc Res, London, England. [Hirsch, A. T.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Jaff, M. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Diehm, C.] Univ Heidelberg, SRH Klinikum Karlsbad Langensteinbach, Dept Vasc Med, Heidelberg, Baden Wurttembe, Germany. [Baumgartner, I.] Univ Hosp Insel, Swiss Cardiovasc Ctr, Bern, Switzerland. [Belch, J. J. F.] Univ Dundee, Ninewells Hosp Med Sch, Inst Cardiovasc Res, Dundee DD1 4HN, Scotland. RP Norgren, L (reprint author), Univ Hosp, Dept Surg, S-70185 Orebro, Sweden. EM lars.norgren@orebroll.se OI Belch, Jill/0000-0001-8280-6689 NR 29 TC 22 Z9 22 U1 1 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1078-5884 J9 EUR J VASC ENDOVASC JI Eur. J. Vasc. Endovasc. Surg. PD SEP PY 2010 VL 40 IS 3 BP 375 EP 380 DI 10.1016/j.ejvs.2010.05.005 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 656QV UT WOS:000282352600014 PM 20554459 ER PT J AU Feuchtner, G Goetti, R Plass, A Baumueller, S Stolzmann, P Scheffel, H Wieser, M Marincek, B Alkadhi, H Leschka, S AF Feuchtner, Gudrun Goetti, Robert Plass, Andre Baumueller, Stephan Stolzmann, Paul Scheffel, Hans Wieser, Monika Marincek, Borut Alkadhi, Hatem Leschka, Sebastian TI Dual-step prospective ECG-triggered 128-slice dual-source CT for evaluation of coronary arteries and cardiac function without heart rate control: a technical note SO EUROPEAN RADIOLOGY LA English DT Article DE Computed tomography; Coronary arteries; Cardiac function; Prospective ECG triggering; Radiation dose ID LEFT-VENTRICULAR FUNCTION; COMPUTED-TOMOGRAPHY; IMAGE QUALITY; SHOOT MODE; ANGIOGRAPHY; REDUCTION; STENOSIS; MOTION AB To describe prospective ECG-triggered dual-source CT dual-step pulsing (pECG(dual_step)) for evaluation of coronary arteries and cardiac function. Fifty-one consecutive patients pre- or post-cardiovascular surgery were examined with adaptive sequential tube current modulated (pECG(dual-step)) 128-slice dual-source CT without heart rate control (main padding window: 40% RR interval > 65 bpm/70% RR interval < 65 bpm). Image quality of coronary arteries was graded (4-point scale), and cardiac function was evaluated. Mean HR was 68 bpm. Thirty-seven patients were in stable sinus rhythm (SR); 14 had arrhythmia. Image quality of coronary arteries was diagnostic in 804/816 (98%) of segments. The number of non-diagnostic segments was higher in patients with arrhythmia as compared to those in SR (4% vs. 0.5%; p = 0.01), and there were fewer segments with excellent image quality (79% vs. 94%; p < 0.001) and more segments with impaired image quality (p < 0.001 and p = 0.002). Global and regional LV function could be evaluated in 41 (80%) and 47 (92%) patients, and valvular function in 48 (94%). In 11/14 of patients with arrhythmia, the second step switched to full mAs, increasing radiation exposure to 8.6 mAs (p < 0.001). The average radiation dose was 3.8 mSv (range, 1.7-7.9) in patients in SR. pECG(dual-step)128-slice DSCT is feasible for the evaluation of coronary arteries and cardiac function without heart rate control in patients in stable sinus rhythm at a low radiation dose. C1 [Feuchtner, Gudrun] Innsbruck Med Univ, Dept Radiol 2, A-6020 Innsbruck, Austria. [Feuchtner, Gudrun; Goetti, Robert; Baumueller, Stephan; Stolzmann, Paul; Scheffel, Hans; Marincek, Borut; Alkadhi, Hatem; Leschka, Sebastian] Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. [Plass, Andre; Wieser, Monika] Univ Zurich Hosp, Div Cardiac & Vasc Surg, CH-8091 Zurich, Switzerland. [Alkadhi, Hatem] Harvard Univ, Sch Med, Boston, MA USA. [Alkadhi, Hatem] Boston Massachussets Gen Hosp, Cardiac MR CT PET Grp, Boston, MA USA. RP Feuchtner, G (reprint author), Innsbruck Med Univ, Dept Radiol 2, Anichstr 35, A-6020 Innsbruck, Austria. EM gudrun.feuchtner@i-med.ac.at RI Goetti, Robert/I-8961-2012 NR 30 TC 34 Z9 39 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD SEP PY 2010 VL 20 IS 9 BP 2092 EP 2099 DI 10.1007/s00330-010-1794-7 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 634PQ UT WOS:000280595800005 PM 20407896 ER PT J AU Eikermann, M Eckert, DJ Chamberlin, NL Jordan, AS Zaremba, S Smith, S Rosow, C Malhotra, A AF Eikermann, M. Eckert, D. J. Chamberlin, N. L. Jordan, A. S. Zaremba, S. Smith, S. Rosow, C. Malhotra, A. TI Effects of pentobarbital on upper airway patency during sleep SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Airway; arousal threshold; lung; obstructive sleep apnoea/hypopnoea syndrome; sleep-disordered breathing ID GENIOGLOSSUS MUSCLE-ACTIVITY; LUNG-VOLUME; VENTILATORY CONTROL; APNEA; INCREASES; PRESSURE; MECHANISMS; AROUSAL; RATS; COLLAPSIBILITY AB We hypothesised that pentobarbital would improve upper airway mechanics based on an increase in latency to arousal and amplitude of the phasic genioglossus electromyogram (EMG), and a decrease in the active upper airway critical closing pressure (Pcrit). 12 healthy subjects received pentobarbital (100 mg) or placebo in a double-blind, crossover protocol. During wakefulness, we measured the genioglossus reflex response to negative pressure pulses. During sleep, carbon dioxide was insufflated into the inspired air. Airway pressure was then decreased in a stepwise fashion until arousal from sleep. With basal breathing during sleep: flow rate was lower in volunteers given pentobarbital; end-tidal CO(2) concentration and upper airway resistance were greater; and Pcrit was unaffected (pentobarbital mean +/- SD -11.7 +/- 4.5 versus placebo -10.25 +/- 3.6 cmH(2)O; p<0.11). Pentobarbital increased the time to arousal (297 +/- 63s versus 232 +/- 67 s; p<0.05), at which time phasic genioglossus EMG was higher (6.2 +/- 4.8% maximal versus 3.1 +/- 3%; p<0.05) as were CO(2) levels. The increase in genioglossus EMG after CO(2) administration was greater after pentobarbital versus placebo. Pentobarbital did not affect the genioglossus negative-pressure reflex. Pentobarbital increases the time to arousal and stimulates genioglossus muscle activity, but it also increases upper airway resistance during sleep. C1 [Eikermann, M.; Rosow, C.] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Eikermann, M.; Eckert, D. J.; Chamberlin, N. L.; Jordan, A. S.; Zaremba, S.; Smith, S.; Rosow, C.; Malhotra, A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Eckert, D. J.; Jordan, A. S.; Smith, S.; Malhotra, A.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Eckert, D. J.; Jordan, A. S.; Smith, S.; Malhotra, A.] Brigham & Womens Hosp, Div Pulm Crit Care, Boston, MA 02115 USA. [Chamberlin, N. L.; Zaremba, S.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Eikermann, M.] Univ Klinikum Essen, Klin Anasthesie & Intens Med, Essen, Germany. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM meikermann@partners.org RI Eckert, Danny/A-6145-2012; OI Eckert, Danny/0000-0003-3503-2363; Jordan, Amy/0000-0001-8561-9766 FU National Institute of Health (NIH) [P50 HL060292, RO1-HL73146, AG024837, R01-HL085188, AHA 0840159N, NIH R01 HL090897, K24 HL-093218]; German Research Council [DFG-EI684/2-1]; National Health and Medical Research Council of Australia [510392] FX This work was supported by grants from the National Institute of Health (NIH) (P50 HL060292, RO1-HL73146, AG024837, R01-HL085188, AHA 0840159N, NIH R01 HL090897, K24 HL-093218), and a grant from the German Research Council (DFG-EI684/2-1). D.J. Eckert is supported by an Overseas Based Biomedical Fellowship from the National Health and Medical Research Council of Australia (510392). NR 42 TC 13 Z9 13 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 SEP PY 2010 VL 36 IS 3 BP 569 EP 576 DI 10.1183/09031936.00153809 PG 8 WC Respiratory System SC Respiratory System GA 658DI UT WOS:000282470000018 PM 20032012 ER PT J AU Katiyar, SK Sampath, A Bihari, S Mamtani, M Kulkarni, H AF Katiyar, S. K. Sampath, A. Bihari, S. Mamtani, M. Kulkarni, H. TI Using a whole-blood interferon-gamma assay to improve diagnosis of tuberculous pleural effusion SO EUROPEAN RESPIRATORY JOURNAL LA English DT Letter ID ANTIGEN; TOOLS; TESTS C1 [Katiyar, S. K.; Sampath, A.] Ganesh Shankar Vidyarthi Mem Med Coll, Dept TB & Resp Dis, Kanpur, Uttar Pradesh, India. [Sampath, A.; Bihari, S.; Mamtani, M.; Kulkarni, H.] Lata Med Res Fdn, Nagpur, Maharashtra, India. [Mamtani, M.; Kulkarni, H.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Mamtani, M.; Kulkarni, H.] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & Infect HIV 1, San Antonio, TX USA. RP Kulkarni, H (reprint author), 12023 Waterway Rdg, San Antonio, TX 78249 USA. EM hemant_kulkarnius@yahoo.com NR 14 TC 1 Z9 1 U1 0 U2 1 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 SEP PY 2010 VL 36 IS 3 BP 679 EP 681 DI 10.1183/09031936.00001110 PG 3 WC Respiratory System SC Respiratory System GA 658DI UT WOS:000282470000032 PM 20930202 ER PT J AU Li, G Lv, G Passias, P Kozanek, M Metkar, US Liu, ZJ Wood, KB Rehak, L Deng, YW AF Li, Gang Lv, Guohua Passias, Peter Kozanek, Michal Metkar, Umesh S. Liu, Zhongjun Wood, Kirkham B. Rehak, Lubos Deng, Youwen TI Complications associated with thoracic pedicle screws in spinal deformity SO EUROPEAN SPINE JOURNAL LA English DT Article DE Complication; Spinal deformity; Surgical treatment; Pedicle screw instrumentation ID ADOLESCENT IDIOPATHIC SCOLIOSIS; LUMBAR SPINE; COMPUTED-TOMOGRAPHY; INSTRUMENTATION; PLACEMENT; FIXATION; ACCURACY; FUSION; THORACOLUMBAR; SAFE AB Thoracic pedicle screws have superior anchoring strength compared with other available fixation techniques. However, these are not universally accepted in many developing countries because of the concerns regarding safety and complications. In addition, there is evidence that pedicle morphology is unique in Chinese patients. The goal of this study was to analyze the complications seen at our institution, while using thoracic pedicle screws for the treatment of thoracic deformity, and to determine the safety of our techniques for the treatment of thoracic deformity in a Chinese population. From 1998 to 2005, there were 208 thoracic deformity patients treated at our institution, 70 of whom were male and 138 were female. Their age ranged from 11 to 55 years (mean of 14.9 years). All of them underwent corrective deformity surgery using posterior pedicle screw systems and follow-up was available for at least 3 years. Etiologic diagnoses included adolescent idiopathic scoliosis in 119 patients, congenital kyphoscoliosis in 38, adult scoliosis in 37 and undetermined in 14. Screw positions were evaluated using intraoperative and postoperative radiographs and a CT scan was performed when a concern for screw malposition was present. All radiographic evaluations were carried out in a double-blinded fashion. A total of 1,123 thoracic pedicle screws were inserted (5.4 thoracic screws/patient). The deformity correction rate was 81, 65 and 62% for idiopathic, congenital and adult scoliosis patients, respectively. The overall complication rate was 16.5% at the final follow-up. Complication rates directly and indirectly related to pedicle screws were 7.2 and 9.3%, respectively. There were no significant screw-related neurologic or visceral complications that adversely affected long-term results. The complications seen with thoracic pedicle screws in a Chinese population were similar to other populations and could be utilized safely for the treatment of thoracic deformity in this population. C1 [Lv, Guohua; Deng, Youwen] Cent S Univ, Dept Orthopaed Spine Surg, Xiangya Hosp 2, Changsha, Hunan, Peoples R China. [Li, Gang; Passias, Peter; Kozanek, Michal; Metkar, Umesh S.; Wood, Kirkham B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Spine Surg, Boston, MA USA. [Li, Gang; Liu, Zhongjun] Peking Univ, Dept Orthopaed Spine Surg, Hosp 3, Beijing 100871, Peoples R China. [Kozanek, Michal; Rehak, Lubos] Comenius Univ, Sch Med, Ruzinov Fac Hosp, Dept Orthopaed Surg, Bratislava, Slovakia. RP Deng, YW (reprint author), Cent S Univ, Dept Orthopaed Spine Surg, Xiangya Hosp 2, Changsha, Hunan, Peoples R China. EM li.gang@mgh.harvard.edu; drywdeng3@gmail.com NR 44 TC 20 Z9 24 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 J9 EUR SPINE J JI Eur. Spine J. PD SEP PY 2010 VL 19 IS 9 BP 1576 EP 1584 DI 10.1007/s00586-010-1316-y PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 644MK UT WOS:000281381500020 PM 20237943 ER PT J AU Panigrahy, D Kaipainen, A Butterfield, CE Chaponis, DM Laforme, AM Folkman, J Kieran, MW AF Panigrahy, Dipak Kaipainen, Arja Butterfield, Catherine E. Chaponis, Deviney M. Laforme, Andrea M. Folkman, Judah Kieran, Mark W. TI Inhibition of tumor angiogenesis by oral etoposide SO EXPERIMENTAL AND THERAPEUTIC MEDICINE LA English DT Article DE etoposide; tumor angiogenesis; metronomic chemotherapy; oral combination therapy; peroxisome-proliferator activated receptor ID ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; METASTATIC BREAST-CANCER; PPAR-GAMMA LIGANDS; METRONOMIC CHEMOTHERAPY; ANTIANGIOGENIC THERAPY; DOSE CYCLOPHOSPHAMIDE; SCHEDULE DEPENDENCY; SOLID TUMORS; PHASE-II AB The chemotherapeutic agent etoposide is a topoisomerase II inhibitor widely used for cancer therapy. Low-dose oral etoposide, administered at close regular intervals, has potent anti-tumor activity in patients who are refractory to intravenous etoposide; however, the mechanism remains unclear. Since endothelial cells may be more sensitive than tumor cells to chemotherapy agents, we determined the effects of etoposide alone and in combination with oral cyclooxygenase-2 inhibitors and peroxisome-proliferator activated receptor gamma ligands on angiogenesis and tumor growth in xenograft tumor models. Optimal anti-angiogenic (metronomic) and anti-tumor doses of etoposide on angiogenesis, primary tumor growth and metastasis were established alone and in combination therapy. Etoposide inhibited endothelial and tumor cell proliferation, decreased vascular endothelial growth factor (VEGF) production by tumor cells and suppressed endothelial tube formation at non-cytotoxic concentrations. In our in vivo studies, oral etoposide inhibited fibroblast growth factor 2 and VEGF-induced corneal neovascularization. EGF-induced vascular permeability and increased levels of the endogenous angiogenesis inhibitor endostatin in mice. in addition, etoposide inhibited Lewis lung carcinoma (LLC) and human glioblastoma (U87) primary tumor growth as well as spontaneous lung metastasis in a LLC resection model. Furthermore, etoposide had synergistic anti-tumor activity in combination with celecoxib and rosiglitazone, which are also oral anti-angiogenic and anti-tumor agents. Etoposide inhibits angiogenesis in vitro and in vivo by indirect and direct mechanisms of action. Combining etoposide with celecoxib and rosiglitazone increases its efficacy and merits further investigation in future clinical trials to determine the potential usefulness of etoposide in combinatory anti-angiogenic chemotherapy. C1 [Panigrahy, Dipak; Butterfield, Catherine E.; Chaponis, Deviney M.; Laforme, Andrea M.; Folkman, Judah; Kieran, Mark W.] Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program,Dept Surg, Boston, MA 02115 USA. [Panigrahy, Dipak; Chaponis, Deviney M.; Laforme, Andrea M.; Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Kaipainen, Arja] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada. RP Kieran, MW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM mark_kieran@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU Stop and Shop Family Pediatric Brain Tumor Fund; C.J. Buckley Pediatric Brain Tumor Research Fund; Department of Defense Innovator [W81XWH-04-1-0316]; private philanthropic funds FX We dedicate this research study to the memory of Dr Judah Folkman. The excellent technical assistance of Ricky Sanchez is acknowledged. We thank Kristin Johnson for photography. We thank Jessica Barnes for the helpful discussion. This study was supported by the Stop and Shop Family Pediatric Brain Tumor Fund and the C.J. Buckley Pediatric Brain Tumor Research Fund (M.W.K., D.P. and A.L.) and by the Department of Defense Innovator Award #W81XWH-04-1-0316 (J.F.) and private philanthropic funds. NR 50 TC 14 Z9 14 U1 0 U2 10 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-0981 J9 EXP THER MED JI Exp. Ther. Med. PD SEP-OCT PY 2010 VL 1 IS 5 BP 739 EP 746 DI 10.3892/etm.2010.127 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 687TD UT WOS:000284799900002 ER PT J AU Ferraro, F Lymperi, S Mendez-Ferrer, S Masselli, E Lin, C Frenette, P Quaini, F Scadden, D AF Ferraro, F. Lymperi, S. Mendez-Ferrer, S. Masselli, E. Lin, C. Frenette, P. Quaini, F. Scadden, D. TI DIABETES IMPAIRS HEMATOPOIETIC STEM CELL TRAFFICKING SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells CY SEP 15-18, 2010 CL Melbourne, AUSTRALIA SP Soc Hematol Stem Cell C1 [Ferraro, F.; Lymperi, S.; Scadden, D.] Massachusetts Gen Hosp, Harvard Stem Cell Inst, CRM, Boston, MA 02114 USA. [Mendez-Ferrer, S.; Frenette, P.] Mt Sinai Sch Med, New York, NY USA. [Masselli, E.; Quaini, F.] Univ Parma, BMT, I-43100 Parma, Italy. [Masselli, E.; Quaini, F.] Univ Parma, Dept Hematol, I-43100 Parma, Italy. [Lin, C.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2010 VL 38 IS 9 SU 1 MA 169 BP S79 EP S80 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 641YM UT WOS:000281168900161 ER PT J AU Lane, SW Sykes, SM Ferraro, F Lin, CP Gilliland, DG Williams, DA Scadden, DT Lo Celso, C AF Lane, S. W. Sykes, S. M. Ferraro, F. Lin, C. P. Gilliland, D. G. Williams, D. A. Scadden, D. T. Lo Celso, C. TI LEUKEMIA STEM CELLS OCCUPY NICHES THAT ARE PHYSICALLY DISTINCT AND INDEPENDENT OF THE NORMAL CONSTRAINTS THAT APPLY TO HEMATOPOIETIC STEM CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells CY SEP 15-18, 2010 CL Melbourne, AUSTRALIA SP Soc Hematol Stem Cell C1 [Lane, S. W.; Williams, D. A.] Childrens Hosp Boston, Brookline, MA USA. [Sykes, S. M.; Ferraro, F.; Lin, C. P.; Scadden, D. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gilliland, D. G.] Merck, N Wales, PA USA. [Lo Celso, C.] Univ London Imperial Coll Sci Technol & Med, London, England. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2010 VL 38 IS 9 SU 1 MA 080 BP S38 EP S38 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 641YM UT WOS:000281168900077 ER PT J AU Lymperi, S Ferraro, F Kobayashi, T Spencer, J Kronenberg, H Lin, C Scadden, D AF Lymperi, S. Ferraro, F. Kobayashi, T. Spencer, J. Kronenberg, H. Lin, C. Scadden, D. TI DISSECTING THE COMPLEXITY OF THE OSTEOBLASTIC CELLS AND THEIR ROLE IN THE HSC NICHE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells CY SEP 15-18, 2010 CL Melbourne, AUSTRALIA SP Soc Hematol Stem Cell C1 [Lymperi, S.; Ferraro, F.; Scadden, D.] Massachusetts Gen Hosp, Harvard Stem Cell Inst, CRM, Boston, MA 02114 USA. [Kobayashi, T.; Kronenberg, H.] Massachusetts Gen Hosp, Endocrine Unit, Harvard Med Sch, Boston, MA 02114 USA. [Spencer, J.; Lin, C.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RI Spencer, Joel/A-4590-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2010 VL 38 IS 9 SU 1 MA 170 BP S80 EP S80 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 641YM UT WOS:000281168900162 ER PT J AU Nombela-Arrieta, C Pivarnik, G Mahoney, JE Harley, B Lu, J Du, K Levantini, E Protopopov, A Tenen, DG Silberstein, LE AF Nombela-Arrieta, C. Pivarnik, G. Mahoney, J. E. Harley, B. Lu, J. Du, K. Levantini, E. Protopopov, A. Tenen, D. G. Silberstein, L. E. TI HEMATOPOIETIC STEM AND PROGENITOR CELLS ARE ASSOCIATED WITH STRUCTURALLY DIVERSE TYPES OF BONE MARROW MICROVESSELS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells CY SEP 15-18, 2010 CL Melbourne, AUSTRALIA SP Soc Hematol Stem Cell C1 [Nombela-Arrieta, C.; Pivarnik, G.; Lu, J.; Du, K.; Silberstein, L. E.] Childrens Hosp, Boston, MA 02115 USA. [Mahoney, J. E.; Protopopov, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Harley, B.] Univ Illinois, Urbana, IL 61801 USA. [Levantini, E.; Tenen, D. G.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2010 VL 38 IS 9 SU 1 MA 162 BP S75 EP S76 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 641YM UT WOS:000281168900154 ER PT J AU Scadden, DT AF Scadden, D. T. TI NICHE INITIATED ONCOGENESIS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells CY SEP 15-18, 2010 CL Melbourne, AUSTRALIA SP Soc Hematol Stem Cell C1 [Scadden, D. T.] Massachusetts Gen Hosp, Harvard Stem Cell Inst, 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2010 VL 38 IS 9 SU 1 MA 233 BP S109 EP S110 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 641YM UT WOS:000281168900223 ER PT J AU Sykes, SM AF Sykes, S. M. TI FOX TRANSCRIPTION FACTORS ARE REQUIRED FOR THE MAINTENANCE OF ACUTE MYELOID LEUKEMIA SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells CY SEP 15-18, 2010 CL Melbourne, AUSTRALIA SP Soc Hematol Stem Cell C1 [Sykes, S. M.] 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2010 VL 38 IS 9 SU 1 MA 158 BP S73 EP S74 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 641YM UT WOS:000281168900150 ER PT J AU Wagers, AJ AF Wagers, A. J. TI STEM CELL TRAFFICKING: IMPLICATIONS FOR STEM CELL FUNCTION SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells CY SEP 15-18, 2010 CL Melbourne, AUSTRALIA SP Soc Hematol Stem Cell C1 [Wagers, A. J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wagers, A. J.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2010 VL 38 IS 9 SU 1 MA 264 BP S122 EP S123 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 641YM UT WOS:000281168900253 ER PT J AU Santillan, AA Zager, JS AF Santillan, Alfredo A. Zager, Jonathan S. TI Isolated limb infusion for melanoma: a less morbid alternative to hyperthermic isolated limb perfusion in the US SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Editorial Material DE melanoma; melphalan; regional arterial infusion; toxicity ID ACUTE REGIONAL TOXICITY; TUMOR-NECROSIS-FACTOR; MELPHALAN; EXPERIENCE; CHEMOTHERAPY; EXTREMITY; TRIAL C1 [Santillan, Alfredo A.] Univ Texas Hlth Sci Ctr San Antonio, Sect Surg Oncol, Dept Surg, Audie L Murphy Vet Affairs Hosp, San Antonio, TX 78229 USA. [Zager, Jonathan S.] Univ S Florida, Dept Oncol Sci & Surg, Tampa, FL 33612 USA. EM jonathan.zager@moffitt.org NR 22 TC 1 Z9 1 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD SEP PY 2010 VL 6 IS 9 BP 1033 EP 1037 DI 10.1517/17425250903559881 PG 5 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 651XP UT WOS:000281961200001 PM 20078252 ER PT J AU Islam, T Harisinghani, MG AF Islam, Tina Harisinghani, Mukesh G. TI Prostate cancer imaging: what the next decade holds SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Editorial Material DE diffusion-weighted MRI; dynamic contrast-enhanced MRI; MR spectroscopy; positron emission tomography; prostate carcinoma; prostate-specific membrane antigen; transrectal ultrasound ID EXTRACAPSULAR EXTENSION; SPATIAL-RESOLUTION; ENDORECTAL MR; LOCALIZATION; PET/CT C1 [Islam, Tina; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02114 USA. RP Islam, T (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM Tina.Islam@mwmc.com NR 19 TC 0 Z9 0 U1 0 U2 3 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1743-4440 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD SEP PY 2010 VL 7 IS 5 BP 577 EP 579 DI 10.1586/ERD.10.43 PG 3 WC Engineering, Biomedical SC Engineering GA 650CU UT WOS:000281826600001 PM 20822379 ER PT J AU Brumberg, JS Guenther, FH AF Brumberg, Jonathan S. Guenther, Frank H. TI Development of speech prostheses: current status and recent advances SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Review DE brain-computer interface; speech prosthesis; speech synthesis ID BRAIN-COMPUTER-INTERFACE; THOUGHT-TRANSLATION DEVICE; LOCKED-IN SYNDROME; INTRACORTICAL ELECTRODE ARRAY; ELECTROCORTICOGRAPHIC SIGNALS; MACHINE INTERFACE; MENTAL PROSTHESIS; CORTICAL-NEURONS; VIRTUAL KEYBOARD; MOVEMENT SIGNAL AB Brain-computer interfaces (BCIs) have been developed over the past decade to restore communication to persons with severe paralysis. In the most severe cases of paralysis, known as locked-in syndrome, patients retain cognition and sensation, but are capable of only slight voluntary eye movements. For these patients, no standard communication method is available, although some can use BCIs to communicate by selecting letters or words on a computer. Recent research has sought to improve on existing techniques by using BCIs to create a direct prediction of speech utterances rather than to simply control a spelling device. Such methods are the first steps towards speech prostheses as they are intended to entirely replace the vocal apparatus of paralyzed users. This article outlines many well known methods for restoration of communication by BCI and illustrates the difference between spelling devices and direct speech prediction or speech prosthesis. C1 [Brumberg, Jonathan S.; Guenther, Frank H.] Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. [Guenther, Frank H.] Boston Univ, Sargent Coll, Boston, MA 02215 USA. [Guenther, Frank H.] Boston Univ, Dept Speech Language & Hearing Sci, Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. [Guenther, Frank H.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Guenther, Frank H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Brumberg, JS (reprint author), Boston Univ, Dept Cognit & Neural Syst, 677 Beacon St, Boston, MA 02215 USA. EM brumberg@bu.edu FU NIH/NIDCD [R01DC002852, R01DC007683]; CELEST, an NSF Science of Learning Center (NSF) [SMA-0835976] FX This work was supported by NIH/NIDCD grants R01DC002852, R01DC007683 and by CELEST, an NSF Science of Learning Center (NSF SMA-0835976). 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 84 TC 6 Z9 6 U1 1 U2 8 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1743-4440 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD SEP PY 2010 VL 7 IS 5 BP 667 EP 679 DI 10.1586/ERD.10.34 PG 13 WC Engineering, Biomedical SC Engineering GA 650CU UT WOS:000281826600016 PM 20822389 ER PT J AU Hamrah, P Singh, PK Hoesl, L Tezel, TH AF Hamrah, P. Singh, P. K. Hoesl, L. Tezel, T. H. TI Development of crystalline keratopathy after intravitreal injections of pegaptanib SO EYE LA English DT Letter ID MACULAR DEGENERATION C1 [Hamrah, P.; Singh, P. K.; Hoesl, L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Cornea Serv,Med Sch, Boston, MA 02115 USA. [Hamrah, P.; Tezel, T. H.] Univ Louisville, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA. RP Hamrah, P (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Cornea Serv,Med Sch, Boston, MA 02115 USA. EM Tongalp.Tezel@louisville.edu FU NEI NIH HHS [K12-EY016335, K12 EY016335, K08 EY020575] NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD SEP PY 2010 VL 24 IS 9 BP 1527 EP 1528 DI 10.1038/eye.2010.81 PG 2 WC Ophthalmology SC Ophthalmology GA 648OU UT WOS:000281704600017 PM 20508650 ER PT J AU Wham, D Vu, T Chan-Smutko, G Kobelka, C Urbauer, D Heald, B AF Wham, Deborah Vu, Thuy Chan-Smutko, Gayun Kobelka, Christine Urbauer, Diana Heald, Brandie TI Assessment of clinical practices among cancer genetic counselors SO FAMILIAL CANCER LA English DT Article DE Cancer genetic counseling; Genetic counseling; Hereditary breast ovarian cancer; Practice efficiency; Results disclosure; Service delivery model ID HUNTINGTONS-DISEASE; PREDICTIVE TEST; GUIDELINES; SERVICES; UPDATE; BREAST; SUSCEPTIBILITY; STATEMENT; ECONOMICS AB Various models of cancer genetics service delivery have been published, and practice guidelines were set forth by the National Society of Genetic Counselors (NSGC) in 2004. While the demand for services has increased, there has not been a comprehensive study of current practice models. An online survey of the NSGC Familial Cancer Risk Counseling Special Interest Group was conducted to study current methods of providing clinical cancer genetics services. Respondents were asked to quantify patient volume, support staff availability, and physician involvement in cases. Two case examples were used to further describe current practices including the number of genetic counseling tasks performed, time spent in these tasks, and number of in-person visits versus phone encounters. Although published cancer genetic counseling guidelines advise a 3-visit model (initial consult, sample draw, and result disclosure), 29.3% of respondents have adopted a 1-visit model, where the sample is drawn at the first visit and phone disclosure replaces the third visit. The content of the initial consult does not vary significantly, and is consistent with the NSGC practice guidelines. Furthermore, 56% report spending > 15 min on case preparation, and 27 respondents self-reported redundancy in tasks such as documentation. It appears that a proportion of genetic counselors are following a new model of service delivery. However, insufficient documentation and case preparation are apparent, and many respondents reported lack of support staff as a barrier to efficient patient care. Factors contributing to the variability in current practice, and how they affect efficiency, require further study. C1 [Wham, Deborah] Aurora Hlth Care, Canc Genet Counseling Program, Milwaukee, WI 53215 USA. [Vu, Thuy] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Chan-Smutko, Gayun] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Risk Assessment, Boston, MA USA. [Kobelka, Christine] Kaiser Permanente, Dept Genet, San Francisco, CA USA. [Urbauer, Diana] Univ Texas MD Anderson Canc Ctr, Div Quantitat Sci, Houston, TX 77030 USA. [Heald, Brandie] Cleveland Clin, Genom Med Inst, Cleveland, OH 44106 USA. RP Wham, D (reprint author), Aurora Hlth Care, Canc Genet Counseling Program, 2900 W Oklahoma Ave, Milwaukee, WI 53215 USA. EM Deborah.wham@aurora.org FU NSGC Familial Cancer Risk Counseling Special Interest Group FX This study was supported by the NSGC Familial Cancer Risk Counseling Special Interest Group Grant Award. The authors would like to thank Dawn Allain and Sarah Coombes for their contribution to the pilot study. NR 22 TC 27 Z9 27 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9600 J9 FAM CANCER JI Fam. Cancer PD SEP PY 2010 VL 9 IS 3 BP 459 EP 468 DI 10.1007/s10689-010-9326-9 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 638UL UT WOS:000280922100030 PM 20140525 ER PT J AU Mroz, P Huang, YY Szokalska, A Zhiyentayev, T Janjua, S Nifli, AP Sherwood, ME Ruzie, C Borbas, KE Fan, DZ Krayer, M Balasubramanian, T Yang, E Kee, HL Kirmaier, C Diers, JR Bocian, DF Holten, D Lindsey, JS Hamblin, MR AF Mroz, Pawel Huang, Ying-Ying Szokalska, Angelika Zhiyentayev, Timur Janjua, Sahar Nifli, Artemissia-Phoebe Sherwood, Margaret E. Ruzie, Christian Borbas, K. Eszter Fan, Dazhong Krayer, Michael Balasubramanian, Thiagarajan Yang, Eunkyung Kee, Hooi Ling Kirmaier, Christine Diers, James R. Bocian, David F. Holten, Dewey Lindsey, Jonathan S. Hamblin, Michael R. TI Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy SO FASEB JOURNAL LA English DT Article DE multidrug resistance; melanosomes; electron microscopy ID OVARIAN-CARCINOMA CELLS; MALIGNANT-MELANOMA; ANTITUMOR IMMUNITY; MELANOGENESIS; PHOTOSENSITIZERS; CANCER; OXYGEN; CYCLOPHOSPHAMIDE; SUBSTITUENTS; MELANOCYTES AB Cutaneous malignant melanoma remains a therapeutic challenge, and patients with advanced disease have limited survival. Photodynamic therapy (PDT) has been successfully used to treat many malignancies, and it may show promise as an antimelanoma modality. However, high melanin levels in melanomas can adversely affect PDT effectiveness. Herein the extent of melanin contribution to melanoma resistance to PDT was investigated in a set of melanoma cell lines that markedly differ in the levels of pigmentation; 3 new bacteriochlorins successfully overcame the resistance. Cell killing studies determined that bacteriochlorins are superior at (LD50 approximate to 0.1 mu M) when compared with controls such as the FDA-approved Photofrin (LD50 approximate to 10 mu M) and clinically tested LuTex (LD50 approximate to 1 mu M). The melanin content affects PDT effectiveness, but the degree of reduction is significantly lower for bacteriochlorins than for Photofrin. Microscopy reveals that the least effective bacteriochlorin localizes predominantly in lysosomes, while the most effective one preferentially accumulates in mitochondria. Interestingly all bacteriochlorins accumulate in melanosomes, and subsequent illumination leads to melanosomal damage shown by electron microscopy. Fluorescent probes show that the most effective bacteriochlorin produces significantly higher levels of hydroxyl radicals, and this is consistent with the redox properties suggested by molecular-orbital calculations. The best in vitro performing bacteriochlorin was tested in vivo in a mouse melanoma model using spectrally resolved fluorescence imaging and provided significant survival advantage with 20% of cures (P<0.01).-Mroz, P., Huang, Y.-Y., Szokalska, A., Zhiyentayev, T., Janjua, S., Nifli, A.-P., Sherwood, M. E., Ruzie, C., Borbas, K. E., Fan, D., Krayer, M., Balasubramanian, T., Yang, E., Kee, H. L., Kirmaier, C., Diers, J. R., Bocian, D. F., Holten, D., Lindsey, J. S., Hamblin, M. R. Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy. FASEB J. 24, 3160-3170 (2010). www.fasebj.org C1 [Mroz, Pawel; Huang, Ying-Ying; Szokalska, Angelika; Zhiyentayev, Timur; Janjua, Sahar; Nifli, Artemissia-Phoebe; Sherwood, Margaret E.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Mroz, Pawel; Huang, Ying-Ying; Nifli, Artemissia-Phoebe; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Szokalska, Angelika] Med Univ Warsaw, Dept Immunol, Ctr Biostruct, Warsaw, Poland. [Zhiyentayev, Timur] MIT, Dept Chem, Cambridge, MA 02139 USA. [Janjua, Sahar] Aga Khan Med Coll, Karachi, Pakistan. [Ruzie, Christian; Borbas, K. Eszter; Fan, Dazhong; Krayer, Michael; Lindsey, Jonathan S.] N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. [Balasubramanian, Thiagarajan] NIRvana Pharmaceut Inc, Raleigh, NC USA. [Yang, Eunkyung; Kee, Hooi Ling; Kirmaier, Christine; Holten, Dewey] Washington Univ, Dept Chem, St Louis, MO 63130 USA. [Diers, James R.; Bocian, David F.] Univ Calif Riverside, Dept Chem, Riverside, CA 92521 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Muchowicz, Angelika/J-7494-2012; Lindsey, Jonathan/J-7761-2012; Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01GM36238, R01AI050875]; Burroughs-Wellcome fellowship; Jimmy V. NCSU Cancer Therapeutics Training Program; National Institute of Allergy and Infectious Diseases [R41AI072854]; Genzyme-Partners Translational Research; Foundation for Polish Science; International Union against Cancer; European Structural Fund; Division of Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences of the U.S. Department of Energy [DE-FG02-05ER15660, DE-FG02-05ER15661] FX This work was supported by grants from the NIH (R01GM36238 to J.S.L. and R01AI050875 to M. R. H.), a Burroughs-Wellcome fellowship (to M. K.), and the Jimmy V. NCSU Cancer Therapeutics Training Program. P. M. and T. B. were supported by a grant (R41AI072854) from the National Institute of Allergy and Infectious Diseases to NIRvana Pharmaceuticals. P. M. was partly supported by Genzyme-Partners Translational Research Grant. A. S. was supported by the Foundation for Polish Science, the International Union against Cancer, and the European Structural Fund: Mazowieckie Stypendium Doktoranckie. Characterization of the photophysical and redox properties of the bacteriochlorins described herein was initially motivated by solar-energy studies and supported by grants from the Division of Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences of the U.S. Department of Energy to D. F. B. (DE-FG02-05ER15660) and D. H. (DE-FG02-05ER15661). The authors thank Pharmacyclics (Sunnyvale, CA, USA) for the gift of LuTex and loan of 730-nm laser and QLT (Vancouver, BC, Canada) for the gift of Photofrin. NR 58 TC 51 Z9 53 U1 4 U2 32 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 SEP PY 2010 VL 24 IS 9 BP 3160 EP 3170 DI 10.1096/fj.09-152587 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 645IK UT WOS:000281446400006 PM 20385618 ER PT J AU Attaman, JA Toth, TL Hauser, R Chavarro, JE AF Attaman, J. A. Toth, T. L. Hauser, R. Chavarro, J. E. TI DIETARY FATS AND SEMEN QUALITY AMONG MEN ATTENDING A FERTILITY CLINIC. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S49 EP S49 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000169 ER PT J AU Chavarro, JE Ehrlich, S Attaman, JA Toth, TL Petrozza, J Hauser, R AF Chavarro, J. E. Ehrlich, S. Attaman, J. A. Toth, T. L. Petrozza, J. Hauser, R. TI BODY MASS INDEX (BMI) AND EARLY TREATMENT OUTCOMES IN WOMEN UNDERGOING IN VITRO FERTILIZATION (IVF). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA USA. RI Ehrlich , Shelley/L-6991-2015 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S92 EP S92 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000314 ER PT J AU Ehrlich, SR Meeker, JD Williams, PL Wright, D Petrozza, J Hauser, R AF Ehrlich, S. R. Meeker, J. D. Williams, P. L. Wright, D. Petrozza, J. Hauser, R. TI URINARY METABOLITES OF DI(2-ETHYLHEXYL) PHTHALATE ARE ASSOCIATED WITH INCREASED RISK OF IMPLANTATION FAILURE AMONG WOMEN UNDERGOING IVF SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Fertil Ctr, Boston, MA 02114 USA. RI Ehrlich , Shelley/L-6991-2015 NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S73 EP S73 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000249 ER PT J AU Ghazal, S Doyle, JO Meeker, JD Souter, IC Petrozza, JC AF Ghazal, S. Doyle, J. O. Meeker, J. D. Souter, I. C. Petrozza, J. C. TI SPERM CONCENTRATION IN OVULATION INDUCTION/INTRAUTERINE INSEMINATION CYCLES (OI/IUI): HOW HIGH IS TOO HIGH? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Massachusetts Gen Hosp, Fertil Ctr, Boston, MA 02114 USA. Univ Michigan, Sch Publ Hlth, Dept Environm Hlth, Ann Arbor, MI 48109 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S164 EP S164 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000558 ER PT J AU Goldman, MB Regan, MM Berger, MJ Oskowitz, SP Reindollar, RH AF Goldman, M. B. Regan, M. M. Berger, M. J. Oskowitz, S. P. Reindollar, R. H. TI THE NATURAL HISTORY OF INFERTILITY TREATMENT IN A STATE WITH MANDATED INSURANCE COVERAGE: THE FAST TRACK AND STANDARD TREATMENT (FASTT) TRIAL. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Dartmouth Hitchcock Med Ctr, Dept Obstet & Gynecol, Lebanon, NH 03766 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Boston IVF, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S245 EP S246 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000842 ER PT J AU Goldman, MB Regan, MM Alper, MM Thornton, KL Reindollar, RH AF Goldman, M. B. Regan, M. M. Alper, M. M. Thornton, K. L. Reindollar, R. H. TI PREGNANCY RATES ACROSS MULTIPLE TREATMENT CYCLES: DATA FROM THE FAST TRACK AND STANDARD TREATMENT (FASTT) TRIAL. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Boston IVF, Waltham, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S1 EP S1 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000002 ER PT J AU Mahalingaiah, S Maity, A Berry, KF Williams, PL Missmer, SA Hauser, R AF Mahalingaiah, S. Maity, A. Berry, K. F. Williams, P. L. Missmer, S. A. Hauser, R. TI ASSOCIATION OF POLYCHLORINATED BIPHENYLS (PCBS) WITH ADVERSE REPRODUCTIVE OUTCOMES DURING IN VITRO FERTILIZATION (IVF) SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproduct Med C1 Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S72 EP S72 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000247 ER PT J AU Mahalingaiah, S Maity, A Berry, KF Williams, PL Missmer, SA Hauser, R AF Mahalingaiah, S. Maity, A. Berry, K. F. Williams, P. L. Missmer, S. A. Hauser, R. TI ASSOCIATION OF PERSISTENT ORGANIC POLLUTANTS HEXACHLOROBENZENE (HCB), DICHLORODIPHENYLTRICHLOROETHANE (DDT), AND DICHLORODIPHENYLDICHLOROETHANE (DDE) WITH IN VITRO FERTILIZATION (IVF) OUTCOMES SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproduct Med C1 Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S72 EP S73 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000248 ER PT J AU Moulder, J Doyle, J Meeker, J Souter, I Petrozza, J AF Moulder, J. Doyle, J. Meeker, J. Souter, I. Petrozza, J. TI WHEN IS FLEXIBILITY IN FOLLICULAR MONITORING SAFEST IN IVF CYCLES? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Massachusetts Gen Hosp, Div Reprod Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S157 EP S157 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000535 ER PT J AU Park, JH Teixeira, JM AF Park, J. H. Teixeira, J. M. TI IN VITRO MATURATION (IVM) AND PARTHENOGENESIS OF ADULT MURINE PRIMARY OVARIAN FOLLICLES IS AMELIORATED IN THE ABSENCE OF ANTI-MULLERIAN HORMONE (AMH). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S140 EP S140 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000478 ER PT J AU Souter, I Dimitriadis, I Ehrlich, S Petrozza, JC Ford, JB Hauser, R AF Souter, I. Dimitriadis, I. Ehrlich, S. Petrozza, J. C. Ford, J. B. Hauser, R. TI URINARY BISPHENOL A (BPA) CONCENTRATIONS AND OVARIAN RESPONSE IN WOMEN UNDERGOING OVULATION INDUCTION/INTRAUTERINE INSEMINATION CYCLES (OI/IUI). SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. RI Ehrlich , Shelley/L-6991-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S227 EP S228 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000780 ER PT J AU Tanaka, Y Park, JH Tanwar, PS Kaneko-Tarui, T Mittal, S Teixeira, J AF Tanaka, Y. Park, J. H. Tanwar, P. S. Kaneko-Tarui, T. Mittal, S. Teixeira, J. TI DELETION OF TSC1 IN OVARIAN SOMATIC CELLS OF THE FEMALE REPRODUCTIVE TRACT CAUSES INFERTILITY. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 [Tanaka, Y.; Park, J. H.; Tanwar, P. S.; Kaneko-Tarui, T.; Mittal, S.; Teixeira, J.] Harvard Univ, Sch Med, Massachusetts 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S135 EP S136 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000461 ER PT J AU Wright, DL Ehrlich, S Berry, K Toth, TL Amarasiriwardena, C Hauser, R AF Wright, D. L. Ehrlich, S. Berry, K. Toth, T. L. Amarasiriwardena, C. Hauser, R. TI THE RELATIONSHIP OF HAIR MERCURY LEVELS WITH EARLY IN VITRO FERTILIZATION (IVF) OUTCOMES. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Massachusetts Gen Hosp, Div Reprod Med & IVF, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Ctr Infertil & Reprod Surg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S228 EP S228 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000781 ER PT J AU Claus, R Plass, C Armstrong, SA Bullingert, L AF Claus, Rainer Plass, Christoph Armstrong, Scott A. Bullingert, Lars TI DNA methylation profiling in acute myeloid leukemia: from recent technological advances to biological and clinical insights SO FUTURE ONCOLOGY LA English DT Review DE acute myeloid leukemia; cytogenetics; DNA; methylation; epigenetics; epigenomics; genomics; microarray; molecular; genetics; next-generation; sequencing ID CPG-ISLAND METHYLATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; SPORADIC BREAST-CANCER; GENE-EXPRESSION; ABERRANT METHYLATION; TUMOR-SUPPRESSOR; PROMOTER METHYLATION; HMLH1 PROMOTER; MYELODYSPLASTIC SYNDROMES; 5-METHYLCYTOSINE CONTENT AB Acute myeloid leukemia represents a heterogeneous malignant hematological disease with a complex underlying biology suggesting multiple patterns of genetic and epigenetic alterations. Recent evidence suggests that epigenetic mechanisms, especially deregulation of DNA methylation, play an important pathogenic role in leukemogenesis and the first epigenetic drugs have entered the clinic. Therefore, an improved understanding of the impact of altered epigenetic patterns on leukemogenesis represents a pre-requisite for improved patient management and outcome. Here, we provide an overview of current advances in deciphering the leukemic epigenome and its clinical relevance. Recent high-throughput analyses and genome-wide studies provide an optimal starting point for future epigenetic and integrative analyses that will further the development and use of predictive and prognostic epigenetic markers in acute myeloid leukemia. C1 [Armstrong, Scott A.; Bullingert, Lars] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Claus, Rainer; Plass, Christoph] German Canc Res Ctr DKF7, Dept Epigenom & Canc Risk Factors, Heidelberg, Germany. [Armstrong, Scott A.; Bullingert, Lars] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Armstrong, Scott A.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Bullingert, Lars] Univ Ulm, Dept Internal Med 3, D-89087 Ulm, Germany. RP Bullingert, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Plass, Christoph/H-7192-2014 NR 127 TC 11 Z9 11 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 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD SEP PY 2010 VL 6 IS 9 BP 1415 EP 1431 DI 10.2217/FON.10.110 PG 17 WC Oncology SC Oncology GA 666JG UT WOS:000283110400011 PM 20919827 ER PT J AU Fernandez-del Castillo, C Adsay, NV AF Fernandez-del Castillo, Carlos Adsay, N. Volkan TI Intraductal Papillary Mucinous Neoplasms of the Pancreas SO GASTROENTEROLOGY LA English DT Editorial Material ID CYSTIC NEOPLASMS; CLINICOPATHOLOGICAL FEATURES; INVASIVE ADENOCARCINOMA; DUCTAL CARCINOMA; FOLLOW-UP; CLASSIFICATION; CONSENSUS; RESECTION; MALIGNANCY; MANAGEMENT C1 [Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pancreas & Biliary Surg Program, Boston, MA 02114 USA. [Adsay, N. Volkan] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pancreas & Biliary Surg Program, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM cfernandez@partners.org NR 48 TC 58 Z9 59 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2010 VL 139 IS 3 BP 708 EP U31 DI 10.1053/j.gastro.2010.07.025 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 644HR UT WOS:000281365500004 PM 20650278 ER PT J AU Furuta, T Graham, DY AF Furuta, Takahisa Graham, David Y. TI Pharmacologic Aspects of Eradication Therapy for Helicobacter pylori Infection SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article DE CYP2C19; Helicobacter pylon; Pharmacogenomics; Proton pump inhibitor; Rapid metabolizer; Intermediate metabolizer; Poor metabolizer ID PROTON PUMP INHIBITOR; 23S RIBOSOMAL-RNA; EARLY GASTRIC-CANCER; DOUBLE-BLIND TRIAL; TRIPLE THERAPY; CYP2C19 GENOTYPE; PEPTIC-ULCER; CURE RATES; DUAL THERAPY; CLARITHROMYCIN RESISTANCE AB The commonly used regimens for the eradication of Helicobacter pylori infection consist of administration of proton pump inhibitors (PPIs) and 1 to 3 antimicrobial agents such as amoxicillin clarithromycin metronidazole fluoroquinolone or tetracycline Each agent has its own pharmacologic characteristics PPIs are metabolized by cytochrome P450 2C19 (CYP2C19) which is polymorphic CYP2C19 genotypic differences in the pharmacokinetics and pharmacodynamics of PPIs influence the eradication rates of H pylori infection by PPI-containing regimens Amoxicillin is a time-dependent antibiotic, whereas clarithromycin metronidazole, tetracycline and fluoroquinolone are not The plasma half-life of antimicrobial agents also differs among these antibiotics To achieve consistently high eradication rates the eradication regimens must be designed based on a good understanding of the resistance patterns of the bacteria and the pharmacologic characteristics of the agents used for H pylori eradication therapy C1 [Furuta, Takahisa] Hamamatsu Univ Sch Med, Clin Res Ctr, Higashi Ku, Hamamatsu, Shizuoka 4313192, Japan. [Graham, David Y.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Furuta, T (reprint author), Hamamatsu Univ Sch Med, Clin Res Ctr, Higashi Ku, 1 20 1 Handayama, Hamamatsu, Shizuoka 4313192, Japan. FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs, Public Health Service [DK56338, R21DK067366] FX Dr Graham is supported in part by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, Public Health Service grant DK56338, which funds the Texas Medical Center Digestive Diseases Center and R21DK067366 The contents are solely the responsibility of the authors and do not necessarily represent the official views of the Department of Veterans Affairs or National Institutes of Health Dr Graham is an unpaid consultant for Novartis in relation to vaccine development for treatment or prevention of Helicobacter pylon infection Dr Graham is also a paid consultant for Otsuka Pharmaceuticals regarding diagnostic testing, and until July 2007, he was a member of the Board of Directors of Meretek Diagnostics, the manufacturer of the 13C-urea breath test Until November 2009, Dr Graham received royalties on the Baylor College of Medicine patent covering materials related to 13C-urea breath test Dr Furuta declares no conflicts NR 68 TC 36 Z9 42 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 2010 VL 39 IS 3 BP 465 EP + DI 10.1016/j.gtc.2010.08.007 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 681DP UT WOS:000284291900005 PM 20951912 ER PT J AU Kang, HJ Kim, DH Jeon, TY Lee, SH Shin, N Chae, SH Kim, GH Song, GA Kim, DH Srivastava, A Park, DY Lauwers, GY AF Kang, Hyun Jeong Kim, Dae Hwan Jeon, Tae-Yong Lee, Soo-Han Shin, Nari Chae, Sue-Hye Kim, Gwang Ha Song, Geum Am Kim, Dong-Heon Srivastava, Amitabh Park, Do Youn Lauwers, Gregory Y. TI Lymph node metastasis from intestinal-type early gastric cancer: experience in a single institution and reassessment of the extended criteria for endoscopic submucosal dissection SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID WESTERN PATHOLOGISTS; RESECTION; PREDICTORS; CARCINOMA; NEOPLASMS; JAPANESE; SURGERY; EMR AB Background: Given the increasing use of endoscopic resection as a therapeutic modality for cases of early gastric cancer (EGC), it is very important to define strict criteria for the use of endoscopic mucosal resection and endoscopic submucosal dissection. To date, the criteria are almost entirely based on Japanese literature evaluating the risk of lymph node (LN) metastasis in patients with EGC. Objective: To analyze our own experience with the factors affecting LN metastasis and to reappraise the extended criteria for endoscopic submucosal dissection. Design: Retrospective, single-center study. Setting: University teaching hospital. Patients: This study involved 478 patients who underwent gastrectomy with LN dissection (n = 270, mucosal [m] EGC; n = 208, submucosal [sm] EGC). Intervention: Gastrectomy with LN dissection. Main Outcome Measurements: LN metastasis. Results: Overall, 12.6% (60/478) of patients with EGCs presented with LN metastasis (mEGC, 3.0% [8/270], smEGC, 25.0% [52/208]). Increased size, macroscopic type (elevated), depth of invasion, and lymphovascular invasion were associated with LN metastasis. In 270 cases of mEGC, there was no relationship between clinicopathologic features and LN metastasis. In the smEGC group, size, depth of invasion, and lymphovascular emboli were associated with an increased risk of LN metastasis. Significantly, LN metastasis was noted in EGCs falling within established extended endoscopic submucosal dissection criteria, that is, intestinal-type mucosal cancer of any size without ulcer and no lymphovascular emboli (2/146[1.4%]) or <= 3 cm with no lymphovascular emboli and irrespective of the presence of ulceration (2/126 [1.6%]) or intestinal-type submucosal cancer (sm1, <500 mu m) without lymphovascular invasion and measuring <= 3 cm in size (3/20 [15.0%]). Limitations: Retrospective review of a single-center study. Conclusion: We recommend that more centers survey their experiences of LN metastasis in cases of EGC to refine the criteria for endoscopic submucosal dissection as a therapeutic modality of intestinal-type EGC. (Gastrointest Endosc 2010;72:508-15.) C1 [Kang, Hyun Jeong; Lee, Soo-Han; Shin, Nari; Chae, Sue-Hye; Park, Do Youn] Pusan Natl Univ, Pusan Natl Univ Hosp, Sch Med, Dept Pathol, Pusan 602739, South Korea. [Kim, Gwang Ha; Song, Geum Am] Pusan Natl Univ, Pusan Natl Univ Hosp, Sch Med, Dept Internal Med, Pusan 602739, South Korea. [Kim, Dae Hwan; Jeon, Tae-Yong; Kim, Dong-Heon] Pusan Natl Univ, Pusan Natl Univ Hosp, Sch Med, Dept Surg, Pusan 602739, South Korea. Pusan Natl Univ, Med Res Inst, Pusan 602739, South Korea. [Srivastava, Amitabh] Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA. Dartmouth Med Sch, Lebanon, NH USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Park, DY (reprint author), Pusan Natl Univ, Pusan Natl Univ Hosp, Sch Med, Dept Pathol, 1-10 Ami Dong, Pusan 602739, South Korea. EM pdy220@pusan.ac.kr FU Ministry for Health, Welfare and Family Affairs, Republic of Korea [0920050] FX This study was supported by grant 0920050 from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea. All other authors disclosed no financial relationships relevant to this publication. H.J. Kang and D.H. Kinr equally contributed in this work. D.Y Park, and G.Y. Lauwers share senior authorship. NR 26 TC 53 Z9 56 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 SEP PY 2010 VL 72 IS 3 BP 508 EP 515 DI 10.1016/j.gie.2010.03.1077 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 648EI UT WOS:000281672800007 PM 20554277 ER PT J AU Cox, AA Jezewski, PA Fang, PK Payne-Ferreira, TL AF Cox, A. A. Jezewski, P. A. Fang, P. -K. Payne-Ferreira, T. L. TI Zebrafish Wnt9a,9b paralog comparisons suggest ancestral roles for Wnt9 in neural, oral-pharyngeal ectoderm and mesendoderm SO GENE EXPRESSION PATTERNS LA English DT Article DE Zebrafish; Wnt signaling ID WHOLE-GENOME DUPLICATION; RAY-FINNED FISHES; GENE-EXPRESSION; CLEFT-PALATE; EVOLUTION; CREST; MORPHOGENESIS; VERTEBRATE; INTEGRITY; EVENTS AB The Wnts are a highly conserved family of secreted glycoproteins involved in cell-cell signaling and pattern formation during early embryonic development. Teasing out the role of individual Wnt molecules through development is challenging. Gene duplications are one of the most important mechanisms for generating evolutionary variations. The current consensus suggests that most anatomical variation is generated by divergence of regulatory control regions rather than by coding sequence divergence. Thus phylogenetic comparisons of divergent gene expression patterns are essential to understanding ancestral morphogenetic patterns from which subsequent anatomy diversified in modern lineages. We previously demonstrated strongest expression of zebrafish wnt9b within its heart tube, limb bud and ventral/anterior ectoderm during oral and pharyngeal arch patterning. Our goal is to compare and contrast zwnt9b to its closest paralog, zwnt9a. Sequenced, fulllength zebrafish wnt9a and wnt9b cDNA clones were used for phylogenetic analysis, which suggests their derivation from a common pre-vertebrate archeolog by gene duplication and divergence. Here we demonstrate that zwnt9a expression is found within unique (CNS, pronephric ducts, sensory organs) and overlapping (pectoral fin buds) expression domains relative to zwnt9b. Apparently, Wnt9 paralogs differentially parsed common ancestral expression domains during their subsequent rounds of gene duplication, divergence and loss in different vertebrate lineages. This expression data suggests ancestral roles for Wnt9s in early patterning of neural/oral-pharyngeal ectoderm and mesendoderm derivatives. (C) 2010 Elsevier B.V. All rights reserved. C1 [Cox, A. A.; Fang, P. -K.; Payne-Ferreira, T. L.] Univ Massachusetts, Dept Biol, N Dartmouth, MA 02747 USA. [Jezewski, P. A.] Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst,Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Payne-Ferreira, TL (reprint author), Univ Massachusetts Dartmouth, Dept Biol, 285 Old Westport Rd, Dartmouth, MA 02747 USA. EM tferreira@umassd.edu FU NIH/NIDCR [DE14528, DE14683]; UMAss Dartmouth Healey FX We wish to thank, Andrea Moreira and Tammy Silva for their technical assistance and The Molecular Genetics Core Facility of children's Hospital Boston. This research was supported in part by NIH/NIDCR Grants DE14528 (P.A.J.), and DE14683 (T.L.F.), and a UMAss Dartmouth Healey endowment grant. NR 31 TC 7 Z9 7 U1 4 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD SEP PY 2010 VL 10 IS 6 BP 251 EP 258 DI 10.1016/j.gep.2010.05.005 PG 8 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 638RT UT WOS:000280914300004 PM 20566374 ER PT J AU Wang, Z Tang, Z Zheng, Y Yu, D Spear, M Iyer, SR Bishop, B Wu, Y AF Wang, Z. Tang, Z. Zheng, Y. Yu, D. Spear, M. Iyer, S. R. Bishop, B. Wu, Y. TI Development of a nonintegrating Rev-dependent lentiviral vector carrying diphtheria toxin A chain and human TRAF6 to target HIV reservoirs SO GENE THERAPY LA English DT Article DE HIV-1; lentiviral vector; Rev; integration; diphtheria toxin; TRAF6 ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS TYPE-1; CD4(+) T-CELLS; NF-KAPPA-B; SUSTAINED VIRAL SUPPRESSION; PHASE-I TRIAL; COMBINATION THERAPY; PERIPHERAL-BLOOD; FUSION PROTEIN; REPLICATION-COMPETENT AB Persistence of human immunodeficiency virus (HIV) despite highly active antiretroviral therapy (HAART) is a lasting challenge to virus eradication. To develop a strategy complementary to HAART, we constructed a series of Rev-dependent lentiviral vectors carrying diphtheria toxin A chain (DT-A) and its attenuated mutants, as well as human tumor necrosis factor receptor-associated factor 6 (TRAF6). Expression of these suicide genes following delivery through viral particles is dependent on Rev, which exists only in infected cells. Among these toxins, DT-A has been known to trigger cell death with as little as a single molecule, whereas two of the attenuated mutants in this study, DT-A(176) and DT-A(Delta N), were well tolerated by cells at low levels. TRAF6 induced apoptosis only with persistent overexpression. Thus, these suicide genes, which induce cell death at different expression levels, offer a balance between efficacy and safety. To minimize possible mutagenesis introduced by retroviral integration in nontarget cells, we further developed a nonintegrating Rev-dependent (NIRD) lentiviral vector to deliver these genes. In addition, we constructed a DT-A-resistant human cell line by introducing a human elongation factor 2 mutant into HEK293T cells. This allowed us to manufacture the first high-titer NIRD lentiviral particles carrying DT-A to target HIV-positive cells. Gene Therapy (2010) 17, 1063-1076; doi:10.1038/gt.2010.53; published online 22 April 2010 C1 [Tang, Z.; Zheng, Y.; Yu, D.; Spear, M.; Iyer, S. R.; Wu, Y.] George Mason Univ, Dept Mol & Microbiol, Manassas, VA 20110 USA. [Wang, Z.] Harvard Univ, Harvard Med Sch, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. [Tang, Z.] Shanxi Agr Univ, Coll Life Sci, Taiyuan, Shanxi, Peoples R China. [Bishop, B.] George Mason Univ, Dept Chem & Biochem, Manassas, VA 20110 USA. RP Wu, Y (reprint author), George Mason Univ, Dept Mol & Microbiol, 10900 Univ Blvd, Manassas, VA 20110 USA. EM ywu8@gmu.edu FU Public Health Service [NS051130]; NINDS [AI069981, AI081568]; NIAID FX We thank the George Mason University Student Health Center for blood donations; the NIH AIDS Research & Reference Reagent Program, NIAID, NIH, for reagents; David M Neville for his help on DT-A cloning and discussions; Jeffrey Guo and Wei Ao for technical assistance; and Jennifer Guernsey for editorial assistance. This work was supported by Public Health Service Grant NS051130 (to YW) from NINDS and AI069981, AI081568 (to YW) from NIAID. Yanfang Zheng was supported by the generous donations of the donors and riders of the 2008 NYCDC AIDS ride organized by Marty Rosen and Day2 Inc. NR 74 TC 7 Z9 7 U1 0 U2 3 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 SEP PY 2010 VL 17 IS 9 BP 1063 EP 1076 DI 10.1038/gt.2010.53 PG 14 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 649HC UT WOS:000281757900001 PM 20410930 ER PT J AU Dismuke, CE Egede, LE AF Dismuke, Clara E. Egede, Leonard E. TI Association between major depression, depressive symptoms and personal income in US adults with diabetes SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID FUNCTIONAL DISABILITY; COMORBID DEPRESSION; CARE USE; INDIVIDUALS; EMPLOYMENT; SAMPLE; PREVALENCE; COMMUNITY; AMERICANS; MORTALITY AB Objective: Although the association between diabetes and depression outcomes has been well studied, very little is known about the association between depression and personal income in adults with diabetes. We examined the association between major depression, number of depressive symptoms and personal income among individuals with diabetes. Methods: We used the two-stage Heckman procedure to estimate adjusted personal income by major depression status and number of depressive symptoms for 1818 adults with diabetes from the nationally representative 2006 Medical Expenditure Panel Survey. STATA V.10 was used for statistical analysis to account for the complex survey design. Results: In a fully adjusted model with major depression as a binary variable, major depression was associated with $2838 lower personal income. In a separate model with depressive symptoms as a continuous variable, each additional symptom was associated with $1235 lower personal income. Compared with being white/non-Hispanic, being black/non-Hispanic (-$4640) was associated with decreased personal income. Compared with excellent health status, fair health status (-$12,172) and poor health status (-$13,835) were associated with lower income. Relative to private insurance, public insurance only (-$8413) and being uninsured (-$9600) were associated with decreased income. Conclusions: Among adults with diabetes, major depression and depressive symptoms are associated with lower personal income, after adjusting for relevant confounders. This finding suggests that aggressively diagnosing and treating depression as well as keeping people free of depressive symptoms can have huge human capital savings over the employment lifetime of individuals with diabetes and depression. (C) 2010 Elsevier Inc. All rights reserved. C1 [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Dismuke, Clara E.] Med Univ S Carolina, Dept Clin Pharm & Outcome Sci, Charleston, SC 29425 USA. [Dismuke, Clara E.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29401 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. EM egedel@musc.edu NR 37 TC 16 Z9 17 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2010 VL 32 IS 5 BP 484 EP 491 DI 10.1016/j.genhosppsych.2010.06.004 PG 8 WC Psychiatry SC Psychiatry GA 657CT UT WOS:000282390500005 PM 20851268 ER PT J AU Kemper, AR Knapp, AA Green, NS Comeau, AM Metterville, DR Perrin, JM AF Kemper, Alex R. Knapp, Alixandra A. Green, Nancy S. Comeau, Anne Marie Metterville, Danielle R. Perrin, James M. TI Weighing the evidence for newborn screening for early-infantile Krabbe disease SO GENETICS IN MEDICINE LA English DT Review DE newborn screening; Krabbe disease; systematic evidence review ID STEM-CELL TRANSPLANTATION; DRIED BLOOD SPOTS; LYSOSOMAL STORAGE DISORDERS; TANDEM MASS-SPECTROMETRY; UMBILICAL-CORD BLOOD; NEW-YORK; ASSAY; ENZYMES AB Purpose: To summarize the evidence regarding screening, diagnosis, and treatment of early-infantile Krabbe disease in consideration of its addition to the core panel for newborn screening as has been done in New York state. Methods: Systematic review of articles indexed in MEDLINE and Embase published between January 1988 and July 2009. Thirteen articles describing studies related to screening, diagnosis, or treatment were included in this review. Results: Case series studies suggest that allogeneic hematopoietic stem-cell transplantation soon after the development of signs or symptoms of early-infantile Krabbe disease decreases early-childhood mortality and may improve neurodevelopment. However, limited data suggest there may be loss of motor function among some children who undergo transplantation. No long-term follow-up data are available from these case series. Of the similar to 550,000 newborns reported to have been screened in New York, 25 tested positive. None of these were clinically recognized to have Krabbe disease prior these results. Four were considered to be high risk for early-onset Krabbe disease. Two were subsequently diagnosed and underwent stem-cell transplantation, of whom one died from complications. No data are available regarding the impact on families of a positive newborn screen. Conclusions: Although early treatment with hematopoietic stem-cell transplant seems to alter early-childhood mortality and some of the morbidity associated with early-infantile Krabbe disease, significant gaps in knowledge exist regarding the accuracy of screening, the strategy for establishing diagnosis, the affect of a positive screen on families, the benefits and harms of treatment, and long-term prognosis. Genet Med 2010:12(9):539-543. C1 [Kemper, Alex R.] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA. [Kemper, Alex R.] Duke Univ, Dept Pediat, Durham, NC 27705 USA. [Knapp, Alixandra A.; Metterville, Danielle R.; Perrin, James M.] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. [Green, Nancy S.] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Comeau, Anne Marie] Univ Massachusetts, Sch Med, New England Newborn Screening Program, Worcester, MA USA. [Comeau, Anne Marie] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. RP Kemper, AR (reprint author), Duke Univ, Duke Clin Res Inst, 2400 Pratt St,Room 0311 Terrace Level, Durham, NC 27705 USA. EM alex.kemper@duke.edu OI Green, Nancy/0000-0002-9877-1561 FU Columbia University; Duke University; MassGeneral Hospital for Children [HHSP23320045014XI]; HHS; HRSA; Maternal and Child Health Bureau (MCHB) FX This work was supported by subcontracts to Columbia University, Duke University, and MassGeneral Hospital for Children under prime contract (HHSP23320045014XI) to Altarum Institute, from HHS, HRSA, and Maternal and Child Health Bureau (MCHB). NR 22 TC 37 Z9 37 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD SEP PY 2010 VL 12 IS 9 BP 539 EP 543 DI 10.1097/GIM.0b013e3181e85721 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 659CS UT WOS:000282545200001 PM 20601893 ER PT J AU McKenna, A Hanna, M Banks, E Sivachenko, A Cibulskis, K Kernytsky, A Garimella, K Altshuler, D Gabriel, S Daly, M DePristo, MA AF McKenna, Aaron Hanna, Matthew Banks, Eric Sivachenko, Andrey Cibulskis, Kristian Kernytsky, Andrew Garimella, Kiran Altshuler, David Gabriel, Stacey Daly, Mark DePristo, Mark A. TI The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data SO GENOME RESEARCH LA English DT Article ID STRUCTURAL VARIATION; QUALITY ASSESSMENT; SHORT-READ; ALIGNMENT; MHC AB Next-generation DNA sequencing (NGS) projects, such as the 1000 Genomes Project, are already revolutionizing our understanding of genetic variation among individuals. However, the massive data sets generated by NGS the 1000 Genome pilot alone includes nearly five terabases-make writing feature-rich, efficient, and robust analysis tools difficult for even computationally sophisticated individuals. Indeed, many professionals are limited in the scope and the ease with which they can answer scientific questions by the complexity of accessing and manipulating the data produced by these machines. Here, we discuss our Genome Analysis Toolkit (GATK), a structured programming framework designed to ease the development of efficient and robust analysis tools for next-generation DNA sequencers using the functional programming philosophy of MapReduce. The GATK provides a small but rich set of data access patterns that encompass the majority of analysis tool needs. Separating specific analysis calculations from common data management infrastructure enables us to optimize the GATK framework for correctness, stability, and CPU and memory efficiency and to enable distributed and shared memory parallelization. We highlight the capabilities of the GATK by describing the implementation and application of robust, scale-tolerant tools like coverage calculators and single nucleotide polymorphism (SNP) calling. We conclude that the GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas. C1 [McKenna, Aaron; Hanna, Matthew; Banks, Eric; Sivachenko, Andrey; Cibulskis, Kristian; Kernytsky, Andrew; Garimella, Kiran; Altshuler, David; Gabriel, Stacey; Daly, Mark; DePristo, Mark A.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Altshuler, David; Daly, Mark] Massachusetts Gen Hosp, Richard B Simches Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. RP DePristo, MA (reprint author), Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM depristo@broadinstitute.org RI Altshuler, David/A-4476-2009; Sincan, Murat /A-3794-2010 OI Altshuler, David/0000-0002-7250-4107; FU National Human Genome Research Institute [54 HG003067, U01 HG005208] FX We thank our colleagues in the Medical and Population Genetics and Cancer Informatics programs at the Broad Institute, who have encouraged and supported us during the development the Genome Analysis Toolkit and have been such enthusiastic early adopters, in particular, Gad Getz, Anthony Philippakis, and Paul de Bakker. We also thank our reviewers for their valuable feedback on the manuscript. This work was supported by grants from the National Human Genome Research Institute, including the Large Scale Sequencing and Analysis of Genomes grant (54 HG003067) and the Joint SNP and CNV calling in 1000 Genomes sequence data grant (U01 HG005208). NR 27 TC 3699 Z9 3744 U1 70 U2 400 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD SEP PY 2010 VL 20 IS 9 BP 1297 EP 1303 DI 10.1101/gr.107524.110 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 646EQ UT WOS:000281520400015 PM 20644199 ER PT J AU Schofield, JW Hausmann, LRM Ye, FF Woods, RL AF Schofield, Janet Ward Hausmann, Leslie R. M. Ye, Feifei Woods, Rochelle L. TI Intergroup friendships on campus: Predicting close and casual friendships between White and African American first-year college students SO GROUP PROCESSES & INTERGROUP RELATIONS LA English DT Article DE intergroup friendships; contact theory ID INTERRACIAL ROOMMATE RELATIONSHIPS; COMMON INGROUP IDENTITY; CROSS-GROUP FRIENDSHIPS; BLACK-AND-WHITE; CONTACT HYPOTHESIS; RACIAL-ATTITUDES; ETHNIC-ATTITUDES; PEER INTERACTION; MEDIATING ROLE; PREJUDICE AB Intergroup friendships have been linked to important outcomes such as reduced prejudice, increased empathy for outgroups, and lower intergroup anxiety. However, little is known about the factors facilitating such friendships. This longitudinal study therefore examined factors associated with the development of friendships between White and African American freshmen at a predominantly White university. African American (vs. White) and male (vs. female) students had more intergroup friendships at the end of freshman year. Friendships between African American and White freshmen were also associated with more direct and indirect intergroup contact during high school, less prejudice upon entering college, having an outgroup roommate (White or African American), having any roommate, and having more contact with outgroup members during the academic year. C1 [Hausmann, Leslie R. M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15206 USA. [Schofield, Janet Ward] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Schofield, Janet Ward] Univ Pittsburgh, Learning Res & Dev Ctr, Pittsburgh, PA 15260 USA. [Ye, Feifei] Univ Pittsburgh, Dept Educ Psychol, Pittsburgh, PA 15260 USA. [Woods, Rochelle L.] Univ Michigan, Off Acad Multicultural Initiat, Ann Arbor, MI 48109 USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM leslie.hausmann@gmail.com NR 59 TC 14 Z9 15 U1 2 U2 11 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1368-4302 J9 GROUP PROCESS INTERG JI Group Process Intergroup Relat. PD SEP PY 2010 VL 13 IS 5 BP 585 EP 602 DI 10.1177/1368430210362437 PG 18 WC Psychology, Social SC Psychology GA 651SZ UT WOS:000281948700004 ER PT J AU Marincevic, M Cahill, N Gunnarsson, R Isaksson, A Mansouri, M Goransson, H Rasmussen, M Jansson, M Ryan, F Karlsson, K Adami, HO Davi, F Jurlander, J Juliusson, G Stamatopoulos, K Rosenquist, R AF Marincevic, Millaray Cahill, Nicola Gunnarsson, Rebeqa Isaksson, Anders Mansouri, Mahmoud Goransson, Hanna Rasmussen, Markus Jansson, Mattias Ryan, Fergus Karlsson, Karin Adami, Hans-Olov Davi, Fred Jurlander, Jesper Juliusson, Gunnar Stamatopoulos, Kostas Rosenquist, Richard TI High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE chronic lymphocytic leukemia; stereotyped B-cell receptors; antigens; leukemogenesis. ID COPY-NUMBER; ANTIGEN RECEPTORS; PATHOGENETIC IMPLICATIONS; MUTATIONAL STATUS; SNP ARRAYS; GENE; ANTIBODIES; SUBSETS; SELECTION; FEATURES AB Background The existence of multiple subsets of chronic lymphocytic leukemia expressing 'stereotyped' B-cell receptors implies the involvement of antigen(s) in leukemogenesis. Studies also indicate that 'stereotypy' may influence the clinical course of patients with chronic lymphocytic leukemia, for example, in subsets with stereotyped IGHV3-21 and IGHV4-34 B-cell receptors; however, little is known regarding the genomic profile of patients in these subsets. Design and Methods We applied 250K single nucleotide polymorphism-arrays to study copy-number aberrations and copy-number neutral loss-of-heterozygosity in patients with stereotyped IGHV3-21 (subset #2, n=29), stereotyped IGHV4-34 (subset #4, n=17; subset #16, n=8) and non-subset #2 ICHV3-21 (n=13) and non-subset #4/16 IGHV4-34 (n=34) patients. Results Over 90% of patients in subset #2 and non-subset #2 carried copy-number aberrations, whereas 75-76% of patients in subset #4 and subset #16 showed copy-number aberrations. Subset #2 and non-subset #2 patients also displayed a higher average number of aberrations compared to patients in subset #4. Deletion of 13q was the only known recurrent aberration detected in subset #4 (35%); this aberration was even more frequent in subset #2 (79%). del(11q) was more frequent in subset #2 and non-subset #2 (31% and 23%) patients than in subset #4 and non-subset #4/16 patients. Recurrent copy-number neutral loss-of-heterozygosity was mainly detected on chromosome 13q, independently of B-cell receptor stereotypy. Conclusions Genomic aberrations were more common in subset #2 and non-subset #2 than in subset #4. The particularly high frequency of del(11q) in subset #2 may be linked to the adverse outcome reported for patients in this subset. Conversely, the lower prevalence of copy-number aberrations and the absence of poor-prognostic aberrations in subset #4 may reflect an inherently low-proliferative disease, which would prevent accumulation of genomic alterations. C1 [Rosenquist, Richard] Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, SE-75185 Uppsala, Sweden. [Cahill, Nicola; Ryan, Fergus] Dublin Inst Technol, Dept Biol Sci, Dublin, Ireland. [Gunnarsson, Rebeqa; Karlsson, Karin; Juliusson, Gunnar] Lund Univ, Dept Lab Med, Stem Cell Ctr, Lund, Sweden. [Isaksson, Anders; Goransson, Hanna; Rasmussen, Markus] Uppsala Univ, Dept Med Sci Canc Pharmacol & Informat, SE-75185 Uppsala, Sweden. [Adami, Hans-Olov] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Adami, Hans-Olov] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Adami, Hans-Olov] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Davi, Fred] Hop La Pitie Salpetriere, Hematol Lab, Paris, France. [Davi, Fred] Univ Paris 06, Paris, France. [Jurlander, Jesper] Rigshosp, Dept Hematol, Leukemia Lab, DK-2100 Copenhagen, Denmark. [Stamatopoulos, Kostas] G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece. [Stamatopoulos, Kostas] G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece. RP Rosenquist, R (reprint author), Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, SE-75185 Uppsala, Sweden. EM richard.rosenquist@genpat.uu.se RI Ryan, Fergus/B-8407-2012; OI Isaksson, Anders/0000-0001-6576-7825 FU Swedish Cancer Society; Swedish Research Council; Medical Faculty of Uppsala University; Uppsala University Hospital; Lion's Cancer Research Foundation in Uppsala, Sweden; ABBEST, Ireland FX Funding: this work was supported by the Swedish Cancer Society, the Swedish Research Council, the Medical Faculty of Uppsala University, Uppsala University Hospital, and Lion's Cancer Research Foundation in Uppsala, Sweden. ABBEST, Ireland, provided a stipend for NC. NR 40 TC 25 Z9 25 U1 0 U2 1 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 SEP PY 2010 VL 95 IS 9 BP 1519 EP 1525 DI 10.3324/haematol.2009.021014 PG 7 WC Hematology SC Hematology GA 651NA UT WOS:000281933200014 PM 20421269 ER PT J AU Nguyen, AD Shenton, ME Levitt, JJ AF Nguyen, An D. Shenton, Martha E. Levitt, James J. TI Olfactory Dysfunction in Schizophrenia: A Review of Neuroanatomy and Psychophysiological Measurements SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID GRAY-MATTER VOLUME; MEDIODORSAL THALAMIC NUCLEUS; MONOZYGOTIC TWINS DISCORDANT; NEUROLEPTIC-NAIVE PATIENTS; ODOR RECOGNITION MEMORY; TEMPORAL-LOBE EPILEPSY; 1ST-DEGREE RELATIVES; IDENTIFICATION ABILITY; DEFICIT SYNDROME; 1ST-EPISODE SCHIZOPHRENIA AB Olfactory processing is thought to be mediated via the frontal and temporolimbic brain regions, both of which, as well as olfactory dysfunction, are implicated in schizophrenia. Likewise, several empirical studies of olfactory dysfunction-in particular, olfactory deficits in identification, odor detection threshold sensitivity, and odor memory, along with associated brain structural changes-have been conducted to illuminate the pathophysiology of schizophrenia. These anomalies have been investigated, more recently, as possible biological markers of that disabling illness. This article summarizes recent research on neuroimaging changes associated with olfactory impairments in schizophrenia patients and on related functional changes in psychophysiological measurements (e.g., odor identification, odor discrimination, odor detection threshold, and odor memory). The possible role of these changes as biological markers of the disorder will be discussed, as will potentially productive directions for future research. 0.05). None of the variants at the other 6 loci were associated with NAFLD. Conclusion: Genetic variation at PNPLA3 confers a markedly increased risk of increasingly severe histological features of NAFLD, without a strong effect on metabolic syndrome component traits. (HEPATOLOGY 2010;52:904-912) C1 [Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Speliotes, Elizabeth K.; Butler, Johannah L.; Palmer, Cameron D.; Voight, Benjamin F.; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet & Metab Initiat, Cambridge, MA USA. [Butler, Johannah L.; Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Butler, Johannah L.; Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Butler, Johannah L.; Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Voight, Benjamin F.] Massachusetts Gen Hosp Boston, Dept Mol Med, Boston, MA USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Speliotes, EK (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM espeliotes@partners.org RI Voight, Benjamin/F-1775-2011 FU National Institutes of Health (NIH) [T32 DK07191-32, F32 DK079466-01, K23DK080145-01, R01DK075787]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713]; National Institute of Child Health and Human Development (NICHD); General Clinical Research Centers [UL1RR024989, M01RR000750, M01RR00188, ULRR02413101, M01RR000827, UL1RR02501401, M01RR000065, M01RR020359]; US National Institutes of Health (NIH); National Heart, Lung, and Blood Institute FX This work was partially supported by National Institutes of Health (NIH) grants T32 DK07191-32 to Daniel Podolsky (for EKS), F32 DK079466-01 to EKS and NIH K23DK080145-01 to EKS and R01DK075787 to INN. The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713), and the National Institute of Child Health and Human Development (NICHD). Several clinical centers use support from General Clinical Research Centers or Clinical and Translational Science Awards in conduct of NASH CRN Studies (grants UL1RR024989, M01RR000750, M01RR00188, ULRR02413101, M01RR000827, UL1RR02501401, M01RR000065, M01RR020359). The MIGen study was funded by the US National Institutes of Health (NIH) and National Heart, Lung, and Blood Institute's STAMPEED genomics research program. NR 28 TC 171 Z9 174 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2010 VL 52 IS 3 BP 904 EP 912 DI 10.1002/hep.23768 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 645AJ UT WOS:000281423000013 PM 20648472 ER PT J AU Moriguchi, H Chung, RT Mihara, M Sato, C AF Moriguchi, Hisashi Chung, Raymond T. Mihara, Makoto Sato, Chifumi TI Generation of Human Induced Pluripotent Stem Cells from Liver Progenitor Cells by Only Small Molecules SO HEPATOLOGY LA English DT Letter C1 [Moriguchi, Hisashi; Mihara, Makoto] Tokyo Univ Hosp, Dept Plast & Reconstruct Surg, Tokyo 113, Japan. [Moriguchi, Hisashi; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Moriguchi, Hisashi; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Moriguchi, Hisashi; Sato, Chifumi] Tokyo Med & Dent Univ, Dept Analyt Sci, Tokyo, Japan. RP Moriguchi, H (reprint author), Tokyo Univ Hosp, Dept Plast & Reconstruct Surg, Tokyo 113, Japan. NR 3 TC 4 Z9 4 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2010 VL 52 IS 3 BP 1169 EP 1169 DI 10.1002/hep.23851 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 645AJ UT WOS:000281423000039 PM 20812362 ER PT J AU Sax, PE Sloan, CE Schackman, BR Grant, PM Rong, JA Zolopa, AR Powderly, W Losina, E Freedberg, KA AF Sax, Paul E. Sloan, Caroline E. Schackman, Bruce R. Grant, Philip M. Rong, Jian Zolopa, Andrew R. Powderly, William Losina, Elena Freedberg, Kenneth A. CA CEPAC US & ACTG A5164 Investigator TI Early Antiretroviral Therapy for Patients With Acute AIDS-Related Opportunistic Infections: A Cost-Effectiveness Analysis of ACTG A5164 SO HIV CLINICAL TRIALS LA English DT Article DE antiretroviral therapy; HIV; cost; cost-effectiveness; opportunistic infection ID RECONSTITUTION INFLAMMATORY SYNDROME; EXPERIENCED HIV-1-INFECTED PATIENTS; MULTIPLE VIROLOGICAL FAILURES; RESISTANT HIV-1 INFECTION; PLACEBO-CONTROLLED TRIAL; RAPID RESPONSE TEAM; CRYPTOCOCCAL MENINGITIS; TMC125 ETRAVIRINE; RISK-FACTORS; DOUBLE-BLIND AB Purpose: ACTG A5164 demonstrated that early antiretroviral therapy (ART) in HIV-infected patients with acute opportunistic infections (OIs) reduced death and AIDS progression compared to ART initiation 1 month later. We project the life expectancies, costs, and incremental cost-effectiveness ratios (ICERs) of these strategies. Method: Using an HIV simulation model, we compared 2 strategies for patients with acute OIs: (1) an intervention to deliver early ART, and (2) deferred ART. Parameters from ACTG A5164 included initial mean CD4 count (47/mu L), linkage to outpatient care (87%), and immune reconstitution inflammatory syndrome 1 month after ART initiation (7%). The estimated intervention cost was $1,650/patient. Results: Early ART lowered projected 1-year mortality from 10.4% to 8.2% and increased life expectancy from 10.07 to 10.39 quality-adjusted life-years (QALYs). Lifetime costs increased from $385,220 with deferred ART to $397,500 with early ART, primarily because life expectancy increased, producing an ICER of $38,600/QALY. Results were most sensitive to increased intervention cost and decreased virologic efficacy in the early ART strategy. Conclusions: An intervention to initiate ART early in patients with acute OIs improves survival and meets US cost-effectiveness thresholds. Programs should be developed to implement this strategy at sites where HIV-infected patients present with OIs. C1 [Sax, Paul E.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Sax, Paul E.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA. [Sloan, Caroline E.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Grant, Philip M.; Zolopa, Andrew R.] Stanford Univ, Dept Infect Dis, Stanford, CA 94305 USA. [Rong, Jian] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Zolopa, Andrew R.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Powderly, William] Univ Coll Dublin, Sch Med & Med Sci, Belfield, Ireland. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Sax, PE (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. EM psax@partners.org FU National Institute of Allergy and Infectious Diseases [R37 AI042006, K24 AI062476, U01 AI068636]; Weill Cornell Medical College AIDS Clinical Trials Unit (ACTU) [U01 AI069419]; Stanford University School of Medicine AIDS Clinical Trials Unit [AI027666, AI069556]; AIDS Clinical Trials Group; Gilead; Merck; Tibotec; GlaxoSmithKline; Bristol-Myers Squibb; Gilead Sciences; Pfizer; VIRxSYS FX Supported by the National Institute of Allergy and Infectious Diseases (R37 AI042006, K24 AI062476, U01 AI068636), the Weill Cornell Medical College AIDS Clinical Trials Unit (ACTU; U01 AI069419), the Stanford University School of Medicine AIDS Clinical Trials Unit (AI027666, AI069556), and the AIDS Clinical Trials Group.; Dr. Sax has been a consultant for Abbott, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck, Tibotec, and ViiV. He has received grant support from Gilead, Merck, and Tibotec. Dr. Grant has received grant support from GlaxoSmithKline and Bristol-Myers Squibb. Dr. Zolopa is a consultant for Bristol-Myers Squibb, Gilead Sciences, Tibotec, and Pfizer and has received grant support from Merck, Bristol-Myers Squibb, Gilead Sciences, Pfizer, and VIRxSYS. NR 49 TC 8 Z9 9 U1 0 U2 1 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD SEP-OCT PY 2010 VL 11 IS 5 BP 248 EP 259 DI 10.1310/hct1105-248 PG 12 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 686FE UT WOS:000284681400002 PM 21126955 ER PT J AU Geevarghese, SK Geller, DA de Haan, HA Horer, M Knoll, AE Mescheder, A Nemunaitis, J Reid, TR Sze, DY Tanabe, KK Tawfik, H AF Geevarghese, Sunil K. Geller, David A. de Haan, Hans A. Hoerer, Markus Knoll, Anette E. Mescheder, Axel Nemunaitis, John Reid, Tony R. Sze, Daniel Y. Tanabe, Kenneth K. Tawfik, Hoda TI Phase I/II Study of Oncolytic Herpes Simplex Virus NV1020 in Patients with Extensively Pretreated Refractory Colorectal Cancer Metastatic to the Liver SO HUMAN GENE THERAPY LA English DT Article ID VIRAL THERAPY; TYPE-1 G207; CELLS; CARCINOMA; COMBINATION; IRINOTECAN; MANAGEMENT; ADENOVIRUS; RESISTANT; EFFICACY AB This multicenter phase I/II study evaluated the safety, pharmacokinetics, and antitumor effects of repeated doses of NV1020, a genetically engineered oncolytic herpes simplex virus, in patients with advanced metastatic colorectal cancer (mCRC). Patients with liver-dominant mCRC received four fixed NV1020 doses via weekly hepatic artery infusion, followed by two or more cycles of conventional chemotherapy. Phase I included cohorts receiving 3x10(6), 1x10(7), 3x10(7), and 1x10(8) plaque-forming units (PFU)/dose to determine the optimal biological dose (OBD) for phase II. Blind independent computed tomography scan review was based on RECIST (response evaluation criteria in solid tumors) to assess hepatic tumor response. Phase I and II enrolled 13 and 19 patients, respectively. Patients experienced transient mild-moderate febrile reactions after each NV1020 infusion. Grade 3/4 virus-related toxicity was limited to transient lymphopenia in two patients. NV1020 shedding was not detected. Simultaneous cytokine and grade 1 coagulation perturbations were dose-limiting at 1x10(8) PFU/dose, considered the OBD. All 22 OBD patients had previously received 5-fluorouracil; most had received oxaliplatin or irinotecan (50% had both), many with at least one targeted agent. After NV1020 administration, 50% showed stable disease. The best overall tumor control rate after chemotherapy was 68% (1 partial response, 14 stable disease); this did not correlate with baseline variables or chemotherapy. Median time to progression was 6.4 months (95% confidence interval: 2, 8.9); median overall survival was 11.8 months (95% confidence interval: 8.3, 20.7). One-year survival was 47.2%. We conclude that NV1020 stabilizes liver metastases with minimal toxicity in mCRC. It may resensitize metastases to salvage chemotherapy and extend overall survival. A randomized phase II/III trial now appears justified. C1 [Reid, Tony R.] Univ Calif San Diego, Div Hematol & Oncol, Dept Med, La Jolla, CA 92093 USA. [Geevarghese, Sunil K.] Vanderbilt Univ, Dept Hepatobiliary Surg & Liver Transplantat, Nashville, TN 37232 USA. [Geller, David A.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, S Pittsburgh, PA 15213 USA. [de Haan, Hans A.] MediGene, Clin Res, San Diego, CA 92030 USA. [Hoerer, Markus; Knoll, Anette E.; Mescheder, Axel; Tawfik, Hoda] MediGene, D-82152 Martinsried, Germany. [Nemunaitis, John] Mary Crowley Med Res Ctr, Dallas, TX 75201 USA. [Sze, Daniel Y.] Stanford Univ, Med Ctr, Div Intervent Radiol, Stanford, CA 94305 USA. [Tanabe, Kenneth K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Div Surg Oncol, Boston, MA 02114 USA. RP Reid, TR (reprint author), Univ Calif San Diego, Div Hematol & Oncol, Dept Med, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA. EM tonyreid@ucsd.edu FU MediGene, Inc. FX For S. K. G., no competing financial interests exist (Vanderbilt University received research funding for this study).; For D. A. G, no competing financial interests exist (the University of Pittsburgh received research funding for this study). H.A.d.H. received consulting fees from MediGene, Inc. M. H. is a paid employee of MediGene AG. A. E. K. is a paid employee of MediGene AG. A. M. is a paid employee of MediGene AG and holds stock in the company. For J.N., no competing financial interests exist (the Mary Crowley Medical Research Center received research funding for this study). For T. R. R, no competing financial interests exist (UCSD received research funding for this study). D.Y.S. received consulting fees from MediGene, Inc. For K. K. T., no competing financial interests exist (Harvard Medical School received research funding for this study). H. T. is a paid employee of MediGene AG. NR 48 TC 44 Z9 52 U1 1 U2 6 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 SEP PY 2010 VL 21 IS 9 BP 1119 EP 1128 DI 10.1089/hum.2010.020 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 648UU UT WOS:000281720700012 PM 20486770 ER PT J AU Pendse, GV Baumgartner, R Schwarz, AJ Coimbra, A Borsook, D Becerra, L AF Pendse, Gautam V. Baumgartner, Richard Schwarz, Adam J. Coimbra, Alexandre Borsook, David Becerra, Lino TI A Statistical Framework for Optimal Design Matrix Generation With Application to fMRI SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Bias variance tradeoff; design matrix; functional magnetic resonance imaging (fMRI); general linear model (GLM); optimization; residual ID QUASI-NEWTON MATRICES; HEMODYNAMIC-RESPONSE; OPTIMIZATION; PERMUTATION; LATENCY; ALGORITHM; TESTS AB The general linear model (GLM) is a well established tool for analyzing functional magnetic resonance imaging (fMRI) data. Most fMRI analyses via GLM proceed in a massively univariate fashion where the same design matrix is used for analyzing data from each voxel. A major limitation of this approach is the locally varying nature of signals of interest as well as associated confounds. This local variability results in a potentially large bias and uncontrolled increase in variance for the contrast of interest. The main contributions of this paper are two fold: 1) we develop a statistical framework that enables estimation of an optimal design matrix while explicitly controlling the bias variance decomposition over a set of potential design matrices and 2) we develop and validate a numerical algorithm for computing optimal design matrices for general fMRI data sets. The implications of this framework include the ability to match optimally the magnitude of underlying signals to their true magnitudes while also matching the "null" signals to zero size thereby optimizing both the sensitivity and specificity of signal detection. By enabling the capture of multiple profiles of interest using a single contrast (as opposed to an F-test) in a way that optimizes for both bias and variance enables the passing of first level parameter estimates and their variances to the higher level for group analysis which is not possible using F-tests. We demonstrate the application of this approach to in vivo pharmacological fMRI data capturing the acute response to a drug infusion, to task-evoked, block design fMRI and to the estimation of a haemodynamic response function (HRF) in event-related fMRI. Although developed with motivation from fMRI, our framework is quite general and has potentially wide applicability to a variety of disciplines. C1 [Pendse, Gautam V.; Borsook, David; Becerra, Lino] Harvard Univ, McLean Hosp, Sch Med, Imaging & Anal Grp IMAG, Belmont, MA 02478 USA. [Pendse, Gautam V.; Baumgartner, Richard; Schwarz, Adam J.; Coimbra, Alexandre; Borsook, David; Becerra, Lino] McLean Hosp, Imaging Consortium Drug Dev ICD, Belmont, MA 02478 USA. [Baumgartner, Richard] Merck Res Labs, Biometr Res, Rahway, NJ 07065 USA. [Schwarz, Adam J.] Lilly Res Labs, Translat Imaging Grp, Indianapolis, IN 46225 USA. [Coimbra, Alexandre] Merck Res Labs, Dept Imaging, West Point, PA 19486 USA. [Borsook, David; Becerra, Lino] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Pendse, GV (reprint author), Harvard Univ, McLean Hosp, Sch Med, Imaging & Anal Grp IMAG, Belmont, MA 02478 USA. EM gpendse@mclean.harvard.edu FU Imaging Consortium for Drug development (ICD) FX This work was supported by the Imaging Consortium for Drug development (ICD). NR 25 TC 2 Z9 2 U1 0 U2 4 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 SEP PY 2010 VL 29 IS 9 BP 1573 EP 1611 DI 10.1109/TMI.2010.2044512 PG 39 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 667VA UT WOS:000283222600001 PM 20304726 ER PT J AU Yeh, FC Wedeen, VJ Tseng, WYI AF Yeh, Fang-Cheng Wedeen, Van Jay Tseng, Wen-Yih Isaac TI Generalized q-Sampling Imaging SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Diffusion magnetic resonance imaging (MRI); diffusion q-space imaging; generalized q-sampling imaging; quantitative anisotropy ID GAUSSIAN WATER DIFFUSION; HUMAN BRAIN; SPHERICAL DECONVOLUTION; WHITE-MATTER; MRI DATA; FIBER ORIENTATIONS; TENSOR MRI; TRACTOGRAPHY; ARCHITECTURE; INFERENCE AB Based on the Fourier transform relation between diffusion magnetic resonance (MR) signals and the underlying diffusion displacement, a new relation is derived to estimate the spin distribution function (SDF) directly from diffusion MR signals. This relation leads to an imaging method called generalized q-sampling imaging (GQI), which can obtain the SDF from the shell sampling scheme used in q-ball imaging (QBI) or the grid sampling scheme used in diffusion spectrum imaging (DSI). The accuracy of GQI was evaluated by a simulation study and an in vivo experiment in comparison with QBI and DSI. The simulation results showed that the accuracy of GQI was comparable to that of QBI and DSI. The simulation study of GQI also showed that an anisotropy index, named quantitative anisotropy, was correlated with the volume fraction of the resolved fiber component. The in vivo images of GQI demonstrated that SDF patterns were similar to the ODFs reconstructed by QBI or DSI. The tractography generated from GQI was also similar to those generated from QBI and DSI. In conclusion, the proposed GQI method can be applied to grid or shell sampling schemes and can provide directional and quantitative information about the crossing fibers. C1 [Tseng, Wen-Yih Isaac] Natl Taiwan Univ Hosp, Dept Med Imaging, Taipei 100, Taiwan. [Yeh, Fang-Cheng] Carnegie Mellon Univ, Dept Biomed Engn, Pittsburgh, PA 15213 USA. [Wedeen, Van Jay] Harvard Univ, Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA. RP Tseng, WYI (reprint author), Natl Taiwan Univ Hosp, Dept Med Imaging, Taipei 100, Taiwan. EM frankyeh@cmu.edu; van@nmr.mgh.harvard.edu; wytseng@ntu.edu.tw RI Yeh, Fang-Cheng/E-9698-2012; OI Yeh, Fang-Cheng/0000-0002-7946-2173; Tseng, Wen-Yih Isaac/0000-0002-2314-6868 FU National Science Council, Taiwan [NSC95-2752-M-002-018-PAE] FX This work was supported by the National Science Council, Taiwan (NSC95-2752-M-002-018-PAE). NR 41 TC 107 Z9 109 U1 0 U2 14 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 SEP PY 2010 VL 29 IS 9 BP 1626 EP 1635 DI 10.1109/TMI.2010.2045126 PG 10 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 667VA UT WOS:000283222600003 PM 20304721 ER PT J AU Das, KK Nishino, HT Chan, AT AF Das, Koushik K. Nishino, Ha Thanh Chan, Andrew T. TI Treatment-associated Acute Myeloid Leukemia in a Patient with Crohn's Disease on 6-Mercaptopurine SO INFLAMMATORY BOWEL DISEASES LA English DT Letter ID INFLAMMATORY-BOWEL-DISEASE C1 [Das, Koushik K.; Chan, Andrew T.] Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. [Nishino, Ha Thanh] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Das, KK (reprint author), Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. FU NCI NIH HHS [K07 CA107412-05, K07 CA107412] NR 9 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2010 VL 16 IS 9 BP 1454 EP 1456 DI 10.1002/ibd.21205 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 648IU UT WOS:000281686900004 PM 20128002 ER PT J AU Dearling, JLJ Park, EJ Dunning, P Baker, A Fahey, F Treves, ST Soriano, SG Shimaoka, M Packard, AB Peer, D AF Dearling, Jason L. J. Park, Eun Jeong Dunning, Patricia Baker, Amanda Fahey, Frederic Treves, S. Ted Soriano, Sulpicio G. Shimaoka, Motomu Packard, Alan B. Peer, Dan TI Detection of Intestinal Inflammation by MicroPET Imaging Using a Cu-64-Labeled Anti-beta(7) lntegrin Antibody SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE colitis; inflammatory bowel disease; radioimmunodetection; integrin targeting; copper-64 ID DEXTRAN SULFATE SODIUM; EXPERIMENTAL COLITIS; ULCERATIVE-COLITIS; BOWEL-DISEASE; NUCLEAR-MEDICINE; T-CELLS; IN-VIVO; LOCALIZATION; LYMPHOCYTES; LIPOSOMES AB Background: The primary function of integrin beta(7) is the recruitment and retention of lymphocytes to the inflamed gut. The aim of this study was to investigate the possibility of imaging colitis radioimmunodetection by targeting the beta(7) integrin with a radiolabeled antibody. Methods: FIB504.64, a monoclonal antibody that binds to beta(7) integrin, was conjugated with a bifunctional chelator and labeled with Cu-64. The antibody (50 mu g, 7 MBq) was injected into C57BL/6 mice with experimentally induced colitis (n = 6). MicroPET images were collected at 1, 24, and 48 hours postinjection and the biodistribution was measured at 48 hours by tissue assay. Data were also obtained for a Cu-64-labeled nonspecific iso-type-matched antibody in mice with colitis and 64Cu-labeled FIB504.64 in healthy mice (n = 5-6). Results: The microPET images showed higher uptake of Cu-64-labeled FIB504.64 in the gut of mice with colitis than for either of the controls. This observation was confirmed by the 48-hour ex vivo biodistribution data: the percentage of injected dose per gram of tissue (%ID/g +/- SD) (large intestine) colitis mice with Cu-64-labeled FIB504.64, 6.49 +/- 2.25; control mice with Cu-64-labeled FIB504.64, 3.64 +/- 1.12; colitis mice, Cu-64-labeled nonspecific antibody 3.97 +/- 0.48%ID/g (P < 0.05 between groups). Conclusions: The selective uptake of Cu-64-labeled FIB504.64 antibody in the gut of animals with colitis suggests that integrin beta(7) may be a promising target for radioimmunodetection of this disease, which would aid diagnosis, assessment, and therapy guidance of this disease. C1 [Dearling, Jason L. J.; Dunning, Patricia; Baker, Amanda; Fahey, Frederic; Treves, S. Ted; Packard, Alan B.] Childrens Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02115 USA. [Dearling, Jason L. J.; Park, Eun Jeong; Fahey, Frederic; Treves, S. Ted; Soriano, Sulpicio G.; Shimaoka, Motomu; Packard, Alan B.] Harvard Univ, Sch Med, Boston, MA USA. [Park, Eun Jeong; Soriano, Sulpicio G.; Shimaoka, Motomu] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Park, Eun Jeong; Soriano, Sulpicio G.; Shimaoka, Motomu] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Soriano, Sulpicio G.] Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Peer, Dan] Tel Aviv Univ, George S Wise Fac Life Sci, Lab Nanomed, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. [Peer, Dan] Tel Aviv Univ, Ctr Nanosci & Nanotechnol, IL-69978 Tel Aviv, Israel. RP Dearling, JLJ (reprint author), Childrens Hosp, Dept Radiol, Div Nucl Med, 300 Longwood Ave, Boston, MA 02115 USA. EM jason.dearling@childrens.harvard.edu; peer@post.tau.ac.il RI Peer, Dan/A-1785-2011 OI Peer, Dan/0000-0001-8238-0673 FU NIH [RC1 DK087348, AI063421, HL048675]; The Leukemia and Lymphoma Society [6004]; Alon Foundation; European Union [IRG-FP7]; National Cancer Institute [R24CA86307]; CHMC Anesthesia Foundation FX Supported by NIH Grant RC1 DK087348 (JD, MS and ABP) CHMC Anesthesia Foundation (to S.G.S.), National Institutes of Health, AI063421 and HL048675, and The Leukemia and Lymphoma Society (#6004) (to M.S.), Alon Foundation, and IRG-FP7, European Union (to D.P.). Copper-64 was produced at Washington University School of Medicine (St. Louis, MO), under the support of National Cancer Institute Grant R24CA86307. NR 32 TC 7 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2010 VL 16 IS 9 BP 1458 EP 1466 DI 10.1002/ibd.21231 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 648IU UT WOS:000281686900006 PM 20186943 ER PT J AU Lu, WD Posner, MR Wayne, P Rosenthal, DS Haddad, RI AF Lu, Weidong Posner, Marshall R. Wayne, Peter Rosenthal, David S. Haddad, Robert I. TI Acupuncture for Dysphagia After Chemoradiation Therapy in Head and Neck Cancer: A Case Series Report SO INTEGRATIVE CANCER THERAPIES LA English DT Article DE acupuncture; chemoradiation therapy; radiation therapy; head and neck cancer; dysphagia; percutaneous endoscopic gastrostomy (PEG) tube ID LOCALLY ADVANCED HEAD; QUALITY-OF-LIFE; RADIATION-INDUCED XEROSTOMIA; ORGAN PRESERVATION; INTRAARTERIAL CHEMORADIATION; INDUCTION CHEMOTHERAPY; OROPHARYNGEAL CANCER; RADIOTHERAPY; CHEMORADIOTHERAPY; IMPACT AB Background: Dysphagia is a common side effect following chemoradiation therapy (CRT) in patients with head and neck cancer (HNC). Methods: In this retrospective case series, 10 patients with HNC were treated with acupuncture for radiation-induced dysphagia and xerostomia. All patients were diagnosed with stage III/IV squamous cell carcinoma. In all, 7 of 10 patients were percutaneous endoscopic gastrostomy (PEG) tube dependent when they began acupuncture. Manual acupuncture and electroacupuncture were used once a week. Results: A total of 9 of 10 patients reported various degrees of subjective improvement in swallowing functions, xerostomia, pain, and fatigue levels. Overall, 6 (86%) of 7 PEG tube-dependent patients had their feeding tubes removed after acupuncture, with a median duration of 114 days (range 49 to 368 days) post CRT. One typical case is described in detail. Conclusions: A relatively short PEG tube duration and reduced symptom severity following CRT were observed in these patients. Formal clinical trials are required to determine the causality of the observations. C1 [Lu, Weidong] Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, Boston, MA 02115 USA. [Lu, Weidong; Wayne, Peter] Harvard Univ, Sch Med, Boston, MA USA. RP Lu, WD (reprint author), Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, 44 Binney St, Boston, MA 02115 USA. EM weidong_lu@dfci.harvard.edu RI Lu, Weidong/C-3844-2008 OI Lu, Weidong/0000-0003-2838-6307 FU National Center for Complementary and Alternative Medicine (NCCAM) [1K01AT004415-01] FX This work was supported by the National Center for Complementary and Alternative Medicine (NCCAM) Grant No. 1K01AT004415-01. NR 39 TC 10 Z9 11 U1 6 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-7354 J9 INTEGR CANCER THER JI Integr. Cancer Ther. PD SEP PY 2010 VL 9 IS 3 BP 284 EP 290 DI 10.1177/1534735410378856 PG 7 WC Oncology; Integrative & Complementary Medicine SC Oncology; Integrative & Complementary Medicine GA 653LD UT WOS:000282091900007 PM 20713374 ER PT J AU Alia, I de la Cal, MA Esteban, A Ferrer, R Molina, F Piner, R Anzueto, A AF Alia, I. de la Cal, M. A. Esteban, A. Ferrer, R. Molina, F. Piner, R. Anzueto, A. TI EVALUATION OF THE EFFICACY OF CORTICOSTEROIDS IN PATIENTS WITH AN ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE RECEIVING VENTILATORY SUPPORT: A PROSPECTIVE, INTERNATIONAL, RANDOMIZED DOUBLE BLIND CLINICAL TRIAL SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-of-Intensive-Care-Medicine CY OCT 09-13, 2010 CL Barcelona, SPAIN SP European Soc Intens Care Med C1 [Alia, I.; de la Cal, M. A.; Esteban, A.] Hosp Univ Getafe, Intens Care Unit, Getafe, Spain. [Ferrer, R.] Hosp Parc Tauli Sabadell, Intens Care Unit, Barcelona, Spain. [Molina, F.] Clin Univ Bolivariana, Intens Care Unit, Medellin, Colombia. [Piner, R.] Hosp Clin Barcelona, Intens Care Unit, Barcelona, Spain. [Anzueto, A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2010 VL 36 SU 2 MA 0474 BP S205 EP S205 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 648GS UT WOS:000281679500475 ER PT J AU Bloom, JD Lu, M Sigl, J Hansell, DM AF Bloom, J. D. Lu, M. Sigl, J. Hansell, D. M. TI POSTOPERATIVE NALOXONE RESCUE FOLLOWING PARENTERAL OPIOIDS AFTER ABDOMINAL SURGERY: INCIDENCE AND COHORT MORBIDITY AND MORTALITY SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-of-Intensive-Care-Medicine CY OCT 09-13, 2010 CL Barcelona, SPAIN SP European Soc Intens Care Med C1 [Bloom, J. D.; Hansell, D. M.] Covidien, Boulder, CO USA. [Lu, M.; Sigl, J.] Covidien, Norwood, MA USA. [Hansell, D. M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. 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 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2010 VL 36 SU 2 MA 0787 BP S283 EP S283 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 648GS UT WOS:000281679500788 ER PT J AU Sulemanji, DS Marchese, A Wysocki, M Kacmarek, R AF Sulemanji, D. S. Marchese, A. Wysocki, M. Kacmarek, R. TI ADAPTIVE SUPPORT VENTILATION WITH END-TIDAL CO2 CLOSED LOOP CONTROL VS. CONVENTIONAL VENTILATION SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT 23rd Annual Meeting of the European-Society-of-Intensive-Care-Medicine CY OCT 09-13, 2010 CL Barcelona, SPAIN SP European Soc Intens Care Med C1 [Sulemanji, D. S.; Kacmarek, R.] Harvard Univ, Sch Med, Boston, MA USA. [Sulemanji, D. S.; Kacmarek, R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Sulemanji, D. S.; Marchese, A.; Kacmarek, R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Wysocki, M.] Hamilton, Bonaduz, Sweden. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2010 VL 36 SU 2 MA 0084 BP S106 EP S106 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 648GS UT WOS:000281679500085 ER PT J AU Reuter, M AF Reuter, Martin TI Hierarchical Shape Segmentation and Registration via Topological Features of Laplace-Beltrami Eigenfunctions SO INTERNATIONAL JOURNAL OF COMPUTER VISION LA English DT Article DE Laplace-Beltrami operator; Hierarchical mesh segmentation; Eigenfunctions; Persistence; Morse-Smale complex ID MESH SEGMENTATION; SIZE FUNCTIONS; SURFACES; RECOGNITION; SPECTRA; POINT; MAPS AB This work introduces a method to hierarchically segment articulated shapes into meaningful parts and to register these parts across populations of near-isometric shapes (e.g. head, arms, legs and fingers of humans in different body postures). The method exploits the isometry invariance of eigenfunctions of the Laplace-Beltrami operator and uses topological features (level sets at important saddles) for the segmentation. Concepts from persistent homology are employed for a hierarchical representation, for the elimination of topological noise and for the comparison of eigenfunctions. The obtained parts can be registered via their spectral embedding across a population of near isometric shapes. This work also presents the highly accurate computation of eigenfunctions and eigenvalues with cubic finite elements on triangle meshes and discusses the construction of persistence diagrams from the Morse-Smale complex as well as the relation to size functions. C1 [Reuter, Martin] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Reuter, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM reuter@mit.edu RI Reuter, Martin/B-3456-2010 OI Reuter, Martin/0000-0002-2665-9693 FU Alexander von Humboldt Foundation FX This work has been funded by a Feodor Lynen fellowship of the Alexander von Humboldt Foundation. The author would like to thank Dr. Nicholas and M. Patrikalakis, MIT, for hosting this research and Dr. Herbert Edelsbrunner, Duke University, for his valuable comments. NR 64 TC 56 Z9 59 U1 1 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-5691 J9 INT J COMPUT VISION JI Int. J. Comput. Vis. PD SEP PY 2010 VL 89 IS 2-3 SI SI BP 287 EP 308 DI 10.1007/s11263-009-0278-1 PG 22 WC Computer Science, Artificial Intelligence SC Computer Science GA 594OS UT WOS:000277547600010 ER PT J AU Lima, XT Kimball, AB Lima, HC de Souza, RCA de Carvalho, VO AF Lima, Xinaida Taligare Kimball, Alexandra Boer Lima, Hermenio Cavalcante Almada de Souza, Rosilene Canzi de Carvalho, Vania Oliveira TI Assessing dermatology board examination competence using questions distribution: a 12-year Brazilian experience SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Letter C1 [Lima, Xinaida Taligare; Kimball, Alexandra Boer; Lima, Hermenio Cavalcante] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Almada de Souza, Rosilene Canzi] Fac Evangelica Parana, Dept Internal Med, Dermatol Unit, Curitiba, Parana, Brazil. [de Carvalho, Vania Oliveira] Univ Fed Parana, Clin Hosp, Pediat Dermatol Div, Curitiba, Parana, Brazil. RP Lima, XT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Suite Boston, Boston, MA 02115 USA. EM jhlima@partners.org RI Lima, Hermenio/A-1616-2010; Lima, Hermenio/G-5379-2010; Carvalho, Vania/H-1870-2013 OI Lima, Hermenio/0000-0003-0950-3731; Carvalho, Vania/0000-0002-4578-8781 NR 5 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD SEP PY 2010 VL 49 IS 9 BP 1080 EP 1082 PG 3 WC Dermatology SC Dermatology GA 644UR UT WOS:000281407300025 PM 20883278 ER PT J AU Bonab, AA Carter, EA Paul, K Kaneki, M Yu, YM Tompkins, RG Fischman, AJ AF Bonab, Ali A. Carter, Edward A. Paul, Kasie Kaneki, Masao Yu, Yong-Ming Tompkins, Ronald G. Fischman, Alan J. TI Effect of simvastatin on burn-induced alterations in tissue specific glucose metabolism: Implications for burn associated insulin resistance SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE burn; glucose; (18)F labeled 2-fluoro-2-deoxy-D-glucose; insulin resistance; brown adipose tissue; simvastatin; sepsis ID ADIPOSE-TISSUE; SKELETAL-MUSCLE; RATS; PRAVASTATIN; EXPRESSION; PATHWAY; SEPSIS AB In addition to their primary role in lowering plasma cholesterol, statins have a variety of other actions. We studied the effect of simvastatin treatment on burn injury-induced changes in regional glucose metabolism. Groups of six CD-1 mice (male, 25 g) were subjected to full thickness 30% total body surface area (TBSA) burn injury. The animals were treated with simvastatin at various doses (0.02, 0.2 and 2.0 mu g/kg, i.p.) for seven days. The following morning, mice were injected with (18)F labeled 2-fluoro-2-deoxy-D-glucose ((18)FDG) (50 mu Ci) via the tail vein. Approximately 60 min after tracer injection, the animals were sacrificed and biodistribution was measured. A sub-set of burned mice with and without statin treatment and sham controls was injected with similar to 1.0 mCi of FDG and tracer distribution was evaluated by mu PET. In addition, oral glucose tolerance tests (OGTT) were performed in other groups of burned mice with and without statin treatment and sham controls. In the heart and brown adipose tissue (BAT), burn injury produced a highly significant increase in (18)FDG accumulation (p<0.01), whereas tracer accumulation in brain was markedly reduced (p<0.01). In the heart and BAT, simvastatin treatment produced dose-dependent reductions in (18)FDG accumulation. In contrast, simvastatin did not affect (18)FDG accumulation in the brain. There was no effect of simvastatin treatment on (18)FDG accumulation in the heart, BAT or brain of sham-treated mice. Less pronounced effects were detected in other tissues that were studied. All animals had normal plasma glucose levels (similar to 90 mg/dl). The OGTTs demonstrated insulin resistance in burn injured mice which was reversed by statin treatment. Our results indicate that simvastatin reverses burn-induced increases in (18)FDG accumulation by the heart and BAT in a close-dependent manner but does not affect burn-induced reductions of (18)FDG accumulation by the brain. These findings suggest that statins exert some of their effects by tissue specific modulation of glucose metabolism. C1 [Bonab, Ali A.; Carter, Edward A.; Paul, Kasie; Kaneki, Masao; Yu, Yong-Ming; Tompkins, Ronald G.; Fischman, Alan J.] Shriners Hosp Children, Boston, MA 02114 USA. [Carter, Edward A.; Yu, Yong-Ming; Tompkins, Ronald G.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Bonab, Ali A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Nucl Med, Boston, MA USA. [Kaneki, Masao] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fischman, AJ (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM aajjff@gmail.com FU National Institutes of Health [2P50 GM21700-27A]; Shriners Hospitals for Children [8540] FX This study was supported in part by grants from the National Institutes of Health (2P50 GM21700-27A) and Shriners Hospitals for Children (#8540). NR 20 TC 6 Z9 6 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD SEP PY 2010 VL 26 IS 3 BP 311 EP 316 DI 10.3892/ijmm_00000467 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 635RL UT WOS:000280673700001 PM 20664945 ER PT J AU Steinhauer, SR Siegle, GJ Condray, R Chakraborty, BH AF Steinhauer, Stuart R. Siegle, Greg J. Condray, Ruth Chakraborty, Beatrice H. TI Working memory deficits in schizophrenia are reflected by deficits in pupillary dilation SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 15th World Congress of Psychophysiology CY SEP 01-04, 2010 CL Budapest, HUNGARY SP Int Org Psychophysiol C1 [Steinhauer, Stuart R.; Siegle, Greg J.; Condray, Ruth; Chakraborty, Beatrice H.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Chakraborty, Beatrice H.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 SEP PY 2010 VL 77 IS 3 SI SI BP 254 EP 255 DI 10.1016/j.ijpsycho.2010.06.071 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 644BA UT WOS:000281344200132 ER PT J AU Drappatz, J Norden, AD Wong, ET Doherty, LM LaFrankie, DC Ciampa, A Kesari, S Sceppa, C Gerard, M Phan, P Schiff, D Batchelor, TT Ligon, KL Young, G Muzikansky, A Weiss, SE Wen, PY AF Drappatz, Jan Norden, Andrew D. Wong, Eric T. Doherty, Lisa M. LaFrankie, Debra C. Ciampa, Abigail Kesari, Santosh Sceppa, Christine Gerard, Mary Phan, Phuong Schiff, David Batchelor, Tracy T. Ligon, Keith L. Young, Geoffrey Muzikansky, Alona Weiss, Stephanie E. Wen, Patrick Y. TI PHASE I STUDY OF VANDETANIB WITH RADIOTHERAPY AND TEMOZOLOMIDE FOR NEWLY DIAGNOSED GLIOBLASTOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Glioblastoma; vandetanib; radiotherapy; temozolomide ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; BEVACIZUMAB PLUS IRINOTECAN; HIGH-GRADE GLIOMA; FACTOR-RECEPTOR; RADIATION-THERAPY; MALIGNANT GLIOMA; VENOUS THROMBOEMBOLISM; TUMOR-GROWTH; RECURRENT GLIOBLASTOMA AB Purpose: Increasing evidence has suggested that angiogenesis inhibition might potentiate the effects of radiotherapy and chemotherapy in patients with glioblastoma (GBM). In addition, epidermal growth factor receptor inhibition might be of therapeutic benefit, because the epidermal growth factor receptor is upregulated in GBM and contributes to radiation resistance. We conducted a Phase I study of vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, in patients with newly diagnosed GBM combined with RT and temozolomide (TMZ). Methods and Materials: A total of 13 GBM patients were treated with vandetanib, radiotherapy, and concurrent and adjuvant TMZ, using a standard "3 + 3" dose escalation. The maximal tolerated dose was defined as the dose with <1 of 6 dose-limiting toxicities during the first 12 weeks of therapy. The eligible patients were adults with newly diagnosed GBM, Karnofsky performance status of >= 60, normal organ function, who were not taking enzyme-inducing antiepileptic drugs. Results: Of the 13 patients, 6 were treated with vandetanib at a dose of 200mg daily. Of the 6 patients, 3 developed dose-limiting toxicities within the first 12 weeks, including gastrointestinal hemorrhage and thrombocytopenia in 1 patient, neutropenia in 1 patient, and diverticulitis with gastrointestinal perforation in 1 patient. The other 7 patients were treated with 100 mg daily, with no dose-limiting toxicities observed, establishing this dose as the maximal tolerated dose combined with TMZ and RT. Conclusion: Vandetanib can be safely combined with RT and TMZ in GBM patients. A Phase II study in which patients are randomized to vandetanib 100 mg daily with RT and TMZ or RT and TMZ alone is underway. (C) 2010 Elsevier Inc. C1 [Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Brigham & Womens Canc Ctr, Ctr Mol Oncol Pathol, Boston, MA USA. [Weiss, Stephanie E.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Drappatz, Jan; Norden, Andrew D.; Kesari, Santosh; Wen, Patrick Y.] Brigham & Womens Hosp, Div Canc Neurol, Dept Neurol, Boston, MA 02115 USA. [Young, Geoffrey] Brigham & Womens Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02115 USA. [Drappatz, Jan; Norden, Andrew D.; Wong, Eric T.; Kesari, Santosh; Batchelor, Tracy T.; Ligon, Keith L.; Young, Geoffrey; Muzikansky, Alona; Weiss, Stephanie E.; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. [Wong, Eric T.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Schiff, David] Univ Virginia, Hlth Sci Ctr, Dept Neurol, Div Neurooncol, Charlottesville, VA 22908 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Wen, PY (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, SW430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org RI Kesari, Santosh/E-8461-2013 FU AstraZeneca FX 1Jan Drappatz and Andrew D. Norden contributed equally to this manuscript. Supported by AstraZeneca. NR 58 TC 58 Z9 58 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2010 VL 78 IS 1 BP 85 EP 90 DI 10.1016/j.ijrobp.2009.07.1741 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 643NY UT WOS:000281304600013 PM 20137866 ER PT J AU Gensheimer, MF Yock, TI Liebsch, NJ Sharp, GC Paganetti, H Madan, N Grant, PE Bortfeld, T AF Gensheimer, Michael F. Yock, Torunn I. Liebsch, Norbert J. Sharp, Gregory C. Paganetti, Harald Madan, Neel Grant, P. Ellen Bortfeld, Thomas TI IN VIVO PROTON BEAM RANGE VERIFICATION USING SPINE MRI CHANGES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Proton radiotherapy; Bone marrow; Magnetic resonance imaging; Dosimetry; Brain neoplasms ID BONE-MARROW; RADIATION-THERAPY; IRRADIATION; PATIENT; FIELD AB Purpose: In proton therapy, uncertainty in the location of the distal dose edge can lead to cautious treatment plans that reduce the dosimetric advantage of protons. After radiation exposure, vertebral bone marrow undergoes fatty replacement that is visible on magnetic resonance imaging (MRI). This presents an exciting opportunity to observe radiation dose distribution in vivo. We used quantitative spine MRI changes to precisely detect the distal dose edge in proton radiation patients. Methods and Materials: We registered follow-up T1-weighted MRI images to planning computed tomography scans from 10 patients who received proton spine irradiation. A radiation dose-MRI signal intensity curve was created using the lateral beam penumbra in the sacrum. This curve was then used to measure range errors in the lumbar spine. Results: In the lateral penumbra, there was an increase in signal intensity with higher dose throughout the full range of 0-37.5 Gy (RBE). In the distal fall-off region, the beam sometimes appeared to penetrate farther than planned. The mean overshoot in 10 patients was 1.9 mm (95% confidence interval, 0.8-3.1 mm), on the order of the uncertainties inherent to our range verification method. Conclusions: We have demonstrated in vivo proton range verification using posttreatment spine MRI changes. Our analysis suggests the presence of a systematic overshoot of a few millimeters in some proton spine treatments, but the range error does not exceed the uncertainty incorporated into the treatment planning margin. It may be possible to extend our technique to MRI sequences that show early bone marrow changes, enabling adaptive treatment modification. (C) 2010 Elsevier Inc. C1 [Gensheimer, Michael F.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Yock, Torunn I.; Liebsch, Norbert J.; Sharp, Gregory C.; Paganetti, Harald; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Madan, Neel; Grant, P. Ellen] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Bortfeld, T (reprint author), Francis H Burr Proton Therapy Ctr, Rm 106,30 Fruit St, Boston, MA 02114 USA. EM tbortfeld@partners.org FU Vanderbilt Medical Scholars program; Massachusetts General Hospital [C06 CA059267] FX Supported by the Vanderbilt Medical Scholars program and the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 16 TC 26 Z9 26 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2010 VL 78 IS 1 BP 268 EP 275 DI 10.1016/j.ijrobp.2009.11.060 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 643NY UT WOS:000281304600037 PM 20472369 ER PT J AU Karel, MJ Emery, EE Molinari, V AF Karel, Michele J. Emery, Erin E. Molinari, Victor CA CoPGTP Task Force Assessment Gerop TI Development of a tool to evaluate geropsychology knowledge and skill competencies SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE psychology; training; competence; geriatrics; assessment; professional practice ID CORE COMPETENCES; PSYCHOLOGISTS; EDUCATION; PEOPLE; MODEL AB Background: Workforce shortages to meet the mental health needs of the world's aging population are well documented. Within the field of professional geropsychology in the U.S.A., a national conferencewas convened in 2006 to delineate competencies for psychological practice with older adults and a training model for the field. The conference produced the Pikes Peak Model of Geropsychology Training. The Council of Professional Geropsychology Training Programs (CoPGTP) aimed to produce a competency evaluation tool to help individuals define training needs for and evaluate progress in development of the Pikes Peak professional geropsychology competencies. Methods: A CoPGTP task force worked for one year to adapt the Pikes Peak Model geropsychology attitude, knowledge, and skill competencies into an evaluation tool for use by supervisors, students and professional psychologists at all levels of geropsychology training. The task force developed a competency rating tool, which included delineation of behavioral anchors for each of the Pikes Peak geropsychology knowledge and skill competencies and use of a developmental rating scale. Pilot testing was conducted, with 13 individuals providing feedback on the clarity and feasibility of the tool for evaluation of oneself or students. Results: The Geropsychology Knowledge and Skills Assessment Tool, Version 1.1, is now posted on the CoPGTP website and is being used by geropsychology training programs in the U. S. A. Conclusions: The evaluation tool has both strengths and limitations. We discuss future directions for its ongoing validation and professional use. C1 [Karel, Michele J.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Karel, Michele J.] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02301 USA. [Emery, Erin E.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Emery, Erin E.] Rush Univ, Dept Behav Sci, Chicago, IL 60612 USA. [Molinari, Victor] Univ S Florida, Dept Aging & Mental Hlth Dispar, Tampa, FL USA. [Molinari, Victor] Louis Parte Florida Mental Hlth Inst, Coll Behav & Community Sci, Tampa, FL USA. RP Karel, MJ (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, 940 Belmont St,3-5-C, Brockton, MA 02301 USA. EM Michele.Karel@va.gov NR 30 TC 19 Z9 19 U1 0 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD SEP PY 2010 VL 22 IS 6 SI SI BP 886 EP 896 DI 10.1017/S1041610209991736 PG 11 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 653GT UT WOS:000282078000005 PM 20149270 ER PT J AU Curtin, E Liao, EC Hickey, GJ AF Curtin, E. Liao, E. C. Hickey, G. J. TI WNT9A IS REQUIRED FOR NEURAL CREST CONDENSATION DURING PALATOGENESIS AND LOWER JAW DEVELOPMENT IN ZEBRAFISH SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Curtin, E.; Liao, E. C.; Hickey, G. J.] Massachusetts Gen Hosp, Dept Plast Surg, 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 SEP PY 2010 VL 179 SU 9 MA 85 BP S361 EP S361 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 651UU UT WOS:000281953500086 ER PT J AU Taylor, AJ Patrick, J Abbara, S Berman, DS Halliburton, SS Hines, JL Hodgson, JM Lesser, JR Wann, S Williams, KA Ziffer, JA Lennon, LJ Edgerton, DM Cerqueira, MD AF Taylor, Allen J. Patrick, Jonathan Abbara, Suhny Berman, Daniel S. Halliburton, Sandra S. Hines, Jerome L. Hodgson, John McB. Lesser, John R. Wann, Samuel Williams, Kim A. Ziffer, Jack A. Lennon, Lorraine J. Edgerton, Dawn M. Cerqueira, Manuel D. TI Relationship Between Previous Training and Experience and Results of the Certification Examination in Cardiovascular Computed Tomography SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiac CT; certification; education AB Examinees of the first Certifying Examination in Cardiovascular Computed Tomography were surveyed regarding their training and experience in cardiac computed tomography. The results support the current training pathways within the American College of Cardiology/American Heart Association competency criteria that include either experience-based or formal training program in cardiovascular computed tomography. Increased duration in clinical practice, the number of scans clinically interpreted in practice, and level 3 competency were associated with higher passing rates. C1 [Taylor, Allen J.] Washington Hosp Ctr, Dept Med, Cardiol Sect, Div Cardiol, Washington, DC 20010 USA. [Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Berman, Daniel S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Halliburton, Sandra S.; Cerqueira, Manuel D.] Cleveland Clin, Imaging Inst, Cardiovasc Imaging Lab, Cleveland, OH 44106 USA. [Hines, Jerome L.] Illinois Heart & Vasc, Hinsdale, IL USA. [Hodgson, John McB.] Geisinger Hlth Syst, Danville, PA USA. [Lesser, John R.] Minneapolis Heart Inst, Minneapolis, MN USA. [Wann, Samuel] Wisconsin Heart & Vasc Clin, Milwaukee, WI USA. [Williams, Kim A.] Wayne State Univ, Sch Med, Detroit, MI USA. [Ziffer, Jack A.] Miami Cardiac & Vasc Inst, Dept Radiol, Miami, FL USA. [Lennon, Lorraine J.; Edgerton, Dawn M.] Certificat Board Cardiovasc Computed Tomog, Gaithersburg, MD USA. RP Taylor, AJ (reprint author), Washington Hosp Ctr, Dept Med, Cardiol Sect, Div Cardiol, 110 Irving St NW,Room 1E12, Washington, DC 20010 USA. EM allen.taylor@medstar.net FU Abbott; GE Healthcare Sciences FX Certification Board of Cardiovascular Computed Tomography, Gaithersburg, Maryland. Dr. Taylor is supported by Abbott. Dr. Berman receives research grant support from GE Healthcare & Sciences. Dr. Lesser is on the Scientific Advisory Board for Vital Images (moderate) and Speakers' Bureau for Siemens Medical (moderate). All other authors report that they have no relationships to disclose. NR 4 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD SEP PY 2010 VL 3 IS 9 BP 976 EP 980 DI 10.1016/j.jcmg.2010.06.015 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 655LP UT WOS:000282251800013 PM 20846635 ER PT J AU Underhill, K Operario, D Skeer, MR Mimiaga, MJ Mayer, KH AF Underhill, Kristen Operario, Don Skeer, Margie R. Mimiaga, Matthew J. Mayer, Kenneth H. TI Packaging PrEP to Prevent HIV: An Integrated Framework to Plan for Pre-Exposure Prophylaxis Implementation in Clinical Practice SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Editorial Material ID TENOFOVIR DISOPROXIL FUMARATE; SIMIAN IMMUNODEFICIENCY VIRUS; RESOURCE-LIMITED SETTINGS; GAY PRIDE EVENTS; ANTIRETROVIRAL PROPHYLAXIS; COST-EFFECTIVENESS; RISK BEHAVIOR; UNITED-STATES; INFECTION; TRANSMISSION C1 [Underhill, Kristen; Operario, Don; Skeer, Margie R.; Mayer, Kenneth H.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Skeer, Margie R.; Mimiaga, Matthew J.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Underhill, K (reprint author), Brown Univ, Dept Community Hlth, Box G-S121-4, Providence, RI 02912 USA. EM kristen_underhill@brown.edu FU NIAAA NIH HHS [T32 AA007459-24, T32 AA007459] NR 46 TC 41 Z9 42 U1 1 U2 5 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 SEP 1 PY 2010 VL 55 IS 1 BP 8 EP 13 DI 10.1097/QAI.0b013e3181e8efe4 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 641YY UT WOS:000281170500002 PM 21423876 ER PT J AU Domchek, SM Friebel, TM Singer, CF Evans, DG Lynch, HT Isaacs, C Garber, JE Neuhausen, SL Matloff, E Eeles, R Pichert, G Van T'veer, L Tung, N Weitzel, JN Couch, FJ Rubinstein, WS Ganz, PA Daly, MB Olopade, OI Tomlinson, G Schildkraut, J Blum, JL Rebbeck, TR AF Domchek, Susan M. Friebel, Tara M. Singer, Christian F. Evans, D. Gareth Lynch, Henry T. Isaacs, Claudine Garber, Judy E. Neuhausen, Susan L. Matloff, Ellen Eeles, Rosalind Pichert, Gabriella Van T'veer, Laura Tung, Nadine Weitzel, Jeffrey N. Couch, Fergus J. Rubinstein, Wendy S. Ganz, Patricia A. Daly, Mary B. Olopade, Olufunmilayo I. Tomlinson, Gail Schildkraut, Joellen Blum, Joanne L. Rebbeck, Timothy R. TI Association of Risk-Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers With Cancer Risk and Mortality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BILATERAL PROPHYLACTIC OOPHORECTOMY; PROSE-STUDY-GROUP; BREAST-CANCER; SALPINGO-OOPHORECTOMY; OVARIAN-CANCER; UNDERWENT OOPHORECTOMY; PREMENOPAUSAL WOMEN; PENETRANCE; MENOPAUSE; THERAPY AB Context Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer. Objective To estimate risk and mortality reduction stratified by mutation and prior cancer status. Design, Setting, and Participants Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009. Main Outcomes Measures Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality. Results No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, womenwho underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancerspecific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancerspecific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]). Conclusions Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality. JAMA. 2010; 304(9): 967-975 www.jama.com C1 [Friebel, Tara M.; Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Domchek, Susan M.; Rebbeck, Timothy R.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Domchek, Susan M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Singer, Christian F.] Med Univ Vienna, Div Special Gynecol, Vienna, Austria. [Evans, D. Gareth] St Marys Hosp, Dept Clin Genet, Manchester M13 0JH, Lancs, England. [Lynch, Henry T.] Creighton Univ, Dept Prevent Med, Omaha, NE 68178 USA. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neuhausen, Susan L.] Univ Calif Irvine, Sch Med, Div Epidemiol, Irvine, CA 92717 USA. [Matloff, Ellen] Yale Univ, Canc Genet Counseling Program, New Haven, CT USA. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, Inst Canc Res, London, England. [Pichert, Gabriella] Guys & St Thomas Fdn Trust, London, England. [Van T'veer, Laura] Netherlands Canc Inst, Amsterdam, Netherlands. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Couch, Fergus J.] Mayo Clin, Coll Med, Rochester, MN USA. [Rubinstein, Wendy S.] NorthShore Univ HealthSyst, Evanston, IL USA. [Rubinstein, Wendy S.; Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Tomlinson, Gail] Univ Texas Hlth Sci Ctr San Antonio, Div Hematol & Oncol, San Antonio, TX 78229 USA. [Schildkraut, Joellen] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Blum, Joanne L.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 217 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM reb-beck@mail.med.upenn.edu OI Eeles, Rosalind/0000-0002-3698-6241; Evans, Gareth/0000-0002-8482-5784 FU Public Health Service [R01-CA83855, R01-CA102776, NO1-CN-6700]; University of Pennsylvania Cancer Center; Cancer Genetics Network [HHSN21620074400C]; Marjorie Cohen Research Fund; Dana-Farber/Harvard Cancer Center [BC P50 CA-089393]; US Department of Defense [DAMD-17-96-I-6088, DAMD-17-94-J-4340, DAMD-17-97-I-7112, DAMD-17-03-I-0619]; Utah State Department of Health; Nebraska State Cancer and Smoking-Related Diseases Research [LB595, P30-CA-16042]; Cancer Research UK [C5047/A7357]; National Cancer Institute [P30 CA51008-12]; Doris Duke Distinguished Clinical Scientist; National Institute for Health Research; [P30-CA51008-15] FX This study was supported by grants R01-CA83855 and R01-CA102776 from the Public Health Service (awarded to Dr Rebbeck); funding from the University of Pennsylvania Cancer Center (awarded to Dr Rebbeck); grant HHSN21620074400C from the Cancer Genetics Network (awarded to Drs Domchek and Isaacs); funding from the Marjorie Cohen Research Fund (awarded to Dr Domchek); SPORE grant BC P50 CA-089393 from the Dana-Farber/Harvard Cancer Center (awarded to Dr Garber); grants DAMD-17-96-I-6088 (awarded to Andrew K. Godwin), DAMD-17-94-J-4340 and DAMD-17-97-I-7112 (awarded to Dr Lynch), and DAMD-17-03-I-0619 (awarded to Dr Domchek) from the US Department of Defense; grant P30-CA51008-15 (awarded to Georgetown University); funding from the Utah Cancer registry (which was funded by Public Health Service grant NO1-CN-6700) and the Utah State Department of Health; Nebraska State Cancer and Smoking-Related Diseases Research Program grants LB595 (awarded to Dr Lynch) and P30-CA-16042 (awarded to Dr Ganz); Cancer Research UK grant C5047/A7357 (awarded to Dr Eeles); and National Cancer Institute grant P30 CA51008-12 (awarded to Dr Isaacs). Dr Olopade receives funding as the Doris Duke Distinguished Clinical Scientist. Dr Eeles received funding from the National Institute for Health Research (awarded to the Biomedical Research Centre at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust). NR 38 TC 400 Z9 410 U1 6 U2 45 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 1 PY 2010 VL 304 IS 9 BP 967 EP 975 DI 10.1001/jama.2010.1237 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 645AD UT WOS:000281422400022 PM 20810374 ER PT J AU Shera, CA Guinan, JJ Oxenham, AJ AF Shera, Christopher A. Guinan, John J., Jr. Oxenham, Andrew J. TI Otoacoustic Estimation of Cochlear Tuning: Validation in the Chinchilla SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE cochlea; frequency selectivity; auditory nerve; basilar membrane; otoacoustic emissions; psychophysical masking; filter theory; coherent reflection; model ID AUDITORY-NERVE FIBERS; OLIVOCOCHLEAR-EFFERENT INHIBITION; COHERENT REFLECTION; BASILAR-MEMBRANE; CHARACTERISTIC FREQUENCY; TRAVELING-WAVE; FILTER SHAPES; TECTORIAL MEMBRANE; EMISSION LATENCY; NOTCHED-NOISE AB We analyze published auditory-nerve and otoacoustic measurements in chinchilla to test a network of hypothesized relationships between cochlear tuning, cochlear traveling-wave delay, and stimulus-frequency otoacoustic emissions (SFOAEs). We find that the physiological data generally corroborate the network of relationships, including predictions from filter theory and the coherent-reflection model of OAE generation, at locations throughout the cochlea. The results support the use of otoacoustic emissions as noninvasive probes of cochlear tuning. Developing this application, we find that tuning ratios-defined as the ratio of tuning sharpness to SFOAE phase-gradient delay in periods-have a nearly species-invariant form in cat, guinea pig, and chinchilla. Analysis of the tuning ratios identifies a species-dependent parameter that locates a transition between "apical-like" and "basal-like" behavior involving multiple aspects of cochlear physiology. Approximate invariance of the tuning ratio allows determination of cochlear tuning from SFOAE delays. We quantify the procedure and show that otoacoustic estimates of chinchilla cochlear tuning match direct measures obtained from the auditory nerve. By assuming that invariance of the tuning ratio extends to humans, we derive new otoacoustic estimates of human cochlear tuning that remain mutually consistent with independent behavioral measurements obtained using different rationales, methodologies, and analysis procedures. The results confirm that at any given characteristic frequency (CF) human cochlear tuning appears sharper than that in the other animals studied, but varies similarly with CF. We show, however, that the exceptionality of human tuning can be exaggerated by the ways in which species are conventionally compared, which take no account of evident differences between the base and apex of the cochlea. Finally, our estimates of human tuning suggest that the spatial spread of excitation of a pure tone along the human basilar membrane is comparable to that in other common laboratory animals. C1 [Shera, Christopher A.; Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Shera, Christopher A.; Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Oxenham, Andrew J.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD, National Institutes of Health [R01 DC03687, DC00235, DC03909] FX We thank Mario Ruggero and Jonathan Siegel for generously sharing their data and for many provocative discussions. We also thank Christopher Bergevin, Paul Fahey, Shirin Farrahi, Jeffery Lichtenhan, Elizabeth Olson, Barbara Shinn-Cunningham, and the two anonymous reviewers for valuable comments on the manuscript. Our work was supported by Grant Nos. R01 DC03687 (CAS), DC00235 (JJG), and DC03909 (AJO) from the NIDCD, National Institutes of Health. NR 86 TC 91 Z9 91 U1 3 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD SEP PY 2010 VL 11 IS 3 BP 343 EP 365 DI 10.1007/s10162-010-0217-4 PG 23 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 634QO UT WOS:000280598300002 PM 20440634 ER PT J AU Maison, SF Le, MN Larsen, E Lee, SK Rosowski, JJ Thomas, SA Liberman, MC AF Maison, Stephane F. Le, Mina Larsen, Erik Lee, Suh-Kyung Rosowski, John J. Thomas, Steven A. Liberman, M. Charles TI Mice Lacking Adrenergic Signaling Have Normal Cochlear Responses and Normal Resistance to Acoustic Injury but Enhanced Susceptibility to Middle-Ear Infection SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE dopamine beta-hydroxylase; sympathetic nervous system; otitis media; olivocochlear ID DOPAMINE-BETA-HYDROXYLASE; PRODUCT OTOACOUSTIC EMISSIONS; CROSSED OLIVOCOCHLEAR BUNDLE; SYMPATHETIC-NERVOUS-SYSTEM; SUPERIOR OLIVARY COMPLEX; INDUCED HEARING-LOSS; GUINEA-PIG; BLOOD-FLOW; AUTONOMIC INNERVATION; IMMUNE-SYSTEM AB The vasculature and neurons of the inner ear receive adrenergic innervation from the cervical sympathetic chain, and adrenergic receptors may be expressed by cells of the organ of Corti and stria vascularis, despite a lack of direct sympathetic innervation. To assess the functional role of adrenergic signaling in the auditory periphery, we studied mice with targeted deletion of the gene for dopamine beta-hydroxylase (DBH), which catalyzes the conversion of dopamine to noradrenaline; thus, these mutant mice have no measurable adrenaline or noradrenaline. Dbh (-/-) mice were more susceptible to spontaneous middle-ear infection than their control littermates, consistent with a role for sympathetics in systemic and/or local immune response. At 6-8 weeks of age, cochlear thresholds and suprathreshold responses assessed by auditory brainstem responses and distortion product otoacoustic emissions, as well as light-microscopic morphology, were indistinguishable from controls, if ears with conductive hearing loss were eliminated. Dbh (-/-) mice were no more susceptible to acoustic injury than controls, despite prior reports that sympathectomy reduces noise damage. Dbh (-/-) mice showed enhancement of shock-evoked olivocochlear suppression of cochlear responses, which may arise from the loss of adrenergic inputs to olivocochlear neurons in the brainstem. However, adrenergic modulation of olivocochlear efferents does not mediate the protective effect of contralateral cochlear destruction on ipsilateral response to acoustic overexposure. C1 [Maison, Stephane F.; Le, Mina; Larsen, Erik; Rosowski, John J.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Maison, Stephane F.; Rosowski, John J.; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Maison, Stephane F.; Larsen, Erik; Lee, Suh-Kyung; Rosowski, John J.; Liberman, M. Charles] Harvard MIT, Program Speech & Hearing Biosci & Technol, Cambridge, MA USA. [Thomas, Steven A.] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. RP Maison, SF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM stephane_maison@meei.harvard.edu FU NIH [R01 DC0188, DC000194, MH063352, P30 DC5029] FX This work was supported by NIH Grants: R01 DC0188 (MCL), DC000194 (JJR), MH063352 (SAT) and P30 DC5029 (MCL). The skillful assistance of Leslie Dodds, Connie Miller and Melissa Woods is gratefully acknowledged. NR 69 TC 5 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD SEP PY 2010 VL 11 IS 3 BP 449 EP 461 DI 10.1007/s10162-010-0220-9 PG 13 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 634QO UT WOS:000280598300009 PM 20503062 ER PT J AU Tyer-Viola, LA Cesario, SK AF Tyer-Viola, Lynda A. Cesario, Sandra K. TI Addressing Poverty, Education, and Gender Equality to Improve the Health of Women Worldwide SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE millennium development goalspovertyeducationequitywomen ID MILLENNIUM DEVELOPMENT GOALS; ACCESS; BRAC AB The Millennium Development Goals (MDG) that target alleviating poverty, improving primary education, and fostering gender equity are important as a foundation to promote world health. Achieving these goals will create an environment for healthy lives for women and children. Poverty, education, and gender equality, although undeniably linked, need to be addressed individually. Nurses have the capacity and political will to address MDGs and to contribute to the health and well-being of the world population. C1 [Tyer-Viola, Lynda A.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02129 USA. [Tyer-Viola, Lynda A.] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Boston, MA 02129 USA. [Tyer-Viola, Lynda A.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02129 USA. [Cesario, Sandra K.] Texas Womans Univ, Coll Nursing, Houston, TX USA. RP Tyer-Viola, LA (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, 36 1st Ave, Boston, MA 02129 USA. EM ltyerviola@mghihp.edu NR 44 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD SEP-OCT PY 2010 VL 39 IS 5 BP 580 EP 589 DI 10.1111/j.1552-6909.2010.01165.x PG 10 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 646NU UT WOS:000281550100013 PM 20673314 ER PT J AU Niessner, H Sinnberg, T Beck, D Flaherty, K Schaller, M Kulms, D Schittek, B Schadendorf, D Garbe, C Meier, F AF Niessner, H. Sinnberg, T. Beck, D. Flaherty, K. Schaller, M. Kulms, D. Schittek, B. Schadendorf, D. Garbe, C. Meier, F. TI The farnesyl transferase inhibitor lonafarnib inhibits mTOR signaling and enforces sorafenib-induced endoplasmic reticulum stress and apoptosis in melanoma cells SO JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT LA German DT Meeting Abstract C1 [Niessner, H.; Sinnberg, T.; Beck, D.; Schaller, M.; Schittek, B.; Garbe, C.; Meier, F.] Univ Tubingen, Dept Dermatol, Div Dermatol Oncol, D-72074 Tubingen, Germany. [Flaherty, K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Kulms, D.] Univ Stuttgart, Inst Cell Biol & Immunol, D-7000 Stuttgart, Germany. [Schadendorf, D.] Univ Essen Gesamthsch, Dept Dermatol, Essen, Germany. RI Kulms, Dagmar/H-1653-2014 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 1610-0379 J9 J DTSCH DERMATOL GES JI J. Dtsch. Dermatol. Ges. PD SEP PY 2010 VL 8 IS 9 BP 739 EP 739 PG 1 WC Dermatology SC Dermatology GA 642MO UT WOS:000281219100014 ER PT J AU Lawrence, D Hamid, O McDermott, D Puzanov, I Sznol, M Clark, J Logan, T Hodi, FS Heller, KN Margolin, K AF Lawrence, D. Hamid, O. McDermott, D. Puzanov, I Sznol, M. Clark, J. Logan, T. Hodi, F. S. Heller, K. N. Margolin, K. TI Phase II trial of ipilimumab monotherapy in melanoma patients with brain metastases SO JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT LA English DT Meeting Abstract C1 [Lawrence, D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hamid, O.] Angeles Clin & Res Inst, Santa Monica, CA USA. [McDermott, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Puzanov, I] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Sznol, M.] Yale Univ, Ctr Canc, New Haven, CT USA. [Clark, J.] Loyola Univ Hlth Syst, Maywood, IL USA. [Logan, T.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Heller, K. N.] Bristol Myers Squibb Co, Plainsboro, NJ USA. [Margolin, K.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1610-0379 J9 J DTSCH DERMATOL GES JI J. Dtsch. Dermatol. Ges. PD SEP PY 2010 VL 8 IS 9 BP 763 EP 764 PG 2 WC Dermatology SC Dermatology GA 642MO UT WOS:000281219100099 ER PT J AU Barth, KS Becker, WC Wiedemer, NL Mavandadi, S Oslin, DW Meghani, SH Gallagher, RM AF Barth, Kelly S. Becker, William C. Wiedemer, Nancy L. Mavandadi, Shahrzad Oslin, David W. Meghani, Salimah H. Gallagher, Rollin M. TI Association Between Urine Drug Test Results and Treatment Outcome in High-Risk Chronic Pain Patients on Opioids SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE urine drug testing; aberrant behavior; opioid pharmacotherapy ID CHRONIC NONCANCER PAIN; METHADONE-MAINTENANCE; SUBSTANCE-ABUSE; PRIMARY-CARE; THERAPY; COCAINE; MANAGEMENT; PREDICTORS; BEHAVIORS; MEDICINE AB Objective: How to best use urine drug test (UDT) results in the management of opioid pharmacotherapy has not been elucidated. The purpose of this study was to describe how the results of UDTs gathered from a group of chronic pain patients in a high-risk monitored opioid pharmacotherapy program apply to treatment outcome. Methods: Retrospective review of the medical records of 335 primary care patients on chronic opioids more than 22 months. Results: Patients with a UDT containing unprescribed opioids were more likely to demonstrate resolution of aberrant behavior (P = 0.02) and less likely to be discharged from treatment (P = 0.04). Patients with cocaine, alone or in combination, in the UDT were less likely to resolve aberrant behavior (P = 0.007 and 0.001), and were more likely to be electively or administratively discharged from treatment (P = 0.012 and 0.001). Discussion: In this group of high-risk pain patients on chronic opioids, information gained from UDT results can be used to predict treatment outcomes and inform appropriate interventions. Patients on chronic opioids who have a UDT positive for an illicit opioid or unprescribed opioids alone are more likely to respond to monitored opioid pharmacotherapy. Patients with a UDT positive for cocaine, alone or in combination, are less likely to resolve aberrant behavior within the structure of a monitored opioid pharmacotherapy program and are more likely to be discharged electively or administratively from the program without significant transition to addiction treatment. Further studies are needed to investigate which patient responded best to structured opioid pharmacotherapy programs and how to appropriately handle abnormal UDT results to improve the management and engagement in appropriate treatment for this population. C1 [Barth, Kelly S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Becker, William C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Wiedemer, Nancy L.; Oslin, David W.; Gallagher, Rollin M.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Mavandadi, Shahrzad; Oslin, David W.; Gallagher, Rollin M.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Univ Penn, Dept Anesthesia, Philadelphia, PA 19104 USA. [Meghani, Salimah H.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Barth, KS (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,POB 250861, Charleston, SC 29425 USA. EM stephen@musc.edu OI Becker, William/0000-0002-0788-1467 FU VISN-4 Competitive Pilot Project FX Supported by VISN-4 Competitive Pilot Project Funding (to N.S.L.). NR 32 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD SEP PY 2010 VL 4 IS 3 BP 167 EP 173 DI 10.1097/ADM.0b013e3181c379ed PG 7 WC Substance Abuse SC Substance Abuse GA 642RP UT WOS:000281234900008 PM 21769031 ER PT J AU Gibbons, CJ Fournier, JC Stirman, SW DeRubeis, RJ Crits-Christoph, P Beck, AT AF Gibbons, Carly J. Fournier, Jay C. Stirman, Shannon Wiltsey DeRubeis, Robert J. Crits-Christoph, Paul Beck, Aaron T. TI The clinical effectiveness of cognitive therapy for depression in an outpatient clinic SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Cognitive therapy; Depression; Effectiveness; Randomized controlled trials ID REPRESENTATIVE CONDITIONS; EMPIRICAL STATUS; PSYCHOTHERAPY; INVENTORY; BENCHMARKING; METAANALYSIS; TRIALS; SAMPLE; ADULTS AB Background: Cognitive therapy (CT) has been shown to be efficacious in the treatment of depression in numerous randomized controlled trials (RCTs). However, little evidence is available that speaks to the effectiveness of this treatment under routine clinical conditions. Method: This paper examines outcomes of depressed individuals seeking cognitive therapy at an outpatient clinic (N=217, Center for Cognitive Therapy; CCT). Outcomes were then compared to those of participants in a large NIMH-funded RCT of cognitive therapy and medications as treatments for depression. Results: The CCT is shown to be a clinically representative setting, and 61% of participants experienced reliable change in symptoms over the course of treatment; of those, 45% (36% of the total sample) met criteria for recovery by the end of treatment. Participants at CCT had similar outcomes to participants treated in the RCT, but there was some evidence that those with more severe symptoms at intake demonstrated greater improvement in the RCT than their counterparts at CCT. Limitations: The CCT may not be representative of all outpatient settings, and the structure of treatment there was considerably different from that in the RCT. Treatment fidelity was not assessed at CCT. Conclusions: Depressed individuals treated with cognitive therapy in a routine clinical care setting showed a significant improvement in symptoms. When compared with outcomes evidenced in RCTs, there was little evidence of superior outcomes in either setting. However, for more severe participants, outcomes were found to be superior when treatment was delivered within an RCT than in an outpatient setting. Clinicians treating such patients in non-research settings may thus benefit from making modifications to treatment protocols to more closely resemble research settings. Published by Elsevier B.V. C1 [Gibbons, Carly J.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Gibbons, Carly J.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Fournier, Jay C.; DeRubeis, Robert J.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Stirman, Shannon Wiltsey] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Stirman, Shannon Wiltsey] Boston Univ, Dept Psychiat, Boston, MA 02118 USA. [Crits-Christoph, Paul; Beck, Aaron T.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Gibbons, CJ (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave 151D, West Haven, CT 06516 USA. EM carly.gibbons@yale.edu OI Fournier, Jay/0000-0001-8967-1668 FU National Institute of Mental Health, Bethesda, MD [MH47383, K99MH080100, MH50129 (R10), MH55875 (R10), MH01697 (K02)]; Center for Disease Control [R49/CCR316866] FX This research and manuscript preparation was supported by grants MH47383 (Dr. Beck), K99MH080100 (Dr. Stirman) and MH50129 (R10) (Dr. DeRubeis) and MH55875 (R10) and MH01697 (K02) (Dr. Hollon) from the National Institute of Mental Health, Bethesda, MD and by grant R49/CCR316866 (Dr. Beck) by the Center for Disease Control. The NIMH and CDC 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. NR 35 TC 17 Z9 17 U1 1 U2 23 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 SEP PY 2010 VL 125 IS 1-3 BP 169 EP 176 DI 10.1016/j.jad.2009.12.030 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 644KW UT WOS:000281377100023 PM 20080305 ER PT J AU Bozic, KJ Chiu, VW Takemoto, SK Greenbaum, JN Smith, TM Jerabek, SA Berry, DJ AF Bozic, Kevin J. Chiu, Vanessa W. Takemoto, Steven K. Greenbaum, Jordan N. Smith, Thomas M. Jerabek, Seth A. Berry, Daniel J. TI The Validity of Using Administrative Claims Data in Total Joint Arthroplasty Outcomes Research SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total joint arthroplasty; administrative claims; ICD-9-CM; health services research ID TOTAL HIP-ARTHROPLASTY; UNITED-STATES; KNEE ARTHROPLASTY; EPIDEMIOLOGY AB The purpose of this study was to evaluate concordance between administrative and clinical diagnosis and procedure codes for revision total joint arthroplasty (TJA). Concordance between administrative and clinical records was determined for 764 consecutive revision TJA procedures from 4 hospitals. For revision total hip arthroplasty, concordance between clinical diagnoses and administrative claims was very good for dislocation, mechanical loosening, and periprosthetic joint infection (all kappa > 0.6), but considerably lower for prosthetic implant failure/breakage and other mechanical complication (both kappa < 0.25). Similarly, for revision total knee arthroplasty diagnoses, concordance was very good for periprosthetic fracture, periprosthetic joint infection, mechanical loosening, and osteolysis (all kappa > 0.60), but much lower for implant failure/breakage and other mechanical complication (both kappa < 0.24). Concordance for TJA-specific procedure codes was very good only for revision total knee arthroplasty patellar component revisions and tibial insert exchange procedures. Total (all-component) revisions were overcoded for hips (00.70) and undercoded for knees (00.80). Improved clinical documentation and continued education are needed to enhance the value of these codes. C1 [Bozic, Kevin J.; Chiu, Vanessa W.; Takemoto, Steven K.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Bozic, Kevin J.; Chiu, Vanessa W.; Takemoto, Steven K.] Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Greenbaum, Jordan N.; Jerabek, Seth A.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Smith, Thomas M.; Berry, Daniel J.] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA. NR 11 TC 43 Z9 43 U1 0 U2 4 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 SEP PY 2010 VL 25 IS 6 SU 1 BP 58 EP 61 DI 10.1016/j.arth.2010.04.006 PG 4 WC Orthopedics SC Orthopedics GA 649FG UT WOS:000281752600013 PM 20570479 ER PT J AU Mattila, ML Hurtig, T Haapsamo, H Jussila, K Kuusikko-Gauffin, S Kielinen, M Linna, SL Ebeling, H Bloigu, R Joskitt, L Pauls, DL Moilanen, I AF Mattila, Marja-Leena Hurtig, Tuula Haapsamo, Helena Jussila, Katja Kuusikko-Gauffin, Sanna Kielinen, Marko Linna, Sirkka-Liisa Ebeling, Hanna Bloigu, Risto Joskitt, Leena Pauls, David L. Moilanen, Irma TI Comorbid Psychiatric Disorders Associated with Asperger Syndrome/High-functioning Autism: A Community- and Clinic-based Study SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Comorbidity; CGAS; Asperger syndrome; Autism; Pervasive developmental disorders; Autism spectrum disorders ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT HYPERACTIVITY DISORDER; GLOBAL ASSESSMENT SCALE; SCHOOL-AGE-CHILDREN; SPECTRUM DISORDERS; PREVALENCE; POPULATION; SYMPTOMS; ADOLESCENTS AB The present study identifies the prevalence and types of comorbid psychiatric disorders associated with Asperger syndrome (AS)/high-functioning autism (HFA) in a combined community- and clinic-based sample of fifty 9- to 16-year-old subjects using the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version. The level of functioning was estimated using the Children's Global Assessment Scale. The results support common (prevalence 74%) and often multiple comorbid psychiatric disorders in AS/HFA; behavioral disorders were shown in 44%, anxiety disorders in 42% and tic disorders in 26%. Oppositional defiant disorder, major depressive disorder and anxiety disorders as comorbid conditions indicated significantly lower levels of functioning. To target interventions, routine evaluation of psychiatric comorbidity in subjects with AS/HFA is emphasized. C1 [Mattila, Marja-Leena; Hurtig, Tuula; Haapsamo, Helena; Jussila, Katja; Kuusikko-Gauffin, Sanna; Linna, Sirkka-Liisa; Ebeling, Hanna; Joskitt, Leena; Moilanen, Irma] Univ Oulu, Clin Child Psychiat, Univ Hosp Oulu, Oulu 90029, Finland. [Hurtig, Tuula; Linna, Sirkka-Liisa] Univ Oulu, Inst Hlth Sci, Oulu 90014, Finland. [Kielinen, Marko] Univ Oulu, Dept Educ Sci & Teacher Educ, Oulu 90014, Finland. [Bloigu, Risto] Univ Oulu, Med Informat Grp, Oulu 90014, Finland. [Pauls, David L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Boston, MA 02114 USA. RP Mattila, ML (reprint author), Univ Oulu, Clin Child Psychiat, Univ Hosp Oulu, POB 26, Oulu 90029, Finland. EM marja-leena.mattila@fimnet.fi; tuula.hurtig@oulu.fi; helena.haapsamo@oulu.fi; katja.jussila@oulu.fi; sanna.kuusikkogauffin@gmail.com; marko.kielinen@oulu.fi; sirkkaliisa.linna@oulu.fi; hanna.ebeling@oulu.fi; risto.bloigu@oulu.fi; leena.joskitt@oulu.fi; dpauls@pngu.mgh.harvard.edu; irma.moilanen@oulu.fi NR 56 TC 107 Z9 107 U1 7 U2 36 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD SEP PY 2010 VL 40 IS 9 BP 1080 EP 1093 DI 10.1007/s10803-010-0958-2 PG 14 WC Psychology, Developmental SC Psychology GA 638QD UT WOS:000280908900004 PM 20177765 ER PT J AU Kanjilal, S Citorik, R LaRocque, RC Ramoni, MF Calderwood, SB AF Kanjilal, Sanjat Citorik, Robert LaRocque, Regina C. Ramoni, Marco F. Calderwood, Stephen B. TI A Systems Biology Approach To Modeling Vibrio cholerae Gene Expression under Virulence-Inducing Conditions SO JOURNAL OF BACTERIOLOGY LA English DT Article ID EL-TOR BIOTYPES; TOXR REGULON; TRANSCRIPTIONAL ACTIVATORS; INTESTINAL COLONIZATION; REGULATORY CASCADE; CULTURE-CONDITIONS; INFECTION; SINGLE; DYNAMICS; PROMOTER AB Vibrio cholerae is a Gram-negative bacillus that is the causative agent of cholera. Pathogenesis in vivo occurs through a series of spatiotemporally controlled events under the control of a gene cascade termed the ToxR regulon. Major genes in the ToxR regulon include the master regulators toxRS and tcpPH, the downstream regulator toxT, and virulence factors, the ctxAB and tcpA operons. Our current understanding of the dynamics of virulence gene expression is limited to microarray analyses of expression at selected time points. To better understand this process, we utilized a systems biology approach to examine the temporal regulation of gene expression in El Tor V. cholerae grown under virulence-inducing conditions in vitro (AKI medium), using high-resolution time series genomic profiling. Results showed that overall gene expression in AKI medium mimics that of in vivo studies but with less clear temporal separation between upstream regulators and downstream targets. Expression of toxRS was unaffected by growth under virulence-inducing conditions, but expression of toxT was activated shortly after switching from stationary to aerating conditions. The tcpA operon was also activated early during mid-exponential-phase growth, while the ctxAB operon was turned on later, after the rise in toxT expression. Expression of ctxAB continued to rise despite an eventual decrease in toxT. Cluster analysis of gene expression highlighted 15 hypothetical genes and six genes related to environmental information processing that represent potential new members of the ToxR regulon. This study applies systems biology tools to analysis of gene expression of V. cholerae in vitro and provides an important comparator for future studies done in vivo. C1 [Ramoni, Marco F.] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA 02115 USA. [Citorik, Robert; LaRocque, Regina C.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Calderwood, SB (reprint author), Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM scalderwood@partners.org OI Citorik, Robert/0000-0002-6397-5417 FU Howard Hughes Medical Institute; National Institute of Allergy and Infectious Diseases [U01 AI058935]; Fogarty International Center [K01 TW07144]; National Human Genome Research Institute [R01 HG003354] FX This work was supported by the Medical Fellows Program at the Howard Hughes Medical Institute (S. K.), grant U01 AI058935 from the National Institute of Allergy and Infectious Diseases (S. B. C.), grant K01 TW07144 from the Fogarty International Center (R. C. L.), a Physician-Scientist Early Career Award from the Howard Hughes Medical Institute (R. C. L.), and grant R01 HG003354 from the National Human Genome Research Institute (M. F. R.). NR 40 TC 8 Z9 9 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2010 VL 192 IS 17 BP 4300 EP 4310 DI 10.1128/JB.00182-10 PG 11 WC Microbiology SC Microbiology GA 638AX UT WOS:000280863000007 PM 20601467 ER PT J AU Kendall, EA Chowdhury, F Begum, Y Khan, AI Li, S Thierer, JH Bailey, J Kreisel, K Tacket, CO LaRocque, RC Harris, JB Ryan, ET Qadri, F Calderwood, SB Stine, OC AF Kendall, Emily A. Chowdhury, Fahima Begum, Yasmin Khan, Ashraful I. Li, Shan Thierer, James H. Bailey, Jason Kreisel, Kristen Tacket, Carol O. LaRocque, Regina C. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi Calderwood, Stephen B. Stine, O. Colin TI Relatedness of Vibrio cholerae O1/O139 Isolates from Patients and Their Household Contacts, Determined by Multilocus Variable-Number Tandem-Repeat Analysis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; O1 EL-TOR; MOLECULAR EPIDEMIOLOGY; RESTRICTION PATTERNS; STRAINS; BANGLADESH; INDIA; ENVIRONMENT; VALIDATION; DIVERSITY AB The genetic relatedness of Vibrio cholerae O1/O139 isolates obtained from 100 patients and 146 of their household contacts in Dhaka, Bangladesh, between 2002 and 2005 was assessed by multilocus variable-number tandem-repeat analysis. Isolate genotypes were analyzed at five loci containing tandem repeats. Across the population, as well as within households, isolates with identical genotypes were clustered in time. Isolates from individuals within the same household were more likely to have similar or identical genotypes than were isolates from different households, but even within a household, isolates from different individuals often had different genotypes. When household contacts were sampled regularly for 3 weeks after the illness of the household index patient, isolates with genotypes related to the index patient appeared in contacts, on average, similar to 3 days after the index patient, while isolates with unrelated genotypes appeared in contacts similar to 6 days after. Limited data revealed that multiple isolates from the same individual collected within days of each other or even from a single stool sample may have identical, similar, or unrelated genotypes as well. Our results demonstrate that genetically related V. cholerae strains cluster in local outbreaks but also suggest that multiple distinct strains of V. cholerae O1 may circulate simultaneously within a household. C1 [Li, Shan; Thierer, James H.; Bailey, Jason; Kreisel, Kristen; Tacket, Carol O.; Stine, O. Colin] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Kendall, Emily A.; Chowdhury, Fahima; Begum, Yasmin; Khan, Ashraful I.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Kendall, Emily A.; LaRocque, Regina C.; Harris, Jason B.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stine, OC (reprint author), Univ Maryland, Sch Med, 585 Howard Hall,660 W Redwood St, Baltimore, MD 21201 USA. EM ostin001@umaryland.edu OI Thierer, James/0000-0002-1679-2255; Kendall, Emily/0000-0002-0083-422X FU NIAID [UO1 AI058935, U01 AI077883, RO3 AI063079]; National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health [N01-AI-40014]; Fogarty International [D43 TW005572, R24 TW007988] FX This research was supported in part by NIAID grants UO1 AI058935 (S. B. C.), U01 AI077883 (E. T. R.), and RO3 AI063079 (F. Q.) and by the University of Maryland Clinical Research Unit of the Food and Waterborne Diseases Integrated Research Network, which is funded by the National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health, under contract N01-AI-40014. E. A. K. is a recipient of a Fogarty International Clinical Research Scholars award (D43 TW005572 and R24 TW007988). NR 51 TC 29 Z9 31 U1 0 U2 0 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 SEP PY 2010 VL 192 IS 17 BP 4367 EP 4376 DI 10.1128/JB.00698-10 PG 10 WC Microbiology SC Microbiology GA 638AX UT WOS:000280863000014 PM 20585059 ER PT J AU Celli, JP Rizvi, I Evans, CL Abu-Yousif, AO Hasan, T AF Celli, Jonathan P. Rizvi, Imran Evans, Conor L. Abu-Yousif, Adnan O. Hasan, Tayyaba TI Quantitative imaging reveals heterogeneous growth dynamics and treatment-dependent residual tumor distributions in a three-dimensional ovarian cancer model SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE ovarian cancer; three-dimensional models; image processing; photodynamic therapy; carboplatin ID INTRAPERITONEAL PHOTODYNAMIC THERAPY; PHASE-II TRIAL; IN-VIVO; EPITHELIAL ACINI; MALIGNANT BREAST; CELLS; CARCINOMATOSIS; FLUORESCENCE; SPHEROIDS; CULTURES AB Three-dimensional tumor models have emerged as valuable in vitro research tools, though the power of such systems as quantitative reporters of tumor growth and treatment response has not been adequately explored. We introduce an approach combining a 3-D model of disseminated ovarian cancer with high-throughput processing of image data for quantification of growth characteristics and cytotoxic response. We developed custom MATLAB routines to analyze longitudinally acquired dark-field microscopy images containing thousands of 3-D nodules. These data reveal a reproducible bimodal log-normal size distribution. Growth behavior is driven by migration and assembly, causing an exponential decay in spatial density concomitant with increasing mean size. At day 10, cultures are treated with either carboplatin or photodynamic therapy (PDT). We quantify size-dependent cytotoxic response for each treatment on a nodule by nodule basis using automated segmentation combined with ratiometric batch-processing of calcein and ethidium bromide fluorescence intensity data (indicating live and dead cells, respectively). Both treatments reduce viability, though carboplatin leaves micronodules largely structurally intact with a size distribution similar to untreated cultures. In contrast, PDT treatment disrupts micronodular structure, causing punctate regions of toxicity, shifting the distribution toward smaller sizes, and potentially increasing vulnerability to subsequent chemotherapeutic treatment. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3483903] C1 [Celli, Jonathan P.; Rizvi, Imran; Evans, Conor L.; Abu-Yousif, Adnan O.; Hasan, Tayyaba] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rizvi, Imran] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, 40 Blossom St, Boston, MA 02114 USA. EM thasan@partners.org OI Rizvi, Imran/0000-0001-9673-4700 FU National Institutes of Health [R01 AR040352-09, 5R01CA119388-03, P01 CA084203-06, F32 CA138153]; Wellman Center for Photomedicine FX We thank Yupeng Tu and Drs. Bryan Spring, Daniel Neuman, and Humra Athar of the Wellman Center for Photomedicine, as well as Dr. Shyamsunder Erramilli of Boston University for helpful discussions of this work. We thank Dr. David Schoenfeld of the Department of Biostatistics at Massachusetts General Hospital and Harvard Medical School for his guidance on interpretation of statistical considerations in our results. This work was supported by National Institutes of Health, Grants R01 AR040352-09, 5R01CA119388-03, and P01 CA084203-06 (to T. H), F32 CA138153 (to C. L. E), and the Wellman Center for Photomedicine Graduate Fellowship (to I.R) NR 29 TC 29 Z9 29 U1 2 U2 24 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2010 VL 15 IS 5 AR 051603 DI 10.1117/1.3483903 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 688GI UT WOS:000284837400005 PM 21054077 ER PT J AU Choma, MA Suter, MJ Vakoc, BJ Bouma, BE Tearney, GJ AF Choma, Michael A. Suter, Melissa J. Vakoc, Benjamin J. Bouma, Brett E. Tearney, Guillermo J. TI Heart wall velocimetry and exogenous contrast-based cardiac flow imaging in Drosophila melanogaster using Doppler optical coherence tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE coherent optical systems; Doppler effect; flows; biomedical optics; biology ID ADULT HEART; FRUIT-FLY; VISUALIZATION; INNERVATION; INSECTS; DISEASE; SYSTEM; MODEL AB Drosophila melanogaster (fruit fly) is a central organism in biology and is becoming increasingly important in the cardiovascular sciences. Prior work in optical imaging of the D. melanogaster heart has focused on static and dynamic structural anatomy. In the study, it is demonstrated that Doppler optical coherence tomography can quantify dynamic heart wall velocity and hemolymph flow in adult D. melanogaster. Since hemolymph is optically transparent, a novel exogenous contrast technique is demonstrated to increase the backscatter-based intracardiac Doppler flow signal. The results presented here open up new possibilities for functional cardiovascular phenotyping of normal and mutant D. melanogaster. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3503418] C1 [Choma, Michael A.] Childrens Hosp, Boston, MA 02115 USA. [Choma, Michael A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Suter, Melissa J.; Vakoc, Benjamin J.; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Suter, Melissa J.; Vakoc, Benjamin J.; Bouma, Brett E.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Vakoc, Benjamin J.; Bouma, Brett E.; Tearney, Guillermo J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Choma, MA (reprint author), Yale Univ, Sch Med, Dept Diagnost Radiol, MRRC, IAC N117,POB 208043, New Haven, CT 06520 USA. EM michael.choma@yale.edu FU American Medical Association Foundation; NIH [R01HL076398, R01CA103769]; Department of Defense Air Force Office of Scientific Research [FA9550-04-1-0079] FX This work was generously supported by the Frederick H. Lovejoy Fund, Children's Hospital Boston (MAC) and by an American Medical Association Foundation Seed Grant (MAC). We additionally acknowledge funding support from NIH R01HL076398 and NIH R01CA103769 (development of the imaging system) and from the Department of Defense Air Force Office of Scientific Research, Medical Free Electron Laser Program FA9550-04-1-0079. NR 33 TC 10 Z9 10 U1 0 U2 2 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2010 VL 15 IS 5 AR 056020 DI 10.1117/1.3503418 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 688GI UT WOS:000284837400042 PM 21054114 ER PT J AU Warren, CB Lohser, S Wene, LC Pogue, BW Bailin, PL Maytin, EV AF Warren, Christine B. Lohser, Sara Wene, Lauren C. Pogue, Brian W. Bailin, Philip L. Maytin, Edward V. TI Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fiber optic applications; fluorescence; photodetection; photometry; medicine ID ACID-PHOTODYNAMIC THERAPY; AMINOLEVULINIC-ACID; CELL CARCINOMAS; IN-VIVO; SKIN; PHOTOTOXICITY AB Topical 5-aminolevulinic acid (ALA) is widely used in photodynamic therapy (PDT) of actinic keratoses (AK), a type of premalignant skin lesion. However, the optimal time between ALA application and exposure to light has not been carefully investigated. Our objective is to study the kinetics of protoporphyrin IX (PpIX) accumulation in AK after short contact ALA and relate this to erythemal responses. Using a noninvasive dosimeter, PpIX fluorescence measurements (5 replicates) were taken at 20-min intervals for 2 h following ALA application, in 63 AK in 20 patients. Data were analyzed for maximal fluorescent signal obtained, kinetic slope, and changes in erythema. Our results show that PpIX accumulation was linear over time, becoming statistically higher than background in 48% of all lesions by 20 min, 92% of lesions by 1 h, and 100% of lesions by 2 h. PpIX accumulation was roughly correlated with changes in lesional erythema post-PDT. We conclude that significant amounts of PpIX are produced in all AK lesions by 2 h. The linear kinetics of accumulation suggest that shorter ALA application times may be efficacious in many patients. Noninvasive fluorescence monitoring of PpIX may be useful to delineate areas of high PpIX accumulation within precancerous areas of the skin. c 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3484255] C1 [Maytin, Edward V.] Cleveland Clin, Dept Biomed Engn, Cleveland, OH 44195 USA. [Warren, Christine B.; Lohser, Sara; Wene, Lauren C.; Bailin, Philip L.] Cleveland Clin, Dermatol & Plast Surg Inst, Dept Dermatol, Cleveland, OH 44195 USA. [Maytin, Edward V.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Maytin, EV (reprint author), Cleveland Clin, Dept Biomed Engn, Desk A61,9500 Euclid Ave, Cleveland, OH 44195 USA. EM maytine@ccf.org FU National Institutes of Health/National Cancer Institute [P01 CA084203] FX We thank Jim Sherer, P. A., and Fran Moore, P. A., for allowing us to coordinate research visits with their PDT clinic patient schedules. Grant support comes from the National Institutes of Health/National Cancer Institute Grant No. P01 CA084203 (T. Hasan, E. Maytin, B. Pogue). The authors state no conflicts of interest to disclose. NR 20 TC 17 Z9 17 U1 0 U2 2 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2010 VL 15 IS 5 AR 051607 DI 10.1117/1.3484255 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 688GI UT WOS:000284837400009 PM 21054081 ER PT J AU Nagler, RH Romantan, A Kelly, BJ Stevens, RS Gray, SW Hull, SJ Ramirez, AS Hornik, RC AF Nagler, Rebekah H. Romantan, Anca Kelly, Bridget J. Stevens, Robin S. Gray, Stacy W. Hull, Shawnika J. Ramirez, A. Susana Hornik, Robert C. TI How Do Cancer Patients Navigate the Public Information Environment? Understanding Patterns and Motivations for Movement Among Information Sources SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Information seeking; Cross-source engagement; Grounded theory; Complementarity theory ID HEALTH INFORMATION; BREAST-CANCER; SEEKING BEHAVIORS; DECISION-MAKING; PROSTATE-CANCER; INTERNET; NEEDS; SERVICE; CARE; SUPPORT AB Little is known about how patients move among information sources to fulfill unmet needs. We interviewed 43 breast, prostate, and colorectal cancer patients. Using a grounded theory approach, we identified patterns and motivations for movement among information sources. Overall, patients reported using one source (e.g., newspaper) followed by the use of another source (e.g., Internet), and five key motivations for such cross-source movement emerged. Patients' social networks often played a central role in this movement. Understanding how patients navigate an increasingly complex information environment may help clinicians and educators to guide patients to appropriate, high-quality sources. C1 [Nagler, Rebekah H.; Romantan, Anca; Kelly, Bridget J.; Stevens, Robin S.; Gray, Stacy W.; Hull, Shawnika J.; Ramirez, A. Susana; Hornik, Robert C.] Univ Penn, Annenberg Sch Commun, Ctr Excellence Canc Commun Res, Philadelphia, PA 19104 USA. [Romantan, Anca] Univ Massachusetts, Dept Commun, Amherst, MA USA. [Kelly, Bridget J.] Res Triangle Inst, Washington, DC USA. [Stevens, Robin S.] Univ Penn, Annenberg Publ Policy Ctr, Ctr Hlth Behav & Commun Res, Philadelphia, PA 19104 USA. [Gray, Stacy W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Nagler, RH (reprint author), Univ Penn, Annenberg Sch Commun, Ctr Excellence Canc Commun Res, 3620 Walnut St, Philadelphia, PA 19104 USA. EM magler@asc.upenn.edu OI Hornik, Robert/0000-0002-2148-8805 FU National Cancer Institute's Center of Excellence in Cancer Communication (CECCR) located at the Annenberg School for Communication, University of Pennsylvania [P50-CA095856-05] FX The authors wish to acknowledge the funding support of the National Cancer Institute's Center of Excellence in Cancer Communication (CECCR) located at the Annenberg School for Communication, University of Pennsylvania (P50-CA095856-05). This publication's contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 62 TC 25 Z9 25 U1 4 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SEP PY 2010 VL 25 IS 3 BP 360 EP 370 DI 10.1007/s13187-010-0054-5 PG 11 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 666HQ UT WOS:000283105800018 PM 20204573 ER PT J AU Sharma, AK Agnihotri, A Schachne, J Heist, EK AF Sharma, Ajay K. Agnihotri, Arvind Schachne, Jay Heist, E. Kevin TI Cardiac Arrest with "Pseudo-Brugada" ECG Pattern in the Setting of a Coronary Artery Anomaly SO JOURNAL OF CARDIAC SURGERY LA English DT Editorial Material ID DEATH AB P>A 36-year-old Hispanic man with no prior cardiac history presented with chest pain and then ventricular fibrillation requiring defibrillation after a physical altercation. His ECG on presentation to the emergency room was suggestive of Brugada syndrome, which later normalized. Cardiac catheterization revealed anomalous origin of right coronary artery from the left coronary cusp (coursing between the pulmonary artery and the aorta) for which he underwent surgical reimplantation, and subsequent pharmacological challenge test did not provoke reappearance of a Brugada ECG pattern. A review of literature on Brugada syndrome and anomalous origin of the coronary arteries is presented. (J Card Surg 2010;25:614-617). C1 [Heist, E. Kevin] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Agnihotri, Arvind] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. [Sharma, Ajay K.] Charlton Mem Hosp, Div Internal Med, Fall River, MA USA. [Schachne, Jay] Charlton Mem Hosp, Div Cardiol, Fall River, MA USA. RP Heist, EK (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM kheist@partners.org NR 8 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD SEP PY 2010 VL 25 IS 5 BP 614 EP 617 DI 10.1111/j.1540-8191.2010.01095.x PG 4 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 646QV UT WOS:000281558000036 PM 20678111 ER PT J AU Matura, LA Carroll, DL AF Matura, Lea Ann Carroll, Diane L. TI Human Responses to Pulmonary Arterial Hypertension Review of the Literature SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Review DE cognition; emotional responses; memory; physical functioning; pulmonary arterial hypertension; pulmonary artery pressure ID LIFE; VALIDATION AB Pulmonary arterial hypertension (PAH) is a devastating disease characterized by elevation in pulmonary artery pressures causing progressive symptoms that lead to functional decline and poor quality of life. There are multiple causes of PAH including familial disease, connective tissue disease, and HIV. The estimated life expectancy is 4 years after onset of symptoms and approximately 6 to 7 years with PAH treatment. Much of the current research has focused on pharmacological treatments to improve functional status and decrease mortality. A comprehensive literature review was conducted using the CINAHL, PubMed, and MEDLINE to identify and synthesize current studies on human responses to PAH organized by emotional responses and physical functioning. Eight studies fulfilled the search criteria. Patients with PAH were learning to cope and live with uncertainty and treatment. Pulmonary arterial hypertension produced the emotional responses of anxiety, depression, and panic attacks along with impairments in cognition and memory as well as reductions in physical functioning. C1 [Matura, Lea Ann] Northeastern Univ, Sch Nursing, Boston, MA 02115 USA. [Carroll, Diane L.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Matura, LA (reprint author), Northeastern Univ, Sch Nursing, 360 Huntington Ave, Boston, MA 02115 USA. EM l.matura@neu.edu NR 28 TC 12 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD SEP-OCT PY 2010 VL 25 IS 5 BP 420 EP 427 DI 10.1097/JCN.0b013e3181d25458 PG 8 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 641GK UT WOS:000281112600057 PM 20714240 ER PT J AU Pischke, CR Elliott-Eller, M Li, MM Mendell, N Ornish, D Weidner, G AF Pischke, Claudia R. Elliott-Eller, Melanie Li, Minmin Mendell, Nancy Ornish, Dean Weidner, Gerdi TI Clinical Events in Coronary Heart Disease Patients With an Ejection Fraction of 40% or Less 3-Year Follow-up Results SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE asymptomatic reduced left ventricular ejection fraction; clinical events; coronary heart disease; lifestyle ID VENTRICULAR SYSTOLIC DYSFUNCTION; STYLE DEMONSTRATION PROJECT; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; ARTERY-DISEASE; RISK-FACTORS; FAILURE; MANAGEMENT; CARE; GUIDELINES AB Background and Research Objective: It is unclear whether lifestyle changes can delay the need for surgical procedures in coronary heart disease (CHD) patients with asymptomatic reduced left ventricular ejection fraction (LVEF). The aim of this pilot study was to examine whether lifestyle changes can delay the need for surgical procedures in this population. Subjects and Methods: We compared 3-year clinical events in 27 CHD patients eligible to receive revascularization (by insurance standards), but underwent lifestyle changes (low-fat diet, exercise, stress management) instead (intervention group [IG], LVEF <= 40%), with those of a historically matched (age, gender, LVEF, and stenosis of the 3 major coronary arteries) control group receiving usual care (UCG; n = 13) who received revascularization at study entry. Both IG and UCG patients were enrolled in the health insurance companies participating in the Multicenter Lifestyle Demonstration Project, an insurance-sponsored, community-based, secondary prevention study implemented at 8 hospital sites in the United States. Results and Conclusion: At 3 months, there were more cardiac events in the UCG (6 events) than in the IG (1 event; P < .006; odds ratio = 13.27; confidence interval = 1.57-111.94). This difference was maintained over 3 years (P < .06; odds ratio = 2.75; confidence interval = 1.05-7.19). Of the 26 surviving (1 cardiac death) IG patients, 23 did not require primary revascularization. In conclusion, CHD patients with asymptomatic reduced LVEF may be able to safely delay revascularization by making changes in lifestyle with no increased risk for cardiac events or overt heart failure over 3 years. C1 [Pischke, Claudia R.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Pischke, Claudia R.] NCI, Bethesda, MD 20892 USA. [Elliott-Eller, Melanie] Palm Drive Hosp, Sebastopol, CA USA. [Li, Minmin; Mendell, Nancy] SUNY Stony Brook, Dept Appl Math & Stat, New York, NY USA. [Ornish, Dean] Res Inst Prevent Med, Sausalito, CA USA. [Weidner, Gerdi] San Francisco State Univ, Romberg Tiburon Ctr, Dept Biol, Tiburon, CA 94920 USA. [Weidner, Gerdi] Johannes Gutenberg Univ Mainz, Mainz, Germany. RP Pischke, CR (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, 44 Binney St,LW703, Boston, MA 02115 USA. EM pischcl@gmx.net; gweidner@sfsu.edu FU NCI NIH HHS [R25 CA 057713-05]; NIMH NIH HHS [MH0711523] NR 31 TC 1 Z9 1 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD SEP-OCT PY 2010 VL 25 IS 5 BP E8 EP E15 DI 10.1097/JCN.0b013e3181d51f9e PG 8 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 641GK UT WOS:000281112600059 PM 20714228 ER PT J AU Ruff, CT Braunwald, E AF Ruff, Christian T. Braunwald, Eugene TI Will Warfarin Ever Be Replaced? SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Review DE warfarin; vitamin K antagonist; thromboembolism; novel anticoagulant ID FACTOR-XA INHIBITOR; ORAL DIRECT THROMBIN; NONVALVULAR ATRIAL-FIBRILLATION; RANDOMIZED CONTROLLED-TRIAL; HEALTHY ELDERLY SUBJECTS; TOTAL KNEE ARTHROPLASTY; TOTAL HIP-REPLACEMENT; SWEET CLOVER DISEASE; VENOUS THROMBOEMBOLISM; DABIGATRAN ETEXILATE AB Arterial and venous thromboembolism account for significant morbidity and mortality worldwide. Warfarin, and other vitamin K antagonists (VKAs), have been the only class of oral anticoagulants currently in clinical use and have been so for over 50 years. Although warfarin is effective in preventing thromboembolism, its use is limited by its narrow therapeutic index that necessitates frequent monitoring and dose adjustments resulting in considerable inconvenience to patients and clinicians. There are now several orally administered anticoagulants in late stages of clinical development that may offer effective, safer, and more convenient anticoagulation. This review summarizes and compares data on novel anticoagulants in the prophylaxis and treatment of venous thromboembolism, acute coronary syndromes, and the prevention of stroke in patients with atrial fibrillation. C1 [Ruff, Christian T.; Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Ruff, Christian T.; Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA. RP Ruff, CT (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM cruff@partners.org FU Bayer; Johnson & Johnson Pharmaceutical Research & Development, LLC; Daiichi Sankyo Inc; Merck Co; Sanofi Aventis FX The authors declared a potential conflict of interest (e.g. a financial relationship with the commercial organizations or products discussed in this article) as follows: The TIMI Study Group conducted ATLAS ACS-TIMI46 (sponsor: Bayer and Johnson & Johnson Pharmaceutical Research & Development, LLC) and is currently conducting ATLAS II-TIMI51 (sponsor: Bayer and Johnson & Johnson Pharmaceutical Research & Development, LLC) and ENGAGE AF-TIMI48 (spnsor: Daiichi Sankyo Inc). Dr Ruff was paid as a consultant for Daiichi Sankyo in 2009. Dr Braunwald served on the Advisory Board for Daiichi Sankyo and Merck & Co, and the TIMI Study group has received grant support from Johnson and Johnson, Merck & Co, Sanofi Aventis and Daiichi Sankyo. NR 59 TC 4 Z9 4 U1 2 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-2484 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD SEP PY 2010 VL 15 IS 3 BP 210 EP 219 DI 10.1177/1074248410366448 PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 636WW UT WOS:000280775800001 PM 20484119 ER PT J AU Lee, JE Ahn, JH Kim, WS Jea, SY AF Lee, Joo Eun Ahn, Jeong Hyo Kim, Wan Soo Jea, Seung Youn TI Optic capture in the anterior capsulorhexis during combined cataract and vitreoretinal surgery SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID POSTERIOR CAPSULORHEXIS; PEDIATRIC CATARACT; LENS AB We describe an optic capture technique that can be used during combined cataract and vitreoretinal surgery if in-the-bag implantation of an intraocular lens (IOL) is not possible The IOL is placed in the ciliary sulcus, and optic capture is performed behind an intact anterior continuous curvilinear capsulorhexis, with the haptics remaining in the sulcus The technique maintains IOL stability and separation of the anterior and posterior segments intraoperatively and postoperatively Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2010; 36.1449-1452 (C) 2010 ASCRS and ESCRS C1 [Lee, Joo Eun; Kim, Wan Soo] Inje Univ, Dept Ophthalmol, Haeundae Paik Hosp, Coll Med, Pusan 612030, South Korea. [Lee, Joo Eun; Ahn, Jeong Hyo] Maryknoll Med Ctr, Dept Ophthalmol, Pusan, South Korea. [Lee, Joo Eun; Jea, Seung Youn] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Lee, JE (reprint author), Inje Univ, Dept Ophthalmol, Haeundae Paik Hosp, Coll Med, 1435 Jwa Dong, Pusan 612030, South Korea. NR 7 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD SEP PY 2010 VL 36 IS 9 BP 1449 EP 1452 DI 10.1016/j.jcrs.2010.06.033 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 649CY UT WOS:000281746200002 PM 20692553 ER PT J AU Bell, TD Demay, MB Burnett-Bowie, SAM AF Bell, Taison D. Demay, Marie B. Burnett-Bowie, Sherri-Ann M. TI The Biology and Pathology of Vitamin D Control in Bone SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE VITAMIN D; RICKETS; OSTEOMALACIA; BONE ID SERUM 25-HYDROXYVITAMIN D; D-DEFICIENCY RICKETS; RANDOMIZED CONTROLLED-TRIALS; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; D-DEPENDENT RICKETS; D-RECEPTOR; D SUPPLEMENTATION; 1,25-DIHYDROXYVITAMIN D-3; PHOSPHATE IONS AB Vitamin D is a steroid pro-hormone, whose active metabolite binds the vitamin D receptor (VDR) which, in turn, binds to DNA sequences on target genes as a heterodimer with the retinoid-X receptor, resulting in regulation or gene expression. The vitamin D pro-hormone can be synthesized in the skin. in response to ultraviolet radiation; however, dietary sources have become increasingly important as a result or cultural changes over the past few centuries. Based on its initial discovery as an anti-rachitic factor, studies of the role of vitamin D and its receptor have largely focused on the skeleton. Investigations into the pathophysiologic basis and therapeutic responses of skeletal disorders associated with impaired vitamin D action have led to the identification or the molecular pathways Involved in hormone activation and regulation of gene expression by the liganded VDR. These studies have also demonstrated that the skeletal actions of the VDR and its ligand are largely redundant if normal mineral ion homeostasis can be maintained by other means. However, investigations in animal models with tissue-specific ablation of the VDR or the enzyme required km hormone activation have demonstrated novel actions in skeletal tissues The active vitamin D metabolite has been shown to have both paractine and endocrine actions in other tissues as well. J. Cell. Biochem. 111: 7-13, 2010. (C) 2010 Wilcy-Liss. Inc C1 [Demay, Marie B.; Burnett-Bowie, Sherri-Ann M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bell, Taison D.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Burnett-Bowie, SAM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM sburnett-bowie@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU National Institute of Health [K23DK073356, RO1 DK46974]; MGH Physician-Scientist Development Award; Boston Area Diabetes and Endocrinology Research Center FX Grant sponsor: National Institute of Health. Grant numbers. K23DK073356, RO1 DK46974, Grant sponsor MGH Physician-Scientist Development Award. Grant sponsor Boston Area Diabetes and Endocrinology Research Center NR 94 TC 16 Z9 16 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD SEP 1 PY 2010 VL 111 IS 1 BP 7 EP 13 DI 10.1002/jcb.22661 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 648JU UT WOS:000281690500002 PM 20506379 ER PT J AU Hoffmann, U Dilekoz, E Kudo, C Ayata, C AF Hoffmann, Ulrike Dilekoz, Ergin Kudo, Chiho Ayata, Cenk TI Gabapentin suppresses cortical spreading depression susceptibility SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cortex; electrophysiology; gabapentin; rat; spreading depression ID CALCIUM-CHANNEL; BRAIN-INJURY; DEPOLARIZATIONS; DRUG; RATS; NEURONTIN; BLOCKADE; PLASMA AB Cortical spreading depression (CSD) is an intense depolarization wave implicated in the pathophysiology of brain injury states and migraine aura. As Ca(v)2.1 channels modulate CSD susceptibility, we tested gabapentin, which inhibits Ca(v)2.1 through high-affinity binding to its alpha(2)delta subunit, on CSD susceptibility in anesthetized rats. Gabapentin, 100 or 200 mg/kg, elevated the electrical threshold for CSD and diminished recurrent CSDs evoked by topical KCl, when administered 1 hour before testing. With its favorable safety and tolerability profile, gabapentin may have a role in suppression of injury depolarizations in stroke, intracranial hemorrhage, and traumatic brain injury. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1588-1592; doi:10.1038/jcbfm.2010.92; published online 30 June 2010 C1 [Hoffmann, Ulrike; Dilekoz, Ergin; Kudo, Chiho; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neurovasc Res Lab, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv & Neurosci Intens Care Unit,Dept Neur, Charlestown, MA 02129 USA. RP Ayata, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neurovasc Res Lab, 149 13th St,Room 6408, Charlestown, MA 02129 USA. EM cayata@partners.org FU National Institute of Health [NS061505, NS055104]; Deutsche Forschungsgemeinschaft [HO 4211/1-1] FX This work was supported by the National Institute of Health (NS061505 and NS055104, Ayata) and Deutsche Forschungsgemeinschaft (HO 4211/1-1, Hoffmann). NR 16 TC 14 Z9 15 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2010 VL 30 IS 9 BP 1588 EP 1592 DI 10.1038/jcbfm.2010.92 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 646SF UT WOS:000281562300005 PM 20588320 ER PT J AU Huang, SL Shen, QA Duong, TQ AF Huang, Shiliang Shen, Qiang Duong, Timothy Q. TI Artificial neural network prediction of ischemic tissue fate in acute stroke imaging SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ANN; DWI; ischemic penumbra; perfusion-diffusion mismatch; predictive model; PWI ID POSITRON-EMISSION-TOMOGRAPHY; FOCAL CEREBRAL-ISCHEMIA; BRAIN-INJURY; QUANTITATIVE PERFUSION; FUNCTIONAL MRI; DIFFUSION; PENUMBRA; OXYGEN; TIME; CONSUMPTION AB Multimodal magnetic resonance imaging of acute stroke provides predictive value that can be used to guide stroke therapy. A flexible artificial neural network (ANN) algorithm was developed and applied to predict ischemic tissue fate on three stroke groups: 30-, 60-minute, and permanent middle cerebral artery occlusion in rats. Cerebral blood flow (CBF), apparent diffusion coefficient (ADC), and spin-spin relaxation time constant (T2) were acquired during the acute phase up to 3 hours and again at 24 hours followed by histology. Infarct was predicted on a pixel-by-pixel basis using only acute (30-minute) stroke data. In addition, neighboring pixel information and infarction incidence were also incorporated into the ANN model to improve prediction accuracy. Receiver-operating characteristic analysis was used to quantify prediction accuracy. The major findings were the following: (1) CBF alone poorly predicted the final infarct across three experimental groups; (2) ADC alone adequately predicted the infarct; (3) CBF + ADC improved the prediction accuracy; (4) inclusion of neighboring pixel information and infarction incidence further improved the prediction accuracy; and (5) prediction was more accurate for permanent occlusion, followed by 60- and 30-minute occlusion. The ANN predictive model could thus provide a flexible and objective framework for clinicians to evaluate stroke treatment options on an individual patient basis. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1661-1670; doi:10.1038/jcbfm.2010.56; published online 28 April 2010 C1 [Huang, Shiliang; Shen, Qiang; Duong, Timothy Q.] UT Hlth Sci San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Shen, Qiang; Duong, Timothy Q.] UT Hlth Sci San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] UT Hlth Sci San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] UT Hlth Sci San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), UT Hlth Sci San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Shen, Qiang/B-8784-2008; Huang, Shiliang/F-3143-2010 OI Shen, Qiang/0000-0002-4287-3403; FU NIH [R01-NS45879]; American Heart Association [SDG-0430020N, SDG-0830293N] FX This work was supported by the NIH (R01-NS45879) and the American Heart Association (SDG-0430020N and SDG-0830293N). NR 36 TC 13 Z9 14 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2010 VL 30 IS 9 BP 1661 EP 1670 DI 10.1038/jcbfm.2010.56 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 646SF UT WOS:000281562300013 PM 20424631 ER PT J AU Bliziotes, M AF Bliziotes, Michael TI Update in Serotonin and Bone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RECEPTOR-RELATED PROTEIN-5; SYSTEM-ACTIVE MEDICATIONS; NURSING-HOME RESIDENTS; REUPTAKE INHIBITOR USE; MINERAL DENSITY; DEPRESSIVE SYMPTOMS; OLDER MEN; POSTMENOPAUSAL WOMEN; HIP FRACTURE; RISK-FACTOR AB Context: Serotonin (5-HT) may be an important regulatory agent in bone, and agents that modify 5-HT signaling, such as selective serotonin reuptake inhibitors (SSRIs), are in widespread clinical use. Evidence Acquisition: Evidence was obtained by PubMed search and the author's knowledge of the field. Evidence Synthesis: Recent data suggest that gut-derived 5-HT may mediate the skeletal effects of LDL receptor-related protein 5, stimulating intense interest in a novel mechanism for regulating bone mass. However, the specific biochemical nature of serotonergic pathways influencing bone and their direct and/or indirect effects on bone metabolism are still unclear. The weight of epidemiological evidence suggests that SSRIs are associated with reduced bone mass, increased bone loss, and increased risk of fractures. Interpretation of these studies is complicated by the confounding effects of depression, the usual indication for treatment with SSRIs. The mechanisms for putative SSRI-induced deleterious effects on the skeleton are unknown, and are likely multifactorial. Conclusions: 5-HT may have regulatory effects on bone. Initial preclinical data suggest that its effects may be deleterious and may be regulated by low-density lipoprotein receptor-related protein 5. These studies need confirmation, as well as elucidation, of the biochemical pathways utilized and the feedback loops involved among bone, gut, and perhaps brain. Paradoxically, targeting of 5-HT synthesis and/or signaling in selective tissues may hold promise as an anabolic intervention for bone. Epidemiological data suggest that clinicians should be vigilant about detection of bone disease in patients who are using SSRIs. (J Clin Endocrinol Metab 95: 4124-4132, 2010) C1 [Bliziotes, Michael] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Bliziotes, Michael] Portland VA Med Ctr, Portland, OR 97239 USA. RP Bliziotes, M (reprint author), 3710 SW Vet Rd,P3-ENDO, Portland, OR 97239 USA. EM bliziote@ohsu.edu FU National Institutes of Health [AR-052018] FX This work was supported by National Institutes of Health Grant AR-052018 (to M.B.). NR 74 TC 36 Z9 36 U1 2 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP 4124 EP 4132 DI 10.1210/jc.2010-0861 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300024 PM 20823465 ER PT J AU Dwyer, AA Hayes, FJ Plummer, L Pitteloud, N Crowley, WF AF Dwyer, Andrew A. Hayes, Frances J. Plummer, Lacey Pitteloud, Nelly Crowley, William F., Jr. TI The Long-Term Clinical Follow-Up and Natural History of Men with Adult-Onset Idiopathic Hypogonadotropic Hypogonadism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; HYPOTHALAMIC AMENORRHEA; KALLMANN-SYNDROME; LUTEINIZING-HORMONE; PROKINETICIN-2 GENE; PITUITARY-FUNCTION; OLFACTORY-BULB; MICE LACKING; MUTATIONS; PUBERTY AB Context and Objective: Adult-onset idiopathic hypogonadotropic hypogonadism (AHH) is a rare disorder characterized by an isolated failure of gonadotropin secretion occurring after an otherwise normal sexual maturation in men. This study aims to examine the etiology and long-term natural history of this disorder. Design and Setting: Long-term follow up, including detailed clinical, biochemical, and genetic examinations, were performed and compared with those at diagnosis. Patients: Patients included 10 men with AHH [serum testosterone (T) <125 ng/dl]. Interventions: Overnight neuroendocrine studies, semen fluid analyses, and genetic screening were performed (KAL1, FGFR1, PROK2, PROKR2, NELF, TAC3, TACR3, and GNRH1) over a decade of longitudinal follow up. Results: Follow-up evaluations were conducted 10.6 +/- 5.9 yr after initial studies and revealed that the clinical characteristics and seminal fluid analyses of AHH men (body mass index, 28.8 +/- 4.1 vs. 27.0 +/- 4.3 kg/m(2); testicular volume, 18 +/- 6 vs. 19 +/- 6 ml) do not change over a decade with no spontaneous reversals. Several men exhibited some variability in their endogenous GnRH-induced LH secretory patterns, including emergence of endogenous pulsatility in three individuals. However, all remained hypogonadal (T <= 130 ng/dl). A single heterozygous DNA sequence change in PROKR2 (V317L) was identified, although this rare sequence variant did not prove to be functionally abnormal in vitro. Seven days of pulsatile GnRH therapy in this subject nearly normalized his serum T, supporting that the site of the defect is hypothalamic and not pituitary. Conclusions: 1) AHH in men appears to be a long-lasting condition. 2) Although minor changes in the abnormal pattern of endogenous GnRH-induced LH secretion occurred in some AHH patients, all remained frankly hypogonadal. (J Clin Endocrinol Metab 95: 4235-4243, 2010) C1 [Dwyer, Andrew A.; Hayes, Frances J.; Plummer, Lacey; Pitteloud, Nelly; Crowley, William F., Jr.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Dwyer, Andrew A.; Hayes, Frances J.; Plummer, Lacey; Pitteloud, Nelly; Crowley, William F., Jr.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. RP Crowley, WF (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX5,55Fruit St, Boston, MA 02114 USA. EM Crowley.William@mgh.harvard.edu RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; FU National Institutes of Health (NIH) [R01 HD15788, RO1 HD056264]; Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH [U54 HD028138]; NIH National Center for Research Resources, General Clinical Research Centers [M01-RR-01066] FX This work was supported by National Institutes of Health (NIH) Grants R01 HD15788 and RO1 HD056264, Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH Cooperative Agreement U54 HD028138 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research, and NIH National Center for Research Resources, General Clinical Research Centers Program Grant M01-RR-01066. NR 45 TC 18 Z9 18 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP 4235 EP 4243 DI 10.1210/jc.2010-0245 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300038 PM 20591981 ER PT J AU Falutz, J Mamputu, JC Potvin, D Moyle, G Soulban, G Loughrey, H Marsolais, C Turner, R Grinspoon, S AF Falutz, Julian Mamputu, Jean-Claude Potvin, Diane Moyle, Graeme Soulban, Graziella Loughrey, Helen Marsolais, Christian Turner, Ralph Grinspoon, Steven TI Effects of Tesamorelin (TH9507), a Growth Hormone-Releasing Factor Analog, in Human Immunodeficiency Virus-Infected Patients with Excess Abdominal Fat: A Pooled Analysis of Two Multicenter, Double-Blind Placebo-Controlled Phase 3 Trials with Safety Extension Data SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ADIPOSE-TISSUE; HIV; LIPODYSTROPHY; ACCUMULATION; RISK; MEN; ATHEROSCLEROSIS; METFORMIN; WEIGHT AB Context: HIV patients treated with antiretroviral therapy (ART) often develop increased visceral adipose tissue (VAT). Objective: Our objective was to perform a pooled analysis of two phase-3 studies of tesamorelin in ART-treated HIV patients with excess abdominal fat. Design and Setting: Two multicenter, international studies were conducted; a 26-wk randomized, placebo-controlled primary intervention phase was followed by a 26-wk safety extension. Patients: A total of 806 ART-treated HIV patients with excess abdominal fat were randomized in a 2: 1 fashion to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) sc daily. At wk 26, patients initially on tesamorelin were rerandomized to 2 mg tesamorelin (T-T group, n = 246) or placebo (T-P, n = 135) for an additional 26 wk, whereas patients on placebo were switched to tesamorelin (P-T, n = 197). Interventions: Tesamorelin (GHRH(1-44)) at a dose of 2 mg or identical placebo, sc, was given daily. Main Outcome Measure: We evaluated percent change in VAT by computed tomography scan at wk 26. Results: At wk 26, VAT decreased significantly in tesamorelin-treated patients (-24 +/- 41 vs. 2 +/- 35 cm(2), tesamorelin vs. placebo, P < 0.001; treatment effect, -15.4%). No significant changes were observed in abdominal sc adipose tissue (-2 +/- 32 vs. 2 +/- 29 cm(2), P = 0.08; treatment effect, -0.6%). Treatment with tesamorelin resulted in significant decreases in triglycerides (-37 +/- 139 vs. 6 +/- 112 mg/dl, P < 0.001; treatment effect, -12.3%) and cholesterol to high-density lipoprotein ratio (-0.18 +/- 1.00 vs. 0.18 +/- 0.94, P < 0.001; treatment effect, -7.2%) vs. placebo. Tesamorelin improved body image [ belly appearance distress (P = 0.002)], patient rating of belly profile (P = 0.003), and physician rating of belly profile (P < 0.001). Mean IGF-I increased 108 +/- 112 vs. -7 +/- 64 ng/ml (P < 0.001 vs. placebo). At wk 52, decreases in VAT [-35 +/- 50 cm(2) (-17.5 +/- 23.3%) +/-, waist circumference (-3.4 +/- 6.0 cm), triglycerides (-48 +/- 182 mg/dl), cholesterol (-8 +/- 38 mg/dl), and non-high-density lipoprotein (+/- 7 +/- 38 mg/dl) were maintained (all P < 0.001 vs. original baseline) in the T-T group. Treatment with tesamorelin was generally well tolerated. No clinically meaningful differences were observed between groups in glucose parameters at wk 26 and 52. Conclusions: Treatment with tesamorelin reduces VAT and maintains the reduction for up to 52 wk, preserves abdominal scadipose tissue, improves body image and lipids, and is overall well tolerated without clinically meaningful changes in glucose parameters. (J Clin Endocrinol Metab 95: 4291-4304, 2010) C1 [Falutz, Julian] McGill Univ, Ctr Hlth, Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. [Mamputu, Jean-Claude; Potvin, Diane; Soulban, Graziella; Loughrey, Helen; Marsolais, Christian] Theratechnologies Inc, Montreal, PQ H4S 2B4, Canada. [Moyle, Graeme] Chelsea & Westminster Hosp, St Stephens Ctr, London SW10 9NH, England. [Turner, Ralph] Phase V Technol Inc, Wellesley, MA 02481 USA. [Grinspoon, Steven] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 5 Longfellow Pl,Suite 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU Tibotec; Theratechnologies; Abbott; Boehringer Ingelheim; Gilead; Bristol-Myers Squibb; Roche; Bristol-Myers Squibb Co., Inc.; GlaxoSmithKline; Gilead Sciences; Merck Inc.; Ardea Biosciences; Pfizer; Amgen FX The studies were funded by Theratechnologies and designed in consultation with S. G. and J.F.. The sponsor collected the data, and analyses were performed by Octagon Research Solutions. S. G. drafted the current manuscript and had access to the data and all analyses.; J.M., D. P, G. S., H. L., and C. M. are employees of Theratechnologies. J.F. has received consultant fees from Tibotec, Theratechnologies, Abbott, and Boehringer Ingelheim; lecture fees from Gilead, Bristol-Myers Squibb, Abbott, and Roche; and grant support from Theratechnologies. G. M. has received grant support from Theratechnologies, Bristol-Myers Squibb Co., Inc., GlaxoSmithKline, Gilead Sciences, Merck Inc., Ardea Biosciences, Abbott, and Pfizer and served as a consultant to Theratechnologies, Bristol-Myers Squibb, GlaxoSmithKline, Gilead Sciences, Merck, Ardea Biosciences, Pfizer, Tobira Pharmaceuticals, Tibotec, and Johnson and Johnson. R. T. has received grant support from Theratechnologies and is employed by Phase V Technologies. S. G. has received grant support from Theratechnologies, Bristol-Myers Squibb, GlaxoSmithKline, and Amgen and served as a consultant to Theratechnologies, EMD Serono, and Elixir Pharmaceuticals. NR 25 TC 39 Z9 39 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP 4291 EP 4304 DI 10.1210/jc.2010-0490 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300045 PM 20554713 ER PT J AU Wu, BA Haigh, PI Hwang, R Ituarte, PHG Liu, ILA Hahn, TJ Yeh, MW AF Wu, Bian Haigh, Philip I. Hwang, Roy Ituarte, Philip H. G. Liu, In-Lu Amy Hahn, Theodore J. Yeh, Michael W. TI Underutilization of Parathyroidectomy in Elderly Patients with Primary Hyperparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM; CLINICAL-TRIAL; SURGERY; DIAGNOSIS; DISEASE; OLDER; NONAGENARIANS; OCTOGENARIANS; EPIDEMIOLOGY; PERSPECTIVE AB Context: Primary hyperparathyroidism (PHPT) disproportionately affects older patients, who may face higher thresholds for surgical intervention compared to young patients. Objective: The aim was to examine for differences in the utilization of parathyroidectomy attributable to age. Design: We conducted a retrospective cohort study. Participants: Patients with biochemically diagnosed PHPT during the years 1995-2008 were identified within an integrated health care delivery system in Southern California encompassing approximately 3 million individuals. Main Outcome Measures: The outcome measures were parathyroidectomy (PTx) and time interval to surgery. Results: We found 3388 patients with PHPT, 964 (28%) of whom underwent PTx. Patients aged 60+ yr comprised 60% of the study cohort. The likelihood of PTx decreased linearly among patients aged 60+ when compared to patients aged 50-59, an effect that persisted in multivariate analysis: odds ratio 0.68 for ages 60-69 (P < 0.05); 0.41 for ages 70-79 (P < 0.0001), and 0.11 for age 80+ (P < 0.0001). The PTx rate for patients aged 70+ was 14%. Among patients meeting 2002 consensus criteria for surgical treatment, 45% of those aged 60-69 and 24% of those aged 70+ underwent PTx. A Cox proportional hazards model showed that patients aged 60+ experienced significantly longer delays from diagnosis to surgery compared to young patients (P < 0.0001). Conclusions: PHPT is undertreated in the elderly. We observed a progressive age-related decline in PTx rate that renders patients aged 70+ unlikely to have definitive treatment, irrespective of comorbidity and eligibility for surgery. (J Clin Endocrinol Metab 95: 4324-4330, 2010) C1 [Wu, Bian; Ituarte, Philip H. G.; Yeh, Michael W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Endocrine Surg Unit, Los Angeles, CA 90095 USA. [Haigh, Philip I.] Kaiser Permanente Los Angeles Med Ctr, Dept Surg, Los Angeles, CA 90027 USA. [Hwang, Roy] Cleveland Clin Lerner Coll Med, Cleveland, OH 44195 USA. [Liu, In-Lu Amy] Kaiser Permanente Reg Off, Ctr Res & Evaluat, Pasadena, CA 91101 USA. [Hahn, Theodore J.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Hahn, Theodore J.] Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. RP Haigh, PI (reprint author), Kaiser Permanente Los Angeles Med Ctr, Dept Surg, 4760 Sunset Blvd, Los Angeles, CA 90027 USA. EM Philip.I.Haigh@kp.org FU University of California-Los Angeles Older Americans Independence Center, National Institutes of Health (NIH)/National Institute on Aging (NIA) [P30-AG028748] FX M.W.Y. received support from the University of California-Los Angeles Older Americans Independence Center, National Institutes of Health (NIH)/National Institute on Aging (NIA) Grant P30-AG028748. The content does not necessarily represent the official views of the NIA or the NIH. NR 36 TC 25 Z9 26 U1 1 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP 4324 EP 4330 DI 10.1210/jc.2009-2819 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300048 PM 20610600 ER PT J AU Fleischman, A Makimura, H Stanley, TL McCarthy, MA Kron, M Sun, N Chuzi, S Hrovat, MI Systrom, DM Grinspoon, SK AF Fleischman, Amy Makimura, Hideo Stanley, Takara L. McCarthy, Meaghan A. Kron, Matthew Sun, Noelle Chuzi, Sarah Hrovat, Mirko I. Systrom, David M. Grinspoon, Steven K. TI Skeletal Muscle Phosphocreatine Recovery after Submaximal Exercise in Children and Young and Middle-Aged Adults SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MITOCHONDRIAL-FUNCTION; BODY; SEX AB Context: Elderly subjects have reduced mitochondrial function. However, it remains unclear whether the decline in mitochondrial function begins earlier in the life span. Objective: The objective of the study was to determine skeletal muscle mitochondrial oxidative phosphorylation by (31)phosphorous-magnetic resonance spectroscopy (MRS) across a variety of age groups. Design: This was a cross-sectional study of 121 healthy normal-weight and overweight individuals from age 8 to 55 yr. Setting: The study was conducted at a single university medical center in Boston, MA. Participants: Participants included 68 children and 53 adults from the Boston community. Interventions and Main Outcome Measures: Phosphocreatine (PCr) recovery was evaluated by (31)phosphorous-MRS after submaximal exercise. Subjects were also evaluated with anthropometric measurements, metabolic profiles, and measures of physical activity. Results: PCr recovery determined by (31)phosphorous-MRS is positively associated with age in univariate analysis in a cohort of individuals aged 8-55 yr (r = +0.55, P < 0.0001). Stratification of subjects into four age groups (prepubertal and early pubertal children, pubertal and postpubertal children < 18 yr, young adults aged 18-39 yr, and middle aged adults aged 40-55 yr) demonstrates prolongation of PCr recovery with increasing age across the four groups (P < 0.0001 by ANOVA). The relationship between PCr recovery and age remains strong when controlling for gender; race; ethnicity; body mass index; measures of physical activity and inactivity; and anthropometric, nutritional, and metabolic parameters (P < 0.004). Conclusions: Skeletal muscle PCr recovery measured by (31)phosphorous-MRS is prolonged with age, even in children and young adults. (J Clin Endocrinol Metab 95: E69-E74, 2010) C1 [Fleischman, Amy; Makimura, Hideo; Stanley, Takara L.; McCarthy, Meaghan A.; Kron, Matthew; Sun, Noelle; Chuzi, Sarah; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Fleischman, Amy; Makimura, Hideo; Stanley, Takara L.; McCarthy, Meaghan A.; Kron, Matthew; Sun, Noelle; Chuzi, Sarah; Grinspoon, Steven K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hrovat, Mirko I.; Systrom, David M.] Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. [Hrovat, Mirko I.] Mirtech Inc, Brockton, MA 02301 USA. RP Makimura, H (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 211, Boston, MA 02114 USA. EM hmakimura@partners.org OI Systrom, David/0000-0002-9610-6330 FU National Institutes of Health [K23DK080658, 1R01HL085268, K24DK064545, UL1RR025758, P41RR14075]; Lawson Wilkins Pediatric Endocrine Society; Children's Hospital Boston FX This work was supported by National Institutes of Health Grants K23DK080658 (to A.F.), 1R01HL085268 (to S.K.G.), K24DK064545 (to S.K.G.), UL1RR025758 (to the Harvard Clinical and Translational Science Center, from the National Center for Research Resources), and P41RR14075 (to the Athinoula A. Martinos Center for Biomedical Imaging). In addition, the study was supported by the Genentech Clinical Scholars Award from the Lawson Wilkins Pediatric Endocrine Society (to A.F.) and a Career Development Award (to A.F.) from the Children's Hospital Boston. NR 24 TC 16 Z9 16 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP E69 EP E74 DI 10.1210/jc.2010-0527 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300012 PM 20554709 ER PT J AU Lindstrom, S Ma, J Altshuler, D Giovannucci, E Riboli, E Albanes, D Allen, NE Berndt, SI Boeing, H Bueno-de-Mesquita, HB Chanock, SJ Dunning, AM Feigelson, HS Gaziano, JM Haiman, CA Hayes, RB Henderson, BE Hunter, DJ Kaaks, R Kolonel, LN Le Marchand, L Martinez, C Overvad, K Siddiq, A Stampfer, M Stattin, P Stram, DO Thun, MJ Trichopoulos, D Tumino, R Virtamo, J Weinstein, SJ Yeager, M Kraft, P Freedman, ML AF Lindstroem, Sara Ma, Jing Altshuler, David Giovannucci, Edward Riboli, Elio Albanes, Demetrius Allen, Naomi E. Berndt, Sonja I. Boeing, Heiner Bueno-de-Mesquita, H. Bas Chanock, Stephen J. Dunning, Alison M. Feigelson, Heather Spencer Gaziano, J. Michael Haiman, Christopher A. Hayes, Richard B. Henderson, Brian E. Hunter, David J. Kaaks, Rudolf Kolonel, Laurence N. Le Marchand, Loic Martinez, Carmen Overvad, Kim Siddiq, Afshan Stampfer, Meir Stattin, Paer Stram, Daniel O. Thun, Michael J. Trichopoulos, Dimitrios Tumino, Rosario Virtamo, Jarmo Weinstein, Stephanie J. Yeager, Meredith Kraft, Peter Freedman, Matthew L. TI A Large Study of Androgen Receptor Germline Variants and Their Relation to Sex Hormone Levels and Prostate Cancer Risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CAG-REPEAT POLYMORPHISM; GROWTH-FACTOR-I; MULTIETHNIC COHORT; GENETIC-VARIATION; REGULATING GENES; STEROID-HORMONES; MEN; NUTRITION; LENGTH; ASSOCIATION AB Background: Androgens are key regulators of prostate gland maintenance and prostate cancer growth, and androgen deprivation therapy has been the mainstay of treatment for advanced prostate cancer for many years. Along-standing hypothesis has been that inherited variation in the androgen receptor (AR) gene plays a role in prostate cancer initiation. However, studies to date have been inconclusive and often suffered from small sample sizes. Objective and Methods: We investigated the association of AR sequence variants with circulating sex hormone levels and prostate cancer risk in 6058 prostate cancer cases and 6725 controls of Caucasian origin within the Breast and Prostate Cancer Cohort Consortium. We genotyped a highly polymorphic CAG microsatellite in exon 1 and six haplotype tagging single nucleotide polymorphisms and tested each genetic variant for association with prostate cancer risk and with sex steroid levels. Results: We observed no association between AR genetic variants and prostate cancer risk. However, there was a strong association between longer CAG repeats and higher levels of testosterone (P = 4.73 x 10(-5)) and estradiol (P = 0.0002), although the amount of variance explained was small (0.4 and 0.7%, respectively). Conclusions: This study is the largest to date investigating AR sequence variants, sex steroid levels, and prostate cancer risk. Although we observed no association between AR sequence variants and prostate cancer risk, our results support earlier findings of a relation between the number of CAG repeats and circulating levels of testosterone and estradiol. (J Clin Endocrinol Metab 95: E121-E127, 2010) C1 [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lindstroem, Sara; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Lindstroem, Sara; Stampfer, Meir; Trichopoulos, Dimitrios; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward; Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ma, Jing; Hunter, David J.; Stampfer, Meir] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. [Altshuler, David] Broad Inst Massachusetts Inst Technol MIT & Harva, Program Med & Populat Genet, Cambridge, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Riboli, Elio; Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Publ Hlth, London, England. [Albanes, Demetrius; Berndt, Sonja I.; Chanock, Stephen J.; Hayes, Richard B.; Weinstein, Stephanie J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Allen, Naomi E.] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge, England. [Feigelson, Heather Spencer; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [Feigelson, Heather Spencer] Kaiser Permanente, Denver, CO USA. [Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA. [Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Haiman, Christopher A.; Henderson, Brian E.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hayes, Richard B.] NYU, Div Epidemiol, Langone Med Ctr, New York, NY USA. [Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Martinez, Carmen] Ctr Invest Biomed Red Epidemiol & Salud Publ, Granada, Spain. [Martinez, Carmen] Andalusian Sch Publ Hlth, Granada, Spain. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Aalborg, Denmark. [Stattin, Paer] Umea Univ, Umea, Sweden. [Tumino, Rosario] Canc Registry Azienda Osped Civile MP Arezzo, Ragusa, Italy. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Yeager, Meredith] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Freedman, Matthew L.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM mfreedman@partners.org RI Altshuler, David/A-4476-2009; Albanes, Demetrius/B-9749-2015; OI Altshuler, David/0000-0002-7250-4107; Dunning, Alison Margaret/0000-0001-6651-7166; Hayes, Richard/0000-0002-0918-661X FU National Cancer Institute [UO1-CA98233, UO1-CA98710, UO1-CA98216, UO1-CA98758]; National Institutes of Health/National Cancer Institute, Division of Cancer Epidemiology and Genetics; Swedish Research Council (Vetenskapsradet) FX This work was supported by National Cancer Institute cooperative agreements UO1-CA98233, UO1-CA98710, UO1-CA98216, and UO1-CA98758, and by the Intramural Research Program of National Institutes of Health/National Cancer Institute, Division of Cancer Epidemiology and Genetics. S. \L. is supported by the Swedish Research Council (Vetenskapsradet). NR 32 TC 26 Z9 27 U1 1 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP E121 EP E127 DI 10.1210/jc.2009-1911 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300020 PM 20534771 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI Meta-Analysis Concludes Angiotensin Receptor Blocker Use Increases the Risk of Developing Cancer: Concerns About the Science and the Message SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material C1 [Bloch, Michael J.] St Marys Reg Med Ctr, Risk Reduct Ctr, Reno, NV 89503 USA. [Bloch, Michael J.] Univ Nevada, Sch Med, Div Gen Internal Med, Div Cardiol, Reno, NV 89557 USA. [Basile, Jan N.] Ralph H Johnson VA Med Ctr, Primary Care Serv Line, Charleston, SC USA. [Basile, Jan N.] Univ S Carolina, Div Gen Internal Med Geriatr, Charleston, SC USA. RP Bloch, MJ (reprint author), St Marys Reg Med Ctr, Risk Reduct Ctr, 645 N Arlington St,Suite 460, Reno, NV 89503 USA. EM mbloch@aol.com NR 3 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD SEP PY 2010 VL 12 IS 9 BP 661 EP 663 DI 10.1111/j.1751-7176.2010.00369.x PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 646QM UT WOS:000281557100001 PM 20883225 ER PT J AU Fan, BJ Wiggs, JL AF Fan, Bao Jian Wiggs, Janey L. TI Glaucoma: genes, phenotypes, and new directions for therapy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID OPEN-ANGLE GLAUCOMA; PRIMARY CONGENITAL GLAUCOMA; NORMAL-TENSION GLAUCOMA; GENOME-WIDE SCAN; GANGLION-CELL SURVIVAL; DNA-SEQUENCE VARIANTS; PIGMENT DISPERSION SYNDROME; FRIZZLED-RELATED PROTEIN; NAIL-PATELLA SYNDROME; BEAVER DAM EYE AB Glaucoma, a leading cause of blindness worldwide, is characterized by progressive optic nerve damage, usually associated with intraocular pressure. Although the clinical progression of the disease is well defined, the molecular events responsible for glaucoma are currently poorly understood and current therapeutic strategies are not curative. This review summarizes the human genetics and genomic approaches that have shed light on the complex inheritance of glaucoma genes and the potential for gene-based and cellular therapies that this research makes possible. C1 [Fan, Bao Jian; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu OI Fan, Baojian/0000-0002-6851-2737 FU NIH [R01 EY009847, R01EY015872, R21EY019161, P30EY014104]; Research to Prevent Blindness; Massachusetts Eye Research Fund FX This work was supported in part by NIH grants R01 EY009847, R01EY015872, R21EY019161, and P30EY014104 and by Research to Prevent Blindness and the Massachusetts Eye Research Fund. NR 143 TC 61 Z9 65 U1 0 U2 17 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 SEP PY 2010 VL 120 IS 9 BP 3064 EP 3072 DI 10.1172/JCI43085 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 645LJ UT WOS:000281458800008 PM 20811162 ER PT J AU Kerschen, E Hernandez, I Zogg, M Jia, SA Hessner, MJ Fernandez, JA Griffin, JH Huettner, CS Castellino, FJ Weiler, H AF Kerschen, Edward Hernandez, Irene Zogg, Mark Jia, Shuang Hessner, Martin J. Fernandez, Jose A. Griffin, John H. Huettner, Claudia S. Castellino, Francis J. Weiler, Hartmut TI Activated protein C targets CD8(+) dendritic cells to reduce the mortality of endotoxemia in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID REGULATORY T-CELLS; IN-VIVO; THROMBIN RECEPTOR; NATURAL-KILLER; SEPTIC SHOCK; DYING CELLS; LIFE-SPAN; KAPPA-B; MOUSE; INFLAMMATION AB Activated protein C (aPC) therapy reduces mortality in adult patients with severe sepsis. In mouse endotoxemia and sepsis models, mortality reduction requires the cell signaling function of aPC, mediated through protease-activated receptor-1 (PAR1) and endothelial protein C receptor (EPCR; also known as Procr). Candidate cellular targets of aPC include vascular endothelial cells and leukocytes. Here, we show that expression of EPCR and PAR1 on hematopoietic cells is required in mice for an aPC variant that mediates full cell signaling activity but only minimal anticoagulant function (5A-aPC) to reduce the mortality of endotoxemia. Expression of EPCR in mature murine immune cells was limited to a subset of CD8(+) conventional dendritic cells. Adoptive transfer of splenic CD11c(hi)PDCA-1(-) dendritic cells from wild-type mice into animals with hematopoietic EPCR deficiency restored the therapeutic efficacy of aPC, whereas transfer of EPCR-deficient CD11c(hi) dendritic cells or wild-type CD11c(hi) dendritic cells depleted of EPCR+ cells did not. In addition, 5A-aPC inhibited the inflammatory response of conventional dendritic cells independent of EPCR and suppressed IFN-gamma production by natural killer-like dendritic cells. These data reveal an essential role for EPCR and PAR1 on hematopoietic cells, identify EPCR-expressing dendritic immune cells as a critical target of aPC therapy, and document EPCR-independent antiinflammatory effects of aPC on innate immune cells. C1 [Kerschen, Edward; Hernandez, Irene; Zogg, Mark; Weiler, Hartmut] Blood Ctr Wisconsin, Blood Res Inst tute, Milwaukee, WI 53226 USA. [Jia, Shuang; Hessner, Martin J.] Med Coll Wisconsin, Max McGee Natl Res Ctr Juvenile Diabet, Dept Pediat, Milwaukee, WI 53226 USA. [Jia, Shuang; Hessner, Martin J.] Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53201 USA. [Fernandez, Jose A.; Griffin, John H.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. [Huettner, Claudia S.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Castellino, Francis J.] Univ Notre Dame Lac, Ctr Transgene Res, Notre Dame, IN USA. RP Weiler, H (reprint author), Blood Ctr Wisconsin, Blood Res Inst tute, 8727 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM hartmut.weiler@bcw.edu RI Fernandez, Jose/A-3211-2008 FU National Institute of Allergy and Infectious Diseases [AI078713, AI080557]; National Heart, Lung and Blood Institute [HL093388, HL31950, HL073750]; Ziegler Family Research Chair Foundation FX We thank Shaun Coughlin for providing PAR1-deficient mice. This work was supported by National Institute of Allergy and Infectious Diseases grants AI078713 (M.J. Hessner) and AI080557 (H. Weiler); National Heart, Lung and Blood Institute grants HL093388 (H. Weiler), HL31950 (J.H. Griffin), and HL073750 (F.J. Castellino); and by the Ziegler Family Research Chair Foundation (H. Weiler) NR 71 TC 62 Z9 64 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 SEP PY 2010 VL 120 IS 9 BP 3167 EP 3178 DI 10.1172/JCI42629 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 645LJ UT WOS:000281458800023 PM 20714108 ER PT J AU Menzies, BE AF Menzies, Barbara E. TI Axillary Abscess Due to Yersinia enterocolitica SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SUPPURATIVE LYMPHADENITIS; ANTIBIOTIC-TREATMENT; CHITTERLINGS; INFECTION AB Yersinia enterocolitica rarely causes extraintestinal disease. A 54-year-old construction worker with chronic hepatitis C developed an axillary abscess following an injury to his finger. An aspirate from the axillary mass grew Y. enterocolitica. Direct inoculation is proposed as the mode of transmission of this classically enteric pathogen. C1 [Menzies, Barbara E.] VA Puget Sound Hlth Care Syst, Infect Dis Sect, Seattle, WA 98108 USA. [Menzies, Barbara E.] Univ Washington, Div Allergy & Infect Dis, Seattle, WA 98195 USA. RP Menzies, BE (reprint author), VA Puget Sound Hlth Care Syst, Infect Dis Sect, S-111 ID,1660 S Columbian Way, Seattle, WA 98108 USA. EM bmenzies@u.washington.edu NR 14 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2010 VL 48 IS 9 BP 3438 EP 3439 DI 10.1128/JCM.00829-10 PG 2 WC Microbiology SC Microbiology GA 645QZ UT WOS:000281480400076 PM 20631098 ER PT J AU Tabernero, J Baselga, J AF Tabernero, Josep Baselga, Jose TI Multigene Assays to Improve Assessment of Recurrence Risk and Benefit From Chemotherapy in Early-Stage Colon Cancer: Has the Time Finally Arrived, or Are We Still Stage Locked? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID COLORECTAL-CANCER; GENE-EXPRESSION; BREAST-CANCER; ADJUVANT TREATMENT; MICROSATELLITE INSTABILITY; PREDICT RECURRENCE; CHROMOSOME 18Q; SURVIVAL; PROGNOSIS; RECOMMENDATIONS C1 [Tabernero, Josep; Baselga, Jose] Vall Hebron Univ Hosp, Vall Hebron Inst Oncol, Barcelona, Spain. [Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Tabernero, J (reprint author), Vall Hebron Univ Hosp, Vall Hebron Inst Oncol, Barcelona, Spain. NR 42 TC 6 Z9 6 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 1 PY 2010 VL 28 IS 25 BP 3904 EP 3907 DI 10.1200/JCO.2010.30.0806 PG 5 WC Oncology SC Oncology GA 645YQ UT WOS:000281502500003 PM 20679612 ER PT J AU Nguyen, PL Ma, J Chavarro, JE Freedman, ML Lis, R Fedele, G Fiore, C Qiu, WL Fiorentino, M Finn, S Penney, KL Eisenstein, A Schumacher, FR Mucci, LA Stampfer, MJ Giovannucci, E Loda, M AF Nguyen, Paul L. Ma, Jing Chavarro, Jorge E. Freedman, Matthew L. Lis, Rosina Fedele, Giuseppe Fiore, Christopher Qiu, Weiliang Fiorentino, Michelangelo Finn, Stephen Penney, Kathryn L. Eisenstein, Anna Schumacher, Fredrick R. Mucci, Lorelei A. Stampfer, Meir J. Giovannucci, Edward Loda, Massimo TI Fatty Acid Synthase Polymorphisms, Tumor Expression, Body Mass Index, Prostate Cancer Risk, and Survival SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Symposium on Gastrointestinal Cancer of the American-Society-of-Clinical-Oncology CY JAN 22-24, 2010 CL Orlando, FL SP Amer Soc Clin Oncol, Royal Marsden Hosp Natl Hlth Serv Fdn Trust ID GENE FAS; ADENOCARCINOMA; ADIPONECTIN; OBESITY; COHORT; CELLS; RATS; MEN AB Purpose Fatty acid synthase (FASN) regulates de novo lipogenesis, body weight, and tumor growth. We examined whether common germline single nucleotide polymorphisms (SNPs) in the FASN gene affect prostate cancer (PCa) risk or PCa-specific mortality and whether these effects vary by body mass index (BMI). Methods In a prospective nested case-control study of 1,331 white patients with PCa and 1,267 age-matched controls, we examined associations of five common SNPs within FASN (and 5 kb upstream/downstream, R(2) > 0.8) with PCa incidence and, among patients, PCa-specific death and tested for an interaction with BMI. Survival analyses were repeated for tumor FASN expression (n = 909). Results Four of the five SNPs were associated with lethal PCa. SNP rs1127678 was significantly related to higher BMI and interacted with BMI for both PCa risk (P(interaction) = .004) and PCa mortality (P(interaction) = .056). Among overweight men (BMI >= 25 kg/m(2)), but not leaner men, the homozygous variant allele carried a relative risk of advanced PCa of 2.49 (95% CI, 1.00 to 6.23) compared with lean men with the wild type. Overweight patients carrying the variant allele had a 2.04 (95% CI, 1.31 to 3.17) times higher risk of PCa mortality. Similarly, overweight patients with elevated tumor FASN expression had a 2.73 (95% CI, 1.05 to 7.08) times higher risk of lethal PCa (P(interaction) = .02). Conclusion FASN germline polymorphisms were significantly associated with risk of lethal PCa. Significant interactions of BMI with FASN polymorphisms and FASN tumor expression suggest FASN as a potential link between obesity and poor PCa outcome and raise the possibility that FASN inhibition could reduce PCa-specific mortality, particularly in overweight men. C1 [Ma, Jing] Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp Boston, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Harvard Med Sch, Boston, MA 02115 USA. Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP Ma, J (reprint author), Brigham & Womens Hosp, 181 Longwood Ave, Boston, MA 02115 USA. EM jing.ma@channing.harvard.edu OI Qiu, Weiliang/0000-0002-9155-6957; Finn, Stephen/0000-0002-8628-5814 FU NCI NIH HHS [CA097193, CA-097193, CA-34944, CA-40360, P01 CA055075, P50 CA090381, P50 CA90381, R01 CA034944, R01 CA040360, R01 CA042182, R01 CA058684, R01 CA097193, R01 CA131945, R01 CA133891, R01CA131945, R01CA133891, R01CA42182, R01CA58684] NR 27 TC 47 Z9 49 U1 1 U2 4 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 1 PY 2010 VL 28 IS 25 BP 3958 EP 3964 DI 10.1200/JCO.2009.27.0793 PG 7 WC Oncology SC Oncology GA 645YQ UT WOS:000281502500012 PM 20679621 ER PT J AU D'Amico, AV Chen, MH Kantoff, PW AF D'Amico, Anthony V. Chen, Ming-Hui Kantoff, Philip W. TI Value of Combined Androgen Blockade in the Neoadjuvant Treatment of Localized Prostate Cancer: The Jury Must Remain Out Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID RADIATION C1 [D'Amico, Anthony V.; Kantoff, Philip W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [D'Amico, Anthony V.; Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Storrs, CT USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, 75 Francis St, 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 1 PY 2010 VL 28 IS 25 BP E447 EP E447 DI 10.1200/JCO.2010.29.5642 PG 1 WC Oncology SC Oncology GA 645YQ UT WOS:000281502500031 ER PT J AU Kelly, PJ Weiss, SE Sher, DJ Perez-Atayde, AR Dal Cin, P Choueiri, TK AF Kelly, Paul J. Weiss, Stephanie E. Sher, David J. Perez-Atayde, Antonio R. Dal Cin, Paola Choueiri, Toni K. TI Sunitinib-Induced Pseudoprogression After Whole-Brain Radiotherapy for Metastatic Renal Cell Carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TYROSINE KINASE INHIBITOR; PANCREATIC-CANCER; MOUSE MODEL; RADIATION; EFFICACY C1 [Kelly, Paul J.; Weiss, Stephanie E.; Sher, David J.; Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Perez-Atayde, Antonio R.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Dal Cin, Paola] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Adv Med Diagnost, Boston, MA 02115 USA. RP Kelly, PJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 13 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2010 VL 28 IS 25 BP E433 EP E435 DI 10.1200/JCO.2009.26.8193 PG 3 WC Oncology SC Oncology GA 645YQ UT WOS:000281502500023 PM 20547999 ER PT J AU Qvarnstrom, M Janket, SJ Jones, JA Jethwani, K Nuutinen, P Garcia, RI Baird, AE Van Dyke, TE Meurman, JH AF Qvarnstrom, Markku Janket, Sok-Ja Jones, Judith A. Jethwani, Kamal Nuutinen, Pekka Garcia, Raul I. Baird, Alison E. Van Dyke, Thomas E. Meurman, Jukka H. TI Association of salivary lysozyme and C-reactive protein with metabolic syndrome SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE atherosclerosis; C-reactive protein; inflammation; metabolic syndrome; salivary lysozyme ID ADVANCED GLYCATION ENDPRODUCTS; CARDIOVASCULAR RISK-FACTORS; CORONARY-ARTERY-DISEASE; HEART-DISEASE; ENDOTHELIAL DYSFUNCTION; VASCULAR EVENTS; ORAL-HEALTH; INFLAMMATION; PERIODONTITIS; IMMUNOASSAY AB P>Introduction Salivary lysozyme (SLZ) is a proteolytic enzyme secreted by oral leucocytes and contains a domain that has an affinity to advanced glycation end products (AGE). Thus, we hypothesized that SLZ would be associated with metabolic syndrome (metS), a pro-inflammatory state. Methods Utilizing cross-sectional data from 250 coronary artery disease (CAD) and 250 non-CAD patients, the association of SLZ with metS was tested by logistic regression analyses controlling for age, sex, smoking, total cholesterol and C-reactive protein (CRP) levels. The analyses were stratified by CAD status to control for the possible effects of CAD. Results MetS was found in 122 persons. The adjusted odds ratio (OR) for metS associated with the highest quartile of SLZ was 1.95 with 95% confidence interval (CI) 1.20-3.12, p-value=0.007, compared with the lower three quartiles combined. Among the 40 subjects with metS but without CAD, the OR was 1.63 (CI: 0.64-4.15, p=0.31), whereas in the CAD group, SLZ was significantly associated with metS [OR=1.96 (1.09-3.52), p=0.02]. In both subgroups, CRP was not significantly associated with metS. Conclusion SLZ was significantly associated with metS (OR=1.95) independent of CRP level. Future longitudinal research is warranted. C1 [Qvarnstrom, Markku] Univ Kuopio, FIN-70211 Kuopio, Finland. [Garcia, Raul I.] Boston Univ, Henry M Goldman Sch Dent Med, Hlth Policy & Hlth Serv Res, Boston, MA 02118 USA. [Jethwani, Kamal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Nuutinen, Pekka] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Baird, Alison E.] Suny Downstate Med Ctr, Cerebrovasc Dis & Stroke Div, Brooklyn, NY USA. [Meurman, Jukka H.] Univ Helsinki, Inst Dent, Helsinki, Finland. [Meurman, Jukka H.] Univ Helsinki, Cent Hosp, Dept Oral & Maxillofacial Dis, Helsinki, Finland. RP Janket, SJ (reprint author), Boston Univ, Sch Dent Med, 100 E Newton St,Rm G-619, Boston, MA 02118 USA. EM skjanket@bu.edu OI Garcia, Raul/0000-0003-2153-4629; Janket, Sok-Ja/0000-0003-0078-3992; Jones, Judith/0000-0002-0126-0790; Meurman, Jukka/0000-0001-6702-6836 FU American Heart Association [0635351N]; Helsinki University Central Hospital, Helsinki, Finland [TYH 3245]; Finnish Medical Society; National Institute of Health [NIH K24 DE018211, DE DE16191, K24 DE000419, R01 DE019833]; USPHS [DE15566] FX This study is supported by a grant from the American Heart Association # 0635351N to Dr. Sok-Ja Janket.; Dr. Meurman is supported by Grant TYH 3245 from the Helsinki University Central Hospital, Helsinki, Finland and a grant from the Finnish Medical Society.; Dr. Jones is supported by NIH K24 DE018211 award from National Institute of Health.; Dr. Van Dyke is supported by NIH Grant DE DE16191 and USPHS Grant DE15566.; Dr. Garcia is supported by NIH Grant K24 DE000419 and R01 DE019833. NR 40 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD SEP PY 2010 VL 37 IS 9 BP 805 EP 811 DI 10.1111/j.1600-051X.2010.01605.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 639RG UT WOS:000280991500003 PM 20666873 ER PT J AU Kunik, ME Snow, AL Davila, JA Steele, AB Balasubramanyam, V Doody, RS Schulz, PE Kalavar, JS Morgan, RO AF Kunik, Mark E. Snow, A. Lynn Davila, Jessica A. Steele, Avila B. Balasubramanyam, Valli Doody, Rachelle S. Schulz, Paul E. Kalavar, Jagadeesh S. Morgan, Robert O. TI Causes of Aggressive Behavior in Patients With Dementia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID NURSING-HOME RESIDENTS; ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC SYMPTOMS; GERIATRIC PSYCHIATRY; CONTROLLED-TRIAL; CACHE COUNTY; CHRONIC PAIN; DEPRESSION; INTERVENTIONS; COMMUNITY AB Objective: To examine factors predicting development of aggression. Method: Community-dwelling patients over 60 years of age in a Veterans Affairs Medical Center who had a documented ICD-9-CM code for dementia within 12 months of screening and no other dementia codes recorded for 2 preceding years but no aggressive behavior during the 12 months preceding study initiation were assessed every 4 months for 24 months for aggression, depression, pain, patient/caregiver relationship quality (mutuality), involvement in pleasant events, and caregiver burden. The study was conducted from September 5, 2003, to June 10, 2005. Results: Of 215 patients, 89 (41%) developed aggression. In individual models, high baseline mutuality decreased risk of aggression; high burden and pain increased risk. Increases in depression and pain and declines in total mutuality also increased risk. In a full model and step-wise model, high levels of baseline caregiver burden, worst pain, and decline in mutuality over time increased risk of aggression. Conclusions: Many dementia patients become aggressive. Higher levels of worst pain, caregiver burden, and declining mutuality over time increase risk of aggression. J Clin Psychiatry 2010;71(9):1145-1152 Copyright (C) 2010 Physicians Postgraduate Press, Inc. C1 [Kunik, Mark E.] Baylor Coll Med, Hlth Serv Res & Dev Serv, Houston Ctr Qual Care & Utilizat Studies, Michael E DeBakey VAMC 152, Houston, TX 77030 USA. [Kunik, Mark E.; Davila, Jessica A.; Steele, Avila B.; Balasubramanyam, Valli; Kalavar, Jagadeesh S.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Kunik, Mark E.; Steele, Avila B.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Kunik, Mark E.; Kalavar, Jagadeesh S.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Doody, Rachelle S.; Schulz, Paul E.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Kunik, Mark E.] Univ Texas Sch Publ Hlth, Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX USA. [Morgan, Robert O.] Univ Texas Sch Publ Hlth, Div Management Policy & Community Hlth, Houston, TX USA. [Snow, A. Lynn] Univ Alabama, Ctr Mental Hlth & Aging, Tuscaloosa, AL USA. [Snow, A. Lynn] Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA. [Snow, A. Lynn] Tuscaloosa Vet Affairs Med Ctr, Tuscaloosa, AL USA. RP Kunik, ME (reprint author), Baylor Coll Med, Hlth Serv Res & Dev Serv, Houston Ctr Qual Care & Utilizat Studies, Michael E DeBakey VAMC 152, 2002 Holcombe, Houston, TX 77030 USA. EM mkunik@bcm.tmc.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (VA HSR&D), Washington, DC [IIR 01-159-2]; Houston Center for Quality of Care and Utilization Studies (Houston VA HSR&D Center of Excellence) [HFP90-020] FX This study was conducted at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas, and was supported by grant #IIR 01-159-2 from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (VA HSR&D), Washington, DC. It was also supported in part by the Houston Center for Quality of Care and Utilization Studies (Houston VA HSR&D Center of Excellence [HFP90-020]), Michael E. DeBakey VA Medical Center, Houston, Texas. NR 56 TC 46 Z9 46 U1 4 U2 15 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 SEP PY 2010 VL 71 IS 9 BP 1145 EP 1152 DI 10.4088/JCP.08m04703oli PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 661EF UT WOS:000282705700006 PM 20361896 ER PT J AU Bender, RE Alloy, LB Sylvia, LG Urosevic, S Abramson, LY AF Bender, Rachel E. Alloy, Lauren B. Sylvia, Louisa G. Urosevic, Snezana Abramson, Lyn Y. TI Generation of Life Events in Bipolar Spectrum Disorders: A Re-examination and Extension of the Stress Generation Theory SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE bipolar spectrum disorder; stress generation; life events; hypomania; depression ID BEHAVIORAL-APPROACH SYSTEM; DEPRESSIVE SYMPTOMS; MOOD DISORDERS; I-DISORDER; CYCLOTHYMIC DISORDER; DIAGNOSTIC-CRITERIA; HOPELESSNESS THEORY; PERSONALITY STYLES; ADOLESCENT WOMEN; MODEL AB The extent to which stress generation occurs in bipolar spectrum disorders (BSD) is not well understood. The present study examined whether 75 BSD participants experienced elevated rates of behavior-dependent life events, as compared with 38 normal control participants. Within the BSD group, we also examined whether depressive or hypomanic symptoms prospectively predicted increases in various types of negative and positive life events. Results indicated that BSD participants experienced overall increases in behavior-dependent events over the follow-up, as compared with normal controls. At the symptom level, the event generation process occurred in more specific event domains. Results suggest that the stress generation theory of unipolar depression can be extended to BSD and that the type of generated events may be polarity-specific. (C) 2010 Wiley Periodicals, Inc. J Clin Psychol: 66:907-926, 2010. C1 [Bender, Rachel E.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Sylvia, Louisa G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Urosevic, Snezana; Abramson, Lyn Y.] Univ Wisconsin, Madison, WI 53706 USA. RP Bender, RE (reprint author), Temple Univ, Dept Psychol, 1701 N 13th St, Philadelphia, PA 19122 USA. EM rachel.bender@temple.edu FU NIMH NIH HHS [R01 MH052617, R01 MH052617-10, R01 MH077908, MH 52617, MH 52662, MH 77908, R01 MH077908-04] NR 61 TC 13 Z9 14 U1 2 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD SEP PY 2010 VL 66 IS 9 BP 907 EP 926 DI 10.1002/jclp.20705 PG 20 WC Psychology, Clinical SC Psychology GA 635SJ UT WOS:000280676200001 PM 20694958 ER PT J AU Mohammadinia, AR Bakhtavar, K Ebrahimi-Daryani, N Habibollahi, P Keramati, MR Fereshtehnejad, SM Abdollahzade, S AF Mohammadinia, Amir Reza Bakhtavar, Khadijeh Ebrahimi-Daryani, Nasser Habibollahi, Peiman Keramati, Mohammad Reza Fereshtehnejad, Seyed Mohammad Abdollahzade, Sina TI Correlation of Hepatic Vein Doppler Waveform and Hepatic Artery Resistance Index with the Severity of Nonalcoholic Fatty Liver Disease SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Article DE nonalcoholic fatty liver disease; hepatic vein waveform; hepatic artery resistance index ID METABOLIC SYNDROME; HEALTHY-SUBJECTS; FLOW PATTERN; STEATOHEPATITIS; ULTRASONOGRAPHY; ULTRASOUND; FIBROSIS; NASH; INFILTRATION; ASSOCIATION AB Purpose. The study was conducted to evaluate the effect of various degrees of fatty infiltration in patients with nonalcoholic fatty liver disease on hepatic artery resistance index and hepatic vein waveform patterns. Methods. After identification and grading of fatty infiltration, 60 patients and 20 normal healthy subjects were examined using color and spectral Doppler sonography. The level of fatty liver infiltration was ascertained and graded by biopsy in patients and excluded by MRI in controls. The patients were allocated to four study groups consecutively, until the required number was reached, according to infiltration level as follows: normal (group A), mild (group B), moderate (group C), and severe (group D). The hepatic vein waveforms were classified into the three following groups: triphasic, biphasic, and monophasic waveform. The hepatic artery resistance index was calculated as the mean of three different measurements. Results. The incidence of monophasic and biphasic hepatic vein waveform was 2 (10%) for group B, 11 (55%) for group C, 16 (80%) for group D, and none for group A. The difference in the distribution of triphasic Doppler waveform pattern between the patients and the control group was significant (p < 0.001). Hepatic artery resistance index was 0.81 (+/- 0.02), 0.78 (+/- 0.03), 0.73 (+/- 0.03), and 0.68 (+/- 0.05), respectively, in groups A, B, C, and D and was significantly different between groups (p < 0.001). Conclusion. As the severity of nonalcoholic fatty infiltration increases, the incidence of abnormal hepatic vein waveforms increases and hepatic artery resistance index decreases. (C) 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:346-352, 2010; Published online in Wiley InterScience (www.interscience. wiley.com). DOI: 10.1002/jcu.20696 C1 [Ebrahimi-Daryani, Nasser] Univ Tehran Med Sci, Dept Gastroenterol, Tehran, Iran. [Mohammadinia, Amir Reza; Bakhtavar, Khadijeh] Univ Tehran Med Sci, Dept Radiol, Tehran, Iran. [Habibollahi, Peiman; Abdollahzade, Sina] Univ Tehran Med Sci, Div Gastroenterol, Tehran, Iran. [Habibollahi, Peiman] Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Keramati, Mohammad Reza; Fereshtehnejad, Seyed Mohammad] Iran Univ Med Sci & Hlth Serv, Tehran, Iran. RP Ebrahimi-Daryani, N (reprint author), Univ Tehran Med Sci, Dept Gastroenterol, Tehran, Iran. RI Keramati, Mohammad Reza/B-4144-2013 OI Keramati, Mohammad Reza/0000-0003-0099-7114 NR 42 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD SEP PY 2010 VL 38 IS 7 BP 346 EP 352 DI 10.1002/jcu.20696 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 640VG UT WOS:000281081200002 PM 20572063 ER PT J AU Giesel, FL Runge, V Kirchin, M Mehndiratta, A Gerigk, L Corell, B von Gall, C Kauczor, HU Essig, M AF Giesel, Frederik L. Runge, Val Kirchin, Miles Mehndiratta, Amit Gerigk, Lars Corell, Body von Gall, Carl Kauczor, Hans-Ulrich Essig, Marco TI Three-Dimensional Multiphase Time-Resolved Low-Dose Contrast-Enhanced Magnetic Resonance Angiography Using TWIST on a 32-Channel Coil at 3 T: A Quantitative and Qualitative Comparison of a Conventional Gadolinium Chelate With a High-Relaxivity Agent SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE low-dose MR angiography; animal studies; contrast media; parallel imaging; 32-channel volume coil ID NEPHROGENIC SYSTEMIC FIBROSIS; GADOBENATE DIMEGLUMINE; MR-ANGIOGRAPHY; GADOPENTETATE DIMEGLUMINE; GD-BOPTA; FIELD STRENGTHS; RENAL-ARTERIES; TESLA; GADODIAMIDE; GADOBUTROL AB Purpose: To evaluate low-dose contrast-enhanced magnetic resonance angiography (CE-MRA) at high temporal and spatial resolution for imaging of abdominal vascular structures. Materials and Methods: Contrast-enhanced magnetic resonance angiography (TWIST [time-resolved angiography with interleaved stochastic trajectories]) was performed in 8 male New Zealand white rabbits at 3 T using a prototype 32-channel coil. Gadoteridol (Gd-HP-DO3A, ProHance; Bracco Imaging SpA, Milan, Italy) and the high-relaxivity agent gadobenate dimeglumine (Gd-BOPTA, MultiHance; Bracco Imaging SpA), each at a dose of 0.04 mmol/kg body weight, were used in an intraindividual comparison. Quantitative analysis of contrast-to-noise ratio (CNR) was performed in regions of interest placed in the aorta and the adjacent tissues. The image quality in the aorta, external iliac artery, and vena cava was categorized by 2 independent blinded readers from excellent (1) to poor (3). Results: A significantly (P < 0.001) higher CNR was obtained with gadobenate dimeglumine. The improved CNR led to a better delineation of the external iliac arteries. Qualitative rating showed the image quality to be excellent for gadobenate dimeglumine and adequate for gadoteridol. Conclusions: Time-resolved CE-MRA performed at 3 T with a 32-channel volume coil can be improved using the high-relaxivity agent gadobenate dimeglumine, which increases quality and quantity of vessel enhancement. C1 [Giesel, Frederik L.; Mehndiratta, Amit; Gerigk, Lars; Essig, Marco] German Canc Res Ctr, Dept Radiol, D-6900 Heidelberg, Germany. [Giesel, Frederik L.; Runge, Val; Corell, Body] Scott & White Mem Hosp & Clin, Dept Radiol, Temple, TX 76508 USA. [Kirchin, Miles] Bracco Imaging SpA, Milan, Italy. [Mehndiratta, Amit] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [von Gall, Carl] Univ Heidelberg, Dept Nucl Med, Heidelberg, Germany. [Kauczor, Hans-Ulrich] Univ Clin, Dept Radiol & Intervent, Heidelberg, Germany. RP Giesel, FL (reprint author), German Canc Res Ctr, Dept Radiol, INF 280, D-69120 Heidelberg, Germany. EM f.giesel@dkfz.de NR 29 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2010 VL 34 IS 5 BP 678 EP 683 DI 10.1097/RCT.0b013e3181e359c2 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 653OD UT WOS:000282100400007 PM 20861769 ER PT J AU Li, L Hsiao, WWL Nandakumar, R Barbuto, SM Mongodin, EF Paster, BJ Fraser-Liggett, CM Fouad, AF AF Li, L. Hsiao, W. W. L. Nandakumar, R. Barbuto, S. M. Mongodin, E. F. Paster, B. J. Fraser-Liggett, C. M. Fouad, A. F. TI Analyzing Endodontic Infections by Deep Coverage Pyrosequencing SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE endodontic infection; pyrosequencing; 16S rRNA gene; bacterial diversity; taxonomy ID HUMAN MICROBIOME PROJECT; RIBOSOMAL-RNA SEQUENCES; HUMAN GUT MICROBIOTA; PHYLOGENETIC ANALYSIS; APICAL PERIODONTITIS; BACTERIAL DIVERSITY; MOLECULAR ANALYSIS; IDENTIFICATION; TAXONOMY; SYNERGISTES AB Bacterial diversity in endodontic infections has not been sufficiently studied. The use of modern pyrosequencing technology should allow for more comprehensive analysis than traditional Sanger sequencing. This study investigated bacterial diversity in endodontic infections through taxonomic classification based on 16S rRNA gene sequences generated by 454 GS-FLX pyrosequencing and conventional Sanger capillary sequencing technologies. Sequencings were performed on 7 specimens from endodontic infections. On average, 47 vs. 28,590 sequences were obtained per sample for Sanger sequencing vs. pyrosequencing, representing a 600-fold difference in "depth-of-coverage". Based on Ribosomal Database Project (RDP II) Classifier analysis, pyrosequencing identified 179 bacterial genera in 13 phyla, which was significantly more than Sanger sequencing. The phylum Bacteroidetes was the most prevalent bacterial phylum. These results indicate that bacterial communities in endodontic infections are more diverse than previously demonstrated. In addition, deep-coverage pyrosequencing of the 16S rRNA gene revealed low-abundance micro-organisms with potential clinical implications. C1 [Li, L.; Fouad, A. F.] Univ Maryland, Sch Dent, Dept Endodont Prosthodont & Operat Dent, Baltimore, MD 21201 USA. [Hsiao, W. W. L.; Mongodin, E. F.; Fraser-Liggett, C. M.] Univ Maryland, Inst Genome Sci, Baltimore, MD 21201 USA. [Nandakumar, R.] Univ Nebraska, Lincoln, NE USA. [Barbuto, S. M.; Paster, B. J.] Forsyth Inst, Boston, MA 02115 USA. RP Fouad, AF (reprint author), Univ Maryland, Sch Dent, Dept Endodont Prosthodont & Operat Dent, 650 W Baltimore St, Baltimore, MD 21201 USA. EM AFouad@umaryland.edu OI Fraser, Claire/0000-0003-1462-2428 FU NIDCR [DE015320-01-A1] FX We thank Dr. Benli Chai from the Ribosomal Database Project, Center for Microbial Ecology, Michigan State University, for his excellent technical support on RDP-related applications. This work was funded by a research grant from the NIDCR (No. DE015320-01-A1). NR 32 TC 39 Z9 42 U1 0 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 2010 VL 89 IS 9 BP 980 EP 984 DI 10.1177/0022034510370026 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 640VI UT WOS:000281081500017 PM 20519493 ER PT J AU Kim, JK Bak, H Kim, B Park, O Wu, X Manstein, D Kositra, G Dotto, GP Chang, S Won, CH Lee, MW Choi, JH Moon, KC AF Kim, Jae-Kyung Bak, Hana Kim, BeomJoon Park, Ounjae Wu, X. Manstein, D. Kositra, G. Dotto, G. P. Chang, SungEun Won, Chong-hyun Lee, Mi-Woo Choi, Jee-ho Moon, Kee-chan TI Expression of Wnt5a, CYR61 and HSP90 in the human skin treated with ablative fractional resurfacing CO2 laser treatment validated by gene expression profiling SO JOURNAL OF DERMATOLOGY LA English DT Meeting Abstract C1 [Kim, Jae-Kyung; Bak, Hana; Park, Ounjae; Chang, SungEun; Won, Chong-hyun; Lee, Mi-Woo; Choi, Jee-ho; Moon, Kee-chan] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Dermatol, Seoul, South Korea. [Kim, BeomJoon] Chung Ang Univ, Dept Dermatol, Seoul, South Korea. [Wu, X.; Manstein, D.; Kositra, G.; Dotto, G. P.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Wellman Ctr, Boston, MA 02114 USA. [Wu, X.; Manstein, D.; Kositra, G.; Dotto, G. P.] Univ Rosanne, Rosanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0385-2407 J9 J DERMATOL JI J. Dermatol. PD SEP PY 2010 VL 37 SU 1 BP 34 EP 35 PG 2 WC Dermatology SC Dermatology GA 648ZF UT WOS:000281733400117 ER PT J AU Pothiawala, S Hsu, MY Yang, FC Kesari, S Ibrahimi, OA AF Pothiawala, Salma Hsu, Mei-Yu Yang, F. Clarissa Kesari, Santosh Ibrahimi, Omar A. TI Urticarial Hypersensitivity Reaction Caused By Temozolomide SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Article ID PHASE-II TRIAL; METASTATIC MELANOMA; MALIGNANCIES; RADIOTHERAPY AB Temozolomide is an oral alkylating agent approved for the treatment of glioblastoma and anaplastic astrocytoma, and is currently under clinical investigation for the treatment of brain metastases from a variety of cancers. Temozolomide is well tolerated, and the reported dermatologic side effects of this medication are limited. Here, the authors report the first case of an urticarial hypersensitivity reaction induced by temozolomide. As this drug will likely be increasingly utilized in the near future, it is important to be aware of its potential to cause adverse cutaneous manifestations. C1 [Ibrahimi, Omar A.] Harvard Univ, Dept Dermatol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pothiawala, Salma] Univ S Florida, Coll Med, Dept Dermatol & Cutaneous Surg, Tampa, FL USA. [Hsu, Mei-Yu] Brigham & Womens Hosp, Dept Pathol, Div Dermatopathol, Boston, MA 02115 USA. [Hsu, Mei-Yu; Yang, F. Clarissa; Kesari, Santosh] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yang, F. Clarissa] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Kesari, Santosh] Dana Farber Canc Inst, Dept Neurol, Boston, MA 02115 USA. RP Ibrahimi, OA (reprint author), Harvard Univ, Dept Dermatol, Sch Med, Massachusetts Gen Hosp, Bartlett Hall 616, Boston, MA 02114 USA. EM omar.ibrahimi@gmail.com RI Kesari, Santosh/E-8461-2013 NR 9 TC 6 Z9 6 U1 1 U2 1 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD SEP PY 2010 VL 9 IS 9 BP 1142 EP 1144 PG 3 WC Dermatology SC Dermatology GA 647KL UT WOS:000281617300015 PM 20865848 ER PT J AU Marsh, RH Levine, AC Noble, VE Brown, DFM Nadel, ES AF Marsh, Regan H. Levine, Adam C. Noble, Vicki E. Brown, David F. M. Nadel, Eric S. TI BLUNT CARDIAC RUPTURE SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID BEDSIDE ECHOCARDIOGRAPHY; PERICARDIAL TAMPONADE; CHEST TRAUMA; HEART; ULTRASOUND; EMERGENCY; MANAGEMENT; INJURY; HEMOPERICARDIUM; SONOGRAPHY C1 [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Marsh, Regan H.] N Shore Med Ctr, Dept Emergency Med, Salem, MA USA. [Levine, Adam C.] Rhode Isl Hosp, Dept Emergency Med, Providence, RI USA. [Noble, Vicki E.; Brown, David F. M.; Nadel, Eric S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. OI Levine, Adam/0000-0003-3982-3824 NR 35 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD SEP PY 2010 VL 39 IS 3 BP 337 EP 340 DI 10.1016/j.jemermed.2010.03.020 PG 4 WC Emergency Medicine SC Emergency Medicine GA 653FD UT WOS:000282072800013 PM 20435425 ER PT J AU Tompkins, M Panuncialman, I Lucas, P Palumbo, M AF Tompkins, Marc Panuncialman, Ian Lucas, Phillip Palumbo, Mark TI SPINAL EPIDURAL ABSCESS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Review DE spinal epidural abscess; early management ID CLINICAL PRESENTATION; PROGNOSTIC FACTORS; MANAGEMENT; DIAGNOSIS; MODEL; CARE AB Background: Spinal epidural abscess is an uncommon disease with a relatively high rate of associated morbidity and mortality. The most important determinant of outcome is early diagnosis and initiation of appropriate treatment. Objectives: We aim to highlight the clinical manifestations, describe the early diagnostic evaluation, and outline the treatment principles for spinal epidural abscess in the adult. Discussion: Spinal epidural abscess should be suspected in the patient presenting with complaints of back pain or a neurologic deficit in conjunction with fever or an elevated erythrocyte sedimentation rate. Gadolinium-enhanced magnetic resonance imaging is the diagnostic modality of choice to confirm the presence and determine the location of the abscess. Emergent surgical decompression and debridement (with or without spinal stabilization) followed by long-term antimicrobial therapy remains the treatment of choice. In select cases, non-operative management can be cautiously considered when the risk of neurologic complications is determined to be low. Conclusion: Patients with a spinal epidural abscess often present first in the emergency department setting. It is imperative for the emergency physician to be familiar with the clinical features, diagnostic work-up, and basic management principles of spinal epidural abscess. (C) 2010 Elsevier Inc. C1 [Tompkins, Marc; Lucas, Phillip; Palumbo, Mark] Brown Alpert Med Sch, Dept Orthopaed Surg, Providence, RI 02903 USA. [Panuncialman, Ian] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Tompkins, M (reprint author), Brown Alpert Med Sch, Dept Orthoped Surg, Dept Orthopaed, COOP 1,593 Eddy St, Providence, RI 02903 USA. NR 35 TC 26 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD SEP PY 2010 VL 39 IS 3 BP 384 EP 390 DI 10.1016/j.jemermed.2009.11.001 PG 7 WC Emergency Medicine SC Emergency Medicine GA 653FD UT WOS:000282072800024 PM 20060254 ER PT J AU Garcez, AS Nunez, SC Hamblim, MR Suzuki, H Ribeiro, MS AF Garcez, Aguinaldo S. Nunez, Silvia C. Hamblim, Michael R. Suzuki, Hideo Ribeiro, Martha S. TI Photodynamic Therapy Associated with Conventional Endodontic Treatment in Patients with Antibiotic-resistant Microflora: A Preliminary Report SO JOURNAL OF ENDODONTICS LA English DT Article DE Antibiotic resistant bacteria; endodontic re-treatment; laser; photodynamic therapy ID STAPHYLOCOCCUS-AUREUS; ENTEROCOCCUS-FAECALIS; ACTIVATED DISINFECTION; PERIAPICAL LESIONS; IN-VITRO; PHOTOINACTIVATION; INFECTION; STRAINS; SUSCEPTIBILITY; DERIVATIVES AB Introduction: This study reports the antimicrobial effect of photodynamic therapy (PDT) combined with endodontic treatment in patients with necrotic pulp infected with microflora resistant to a previous antibiotic therapy. Methods: Thirty anterior teeth from 21 patients with periapical lesions that had been treated with conventional endodontic treatment and antibiotic therapy were selected. Microbiological samples were taken (1) after accessing the root canal, (2) after endodontic therapy, and (3) after PDT. Results: All the patients had at least 1 microorganism resistant to antibiotics. PDT used polyethylenimine chlorin(e6) as a photosensitizer and a diode laser as a light source (P = 40 mW, t = 4minutes, E = 9.6 J). Endodontic therapy alone produced a significant reduction in numbers of microbial species but only 3 teeth were free of bacteria, whereas the combination of endodontic therapy with PDT eliminated all drug-resistant species and all teeth were bacteria-free. Conclusions: The use of PDT added to conventional endodontic treatment leads to a further major reduction of microbial load. PDT is an efficient treatment to kill multi-drug resistant microorganisms. (J Endod 2010;36:1463-1466) C1 [Garcez, Aguinaldo S.; Suzuki, Hideo] Ctr Pesquisa & Posgrad Sao Leopoldo Mandic, Campinas, SP, Brazil. [Nunez, Silvia C.] CETAO, Sao Paulo, Brazil. [Hamblim, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblim, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblim, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Ribeiro, Martha S.] IPEN CNEN SP, Ctr Lasers & Applicat, Sao Paulo, Brazil. RP Garcez, AS (reprint author), Sao Leopoldo Mandic Univ, Campinas, SP, Brazil. EM garcez.segundo@terra.com.br RI Ribeiro, Martha/G-3517-2012; Garcez, Aguinaldo/B-3556-2013; Nunez, Silvia/C-7241-2017 OI Ribeiro, Martha/0000-0002-4203-1134; Garcez, Aguinaldo/0000-0003-2037-7211; Nunez, Silvia/0000-0003-2101-8333 NR 33 TC 47 Z9 49 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD SEP PY 2010 VL 36 IS 9 BP 1463 EP 1466 DI 10.1016/j.joen.2010.06.001 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 647YP UT WOS:000281657100005 PM 20728710 ER PT J AU Eisner, BH Kurtz, MP Gershman, B Arsovska, O Patterson, RF Chew, BH AF Eisner, B. H. Kurtz, M. P. Gershman, B. Arsovska, O. Patterson, R. F. Chew, B. H. TI POST-OPERATIVE ANTIBIOTICS ARE NOT NECESSARY AFTER URETEROSCOPIC STONE TREATMENT SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Eisner, B. H.; Kurtz, M. P.; Gershman, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arsovska, O.] Vancouver Gen Hosp, Vancouver, BC, Canada. [Chew, B. H.] Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD SEP PY 2010 VL 24 SU 1 BP A165 EP A165 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 675UR UT WOS:000283864900460 ER PT J AU Eswara, JR Sacco, D AF Eswara, J. R. Sacco, D. TI STONE CULTURE IS ASSOCIATED WITH ADMISSION FOR UROSEPSIS AFTER ENDOUROLOGICAL PROCEDURES SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Eswara, J. R.; Sacco, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD SEP PY 2010 VL 24 SU 1 BP A202 EP A203 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 675UR UT WOS:000283864901015 ER PT J AU Gershman, B Kulkarni, N Sahani, DV Eisner, BH AF Gershman, B. Kulkarni, N. Sahani, D. V. Eisner, B. H. TI CAUSES OF RENAL FORNICEAL RUPTURE SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Gershman, B.; Kulkarni, N.; Sahani, D. V.; Eisner, B. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD SEP PY 2010 VL 24 SU 1 BP A198 EP A198 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 675UR UT WOS:000283864901001 ER PT J AU Gershman, B Eisner, BH Sacco, D AF Gershman, B. Eisner, B. H. Sacco, D. TI OFFICE-BASED ENDOUROLOGY USING FLUOROSCOPIC GUIDANCE: CLINICAL OUTCOMES AND COST-EFFECTIVENESS SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Gershman, B.; Eisner, B. H.; Sacco, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD SEP PY 2010 VL 24 SU 1 BP A133 EP A134 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 675UR UT WOS:000283864900372 ER PT J AU Jura, YH Lahey, S Eisner, BH Dretler, SP AF Jura, Y. H. Lahey, S. Eisner, B. H. Dretler, S. P. TI RESOLUTION OF PAIN FOLLOWING URETEROSCOPIC TREATMENT OF SMALL, NON-OBSTRUCTING RENAL CALYCEAL STONES SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 [Jura, Y. H.; Lahey, S.; Eisner, B. H.; Dretler, S. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD SEP PY 2010 VL 24 SU 1 BP A196 EP A196 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 675UR UT WOS:000283864900550 ER PT J AU Nicklas, BJ McEneaney, PA Lichniak, JE Baron, RL Brownell, BA AF Nicklas, Bonnie J. McEneaney, Patrick A. Lichniak, James E. Baron, Robert L. Brownell, Benjamin A. TI Surgical Repair of Abductor Hallucis Muscle Herniation: A Case Report SO JOURNAL OF FOOT & ANKLE SURGERY LA English DT Article DE foot; hernia; rupture; surgery; trauma ID COMPARTMENT SYNDROME; TIBIALIS ANTERIOR; MESH AB Herniation of the abductor hallucis muscle has rarely been reported in the literature. This condition causes localized pain, especially while weight bearing, as a result of a complex cascade of biomechanical events directly related to loss of integrity of the medial wall of the foot. The authors present a case of a flexor retinaculum tear with subsequent herniation of the abductor hallucis muscle. When conservative treatment options failed to provide significant relief, surgical intervention was performed, which revealed ischemic muscle tissue and a partial flexor retinaculum tear. The nonviable muscle was surgically debrided and the fascial defect was repaired with a polypropylene nonabsorbable synthetic surgical mesh. This herniorrhaphy reestablished medial compartment support, thus allowing the patient to return to pain-free ambulation. (C) 2010 by the American College of Foot and Ankle Surgeons. All rights reserved. C1 [McEneaney, Patrick A.] Thorek Mem Hosp, Weil Foot & Ankle Inst, Chicago, IL 60613 USA. [Nicklas, Bonnie J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Lichniak, James E.] Ohio Coll Podiatr Med, Dept Podiatr Biomech & Orthoped, Independence, OH USA. [Lichniak, James E.] Cuyahoga Community Coll, Parma, OH USA. [Baron, Robert L.] Franklin Univ Med & Sci, Dept Radiol, William M Scholl Coll Podiatr Med Rosalind, N Chicago, IL USA. [Brownell, Benjamin A.] Vet Affairs Med Ctr, Cent Calif Dept, Fresno, CA USA. RP McEneaney, PA (reprint author), Thorek Mem Hosp, Weil Foot & Ankle Inst, 850 W Irving Pk Rd, Chicago, IL 60613 USA. EM mceneaneydpm@hotmail.com NR 26 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 1067-2516 J9 J FOOT ANKLE SURG JI J. Foot Ankle Surg. PD SEP-OCT PY 2010 VL 49 IS 5 DI 10.1053/j.jfas.2010.06.020 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 642LQ UT WOS:000281215600019 ER PT J AU Egan, JE Casadonte, P Gartenmann, T Martin, J McCance-Katz, EF Netherland, J Renner, JA Weiss, L Saxon, AJ Fiellin, DA AF Egan, James E. Casadonte, Paul Gartenmann, Tracy Martin, Judith McCance-Katz, Elinore F. Netherland, Julie Renner, John A. Weiss, Linda Saxon, Andrew J. Fiellin, David A. TI The Physician Clinical Support System-Buprenorphine (PCSS-B): a Novel Project to Expand/Improve Buprenorphine Treatment SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE buprenorphine; opioid-related disorders; primary health care; education; distance ID OPIOID DEPENDENCE; PRIMARY-CARE; METHADONE-MAINTENANCE; RANDOMIZED-TRIAL; MANAGEMENT; USERS AB Opioid dependence is largely an undertreated medical condition in the United States. The introduction of buprenorphine has created the potential to expand access to and use of opioid agonist treatment in generalist settings. Physicians, however, often have limited training and experience providing this type of care. Some physicians believe having a mentoring relationship with an experienced provider during their initial introduction to the use of buprenorphine would ease implementation. Our goal was to describe the development, implementation, resources, and evaluation of the Physician Clinical Support System-Buprenorphine (PCSS-B), a federally funded program to improve access to and quality of treatment with buprenorphine. We provide a description of the PCSS-B, a national network of 88 trained physician mentors with expertise in buprenorphine treatment and skills in clinical education. We provide information regarding the use the PCSS-B core services including telephone, email and in-person support, a website, clinical guidances, a warmline and outreach to primary care and specialty organizations. Between July 2005 and July 2009, 67 mentors and 4 clinical experts reported providing mentoring services to 632 participants in 48 states, Washington DC and Puerto Rico. A total of 1,455 contacts were provided through email (45%), telephone (34%) and in-person visits (20%). Seventy-six percent of contacts addressed a clinical issue. Eighteen percent of contacts addressed a logistical issue. The number of contacts per participant ranged from 1-125. Between August 2005 and April 2009 there were 72,822 visits to the PCSS-B website with 179,678 pages viewed. Seven guidances were downloaded more than 1000 times. The warmline averaged more than 100 calls per month. The PCSS-B model provides support for a mentorship program to assist non-specialty physicians in the provision of buprenorphine and may serve as a model for dissemination of other types of care. C1 [Egan, James E.; Netherland, Julie; Weiss, Linda] New York Acad Med, New York, NY 10029 USA. [Casadonte, Paul] NYU, Sch Med, New York, NY USA. [Gartenmann, Tracy] ASAM, Chevy Chase, MD USA. [Martin, Judith] BAART Turk St Clin, San Francisco, CA USA. [McCance-Katz, Elinore F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Renner, John A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Renner, John A.] VA Boston Healthcare Syst, Boston, MA USA. [Saxon, Andrew J.] Univ Washington, Addict Care Line VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Fiellin, David A.] Yale Univ, Sch Med, New Haven, CT USA. RP Egan, JE (reprint author), New York Acad Med, 1216 5th Ave, New York, NY 10029 USA. EM jegan@nyam.org OI Fiellin, David/0000-0002-4006-010X FU Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment; National Institute on Drug Abuse (NIDA) [R01 DA019511, R01 DA025991, R01 DA020576]; Titan Pharmaceuticals FX The Physician Clinical Support System-Buprenorphine (PCSS-B) project is funded by the Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment. Dr. Fiellin is supported by the National Institute on Drug Abuse (NIDA R01 DA019511, R01 DA025991, R01 DA020576). We thank Michael L. Green, M.D., M.Sc. for his thoughtful review of an earlier version of this manuscript.; Judith Martin is employed by BAART Programs, a substance abuse treatment program which provides treatment to patients with buprenorphine. Elinore McCance-Katz is on the Data Safety Monitoring Board of Synosia. John Renner has consulted as an author and Advisory Board member with Shire Pharmaceuticals; has received honoraria from Alkermes/Cephalon, Forest Labs, and Reed Medical Education; and owns Johnson & Johnson stock. Andrew Saxon has consulted with Reckitt Benckiser Corporation; has received honoraria from Direct Success, Inc. and Schering-Plough Canada; has received a grant and has another pending from Titan Pharmaceuticals. David Fiellin serves on an expert advisory board to monitor for misuse, abuse, and diversion of buprenorphine for Pinney Associates. NR 39 TC 25 Z9 25 U1 0 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 SEP PY 2010 VL 25 IS 9 BP 936 EP 941 DI 10.1007/s11606-010-1377-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 636JL UT WOS:000280728300015 PM 20458550 ER PT J AU Hausmann, LRM Mor, M Hanusa, BH Zickmund, S Cohen, PZ Grant, R Kresevic, DM Gordon, HS Ling, BS Kwoh, CK Ibrahim, SA AF Hausmann, Leslie R. M. Mor, Maria Hanusa, Barbara H. Zickmund, Susan Cohen, Peter Z. Grant, Richard Kresevic, Denise M. Gordon, Howard S. Ling, Bruce S. Kwoh, C. Kent Ibrahim, Said A. TI The Effect of Patient Race on Total Joint Replacement Recommendations and Utilization in the Orthopedic Setting SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE healthcare disparities; total joint replacement; orthopedic surgery; osteoarthritis; patient preference ID FUNCTIONAL HEALTH LITERACY; TOTAL KNEE REPLACEMENT; TOTAL HIP-ARTHROPLASTY; SURVEY NHANES-I; ETHNIC-DIFFERENCES; RACIAL DISPARITIES; AFRICAN-AMERICAN; NATIONAL-HEALTH; OSTEOARTHRITIS; ARTHRITIS AB The extent to which treatment recommendations in the orthopedic setting contribute to well-established racial disparities in the utilization of total joint replacement (TJR) in the treatment of advanced knee/hip osteoarthritis has not been explored. To examine whether orthopedic surgeons are less likely to recommend TJR to African-American patients compared to white patients with similar clinical indications, and whether there are racial differences in the receipt of TJR within six months of study enrollment. Prospective, observational study. African-American (AA; n = 120) and white (n = 337) patients seeking treatment for knee or hip osteoarthritis in Veterans Affairs orthopedic clinics. Patients completed surveys that assessed socio-demographic and clinical variables that could influence osteoarthritis treatment. Orthopedic surgeons' notes were reviewed to determine whether patients had been recommended for TJR and whether they underwent the procedure within 6 months of study enrollment. Rate of TJR recommendation was 19.5%. Odds of receiving a TJR recommendation were lower for AA than white patients of similar age and disease severity (OR = 0.46, 95% CI = 0.26-0.83; P = 0.01). However, this difference was not significant after adjusting for patient preference for TJR (OR = 0.69, 95% CI = 0.36-1.31, P = 0.25). Overall, 10.3% of patients underwent TJR within 6 months. TJR was less likely for AA patients than for white patients of similar age and disease severity (OR = 0.41, 95% CI = 0.16-1.05, P = 0.06), but this difference was reduced after adjusting for whether patients had received a recommendation for the procedure at the index visit (OR = 0.57, 95% CI = 0.21-1.54, P = 0.27). In this study, race differences in patient preferences for TJR appeared to underlie race differences in TJR recommendations, which led to race differences in utilization of the procedure. Our findings suggest that patient treatment preferences play an important role in racial disparities in TJR utilization in the orthopedic setting. C1 [Hausmann, Leslie R. M.; Mor, Maria; Hanusa, Barbara H.; Zickmund, Susan; Ling, Bruce S.; Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Mor, Maria] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Hanusa, Barbara H.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Grant, Richard; Kresevic, Denise M.] Louis Stokes DVA Med Ctr, Cleveland, OH USA. [Grant, Richard; Kresevic, Denise M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Gordon, Howard S.] Jesse Brown VA Med Ctr, Ctr Complex Chron Care, Chicago, IL USA. [Gordon, Howard S.] Univ Illinois, Coll Med, Chicago, IL USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM leslie.hausmann@gmail.com RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 FU Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; Health Services Research and Development Service [IIR 04-137]; Veterans Affairs Health Services Research and Development [RCD 06-287, ER 0280-1]; VA Health Services; Harold Amos Robert Wood Johnson Scholar Award; National Institutes of Musculoskeletal and Skin Disorders [1K24AR055259-01] FX This study was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (IIR 04-137, PI: Said A. Ibrahim). Dr. Hausmann's effort was supported by the Veterans Affairs Health Services Research and Development Career Development Program (RCD 06-287 and ER 0280-1). Dr. Ibrahim is a previous recipient of a VA Health Services Research Career Development Award and the Harold Amos Robert Wood Johnson Scholar Award. Dr. Ibrahim is also supported by a K24 Award (1K24AR055259-01) from the National Institutes of Musculoskeletal and Skin Disorders. The views expressed here are those of the authors and do not represent those of the Department of Veterans Affairs or the United States Government. The authors would like to thank project coordinator Margaret Kerr and members of the research staff: Elizabeth Flatley, Michael Hannon, Laura Johnson, Renee McDade, Matthew McShane, Rebecca Meiksin, Christine Schneider, Rebecca Siders, Lisa Stewart, and Sandra Truax. The authors would also like to thank Kim Hansen and Hilary Peterson for editorial input on this manuscript. NR 47 TC 29 Z9 29 U1 1 U2 1 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 SEP PY 2010 VL 25 IS 9 BP 982 EP 988 DI 10.1007/s11606-010-1399-5 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 636JL UT WOS:000280728300022 PM 20509053 ER PT J AU Pierce, RG Wong, M Skalet, AB AF Pierce, Read G. Wong, Melisa Skalet, Alison B. TI More to Mutton than Meets the Eye SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE panuveitis; conjunctival injection; slit lamp; tuberculosis AB A 64-year-old Mexican fisherman with a history of syphilis is diagnosed with panuveitis of the right eye after presenting with unilateral blurry vision, redness, and pain. A PPD was 35X30mm, and chest X-ray suggested tuberculosis. The patient's pain and vision improved with 4-drug anti-tuberculous therapy, topical steroids, and cycloplegic eye drops. C1 [Pierce, Read G.; Wong, Melisa; Skalet, Alison B.] UCSF Internal Med & Ophthalmol, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Pierce, RG (reprint author), UCSF Internal Med & Ophthalmol, San Francisco VA Med Ctr, 4150 Clement St,Rm 1A-81,Bldg 203, San Francisco, CA 94121 USA. EM read.pierce@ucsf.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2010 VL 25 IS 9 BP 989 EP 989 DI 10.1007/s11606-010-1406-x PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 636JL UT WOS:000280728300023 PM 20532658 ER PT J AU Singh, PP Newton, DP Estrada, CA AF Singh, Preet Paul Newton, David P. Estrada, Carlos A. TI An Uncommon Cause of Headache SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Singh, Preet Paul; Newton, David P.; Estrada, Carlos A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA. [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. RP Estrada, CA (reprint author), 732 Fac Off Tower,510 20th St S, Birmingham, AL 35294 USA. EM cestrada@uab.edu OI Singh, Preet Paul/0000-0001-8936-8191 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2010 VL 25 IS 9 BP 990 EP 990 DI 10.1007/s11606-010-1366-1 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 636JL UT WOS:000280728300024 PM 20467828 ER PT J AU Rosenbloom-Brunton, DA Henneman, EA Inouye, SK AF Rosenbloom-Brunton, Deborah A. Henneman, Elizabeth A. Inouye, Sharon K. TI Feasibility of Family Participation in a Delirium Prevention Program for Hospitalized Older Adults SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID CONFUSION ASSESSMENT METHOD; ELDER LIFE PROGRAM; MEDICAL INPATIENTS; CARE; INTERVENTION; OUTCOMES; CAREGIVERS; PSYCHOSIS; QUALITY; PEOPLE AB Delirium is the leading complication of hospitalization for older adults. The role family caregivers could play in delirium prevention and how nurses could facilitate family participation has been largely unexplored. This study examined the feasibility of family participation in a multicomponent intervention program for delirium prevention in hospitalized older adults called Family-HELP, as an adaptation and extension of the Hospital Elder Life Program (HELP). Family-HELP demonstrates that active engagement of family caregivers in preventive interventions for delirium is feasible. Intervention completion occurred at least 55% of the time. Three themes emerged on barriers and facilitators for family participation: therapeutic relationships, partnership, and environment. Key to successful implementation of the program is attention to the identified barriers and facilitators. These findings have implications for clinicians committed to delivering quality inpatient care to older adults and their families, with the benefits of HELP being extended to include family caregivers with an important role in delirium prevention efforts. C1 [Rosenbloom-Brunton, Deborah A.] Massachusetts Gen Hosp, Acute Care Nurse Practitioner Program, Grad Program Nursing, Inst Hlth Profess, Boston, MA 02129 USA. [Henneman, Elizabeth A.] Univ Massachusetts, Sch Nursing, Amherst, MA 01003 USA. [Inouye, Sharon K.] Hebrew SeniorLife, Inst Aging Res, Aging Brain Ctr, Milton & Shirley Levy Family Chair, Boston, MA USA. [Inouye, Sharon K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Inouye, Sharon K.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Rosenbloom-Brunton, DA (reprint author), Massachusetts Gen Hosp, Acute Care Nurse Practitioner Program, Grad Program Nursing, Inst Hlth Profess, 36 1st Ave, Boston, MA 02129 USA. EM drosenbloom@mghihp.edu FU Honor Society of Nursing, Sigma Theta Tau International; MGH Institute of Health Professions; National Institute on Aging [K24AG00949]; Retirement Research Foundation [2007225]; Alzheimer's Association [IIRG-08-88737]; Hospital Elder Life Program FX Dr. Rosenbloom-Brunton, Dr. Henneman, and Dr. Inouye disclose that they have no significant financial interests in any product or class of products discussed directly or indirectly in this activity. This study was supported in part by grants from the Honor Society of Nursing, Sigma Theta Tau International (D.A.R.B.), the MGH Institute of Health Professions Geriatric Research Fellowship (D.A.R.B.), National Institute on Aging (grant K24AG00949, S.K.I.), Retirement Research Foundation (grant 2007225, S.K.I.), Alzheimer's Association (grant IIRG-08-88737, S. K. I), and the Hospital Elder Life Program (C) 1999, Sharon K. Inouye, MD, MPH. NR 46 TC 23 Z9 24 U1 2 U2 9 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD SEP PY 2010 VL 36 IS 9 BP 22 EP 33 DI 10.3928/00989134-20100330-02 PG 12 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 719ZK UT WOS:000287249800005 PM 20438016 ER PT J AU Fan, BJ Sena, DRF Pasquale, LR Grosskreutz, CL Rhee, DJ Chen, TC DelBono, EA Haines, JL Wiggs, JL AF Fan, Bao Jian Sena, Dayse R. Figuieredo Pasquale, Louis R. Grosskreutz, Cynthia L. Rhee, Douglas J. Chen, Teresa C. DelBono, Elizabeth A. Haines, Jonathan L. Wiggs, Janey L. TI Lack of Association of Polymorphisms in Elastin With Pseudoexfoliation Syndrome and Glaucoma SO JOURNAL OF GLAUCOMA LA English DT Article DE pseudoexfoliation glaucoma; elastin; polymorphisms ID LOXL1 GENE POLYMORPHISMS; UNITED-STATES POPULATION; COMMON SEQUENCE VARIANTS; OPEN-ANGLE GLAUCOMA; EXFOLIATION-SYNDROME; JAPANESE POPULATION; PREVALENCE; PEOPLE; INDIA; SET AB Purpose: To evaluate the elastin gene (ELN) as a secondary risk factor for pseudoexfoliation syndrome (PXFS) and the associated glaucoma pseudoexfoliation glaucoma (PXFG). Methods: One hundred seventy-eight unrelated patients with PXFS, including 132 patients with PXFG, and 113 unrelated controls were recruited from the Massachusetts Eye and Ear Infirmary. All the patients and controls were white of European ancestry. Three tag SNPs (rs2071307, rs3823879, and rs3757587) that capture the majority of alleles in ELN were genotyped. Single-SNP association was analyzed using Fisher exact test. Haplotype analysis and the set-based test were used to assess the association for the whole gene. Interaction analysis was done between the ELN SNP rs2071307 and LOXL1 SNP rs2165241 using logistic regression. Multiple comparisons were corrected using the Bonferroni method. Results: All 3 ELN tag SNPs were not significantly associated with PXFS and PXFG (P > 0.20). The minor allele frequencies in PXFS, PXFG, and controls were 40.7%, 39.8%, and 45.6%, respectively for rs2071307, 6.7%, 6.3%, and 5.4% for rs3823879, and 14.8%, 16.2%, and 13.6% for rs3757587. Haplotype analysis and the set-based test did not find significant association of ELN with PXFS (P = 0.94 and 0.99, respectively). No significant interaction effects on PXFS were identified between the ELN and LOXL1 SNPs (P = 0.55). Conclusions: Our results suggest that common polymorphisms of ELN are not associated with PXFS and PXFG in white populations. Further studies are required to identify secondary genetic factors that contribute to PXFS. C1 [Fan, Bao Jian; Sena, Dayse R. Figuieredo; Pasquale, Louis R.; Grosskreutz, Cynthia L.; Rhee, Douglas J.; Chen, Teresa C.; DelBono, Elizabeth A.; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Haines, Jonathan L.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu RI Haines, Jonathan/C-3374-2012; OI Fan, Baojian/0000-0002-6851-2737 FU National Eye Institute [R01 EY015882, P30 EY014104]; Research to Prevent Blindness; Massachusetts Lions Eye Research Fund FX Grant Support: In part by National Eye Institute Grants R01 EY015882 and P30 EY014104, Research to Prevent Blindness and The Massachusetts Lions Eye Research Fund. NR 38 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD SEP PY 2010 VL 19 IS 7 BP 432 EP 436 DI 10.1097/IJG.0b013e3181c4b0fe PG 5 WC Ophthalmology SC Ophthalmology GA 651EX UT WOS:000281909100002 PM 20051886 ER EF