FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Snider, AJ Gandy, KAO Obeid, LM AF Snider, Ashley J. Gandy, K. Alexa Orr Obeid, Lina M. TI Sphingosine kinase: Role in regulation of bioactive sphingolipid mediators in inflammation SO BIOCHIMIE LA English DT Review DE Sphingosine-1-phosphate; Sphingosine kinase; Inflammation; Ceramide; Tumor necrosis factor-alpha ID NECROSIS-FACTOR-ALPHA; COLLAGEN-INDUCED ARTHRITIS; CIRCULATING MATURE LYMPHOCYTES; PROTEIN-COUPLED RECEPTORS; CELL-PROLIFERATION; TNF-ALPHA; SPHINGOSINE-1-PHOSPHATE RECEPTORS; PLASMA-MEMBRANE; IN-VIVO; DEPENDENT TRANSLOCATION AB Sphingolipids and their synthetic enzymes are emerging as important mediators in inflammatory responses and as regulators of immune cell functions. In particular, sphingosine kinase (SK) and its product sphingosine-1-phosphate (S1P) have been extensively implicated in these processes. SK catalyzes the phosphorylation of sphingosine to SIP and exists as two isoforms, SK1 and SK2. SK1 has been shown to be activated by cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL1-beta). The activation of SK1 in this pathway has been shown to be, at least in part, required for mediating TNF-alpha and IL1-beta inflammatory responses in cells, including induction of cyclo-oxygenase 2 (COX2). In addition to their role in inflammatory signaling, SK and SIP have also been implicated in various immune cell functions including, mast cell degranulation, migration of neutrophils, and migration and maturation of lymphocytes. The involvement of sphingolipids and sphingolipid metabolizing enzymes in inflammatory signaling and immune cell functions has implicated these mediators in numerous inflammatory disease states as well. The contribution of these mediators, specifically SK1 and S1P, to inflammation and disease are discussed in this review. Published by Elsevier Masson SAS. C1 [Snider, Ashley J.; Gandy, K. Alexa Orr; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA. [Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29403 USA. [Obeid, Lina M.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,MSC 779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [1F32KD084604-01, GM062887]; GAANN fellowship [P200A070596]; Institutional Training Grant [HL007260]; VA Merit Award; VAMC Research Excellence Award FX This work was supported by National Institutes of Health Grants 1F32KD084604-01 (AJS), GM062887 (LMO), and GAANN fellowship P200A070596 and Institutional Training Grant, HL007260 (KAOG). As well as, VA Merit Award (LMO) and by the VAMC Research Excellence Award Program (REAP) (LMO and AJS). We would like to thank Kathy Wiita-Fisk for her administrative assistance. NR 124 TC 65 Z9 66 U1 0 U2 10 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD JUN PY 2010 VL 92 IS 6 SI SI BP 707 EP 715 DI 10.1016/j.biochi.2010.02.008 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 614YF UT WOS:000279095000019 PM 20156522 ER PT J AU Yu, WH Hovik, H Chen, T AF Yu, Wen-Han Hovik, Hedda Chen, Tsute TI A hidden Markov support vector machine framework incorporating profile geometry learning for identifying microbial RNA in tiling array data SO BIOINFORMATICS LA English DT Article ID TRANSCRIPTIONAL ACTIVITY; GLOBAL IDENTIFICATION; GENOME; EXPRESSION; MICROARRAYS; MODELS; VALIDATION; REGIONS; MAP AB Motivation: RNA expression signals detected by high-density genomic tiling microarrays contain comprehensive transcriptomic information of the target organism. Current methods for determining the RNA transcription units are still computation intense and lack the discriminative power. This article describes an efficient and accurate methodology to reveal complicated transcriptional architecture, including small regulatory RNAs, in microbial transcriptome profiles. Results: Normalized microarray data were first subject to support vector regression to estimate the profile tendency by reducing noise interruption. A hybrid supervised machine learning algorithm, hidden Markov support vector machines, was then used to classify the underlying state of each probe to 'expression' or 'silence' with the assumption that the consecutive state sequence was a heterogeneous Markov chain. For model construction, we introduced a profile geometry learning method to construct the feature vectors, which considered both intensity profiles and changes of intensities over the probe spacing. Also, a robust strategy was used to dynamically evaluate and select the training set based only on prior computer gene annotation. The algorithm performed better than other methods in accuracy on simulated data, especially for small expressed regions with lower (< 1) SNR (signal-to-noise ratio), hence more sensitive for detecting small RNAs. C1 [Yu, Wen-Han; Chen, Tsute] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. [Yu, Wen-Han] Boston Univ, Bioinformat Grad Program, Boston, MA 02118 USA. [Hovik, Hedda] Univ Oslo, Fac Dent, Dept Oral Biol, Oslo, Norway. RP Chen, T (reprint author), Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. EM tchen@forsyth.org FU National Institute for Dental and Craniofacial Research [R21 DE018803-01A1]; Faculty of Dentistry, University of Oslo, Oslo, Norway FX Funding: National Institute for Dental and Craniofacial Research (grant no. R21 DE018803-01A1); Mobility grant from the Faculty of Dentistry, University of Oslo, Oslo, Norway (to H. H.). NR 31 TC 4 Z9 5 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN 1 PY 2010 VL 26 IS 11 BP 1423 EP 1430 DI 10.1093/bioinformatics/btq162 PG 8 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 600KT UT WOS:000277985500006 PM 20395286 ER PT J AU Perlis, RH Fijal, B Dharia, S Heinloth, AN Houston, JP AF Perlis, Roy H. Fijal, Bonnie Dharia, Sweta Heinloth, Alexandra N. Houston, John P. TI Failure to Replicate Genetic Associations with Antidepressant Treatment Response in Duloxetine-Treated Patients SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ABCB1; GRIK4; OPRM1; phosphodiesterases; SLC6A4; SNP ID MAJOR DEPRESSIVE DISORDER; SEROTONIN TRANSPORTER; POLYMORPHISMS; CITALOPRAM AB Background: Recent studies have identified associations of polymorphisms in several target genes with antidepressant treatment response of serotonin reuptake inhibitors and a tricyclic antidepressant. We sought to replicate these associations in a study of a serotonin-norepinephrine reuptake inhibitor. Methods: In 250 outpatients with nonpsychotic major depressive disorder, response to treatment with once-daily duloxetine (60 mg/day) over 6 weeks was examined for associations with polymorphisms in eight candidate genes previously associated with antidepressant response using mixed-effect model repeated-measures analysis. Treatment response was quantified on the basis of changes from baseline using 17-item Hamilton Depression Rating Scale total scores. Results: Polymorphisms in PDE1A, PDE1C, PDE6A PDE11A, ABCB1, GRIK4, SLC6A4, and OPRM1 genes showed no statistically significant associations (uncorrected, two-tailed p > .05) with duloxetine treatment response. Conclusions: Previously, described associations between polymorphisms in candidate genes and antidepressant treatment response were not replicated in this study. This result may suggest that previous associations are specific to serotonin reuptake inhibitors. C1 [Fijal, Bonnie; Houston, John P.] Lilly USA LLC, Indianapolis, IN 46285 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Pharmacogenom Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Dharia, Sweta; Heinloth, Alexandra N.] UnitedHlth Grp, Statprobe, Ann Arbor, MI USA. RP Houston, JP (reprint author), Lilly USA LLC, Mail Code 4103, Indianapolis, IN 46285 USA. EM houston_john_p@lilly.com FU Lilly and Company; AstraZeneca; Bristol-Myers Squibb; GlaxoSmithKline; Pfizer; Proteus FX This work was sponsored by Lilly and Company and/or any of its subsidiaries. Drs. Fijal and Houston are full-time employees of Lilly, USA, LLC. and minor stockholders of Eli Lilly and Company. Dr. Perlis has received honoraria or consulting fees from Eli Lilly and Company, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, and Proteus and is a stockholder in Concordant Rater Systems, LLC. Ms. Dharia and Dr. Heinloth are full-time employees of i3 Statprobe, a division of Ingenix, which is a subsidiary of UnitedHealth Group. Eli Lilly and Company and/or any of its subsidiaries contracted editorial assistance for this article with i3 Statprobe. NR 19 TC 41 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2010 VL 67 IS 11 BP 1110 EP 1113 DI 10.1016/j.biopsych.2009.12.010 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 599MT UT WOS:000277918000015 PM 20110084 ER PT J AU Cairo, MS Jordan, CT Maley, CC Chao, C Melnick, A Armstrong, SA Shlomchik, W Molldrem, J Ferrone, S Mackall, C Zitvogel, L Bishop, MR Giralt, SA June, CH AF Cairo, Mitchell S. Jordan, Craig T. Maley, Carlo C. Chao, Clifford Melnick, Ari Armstrong, Scott A. Shlomchik, Warren Molldrem, Jeff Ferrone, Soldano Mackall, Crystal Zitvogel, Laurence Bishop, Michael R. Giralt, Sergio A. June, Carl H. TI NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on the Biological Considerations of Hematological Relapse following Allogeneic Stem Cell Transplantation Unrelated to Graft-versus-Tumor Effects: State of the Science SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Relapse; Allogeneic stem cell transplant; Biology; Resistance; Cancer stem cells ID ACUTE MYELOID-LEUKEMIA; MINIMAL RESIDUAL DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; HISTONE DEACETYLASE INHIBITORS; HEDGEHOG PATHWAY ACTIVATION; 2 IRRADIATION REGIMENS; TOTAL-BODY IRRADIATION; SELF-RENEWAL CAPACITY; HUMAN PROSTATE-CANCER AB Hematopoietic malignant relapse still remains the major cause of death following allogeneic hematopoietic stem cell transplantation (HSCT). Although there has been a large focus on the immunologic mechanisms responsible for the graft-versus-tumor (GVT) effect or lack thereof, there has been little attention paid to investigating the biologic basis of hematologic malignant disease relapse following allogeneic HSCT. There are a large number of factors that are responsible for the biologic resistance of hematopoietic tumors following allogeneic HSCT. We have focused on 5 major areas including clonal evolution of cancer drug resistance, cancer radiation resistance, genomic basis of leukemia resistance, cancer epigenetics, and resistant leukemia stem cells. We recommend increased funding to pursue 3 broad areas that will significantly enhance our understanding of the biologic basis of malignant relapse after allogeneic HSCT, including: ( I) genomic and epigenetic alterations, (2) cancer stem cell biology, and (3) clonal cancer drug and radiation resistance. Biol Blood Marrow Transplant 16: 709-728 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Cairo, Mitchell S.] Columbia Univ, Morgan Stanley Childrens Hosp, New York Presbyterian Hosp, Dept Pediat Med & Pathol, New York, NY 10032 USA. [Jordan, Craig T.] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA. [Jordan, Craig T.] Univ Rochester, Med Ctr, Dept Biomed Genet, Rochester, NY 14642 USA. [Maley, Carlo C.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Chao, Clifford] Columbia Univ, Dept Radiat Oncol, New York, NY 10032 USA. [Melnick, Ari] Yeshiva Univ, Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY USA. [Armstrong, Scott A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Shlomchik, Warren] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Molldrem, Jeff] MD Anderson, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Surg, Pittsburgh, PA USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Immunol, Pittsburgh, PA USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Pathol, Pittsburgh, PA USA. [Mackall, Crystal] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Zitvogel, Laurence] Inst Gustave Roussy, Rouen, France. [Bishop, Michael R.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Giralt, Sergio A.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [June, Carl H.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [June, Carl H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Cairo, MS (reprint author), Columbia Univ, Div Pediat Blood & Marrow Transplantat, 3959 Broadway,CHN 10-03, New York, NY 10032 USA. EM mc1310@columbia.edu FU National Cancer Institute FX This article was supported by the National Cancer Institute. NR 157 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2010 VL 16 IS 6 BP 709 EP 728 DI 10.1016/j.bbmt.2010.03.002 PG 20 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 601GQ UT WOS:000278046700001 PM 20227509 ER PT J AU Koreth, J Aldridge, J Kim, HT Alyea, EP Cutler, C Armand, P Ritz, J Antin, JH Soiffer, RJ Ho, VT AF Koreth, John Aldridge, Julie Kim, Haesook T. Alyea, Edwin P., III Cutler, Corey Armand, Philippe Ritz, Jerome Antin, Joseph H. Soiffer, Robert J. Ho, Vincent T. TI Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation in Patients Over 60 Years: Hematologic Malignancy Outcomes Are Not Impaired in Advanced Age SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Nonmyeloablative; Allogeneic; Elderly ID ACUTE-MYELOID-LEUKEMIA; ELDERLY-PATIENTS; MYELODYSPLASTIC-SYNDROME; HODGKINS-LYMPHOMA; UNRELATED DONORS; OLDER PATIENTS; RISK; DISEASE; MODEL; INDEX AB Reduced-intensity-conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is markedly underutilized in the elderly, in part because the impact of advanced age on outcomes is poorly understood. We retrospectively analyzed outcomes in 158 consecutive hematologic malignancy patients aged >= 60 years (median, 63 years; range: 60-71 years) undergoing fludarabine/busulfan-based RIC, with a median-follow-up of 34 months (range: 12.0-85.7). Multivariate analysis was undertaken for factors having an impact on outcome. For the patients aged >= 60 years, 2-year nonrelapse mortality (NRM) and relapse was 10% and 54.6%, respectively. Two-year overall and progression-free survival (OS, PFS) was 46% and 35%, respectively. Grade II-IV acute and chronic graft-versus-host disease (aGVHD, cGVHD) incidence was 19.6% and 45.9%, respectively. Comparing 110 patients aged 60-64 years versus 48 patients aged >= 65 years, 2-year NRM and relapse was 10.5% versus 8.3% (P = .84) and 53.5% versus 56.3% (P = .31), respectively. Grade II-IV aGVHD and cGVHD incidence was 19.1% versus 22.9% (P = .52) and 51.8% versus 32.5% (P = .01), respectively. Two-year OS and PFS was 49% versus 41% (P = .11) and 36% versus 35% (P = .24), respectively. In a multivariate Cox-model, high-risk disease associated with poorer PFS (hazard ratio [HR] = 2.1, P = .01) and OS (HR = 1.84, P = .03); acute myelogenous leukemia/myelodysplastic syndrome diagnosis (HR = 1.66, P = .03) and matched-related donor (HR = 1.62, P =.03) associated with poorer PFS. RIC HSCT is well tolerated, with reasonable survival in elderly patients. Age is not associated with impaired outcomes. HSCT should not be excluded solely based on advanced patient age. Biol Blood Marrow Transplant 16: 792-800 (2010) (C) 2010 Elsevier Inc. All rights reserved. C1 [Koreth, John; Alyea, Edwin P., III; Cutler, Corey; Armand, Philippe; Ritz, Jerome; Antin, Joseph H.; Soiffer, Robert J.; Ho, Vincent T.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Aldridge, Julie; Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Koreth, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM john_koreth@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU NIH [CA142106] FX Clinical Trial ID: NA. This work was supported in part by NIH Grant CA142106. NR 24 TC 44 Z9 47 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2010 VL 16 IS 6 BP 792 EP 800 DI 10.1016/j.bbmt.2009.12.537 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 601GQ UT WOS:000278046700007 PM 20074656 ER PT J AU Baggish, AL van Kimmenade, RRJ Pinto, Y Richards, AM Lainchbury, J Bayes-Genis, A Santalo, M Ordonez-Llanos, J Januzzi, JL AF Baggish, Aaron L. van Kimmenade, Roland R. J. Pinto, Yigal Richards, A. Mark Lainchbury, John Bayes-Genis, Antoni Santalo, Miquel Ordonez-Llanos, Jordi Januzzi, James L. TI New York Heart Association class versus amino-terminal pro-B type natriuretic peptide for acute heart failure prognosis SO BIOMARKERS LA English DT Article DE Acute decompensated heart failure; NYHA; prognosis; NT-proBNP; natriuretic peptides ID NT-PROBNP; VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; EMERGENCY DIAGNOSIS; EJECTION FRACTION; MORTALITY; CLASSIFICATION; PREDICTION; OUTCOMES; MANAGEMENT AB Background: The prognostic value of the New York Heart Association classification (NYHAC) in acutely decompensated heart failure (ADHF) is unknown. Objectives: We sought to determine the relative value of NYHAC among patients with concomitantly measured amino-terminal pro-B type natriuretic peptide (NT-proBNP) at presentation with ADHF. Materials and methods: NYHAC was determined for 720 patients with ADHF and 1-year mortality status was examined. Cox-proportional hazards analysis compared the prognostic accuracy of NYHAC with other ADHF risk measures. Results: NYHAC had a significant univariate association with 1-year mortality status (HR 1.41, 95% confidence interval (CI) 1.03-1.94; p = 0.03) but was not a significant predictor of death in a multivariable model that included NT-proBNP (HR 2.14; 95% CI 1.65-2.81, p<0.001). Conclusions: In contrast to objective measures such as NT-proBNP, the NYHAC appears to provide limited prognostic information among individuals with ADHF. C1 [Baggish, Aaron L.; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Baggish, Aaron L.; Januzzi, James L.] Harvard Univ, Sch Med, Boston, MA USA. [van Kimmenade, Roland R. J.; Pinto, Yigal] Univ Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. [Richards, A. Mark; Lainchbury, John] Christchurch Sch Med & Hlth Sci, Christchurch Cardioendocrine Res Grp, Christchurch, New Zealand. [Bayes-Genis, Antoni; Santalo, Miquel; Ordonez-Llanos, Jordi] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Cardiol, E-08193 Barcelona, Spain. [Bayes-Genis, Antoni; Santalo, Miquel; Ordonez-Llanos, Jordi] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Biochem & Mol Biol, E-08193 Barcelona, Spain. [Bayes-Genis, Antoni; Santalo, Miquel; Ordonez-Llanos, Jordi] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Emergency Med, E-08193 Barcelona, Spain. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,32 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org RI Ordonez-Llanos, Jorge/A-9335-2010; Ordonez-Llanos, Jordi/B-4961-2011; Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Ordonez-Llanos, Jordi/0000-0003-4896-5832; Bayes-Genis, Antoni/0000-0002-3044-197X; FU Roche Diagnostics FX J.L.J. and A.M.R have received grant support and speaking fees from Roche Diagnostics. NR 28 TC 10 Z9 10 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD JUN PY 2010 VL 15 IS 4 BP 307 EP 314 DI 10.3109/13547501003632580 PG 8 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 612OC UT WOS:000278908100003 PM 20370326 ER PT J AU Cai, T Tian, L Uno, H Solomon, SD Wei, LJ AF Cai, T. Tian, L. Uno, Hajime Solomon, Scott D. Wei, L. J. TI Calibrating parametric subject-specific risk estimation SO BIOMETRIKA LA English DT Article DE Cardiovascular diseases; Cox model; Nonparametric functional estimation; Risk index; ROC analysis; Survival analysis ID CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; NONPARAMETRIC REGRESSION; PREDICTION RULES; MODELS; MARKER; SCORE; LIMITATIONS; DYSFUNCTION; VALSARTAN AB For modern evidence-based medicine, decisions on disease prevention or management strategies are often guided by a risk index system. For each individual, the system uses his/her baseline information to estimate the risk of experiencing a future disease-related clinical event. Such a risk scoring scheme is usually derived from an overly simplified parametric model. To validate a model-based procedure, one may perform a standard global evaluation via, for instance, a receiver operating characteristic analysis. In this article, we propose a method to calibrate the risk index system at a subject level. Specifically, we developed point and interval estimation procedures for t-year mortality rates conditional on the estimated parametric risk score. The proposals are illustrated with a dataset from a large clinical trial with post-myocardial infarction patients. C1 [Cai, T.; Wei, L. J.] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Tian, L.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Uno, Hajime] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Cai, T (reprint author), Harvard Univ, Dept Biostat, Boston, MA 02115 USA. EM tcai@hsph.harvard.edu; lutian@stanford.edu; huno@jimmy.harvard.edu; ssolomon@partners.org; wei@hsph.harvard.edu RI Solomon, Scott/I-5789-2013 FU National Institutes of Health, U.S.A FX The authors are grateful to the editor and the reviewers for their insightful comments on the article. The work was partially supported by grants from the National Institutes of Health, U.S.A. NR 38 TC 19 Z9 19 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD JUN PY 2010 VL 97 IS 2 BP 389 EP 404 DI 10.1093/biomet/asq012 PG 16 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 634DM UT WOS:000280559700010 PM 23049123 ER PT J AU Estiu, G West, N Mazitschek, R Greenberg, E Bradner, JE Wiest, O AF Estiu, Guillermina West, Nathan Mazitschek, Ralph Greenberg, Edward Bradner, James E. Wiest, Olaf TI On the inhibition of histone deacetylase 8 SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE HDAC; Computational drug design; Molecular dynamics; Enzymology ID CATION-PI INTERACTIONS; MESH EWALD METHOD; MOLECULAR-DYNAMICS; CLASS-II; CRYSTAL-STRUCTURE; INTERNAL CAVITY; CANCER-THERAPY; HUMAN HDAC8; SUBSTRATE; PROTEIN AB Histone deacetylases are key regulators of gene expression and have recently emerged as important therapeutic targets for cancer and a growing number of non-malignant diseases. Many widely studied inhibitors of HDACs such as SAHA are thought to have low selectivity within or between the human HDAC isoform classes. Using an isoform-selective assay, we have shown that a number of the known inhibitors have in fact a low activity against HDAC8. Based on the wealth of structural information available for human HDAC8, we use a combination of docking and molecular dynamics simulations to determine the structural origin of the experimental results. A close relationship is found between the activity and the high surface malleability of HDAC8. These results provide a rationale for the recently described 'linkerless' HDAC8 selective inhibitors and design criteria for HDAC8 selective inhibitors. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Estiu, Guillermina; Wiest, Olaf] Univ Notre Dame, Walther Canc Res Ctr, Notre Dame, IN 46556 USA. [Estiu, Guillermina; Wiest, Olaf] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [West, Nathan; Mazitschek, Ralph; Greenberg, Edward; Bradner, James E.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. [West, Nathan; Mazitschek, Ralph; Greenberg, Edward; Bradner, James E.] MIT, Cambridge, MA 02142 USA. [West, Nathan; Greenberg, Edward; Bradner, James E.] Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Wiest, O (reprint author), Univ Notre Dame, Walther Canc Res Ctr, Notre Dame, IN 46556 USA. EM owiest@nd.edu RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X FU Walther Cancer Institute; Multiple Myeloma Research Foundation; National Cancer Institute Initiative for Chemical Genetics FX We thank the Walther Cancer Institute (G. E. and O.W.), the Multiple Myeloma Research Foundation (J.E.B. and E. G.) and the National Cancer Institute Initiative for Chemical Genetics (R. M.) for support of this research. The computations were performed on Kraken (a Cray XT5) at the National Institute for Computational Sciences (http://www.nics.tennessee.edu/) and in Queen Bee at the Louisiana Optical Network Initiative. Generous allocation of computing resources by the Center for Research Computing at the University of Notre Dame is also acknowledged. NR 58 TC 45 Z9 45 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 1 PY 2010 VL 18 IS 11 BP 4103 EP 4110 DI 10.1016/j.bmc.2010.03.080 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 601QR UT WOS:000278078600051 PM 20472442 ER PT J AU Jiang, JK Boxer, MB Vander Heiden, MG Shen, M Skoumbourdis, AP Southall, N Veith, H Leister, W Austin, CP Park, HW Inglese, J Cantley, LC Auld, DS Thomas, CJ AF Jiang, Jian-kang Boxer, Matthew B. Vander Heiden, Matthew G. Shen, Min Skoumbourdis, Amanda P. Southall, Noel Veith, Henrike Leister, William Austin, Christopher P. Park, Hee Won Inglese, James Cantley, Lewis C. Auld, Douglas S. Thomas, Craig J. TI Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Warburg effect; Pyruvate kinase; Cellular metabolism; Anti-cancer strategies; Small molecule activators ID CANCER CELLS; M-GENE; GROWTH; RAT; IDENTIFICATION; METABOLISM; INHIBITORS; ISOZYMES; HALIDES; M2-PK AB Cancer cells have distinct metabolic needs that are different from normal cells and can be exploited for development of anti-cancer therapeutics. Activation of the tumor specific M2 form of pyruvate kinase (PKM2) is a potential strategy for returning cancer cells to a metabolic state characteristic of normal cells. Here, we describe activators of PKM2 based upon a substituted thieno[3,2-b]pyrrole[3,2-d]pyridazinone scaffold. The synthesis of these agents, structure-activity relationships, analysis of activity at related targets (PKM1, PKR and PKL) and examination of aqueous solubility are investigated. These agents represent the second reported chemotype for activation of PKM2. Published by Elsevier Ltd. C1 [Jiang, Jian-kang; Boxer, Matthew B.; Shen, Min; Skoumbourdis, Amanda P.; Southall, Noel; Veith, Henrike; Leister, William; Austin, Christopher P.; Inglese, James; Auld, Douglas S.; Thomas, Craig J.] NHGRI, Chem Genom Ctr, NIH, Rockville, MD 20850 USA. [Vander Heiden, Matthew G.] MIT, Robert Koch Inst, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.; Cantley, Lewis C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vander Heiden, Matthew G.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Park, Hee Won] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L5, Canada. [Park, Hee Won] Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. RP Thomas, CJ (reprint author), NHGRI, Chem Genom Ctr, NIH, 9800 Med Ctr Dr,Bldg B,Room 3005,MSC 3370, Bethesda, MD 20892 USA. EM craigt@nhgri.nih.gov RI Southall, Noel/H-8991-2012; Cantley, Lewis/D-1800-2014 OI Southall, Noel/0000-0003-4500-880X; Cantley, Lewis/0000-0002-1298-7653 FU National Institutes of Health Roadmap for Medical Research; National Human Genome Research Institute, National Institutes of Health [R03MH085679]; Canadian Institutes for Health Research; Canadian Foundation for Innovation; Genome Canada through the Ontario Genomics Institute; GlaxoSmithKline; Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Merck Co., Inc.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust FX The authors thank Jeremy Smith, Paul Shinn, and Danielle van Leer for assistance with compound management. We thank Ms. Allison Mandich for critical reading of this manuscript. This research was supported by the Molecular Libraries Program of the National Institutes of Health Roadmap for Medical Research and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health and R03MH085679. The Structural Genomics Consortium is a registered charity (No. 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co., Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research, and the Wellcome Trust. NR 34 TC 48 Z9 51 U1 0 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 1 PY 2010 VL 20 IS 11 BP 3387 EP 3393 DI 10.1016/j.bmcl.2010.04.015 PG 7 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 597UY UT WOS:000277788900042 PM 20451379 ER PT J AU Harvey, PD Wingo, AP Burdick, KE Baldessarini, RJ AF Harvey, Philip D. Wingo, Aliza P. Burdick, Katherine E. Baldessarini, Ross J. TI Cognition and disability in bipolar disorder: lessons from schizophrenia research SO BIPOLAR DISORDERS LA English DT Review DE bipolar disorder; cognition; disability; schizophrenia; treatment ID MEDICATION MANAGEMENT ABILITY; QUALITY-OF-LIFE; NEUROCOGNITIVE IMPAIRMENT; I DISORDER; FUNCTIONAL-CAPACITY; EUTHYMIC PATIENTS; NEUROPSYCHOLOGICAL DEFICITS; EXECUTIVE FUNCTION; OLDER-ADULTS; 1ST-DEGREE RELATIVES AB Background: Cognitive and functional impairments occur in patients diagnosed with bipolar disorder (BPD), although they are usually less severe and far less studied than in schizophrenia. There may be value in applying approaches developed in schizophrenia research to study cognitive functioning among BPD patients in areas including performance-based disability assessment, cognitive remediation treatments, enhancement of the accuracy of real-world functioning, and studying cognition and disability in relatives. Methods: We reviewed current research on cognitive and functional disability in BPD, noted areas of similarity and discrepancy to research on schizophrenia, and highlighted methods and approaches used to study schizophrenia that can be applied to study unmet needs of BPD patients. Results: Research in schizophrenia increasingly separates potential functional capacity from real-world outcome status, and has assessed contributions of cognitive impairment and other illness factors to functional outcomes. For schizophrenia, various behavioral and pharmacological treatments aimed at cognitive enhancement have been attempted, with moderate success, compared to rare studies of treatment effects on cognitive impairment in BPD. Very little research has been performed in the occurrence of cognitive impairments in first-degree relatives of people with BPD, despite evidence that cognitive impairments may be stable traits across symptomatic status in people with BPD. Conclusions: Research and treatment approaches developed for schizophrenia can productively be applied to the study and treatment of patients diagnosed with BPD, notably including studies of the characteristics of and treatments for functional impairment related to cognitive deficits. C1 [Harvey, Philip D.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Burdick, Katherine E.] Zucker Hillside Hosp N Shore Long Isl Jewish Hlth, Div Psychiat Res, Dept Psychiat, Glen Oaks, NY USA. [Burdick, Katherine E.] Feinstein Inst Med Res, Ctr Translat Psychiat, Manhasset, NY USA. [Burdick, Katherine E.] Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10467 USA. [Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Baldessarini, Ross J.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Psychopharmacol Program, Belmont, MA USA. [Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Mailman Res Ctr, Belmont, MA USA. RP Harvey, PD (reprint author), Emory Univ, Sch Med, Dept Psychiat & Behav Sci, 101 Woodruff Circle,NE,Suite 4000, Atlanta, GA 30322 USA. EM philip.harvey@emory.edu RI Burdick, Katherine/G-6124-2012 FU AstraZeneca; NIH [MH63116, MH78775, MH077807, MH079995]; American Psychiatric Institute for Research and Education; Bruce J. Anderson Foundation; McLean Private Donors Research Fund FX PDH has received current research support from AstraZeneca and has served as an advisor or consultant in the past year to Eli Lilly & Co., Dainippon Sumitomo America, Solvay Pharma, Abbott, and Shire. KEB is a member of the Merck speakers bureau. RJB has been a consultant or investigator-initiated research collaborator with Auritec, Biotrofix, IFI, Janssen, JDS, Eli Lilly & Co., Luitpold, Merck, NeuroHealing, Novartis, and SK-BioPharmaceuticals. APW has no relevant potential conflicts of interest to report. The authors and their family members do not hold equity positions in any pharmaceutical or biomedical companies.; This research was supported by NIH Grants MH63116 and MH78775 (PDH); a research fellowship from the American Psychiatric Institute for Research and Education (APW); NIH Grants MH077807 and MH079995 (KEB); and by a grant from the Bruce J. Anderson Foundation, and by the McLean Private Donors Research Fund (RJB). NR 118 TC 70 Z9 70 U1 5 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2010 VL 12 IS 4 BP 364 EP 375 DI 10.1111/j.1399-5618.2010.00831.x PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 613YJ UT WOS:000279020900002 PM 20636633 ER PT J AU Kling, DE Cavicchio, AJ Sollinger, CA Schnitzer, JJ Kinane, TB Newburg, DS AF Kling, David E. Cavicchio, Amanda J. Sollinger, Christina A. Schnitzer, Jay J. Kinane, T. Bernard Newburg, David S. TI Nitrofen Induces Apoptosis Independently of Retinaldehyde Dehydrogenase (RALDH) Inhibition SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE retinaldehyde dehydrogenase (RALDH); apoptosis; dose-response; retinal; lung; differentiation; retinol; vitamin A; teratogenesis ID CONGENITAL DIAPHRAGMATIC-HERNIA; RETINOIC ACID; PULMONARY HYPOPLASIA; CELL-DEATH; VITAMIN-A; TERATOGEN NITROFEN; LUNG DEVELOPMENT; ANIMAL-MODEL; STEM-CELLS; NILE-RED AB BACKGROUND: Nitrofen is a diphenyl ether that induces congenital diaphragmatic hernia (CDH) in rodents. Its mechanism of action has been hypothesized as inhibition of the retinaldehyde dehydrogenase (RALDH) enzymes with consequent reduced retinoic acid signaling. METHODS: To determine if nitrofen inhibits RALDH enzymes, a reporter gene construct containing a retinoic acid response-element (RARE) was transfected into HEK-293 cells and treated with varying concentrations of nitrofen in the presence of retinaldehyde (retinal). Cell death was characterized by caspace-cleavage microplate assays and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assays. Ex vivo analyses of cell viability were characterized in fetal rat lung explants using Live/Dead staining. Cell proliferation and apoptosis were assessed using fluorescent immunohistochemistry with phosphorylated histone and activated caspase antibodies on explant tissues. Nile red staining was used to identify intracellular lipid droplets. RESULTS: Nitrofen-induced dose-dependent declines in RARE-reporter gene expression. However, similar reductions were observed in control-reporter constructs suggesting that nitrofen compromised cell viability. These observed declines in cell viability resulted from increased cell death and were confirmed using two independent assays. Ex vivo analyses showed that mesenchymal cells were particularly susceptible to nitrofen-induced apoptosis while epithelial cell proliferation was dramatically reduced in fetal rat lung explants. Nitrofen treatment of these explants also showed profound lipid redistribution, primarily to phagocytes. CONCLUSIONS: The observed declines in nitrofen-associated retinoic acid signaling appear to be independent of RALDH inhibition and likely result from nitrofen induced cell death/apoptosis. These results support a cellular apoptotic mechanism of CDH development, independent of RALDH inhibition. Birth Defects Res (Part B) 89:223-232, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Kling, David E.] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Cavicchio, Amanda J.; Sollinger, Christina A.; Schnitzer, Jay J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA USA. [Kinane, T. Bernard] Harvard Univ, Sch Med, Dept Pediat, Lab Dev Immunol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Newburg, David S.] Harvard Univ, Program Glycobiol Pediat Gastroenterol & Nutr, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. RP Kling, DE (reprint author), Boston Coll, Dept Biol, Higgins Hall,Rm 480,140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM klingd@bc.edu NR 55 TC 11 Z9 11 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD JUN PY 2010 VL 89 IS 3 BP 223 EP 232 DI 10.1002/bdrb.20247 PG 10 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 616AX UT WOS:000279181100007 PM 20549697 ER PT J AU Harnisch, BA Stolzmann, KL Lerner, LB AF Harnisch, Brooke A. Stolzmann, Kelly L. Lerner, Lori B. TI Mentoring, fellowship training and academic careers of women urologists SO BJU INTERNATIONAL LA English DT Editorial Material ID MEDICINE; RESIDENTS; CHOICE C1 [Harnisch, Brooke A.] Boston Med Ctr, Boston, MA USA. [Stolzmann, Kelly L.; Lerner, Lori B.] Vet Affairs Boston Healthcare Syst, W Roxbury, MA USA. RP Lerner, LB (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02130 USA. EM Lerner_lori@hotmail.com NR 15 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JUN PY 2010 VL 105 IS 12 BP 1629 EP 1631 DI 10.1111/j.1464-410X.2010.09391.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 601BT UT WOS:000278033700002 PM 20456337 ER PT J AU Schroeck, FR Kattan, MW Moul, JW Aronson, WJ Presti, JC Terris, MK Kane, CJ Amling, CL Sun, L Freedland, SJ AF Schroeck, Florian R. Kattan, Michael W. Moul, Judd W. Aronson, William J. Presti, Joseph C., Jr. Terris, Martha K. Kane, Christopher J. Amling, Christopher L. Sun, Leon Freedland, Stephen J. TI Re-calibration and external validation of an existing nomogram to predict aggressive recurrences after radical prostatectomy SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; biochemical recurrence; PSA doubling time; aggressive recurrence; nomogram ID BIOCHEMICAL RECURRENCE; DOUBLING TIME; CANCER; RADIOTHERAPY; PROGRESSION; MORTALITY; FAILURE; TRIAL; RACE AB OBJECTIVE To re-calibrate the previously published Duke Prostate Center (DPC) nomogram for the prediction of biochemical recurrence (BCR) after radical prostatectomy (RP) to not only predict overall BCR but also the clinically more relevant endpoint of an aggressive recurrence (i.e. a BCR with a postoperative PSA doubling time (PSADT) of < 9 months). PATIENTS AND METHODS Using the established point-scale system based upon the previously published DPC nomogram, we re-calibrated this point system to predict not just BCR, but also aggressive BCR within 2599 men treated with RP from the DPC database. PSADT was computed on all patients meeting the recurrence definition who had a minimum of two PSA values, separated by at least 3 months, and < 2 years after recurrence. External validation was performed using data from 1695 men treated with RP within the Shared Equal Access Regional Cancer Hospital (SEARCH) database by calculating the concordance index c and by plotting calibration curves. RESULTS The median follow-up for patients with no BCR was 56 and 47 months for DPC and SEARCH, respectively. In the DPC modelling cohort and the SEARCH validation cohort, 645 (25%) and 557 (33%) men had BCR, while 83 (3.2%) and 71 (4.2%) patients had an aggressive recurrence. In external validation, predictive accuracy for an aggressive BCR was high (c = 0.83) and the nomogram showed good calibration. CONCLUSIONS We re-calibrated an existing nomogram to not only predict overall BCR after RP but also aggressive recurrence after RP. Our new tool can provide valuable information for patient counselling and patient selection for adjuvant therapy trials. C1 [Freedland, Stephen J.] Duke Univ, Sch Med, Div Urol, Dept Pathol, Durham, NC 27710 USA. [Schroeck, Florian R.; Moul, Judd W.; Sun, Leon; Freedland, Stephen J.] Duke Univ, Sch Med, Dept Surg, Div Urol Surg, Durham, NC 27710 USA. [Schroeck, Florian R.; Moul, Judd W.; Sun, Leon; Freedland, Stephen J.] Duke Univ, Sch Med, Duke Prostate Ctr, Durham, NC 27710 USA. [Schroeck, Florian R.; Sun, Leon; Freedland, Stephen J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Kattan, Michael W.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Aronson, William J.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. [Presti, Joseph C., Jr.] VA Med Ctr, Urol Sect, Palo Alto, CA USA. [Terris, Martha K.] VA Med Ctr, Urol Sect, Augusta, GA USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Kane, Christopher J.] Univ Calif San Diego, Med Ctr, Dept Surg, Div Urol, San Diego, CA 92103 USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Dept Surg, Div Urol, Portland, OR USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, Div Urol, Dept Pathol, Box 2626 DUMC, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270; Schroeck, Florian/0000-0002-1860-2611 FU Department of Defense; Department of Veterans Affairs, National Institute of Health [R01CA100938]; NIH [P50 CA92131-01A1]; Georgia Cancer Coalition; American Urological Association Foundation/Astellas; Committee for Urologic Research, Education, and Development (CURED) at Duke University FX Research support: Department of Defense, Prostate Cancer Research Program (S.J.F.); Department of Veterans Affairs, National Institute of Health R01CA100938 (W.J.A.), NIH Specialized Programs of Research Excellence Grant P50 CA92131-01A1 (W.J.A.), the Georgia Cancer Coalition (M.K.T.), the American Urological Association Foundation/Astellas Rising Star in Urology Award (S.J.F.), and Committee for Urologic Research, Education, and Development (CURED) at Duke University (F.R.S., J.W.M., L.S., S.J.F.). NR 18 TC 6 Z9 6 U1 0 U2 0 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 JUN PY 2010 VL 105 IS 12 BP 1654 EP 1659 DI 10.1111/j.1464-410X.2009.09060.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 601BT UT WOS:000278033700007 PM 19912203 ER PT J AU Cao, HH Nazarian, A Ackerman, JL Snyder, BD Rosenberg, AE Nazarian, RM Hrovat, MI Dai, GP Mintzopoulos, D Wu, YT AF Cao, Haihui Nazarian, Ara Ackerman, Jerome L. Snyder, Brian D. Rosenberg, Andrew E. Nazarian, Rosalynn M. Hrovat, Mirko I. Dai, Guangping Mintzopoulos, Dionyssios Wu, Yaotang TI Quantitative P-31 NMR spectroscopy and H-1 MRI measurements of bone mineral and matrix density differentiate metabolic bone diseases in rat models SO BONE LA English DT Article DE Bone mineralization; MRI; WASPI; Osteoporosis; Osteomalacia ID PROTON PROJECTION MRI; OVARIECTOMIZED RATS; CORTICAL BONE; MECHANICAL-PROPERTIES; COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; IN-VIVO; RENAL-INSUFFICIENCY; MOLECULAR-DYNAMICS; OSTEOPENIC RATS AB In this study, bone mineral density (BMD) of normal (CON), ovariectomized (OVX), and partially nephrectomized (NFR) rats was measured by P-31 NMR spectroscopy; bone matrix density was measured by H-1 water- and fat-suppressed projection imaging (WASPI); and the extent of bone mineralization (EBM) was obtained by the ratio of BMD/bone matrix density. The capability of these MR methods to distinguish the bone composition of the CON, OVX, and NFR groups was evaluated against chemical analysis (gravimetry). For cortical bone specimens, BMD of the CON and OVX groups was not significantly different; BMD of the NFR group was 22.1% (by P-31 NMR) and 17.5% (by gravimetry) lower than CON. For trabecular bone specimens, BMD of the OVX group was 40.5% (by P-31 NMR) and 24.6% (by gravimetry) lower than CON; BMD of the NFR group was 26.8% (by P-31 NMR) and 21.5% (by gravimetry) lower than CON. No significant change of cortical bone matrix density between CON and OVX was observed by WASPI or gravimetry; NFR cortical bone matrix density was 10.3% (by WASPI) and 13.9% (by gravimetry) lower than CON. OVX trabecular bone matrix density was 38.0% (by WASPI) and 30.8% (by gravimetry) lower than CON, while no significant change in NFR trabecular bone matrix density was observed by either method. The EBMs of OVX cortical and trabecular specimens were slightly higher than CON but not significantly different from CON. Importantly, EBMs of NFR cortical and trabecular specimens were 12.4% and 26.3% lower than CON by P-31 NMR/WASPI, respectively, and 4.0% and 11.9% lower by gravimetry. Histopathology showed evidence of osteoporosis in the OVX group and severe secondary hyperparathyroidism (renal osteodystrophy) in the NFR group. These results demonstrate that the combined 31P NMR/WASPI method is capable of discerning the difference in EBM between animals with osteoporosis and those with impaired bone mineralization. (C) 2010 Elsevier Inc. All rights reserved. C1 [Cao, Haihui; Ackerman, Jerome L.; Snyder, Brian D.; Wu, Yaotang] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Nazarian, Ara; Snyder, Brian D.] Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA. [Cao, Haihui; Ackerman, Jerome L.; Dai, Guangping; Mintzopoulos, Dionyssios; Wu, Yaotang] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ackerman, Jerome L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Rosenberg, Andrew E.; Nazarian, Rosalynn M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hrovat, Mirko I.] Mirtech Inc, Brockton, MA 02301 USA. [Cao, Haihui; Nazarian, Ara; Ackerman, Jerome L.; Snyder, Brian D.; Rosenberg, Andrew E.; Nazarian, Rosalynn M.; Dai, Guangping; Mintzopoulos, Dionyssios; Wu, Yaotang] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wu, YT (reprint author), Childrens Hosp, Dept Orthopaed Surg, 300 Longwood Ave,Room 930,Enders Bldg, Boston, MA 02115 USA. EM yaotang.wu@childrens.harvard.edu RI Ackerman, Jerome/E-2646-2015; OI Ackerman, Jerome/0000-0001-5176-7496; Nazarian, Rosalynn/0000-0003-4003-7193 FU National Institutes of Health [EB004012]; National Center for Research Resources, National Institutes of Health [P41RR14075]; MIND Institute; Athinoula A. Martinos Center for Biomedical Imaging FX This work was supported by a grant from National Institutes of Health (EB004012). MR facilities were supported in part by National Institutes of Health grant P41RR14075 from the National Center for Research Resources, the MIND Institute, and the Athinoula A. Martinos Center for Biomedical Imaging. We thank Dr. Robert M. Neer of Massachusetts General Hospital for helpful discussions and Dr. Melvin J. Glimcher of Children's Hospital Boston for inspiration and guidance during the research and spirited discussions about the manuscript. NR 50 TC 17 Z9 17 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2010 VL 46 IS 6 BP 1582 EP 1590 DI 10.1016/j.bone.2010.02.020 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 607EF UT WOS:000278481000013 PM 20188225 ER PT J AU Mawardi, H Stevenson, K Gokani, B Soiffer, R Treister, N AF Mawardi, H. Stevenson, K. Gokani, B. Soiffer, R. Treister, N. TI Combined topical dexamethasone/tacrolimus therapy for management of oral chronic GVHD SO BONE MARROW TRANSPLANTATION LA English DT Article DE topical; dexamethasone; tacrolimus; cGVHD; oral ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; CLINICAL-TRIALS; TACROLIMUS OINTMENT; ATOPIC-DERMATITIS; MANIFESTATIONS; CRITERIA; ABSORPTION AB Chronic GVHD (cGVHD) frequently affects the oral cavity. The purpose of this study was to estimate the efficacy of combined topical dexamethasone (DEX) and tacrolimus (TAC) solutions in the management of oral cGVHD. The records of 14 patients with oral cGVHD treated with combined topical DEX/TAC were reviewed retrospectively. Pre-to-post treatment changes in subjective and objective measures were evaluated at a median follow-up of 60 days. Serum TAC levels were examined. Marginal objective improvement was detected at follow-up. The median pre-to-post treatment differences were 0.5 (range, -1 to 1) for erythema score, and 0.5 (range, 0 to 2) for lichenoid score, (P = 0.06, 0.07 and 0.02, respectively). Subjective improvement was noted in three of four measures at the follow-up visit. The median differences in pain, sensitivity and dryness scores were 1 (range -1 to 6), 1 (range -3 to 5) and 2.5 (range, -5 to 5), respectively (0-10 scale, P<0.05). Four patients (37%) showed increased serum TAC levels; however, all remained within therapeutic range. In conclusion, combined topical DEX/TAC therapy appears to be effective in reducing symptoms attributable to oral cGVHD. Our data has shown minimal evidence of systemic TAC absorption. Bone Marrow Transplantation (2010) 45, 1062-1067; doi:10.1038/bmt.2009.301; published online 2 November 2009 C1 [Mawardi, H.; Treister, N.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Mawardi, H.; Treister, N.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Stevenson, K.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gokani, B.] Univ London Imperial Coll Sci Technol & Med, London, England. [Soiffer, R.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Mawardi, H (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 75 Francis St, Boston, MA 02115 USA. EM hmawardi@partners.org NR 31 TC 9 Z9 10 U1 0 U2 0 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 JUN PY 2010 VL 45 IS 6 BP 1062 EP 1067 DI 10.1038/bmt.2009.301 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 608HG UT WOS:000278573600016 PM 19881552 ER PT J AU Keller, CJ Truccolo, W Gale, JT Eskandar, E Thesen, T Carlson, C Devinsky, O Kuzniecky, R Doyle, WK Madsen, JR Schomer, DL Mehta, AD Brown, EN Hochberg, LR Ulbert, I Halgren, E Cash, SS AF Keller, Corey J. Truccolo, Wilson Gale, John T. Eskandar, Emad Thesen, Thomas Carlson, Chad Devinsky, Orrin Kuzniecky, Ruben Doyle, Werner K. Madsen, Joseph R. Schomer, Donald L. Mehta, Ashesh D. Brown, Emery N. Hochberg, Leigh R. Ulbert, Istvan Halgren, Eric Cash, Sydney S. TI Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex SO BRAIN LA English DT Article DE microelectrodes; focal epilepsy; spike-wave; single unit; microphysiology ID TEMPORAL-LOBE EPILEPSY; HUMAN HIPPOCAMPAL-NEURONS; HUMAN LIMBIC NEURONS; SPIKE GENERATION; HUMAN NEOCORTEX; MOTOR CORTEX; IN-VIVO; EEG; EPILEPTOGENESIS; SEIZURES AB Epileptic cortex is characterized by paroxysmal electrical discharges. Analysis of these interictal discharges typically manifests as spike-wave complexes on electroencephalography, and plays a critical role in diagnosing and treating epilepsy. Despite their fundamental importance, little is known about the neurophysiological mechanisms generating these events in human focal epilepsy. Using three different systems of microelectrodes, we recorded local field potentials and single-unit action potentials during interictal discharges in patients with medically intractable focal epilepsy undergoing diagnostic workup for localization of seizure foci. We studied 336 single units in 20 patients. Ten different cortical areas and the hippocampus, including regions both inside and outside the seizure focus, were sampled. In three of these patients, high density microelectrode arrays simultaneously recorded between 43 and 166 single units from a small (4 mm x 4 mm) patch of cortex. We examined how the firing rates of individual neurons changed during interictal discharges by determining whether the firing rate during the event was the same, above or below a median baseline firing rate estimated from interictal discharge-free periods (Kruskal-Wallis one-way analysis, P < 0.05). Only 48% of the recorded units showed such a modulation in firing rate within 500 ms of the discharge. Units modulated during the discharge exhibited significantly higher baseline firing and bursting rates than unmodulated units. As expected, many units (27% of the modulated population) showed an increase in firing rate during the fast segment of the discharge (+/- 35 ms from the peak of the discharge), while 50% showed a decrease during the slow wave. Notably, in direct contrast to predictions based on models of a pure paroxysmal depolarizing shift, 7.7% of modulated units recorded in or near the seizure focus showed a decrease in activity well ahead (0-300 ms) of the discharge onset, while 12.2% of units increased in activity in this period. No such pre-discharge changes were seen in regions well outside the seizure focus. In many recordings there was also a decrease in broadband field potential activity during this same pre-discharge period. The different patterns of interictal discharge-modulated firing were classified into more than 15 different categories. This heterogeneity in single unit activity was present within small cortical regions as well as inside and outside the seizure onset zone, suggesting that interictal epileptiform activity in patients with epilepsy is not a simple paroxysm of hypersynchronous excitatory activity, but rather represents an interplay of multiple distinct neuronal types within complex neuronal networks. C1 [Keller, Corey J.; Truccolo, Wilson; Hochberg, Leigh R.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Keller, Corey J.] Albert Einstein Coll Med, Bronx, NY 10461 USA. [Truccolo, Wilson] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Gale, John T.; Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Keller, Corey J.; Truccolo, Wilson; Gale, John T.; Eskandar, Emad; Brown, Emery N.; Hochberg, Leigh R.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gale, John T.; Eskandar, Emad] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nayef Al Rodhan Labs Cellular Neurosurg & Neurros, Boston, MA 02114 USA. [Thesen, Thomas; Carlson, Chad; Devinsky, Orrin; Kuzniecky, Ruben; Doyle, Werner K.] New York Univ, Sch Med, Comprehens Epilepsy Ctr, New York, NY 10016 USA. [Madsen, Joseph R.] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Madsen, Joseph R.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Schomer, Donald L.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. [Mehta, Ashesh D.] N Shore LIJ Hlth Syst, Dept Neurol, Manhasset, NY 11030 USA. [Mehta, Ashesh D.] N Shore LIJ Hlth Syst, Dept Neurosurg, Manhasset, NY 11030 USA. [Mehta, Ashesh D.] N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] Massachusetts Inst Technol, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.; Hochberg, Leigh R.] Dept Vet Affairs, Rehabil Res & Dev Serv, Providence, RI 02912 USA. [Hochberg, Leigh R.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Hochberg, Leigh R.] Brown Univ, Div Engn, Providence, RI 02912 USA. [Ulbert, Istvan] Natl Inst Neurosci, Budapest, Hungary. [Ulbert, Istvan] Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. [Ulbert, Istvan] Peter Pazmany Catholic Univ, Dept Informat Technol, Budapest, Hungary. [Halgren, Eric] Univ Calif San Diego, Dept Radiol, San Diego, CA 92093 USA. [Halgren, Eric] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92093 USA. [Halgren, Eric] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA. RP Cash, SS (reprint author), 30 Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM scash@partners.org RI Ulbert, Istvan/F-2213-2010; OI Keller, Corey/0000-0003-0529-3490; Devinsky, Orrin/0000-0003-0044-4632 FU CIMIT under U.S. Army Medical Research Acquisition [W81XWH-09-2-0001]; EFA-Grass-Morison Fellowship; Rappaport Fellowship; National Institutes of Health [NIH-NS062092, NIH-NS018741]; NEI [R01EY017658]; NIDA [R01NS063249]; NSF [IOB 0645886]; HHMI; Klingenstein Foundation; [DP1-0D003646] FX This work was supported by CIMIT under U.S. Army Medical Research Acquisition Activity Cooperative Agreement W81XWH-09-2-0001, an EFA-Grass-Morison Fellowship, Rappaport Fellowship and the National Institutes of Health: NIH-NS062092 to SSC.; NIH-NS018741 to EH.; EE was supported by NEI R01EY017658, NIDA R01NS063249, NSF IOB 0645886, the HHMI, and the Klingenstein Foundation; ENB was supported by DP1-0D003646. The information contained herein does not necessarily reflect the position or policy of the Government, and no official endorsement should be inferred. NR 68 TC 55 Z9 57 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 2010 VL 133 BP 1668 EP 1681 DI 10.1093/brain/awq112 PN 6 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 603RW UT WOS:000278226700010 PM 20511283 ER PT J AU Obler, LK Rykhlevskaia, E Schnyer, D Clark-Cotton, MR Spiro, A Hyun, J Kim, DS Goral, M Albert, ML AF Obler, Loraine K. Rykhlevskaia, Elena Schnyer, David Clark-Cotton, Manuella R. Spiro, Avron, III Hyun, JungMoon Kim, Dae-Shik Goral, Mira Albert, Martin L. TI Bilateral brain regions associated with naming in older adults SO BRAIN AND LANGUAGE LA English DT Article DE Naming; Aging; MRI; DTI; Bilaterality ID HUMAN CEREBRAL-CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; LEFT FRONTAL-CORTEX; SHORT-TERM-MEMORY; VERBAL FLUENCY; WHITE-MATTER; BROCAS AREA; LIFE-SPAN AB To determine structural brain correlates of naming abilities in older adults, we tested 24 individuals aged 56-79 on two confrontation-naming tests (the Boston Naming Test (BNT) and the Action Naming Test (ANT)), then collected from these individuals structural Magnetic-Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) data. Overall, several regions showed that greater gray and white matter volume/ integrity measures were associated with better task performance. Left peri-Sylvian language regions and their right-hemisphere counterparts, plus left mid-frontal gyrus correlated with accuracy and/or negatively with response time (RT) on the naming tests. Fractional anisotropy maps derived from DTI showed robust positive correlations with ANT accuracy bilaterally in the temporal lobe and in right middle frontal lobe, as well as negative correlations with BNT RT, bilaterally, in the white matter within middle and inferior temporal lobes. We conclude that those older adults with relatively better naming skills can rely on right-hemisphere peri-Sylvian and mid-frontal regions and pathways, in conjunction with left-hemisphere peri-Sylvian and mid-frontal regions, to achieve their success. Published by Elsevier Inc. C1 [Obler, Loraine K.; Hyun, JungMoon; Goral, Mira] CUNY, Grad Ctr, Program Speech Language Hearing Sci, New York, NY 10016 USA. [Obler, Loraine K.; Clark-Cotton, Manuella R.; Albert, Martin L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Obler, Loraine K.; Spiro, Avron, III; Hyun, JungMoon; Albert, Martin L.] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Rykhlevskaia, Elena] Stanford Univ, Palo Alto, CA 94304 USA. [Schnyer, David] Univ Texas Austin, Austin, TX 78712 USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Kim, Dae-Shik] Korea Adv Inst Sci & Technol, Taejon 305701, South Korea. [Goral, Mira] CUNY Herbert H Lehman Coll, New York, NY USA. RP Obler, LK (reprint author), CUNY, Grad Ctr, Program Speech Language Hearing Sci, 365 5th Ave, New York, NY 10016 USA. EM Loraine.obler@gmail.com RI Kim, Dae-Shik/C-2071-2011 FU Clinical Science Research and Development Service, US Department of Veterans Affairs; National Institute on Aging [AG14345] FX This project was supported in part by the Clinical Science Research and Development Service, US Department of Veterans Affairs, by Grant AG14345 (PI: Martin L. Albert) from the National Institute on Aging, and by a Merit Review to Avron Spiro by the Clinical Science Research and Development Service, US Department of Veterans Affairs. We thank all our participants and are particularly appreciative of the helpful suggestions made by two anonymous reviewers. NR 80 TC 20 Z9 20 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD JUN PY 2010 VL 113 IS 3 BP 113 EP 123 DI 10.1016/j.band1.2010.03.001 PG 11 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 594PC UT WOS:000277548600002 PM 20399492 ER PT J AU Pierce, LJ Phillips, KA Griffith, KA Buys, S Gaffney, DK Moran, MS Haffty, BG Ben-David, M Kaufman, B Garber, JE Merajver, SD Balmana, J Meirovitz, A Domchek, SM AF Pierce, Lori J. Phillips, Kelly-Anne Griffith, Kent A. Buys, Saundra Gaffney, David K. Moran, Meena S. Haffty, Bruce G. Ben-David, Merav Kaufman, Bella Garber, Judy E. Merajver, Sofia D. Balmana, Judith Meirovitz, Amichay Domchek, Susan M. TI Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Hereditary breast cancer; BRCA1/ 2; Breast conservation; Mastectomy; Radiotherapy ID SURGICAL ADJUVANT BREAST; 20-YEAR FOLLOW-UP; LOCOREGIONAL RECURRENCES; CONSERVING SURGERY; GERMLINE MUTATIONS; TUMOR RECURRENCE; RISK; RADIOTHERAPY; WOMEN; CHEMOTHERAPY AB Women with BRCA1 and BRCA2 mutations have an elevated risk of breast cancer and ovarian cancer, but also of developing second primary breast cancer. BRCA1/2 mutation carriers with breast cancer must choose between breast conservation (BCT) and mastectomy (M) yet data on outcomes are limited. The purpose of this study is to compare long-term outcome following BCT and M in BRCA1/2 carriers. 655 women with BRCA1/2 mutations diagnosed with breast cancer and treated with BCT (n = 302) or M (n = 353) were identified and underwent follow-up to assess local, regional, and systemic recurrence. Local failure as first failure was significantly more likely in those treated with BCT compared to M, with a cumulative estimated risk of 23.5 vs. 5.5%, respectively, at 15 years (P < 0.0001); 15-year estimates in carriers treated with BCT and chemotherapy was 11.9% (P = 0.08 when Presented, in part, at the 2010 European Breast Cancer Conference, compared to M). Most events appeared to be second primary cancers rather than failure to control the primary tumor. The risk of contralateral breast cancer was high in all groups, exceeding 40%, but was not statistically significantly different by use of adjuvant radiotherapy (RT) or not, suggesting no added risk from scatter RT at 10 and 15 years. There were no differences seen in regional or systemic recurrences between the BCT and M groups, and no difference in overall survival. In conclusion, BRCA1/2 mutation carriers with breast cancer have similar survival whether treated with M or BCT. However, women undergoing BCT have an elevated risk of a second in-breast event that is significantly reduced in the presence of chemotherapy. C1 [Pierce, Lori J.] Univ Michigan, Dept Radiat Oncol, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Phillips, Kelly-Anne] Univ Melbourne, St Vincents Hosp, Div Hematol & Med Oncol, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Phillips, Kelly-Anne] Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, Australia. [Griffith, Kent A.] Univ Michigan, Biostat Unit, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Buys, Saundra] Univ Utah, Dept Internal Med, Huntsman Canc Inst, Div Med Oncol, Salt Lake City, UT 84112 USA. [Gaffney, David K.] Univ Utah, Dept Radiat Oncol, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Moran, Meena S.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. [Haffty, Bruce G.] Canc Inst New Jersey UMDNJ RWJMS, Dept Radiat Oncol, New Brunswick, NJ USA. [Ben-David, Merav; Kaufman, Bella] Tel Aviv Univ, Sheba Med Ctr, Dept Oncol, IL-69978 Tel Aviv, Israel. [Garber, Judy E.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Merajver, Sofia D.] Univ Michigan, Dept Internal Med, Div Med Oncol, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Balmana, Judith] Univ Autonoma Barcelona, Med Oncol Serv, Hosp Vall Hebron, E-08193 Barcelona, Spain. [Meirovitz, Amichay] Hadassah Hebrew Univ, Dept Oncol, Med Ctr, Jerusalem, Israel. [Domchek, Susan M.] Univ Penn, Div Med Oncol, Dept Internal Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Pierce, LJ (reprint author), Univ Michigan, Dept Radiat Oncol, Ctr Comprehens Canc, 1500 E Med Ctr Dr,Room 4308, Ann Arbor, MI 48109 USA. EM ljpierce@umich.edu OI Phillips, Kelly-Anne/0000-0002-0475-1771 FU Breast Cancer Research Foundation; Colebatch Clinical Research Fellowship of the Cancer Council Victoria; National Health and Medical Research Council (NHMRC) of Australia [145684, 288704, 454508]; National Breast Cancer Foundation; NHMRC; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia (kConFab); Susan G. Komen Breast Cancer Foundation; Dana Farber/Harvard Cancer Center SPORE in Breast Cancer; Cancer Genetics Network [HHSN21620074400C] FX This research was supported by the Breast Cancer Research Foundation (LJP, SDM); the Colebatch Clinical Research Fellowship of the Cancer Council Victoria (KAP), the National Health and Medical Research Council (NHMRC) of Australia (# 145684, 288704, 454508) and grants from the National Breast Cancer Foundation, the NHMRC and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia (kConFab); Susan G. Komen Breast Cancer Foundation (BGH); Dana Farber/Harvard Cancer Center SPORE in Breast Cancer (JEG); and Cancer Genetics Network (HHSN21620074400C) (SMD). We thank follow-up study investigators, research nurses and staff at kConFab and all study sites, the heads and staff of the Australian and New Zealand Family Cancer Clinics, and the families who contribute to kConFab and to this international collaboration. NR 26 TC 52 Z9 53 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2010 VL 121 IS 2 BP 389 EP 398 DI 10.1007/s10549-010-0894-z PG 10 WC Oncology SC Oncology GA 599JC UT WOS:000277906500014 PM 20411323 ER PT J AU Kouri, EM He, YL Winer, EP Keating, NL AF Kouri, Elena M. He, Yulei Winer, Eric P. Keating, Nancy L. TI Influence of birthplace on breast cancer diagnosis and treatment for Hispanic women SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Early diagnosis; Hispanic Americans; Immigrants; Surgery ID HEALTH-INSURANCE COVERAGE; UNITED-STATES; WHITE WOMEN; MAMMOGRAPHY UTILIZATION; SCREENING MAMMOGRAPHY; CLINICAL PRESENTATION; SOCIOECONOMIC-STATUS; CITIZENSHIP STATUS; REGISTRY DATA; STAGE AB Research has shown that Hispanic women in the United States are diagnosed with breast cancer at more advanced stages and initiate treatment later than non-Hispanic white women. We investigated whether stage at breast cancer diagnosis and receipt of primary therapy differ by ethnicity and birthplace among US-born Hispanic, foreign-born Hispanic, and white women. We studied 31,012 Hispanic women and 372,313 white women with a first diagnosis of invasive breast cancer during 1988 and 2005 living in a SEER area. We used multinomial logistic regression to assess the association of ethnicity and birthplace with stage at diagnosis and, among women with stage I or II cancers, primary therapy [mastectomy, breast-conserving surgery (BCS) with radiation, BCS without radiation], adjusting for other patient and tumor characteristics. Rates of stage at diagnosis differed significantly by race/ethnicity and birthplace (P < 0.001). Foreign-born Hispanics had lower adjusted rates of stage I breast cancer at diagnosis (35.4%) than US-born Hispanics (40.6%), birthplace-unknown Hispanics (42.3%), and whites (47.4%). Receipt of primary therapy also differed significantly by race/ethnicity and birthplace (P < 0.001). Foreign-born Hispanics and birthplace-unknown Hispanics had lower rates of BCS with radiation (34.9%, 30.7%) than US-born Hispanics (41.5%) and whites (38.8%). Foreign-born Hispanic women in the United States have a lower probability of being diagnosed at earlier stages of breast cancer and, for women with early-stage disease, of receiving radiation following BCS compared to US-born Hispanics and whites. Identifying factors mediating these disparities may help in developing culturally and linguistically appropriate interventions and improving outcomes. C1 [Kouri, Elena M.; He, Yulei; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. [Winer, Eric P.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU SEER; Susan G. Komen for the Cure FX This study was funded by Susan G. Komen for the Cure and used the SEER database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors would like to thank Yang Xu, M. S., for expert programming assistance. NR 64 TC 22 Z9 22 U1 3 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2010 VL 121 IS 3 BP 743 EP 751 DI 10.1007/s10549-009-0643-3 PG 9 WC Oncology SC Oncology GA 595TM UT WOS:000277636000023 PM 19949856 ER PT J AU Karila, L Weinstein, A Aubin, HJ Benyamina, A Reynaud, M Batki, SL AF Karila, Laurent Weinstein, Aviv Aubin, Henri-Jean Benyamina, Amine Reynaud, Michel Batki, Steven L. TI Pharmacological approaches to methamphetamine dependence: a focused review SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Review DE addiction; amphetamine; clinical trials; dependence; medication; methamphetamine; treatment ID PLACEBO-CONTROLLED TRIAL; VESICULAR MONOAMINE TRANSPORTERS; INDUCED BEHAVIORAL SENSITIZATION; MODAFINIL IMPROVES COGNITION; DOUBLE-BLIND; AMPHETAMINE DEPENDENCE; COCAINE-DEPENDENCE; DRUG-ADDICTION; MONOCLONAL-ANTIBODIES; POTENTIAL PHARMACOTHERAPY AB Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronal mechanisms implicated in methamphetamine dependence have suggested several pharmacological approaches. A literature search from a range of electronic databases (PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov) was conducted for the period from January 1985 to October 2009. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type. A variety of medications have failed to show efficacy in clinical trials, including a dopamine partial agonist (aripiprazole), GABAergic agents (gabapentin) and serotonergic agents (SSRI, ondansetron, mirtazapine). Three double-blind placebo-controlled trials using modafinil, bupropion and naltrexone have shown positive results in reducing amphetamine or methamphetamine use. Two studies employing agonist replacement medications, one with d-amphetamine and the other with methylphenidate, have also shown promise. Despite the lack of success in most studies to date, increasing efforts are being made to develop medications for the treatment of methamphetamine dependence and several promising agents are targets of further research. C1 [Karila, Laurent] Univ Paris 11, Hop Paul Brousse, INSERM, Addict Res & Treatment Ctr,AP HP,CEA,U1000, Villejuif, France. [Weinstein, Aviv] Hadassah Hosp Ein Kerem, Dept Med Biophys & Nucl Med, Jerusalem, Israel. [Aubin, Henri-Jean; Benyamina, Amine; Reynaud, Michel] Univ Paris 11, Hop Paul Brousse, INSERM, Addict Res & Treatment Ctr,AP HP,U669, Villejuif, France. [Batki, Steven L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Karila, L (reprint author), Univ Paul Brousse, CERTA, 12 Ave Paul Vaillant Couturier, F-94800 Villejuif, France. EM laurent.karila@pbr.aphp.fr FU MILDT (Mission Interministrielle de Lutte contre les Drogues et la Toxicomanie) INSERM; Assistance Publique- H pitaux de Paris. Dr Weinstein (Israel); National Institute for Psychobiology (Israel); National Institute of Health, National Institute on Drug Abuse (NIDA) [5R01 DA016764- 05, U10 DA015815]; National Institute on Alcohol Abuse and Alcoholism and a Department of Veterans Affairs FX Dr Karila (France) received support from the MILDT (Mission Interministerielle de Lutte contre les Drogues et la Toxicomanie) INSERM and Assistance Publique- Hopitaux de Paris. Dr Weinstein (Israel) is supported by the National Institute for Psychobiology (Israel). Dr Batki (USA) received support from National Institute of Health, National Institute on Drug Abuse (NIDA) Grants N. 5R01 DA016764- 05 and U10 DA015815, National Institute on Alcohol Abuse and Alcoholism and a Department of Veterans Affairs Grant for the VISN 2 Center for Integrated Healthcare. NR 139 TC 80 Z9 83 U1 4 U2 23 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD JUN PY 2010 VL 69 IS 6 BP 578 EP 592 DI 10.1111/j.1365-2125.2010.03639.x PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 594FT UT WOS:000277522100003 PM 20565449 ER PT J AU Tucker, JD Hawkes, SJ Yin, YP Peeling, RW Cohen, MS Chen, XS AF Tucker, Joseph D. Hawkes, Sarah J. Yin, Yue-Pin Peeling, Rosanna W. Cohen, Myron S. Chen, Xiang-Sheng TI Scaling up syphilis testing in China: implementation beyond the clinic SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; FEMALE SEX WORKERS; CONGENITAL-SYPHILIS; COST-EFFECTIVENESS; EASTERN CHINA; HIV; HEALTH; INTERVENTION; INFECTIONS; MANAGEMENT AB China is experiencing a syphilis epidemic of enormous proportions. The regions most heavily affected by syphilis correspond to regions where sexually transmitted HIV infection is also a major public health threat. Many high-risk patients in China fail to receive routine syphilis screening. This missed public health opportunity stems from both a failure of many high-risk individuals to seek clinical care and a disconnect between policy and practice. New point-of-care syphilis testing enables screening in non-traditional settings such as community organizations or sex venues. This paper describes the current Chinese syphilis policies, suggests a spatiotemporal framework (based on targeting high-risk times and places) to improve screening and care practices, and emphasizes a syphilis control policy extending beyond the clinical setting. C1 [Tucker, Joseph D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hawkes, Sarah J.] UCL, London, England. [Yin, Yue-Pin; Chen, Xiang-Sheng] Chinese Acad Med Sci, Natl Ctr STD Control, Nanjing, Peoples R China. [Yin, Yue-Pin; Chen, Xiang-Sheng] Peking Union Med Coll, Inst Dermatol, Nanjing, Peoples R China. [Peeling, Rosanna W.] London Sch Hyg & Trop Med, London WC1, England. [Cohen, Myron S.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. RP Tucker, JD (reprint author), Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA. EM jtucker4@partners.org OI Hawkes, Sarah/0000-0003-1062-3538 FU China Syphilis Working Group; University of North Carolina (NIH FIC) [D43 TWO 1039]; University of North Carolina Social Science Research on HIV/AIDS in China (NIH NICHD) [R24 HD056670-01]; WHO [WHO OD/TS-08-00088]; Harvard Initiative for Global Health; American Society of Tropical Medicine and Hygiene; United States National Institutes of Health Fogarty International Center FX We thank the China Syphilis Working Group, the University of North Carolina Fogarty AIDS International Research and Training Program (NIH FIC D43 TWO 1039), the University of North Carolina Social Science Research on HIV/AIDS in China (NIH NICHD R24 HD056670-01), the WHO Rapid Syphilis Test Project (WHO OD/TS-08-00088), the Harvard Initiative for Global Health, the American Society of Tropical Medicine and Hygiene and the United States National Institutes of Health Fogarty International Center International Clinical Fellowship. We also thank Peter Leone for helpful discussions. NR 44 TC 20 Z9 21 U1 1 U2 3 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PD JUN PY 2010 VL 88 IS 6 BP 452 EP 457 DI 10.2471/BLT.09.070326 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 610PR UT WOS:000278746400012 PM 20539859 ER PT J AU Parrett, BM Donelan, MB AF Parrett, Brian M. Donelan, Matthias B. TI Pulsed dye laser in burn scars: Current concepts and future directions SO BURNS LA English DT Review DE Pulsed dye laser; Hypertrophic burn scars; Facial burns; Laser; z-Plasty ID ND-YAG LASER; HYPERTROPHIC SCARS; SELECTIVE PHOTOTHERMOLYSIS; STERNOTOMY SCARS; KELOID SCARS; Z-PLASTY; MANAGEMENT; EXCISION; TRIAMCINOLONE; EXPRESSION AB Hypertrophic scarring after partial-thickness burns is common, resulting in raised, erythematous, pruritic, and contracted scars. Treatment of hypertrophic scars, especially on the face, is challenging and has high failure rates. Excisional treatment has morbidity and can create iatrogenic deformities. After an extensive experience over 10 years with laser therapy for the treatment of difficult scars, the pulsed dye laser (PDL) has emerged as a successful alternative to excision in patients with hypertrophic burn scars. Multiple studies have shown its ability to decrease scar erythema and thickness while significantly decreasing pruritis and improving the cosmetic appearance of the scar. The history of laser therapy and the mechanism of action and results of the PDL in burn scars will be reviewed. The PDL should become an integral part of the management of burn scarring and will significantly decrease the need for excisional surgery. (C) 2009 Elsevier Ltd and ISBI. All rights reserved. C1 [Parrett, Brian M.; Donelan, Matthias B.] Shriners Burns Hosp, Div Plast Surg, Boston, MA 02114 USA. [Parrett, Brian M.; Donelan, Matthias B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Donelan, MB (reprint author), Shriners Burns Hosp, Div Plast Surg, 51 Blossom St, Boston, MA 02114 USA. EM mdonelan@partners.org NR 46 TC 23 Z9 24 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 J9 BURNS JI Burns PD JUN PY 2010 VL 36 IS 4 BP 443 EP 449 DI 10.1016/j.burns.2009.08.015 PG 7 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA 598RQ UT WOS:000277856300001 PM 20022430 ER PT J AU Channick, RN AF Channick, Richard N. TI Pulmonary hypertension: Classification and treatment SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Article DE Classification; Pulmonary Hypertension; WHO group ID CONNECTIVE-TISSUE DISEASE; SYSTEMIC LUPUS-ERYTHEMATOSUS; CALCIUM-CHANNEL BLOCKERS; ARTERIAL-HYPERTENSION; INTRAVENOUS EPOPROSTENOL; DOUBLE-BLIND; LUNG TRANSPLANTATION; INHALED ILOPROST; CONTROLLED-TRIAL; THERAPY AB RN Channick. Pulmonary hypertension: Classification and treatment. Can J Cardiol 2010;26(Suppl B):5B-11B. Pulmonary hypertension (PH) comprises a variety of conditions that lead to elevated pulmonary arterial pressure. Because the treatment for PH depends on the cause, it is critical to accurately classify the cause of the problem. A useful classification system, developed and refined at the World Conference on Pulmonary Hypertension, held every five years, has been developed. In this system, patients can be classified as having PH due to the following: pulmonary arterial hypertension (PAH); left-sided heart disease; lung or respiratory disease; chronic thromboembolic disease; or multi factorial or unclear mechanisms. Although challenges in classifying patients remain, such as the patient with some left-sided heart disease but 'out of proportion' PH, this system has been critical in helping guide therapy. For patients who are deemed to be in group 1 (PAH) several approved therapies are available, including prostanoids (available in intravenous, subcutaneous and inhaled forms), endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. Each of these agents has been approved based on improvement in exercise capacity demonstrated in randomized controlled trials. A treatment algorithm that provides guidance for choosing the appropriate treatment for PAH patients has been published. Patients who are considered to be 'high risk', such is those with overt right heart failure, are generally appropriate for parenteral therapy, whereas those who are only moderate or low risk ire usually candidates for initial oral therapy. In addition, close follow-up allows for the consideration of additional therapies. Many current trials, in fact, are studying this 'goal-directed' approach to the treatment of PAH. C1 Massachusetts Gen Hosp, Pulm Hypertens Ctr, Boston, MA 02114 USA. RP Channick, RN (reprint author), Massachusetts Gen Hosp, Pulm Hypertens Ctr, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM rchannick@partners.org FU Actelion Pharmaceuticals; Gilead Sciences; United Therapeutics Corporation FX Dr Richard N Channick has received research funding from Actelion Pharmaceuticals, Gilead Sciences and United Therapeutics Corporation. He has received compensation for consulting services for Actelion, Gilead and United Therapeutics. He has receieved honoraria for lectures from Actelion. NR 48 TC 2 Z9 2 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0828-282X J9 CAN J CARDIOL JI Can. J. Cardiol. PD JUN-JUL PY 2010 VL 26 SU B BP 5B EP 11B PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 742UP UT WOS:000288971000002 ER PT J AU Chou, JF Row, D Gonen, M Liu, YH Schrag, D Weiser, MR AF Chou, Joanne F. Row, David Gonen, Mithat Liu, Yi-Hai Schrag, Deborah Weiser, Martin R. TI Clinical and Pathologic Factors That Predict Lymph Node Yield From Surgical Specimens in Colorectal Cancer A Population-Based Study SO CANCER LA English DT Article DE colorectal cancer; lymph node yield; staging; Surveillance; Epidemiology; and End Results; clinicopathologic factors ID TOTAL MESORECTAL EXCISION; RECTAL-CANCER; COLON-CANCER; MINIMUM NUMBER; OPERATIVE TREATMENT; RESECTION; SURVIVAL; ADENOCARCINOMA; RETRIEVAL; RECOMMENDATIONS AB BACKGROUND: The National Quality Forum endorses the recommendation of examining at least 12 lymph nodes (LNs) from colorectal cancer (CRC) specimens. However, heterogeneity in LN harvest exists. The objective of this study was to investigate the clinicopathologic factors that influence LN yield. METHODS: The authors used the Surveillance, Epidemiology, and End Results database to identify patients who were diagnosed with stage I, II, and III CRC between 1994 and 2005. Poisson regression was used to model the number of LNs examined as a function of individual clinicopathologic factors, including age, sex, race, year of diagnosis, geographic region, anatomic site, preoperative radiation, tumor size, tumor classification, tumor differentiation, and LN positivity. RESULTS: In total, 153,483 patients with CRC were identified. The mean number of LNs examined (+/- standard deviation) was 12 (+/- 9.3). Separate multivariate analyses revealed that age, year of diagnosis, tumor size, and tumor classification were significant predictors of LN yield for colon and extraperitoneal rectal cancers (P < .01 for all covariates). Tumor location and radiotherapy were significant predictors of LN yield in patients with colon cancer and rectal cancer, respectively. Overall LN yields increased between 2% and 3% annually. CONCLUSIONS: Despite the increasing yields observed over time, patients with rectal cancer and older patients who had distally located, early colon cancer were less likely to meet the benchmark yield of 12 LNs. Further investigation into how LN yield is influenced by alterable factors, such as the extent of mesenteric resection and the pathologic technique, as well as nonalterable factors, such as patient age and tumor location, may reveal innovative ways to improve current staging methods. Cancer 2010;116:2560-70. (C) 2070 American Cancer Society. C1 [Weiser, Martin R.] Mem Sloan Kettering Canc Ctr, Colorectal Serv, Dept Surg, New York, NY 10065 USA. [Chou, Joanne F.; Gonen, Mithat; Liu, Yi-Hai; Schrag, Deborah] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weiser, MR (reprint author), Mem Sloan Kettering Canc Ctr, Colorectal Serv, Dept Surg, 1275 York Ave,Room C-1075, New York, NY 10065 USA. EM weiser1@mskcc.org RI Gonen, Mithat/E-4826-2012 FU NCI NIH HHS [P30 CA008748] NR 35 TC 68 Z9 73 U1 0 U2 1 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 JUN 1 PY 2010 VL 116 IS 11 BP 2560 EP 2570 DI 10.1002/cncr.25032 PG 11 WC Oncology SC Oncology GA 600LZ UT WOS:000277989100009 PM 20499400 ER PT J AU Hoffman, KE Chen, MH Moran, BJ Braccioforte, MH Dosoretz, D Salenius, S Katin, MJ Ross, R D'Amico, AV AF Hoffman, Karen E. Chen, Ming-Hui Moran, Brian J. Braccioforte, Michelle H. Dosoretz, Daniel Salenius, Sharon Katin, Michael J. Ross, Rudi D'Amico, Anthony V. TI Prostate Cancer-Specific Mortality and the Extent of Therapy in Healthy Elderly Men With High-Risk Prostate Cancer SO CANCER LA English DT Article DE high-risk prostate cancer; elderly; radiation therapy; brachytherapy; androgen-suppression therapy ID ANDROGEN DEPRIVATION THERAPY; RADICAL PROSTATECTOMY; COMPETING RISK; OLDER MEN; RADIATION; SURVIVAL; BRACHYTHERAPY; DEATH; AGE AB BACKGROUND: The risk of prostate cancer-specific mortality (PCSM) in healthy elderly men may depend on extent of treatment. The authors of this report compared the use of brachytherapy alone with combined brachytherapy, external-beam radiation to the prostate and seminal vesicles, and androgen-suppression therapy (CMT) in this population. METHODS: The study cohort comprised 764 men aged >= 65 years with high-risk prostate cancer (T3 or T4N0M0, prostate-specific antigen >20 ng/mL, and/or Gleason score 8-10) who received either brachytherapy alone (n = 206) or CMT (n = 558) at the Chicago Prostate Cancer Center or at a 21st Century Oncology facility. Men either had no history of myocardial infarction (MI) or had a history of MI treated with a stent or surgical intervention. Fine and Gray regression analysis was used to identify the factors associated with PCSM. RESULTS: The median patient age was 73 years (interquartile range, 70-77 years). After a median follow-up of 4.9 years, 25 men died of prostate cancer. After adjusting for age and prostate cancer prognostic factors, the risk of PCSM was significantly less (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12-0.68; P = .004) for men who received CMT than for men who received brachytherapy alone. Other factors that were associated significantly with an increased risk of PCSM included a Gleason score of 8 to 10 (P = .017). CONCLUSIONS: Elderly men who had high-risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had a lower risk of PCSM when they received CMT than when they received brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high-risk prostate cancer. Cancer 2010;116:2590-5. (C) 2070 American Cancer Society. C1 [Hoffman, Karen E.; D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Hoffman, Karen E.; D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hoffman, Karen E.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Moran, Brian J.; Braccioforte, Michelle H.; Dosoretz, Daniel] Prostate Canc Fdn Chicago, Westmont, IL USA. [Salenius, Sharon; Katin, Michael J.; Ross, Rudi] 21st Century Oncol, Ft Myers, FL USA. RP Hoffman, KE (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 1202, Houston, TX 77030 USA. EM khoffman1@mdanderson.org NR 24 TC 11 Z9 12 U1 0 U2 1 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 JUN 1 PY 2010 VL 116 IS 11 BP 2590 EP 2595 DI 10.1002/cncr.24974 PG 6 WC Oncology SC Oncology GA 600LZ UT WOS:000277989100012 PM 20310055 ER PT J AU Lee, MS Su, L Christiani, DC AF Lee, Mi-Sun Su, Li Christiani, David C. TI Synergistic Effects of NAT2 slow and GSTM1 null Genotypes on Carcinogen DNA Damage in the Lung SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; CANCER-RISK; GENETIC POLYMORPHISMS; SUSCEPTIBILITY FACTOR; BLADDER-CANCER; ADDUCT LEVELS; RAT LUNG; EXPOSURE; SMOKING; ACETYLATION AB Background: Polymorphisms in carcinogen detoxification enzymes, NAT2 and GSTM1, have been suggested as susceptibility factors for DNA damage and lung cancer. However, little information is available on DNA adduct burden in the lung tissue and polymorphisms in NAT2 and GST genes. We investigated the independent and combined effects of the metabolic gene polymorphisms of NAT2 and GSTs on DNA adduct formation in different tissues (lung and blood) in lung cancer patients. Methods: DNA adducts were measured in lung and blood by the (32)P-postlabeling assay. Multiple regression models were used to assess adjusted percent change in DNA adduct levels associated with GST and NAT2 genotypes. Results: After adjusting for potential confounders, as well as for other GST gene variants, lung adduct levels significantly increased by 150.3% [95% confidence interval (95% CI), 35.4-362.6%] for the GSTM1 null and by 73.9% (95% CI, -3.2% to 212.4%) for theNAT2 slow acetylator genotype, respectively. No association was seen with polymorphisms of other GST genes such as GSTT1 and GSTP1. The high-risk group, the combined GSTM1 null plus NAT2 slow, had significantly enhanced levels of lung adducts by 295% (95% CI, 72.7-803.5%) over those associated with single genes, suggesting a synergistic effect on DNA damage in the target lung tissue. Conclusions: The increase in DNA adduct levels in lung is associated with the GSTM1 null and NAT2 slow genotypes alone or in combination. Impact: These results suggest that GSTM1 and NAT2 genotypes play an independent and interactive role in the formation of carcinogen DNA adduct in the lung. Cancer Epidemiol Biomarkers Prev; 19(6); 1492- 7. (C) 2010 AACR. C1 [Lee, Mi-Sun; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave,Bldg 1,Room 1401, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU NIH [CA074386, CA092824, CA090578] FX NIH grants CA074386, CA092824, and CA090578. NR 32 TC 15 Z9 16 U1 0 U2 1 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 JUN PY 2010 VL 19 IS 6 BP 1492 EP 1497 DI 10.1158/1055-9965.EPI-09-1195 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607MD UT WOS:000278507300013 PM 20501762 ER PT J AU Kachnic, LA Li, L Fournier, L Willers, H AF Kachnic, Lisa A. Li, Li Fournier, Loreen Willers, Henning TI Fanconi Anemia pathway heterogeneity revealed by cisplatin and oxaliplatin treatments SO CANCER LETTERS LA English DT Article DE Fanconi Anemia; FANCD2; FANCA; Platinum drugs ID DNA-REPAIR; CELL-LINES; MONOUBIQUITINATED FANCD2; GENOMIC INSTABILITY; NECK-CANCER; DAMAGE; HEAD; PROTEINS; COMPLEX; SUSCEPTIBILITY AB Genetic or epigenetic inactivation of the pathway formed by the Fanconi Anemia (FA) proteins occurs in several cancer types, including head and neck squamous cell carcinomas (HNSCC), rendering the affected tumors potentially hypersensitive to DNA crosslinking agents. However, the cytotoxicity of other commonly used cancer therapeutics in cells with FA pathway defects remains to be defined. Here, we focused on the effects of cisplatin and oxaliplatin in a panel of HNSCC and fibroblast cell lines. We found that FANCC- and FANCD2-mutant cells were unexpectedly more sensitive to platinum drugs than FANCA-mutant cells, and mono-ubiquitination of FANCD2, which is mediated by the FANCA and FANCC containing FA core complex was not required for platinum resistance. Interestingly, platinum hypersensitivity could be dissociated from mitomycin C hypersensitivity suggesting different underlying mechanisms. FANCD2 or RAD51 subnuclear foci were not useful as biomarkers of platinum hypersensitivity of FANCC/FANCD2-mutant cells. Our data add to an emerging body of evidence indicating that the FA pathway is not linear and that several protein subcomplexes with different functions exist. It will be important to establish biomarkers that can predict the sensitivity of tumors with specific FA defects to chemotherapeutic agents. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Kachnic, Lisa A.] Boston Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA. [Kachnic, Lisa A.; Li, Li; Fournier, Loreen; Willers, Henning] Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Lab Cellular & Mol Radiat Oncol, Charlestown, MA 02129 USA. RP Kachnic, LA (reprint author), Moakley LL Boston Med Ctr, Dept Radiat Oncol, 830 Harrison Ave, Boston, MA 02118 USA. EM lisa.kachnic@bmc.org; hwillers@partners.org NR 34 TC 18 Z9 18 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 1 PY 2010 VL 292 IS 1 BP 73 EP 79 DI 10.1016/j.canlet.2009.11.009 PG 7 WC Oncology SC Oncology GA 597GN UT WOS:000277744800010 PM 20034732 ER PT J AU O'Donovan, PJ Livingston, DM AF O'Donovan, Peter J. Livingston, David M. TI BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair SO CARCINOGENESIS LA English DT Review ID DEPENDENT PROTEIN-KINASE; HOMOLOGY-DIRECTED REPAIR; END-JOINING PATHWAYS; HOLLIDAY JUNCTION RESOLVASE; CELL-CYCLE; DAMAGE RESPONSE; MAMMALIAN-CELLS; S-PHASE; LIGASE-IV; RADIATION HYPERSENSITIVITY AB BRCA1 and BRCA2 are tumor suppressor genes, familial mutations in which account for similar to 5% of breast cancer cases in the USA annually. Germ line mutations in BRCA1 that truncate or inactivate the protein lead to a cumulative risk of breast cancer, by age 70, of up to 80%, whereas the risk of ovarian cancer is 30-40%. For germ line BRCA2 mutations, the breast cancer cumulative risk approaches 50%, whereas for ovarian cancers, it is between 10 and 15%. Both BRCA1 and BRCA2 are involved in maintaining genome integrity at least in part by engaging in DNA repair, cell cycle checkpoint control and even the regulation of key mitotic or cell division steps. Unsurprisingly, the complete loss of function of either protein leads to a dramatic increase in genomic instability. How they function in maintaining genome integrity after the onset of DNA damage will be the focus of this review. C1 [O'Donovan, Peter J.; Livingston, David M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM david_livingston@dfci.harvard.edu NR 128 TC 112 Z9 120 U1 3 U2 29 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2010 VL 31 IS 6 BP 961 EP 967 DI 10.1093/carcin/bgq069 PG 7 WC Oncology SC Oncology GA 603OS UT WOS:000278218500002 PM 20400477 ER PT J AU Boden, WE Flather, MD Bhatt, DL AF Boden, William E. Flather, Marcus D. Bhatt, Deepak L. TI Role of Dual Antiplatelet Therapy in Symptomatic Patients with Established Vascular Disease: Putting the CHARISMA Trial into Therapeutic Perspective SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Article DE Aspirin; Cardiovascular disease; Clopidogrel; Clinical trial design; Subgroup analysis ID CORONARY-BYPASS SURGERY; RANDOMIZED CONTROLLED-TRIAL; PERIPHERAL ARTERIAL-DISEASE; PLACEBO-CONTROLLED TRIAL; ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; SUBGROUP ANALYSIS; STATISTICS NOTES; UNSTABLE ANGINA AB The CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial has spurred debate over subgroup analysis interpretation and prompted renewed consideration of the long-term role of dual aspirin and clopidogrel therapy (DAPT) in patients with established vascular disease. Previous DAPT studies consistently demonstrated greater efficacy but an increased risk of bleeding compared with aspirin alone in patients with acute coronary syndromes or undergoing percutaneous coronary intervention. However, CHARISMA data were inconclusive and difficult to interpret. The principal subgroup analysis showed a significant benefit for clopidogrel plus aspirin in the 80% of patients with documented vascular disease, but unexpectedly showed potential harm in the similar to 20% of asymptomatic patients. Hypothesizing that dual antiplatelet therapy would provide benefit across the broad spectrum of atherothrombotic disease was plausible. In retrospect, it is apparent that by combining such a heterogeneous population, CHARISMA failed to show a clear treatment effect for DAPT and potentially masked important benefits in specific populations. Given the inherent clinical and biological variability among patients and disease states, difficult-to-interpret clinical data should not be dismissed. The current challenge is identifying clinically useful data from CHARISMA to determine the role of DAPT in contemporary clinical practice. C1 [Boden, William E.] SUNY Buffalo, Sch Med, Buffalo Gen Hosp, Div Cardiol, Buffalo, NY 14203 USA. [Boden, William E.] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Flather, Marcus D.] Univ London Imperial Coll Sci Technol & Med, London, England. [Flather, Marcus D.] Royal Brompton Hosp, Clin Trials & Evaluat Unit, London SW3 6LY, England. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. RP Boden, WE (reprint author), SUNY Buffalo, Sch Med, Buffalo Gen Hosp, Div Cardiol, 100 High St, Buffalo, NY 14203 USA. EM wboden@kaleidahealth.org FU AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Heartscape; Sanofi-aventis; The Medicines Company; GlaxoSmithKline; Actelion; Abbott Laboratories; CV Therapeutics; Merck; PDL BioPharma; Bristol-Myers Squibb (New York, NY)/Sanofi Pharmaceuticals (Paris, France) FX The editorial assistance was funded by the Bristol-Myers Squibb (New York, NY)/Sanofi Pharmaceuticals (Paris, France) Partnership and performed in compliance with the good publishing practices outlined by the International Committee of Medical Journal Editors. The authors, who did not receive compensation for this work, had complete control of the writing and editing process and take full responsibility for all content.; Dr. Bhatt has received research grants (to the institution) from: AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, sanofi-aventis, and The Medicines Company. He served as the international primary investigator of the CHARISMA trial, which was funded by sanofi-aventis and Bristol-Myers Squibb.; Dr. Flather has received institutional research grants from sanofi-aventis and Bristol-Myers Squibb and honoraria for speaker meetings. He was also an investigator in the CHARISMA trial, which was funded by sanofi-aventis and Bristol-Myers Squibb. He has also received institutional research grants from GlaxoSmithKline and Actelion, honoraria for speaker meetings and advisory panels from Eli Lilly & Co., Pfizer, and Daiichi Sankyo, Inc., and holds a consultancy contract with Eisai.; Dr. Boden has served as a consultant or received consulting fees or honoraria from Abbott Laboratories, Bristol-Myers Squibb, CV Therapeutics, Merck, PDL BioPharma, Pfizer, and sanofi-aventis. NR 58 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD JUN PY 2010 VL 24 IS 3 BP 207 EP 216 DI 10.1007/s10557-010-6245-9 PG 10 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 647ES UT WOS:000281601200003 PM 20593231 ER PT J AU Moore, K Lovercamp, K Feng, DY Antelman, J Sutovsky, M Manandhar, G van Leyen, K Safranski, T Sutovsky, P AF Moore, Kelly Lovercamp, Kyle Feng, Dongyan Antelman, Jennifer Sutovsky, Miriam Manandhar, Gaurishankar van Leyen, Klaus Safranski, Timothy Sutovsky, Peter TI Altered epididymal sperm maturation and cytoplasmic droplet migration in subfertile male Alox15 mice SO CELL AND TISSUE RESEARCH LA English DT Article DE Sperm; Epididymis; Cytoplasmic droplet; 15-Lipoxygenase; Ubiquitin; Mouse (C57BL/6J, transgenic Alox15) ID ACROSOME REACTION; ARACHIDONATE 15-LIPOXYGENASE; ORGANELLE DEGRADATION; RABBIT RETICULOCYTES; IN-VITRO; SPERMATOZOA; LIPOXYGENASE; GOSSYPOL; MITOCHONDRIA; FERTILITY AB Mammalian spermatozoa complete their morphogenesis and acquire their fertilizing potential in the epididymis. Prominent among the hallmarks of epididymal sperm maturation is the proximal-distal migration of the cytoplasmic droplet (CD), the last remnant of the spermatogenic cell cytoplasm, down the sperm flagellum. Failure to shed the CD has been associated with male infertility. Because of the presence of the organelle degradation enzyme 15-lipoxygenase (15LOX) in sperm CD, we hypothesize that subfertile male Alox15 mice lacking the 15Lox gene display sperm CD anomalies. Caput and cauda epididymal sperm samples from seven adult Alox15 and seven wild-type (wt) males of equal age were examined by differential interference contrast microscopy (DIC) and transmission electron microscopy (TEM). Compared with wt males, Alox15 males had significantly more spermatozoa with a retained CD in both caput (P = 0.004) and cauda (P = 0.005) epididymidis. TEM and DIC analyses revealed intact mitochondria present in the CDs of epididymal Alox15 spermatozoa. The CDs of wt spermatozoa, however, had a smooth appearance and contained only hollow membrane vesicles, with no intact mitochondria embedded in their CD matrix. Epithelial lesions, phagocytosis-like figures, and missing or aberrant apical blebs were observed in the caput epididymidis of Alox15 males. Thus, the process of epididymal sperm maturation and CD migration is altered in Alox15 males. Aberrant sperm maturation might contribute to the reduced fertility and smaller litter size of Alox15 mice, a rare example of subfertile mutants displaying normal spermatogenesis but altered epididymal sperm maturation. C1 [Moore, Kelly; Lovercamp, Kyle; Antelman, Jennifer; Sutovsky, Miriam; Manandhar, Gaurishankar; Safranski, Timothy; Sutovsky, Peter] Univ Missouri, Div Anim Sci, Columbia, MO 65211 USA. [Moore, Kelly; Lovercamp, Kyle; Antelman, Jennifer; Sutovsky, Miriam; Manandhar, Gaurishankar; Safranski, Timothy; Sutovsky, Peter] Univ Missouri, Dept Obstet, Columbia, MO 65211 USA. [Moore, Kelly; Lovercamp, Kyle; Antelman, Jennifer; Sutovsky, Miriam; Manandhar, Gaurishankar; Safranski, Timothy; Sutovsky, Peter] Univ Missouri, Dept Gynecol, Columbia, MO 65211 USA. [Moore, Kelly; Lovercamp, Kyle; Antelman, Jennifer; Sutovsky, Miriam; Manandhar, Gaurishankar; Safranski, Timothy; Sutovsky, Peter] Univ Missouri, Dept Womens Hlth, Columbia, MO 65211 USA. [Feng, Dongyan] Washington Univ, Sch Med, St Louis, MO 63110 USA. [van Leyen, Klaus] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. RP Sutovsky, P (reprint author), ASRC-S141,920 E Campus Dr, Columbia, MO 65211 USA. EM sutovskyp@missouri.edu RI van Leyen, Klaus/C-9126-2013 FU National Research Initiative Competitive [2002-35203-12237, 2007-01319]; University of Missouri-Columbia FX This work was in part supported by National Research Initiative Competitive Grants (nos. 2002-35203-12237 and 2007-01319 to P. S.). Core funding was provided by the Food for the 21st Century Program of the University of Missouri-Columbia (to P.S.). NR 41 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JUN PY 2010 VL 340 IS 3 BP 569 EP 581 DI 10.1007/s00441-010-0972-x PG 13 WC Cell Biology SC Cell Biology GA 607QH UT WOS:000278520900016 PM 20449608 ER PT J AU Peled, JU Yu, JJ Venkatesh, J Bi, EG Ding, BB Krupski-Downs, M Shaknovich, R Sicinski, P Diamond, B Scharff, MD Ye, BH AF Peled, Jonathan U. Yu, J. Jessica Venkatesh, Jeganathan Bi, Enguang Ding, B. Belinda Krupski-Downs, Melissa Shaknovich, Rita Sicinski, Piotr Diamond, Betty Scharff, Matthew D. Ye, B. Hilda TI Requirement for cyclin D3 in germinal center formation and function SO CELL RESEARCH LA English DT Article DE B cell development; germinal center; cell cycle; cyclin D3 ID CLASS-SWITCH RECOMBINATION; B-CELL DEVELOPMENT; TRANSCRIPTIONAL PROGRAM; SOMATIC HYPERMUTATION; POSITIVE SELECTION; IMMUNE-RESPONSE; GENE-EXPRESSION; IN-VIVO; BCL-6; PROLIFERATION AB Germinal centers (GC) of secondary lymphoid tissues are critical to mounting a high-affinity humoral immune response. B cells within the GC undergo rapid clonal expansion and selection while diversifying their antibody genes. Although it is generally believed that GC B cells employ a unique proliferative program to accommodate these processes, little is known about how the GC-associated cell cycle is orchestrated. The D-type cyclins constitute an important component of the cell cycle engine that enables the cells to respond to physiological changes. Cell type-and developmental stage-specific roles of D-type cyclins have been described but the cyclin D requirement during GC reaction has not been addressed. In this study, we report that cyclin D3 is largely dispensable for proliferation and Ig class switching of in vitro activated B cells. In contrast, GC development in Ccnd3(-/-) mice is markedly impaired, as is the T cell-dependent antibody response. Within the GC, although both switched and unswitched B cells are affected by cyclin D3 inactivation, the IgM(-) pool is more severely reduced. Interestingly, despite a compensatory increase in cyclin D2 expression, a significant number of Ccnd3(-/-) GC B cells accumulate in quiescent G0 state. Lastly, although cyclin D3 inactivation did not disrupt BCL6 expression in GC B cells, it completely blocked the GC promoting effect of BCL6 overexpression, suggesting that cyclin D3 acts downstream of BCL6 to regulate GC formation. This is the first demonstration that cyclin D3 plays an important and unique role at the GC stage of B cell development. C1 [Peled, Jonathan U.; Yu, J. Jessica; Bi, Enguang; Ding, B. Belinda; Krupski-Downs, Melissa; Scharff, Matthew D.; Ye, B. Hilda] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. [Venkatesh, Jeganathan; Diamond, Betty] Feinstein Inst Med Res, Ctr Autoimmune & Musculoskeletal Dis, Manhasset, NY 11030 USA. [Shaknovich, Rita] Weill Cornell Coll Med, Dept Med, New York, NY 10021 USA. [Shaknovich, Rita] Weill Cornell Coll Med, Dept Pathol, New York, NY 10021 USA. [Sicinski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Sicinski, Piotr] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ye, BH (reprint author), Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM hilda.ye@einstein.yu.edu RI BI, ENGUANG/K-4033-2014; OI BI, ENGUANG/0000-0003-0850-8135; Peled, Jonathan/0000-0002-4029-7625 FU Medical Scientist Training Program [T32GM007288]; National Institutes of Health [R01 CA85573, R01 CA72649, CA102705, K08 CA127353, R01 AR049126, AI051392, P01 CA109901]; National Women's Division FX We thank Dr Riccardo Dalla-Favera (Columbia University, USA) for sharing the I mu-HA-BCL6 mouse strain, Drs Ulf Klein (Columbia University, USA) and Liang Zhu (Albert Einstein College of Medicine (AECOM), USA) for insightful suggestions, Dr Mimi Kim (AECOM) for expert statistical analysis, Drs Sergio Roa, Lydia Zhao and Susan Buhl (AECOM), and Lucas Tsikitas (Weill Cornell College of Medicine, USA) for their invaluable technical support. We are also indebted to Drs Arthur Skoultchi, Liang Zhu and Ganjam Kalpana (AECOM) for reagents. The AECOM Flow Cytometry Facility and Histopathology Facility are gratefully acknowledged. This work was supported by the Medical Scientist Training Program T32GM007288 (J.U.P.) and grants from the National Institutes of Health R01 CA85573 (B.H.Y), R01 CA72649 and CA102705 (M.D.S.), K08 CA127353 (R.S.), R01 AR049126 and AI051392 (B.D.), and P01 CA109901 (P.S). Support also came from the Harry Eagle Chair provided by the National Women's Division to M.D.S. NR 49 TC 26 Z9 26 U1 0 U2 1 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD JUN PY 2010 VL 20 IS 6 BP 631 EP 646 DI 10.1038/cr.2010.55 PG 16 WC Cell Biology SC Cell Biology GA 610IX UT WOS:000278726600007 PM 20404856 ER PT J AU Imielinski, M Belta, C AF Imielinski, Marcin Belta, Calin TI Deep epistasis in human metabolism SO CHAOS LA English DT Article ID BIOCHEMICAL REACTION NETWORKS; MINIMAL CUT SETS; FUNCTIONAL-ANALYSIS; GENETIC REDUNDANCY; PATHWAY STRUCTURE; RECONSTRUCTION; ROBUSTNESS; MODEL; CONSERVATION; ESSENTIALITY AB We extend and apply a method that we have developed for deriving high-order epistatic relationships in large biochemical networks to a published genome-scale model of human metabolism. In our analysis we compute 33 328 reaction sets whose knockout synergistically disables one or more of 43 important metabolic functions. We also design minimal knockouts that remove flux through fumarase, an enzyme that has previously been shown to play an important role in human cancer. Most of these knockout sets employ more than eight mutually buffering reactions, spanning multiple cellular compartments and metabolic subsystems. These reaction sets suggest that human metabolic pathways possess a striking degree of parallelism, inducing "deep" epistasis between diversely annotated genes. Our results prompt specific chemical and genetic perturbation follow-up experiments that could be used to query in vivo pathway redundancy. They also suggest directions for future statistical studies of epistasis in genetic variation data sets. (C) 2010 American Institute of Physics. [doi: 10.1063/1.3456056] C1 [Imielinski, Marcin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Belta, Calin] Boston Univ, Dept Mech Engn, Dept Syst Engn, Boston, MA 02215 USA. [Belta, Calin] Boston Univ, Dept Bioinformat, Boston, MA 02215 USA. RP Imielinski, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM mimielinski@partners.org NR 42 TC 10 Z9 10 U1 0 U2 4 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 1054-1500 J9 CHAOS JI Chaos PD JUN PY 2010 VL 20 IS 2 AR 026104 DI 10.1063/1.3456056 PG 12 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA 630WB UT WOS:000280304600037 PM 20590333 ER PT J AU Chen, Z Zhou, SY Chen, JC Deng, YC Luo, ZP Chen, HW Hamblin, MR Huang, MD AF Chen, Zhuo Zhou, Shanyong Chen, Jincan Deng, Yicai Luo, Zhipu Chen, Hongwei Hamblin, Michael R. Huang, Mingdong TI Pentalysine beta-Carbonylphthalocyanine Zinc: An Effective Tumor-Targeting Photosensitizer for Photodynamic Therapy SO CHEMMEDCHEM LA English DT Article DE cancer; cytotoxicity; pharmacokinetics; photodynamic therapy; synthesis ID DISULFONATED ALUMINUM PHTHALOCYANINE; MITOCHONDRIA-DEPENDENT APOPTOSIS; INTENSITY LASER THERAPY; CHINESE-HAMSTER CELLS; BIOLOGICAL-ACTIVITIES; PHOTOCHEMICAL PROPERTIES; DIFFERENT MECHANISMS; CANCER; SERIES; PHOTOFRIN AB Unsymmetrical phthalocyanine derivatives have been widely studied as photosensitizers for photodynamic therapy (PDT), targeting various tumor types. However, the preparation of unsymmetrical phthalocyanines is always a challenge due to the presence of many possible structural isomers. Herein we report a new unsymmetrical zinc phthalocyanine, pentalysine beta-carbonylphthalocyanine zinc (ZnPc-(Lys)(5)), that was prepared in large quantity and high purity. This is a water-soluble cationic photosensitizer and maintains a high quantum yield of singlet oxygen generation similar to that of unsubstituted zinc phthalocyanine (ZnPc). Compared with anionic ZnPc counterparts, ZnPc-(Lys)(5) shows a higher level cellular uptake and 20-fold higher phototoxicity toward tumor cells. Pharmacokinetics and PDT studies of ZnPc-(Lys)(5) in S180 tumor-bearing mice showed a high ratio of tumor versus skin retention and significant tumor inhibition. This new molecular framework will allow synthetic diversity in the number of lysine residues incorporated and will facilitate future QSAR studies. C1 [Chen, Zhuo; Luo, Zhipu; Chen, Hongwei; Huang, Mingdong] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China. [Chen, Zhuo; Zhou, Shanyong; Chen, Jincan; Luo, Zhipu; Chen, Hongwei; Huang, Mingdong] Chinese Acad Sci, Fujian Inst Res Struct Matter, China Denmark Ctr Proteases & Canc, State Key Lab Struct Chem,Div Chem Biol, Fuzhou 350002, Fujian, Peoples R China. [Deng, Yicai] Sun Yat Sen Univ, Guangzhou 510080, Guangdong, Peoples R China. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Chen, Z (reprint author), Chinese Acad Sci, Grad Univ, 19 Yuquan Rd, Beijing 100049, Peoples R China. EM mhuang@fjirsm.ac.cn RI Luo, Zhipu/P-9168-2014; Chen, Zhuo/A-6144-2011 OI Chen, Zhuo/0000-0002-6351-8689 FU FJIRSM [SZD08003, 200910029]; Natural Science Foundation [30973567, 30625011, 30811130467]; Chinese Ministry of Science and Technology [2006AA02A313] FX We gratefully acknowledge financial support of our research by FJIRSM (SZD08003, 200910029), the Natural Science Foundation (30973567, 30625011, and 30811130467), and the Chinese Ministry of Science and Technology (2006AA02A313). NR 42 TC 22 Z9 26 U1 4 U2 25 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD JUN PY 2010 VL 5 IS 6 BP 890 EP 898 DI 10.1002/cmdc.201000042 PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 613HE UT WOS:000278969200011 PM 20458713 ER PT J AU Hess, DR AF Hess, Dean R. TI Ventilator Modes Where Have We Come From and Where Are We Going? SO CHEST LA English DT Editorial Material ID INTERMITTENT MANDATORY VENTILATION; MECHANICAL VENTILATION; WEANING PATIENTS; OUTPUT C1 [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02115 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Ellison 401,55 Fruit St, Boston, MA 02115 USA. EM dhess@partners.org NR 16 TC 5 Z9 5 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2010 VL 137 IS 6 BP 1256 EP 1258 DI 10.1378/chest.10-0205 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 608DB UT WOS:000278561400002 PM 20525646 ER PT J AU Corcoran, AM Casarett, DJ AF Corcoran, Amy M. Casarett, David J. TI Improving Communication and Rethinking Hospice Care SO CHEST LA English DT Editorial Material ID SERIOUSLY ILL; CANCER; LIFE; DISCUSSIONS; END C1 [Corcoran, Amy M.] Univ Penn, Dept Clin Med, Div Geriatr, Philadelphia, PA 19104 USA. [Casarett, David J.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Corcoran, AM (reprint author), Penn Ralston Ctr, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM amym.corcoran@uphs.upenn.edu NR 11 TC 0 Z9 0 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2010 VL 137 IS 6 BP 1262 EP 1263 DI 10.1378/chest.10-0040 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 608DB UT WOS:000278561400005 PM 20525649 ER PT J AU Ortiz, G Frutos-Vivar, F Ferguson, ND Esteban, A Raymondos, K Apezteguia, C Hurtado, J Gonzalez, M Tomicic, V Elizalde, J Abroug, F Arabi, Y Pelosi, P Anzueto, A AF Ortiz, Guillermo Frutos-Vivar, Fernando Ferguson, Niall D. Esteban, Andres Raymondos, Konstantinos Apezteguia, Carlos Hurtado, Javier Gonzalez, Marco Tomicic, Vinko Elizalde, Jose Abroug, Fekri Arabi, Yaseen Pelosi, Paolo Anzueto, Antonio CA Ventila Grp TI Outcomes of Patients Ventilated With Synchronized Intermittent Mandatory Ventilation With Pressure Support A Comparative Propensity Score Study SO CHEST LA English DT Article ID MECHANICAL VENTILATION; WEANING PATIENTS; CARDIAC-SURGERY; IMV; OUTPUT AB Background: Few data are available regarding the benefits of one mode over another for ventilatory support. We set out to compare clinical outcomes of patients receiving synchronized intermittent mandatory ventilation with pressure support (SIMV-PS) compared with assist-control (A/C) ventilation as their primary mode of ventilatory support. Methods: This was a secondary analysis of an observational study conducted in 349 ICUs from 23 countries. A propensity score stratified analysis was used to compare 350 patients ventilated with SIMV-PS with 1,228 patients ventilated with A/C ventilation. The primary outcome was in-hospital mortality. Results: in a logistic regression model, patients were more likely to receive SIMV-PS if they were from North America, had lower severity of illness, or were ventilated postoperatively or for trauma. SIMV-PS was less likely to be selected if patients were ventilated because of asthma or coma, or if they developed complications such as sepsis or cardiovascular failure during mechanical ventilation. In the stratified analysis according to propensity score, we did not find significant differences in the in-hospital mortality. After adjustment for propensity score, overall effect of SIMV-PS on in-hospital mortality was not significant (odds ratio, 1.04; 95% CI, 0.77-1.42; P = .78). Conclusions: In our cohort of ventilated patients, ventilation with SIMV-PS compared with A/C did not offer any advantage in terms of clinical outcomes, despite treatment-allocation bias that would have favored SIMV-PS. CHEST 2010; 137(6):1265-1277 C1 [Esteban, Andres] Hosp Univ Getafe, Intens Care Unit, Madrid 28905, Spain. [Ortiz, Guillermo] Hosp Santa Clara, Bogota, Colombia. [Frutos-Vivar, Fernando; Esteban, Andres] CIBER Enfermedades Resp, Madrid, Spain. [Ferguson, Niall D.] Univ Toronto, Interdept Div Crit Care Med, Univ Hlth Network, Div Respirol, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Toronto, Dept Med, Univ Hlth Network, Div Respirol, Toronto, ON, Canada. Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Raymondos, Konstantinos] Hannover Med Sch, D-30623 Hannover, Germany. [Apezteguia, Carlos] Hosp Profesor A Posadas, Buenos Aires, DF, Argentina. [Hurtado, Javier] Hosp Clin Montevideo, Montevideo, Uruguay. [Gonzalez, Marco] Clin Medellin & Univ Pontificia Bolivariana, Medellin, Colombia. [Tomicic, Vinko] Clin Alemana Santiago, Santiago, Chile. [Elizalde, Jose] Hosp ABC, Mexico City, DF, Mexico. [Abroug, Fekri] Fattouma Bourguiba Monastir, Monastir, Tunisia. [Arabi, Yaseen] King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia. [Pelosi, Paolo] Univ Insubria, Osped Circolo, Varese, Italy. [Anzueto, Antonio] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Esteban, A (reprint author), Hosp Univ Getafe, Intens Care Unit, Carretera Toledo Km 12,500, Madrid 28905, Spain. EM aesteban@ucigetafe.com OI Frutos-Vivar, Fernando/0000-0002-4648-9636; Ferguson, Niall/0000-0002-6213-5264 FU Instituto de Salud Carlos III, Spain; Canadian Institutes of Health (Ottawa, ON, Canada) FX Funding/Support: This study was funded by CIBER Enfermedades Respiratorias from Instituto de Salud Carlos III, Spain. Dr Ferguson is supported by a Canadian Institutes of Health Research New Investigator Award (Ottawa, ON, Canada). NR 22 TC 16 Z9 16 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2010 VL 137 IS 6 BP 1265 EP 1277 DI 10.1378/chest.09-2131 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 608DB UT WOS:000278561400006 PM 20022967 ER PT J AU Raoof, S Goulet, K Esan, A Hess, DR Sessler, CN AF Raoof, Suhail Goulet, Keith Esan, Adebayo Hess, Dean R. Sessler, Curtis N. TI Severe Hypoxemic Respiratory Failure Part 2-Nonventilatory Strategies SO CHEST LA English DT Article ID ACUTE LUNG INJURY; INHALED NITRIC-OXIDE; RANDOMIZED CONTROLLED-TRIAL; EXTRACORPOREAL MEMBRANE-OXYGENATION; NEUROMUSCULAR BLOCKING-AGENTS; SEVERE PULMONARY-HYPERTENSION; CRITICALLY ILL PATIENTS; INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED PATIENTS; END-EXPIRATORY PRESSURE AB ARDS is characterized by hypoxemic respiratory failure, which can be refractory and life-threatening. Modifications to traditional mechanical ventilation and nontraditional modes of ventilation are discussed in Part 1 of this two-part series. In this second article, we examine nonventilatory strategies that can influence oxygenation, with particular emphasis on their role in rescue from severe hypoxemia. A literature search was conducted and a narrative review written to summarize the use of adjunctive, nonventilatory interventions intended to improve oxygenation in ARDS. Several adjunctive interventions have been demonstrated to rapidly ameliorate severe hypoxemia in many patients with severe ARDS and therefore may be suitable as rescue therapy for hypoxemia that is refractory to prior optimization of mechanical ventilation. These include neuromuscular blockade, inhaled vasoactive agents, prone positioning, and extracorporeal life support. Although these interventions have been linked to physiologic improvement, including relief from severe hypoxemia, and some are associated with outcome benefits, such as shorter duration of mechanical ventilation, demonstration of survival benefit has been rare in clinical trials. Furthermore, some of these nonventilatory interventions carry additional risks and/or high cost; thus, when used as rescue therapy for hypoxemia, it is important that they be demonstrated to yield clinically significant improvement in gas exchange, which should be periodically reassessed. Additionally, various management strategies can produce a more gradual improvement in oxygenation in ARDS, such as conservative fluid management, intravenous corticosteroids, and nutritional modification. Although improvement in oxygenation has been reported with such strategies, demonstration of additional beneficial outcomes, such as reduced duration of mechanical ventilation or ICU length of stay, or improved survival in randomized controlled trials, as well as consideration of potential adverse effects should guide decisions on their use. Various nonventilatory interventions can positively impact oxygenation as well as outcomes of ARDS. These interventions may be considered for use, particularly for cases of refractory severe hypoxemia, with proper appreciation of potential costs and adverse effects. CHEST 2010; 137(6):1437-1448 C1 [Raoof, Suhail; Esan, Adebayo] New York Methodist Hosp, Div Pulm & Crit Care Med, Brooklyn, NY 11215 USA. [Goulet, Keith] Virginia Commonwealth Univ, Dept Pulm & Crit Care Med, Richmond, VA 23284 USA. [Sessler, Curtis N.] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23284 USA. [Hess, Dean R.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. RP Raoof, S (reprint author), New York Methodist Hosp, Div Pulm & Crit Care Med, 506 6th St, Brooklyn, NY 11215 USA. EM sur9016@nyp.org NR 108 TC 60 Z9 66 U1 1 U2 6 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2010 VL 137 IS 6 BP 1437 EP 1448 DI 10.1378/chest.09-2416 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 608DB UT WOS:000278561400031 PM 20525656 ER PT J AU Albert, CM MacRae, CA Chasman, DI VanDenburgh, M Buring, JE Manson, JE Cook, NR Newton-Cheh, C AF Albert, Christine M. MacRae, Calum A. Chasman, Daniel I. VanDenburgh, Martin Buring, Julie E. Manson, Joann E. Cook, Nancy R. Newton-Cheh, Christopher TI Common Variants in Cardiac Ion Channel Genes Are Associated With Sudden Cardiac Death SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE death; sudden; genetics; ion channels; epidemiology ID QT INTERVAL DURATION; UNITED-STATES; POLYMORPHISM; RISK; REPOLARIZATION; ARRHYTHMIAS; EXPRESSION; COMMUNITY; DISEASE; WOMEN AB Background-Rare variants in cardiac ion channel genes are associated with sudden cardiac death in rare primary arrhythmic syndromes; however, it is unknown whether common variation in these same genes may contribute to sudden cardiac death risk at the population level. Methods and Results-We examined the association between 147 single nucleotide polymorphisms (SNPs) (137 tag, 5 noncoding SNPs associated with QT interval duration, and 5 nonsynonymous SNPs) in 5 cardiac ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2, and sudden and/or arrhythmic death in a combined nested case-control analysis among 516 cases and 1522 matched control subjects of European ancestry enrolled in 6 prospective cohort studies. After accounting for multiple testing, 2 SNPs (rs2283222 located in intron 11 in KCNQ1 and rs11720524 located in intron 1 in SCN5A) remained significantly associated with sudden/arrhythmic death (false discovery rate=0.01 and 0.03, respectively). Each increasing copy of the major T-allele of rs2283222 or the major C-allele of rs1172052 was associated with an odds ratio of 1.36 (95% confidence interval, 1.16 to 1.60; P=0.0002) and 1.30 (95% confidence interval, 1.12 to 1.51; P=0.0005), respectively. Control for cardiovascular risk factors and/or limiting the analysis to definite sudden cardiac death did not significantly alter these relationships. Conclusion-In this combined analysis of 6 prospective cohort studies, 2 common intronic variants in KCNQ1 and SCN5A were associated with sudden cardiac death in individuals of European ancestry. Further study in other populations and investigation into the functional abnormalities associated with noncoding variation in these genes may lead to important insights into predisposition to lethal arrhythmias. (Circ Arrhythm Electrophysiol. 2010;3:222-229.) C1 [Albert, Christine M.] Harvard Univ, Sch Med, Brigham & Womens Hosp,Div Prevent Med, Div Cardiovasc,Ctr Arrhythmia Prevent,Dept Med, Boston, MA 02115 USA. [Manson, Joann E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging,Dept Med, Boston, MA 02115 USA. [Newton-Cheh, Christopher] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02115 USA. [Newton-Cheh, Christopher] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Albert, CM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Div Prevent Med, Div Cardiovasc,Ctr Arrhythmia Prevent,Dept Med, 900 Commonwealth Ave E, Boston, MA 02115 USA. EM calbert@partners.org FU National Heart, Lung, and Blood Institute [HL068070, CA-34944, HL-26490, HL-34595, HL-34594, HL-35464, HL-043851, HL-46959]; Doris Duke Foundation; Donald W. Reynolds Foundation; American Heart Association; NIH [K23HL080025]; Doris Duke Charitable Foundation Clinical Scientist Development Award; Burroughs Wellcome Fund Career Award for Medical Scientists; National Cancer Institute [CA-34944, CA 40360, CA-47988, CA55075, CA-87969, CA 97193] FX This project was supported by grants from the National Heart, Lung, and Blood Institute (HL068070 to Dr Albert) and the Doris Duke Foundation (Clinical Innovation Award to Drs Albert and MacRae). Additional support for the DNA extraction in the Women's Health Study came from the Donald W. Reynolds Foundation. Dr Albert is also supported by an Established Investigator Award from the American Heart Association. Dr Newton-Cheh was supported by an award from the NIH (K23HL080025), a Doris Duke Charitable Foundation Clinical Scientist Development Award, and a Burroughs Wellcome Fund Career Award for Medical Scientists. The cohort studies were supported by grants HL-26490, HL-34595, HL-34594, HL-35464, HL-043851, HL-46959, and HL-080467 from the National Heart, Lung, and Blood Institute and CA-34944, CA 40360, CA-47988, CA55075, CA-87969, and CA 97193 from the National Cancer Institute. NR 34 TC 27 Z9 27 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD JUN PY 2010 VL 3 IS 3 BP 222 EP U22 DI 10.1161/CIRCEP.110.944934 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 611EB UT WOS:000278793000002 PM 20400777 ER PT J AU Lubitz, SA Ozcan, C Magnani, JW Kaab, S Benjamin, EJ Ellinor, PT AF Lubitz, Steven A. Ozcan, Cevher Magnani, Jared W. Kaeaeb, Stefan Benjamin, Emelia J. Ellinor, Patrick T. TI Genetics of Atrial Fibrillation Implications for Future Research Directions and Personalized Medicine SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial flutter; atrium; electrophysiology; epidemiology; fibrillation; genetics; ion channels; risk factors ID OF-FUNCTION MUTATION; CONGESTIVE-HEART-FAILURE; LEFT-RIGHT ASYMMETRY; SHORT QT SYNDROME; DILATED CARDIOMYOPATHY; FAMILIAL AGGREGATION; CHROMOSOME 4Q25; COMMON VARIANTS; ISCHEMIC-STROKE; SODIUM-CHANNEL C1 [Ozcan, Cevher; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Kaeaeb, Stefan] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Benjamin, Emelia J.] Boston Univ, Framingham, MA USA. [Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Magnani, Jared W.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM pellinor@partners.org OI Benjamin, Emelia/0000-0003-4076-2336 FU NIH [T32HL007575, HL092577, AG028321, RC1-HL01056, DA027021]; Fondation Leducq [07-CVD 03]; Bundesministerium fur Bildung und Forschung (BMBF), in the context of the German National Genome Research Network (NGFN) [01GS0838]; German AF-Net [01 GI 0204/N]; Exzellen-zinitiative at Ludwig-Maximilians University, Munich FX Dr Lubitz is supported by an NIH training grant in the Epidemiology of Cardiovascular Disease (T32HL007575). Dr Magnani is supported by an AHA grant (09FTF2190028). This work was supported by grants from the NIH to Drs Benjamin and Ellinor (HL092577), Dr Benjamin (AG028321, RC1-HL01056), and Dr Ellinor (DA027021). Drs Benjamin, Ellinor, and Kaab are supported by a grant from the Fondation Leducq (07-CVD 03). Dr Kaab is supported by Bundesministerium fur Bildung und Forschung (BMBF) in the context of the German National Genome Research Network (NGFN, 01GS0838), the German AF-Net (01 GI 0204/N), and the Exzellen-zinitiative at Ludwig-Maximilians University, Munich. NR 100 TC 43 Z9 43 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD JUN PY 2010 VL 3 IS 3 BP 291 EP 299 DI 10.1161/CIRCEP.110.942441 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 611EB UT WOS:000278793000012 PM 20551423 ER PT J AU Peralta, CA Li, YM Wassel, C Choudhry, S Palmas, W Seldin, MF Risch, N Siscovick, D Arnett, D Psaty, B Shlipak, MG AF Peralta, Carmen A. Li, Yongmei Wassel, Christina Choudhry, Shweta Palmas, Walter Seldin, Michael F. Risch, Neil Siscovick, David Arnett, Donna Psaty, Bruce Shlipak, Michael G. TI Differences in Albuminuria Between Hispanics and Whites: An Evaluation by Genetic Ancestry and Country of Origin The Multi-Ethnic Study of Atherosclerosis SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE genetics; kidney; albuminuria; ancestry ID CHRONIC KIDNEY-DISEASE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; MULTILOCUS GENOTYPE DATA; STAGE RENAL-DISEASE; SURVEY NHANES-III; POPULATION-STRUCTURE; ADMIXED POPULATIONS; MEXICAN-AMERICANS; LATINO POPULATIONS AB Background-Reports show higher prevalence of albuminuria among Hispanics compared with whites. Differences by country of origin or genetic background are unknown. Methods and Results-In Multi-Ethnic Study of Atherosclerosis, we studied the associations of both genetic ancestry and country of origin with albumin to creatinine ratio among 1417 Hispanic versus white participants using multivariable linear regression and back transforming beta coefficients into relative difference (%RD, 95% CI). Percentage European, Native American, and African ancestry components for Hispanics were estimated using genetic admixture analysis. The proportions of European, Native American, and African genetic ancestry differed significantly by country of origin (P<0.0001); Mexican/Central Americans had the highest Native American (41 +/- 13%), Puerto Ricans had the highest European (61 +/- 15%), and Dominicans had the highest African (39 +/- 21%) ancestry. Hispanic ethnicity was associated with higher albumin/creatinine ratio compared with whites, but the association varied with the country of origin (adjusted P interaction=0.04). Mexican/Central Americans and Dominicans had higher albumin/creatinine ratio compared with whites after adjustment (RD 19%, 2% to 40% and RD 27%, 1% to 61%), but not Puerto Ricans (RD 8%, -12% to 34%). Higher Native American ancestry was associated with higher albuminuria after age and sex adjustment among all Hispanics (RD 11%, 1% to 21%) but was attenuated after further adjustment. Higher European ancestry was independently associated with lower albumin/creatinine ratio among Puerto Ricans (-21%, -34% to -6%) but not among Mexican/Central Americans and Dominicans. Conclusions-Hispanics are a heterogeneous group with varying genetic ancestry. Risks of albuminuria differ across the country of origin groups. These differences may be due, in part, to differences in genetic ancestral components. (Circ Cardiovasc Genet. 2010;3:240-247.) C1 [Peralta, Carmen A.; Choudhry, Shweta; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Peralta, Carmen A.; Li, Yongmei; Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Wassel, Christina] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Palmas, Walter] Columbia Univ, Dept Med, New York, NY USA. [Seldin, Michael F.] Univ Calif Davis, Dept Biochem, Davis, CA 95616 USA. [Seldin, Michael F.] Univ Calif Davis, Dept Mol Med & Med, Davis, CA 95616 USA. [Risch, Neil] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Risch, Neil] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Arnett, Donna] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Psaty, Bruce] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA. [Psaty, Bruce] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce] Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce] Grp Hlth, Ctr Hlth Studies, Seattle, WA USA. RP Peralta, CA (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM CarmenAlicia.Peralta@ucsf.edu FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165, N01-HC-95169]; National Institute of Diabetes and Digestive and Kidney Diseases [1K23DK082793-01] FX This work was supported by contracts (N01-HC-95159 through N01-HC-95165) and (N01-HC-95169) from the National Heart, Lung, and Blood Institute. This work was also funded by the National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK082793-01 to C.A.P.). NR 45 TC 22 Z9 23 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2010 VL 3 IS 3 BP 240 EP 247 DI 10.1161/CIRCGENETICS.109.914499 PG 8 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 611GH UT WOS:000278799900005 PM 20445135 ER PT J AU Morrison, AC Felix, JF Cupples, LA Glazer, NL Loehr, LR Dehghan, A Demissie, S Bis, JC Rosamond, WD Aulchenko, YS Wang, YA Haritunians, T Folsom, AR Rivadeneira, F Benjamin, EJ Lumley, T Couper, D Stricker, BH O'Donnell, CJ Rice, KM Chang, PP Hofman, A Levy, D Rotter, JI Fox, ER Uitterlinden, AG Wang, TJ Psaty, BM Willerson, JT van Duijn, CM Boerwinkle, E Witteman, JCM Vasan, RS Smith, NL AF Morrison, Alanna C. Felix, Janine F. Cupples, L. Adrienne Glazer, Nicole L. Loehr, Laura R. Dehghan, Abbas Demissie, Serkalem Bis, Joshua C. Rosamond, Wayne D. Aulchenko, Yurii S. Wang, Ying A. Haritunians, Talin Folsom, Aaron R. Rivadeneira, Fernando Benjamin, Emelia J. Lumley, Thomas Couper, David Stricker, Bruno H. O'Donnell, Christopher J. Rice, Kenneth M. Chang, Patricia P. Hofman, Albert Levy, Daniel Rotter, Jerome I. Fox, Ervin R. Uitterlinden, Andre G. Wang, Thomas J. Psaty, Bruce M. Willerson, James T. van Duijn, Cornelia M. Boerwinkle, Eric Witteman, Jacqueline C. M. Vasan, Ramachandran S. Smith, Nicholas L. TI Genomic Variation Associated With Mortality Among Adults of European and African Ancestry With Heart Failure The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE heart failure; all-cause mortality; genetics; genome-wide variation; mortality ID CORONARY SMOOTH-MUSCLE; QT INTERVAL DURATION; WIDE ASSOCIATION; ATHEROSCLEROSIS RISK; COMMON VARIANTS; EXPRESSION; DESIGN; CHANNELS; SUBUNIT; DISEASE AB Background-Prognosis and survival are significant concerns for individuals with heart failure (HF). To better understand the pathophysiology of HF prognosis, the association between 2 366 858 single-nucleotide polymorphisms (SNPs) and all-cause mortality was evaluated among individuals with incident HF from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. Methods and Results-Participants were 2526 individuals of European ancestry and 466 individuals of African ancestry who experienced an incident HF event during follow-up in the respective cohorts. Within each study, the association between genetic variants and time to mortality among individuals with HF was assessed by Cox proportional hazards models that included adjustment for sex and age at the time of the HF event. Prospective fixed-effect meta-analyses were conducted for the 4 study populations of European ancestry (N=1645 deaths) and for the 2 populations of African ancestry (N=281 deaths). Genome-wide significance was set at P=5.0x10(-7). Meta-analytic findings among individuals of European ancestry revealed 1 genome-wide significant locus on chromosome 3p22 in an intron of CKLF-like MARVEL transmembrane domain containing 7 (CMTM7, P=3.2x10(-7)). Eight additional loci in individuals of European ancestry and 4 loci in individuals of African ancestry were identified by high-signal SNPs (P<1.0x10(-5)) but did not meet genome-wide significance. Conclusions-This study identified a novel locus associated with all-cause mortality among individuals of European ancestry with HF. This finding warrants additional investigation, including replication, in other studies of HF. (Circ Cardiovasc Genet. 2010;3:248-255.) C1 [Morrison, Alanna C.; Willerson, James T.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77225 USA. [Chang, Patricia P.] Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA. [Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA. [Rosamond, Wayne D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. [Loehr, Laura R.; Rosamond, Wayne D.] Nat Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Fox, Ervin R.] Univ Mississippi, Med Ctr, Dept Med, University, MS 38677 USA. [Fox, Ervin R.] NHLBI, Jackson Heart Study, Houston, TX USA. [Willerson, James T.] Texas Heart Inst, Houston, TX 77025 USA. [Felix, Janine F.; Dehghan, Abbas; Aulchenko, Yurii S.; Stricker, Bruno H.; Hofman, Albert; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Felix, Janine F.; Witteman, Jacqueline C. M.] Netherlands Consortium Healthy Aging, Leiden, Netherlands. [Cupples, L. Adrienne; Demissie, Serkalem; Wang, Ying A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med & Prevent Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Cupples, L. Adrienne; Benjamin, Emelia J.; O'Donnell, Christopher J.; Levy, Daniel; Vasan, Ramachandran S.] Natl Heart Lung Blood Inst, Framingham Heart Study, Framingham, MA USA. [O'Donnell, Christopher J.; Wang, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Psaty, Bruce M.; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Glazer, Nicole L.; Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Lumley, Thomas; Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Smith, Nicholas L.] Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Seattle, WA USA. [Haritunians, Talin; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Psaty, Bruce M.; Smith, Nicholas L.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. RP Morrison, AC (reprint author), Univ Texas Houston Hlth Sci Ctr, Ctr Human Genet, 1200 Herman Pressler,Suite 453E, Houston, TX 77030 USA. EM Alanna.C.Morrison@uth.tmc.edu RI Rice, Kenneth/A-4150-2013; Aulchenko, Yurii/M-8270-2013; Rivadeneira, Fernando/O-5385-2015; OI Rice, Kenneth/0000-0001-5779-4495; Aulchenko, Yurii/0000-0002-7899-1575; Rivadeneira, Fernando/0000-0001-9435-9441; Felix, Janine/0000-0002-9801-5774; Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Dehghan, Abbas/0000-0001-6403-016X FU National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C]; National Institutes of Health, National Institutes of Environmental Health Sciences; National Heart Lung and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL 087652, N01-HC-25195]; National Center for Research Resources [M01RR00425-39]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; National Heart Lung Blood Institute [2K24HL04334, R01HL077477, R01HL093328]; Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Heart Foundation; Ministry of Health, Welfare and Sports; Ministry of Education, Culture and Science; European Commission; Municipality of Rotterdam; Netherlands Organization for Scientific Research (NWO) [918-76-619]; Netherlands Organization for Scientific Research [175.010.2005.011, 911.03.012]; Research Institute for Diseases; Netherlands Genomics Initiative/Netherlands Organization for Scientific Research [050-60-810]; [UL1RR025005] FX The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, and R01HL086694); National Human Genome Research Institute (U01HG004402); and National Institutes of Health (HHSN268200625226C). Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. This research was supported in part by the intramural research program of the National Institutes of Health, National Institutes of Environmental Health Sciences. The Cardiovascular Health Study is supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295, and R01 HL 087652 from National Heart Lung and Blood Institute with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal Cardiovascular Health Study investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was supported in part by National Center for Research Resources grant M01RR00425-39 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The Framingham Heart Study was supported by National Heart Lung and Blood Institute (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). This work was also supported in part by grants from the National Heart Lung Blood Institute 2K24HL04334, R01HL077477, and R01HL093328 (all to Dr Vasan). This study is based on analyses by Framingham Heart Study investigators participating in the SNP Health Association Resource project. The Rotterdam Study 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 Netherlands Heart Foundation; the Ministry of Health, Welfare and Sports; the Ministry of Education, Culture and Science; the European Commission (DG XII); and the Municipality of Rotterdam. Abbas Dehghan and Janine Felix are supported by a VICI grant from the Netherlands Organization for Scientific Research (NWO) no. 918-76-619. The GWAS database of the Rotterdam study was funded through Netherlands Organization for Scientific Research (175.010.2005.011, 911.03.012) and Research Institute for Diseases in the Elderly. This study was supported by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research, project number 050-60-810. NR 28 TC 48 Z9 52 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2010 VL 3 IS 3 BP 248 EP U64 DI 10.1161/CIRCGENETICS.109.895995 PG 10 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 611GH UT WOS:000278799900006 PM 20400778 ER PT J AU Smith, NL Felix, JF Morrison, AC Demissie, S Glazer, NL Loehr, LR Cupples, LA Dehghan, A Lumley, T Rosamond, WD Lieb, W Rivadeneira, F Bis, JC Folsom, AR Benjamin, E Aulchenko, YS Haritunians, T Couper, D Murabito, J Wang, YA Stricker, BH Gottdiener, JS Chang, PP Wang, TJ Rice, KM Hofman, A Heckbert, SR Fox, ER O'Donnell, CJ Uitterlinden, AG Rotter, JI Willerson, JT Levy, D van Duijn, CM Psaty, BM Witteman, JCM Boerwinkle, E Vasan, RS AF Smith, Nicholas L. Felix, Janine F. Morrison, Alanna C. Demissie, Serkalem Glazer, Nicole L. Loehr, Laura R. Cupples, L. Adrienne Dehghan, Abbas Lumley, Thomas Rosamond, Wayne D. Lieb, Wolfgang Rivadeneira, Fernando Bis, Joshua C. Folsom, Aaron R. Benjamin, Emelia Aulchenko, Yurii S. Haritunians, Talin Couper, David Murabito, Joanne Wang, Ying A. Stricker, Bruno H. Gottdiener, John S. Chang, Patricia P. Wang, Thomas J. Rice, Kenneth M. Hofman, Albert Heckbert, Susan R. Fox, Ervin R. O'Donnell, Christopher J. Uitterlinden, Andre G. Rotter, Jerome I. Willerson, James T. Levy, Daniel van Duijn, Cornelia M. Psaty, Bruce M. Witteman, Jacqueline C. M. Boerwinkle, Eric Vasan, Ramachandran S. TI Association of Genome-Wide Variation With the Risk of Incident Heart Failure in Adults of European and African Ancestry A Prospective Meta-Analysis From the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE epidemiology; genetics; heart failure; genome; wide variation; incidence ID ATHEROSCLEROSIS RISK; LIFETIME RISK; FRAMINGHAM; DISEASE; COMMUNITIES; PREVALENCE; ROTTERDAM; DESIGN; CARDIOMYOPATHY; DYSFUNCTION AB Background-Although genetic factors contribute to the onset of heart failure (HF), no large-scale genome-wide investigation of HF risk has been published to date. We have investigated the association of 2 478 304 single-nucleotide polymorphisms with incident HF by meta-analyzing data from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. Methods and Results-Eligible participants for these analyses were of European or African ancestry and free of clinical HF at baseline. Each study independently conducted genome-wide scans and imputed data to the approximate to 2.5 million single-nucleotide polymorphisms in HapMap. Within each study, Cox proportional hazards regression models provided age-and sex-adjusted estimates of the association between each variant and time to incident HF. Fixed-effect meta-analyses combined results for each single-nucleotide polymorphism from the 4 cohorts to produce an overall association estimate and P value. A genome-wide significance P value threshold was set a priori at 5.0 x 10(-7). During a mean follow-up of 11.5 years, 2526 incident HF events (12%) occurred in 20 926 European-ancestry participants. The meta-analysis identified a genome-wide significant locus at chromosomal position 15q22 (1.4 x 10(-8)), which was 58.8 kb from USP3. Among 2895 African-ancestry participants, 466 incident HF events (16%) occurred during a mean follow-up of 13.7 years. One genome-wide significant locus was identified at 12q14 (6.7 x 10-(8)), which was 6.3 kb from LRIG3. Conclusions-We identified 2 loci that were associated with incident HF and exceeded genome-wide significance. The findings merit replication in other community-based settings of incident HF. (Circ Cardiovasc Genet. 2010;3:256-266.) C1 [Smith, Nicholas L.; Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Study, Seattle, WA 98195 USA. [Glazer, Nicole L.; Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Lumley, Thomas; Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Smith, Nicholas L.] Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Seattle, WA USA. [Smith, Nicholas L.; Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Gottdiener, John S.] Univ Maryland, Dept Cardiol, Baltimore, MD 21201 USA. [Haritunians, Talin; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Morrison, Alanna C.; Benjamin, Emelia; Willerson, James T.] Univ Texas Houston Hlth Sci Ctr, Artherosclerosis Risk Communities Study, Houston, TX USA. [Loehr, Laura R.; Chang, Patricia P.] Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA. [Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA. [Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA. [Loehr, Laura R.; Rosamond, Wayne D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. [Loehr, Laura R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Fox, Ervin R.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Willerson, James T.] Texas Heart Inst, Houston, TX 77025 USA. [Demissie, Serkalem; Cupples, L. Adrienne; Wang, Ying A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Framingham Heart Study, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Bethesda, MD 20892 USA. [Wang, Thomas J.; O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cupples, L. Adrienne; Lieb, Wolfgang; Benjamin, Emelia; Murabito, Joanne; Wang, Thomas J.; O'Donnell, Christopher J.; Levy, Daniel; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Felix, Janine F.; Dehghan, Abbas; Aulchenko, Yurii S.; Stricker, Bruno H.; Hofman, Albert; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam Study, Rotterdam, Netherlands. RP Smith, NL (reprint author), Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98105 USA. EM nlsmith@u.washington.edu RI Lieb, Wolfgang/C-1990-2012; Rice, Kenneth/A-4150-2013; Aulchenko, Yurii/M-8270-2013; Rivadeneira, Fernando/O-5385-2015; OI Dehghan, Abbas/0000-0001-6403-016X; Rice, Kenneth/0000-0001-5779-4495; Aulchenko, Yurii/0000-0002-7899-1575; Rivadeneira, Fernando/0000-0001-9435-9441; Murabito, Joanne/0000-0002-0192-7516; Felix, Janine/0000-0002-9801-5774; Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute (NHLBI) [N01HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01HC- 55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health (NIH) [HHSN268200625226C]; NIH, National Institutes of Environmental Health Sciences; NHLBI [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL 087652, N01-HC25195, 2K24HL04334, R01HL077477, R01HL093328]; National Center for Research Resources [M01RR00425]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; NWO [175.010.2005.011, 911.03.012]; Netherlands Genomics Initiative (NGI)/NWO [050-060-810]; Netherlands Foundation for Scientific Research (NWO, VICI) [918-76-619]; [UL1RR025005] FX We acknowledge the essential role of the CHARGE Consortium in developing this article and for the support. CHARGE members include National Heart, Lung, and Blood Institute's ARIC Study, NIA's Iceland Age, Gene/Environment Susceptibility Study, National Heart, Lung, and Blood Institute's Cardiovascular Health Study and Framingham Heart Study, and the Netherland's Rotterdam Study. The authors also acknowledge the thousands of study participants who volunteered their time to help advance science and the scores of research staff and scientists who have made this research possible. The Rotterdam Study authors thank Mila Jhamai, Pascal Arp, Dr Michael J. Moorhouse, Marijn Verkerk, and Sander Bervoets for their help in creating the database and Maxim Struchalin for his contributions to the imputations of the data.; The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts N01HC- 55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01HC- 55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health (NIH) contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This research was supported in part by the intramural research program of the NIH, National Institutes of Environmental Health Sciences.; The CHS is supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295 and R01 HL 087652 from NHLBI with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www. chs-nhlbi. org/pi. htm. DNA handling and genotyping was supported in part by National Center for Research Resources grant M01RR00425 to the Cedars-Sinai General Clinical Research Center Genotyping core, National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center, and Cedars-Sinai Board of Governors' Chair in Medical Genetics (JIR).; The FHS was supported by NHLBI (Contract No. N01-HC25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). This work was also supported in part by grants from the NHLBI 2K24HL04334, R01HL077477, and R01HL093328 (all to RSV). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The analyses reflect intellectual input and resource development from the FHS investigators participating in the SNP Health Association Resource (SHARe) project.; The RS is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Heart Foundation (Nederlandse hartstichting); the Ministry of Health Welfare and Sports; the Ministry of Education, Culture and Science; the European Commission (DG XII); and the Municipality of Rotterdam. Support for genotyping was given by NWO (175.010.2005.011, 911.03.012) and RIDE. This study was supported by the Netherlands Genomics Initiative (NGI)/NWO project number 050-060-810 (Netherlands Consortium for Healthy Ageing). The Netherlands Foundation for Scientific Research (NWO, VICI no. 918-76-619) also provided investigator support (A.D., and J.F.F.); The funding sources had no role in the study design, analyses, or drafting of the article. The NHLBI reviews all articles submitted for publication but it was not involved in the decision to publish. Drs NL Smith, JF Felix, AC Morrison, and S Demissie had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 49 TC 72 Z9 74 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2010 VL 3 IS 3 BP 256 EP U79 DI 10.1161/CIRCGENETICS.109.895763 PG 13 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 611GH UT WOS:000278799900007 PM 20445134 ER PT J AU Musunuru, K Lettre, G Young, T Farlow, DN Pirruccello, JP Ejebe, KG Keating, BJ Yang, Q Chen, MH Lapchyk, N Crenshaw, A Ziaugra, L Rachupka, A Benjamin, EJ Cupples, LA Fornage, M Fox, ER Heckbert, SR Hirschhorn, JN Newton-Cheh, C Nizzari, MM Paltoo, DN Papanicolaou, GJ Patel, SR Psaty, BM Rader, DJ Redline, S Rich, SS Rotter, JI Taylor, HA Tracy, RP Vasan, RS Wilson, JG Kathiresan, S Fabsitz, RR Boerwinkle, E Gabriel, SB AF Musunuru, Kiran Lettre, Guillaume Young, Taylor Farlow, Deborah N. Pirruccello, James P. Ejebe, Kenechi G. Keating, Brendan J. Yang, Qiong Chen, Ming-Huei Lapchyk, Nina Crenshaw, Andrew Ziaugra, Liuda Rachupka, Anthony Benjamin, Emelia J. Cupples, L. Adrienne Fornage, Myriam Fox, Ervin R. Heckbert, Susan R. Hirschhorn, Joel N. Newton-Cheh, Christopher Nizzari, Marcia M. Paltoo, Dina N. Papanicolaou, George J. Patel, Sanjay R. Psaty, Bruce M. Rader, Daniel J. Redline, Susan Rich, Stephen S. Rotter, Jerome I. Taylor, Herman A., Jr. Tracy, Russell P. Vasan, Ramachandran S. Wilson, James G. Kathiresan, Sekar Fabsitz, Richard R. Boerwinkle, Eric Gabriel, Stacey B. CA NHLBI Candidate Gene Assoc TI Candidate Gene Association Resource (CARe) Design, Methods, and Proof of Concept SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE genetics; lipids; epidemiology ID DENSITY-LIPOPROTEIN CHOLESTEROL; ATHEROSCLEROSIS; RECRUITMENT; HEART; POLYMORPHISMS; OBJECTIVES; HAPLOTYPE; ALLELES; DISEASE AB Background-The National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe), a planned cross-cohort analysis of genetic variation in cardiovascular, pulmonary, hematologic, and sleep-related traits, comprises >40 000 participants representing 4 ethnic groups in 9 community-based cohorts. The goals of CARe include the discovery of new variants associated with traits using a candidate gene approach and the discovery of new variants using the genome-wide association mapping approach specifically in African Americans. Methods and Results-CARe has assembled DNA samples for >40 000 individuals self-identified as European American, African American, Hispanic, or Chinese American, with accompanying data on hundreds of phenotypes that have been standardized and deposited in the CARe Phenotype Database. All participants were genotyped for 7 single-nucleotide polymorphisms (SNPs) selected based on prior association evidence. We performed association analyses relating each of these SNPs to lipid traits, stratified by sex and ethnicity, and adjusted for age and age squared. In at least 2 of the ethnic groups, SNPs near CETP, LIPC, and LPL strongly replicated for association with high-density lipoprotein cholesterol concentrations, PCSK9 with low-density lipoprotein cholesterol levels, and LPL and APOA5 with serum triglycerides. Notably, some SNPs showed varying effect sizes and significance of association in different ethnic groups. Conclusions-The CARe Pilot Study validates the operational framework for phenotype collection, SNP genotyping, and analytic pipeline of the CARe project and validates the planned candidate gene study of approximate to 2000 biological candidate loci in all participants and genome-wide association study in similar to 8000 African American participants. CARe will serve as a valuable resource for the scientific community. ( Circ Cardiovasc Genet. 2010;3:267-275.) C1 [Musunuru, Kiran; Lettre, Guillaume; Young, Taylor; Farlow, Deborah N.; Pirruccello, James P.; Ejebe, Kenechi G.; Lapchyk, Nina; Crenshaw, Andrew; Ziaugra, Liuda; Rachupka, Anthony; Hirschhorn, Joel N.; Newton-Cheh, Christopher; Kathiresan, Sekar; Gabriel, Stacey B.] Broad Inst, Cambridge, MA 02142 USA. [Musunuru, Kiran; Pirruccello, James P.; Ejebe, Kenechi G.; Newton-Cheh, Christopher; Kathiresan, Sekar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Musunuru, Kiran; Hirschhorn, Joel N.; Newton-Cheh, Christopher; Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA. [Musunuru, Kiran; Pirruccello, James P.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Lettre, Guillaume] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Yang, Qiong; Chen, Ming-Huei; Benjamin, Emelia J.; Cupples, L. Adrienne; Vasan, Ramachandran S.] Boston Univ, Boston, MA USA. [Yang, Qiong; Chen, Ming-Huei; Benjamin, Emelia J.; Cupples, L. Adrienne; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Ervin R.; Taylor, Herman A., Jr.; Wilson, James G.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77225 USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Seattle, WA 98195 USA. [Hirschhorn, Joel N.] Childrens Hosp, Boston, MA 02115 USA. [Farlow, Deborah N.; Papanicolaou, George J.; Fabsitz, Richard R.] NHLBI, NIH, Bethesda, MD 20892 USA. [Patel, Sanjay R.; Redline, Susan] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Patel, Sanjay R.; Redline, Susan] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Rich, Stephen S.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Burlington, VT USA. RP Gabriel, SB (reprint author), Broad Inst, 5 Cambridge Ctr, Cambridge, MA 02142 USA. EM stacey@broadinstitute.org; stacey@broadinstitute.org RI Yang, Qiong/G-5438-2014; Ejebe, Kenechi/I-9238-2016; OI Ejebe, Kenechi/0000-0002-6090-8657; Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Patel, Sanjay/0000-0002-9142-5172 FU DNA [N01-HC-65226]; University of North Carolina at Chapel Hill [N01-HC-55015, N01-HC-55018]; Baylor Medical College [N01-HC-55016]; University of Mississippi Medical Center [N01-HC-55021]; University of Minnesota [N01-HC-55019, N01-HC-48048]; Johns Hopkins University [N01-HC-55020, N01-HC-85081, N01-HC-15103]; University of Texas, Houston [N01-HC-55022]; Cardiovascular Health Study: University of Washington [N01-HC-85079, N01-HC-55222, U01-HL-080295]; Wake Forest University [N01-HC-85080, N01-HC-05187]; University of Pittsburgh [N01HC-85082]; University of California [N01-HC-85083, N01-HC-85084, N01-HC-45134, N01-HC-95100]; New England Medical Center [N01-HC-85085]; University of Vermont [N01-HC-85086]; Georgetown University [N01-HC-35129]; University of Wisconsin [N01-HC-75150]; Cleveland Family Study: Case Western Reserve University [R01-HL-46380, M01-RR-00080]; Cooperative Study of Sickle Cell Disease: University of Illinois [N01-HB-72982, N01HB- 97062]; Howard University [N01-HB-72991, N01-HB-97061]; University of Miami [N01-HB-72992, N01-HB-97064]; Duke University [N01-HB-72993]; George Washington University [N01-HB72994]; University of Tennessee [N01-HB-72995, N01-HB-97070]; Yale University [N01-HB-72996, N01-HB-97072]; Children's Hospital-Philadelphia [N01-HB-72997, N01-HB-97056]; University of Chicago [N01-HB-72998, N01-HB-97053]; Medical College of Georgia [N01-HB-73000, N01-HB-97060]; Washington University [N01-HB-73001, N01-HB-97071]; Jewish Hospital and Medical Center of Brooklyn [N01-HB-73002]; Trustees of Health and Hospitals of the City of Boston, Inc [N01-HB-73003]; Children's Hospital-Oakland [N01-HB-73004, N01-HB-97054]; University of Mississippi [N01-HB-73005]; St Luke's Hospital-New York [N01HB- 73006]; Alta Bates-Herrick Hospital [N01-HB-97051]; Columbia University [N01-HB-97058]; St Jude's Children's Research Hospital [N01-HB-97066]; Research Foundation, State University of New York-Albany [N01-HB-97068, N01-HB-97069]; New England Research Institute [N01-HB-97073]; Interfaith Medical CenterBrooklyn [N01-HB-97085]; Coronary Artery Risk in Young Adults: University of Alabama at Birmingham [N01-HC-48047, N01-HC95095]; Northwestern University [N01-HC-48049]; Kaiser Foundation Research Institute [N01-HC-48050]; Tufts-New England Medical Center [N01-HC45204]; Harbor-UCLA Research and Education Institute [N01-HC-05187]; Framingham Heart Study: Boston University [N01-HC-25195, R01-HL-092577, R01-HL-076784, R01-AG-028321]; Jackson Heart Study: Jackson State University FX The following 9 parent studies, funded by the listed National Institutes of Health grants, have contributed parent study data, ancillary study data, and samples through the Broad Institute (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community: Atherosclerotic Risk in Communities: University of North Carolina at Chapel Hill (N01-HC-55015, N01-HC-55018), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55022); Cardiovascular Health Study: University of Washington (N01-HC-85079, N01-HC-55222, U01-HL-080295), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081, N01-HC-15103), University of Pittsburgh (N01HC-85082), University of California, Davis (N01-HC-85083), University of California, Irvine (N01-HC-85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), University of Wisconsin (N01-HC-75150); Cleveland Family Study: Case Western Reserve University (R01-HL-46380, M01-RR-00080); Cooperative Study of Sickle Cell Disease: University of Illinois (N01-HB-72982, N01HB- 97062), Howard University (N01-HB-72991, N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke University (N01-HB-72993), George Washington University (N01-HB72994), University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University (N01-HB-72996, N01-HB-97072), Children's Hospital-Philadelphia (N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998, N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060), Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and Hospitals of the City of Boston, Inc (N01-HB-73003), Children's Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi (N01-HB-73005), St Luke's Hospital-New York (N01HB- 73006), Alta Bates-Herrick Hospital (N01-HB-97051), Columbia University (N01-HB-97058), St Jude's Children's Research Hospital (N01-HB-97066), Research Foundation, State University of New York-Albany (N01-HB-97068, N01-HB-97069), New England Research Institute (N01-HB-97073), Interfaith Medical CenterBrooklyn (N01-HB-97085); Coronary Artery Risk in Young Adults: University of Alabama at Birmingham (N01-HC-48047, N01-HC95095), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), Tufts-New England Medical Center (N01-HC45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California, Irvine (N01-HC-45134, N01-HC-95100); Framingham Heart Study: Boston University (N01-HC-25195, R01-HL-092577, R01-HL-076784, R01-AG-028321); Jackson Heart Study: Jackson State University (N01-HC-95170), University of Mississippi (N01HC- 95171), Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis: University of Washington (N01-HC95159), University of California, Los Angeles (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162, N01-HC-95168), University of Minnesota (N01HC- 95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01HC- 95166), New England Medical Center (N01-HC-95167), Harbor-UCLA Research and Education Institute (N01-HC-95169), Cedars-Sinai Medi; al Center (R01-HL-071205), University of Virginia (subcontract to R01-HL-071205); Sleep Heart Health Study: Johns Hopkins University (U01-HL-064360), Case Western University (U01-HL-063463), University of California, Davis (U01-HL053916), University of Arizona (U01-HL-053938, U01-HL053934), University of Pittsburgh (U01-HL-077813), Boston University (U01-HL-053941), MedStar Research Institute (U01-HL063429), Johns Hopkins University (U01-HL-053937). NR 24 TC 98 Z9 100 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2010 VL 3 IS 3 BP 267 EP U94 DI 10.1161/CIRCGENETICS.109.882696 PG 13 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 611GH UT WOS:000278799900008 PM 20400780 ER PT J AU Tsai, TT Ho, PM Xu, S Powers, JD Carroll, NM Shetterly, SM Maddox, TM Rumsfeld, JS Margolis, K Go, AS Magid, DJ AF Tsai, Thomas T. Ho, P. Michael Xu, Stanley Powers, J. David Carroll, Nikki M. Shetterly, Susan M. Maddox, Thomas M. Rumsfeld, John S. Margolis, Karen Go, Alan S. Magid, David J. TI Increased Risk of Bleeding in Patients on Clopidogrel Therapy After Drug-Eluting Stents Implantation Insights From the HMO Research Network-Stent Registry (HMORN-Stent) SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE angioplasty; revascularization; myocardial infarction; hemorrhage ID PERCUTANEOUS CORONARY INTERVENTION; MARGINAL STRUCTURAL MODELS; CONTROLLED TRIAL; ASPIRIN; OUTCOMES; STROKE AB Background-Studies suggest that extended clopidogrel use after drug-eluting stent (DES) implantation may decrease the risk of myocardial infarction (MI) and death. Little is known about the competing risk of bleeding from clopidogrel in "real world" clinical practice. Methods and Results-We studied 7689 patients undergoing drug-eluting stent implantation enrolled in the HMO Research Network-Stent Registry between 2004 and 2007. Patients were analyzed in 6-month intervals for the occurrence of major bleeding, MI, and death. Clopidogrel use was determined by pharmacy dispensing data. Regression models assessed the association between clopidogrel use and outcomes. Overall, 3603 patients (49.1%) received clopidogrel for >6 months. During a mean follow-up of 418 days (SD, +/- 168 days), 217 (2.9%) patients died, 279 (3.7%) had a MI, and 271 (3.6%) had major bleeding. After adjustment, patients on clopidogrel therapy were associated with increased major bleeding in all time intervals (0 to 6 months: relative risk (RR)=2.70, 95% CI=1.41 to 5.19; 7 to 12 months: RR=1.71, 95% CI=1.05 to 2.79; 13 to 18 months: RR=2.34, 95% CI=1.26 to 4.34), compared with patients off clopidogrel. Clopidogrel use was also associated with decreased risk of MI for all time intervals (0 to 6 months: RR=0.52, 95% CI=0.36 to 0.77; 7 to 12 months: RR=0.46, 95% CI=0.30 to 0.70; 13 to 18 months: RR=0.53, 95% CI=0.29 to 0.99) and decreased death in the 7 to 12 month interval (RR=0.50, 95% CI=0.30 to 0.83). Conclusions-Clopidogrel use was associated with increased major bleeding and decreased MI persisting to 18 months. Bleeding risks on clopidogrel therapy deserve consideration in the ongoing debate regarding optimal clopidogrel duration after PCI. (Circ Cardiovasc Interv. 2010;3:230-235.) C1 [Tsai, Thomas T.; Maddox, Thomas M.; Rumsfeld, John S.] Denver VA Med Ctr, Cardiol Sect 111B, Denver, CO 80220 USA. [Tsai, Thomas T.; Xu, Stanley; Powers, J. David; Carroll, Nikki M.; Shetterly, Susan M.; Maddox, Thomas M.; Rumsfeld, John S.; Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Tsai, Thomas T.; Powers, J. David; Maddox, Thomas M.; Rumsfeld, John S.; Magid, David J.] Univ Colorado, Denver, CO 80202 USA. [Tsai, Thomas T.; Xu, Stanley; Powers, J. David; Carroll, Nikki M.; Shetterly, Susan M.; Maddox, Thomas M.; Rumsfeld, John S.; Magid, David J.] Colorado Cardiovasc Outcomes Res Grp, Denver, CO USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Go, Alan S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Margolis, Karen] HealthPartners Res Fdn, Minneapolis, MN USA. RP Tsai, TT (reprint author), Denver VA Med Ctr, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. EM thomas.tsai@coloradooutcomes.org FU Agency for Healthcare Research and Quality, US Department of Health and Human Services [290-05-0033I]; National Heart, Lung, and Blood Institute [U19 HL091179]; VA Research and Development Career Development Award [05-026-2]; [0875162N] FX This project was funded under contract No. 290-05-0033I, task order No. 5 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.; Drs Magid and Go are supported by the National Heart, Lung, and Blood Institute funded Cardiovascular Research Network (U19 HL091179). Dr Go receives funding for the AHA Pharmaceutical Roundtable Outcomes Research Center (AHA #0875162N) for relevant work. Dr Ho is supported by a VA Research and Development Career Development Award (05-026-2). NR 21 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD JUN PY 2010 VL 3 IS 3 BP 230 EP 235 DI 10.1161/CIRCINTERVENTIONS.109.919001 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 623CC UT WOS:000279714200006 PM 20442361 ER PT J AU Laird, JR Katzen, BT Scheinert, D Lammer, J Carpenter, J Buchbinder, M Dave, R Ansel, G Lansky, A Cristea, E Collins, TJ Goldstein, J Jaff, MR AF Laird, John R. Katzen, Barry T. Scheinert, Dierk Lammer, Johannes Carpenter, Jeffrey Buchbinder, Maurice Dave, Rajesh Ansel, Gary Lansky, Alexandra Cristea, Ecaterina Collins, Tyrone J. Goldstein, Jeffrey Jaff, Michael R. CA RESILIENT Investigators TI Nitinol Stent Implantation Versus Balloon Angioplasty for Lesions in the Superficial Femoral Artery and Proximal Popliteal Artery Twelve-Month Results From the RESILIENT Randomized Trial SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE angioplasty; stents; peripheral vascular disease ID FEMOROPOPLITEAL ARTERY; TRANSLUMINAL ANGIOPLASTY; DISEASE; PLACEMENT; OBSTRUCTIONS; FRACTURES; PTA AB Background-Controversy still exists regarding the best endovascular treatment strategy for patients with symptomatic disease of the superficial femoral artery. There are conflicting data regarding the benefits of superficial femoral artery stenting and the role of primary stenting compared with balloon angioplasty with provisional stent implantation. Methods and Results-A total of 206 patients from 24 centers in the United States and Europe with obstructive lesions of the superficial femoral artery and proximal popliteal artery and intermittent claudication were randomized to implantation of nitinol stents or percutaneous transluminal angioplasty. The mean total lesion length was 71 mm for the stent group and 64 mm for the angioplasty group. Acute lesion success (<30% residual stenosis) was superior for the stent group compared with the angioplasty group (95.8% versus 83.9%; P<0.01). Twenty-nine (40.3%) patients in the angioplasty group underwent bailout stenting because of a suboptimal angiographic result or flow-limiting dissection. Bailout stenting was treated as a target lesion revascularization and loss of primary patency in the final analysis. At 12 months, freedom from target lesion revascularization was 87.3% for the stent group compared with 45.1% for the angioplasty group (P<0.0001). Duplex ultrasound-derived primary patency at 12 months was better for the stent group (81.3% versus 36.7%; P<0.0001). Through 12 months, fractures occurred in 3.1% of stents implanted. No stent fractures resulted in loss of patency or target lesion revascularization. Conclusions-In this multicenter trial, primary implantation of a self-expanding nitinol stent for moderate-length lesions in the superficial femoral artery and proximal popliteal artery was associated with better acute angiographic results and improved patency compared with balloon angioplasty alone. Clinical Trial Registration-URL: http://www.clinicaltrials.gov.Unique identifier: NCT00673985. (Circ Cardiovasc Interv. 2010;3:267-276.) C1 [Laird, John R.] Univ Calif Davis Hlth Syst, Dept Med, Div Cardiovasc Dis, Sacramento, CA USA. [Katzen, Barry T.] Baptist Heart & Vasc Ctr, Miami, FL USA. [Scheinert, Dierk] Leipzig Heart Ctr, Leipzig, Germany. [Lammer, Johannes] Med Univ Vienna, Dept Angiog & Intervent Radiol, Vienna, Austria. [Carpenter, Jeffrey] Univ Penn, Div Vasc Surg, Philadelphia, PA 19104 USA. [Buchbinder, Maurice] Scripps Clin, San Diego, CA USA. [Dave, Rajesh] Pinnacle Hlth Syst, Harrisburg, PA USA. [Ansel, Gary] Riverside Methodist Hosp, Columbus, OH 43214 USA. [Lansky, Alexandra; Cristea, Ecaterina] Cardiovasc Res Fdn, New York, NY USA. [Collins, Tyrone J.] Oschner Clin Fdn, Dept Cardiol, New Orleans, LA USA. [Goldstein, Jeffrey] Prairie Educ & Res Ctr, Springfield, IL USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. RP Laird, JR (reprint author), Univ Calif Davis, Vasc Ctr, Lawrence J Ellison Ambulatory Care Ctr, 4860 Y St,Suite 3400, Sacramento, CA 95817 USA. EM john.laird@ucdmc.ucdavis.edu RI Collins, Tyrone/H-1695-2014 FU Bard Peripheral Vascular FX Dr Laird is a paid consultant to Bard Peripheral Vascular and a past advisory board member for Edwards Lifesciences (2005-2007). Dr Ansel is a past advisory board member for Edwards Lifesciences (2005-2007). Dr Lansky receives research support from Bard Peripheral Vascular. Dr Lammer is a past advisory board member for Edwards Lifesciences (2005-2007). Dr Katzen is a past advisory board member for Edwards Lifesciences (2005-2007) and a member of the speaker's bureau for Bard Peripheral Vascular. NR 33 TC 288 Z9 303 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD JUN PY 2010 VL 3 IS 3 BP 267 EP 276 DI 10.1161/CIRCINTERVENTIONS.109.903468 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 623CC UT WOS:000279714200011 PM 20484101 ER PT J AU Hage, FG de Mattos, AM Khamash, H Mehta, S Warnock, D Iskandrian, AE AF Hage, Fadi G. de Mattos, Angelo M. Khamash, Hasan Mehta, Shikha Warnock, David Iskandrian, Ami E. TI QT Prolongation Is an Independent Predictor of Mortality in End-Stage Renal Disease SO CLINICAL CARDIOLOGY LA English DT Article ID HEART-ASSOCIATION ELECTROCARDIOGRAPHY; FOR-COMPUTERIZED-ELECTROCARDIOLOGY; OF-CARDIOLOGY FOUNDATION; AHA/ACCF/HRS RECOMMENDATIONS; ARRHYTHMIAS COMMITTEE; SCIENTIFIC STATEMENT; CLINICAL CARDIOLOGY; MAINTENANCE HEMODIALYSIS; INTERVAL PROLONGATION; CARDIAC-ARREST AB Background: Coronary artery disease (CAD) is the predominant cause of sudden cardiac death in the general population, and sudden cardiac death is the leading cause of mortality in end-stage renal disease (ESRD). Hypothesis: QT-interval prolongation is an independent prognosticator in ESRD. Methods: We reviewed clinical, electrocardiographic, stress test, and coronary angiography data on ESRD patients evaluated for transplantation at our institution between 2000 and 2004 who underwent coronary angiography. The QT interval was corrected for heart rate and QRS duration (QTc). All-cause mortality data were prospectively collected and verified against the Social Security Death Index database. Results: During 40 +/- 28 months of follow-up, 132 of the 280(47%) patients died prior to renal transplantation. Patients with a prolonged QTc (39%) had 1-, 3-, and 5-year death-rates of 12%, 36%, and 47%, respectively, vs 8%, 24%, and 36% for those with normal QTc (log-rank P = 0.03). In a multivariate Cox regression model that adjusted for age, gender, diabetes mellitus, myocardial infarction, presence and severity of CAD on angiography, left ventricular (LV) hypertrophy, LV ejection fraction (EF), and multiple other variables, QTc remained to be an independent predictor of survival (hazard ratio pin 1.008, 95% confidence interval [CI]: 1.001-1.014, P = 0.016). Female gender, decreasing LVEF, and decreasing severity of CAD on angiography were independent predictors of prolonged QTc. Conclusions: QTc prolongation is an independent predictor of mortality in ESRD patients being evaluated for renal transplantation. The prognostic information gained from the QTc is additive to that provided by the LVEF and the severity of CAD. C1 [Hage, Fadi G.; Iskandrian, Ami E.] Univ Alabama, Div Cardiovasc Dis, Birmingham, AL USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. [de Mattos, Angelo M.] Univ Calif Davis, Div Nephrol, Davis, CA 95616 USA. [Khamash, Hasan; Mehta, Shikha; Warnock, David] Univ Alabama, Div Nephrol, Birmingham, AL USA. RP Hage, FG (reprint author), Zeigler Res Bldg 1024 1530 3rd Ave S, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 33 TC 21 Z9 22 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUN PY 2010 VL 33 IS 6 BP 361 EP 366 DI 10.1002/clc.20768 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 621PW UT WOS:000279594600007 PM 20556806 ER PT J AU Singh, H Schiesser, R Anand, G Richardson, PA El-Serag, HB AF Singh, Hardeep Schiesser, Rachel Anand, Gobind Richardson, Peter A. El-Serag, Hashem B. TI Underdiagnosis of Lynch Syndrome Involves More Than Family History Criteria SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Lynch Syndrome; Health Outcomes; Familial Colorectal Cancer; Practice Patterns; Missed Diagnosis; Guideline Non-adherence; Genetic Evaluation; Delayed Cancer Diagnosis ID NONPOLYPOSIS COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; BETHESDA GUIDELINES; CLINICAL-CRITERIA; GENOMIC MEDICINE; MUTATIONS; ERRORS; MLH1; MSH2; CARRIERS AB BACKGROUND & AIMS: Physicians' cancer-related family history assessment for Lynch syndrome is often Inadequate Furthermore, the extent to which clinicians recognize non-family history-related clues for Lynch syndrome is unclear We reviewed an integrated electronic health record (EHR) to determine diagnostic evaluation for Lynch syndrome in patients diagnosed with colorectal cancer (CRC) METHODS: We conducted a retrospective cohort study of consecutive patients with CRC, newly diagnosed at a ternary care Veterans Affairs facility, between 1999 and 2007 A detailed review of the EHR was conducted to evaluate the presence of family history-related and non-family history-related criteria of the Bethesda guidelines Patient outcomes (identification in clinical practice and referral for genetic testing) were also determined RESULTS: We identified a total of 499 patients (mean age, 65 4 years, 98 6% male, 51 1% non-Hispanic white) At least 1 of the Bethesda criteria was met for 57 patients (11 4%), none was met for 198 (39 7%), and there was uncertainty for 244 (48 9%) because of inadequate family history documentation and/or the patient was unsure about their family history Forty-nine patients met criteria unrelated to family history Only 4 of 57 patients (7%) who met the Bethesda guidelines had documentation of counseling. Among 244 patients with uncertainty, a suspicion for Lynch syndrome was documented in the EH R of 6 patients (2.5%), 3 received counseling CONCLUSIONS: Lynch syndrome is under-recognized, even when patients have clear criteria unrelated to family history. Multifaceted strategies focused on reducing providers' cognitive errors and harnessing EHR capabilities to improve recognition of Lynch syndrome are needed. C1 [Singh, Hardeep; Richardson, Peter A.; El-Serag, Hashem B.] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA. [Singh, Hardeep] Baylor Coll Med, Ctr Inquiry Improve Outpatient Safety Effect Elec, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep; Richardson, Peter A.; El-Serag, Hashem B.] Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. [Anand, Gobind] Johns Hopkins Sch Med, Baltimore, MD USA. [El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu FU NIH [K23CA125585]; Houston VA HSR&D Center of Excellence [HFP90-020] FX The study was supported by an NIH K23 career development award (K23CA125585) to Dr Singh and in part by the Houston VA HSR&D Center of Excellence (HFP90-020) NR 26 TC 24 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUN PY 2010 VL 8 IS 6 BP 523 EP 529 DI 10.1016/j.cgh.2010.03.010 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 610PV UT WOS:000278747200014 PM 20303416 ER PT J AU Singh, N Sun, HY AF Singh, Nina Sun, Hsin-Yun TI Lipid Formulations of Amphotericin B and Solid Organ Transplant Recipients with Central Nervous System Cryptococcosis Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Singh, Nina; Sun, Hsin-Yun] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA. [Sun, Hsin-Yun] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. RP Singh, N (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu NR 3 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2010 VL 50 IS 11 BP 1544 EP 1545 DI 10.1086/652715 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 590AF UT WOS:000277194800020 ER PT J AU Winters, L Habin, K Flanagan, J Cashavelly, BJ AF Winters, Loren Habin, Karleen Flanagan, Jane Cashavelly, Barbara J. TI "I Feel Like I Am 100 Years Old!" Managing Arthralgias From Aromatase Inhibitors SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Editorial Material ID BREAST-CANCER SURVIVORS; MUSCULOSKELETAL SYMPTOMS; JOINT SYMPTOMS; RISK-FACTORS; ATAC TRIAL; THERAPY; MANAGEMENT; TAMOXIFEN; WOMEN AB Aromatase inhibitors (AIs) are recommended for the treatment of estrogen-sensitive breast cancer in postmenopausal women and provide a superior risk reduction compared to five years of tamoxifen alone. Arthralgias, a common side effect of AIs, may adversely affect quality of life, treatment adherence, and persistence. Early discontinuation of AIs may result in an inadequate clinical response. Over-the-counter analgesics, exercise, and drug holidays are common strategies used to manage arthralgias, however few interventions are evidence-based. Patients experiencing arthralgias may experience distress and, therefore would benefit from ongoing nursing support. When caring for patients with arthralgias, nurses should assess for potential modifiable risk factors, recommend lifestyle changes and/or pharmacologic interventions, and offer ongoing education and follow-up. C1 [Winters, Loren; Habin, Karleen] Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA. [Flanagan, Jane] Boston Coll, Connell Sch Nursing, Chestnut Hill, MA 02167 USA. RP Winters, L (reprint author), Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA. EM lwinters@partners.org NR 21 TC 15 Z9 15 U1 0 U2 6 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD JUN PY 2010 VL 14 IS 3 BP 379 EP 382 DI 10.1188/10.CJON.379-382 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA 607YE UT WOS:000278542400015 PM 20529801 ER PT J AU Jun, M Lambers Heerspink, HJ Ninomiya, T Gallagher, M Bellomo, R Myburgh, J Finfer, S Palevsky, PM Kellum, JA Perkovic, V Cass, A AF Jun, Min Lambers Heerspink, Hiddo J. Ninomiya, Toshiharu Gallagher, Martin Bellomo, Rinaldo Myburgh, John Finfer, Simon Palevsky, Paul M. Kellum, John A. Perkovic, Vlado Cass, Alan TI Intensities of Renal Replacement Therapy in Acute Kidney Injury: A Systematic Review and Meta-Analysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID CRITICALLY-ILL PATIENTS; CONTINUOUS VENOVENOUS HEMOFILTRATION; RANDOMIZED CLINICAL-TRIALS; FAILURE; SURVIVAL; DIALYSIS; QUALITY; RECOVERY; STANDARD; OUTCOMES AB Background and objectives: Clinical trials of the intensity of renal replacement therapy (RRT) for people with acute kidney injury (AKI) have produced conflicting results. A systematic review and meta-analysis was undertaken to assess the effect of different intensities of RRT on all-cause mortality and renal recovery in AKI patients. Design, setting, participants, & measurements: MEDLINE, EMBASE, and the Cochrane Library database were systematically searched for trials published between 1950 and 2009. Inclusion criteria were completed, prospective, adult-population, randomized controlled studies. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Summary estimates of RR were obtained using a random effects model. Heterogeneity, metaregression, publication bias, and subgroup analyses were conducted. Results: Eight trials were identified that provided data on 3841 patients and 1808 deaths. More intense RRT (35 to 48 ml/kg per h or equivalent) had no overall effect on the risk of death (RR 0.89, 95% CI 0.76 to 1.04, P = 0.143) or recovery of renal function (RR 1.12, 95% CI 0.95 to 1.31, P = 0.181) compared with less-intensive regimens (20 to 25 ml/kg per h or equivalent). Significant heterogeneity was identified with contributing factors including publication year (P = 0.004) and Jadad score (P = 0.048). Conclusions: Within the intensity ranges studied, higher intensity RRT does not reduce mortality rates or improve renal recovery among patients with AKI. The results do not negate the importance of RRT intensity in the treatment of AKI patients but rather reinforce the need to better understand the effects of treatment modalities, doses, and timing in this varied, high-risk population. Clin J Am Soc Nephrol 5: 956-963, 2010. doi: 10.2215/CJN.09111209 C1 [Jun, Min; Lambers Heerspink, Hiddo J.; Ninomiya, Toshiharu; Gallagher, Martin; Myburgh, John; Finfer, Simon; Perkovic, Vlado; Cass, Alan] Univ Sydney, George Inst Int Hlth, Sydney, NSW 2050, Australia. [Lambers Heerspink, Hiddo J.] Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharmacol, Groningen, Netherlands. [Bellomo, Rinaldo] Austin Hlth, Dept Intens Care & Med, Melbourne, Vic, Australia. [Myburgh, John] St George Hosp, Dept Intens Care Med, Sydney, NSW, Australia. [Finfer, Simon] Royal N Shore Hosp, Intens Care Unit, Sydney, NSW, Australia. [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Kellum, John A.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA USA. RP Cass, A (reprint author), Univ Sydney, George Inst Int Hlth, POB M201,Missenden Rd, Sydney, NSW 2050, Australia. EM acass@george.org.au RI Lambers Heerspink, Hiddo/K-3358-2014; OI Lambers Heerspink, Hiddo/0000-0002-3126-3730; Perkovic, Vlado/0000-0002-4257-7620; Palevsky, Paul/0000-0002-7334-5400 FU Australasian Kidney Trials Network (AKTN); Dutch Kidney Foundation; Foundation of High Blood Pressure Research Council of Australia; Australian National Health and Medical Research Council FX M.J. was supported by a postgraduate scholarship from the Australasian Kidney Trials Network (AKTN). H.J.L.H. was supported by a fellowship from the Dutch Kidney Foundation and International Society of Hypertension Visiting Postdoctoral Fellowship awarded by the Foundation of High Blood Pressure Research Council of Australia. A.C. was supported by a Senior Research Fellowship from the Australian National Health and Medical Research Council. M.J., H.J.L.H., T.N., M.G., V.P., and A.C. were responsible for data collection, analysis, interpretation, and manuscript preparation. R.B. and J.M. contributed to data interpretation. A.C., V.P., H.J.L.H., M.G., R.B., J.M., S.F., J.A.K., and P.M.P. contributed to critical revision of the publication. The corresponding author had full access to all data in the study and takes responsibility for the integrity of the data and accuracy of the analysis. NR 22 TC 38 Z9 40 U1 0 U2 3 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 JUN PY 2010 VL 5 IS 6 BP 956 EP 963 DI 10.2215/CJN.09111209 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 608OY UT WOS:000278596200003 PM 20395356 ER PT J AU Rost, NS Rosand, J Woo, D AF Rost, Natalia S. Rosand, Jonathan Woo, Daniel TI Can hyperlipidemia be protective to the brain? The paradox of lowering lipid levels in cerebrovascular disease SO CLINICAL LIPIDOLOGY LA English DT Editorial Material ID ASSOCIATION/AMERICAN-STROKE-ASSOCIATION; WHITE-MATTER LESIONS; INTERDISCIPLINARY WORKING GROUP; TRANSIENT ISCHEMIC ATTACK; OF-NEUROLOGY AFFIRMS; INTRACEREBRAL HEMORRHAGE; CHOLESTEROL-METABOLISM; HYPERINTENSITY VOLUME; MULTIPLE MECHANISMS; BLOOD CHOLESTEROL C1 [Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org NR 54 TC 1 Z9 1 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-4299 J9 CLIN LIPIDOL JI Clin. Lipidol. PD JUN PY 2010 VL 5 IS 3 BP 295 EP 298 DI 10.2217/CLP.10.31 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 615KF UT WOS:000279133400001 ER PT J AU Dunleavy, K Shapiro, G Disinski, M Chirieac, L Pittaluga, S Jaffe, ES Janik, JE Wiestner, A Wilson, WH AF Dunleavy, Kieron Shapiro, Geoff Disinski, Megan Chirieac, Lucian Pittaluga, Stefania Jaffe, Elaine S. Janik, John E. Wiestner, Adrian Wilson, Wyndham H. TI A Phase I/II Study of a Hybrid Schedule of Flavopiridol in Relapsed/Refractory Mantle Cell Lymphoma and Diffuse Large B-Cell Lymphoma SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Meeting Abstract C1 [Dunleavy, Kieron; Disinski, Megan; Pittaluga, Stefania; Jaffe, Elaine S.; Janik, John E.; Wiestner, Adrian; Wilson, Wyndham H.] NCI, Bethesda, MD 20892 USA. [Shapiro, Geoff; Chirieac, Lucian] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD JUN PY 2010 VL 10 IS 3 MA 2 BP E27 EP E27 DI 10.3816/CLML.2010.n.037 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 602DX UT WOS:000278119800013 ER PT J AU Michaelides, C Nguyen, TN Chiappa, KH Kwolek, CJ Simon, MV AF Michaelides, Costas Nguyen, Thanh N. Chiappa, Keith H. Kwolek, Christopher J. Simon, Mirela V. TI Cerebral embolism during elective carotid endarterectomy treated with tissue plasminogen activator: Utility of intraoperative EEG monitoring SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE Intraoperative monitoring; Intraoperative encephalogram; EEG; Carotid endarterectomy; CEA; Tissue plasminogen activator; tPA; Embolism ID MICROEMBOLISM; STROKE AB Electroencephalography (EEG) is routinely used during elective carotid endarterectomy (CEA) for monitoring cerebral perfusion. The period most frequently associated with cerebral hypoperfusion is the one during the clamping of the carotid artery. We present a case whereby acute hypoperfusion, as detected by ipsilateral hemispheric slowing and attenuation of the fast frequencies on EEG, was detected in the period prior to clamping of the carotid artery. The acute changes were caused by a cerebral embolism. Following emergent treatment with intraoperative thrombolytic therapy with intra-arterial tissue plasminogen activator (t-PA) the EEG changes reversed fully. We discuss the utility of intraoperative EEG monitoring in the detection and treatment of cerebral embolism. The ability of EEG to intraoperatively measure the function of the at-risk cerebral cortex makes it not only a useful tool in detecting acute changes such as from a large embolism, but also in guiding necessary treatment by offering direct feedback in the absence of reliable imaging and clinical examination. (C) 2010 Elsevier B.V. All rights reserved. C1 [Michaelides, Costas; Chiappa, Keith H.; Simon, Mirela V.] Massachusetts Gen Hosp, Dept Clin Neurophysiol, Boston, MA 02114 USA. [Kwolek, Christopher J.] Massachusetts Gen Hosp, Dept Vasc & Endovasc Surg, Boston, MA 02114 USA. [Nguyen, Thanh N.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Nguyen, Thanh N.] Boston Univ, Sch Med, Dept Neurosurg & Radiol, Boston, MA 02118 USA. RP Michaelides, C (reprint author), Massachusetts Gen Hosp, Dept Epilepsy & Clin Neurophysiol, 55 Fruit St,WACC 735, Boston, MA 02114 USA. EM Dr.Michaelides@gmail.com; Thanh.Nguyen@bmc.org NR 14 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD JUN PY 2010 VL 112 IS 5 BP 446 EP 449 DI 10.1016/j.clineuro.2010.01.009 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 609NP UT WOS:000278663800013 PM 20188460 ER PT J AU Melis, B DeFranco, MJ Chuinard, C Walch, G AF Melis, Barbara DeFranco, Michael J. Chuinard, Christopher Walch, Gilles TI Natural History of Fatty Infiltration and Atrophy of the Supraspinatus Muscle in Rotator Cuff Tears SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID CT SCAN; REPAIR; DEGENERATION; CLASSIFICATION; INTEGRITY; DIAGNOSIS; MRI AB In some patients nonoperative treatment of a rotator cuff tear is sufficient, while in others it is only the first stage of treatment prior to surgery. Fatty infiltration progresses throughout the nonoperative treatment although it is not known at what point fatty infiltration contributes to poor functional outcomes, absence of healing, or increased rerupture rates. We therefore identified factors related to the appearance of supraspinatus muscle fatty infiltration, determined the speed of appearance and progression of this phenomenon, and correlated fatty infiltration with muscular atrophy. We retrospectively reviewed 1688 patients with rotator cuff tears and recorded the following: number of tendons torn, etiology of the tear, time between onset of shoulder symptoms and diagnosis of rotator cuff tear. Fatty infiltration of the supraspinatus was graded using either CT or MRI classification. Muscular atrophy was measured indirectly using the tangent sign. Moderate supraspinatus fatty infiltration appeared an average of 3 years after onset of symptoms and severe fatty infiltration at an average of 5 years after the onset of symptoms. A positive tangent sign appeared at an average of 4.5 years after the onset of symptoms. Our results suggest that rotator cuff repair should be performed before the appearance of fatty infiltration (Stage 2) and atrophy (positive tangent sign)-especially when the tear involves multiple tendons. Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Melis, Barbara; Walch, Gilles] Ctr Orthoped Santy, Lyon, France. [DeFranco, Michael J.] Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Harvard Shoulder Serv, Boston, MA 02114 USA. [Chuinard, Christopher] Great Lakes Orthopaed Ctr, Shoulder & Elbow Serv, Traverse City, MI 49684 USA. RP Chuinard, C (reprint author), Great Lakes Orthopaed Ctr, Shoulder & Elbow Serv, 4045 W Royal Dr, Traverse City, MI 49684 USA. EM cchuinard@hotmail.com NR 26 TC 62 Z9 63 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUN PY 2010 VL 468 IS 6 BP 1498 EP 1505 DI 10.1007/s11999-009-1207-x PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 592WG UT WOS:000277411700007 PM 20094853 ER PT J AU Funakoshi, T Martin, SD Schmid, TM Spector, M AF Funakoshi, Tadanao Martin, Scott D. Schmid, Thomas M. Spector, Myron TI Distribution of Lubricin in the Ruptured Human Rotator Cuff and Biceps Tendon: A Pilot Study SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SUPERFICIAL ZONE PROTEIN; ARTICULAR-CARTILAGE; SYNOVIAL-FLUID; SUPRASPINATUS TENDON; EXTRACELLULAR-MATRIX; MOLECULAR-STRUCTURE; GROWTH-FACTORS; EXPRESSION; PROTEOGLYCAN; REPAIR AB Lubricin is a lubricant for diarthrodial joint tissues and has antiadhesion properties; its presence in the (caprine) rotator cuff suggests it may have a role in intrafascicular lubrication. To preliminarily address this role, we asked: (1) What is the distribution of lubricin in human ruptured supraspinatus and biceps tendons? (2) What are the potential cellular sources of lubricin? We obtained seven torn rotator cuff samples and four torn biceps tendon samples from 10 patients; as control tissues, we obtained the right and left supraspinatus tendons from each of six cadavers. Specimens were fixed in formalin and processed for immunohistochemical evaluation using a monoclonal antibody for lubricin. We found lubricin as a discrete layer on the torn edges of all of the ruptured supraspinatus and biceps tendon samples. None of the transected edges of the tissues produced during excision of the tissues showed the presence of lubricin. Lubricin was found in 3% to 10% of the tendon cells in the cadaveric controls and in 1% to 29% of the tendon cells in the torn supraspinatus and biceps tendon samples. The lubricin layer on the torn edges of ruptured human supraspinatus and biceps tendons may interfere with the integrative bonding of the torn edges necessary for repair. C1 [Funakoshi, Tadanao; Spector, Myron] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Funakoshi, Tadanao; Martin, Scott D.; Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA USA. [Funakoshi, Tadanao] Hokkaido Univ, Grad Sch Med, Dept Orthopaed Surg, Sapporo, Hokkaido, Japan. [Schmid, Thomas M.] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,MS 151, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU Office of Research and Development, Rehabilitation Research and Development Service, Department of Veterans Affairs FX This material is based on work supported by the Office of Research and Development, Rehabilitation Research and Development Service, Department of Veterans Affairs (MS). MS is a VA Research Career Scientist. NR 35 TC 9 Z9 9 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUN PY 2010 VL 468 IS 6 BP 1588 EP 1599 DI 10.1007/s11999-009-1108-z PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 592WG UT WOS:000277411700019 PM 19798542 ER PT J AU Kaewlai, R Digumarthy, SR Smith, BL Corben, AD Austen, WG Shepard, JAO Sharma, A AF Kaewlai, R. Digumarthy, S. R. Smith, B. L. Corben, A. D. Austen, W. G., Jr. Shepard, J. -A. O. Sharma, A. TI Significance of internal mammary lymph nodes in patients after mastectomy with tissue-expander reconstruction: a case-control study SO CLINICAL RADIOLOGY LA English DT Article ID BREAST-CANCER; MR LYMPHANGIOGRAPHY; METASTASES; LYMPHADENOPATHY; MANAGEMENT; DIAGNOSIS; PATTERNS; AXILLA AB AIM: To retrospectively assess the frequency of internal mammary lymph nodes (IMNs) in patients after mastectomy and tissue-expander reconstruction. MATERIALS AND METHODS: Statistical analysis was performed for all available data in patients with mastectomy and tissue-expander reconstruction from 2004-2007 (study group). The data were compared with that of a control population with mastectomy who did not have reconstruction (control group). Patients with recurrent breast cancers, previous breast reconstruction, surgeries performed at outside hospitals, no available pre- or postoperative computed tomography (CT) or magnetic resonance imaging (MRI) data, or inadequate imaging follow-up were excluded. RESULTS: There were eight patients in the study group (median age 50.5 years, seven breast cancers), and eight patients in the control group (median age 52 years, seven breast cancers). No patients had IMNs on their preoperative imaging examinations. New IMNs were present in postoperative imaging in seven of eight patients (7/8, 87.5%) in the study group. All of them were stable or decreased in size on subsequent imaging examinations. None of the patients in the control group had IMNs (0/8). CONCLUSION: IMNs are common on imaging after mastectomy and tissue-expander placement. The IMNs decreased or remained stable on follow-up imaging and may represent reactive nodes. (c) 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Kaewlai, R.; Digumarthy, S. R.; Shepard, J. -A. O.; Sharma, A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kaewlai, R.; Digumarthy, S. R.; Smith, B. L.; Corben, A. D.; Austen, W. G., Jr.; Shepard, J. -A. O.; Sharma, A.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, B. L.; Austen, W. G., Jr.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Corben, A. D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kaewlai, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND-210, Boston, MA 02114 USA. EM rathachai@gmail.com OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 21 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD JUN PY 2010 VL 65 IS 6 BP 453 EP 459 DI 10.1016/j.crad.2010.01.015 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 608RW UT WOS:000278604700004 PM 20451012 ER PT J AU Sunwoo, B Kuna, ST AF Sunwoo, Bernie Kuna, Samuel T. TI Ambulatory Management of Patients with Sleep Apnea: Is There a Place for Portable Monitor Testing? SO CLINICS IN CHEST MEDICINE LA English DT Article DE Polysomnogram; Apnea-hypopnea index; Continuous positive airway pressure; Cost-effectiveness; Comparative effectiveness ID POSITIVE AIRWAY PRESSURE; PRACTICE PARAMETERS; CARDIOVASCULAR-DISEASE; HOME DIAGNOSIS; ADULT PATIENTS; POLYSOMNOGRAPHY; ASSOCIATION; DEVICES; HEALTH; EPIDEMIOLOGY AB Portable monitor testing is being increasingly used as an alternative strategy for the diagnosis and treatment of patients with obstructive sleep apnea. Portable monitors have become progressively sophisticated but lack standardization. Recent studies comparing clinical outcomes of ambulatory management pathways using portable monitor testing support their use in patients with a high pretest probability for obstructive sleep apnea. Whether ambulatory management is cost-effective and will improve patient access to diagnosis and treatment requires further investigation. C1 [Sunwoo, Bernie] Univ Penn, Hosp Univ Penn, Dept Med, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Philadelphia VA Med Ctr, Dept Med, Pulm Crit Care & Sleep Med Sect, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Univ Penn, Dept Med, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. RP Sunwoo, B (reprint author), Univ Penn, Hosp Univ Penn, Dept Med, Div Pulm Allergy & Crit Care Med, 844 W Gates, Philadelphia, PA 19104 USA. EM Bernie.Sunwoo@uphs.upenn.edu FU [HSRD 04-021-2] FX This work was supported by Grant No. HSR&D 04-021-2. NR 49 TC 2 Z9 2 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 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD JUN PY 2010 VL 31 IS 2 BP 299 EP + DI 10.1016/j.ccm.2010.02.003 PG 11 WC Respiratory System SC Respiratory System GA 612AQ UT WOS:000278868900010 PM 20488288 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI The Congressional Antidepressant Hearings: Exploring the Relationship Between Medication and Veteran Suicide SO CNS SPECTRUMS LA English DT Editorial Material C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Cambridge, 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, Cambridge, MA 02138 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD JUN PY 2010 VL 15 IS 6 BP 348 EP 349 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 621XE UT WOS:000279618600001 PM 20625367 ER PT J AU Sunderajan, P Gaynes, BN Wisniewski, SR Miyahara, S Fava, M Akingbala, F DeVeaugh-Geiss, J Rush, AJ Trivedi, MH AF Sunderajan, Prabha Gaynes, Bradley N. Wisniewski, Stephen R. Miyahara, Sachiko Fava, Maurizio Akingbala, Felicia DeVeaugh-Geiss, Joanne Rush, A. John Trivedi, Madhukar H. TI Insomnia in Patients With Depression: A STAR*D Report SO CNS SPECTRUMS LA English DT Article ID DIAGNOSTIC SCREENING QUESTIONNAIRE; SEQUENCED TREATMENT ALTERNATIVES; COGNITIVE-BEHAVIORAL THERAPY; QUALITY-OF-LIFE; REPORT QIDS-SR; MAJOR DEPRESSION; PSYCHOMETRIC EVALUATION; SLEEP DISTURBANCES; GENERAL-POPULATION; QUICK INVENTORY AB Introduction: Insomnia symptoms, which are common in depression, have a significant impact on function and quality of life. However, little is known about the prevalence and associated features of insomnia symptoms in representative treatment-seeking patients with depression. Methods: Data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were analyzed. STAR*D recruited 3,743 adult outpatients diagnosed with nonpsychotic major depressive disorder (MDD) from primary (n=18) and psychiatric care (n=23) clinics across the United States. Baseline sociodemographic and clinical features were compared between those with insomnia symptoms (84.7%) and those without (15.3%). Results: The most common presentation was the simultaneous presence of sleep onset, mid-nocturnal, and early morning insomnia symptoms (27.1%). Of these three types of insomnia symptoms, mid-nocturnal insomnia symptoms were the most commonly found alone (13.5%) and in combination with one or more other types (82.3%). Insomnia symptoms were associated with several indicators of a more severe depressive illness. Only a small proportion of participants with insomnia symptoms were receiving treatment for sleep disturbances at study initiation, and the vast majority of those receiving treatment still reported having insomnia symptoms. Conclusion: In outpatients who seek treatment for nonpsychotic MDD in typical clinical settings, insomnia symptoms are very common, undertreated, and indicative of a more severe depression. CNS Spectr. 2010;15(6):394-404. C1 [Sunderajan, Prabha; Rush, A. John; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Gaynes, Bradley N.; DeVeaugh-Geiss, Joanne] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. [Miyahara, Sachiko] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Depress Res & Clin Program, Boston, MA 02114 USA. [Akingbala, Felicia] Baylor Coll Med, Dept Child Psychiat, Houston, TX 77030 USA. RP Sunderajan, P (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 6363 Forest Pk Rd,Ste FL13-354, Dallas, TX 75390 USA. EM prabha.sunderajan@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 FU Bristol-Myers Squibb; Eli Lilly; Takeda; Agency for Healthcare Research and Quality; National Institute of Mental Health (NIMH); Novartis; M-3 Corporation; Abbott; Alkermes; Aspect Medical Systems; AstraZeneca; Cephalon; Forest Pharmaceuticals; Ganeden; GlaxoSmithKline; Johnson Johnson; Lichtwer Pharma GmbH; Lorex; National Alliance for Research in Schizophrenia and Depression (NARSAD); National Center for Complementary and Alternative Medicine; National Institute on Drug Abuse (NIDA); NIMH; Organon; Pamlab; Pfizer; Pharmavite; Roche; sanoffaventis; Shire; Solvay; Synthelabo; Wyeth; Stanley Medical Research Institute; Society of Biological Psychiatry; Corcept; Cyberonics; Merck; NIDA; NARSAD; Pharmacia Upjohn; Predix; Targacept; NIMH, Notional Institutes of Health [NO1MH90003] FX Dr. Sunderajan has received grant/research support from Bristol-Myers Squibb, Eli Lilly, and Takeda. Dr. Gaynes has received grant/research support from the Agency for Healthcare Research and Quality, Bristol-Myers Squibb, the National Institute of Mental Health (NIMH), Novartis, and M-3 Corporation; and has performed as an advisor for Bristol-Myers Squibb. Dr. Wisniewski is consultant to Bristol-Myers Squibb, Case Western University, Cyberonics, and ImaRx Therapeutics. Ms. Miyahara reports no affiliation with or financial interest in any organization that may pose a conflict of interest. Dr. Fava is a consultant/advisor to Abbott, Amarin, Aspect Medical Systems, AstraZeneca, Auspex, Bayer AG, Best Practice Project Management, Biovail, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress, Don, Eli Lilly, EPIX, Fabre-Kramer, Forest Pharmaceuticals, GlaxoSmithKline, Grunenthal GmBH, Janssen, Jazz, Johnson & Johnson, Knoll, Labopharm, Lore, Lundbeck, MedAvante, Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon, Pamlab, Pfizer, PharmaStar, Pharmavite, Precision Human Biolaboratory, Roche, sanofi-aventis, Sepracor, Solvay, Somaxon, Somerset, Synthelabo, Takeda, Tetragenex, Transcept, Vanda, and Wyeth; is on the speaker's bureus of Advanced Meeting Partners, the American Psychiatric Association, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Imedex, Novartis, Organon, Pfizer, PharmaStar, MGH Psychiatry Academy/Primedia and Reed-Elsevier, UBC, and Wyeth; has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals, Ganeden, GlaxoSmithKline, Johnson & Johnson, Lichtwer Pharma GmbH, Lorex, National Alliance for Research in Schizophrenia and Depression (NARSAD), National Center for Complementary and Alternative Medicine, National Institute on Drug Abuse (NIDA), the NIMH, Novartis, Organon, Pamlab, Pfizer, Pharmavite, Roche, sanoffaventis, Shire, Solvay, Synthelabo, and Wyeth; owns equity in Compellis; receives copyright royalties for the MGH CPFQ, SFI, ATRQ, DESS, and SAFER instruments; and has submitted patent applications for SPCD and for a combination of azapirone and bupropion in major depressive disorder. Dr. Akingbala reports no affiliation with or financial interest in any organization that may pose a conflict of interest. Ms. DeVeaughGeiss receives grant/research support from M-3 Corporation and the NIMH; owns equity in GlaxoSmithKline; and her husband owns Brainstorms CNS, LLC. Dr. Rush is a consultant/advisor to Advanced Neuromodulation Systems, AstraZeneca, Best Practice Project Management, Bristol-Myers Squibb, Cyberonics, Forest Pharmaceuticals, Gerson Lehman Group, GlaxoSmithKline, Jazz, Magellan Health Services, Merck, Neuronetics, Novortis, Ono, Organon, Otsuka, Pamlab, Pfizer, Transcept, The Urban Institute, and Wyeth; is on the speaker's bureaus of Cyberonics, Forest Pharmaceuticals, and GlaxoSmithKline; receives grant/research support from the NIMH and the Stanley Medical Research Institute; owns equity in Pfizer; receives royalties from Guilford Publications and Healthcare Technology Systems; and receives a stipend from the Society of Biological Psychiatry for his role as treasurer. Dr.; Trivedi is a consultant/advisor to and on the speaker's bureaus of Abbott, Abdi Brahim' Akzo, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Fabre-Kramer, Forest Pharmaceuticals, GlaxoSmithKline,Janssen, Products LP, Johnson & Johnson, Meade Johnson, Neuronetics, Parke-Davis, Pfizer, Sepracor, VantagePoint, and Wyeth; and receives grant/research support from Agency for Healthcare Research and Quality, Corcept, Cyberonics, Merck, the NIDA, the NIMH, NARSAD, Novartis, Pharmacia & Upjohn, Predix, Solvay, and Targacept.; Funding/Support: This project was funded with Federal funds from the NIMH, Notional Institutes of Health, under contract NO1MH90003 to UT Southwestern Medical Center at Dallas (RI.: AJ. Rush). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. This work was independent of the funders tie, the hinders had no involvement in the collection, analysis, and interpretation of data; writing of this report; or the decision to submit the article). NR 60 TC 42 Z9 46 U1 1 U2 12 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD JUN PY 2010 VL 15 IS 6 BP 394 EP 404 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 621XE UT WOS:000279618600010 PM 20625372 ER PT J AU Kremen, SA Solis, OE Shapira, JS Vinters, HV Mendez, MF AF Kremen, Sarah A. Solis, Orestes E. Shapira, Jill S. Vinters, Harry V. Mendez, Mario F. TI "Fantastic Thinking'' in Pathologically Proven Pick Disease SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE frontotemporal dementia; Pick disease; confabulations; delusions; fantasy ID FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; CONFABULATION; DELUSIONS; SYMPTOMS AB Background: Reports of false beliefs may be a unique feature of behavioral variant frontotemporal dementia (bvFTD) but the nature of these experiences is unclear. Objective: To report a case of pathologically verified Pick disease in a patient presenting with prominent and recurrent fantasies. Methods: We describe the clinical, neuroradiologic, and neuropathologic findings of a 53-year-old woman presenting with fantasies and meeting Clinical Consensus Criteria for bvFTD. Results: Early in her course, she reported interactions with different actors, having torrid affairs with them, and other related fantasies. When confronted with her false beliefs, she admitted that these relationships were imaginary. Autopsy revealed Pick disease with t-immunoreactive Pick bodies in the frontal and temporal cortices, and in the hippocampi. Conclusions: Fantastic thinking, or vividly experienced imagination, may be a manifestation of bvFTD that is distinct from delusions and confabulations and could be the source of previously reported delusions and confabulations in bvFTD. C1 [Kremen, Sarah A.; Mendez, Mario F.] VA Greater Angeles Healthcare Syst, Neurobehav Unit, Dept Neurol, Los Angeles, CA 90073 USA. [Kremen, Sarah A.; Shapira, Jill S.; Vinters, Harry V.; Mendez, Mario F.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Solis, Orestes E.; Vinters, Harry V.] Univ Calif Los Angeles, Div Neuropathol, Dept Pathol, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Kremen, SA (reprint author), VA Greater Angeles Healthcare Syst, Neurobehav Unit, Dept Neurol, Bldg 500 3S 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM skremen@ucla.edu FU UCLA Alzheimer Disease Research Center [P50AG16570]; Daljit S. & Elaine Sarkaria Chair in Diagnostic Medicine FX Harry V. Vinters, MD is supported in part by the UCLA Alzheimer Disease Research Center grant P50AG16570 and the Daljit S. & Elaine Sarkaria Chair in Diagnostic Medicine. NR 17 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1543-3633 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD JUN PY 2010 VL 23 IS 2 BP 130 EP 134 DI 10.1097/WNN.0b013e3181df3007 PG 5 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA 608GD UT WOS:000278570500010 PM 20535063 ER PT J AU Kanoff, JM Colby, K Jakobiec, FA AF Kanoff, Justin M. Colby, Kathryn Jakobiec, Frederick A. TI Incipient Corneoscleral Xanthogranuloma With S-100 Positivity in a Teenager SO CORNEA LA English DT Article DE juvenile xanthogranuloma; corneoscleral mass; immunohistochemistry; S-100; CD1a ID LANGERHANS CELL HISTIOCYTOSIS; JUVENILE XANTHOGRANULOMA; LIMBUS AB Purpose: To present a case of a corneoscleral juvenile xanthogranuloma (JXG) with diagnostically challenging features. Methods: A 15-year-old boy's small corneoscleral mass of recent onset was examined histologically and immunohistochemically. Results: The biopsy had some superficially misleading histological and immunohistochemical features: S-100 positivity (however, observable in 30% of JXG lesions) and lack of Touton giant cells (often absent in early lesions). Most importantly, the histiocytes stained negatively for CD1a and strongly positively for both lysozyme and CD68 antigen. Conclusions: JXG is a benign histiocytic disorder that usually appears early in childhood but is also encountered in 13%-18% of cases in the second decade. The histiocytes usually stain positively for CD68 and negatively for S-100 and CD1a. Correctly distinguishing JXG from the more aggressive spectrum of Langerhans cell diseases (100% have CD1a positivity) is essential for patient treatment. C1 [Jakobiec, Frederick A.] Harvard Univ, David G Cogan Lab Ophthalm Pathol, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Kanoff, Justin M.; Colby, Kathryn; Jakobiec, Frederick A.] Harvard Univ, Dept Ophthalmol, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Colby, Kathryn] Harvard Univ, Cornea Serv, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, David G Cogan Lab Ophthalm Pathol, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 10 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUN PY 2010 VL 29 IS 6 BP 688 EP 690 PG 3 WC Ophthalmology SC Ophthalmology GA 604GD UT WOS:000278265000020 PM 20458239 ER PT J AU Pineda, R Jain, V Gupta, P Jakobiec, FA AF Pineda, Roberto, II Jain, Vandana Gupta, Pankaj Jakobiec, Frederick A. TI Descemet's Stripping Endothelial Keratoplasty: An Effective Treatment for Toxic Anterior Segment Syndrome with Histopathologic Findings SO CORNEA LA English DT Article DE DSEK; TASS; penetrating keratoplasty; endothelium; cytokeratin; vimentin; alpha-smooth muscle actin ID POLYMORPHOUS CORNEAL-DYSTROPHY AB Purpose: To report Descemet's stripping endothelial keratoplasty (DSEK) as a treatment for corneal edema associated with toxic anterior segment syndrome. Methods: A 75-year-old woman presented with decreased vision in her left eye after uneventful phacoemulsification. She was diagnosed with toxic anterior segment syndrome and a DSEK was performed. Histologic sections were examined after staining with hematoxylin and eosin, periodic acid Schiff, and Masson trichrome; immunoperoxidase reactions were used to identify cytokeratins, vimentin, and alpha-smooth muscle actin. Results: The corneal endothelium was selectively replaced by the DSEK technique. Descemet's membrane and endothelium were stripped from the recipient's stroma, and an 8-mm-diameter donor button consisting of posterior stroma and healthy endothelium was folded and implanted through a 5-mm incision. An air bubble was used to press the donor tissue against the recipient cornea, allowing it to attach without sutures. Corneal edema and visual acuity improved. Histopathologic evaluation of the DSEK specimen disclosed a multilaminar retro-Descemet's fibrous membrane in which many of the constituent fibroblasts contained scattered pigment granules and stained for both vimentin and cytokeratin with immunoperoxidase methods. Conclusions: To the best of our knowledge, this is the first reported case of successful DSEK m a patient with corneal decompensation resulting from toxic anterior segment syndrome exhibiting a retrocorneal fibrous membrane. Visual recovery was rapid, and refractive changes were minimal compared with traditional penetrating keratoplasty. The immunoperoxidase staining strongly suggests that the retrocorneal fibrous membrane was created by dysplastic corneal endothelial cells. C1 [Pineda, Roberto, II; Jain, Vandana; Gupta, Pankaj] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Cornea & Refract Surg Serv, Boston, MA 02114 USA. [Jain, Vandana] Aditya Jyot Eye Hosp, Dept Cornea & External Dis, Mumbai, Maharashtra, India. [Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. RP Pineda, R (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM rpineda@partners.org NR 11 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUN PY 2010 VL 29 IS 6 BP 694 EP 697 PG 4 WC Ophthalmology SC Ophthalmology GA 604GD UT WOS:000278265000022 PM 20458241 ER PT J AU Calfee, CS Thompson, BT Parsons, PE Ware, LB Matthay, MA Wong, HR AF Calfee, Carolyn S. Thompson, B. Taylor Parsons, Polly E. Ware, Lorraine B. Matthay, Michael A. Wong, Hector R. TI Plasma interleukin-8 is not an effective risk stratification tool for adults with vasopressor-dependent septic shock SO CRITICAL CARE MEDICINE LA English DT Article DE interleukin-8; acute lung injury; sensitivity; specificity; negative predictive value; risk stratification ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; UNITED-STATES; DISEASE SEVERITY; CRITICALLY-ILL; SEVERE SEPSIS; VENTILATION; MARKERS; EPIDEMIOLOGY; MORTALITY AB Objective: Plasma interleukin-8 levels of < 220 pg/mL have an excellent negative predictive value (94% to 95%) for death at 28 days in children with septic shock and thus may be useful for risk stratification in clinical trial enrollment in this population. Whether plasma interleukin-8 would have similar utility in adults with septic shock is unknown. Design: Analysis of plasma interleukin-8 levels and prospectively collected clinical data from patients enrolled in two large randomized controlled trials of ventilator strategy for acute lung injury. Setting: Intensive care units of university hospitals participating in the National Institutes of Health Acute Respiratory Distress Syndrome Network. Patients: One hundered ninety-two adult patients with vasopressor-dependent septic shock. Interventions: None. Measurements and Main Results: Plasma interleukin-8 levels >= 220 pg/mL were significantly associated with death at 28 days in this cohort (odds ratio, 2.92; 95% confidence interval, 1.42 to 5.99; p = .001). However, in contrast to the findings in pediatric septic shock, a plasma interleukin-8 cutoff < 220 pg/mL had a negative predictive value for death of only 74% (95% confidence interval, 66% to 81%) in adults with septic shock. Receiver operating characteristic analysis found an area under the curve of 0.59 for plasma interleukin-8, indicating that plasma interleukin-8 is a poor predictor of mortality in this group. In adults aged < 40 yrs, a plasma interleukin-8 cutoff < 220 pg/mL had a negative predictive value of 92%. Conclusions: In contrast to similar pediatric patients, plasma interleukin-8 levels are not an effective risk stratification tool in older adults with septic shock. Future studies of biomarkers for risk stratification in critically ill subjects will need to be replicated in multiple different populations before being applied in screening for clinical trials. (Crit Care Med 2010; 38: 1436-1441) C1 [Calfee, Carolyn S.; Matthay, Michael A.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Calfee, Carolyn S.; Matthay, Michael A.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. [Calfee, Carolyn S.; Matthay, Michael A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA. [Parsons, Polly E.] Univ Vermont, Dept Med, Div Pulm & Crit Care Med, Burlington, VT USA. [Ware, Lorraine B.] Vanderbilt Univ, Dept Med, Div Allergy Pulm & Crit Care, Nashville, TN USA. [Wong, Hector R.] Cincinnati Childrens Hosp, Div Crit Care Med, Med Ctr, Cincinnati, OH USA. Cincinnati Childrens Res Fdn, Cincinnati, OH USA. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. RP Calfee, CS (reprint author), Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. EM carolyn.calfee@ucsf.edu OI Wong, Hector/0000-0001-7989-1173 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HR 46054, N01-HR 46055, N01-HR 46056, N01-HR 46057, N01-HR 46058, N01-HR 46059, N01-HR 46060, N01-HR 46061, N01-HR 46062, N01-HR 46063, N01-HR 46064]; Flight Attendant Medical Research Institute; National Institutes of Health/National Center for Research Resources/University of California San Francisco-Clinical and Translational Sciences Institute [KL2 RR024130]; [HL090833]; [HL 51856]; [HL081332]; [R01 GM064619] FX Supported by contracts (N01-HR 46054, 46055, 46056, 46057, 46058, 46059, 46060, 46061, 46062, 46063, and 46064) with the National Heart, Lung, and Blood Institute (NHLBI). Dr. Calfee was supported by HL090833 and by the Flight Attendant Medical Research Institute and by National Institutes of Health/National Center for Research Resources/University of California San Francisco-Clinical and Translational Sciences Institute Grant KL2 RR024130. Dr. Matthay was supported by HL 51856. Dr. Ware was supported by HL081332. Dr. Wong was supported by R01 GM064619. NR 31 TC 16 Z9 18 U1 0 U2 1 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 JUN PY 2010 VL 38 IS 6 BP 1436 EP 1441 DI 10.1097/CCM.0b013e3181de42ad PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 603TT UT WOS:000278231700007 PM 20386309 ER PT J AU Sox, HC Helfand, M Grimshaw, J Dickersin, K Tovey, D Knottnerus, JA Tugwell, P AF Sox, Harold C. Helfand, Mark Grimshaw, Jeremy Dickersin, Kay Tovey, David Knottnerus, J. Andre Tugwell, Peter CA PLoS Med Editors TI Comparative Effectiveness Research: Challenges for Medical Journals SO CROATIAN MEDICAL JOURNAL LA English DT Editorial Material C1 [Sox, Harold C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dartmouth Inst, Hanover, NH 03756 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Grimshaw, Jeremy] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Dickersin, Kay] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Tovey, David] Cochrane Lib, London, England. [Knottnerus, J. Andre] Univ Maastricht, Dept Gen Practice, Maastricht, Netherlands. [Tugwell, Peter] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Tugwell, Peter] Univ Ottawa, Dept Epidemiol, Ottawa, ON, Canada. [Tugwell, Peter] Univ Ottawa, Dept Community Med, Ottawa, ON, Canada. RP Sox, HC (reprint author), Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dartmouth Inst, Hanover, NH 03756 USA. EM helfand@ohsu.edu RI Knottnerus, Johannes/A-3829-2009; OI Grimshaw, Jeremy/0000-0001-8015-8243; Tugwell, Peter/0000-0001-5062-0556 NR 7 TC 1 Z9 1 U1 0 U2 1 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-9504 J9 CROAT MED J JI Croat. Med. J. PD JUN PY 2010 VL 51 IS 3 BP 191 EP 194 DI 10.3325/cmj.2010.51.191 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 656RM UT WOS:000282354300002 PM 20578332 ER PT J AU Sitaula, R Fowler, A Toner, M Bhowmick, S AF Sitaula, Ranjan Fowler, Alex Toner, Mehmet Bhowmick, Sankha TI A study of the effect of sorbitol on osmotic tolerance during partial desiccation of bovine sperm SO CRYOBIOLOGY LA English DT Article DE Sorbitol; Bovine; Sperm; Desiccation; Osmolyte; Volume; Motility; Trehalose; Osmotic; Hypertonic ID VOLUME REGULATION; POLYOL PATHWAY; CELLS; RAT; EPIDIDYMIS; MOTILITY AB The goal of the study was to improve the partial desiccation survival of bovine sperm by decreasing the dehydration induced osmotic injury. The protective role of sorbitol, a polyol, was investigated by (i) studying the osmotic behavior of sperm in hypertonic Tyrode's buffer in the presence of sorbitol and trehalose, (ii) studying the effect of sorbitol and trehalose on sperm motility following partial dehydration. The osmotic behavior studies included the assessment of motility and volumetric responses in the presence of the additives. For the drying experiments, motility was assayed after drying the samples to different end water content followed by immediate rehydration. Compared to the effect of "intracellular + extracellular" trehalose alone, results showed a much improved motility in the presence of sorbitol and trehalose. While the drying results suggest an enhanced osmotolerance in the presence of sorbitol, the study of motility under hypertonic conditions combined with the sperm volume excursion experiments suggest that sorbitol imparts the enhancement by permeating into the cell cytoplasm. (C) 2010 Elsevier Inc. All rights reserved. C1 [Sitaula, Ranjan; Fowler, Alex; Bhowmick, Sankha] Univ Massachusetts Dartmouth, Biomed Engn & Biotechnol Program, N Dartmouth, MA 02747 USA. [Fowler, Alex; Bhowmick, Sankha] Univ Massachusetts Dartmouth, Dept Mech Engn, N Dartmouth, MA 02747 USA. [Sitaula, Ranjan; Fowler, Alex; Toner, Mehmet; Bhowmick, Sankha] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. [Sitaula, Ranjan; Fowler, Alex; Toner, Mehmet; Bhowmick, Sankha] Shriners Hosp Children, Boston, MA USA. RP Bhowmick, S (reprint author), Univ Massachusetts Dartmouth, Biomed Engn & Biotechnol Program, 285 Old Westport Rd,Room Text 210, N Dartmouth, MA 02747 USA. EM sbhowmick@umassd.edu FU ABS Global, Deforest, WI FX This work was funded by a grant from ABS Global, Deforest, WI. NR 26 TC 4 Z9 6 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD JUN PY 2010 VL 60 IS 3 BP 331 EP 336 DI 10.1016/j.cryobiol.2010.03.004 PG 6 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 599ZH UT WOS:000277952600012 PM 20233588 ER PT J AU Hinton, DE Lewis-Fernandez, R AF Hinton, Devon E. Lewis-Fernandez, Roberto TI Idioms of Distress Among Trauma Survivors: Subtypes and Clinical Utility SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Editorial Material DE Trauma; PTSD; Idioms of distress; Cultural syndromes; Clinical utility ID ANXIETY SENSITIVITY; DE-NERVIOS; LOW-BACK; CULTURE; PREVALENCE; SYMPTOMS; ATAQUE; PAIN AB In this introduction to the Special Issue on Trauma and Idioms of Distress, we provide an overview of the concept and typology of "idioms of distress," focusing particularly on their clinical utility. This includes the role of idioms as indicators of trauma exposure, of various types of psychopathology and of levels of distress, risk and functioning. It likewise includes the fact that idioms of distress may profoundly influence the personal meaning of having a trauma-related disorder, may shape the interpersonal course of the disorder and may pattern help-seeking and self-treatment. Finally, it illustrates the fact that idioms may also help clinicians understand sufferers' views of the causes of their distress, constitute key therapeutic targets and help increase therapeutic empathy and treatment adherence. This special issue focuses on the role played by idioms of distress in the local trauma ontology, the associations between the idioms and psychiatric disorders occurring in the context of trauma and the mechanisms by which the idioms profoundly influence the personal and interpersonal course of trauma-related disorders. C1 [Hinton, Devon E.; Lewis-Fernandez, Roberto] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu NR 19 TC 33 Z9 34 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0165-005X J9 CULT MED PSYCHIAT JI Cult. Med. Psychiatr. PD JUN PY 2010 VL 34 IS 2 BP 209 EP 218 DI 10.1007/s11013-010-9175-x PG 10 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA 603AA UT WOS:000278179100001 PM 20407812 ER PT J AU Hinton, DE Pich, V Marques, L Nickerson, A Pollack, MH AF Hinton, Devon E. Pich, Vuth Marques, Luana Nickerson, Angela Pollack, Mark H. TI KhyA cent l Attacks: A Key Idiom of Distress Among Traumatized Cambodia Refugees SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article DE Idioms of distress; Cultural syndromes; Post-traumatic stress disorder; Panic disorder; Cambodian refugees ID ANXIETY SENSITIVITY; DISORDER; SYMPTOMS; NERVIOS; ATAQUE; PTSD AB Traumatized Cambodian refugees with PTSD often complain of khyA cent l attacks. The current study investigates khyA cent l attacks from multiple perspectives and examines the validity of a model of how khyA cent l attacks are generated. The study found that khyA cent l attacks had commonly been experienced in the previous 4 weeks and that their severity was strongly correlated with the severity of PTSD (PTSD Checklist). It was found that khyA cent l attacks were triggered by various processes-such as worry, trauma recall, standing up, going to a mall-and that khyA cent l attacks almost always met panic attack criteria. It was also found that during a khyA cent l attack there was great fear that death might occur from bodily dysfunction. It was likewise found that a complex nosology of khyA cent l attacks exists that rates the attacks on a scale of severity, that the severity determines how the khyA cent l attacks should be treated and that those treatments are often complex. As illustrated by the article, khyA cent l attacks constitute a key aspect of trauma ontology in this group, a culturally specific experiencing of anxiety and trauma-related disorder. The article also contributes to the study of trauma somatics, that is, to the study of how trauma results in specific symptoms in a specific cultural context, showing that a key part of the trauma-somatic reticulum is often a cultural syndrome. C1 [Hinton, Devon E.; Marques, Luana; Pollack, Mark H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Pich, Vuth] Arbour Counseling Serv, Lowell, MA 01852 USA. [Nickerson, Angela] Univ S Wales, Sydney, NSW, Australia. RP Hinton, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu NR 37 TC 23 Z9 23 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0165-005X J9 CULT MED PSYCHIAT JI Cult. Med. Psychiatr. PD JUN PY 2010 VL 34 IS 2 BP 244 EP 278 DI 10.1007/s11013-010-9174-y PG 35 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA 603AA UT WOS:000278179100003 PM 20407813 ER PT J AU Wang, X Wang, Y Yu, L Sakakura, K Visus, C Schwab, JH Ferrone, CR Favoino, E Koya, Y Campoli, MR McCarthy, JB DeLeo, AB Ferrone, S AF Wang, X. Wang, Y. Yu, L. Sakakura, K. Visus, C. Schwab, J. H. Ferrone, C. R. Favoino, E. Koya, Y. Campoli, M. R. McCarthy, J. B. DeLeo, A. B. Ferrone, S. TI CSPG4 in Cancer: Multiple Roles SO CURRENT MOLECULAR MEDICINE LA English DT Review DE CSPG4; immunotherapy; monoclonal antibody; cancer stem cells ID MELANOMA-ASSOCIATED ANTIGEN; HIGH-MOLECULAR-WEIGHT; ANTIIDIOTYPIC MONOCLONAL-ANTIBODIES; CHONDROITIN SULFATE PROTEOGLYCAN; ALDEHYDE DEHYDROGENASE 1; NG2 PROTEOGLYCAN; STEM-CELLS; WHOLE IMMUNOGLOBULIN; MALIGNANT-MELANOMA; TUMOR VASCULATURE AB Chondroitin sulfate proteoglycan 4 (CSPG4), also known as High Molecular Weight-Melanoma Associated Antigen, is a cell surface proteoglycan which has been recently shown to be expressed not only by melanoma cells, but also by various types of human carcinoma and sarcoma. Furthermore, at least in squamous cell carcinoma of head and neck and in basal breast carcinoma, CSPG4 is expressed by cancer stem cells. CSPG4 plays an important role in tumor cell growth and survival. These CSPG4-associated functional properties of tumor cells are inhibited by CSPG4-specific monoclonal antibodies (mAb) in vitro. Moreover, CSPG4-specific mAb can also inhibit tumor growth and metastasis in vivo. The anti-tumor effects of CSPG4-specific mAb are likely to reflect the blocking of important migratory, mitogenic and survival signaling pathways in tumor cells. These results indicate that CSPG4 is a promising new target to implement mAb-based immunotherapy of various types of cancer. C1 [Visus, C.; DeLeo, A. B.; Ferrone, S.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15232 USA. [Wang, X.; Wang, Y.; Yu, L.; Sakakura, K.; Visus, C.; Favoino, E.; Koya, Y.; DeLeo, A. B.; Ferrone, S.] Univ Pittsburgh, Sch Med, Univ Pittsburgh Canc Inst, Pittsburgh, PA 15232 USA. [Wang, X.; Yu, L.; Ferrone, S.] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA 15232 USA. [Wang, Y.; Sakakura, K.; Favoino, E.; Koya, Y.; Ferrone, S.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15232 USA. [Schwab, J. H.] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. [Ferrone, C. R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Campoli, M. R.] Univ Colorado, Hlth Sci Ctr, Dept Dermatol, Denver, CO 80262 USA. [McCarthy, J. B.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [McCarthy, J. B.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA. RP DeLeo, AB (reprint author), Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15232 USA. EM deleo@imap.pitt.edu RI Wang, Yangyang/E-1549-2013; Favoino, Elvira/D-4804-2014; Yu, Ling/J-4286-2016; OI Favoino, Elvira/0000-0002-4664-1394 FU Elsa U. Pardee Foundation; National Cancer Institute [RO3CA141086-01, RO1CA82295, RO1CA138188, RO1CA105500]; Hillman Foundation; DOD Concept Award; Hirshberg Foundation for Pancreatic Cancer Research FX This work was supported by the Elsa U. Pardee Foundation, and RO3CA141086-01 (XW), RO1CA82295 (JBM), RO1CA138188 (SF), and RO1CA105500 (SF) from the National Cancer Institute, the Hillman Foundation (XW, ADL), DOD Concept Award (ADL) and Hirshberg Foundation for Pancreatic Cancer Research (CV). NR 58 TC 47 Z9 49 U1 0 U2 21 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD JUN PY 2010 VL 10 IS 4 BP 419 EP 429 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 599KC UT WOS:000277909700010 PM 20455858 ER PT J AU Lo, J Grinspoon, SK AF Lo, Janet Grinspoon, Steven K. TI Adrenal function in HIV infection SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE adrenal gland; aldosterone; cortisol; dehydroepiandrosterone; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY-SYNDROME; PLACEBO-CONTROLLED TRIAL; PSEUDO-CUSHINGS-SYNDROME; CD4 CELL COUNTS; ADRENOCORTICAL FUNCTION; DEHYDROEPIANDROSTERONE DHEA; ORAL DEHYDROEPIANDROSTERONE; SYNDROME AIDS; DOUBLE-BLIND AB Purpose of review Adrenal dysfunction can increase morbidity and mortality among patients with HIV infection. Disorders and medications affecting cortisol, aldosterone or adrenal androgens in patients with HIV infection are reviewed. Recent findings Iatrogenic Cushing's syndrome and hypothalamic-pituitary-adrenal suppression from concomitant use of ritonavir with nonsystemic corticosteroids such as intra-articular triamcinolone in addition to the previously reported interactions with inhaled fluticasone are increasingly recognized in HIV patients. Integrated measure of aldosterone throughout the day is higher in patients with HIV-associated visceral adipose tissue accumulation. Summary Abnormalities in adrenal function are more common in HIV patients than in the general population. HIV care providers should pursue workup for adrenal dysfunction in HIV patients when symptoms or signs are present, especially in patients with advanced AIDS or receiving medications that can affect adrenal function. The clinical implications of aldosterone elevation in HIV patients with visceral adiposity will need to be examined in future research studies. C1 [Grinspoon, Steven K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Clin, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Nutr Metab, 5 Longfellow Pl,Suite 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org NR 43 TC 8 Z9 8 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD JUN PY 2010 VL 17 IS 3 BP 205 EP 209 DI 10.1097/MED.0b013e3283394441 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691EL UT WOS:000285063000005 PM 20404726 ER PT J AU Faris, JE Smith, MR AF Faris, Jason E. Smith, Matthew R. TI Metabolic sequelae associated with androgen deprivation therapy for prostate cancer SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE androgen deprivation therapy; cardiovascular disease; diabetes; gonadotropin-releasing hormone agonists; prostate cancer ID CORONARY-HEART-DISEASE; MIDDLE-AGED MEN; LEAN BODY-MASS; TESTOSTERONE REPLACEMENT THERAPY; PLASMINOGEN-ACTIVATOR INHIBITOR; HORMONE AGONIST TREATMENT; LOW SERUM TESTOSTERONE; BONE-MINERAL DENSITY; CARDIOVASCULAR-DISEASE; ARTERIAL STIFFNESS AB Purpose of review To summarize the metabolic alterations associated with androgen deprivation therapy (ADT) for prostate cancer and to evaluate the evidence linking ADT with an increased risk of diabetes and cardiovascular disease. Recent findings ADT by either bilateral orchiectomy or treatment with gonadotropin-releasing hormone agonists causes changes in body composition, alterations in lipid profiles, and decreased insulin sensitivity. The spectrum of metabolic changes during ADT is distinct from classically described metabolic syndrome. Population-based, linked cancer registry studies have consistently reported significant associations between ADT and greater risk for diabetes mellitus. Some but not all studies have reported a link between ADT and cardiovascular disease risk. Most studies have reported no increase in cardiovascular mortality following ADT. Summary ADT appears causally associated with diabetes mellitus. ADT is also linked to cardiovascular morbidity, although there is less evidence that this relationship is causal. C1 [Faris, Jason E.; Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NIH; Prostate Cancer Foundation; Lance Armstrong Foundation FX M.R. Smith is supported by an NIH K24 Midcareer Investigator Award and grants from the Prostate Cancer Foundation and Lance Armstrong Foundation. The authors (J.E. Faris and M. R. Smith) declare no conflict of interest related to the contents of this manuscript. NR 85 TC 33 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD JUN PY 2010 VL 17 IS 3 BP 240 EP 246 DI 10.1097/MED.0b013e3283391fd1 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691EL UT WOS:000285063000010 PM 20404727 ER PT J AU Walker, LM Burton, DR AF Walker, Laura M. Burton, Dennis R. TI Rational antibody-based HIV-1 vaccine design: current approaches and future directions SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING MONOCLONAL-ANTIBODIES; VESICULAR STOMATITIS-VIRUS; MUCOSAL SHIV CHALLENGE; POLYVALENT DNA PRIME; ENVELOPE GLYCOPROTEIN; IN-VITRO; MONOMERIC GP120; CELL REPERTOIRE; RHESUS MACAQUES AB Many antiviral vaccines elicit neutralizing antibodies as a correlate of protection. For HIV, given the huge variability of the virus, it is widely believed that the induction of a broadly neutralizing antibody (bNAb) response will be crucial in a successful vaccine against the virus. Unfortunately, despite many efforts, the development of an immunogen that elicits bNAbs remains elusive. However, recent structural studies of HIV-1 Env proteins, generation of novel bNAbs, maturation of technologies for the isolation of further antibodies, insights into the requirements for antibody-mediated protection, and novel vaccination approaches are providing grounds for renewed optimism. C1 [Walker, Laura M.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Walker, Laura M.; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Burton, Dennis R.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA. [Burton, Dennis R.] Harvard, Boston, MA 02114 USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM burton@scripps.edu FU NIAID; International AIDS Vaccine Initiative; Ragon Institute of MGH, MIT, and Harvard FX We thank William Schief for providing us with the model used in Figure 2. We also thank Christina Corbaci for artwork in Figure 2 and Samantha Arnett, Katie Doores, Rich Wyatt, and Wayne Koff for helpful comments on the manuscript. Our laboratory is supported by funds from NIAID, the International AIDS Vaccine Initiative, and the Ragon Institute of MGH, MIT, and Harvard. NR 85 TC 136 Z9 141 U1 2 U2 33 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2010 VL 22 IS 3 BP 358 EP 366 DI 10.1016/j.coi.2010.02.012 PG 9 WC Immunology SC Immunology GA 619JD UT WOS:000279425500015 PM 20299194 ER PT J AU Brown, KE Freeman, GJ Wherry, EJ Sharpe, AH AF Brown, Keturah E. Freeman, Gordon J. Wherry, E. John Sharpe, Arlene H. TI Role of PD-1 in regulating acute infections SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CHRONIC VIRAL-INFECTION; T-CELL DIFFERENTIATION; PROTECTIVE IMMUNITY; MEMORY; EXPRESSION; EFFECTOR; RECEPTOR; LIGANDS; PRECURSOR; BLOCKADE AB While the role of PD-1 in inhibiting immunity during chronic infections is well established, its functions during acute infections are much less clear. The PD-1 pathway can dampen CD8 T cell responses during some acute infections and restrain responses by 'helpless' CD8 memory T cells. An emerging role for PD-1 in innate immunity has been revealed by recent studies showing that PD-1 can limit function of DC and macrophages as well as T cell independent B cell responses. Thus, PD-1 can influence adaptive immune responses during acute infections, though precisely how this regulation occurs is only just beginning to be appreciated. C1 [Brown, Keturah E.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Dept Med Oncol,Dana Farber Canc Ctr, Boston, MA 02115 USA. [Wherry, E. John] Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. RP Sharpe, AH (reprint author), Harvard Univ, Sch Med, Dept Pathol, NRB 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM arlene_sharpe@hms.harvard.edu FU National Institutes of Health (NIH) [BAA-05-11, P01 AI078897, P01 AI56299, 1U19AI082630, AI08080192, HL92565, AI071309]; Dana Foundation; Ellison Medical Foundation FX This work was supported by grants from the National Institutes of Health (NIH), BAA-05-11 and P01 AI078897 (to AHS, GJF and EJW), P01 AI56299 (to AHS and CIF), 1U19AI082630 (to GJF and EJW), AI08080192 and HL92565 (to GJF), and AI071309 (to EJW), and grants from the Dana Foundation and Ellison Medical Foundation (to EJW). Because of space restrictions, we were able to cite only a fraction of the relevant literature and apologize to colleagues whose contributions may not be appropriately acknowledged. NR 32 TC 51 Z9 52 U1 2 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2010 VL 22 IS 3 BP 397 EP 401 DI 10.1016/j.coi.2010.03.007 PG 5 WC Immunology SC Immunology GA 619JD UT WOS:000279425500020 PM 20427170 ER PT J AU Nielsen, J Vidal, M AF Nielsen, Jens Vidal, Marc TI Systems biology of microorganisms SO CURRENT OPINION IN MICROBIOLOGY LA English DT Editorial Material C1 [Nielsen, Jens] Chalmers, Dept Biol & Chem Engn, SE-41296 Gothenburg, Sweden. [Vidal, Marc] Harvard Univ, CCSB, Sch Med, Boston, MA 02115 USA. [Vidal, Marc] Harvard Univ, Dept Canc Biol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Vidal, Marc] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02115 USA. RP Nielsen, J (reprint author), Chalmers, Dept Biol & Chem Engn, Kemivagen 10, SE-41296 Gothenburg, Sweden. EM nielsenj@chalmers.se; Marc_Vidal@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD JUN PY 2010 VL 13 IS 3 BP 335 EP 336 DI 10.1016/j.mib.2010.04.005 PG 2 WC Microbiology SC Microbiology GA 617SV UT WOS:000279302600012 PM 20434944 ER PT J AU Moody, SE Boehm, JS Barbie, DA Hahn, WC AF Moody, Susan E. Boehm, Jesse S. Barbie, David A. Hahn, William C. TI Functional genomics and cancer drug target discovery SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Review DE Cancer; functional genomics; molecular target; oncogene; synthetic lethality; tumor suppressor ID RNA INTERFERENCE SCREEN; ACUTE MYELOID-LEUKEMIA; SYNTHETIC LETHAL SCREEN; BETA-CATENIN ACTIVITY; DOUBLE-STRANDED-RNA; FULL-LENGTH HUMAN; CELL LUNG-CANCER; GENETIC SCREEN; COLORECTAL-CANCER; BREAST-CANCER AB The recent development of technologies for whole-genome sequencing, copy number analysis and expression profiling enables the generation of comprehensive descriptions of cancer genomes. However, although the structural analysis and expression profiling of tumors and cancer cell lines can allow the identification of candidate molecules that are altered in the malignant state, functional analyses are necessary to confirm such genes as oncogenes or tumor suppressors. Moreover, recent research suggests that tumor cells also depend on synthetic lethal targets, which are not mutated or amplified in cancer genomes; functional genomics screening can facilitate the discovery of such targets. This review provides an overview of the tools available for the study of functional genomics, and discusses recent research involving the use of these tools to identify potential novel drug targets in cancer. C1 [Moody, Susan E.; Barbie, David A.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Moody, Susan E.; Hahn, William C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Moody, Susan E.; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Moody, Susan E.; Boehm, Jesse S.; Barbie, David A.; Hahn, William C.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. [Moody, Susan E.; Boehm, Jesse S.; Barbie, David A.; Hahn, William C.] MIT, Cambridge, MA 02142 USA. [Barbie, David A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM William_Hahn@dfci.harvard.edu FU NCI NIH HHS [T32 CA009172] NR 96 TC 7 Z9 8 U1 0 U2 4 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD JUN PY 2010 VL 12 IS 3 BP 284 EP 293 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 604MI UT WOS:000278282700003 PM 20521217 ER PT J AU Deliyski, DD Hillman, RE AF Deliyski, Dimitar D. Hillman, Robert E. TI State of the art laryngeal imaging: research and clinical implications SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY LA English DT Article DE high-speed videoendoscopy; kymography; optical coherence tomography; videostroboscopy; voice assessment ID VOCAL FOLD VIBRATIONS; OPTICAL COHERENCE TOMOGRAPHY; HIGH-SPEED VIDEOENDOSCOPY; DEPTH-KYMOGRAPHY; NORMAL SPEAKERS; DYNAMICS; SYSTEM; MODEL; VIDEOKYMOGRAPHY; VIDEO AB Purpose of review This study provides a review of the latest advances in videostroboscopy, videokymography and high-speed videoendoscopy, and outlines the development of new laryngeal imaging modalities based on optical coherence tomography, laser depth-kymography, and magnetic resonance imaging (MRI), published in the past 2 years. Recent findings Videostroboscopy and videokymography: image quality has improved and several image processing and measurement techniques have been published. High-speed videoendoscopy: significant progress has been made through increased sensitivity and frame rates of the cameras, and the development of facilitative playbacks, phonovibrography and several image segmentation and measurement methods. Clinical evidence was presented through applications in phonosurgery, comparisons with videostroboscopy, normative data, and better understanding of voice production. Optical coherence tomography: latest developments allow the capture of dynamic high-resolution cross-sectional images of the vibrating vocal fold mucosa during phonation. Depth-kymography: new laser technique allowing recording of the vertical movements of the vocal folds during phonation in calibrated spatial values. Laryngeal magnetic resonance: new methods allow high-resolution imaging of laryngeal tissue microstructure, or measuring of dynamic laryngeal structures during phonation. Summary The endoscopic laryngeal imaging techniques have made significant advances increasing their clinical value, whereas techniques providing new types of potentially clinically relevant information have emerged. C1 [Deliyski, Dimitar D.] Univ S Carolina, Dept Commun Sci & Disorders, Columbia, SC 29208 USA. [Deliyski, Dimitar D.] Univ S Carolina, Dept Comp Sci & Engn, Columbia, SC 29208 USA. [Deliyski, Dimitar D.] Univ S Carolina, Interdisciplinary Math Inst, Columbia, SC 29208 USA. [Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Hillman, Robert E.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Hillman, Robert E.] Harvard Univ, Sch Med, Dept Hlth Sci & Technol, Boston, MA USA. RP Deliyski, DD (reprint author), Univ S Carolina, Dept Commun Sci & Disorders, 1621 Greene St,6th Floor, Columbia, SC 29208 USA. EM ddeliyski@sc.edu FU NIH National Institute on Deafness and Other Communication Disorders [R01 DC007640]; Institute for Laryngology and Voice Restoration FX The work was supported by grants from the NIH National Institute on Deafness and Other Communication Disorders (R01 DC007640) and by the Institute for Laryngology and Voice Restoration. NR 52 TC 31 Z9 32 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9508 J9 CURR OPIN OTOLARYNGO JI Curr. Opin. Otolaryngol. Head Neck Surg. PD JUN PY 2010 VL 18 IS 3 BP 147 EP 152 DI 10.1097/MOO.0b013e3283395dd4 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 601ZC UT WOS:000278105800001 PM 20463479 ER PT J AU Gordon, BR AF Gordon, Bruce R. TI Patch testing for allergies SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY LA English DT Article DE contact allergy; eczema; food allergy; metal allergy; patch test ID CONTACT-DERMATITIS; ATOPIC-DERMATITIS; FOOD ALLERGY; CHILDREN AB Purpose of review Patch testing has rapidly become an important clinical allergy tool, but is underutilized in the evaluation of complex patients, especially when these patients have skin disorders and respiratory allergies, food allergies, or eosinophilic enteritis. Learning when and how to use patch tests thus adds to any practitioner's diagnostic abilities. Recent findings This review discusses selected studies from the past year, grouped into immunology, pediatric testing, contact allergy, food allergy, and drug allergy. Summary Patch tests can detect a wide range of sensitivities to inorganic and organic chemicals, drugs, biologic molecules, inhalants acting as contactants, food allergens, allergens that have not been commercially extracted, and solid allergens. Because patch tests detect the full range of immunologic reactions, Gell and Coombs type I to IV, they may be uniquely reactive when other allergy tests are negative. Because of the large number of published studies that utilize patch testing, clinicians often can use a literature search of prior studies of similar problems, or for particular allergens, to choose technical details that make successful patch testing more likely. C1 [Gordon, Bruce R.] Cape Cod Hosp, Hyannis, MA USA. [Gordon, Bruce R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Gordon, Bruce R.] Harvard Univ, Cambridge, MA 02138 USA. RP Gordon, BR (reprint author), Cape Cod ENT, 65 Cedar St, Hyannis, MA 02601 USA. EM docbruce@comcast.net NR 24 TC 0 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9508 J9 CURR OPIN OTOLARYNGO JI Curr. Opin. Otolaryngol. Head Neck Surg. PD JUN PY 2010 VL 18 IS 3 BP 191 EP 194 DI 10.1097/MOO.0b013e3283376a4e PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 601ZC UT WOS:000278105800009 PM 20463482 ER PT J AU Shih, WM Lin, CX AF Shih, William M. Lin, Chenxiang TI Knitting complex weaves with DNA origami SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID FOLDING DNA; DIRECTED NUCLEATION; NANOSCALE SHAPES; TILES; ACID; DESIGN; NANOSTRUCTURES; NANOTECHNOLOGY; NANOPARTICLES; MOLECULES AB The past three decades have witnessed steady growth in our ability to harness DNA branched junctions as building blocks for programmable self-assembly of diverse supramolecular architectures. The DNA-origami method, which exploits the availability of long DNA sequences to template sophisticated nanostructures, has played a major role in extending this trend through the past few years. Today, two-dimensional and three-dimensional custom-shaped nanostructures comparable in mass to a small virus can be designed, assembled, and characterized with a prototyping cycle on the order of a couple of weeks. C1 [Shih, William M.; Lin, Chenxiang] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Shih, William M.; Lin, Chenxiang] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Shih, William M.; Lin, Chenxiang] Wyss Inst Biologically Inspired Engn Harvard, Cambridge, MA 02138 USA. RP Shih, WM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM William_Shih@dfci.harvard.edu RI Lin, Chenxiang/G-2303-2010; OI Lin, Chenxiang/0000-0001-7041-1946 FU Claudia Adams Barr Program Investigator; Wyss Institute for Biologically Inspired Engineering; NIH [1DP2OD004641-01] FX This work was supported by Claudia Adams Barr Program Investigator, Wyss Institute for Biologically Inspired Engineering, and NIH New Innovator (1DP2OD004641-01) grants to W.M.S. NR 48 TC 74 Z9 75 U1 3 U2 52 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD JUN PY 2010 VL 20 IS 3 BP 276 EP 282 DI 10.1016/j.sbi.2010.03.009 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 614LV UT WOS:000279061300003 PM 20456942 ER PT J AU Kumai, Y Kobler, JB Herrera, VLM Zeitels, SM AF Kumai, Yoshihiko Kobler, James B. Herrera, Victoria L. M. Zeitels, Steven M. TI Perspectives on Adipose-Derived Stem/Stromal Cells as Potential Treatment for Scarred Vocal Folds: Opportunity and Challenges SO CURRENT STEM CELL RESEARCH & THERAPY LA English DT Review DE Vocal fold scar; adipose derived stem cell; regenerative therapy; hepatocyte growth foactor AB Regenerative therapy using stem cells for the treatment of vocal fold wound healing and fibrosis is a very active area of research in Otolaryngology. Although modern phonosurgical methods can deal with many types of vocal fold pathology, vocal fold scar remains a clinical challenge. Trauma (e.g. vocal abuse, phonosurgery) and inflammation (e. g. laryngitis) are the two main causes of the vocal fold scarring. Several recent reviews detail the problem of vocal fold scarring and the array of possible solutions under investigation. The search for solutions includes autologous tissues, biomaterial implants, growth factors, anti-fibrotic agents and stem cells. This review focuses on emerging research on stem cells for vocal fold regeneration and our own studies of interactions between adipose-derived stem/stromal cells and vocal fold fibroblasts using an in vitro model. While clearly an opportunity, the challenging approach of treating vocal scarring using ASCs has just started. For future in vivo studies, improvements in cell viability and markers of stem-cell differentiation into normal fibroblasts are needed. The roles of stem cell-derived cytokines in paracrine signaling need to be further explored at a cellular level in vitro, and then extended to in vivo experiments. C1 [Kumai, Yoshihiko; Kobler, James B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Herrera, Victoria L. M.] Boston Univ, Sch Med, Sect Mol Med, Dept Med, Boston, MA 02118 USA. [Herrera, Victoria L. M.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Zeitels, Steven M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, FACS Dept Surg,Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Kumai, Y (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. EM kumayoshi426yk@gamil.com NR 46 TC 12 Z9 12 U1 3 U2 19 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1574-888X J9 CURR STEM CELL RES T JI Curr. Stem Cell Res. Ther. PD JUN PY 2010 VL 5 IS 2 BP 175 EP 181 DI 10.2174/157488810791268591 PG 7 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA V22GC UT WOS:000208262700015 PM 19941448 ER PT J AU Zhong, WW Zhang, ZL Hinrichs, D Wu, XM Hall, M Xia, ZW Rosenbaum, JT AF Zhong, Wenwei Zhang, Zili Hinrichs, David Wu, Xiumei Hall, Mark Xia, Zhenwei Rosenbaum, James T. TI OX40 induces CCL20 expression in the context of antigen stimulation: An expanding role of co-stimulatory molecules in chemotaxis SO CYTOKINE LA English DT Article DE CCL20; CD4+T cells; Co-stimulatory molecule; OX40; T cell co-stimulation ID T-CELL TRAFFICKING; INFLAMMATORY PROTEIN-3-ALPHA; CYTOKINE DIFFERENTIATION; CHEMOKINE RECEPTOR; TH17 CELLS; ACTIVATION; DISEASE; INTERLEUKIN-8; MIGRATION; MEMORY AB OX40 is an inducible co-stimulatory molecule expressed by activated T cells. It plays an important role in the activation and proliferation of T lymphocytes. Recently, some co-stimulatory molecules have been shown to direct leukocyte trafficking. Chemotaxis is essential for achieving an effective immune response. CCL20 is an important chemoattractant produced by activated T cells. In this study, using DO11.10 mice whose transgenic T cell receptor specifically recognizes ovalbumin, we demonstrate that ovalbumin induces OX40 expression in CD4+ lymphocytes. Further stimulation of OX40 by OX40 activating antibody up-regulates CCL20 production. Both NF-kappa B dependent and independent signaling pathways are implicated in the induction of CCL20 by OX40. Finally, we primed the DO11.10 splenocytes with or without OX40 activating antibody in the presence of ovalbumin. Intranasal administration of the cell lysates derived from the cells with OX40 stimulation results in more severe leukocyte infiltration in the lung of DO11.10 mice, which is substantially attenuated by CCL20 blocking antibody. Taken together, this study has shown that activation of OX40 induces CCL20 expression in the presence of antigen stimulation. Thus, our results broaden the role of OX40 in chemotaxis, and reveal a novel effect of costimulatory molecules in orchestrating both T cell up-regulation and migration. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA. [Hinrichs, David] Portland VA Med Ctr, Portland, OR 97239 USA. [Zhong, Wenwei; Zhang, Zili; Wu, Xiumei; Hall, Mark] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA. [Zhong, Wenwei; Xia, Zhenwei] RuiJin Hosp, Dept Pediat, Shanghai 200025, Peoples R China. RP Zhang, ZL (reprint author), CDRCP, 707 Gaines St, Portland, OR 97239 USA. EM zhangzi@ohsu.edu FU National Institutes of Health [EY016788, EY013093, EY006484]; Child Digestive Health and Nutrition Foundation/CCFA; Stan and Madelle Rosenfeld Family Trust; Research to Prevent Blindness; William and Mary Bauman Foundation; Fund for Arthritis and Infectious Disease Research FX We thank Judie McDonald for help in preparing the manuscript. This study was supported by National Institutes of Health Grants EY016788 (ZZ), EY013093 (JTR), EY006484 (JTR), and Child Digestive Health and Nutrition Foundation/CCFA Young Investigator Award (ZZ). JTR Funds from the Stan and Madelle Rosenfeld Family Trust, Research to Prevent Blindness, the William and Mary Bauman Foundation, and the Fund for Arthritis and Infectious Disease Research also contributed to this work. NR 47 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUN PY 2010 VL 50 IS 3 BP 253 EP 259 DI 10.1016/j.cyto.2010.03.021 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 606GU UT WOS:000278411600006 PM 20400327 ER PT J AU Tambouret, R Nayar, R Pitman, MB Ehya, H AF Tambouret, R. Nayar, R. Pitman, M. B. Ehya, H. TI Standardized Cytopathology Training through Accreditation in the United States SO CYTOPATHOLOGY LA English DT Editorial Material ID CURRICULUM; PATHOLOGY; RESIDENT C1 [Tambouret, R.; Pitman, M. B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Nayar, R.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. [Ehya, H.] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. RP Tambouret, R (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM Hormoz.Ehya@fccc.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0956-5507 J9 CYTOPATHOLOGY JI Cytopathology PD JUN PY 2010 VL 21 IS 3 BP 139 EP 141 DI 10.1111/j.1365-2303.2010.00767.x PG 3 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 592TI UT WOS:000277402800001 PM 20557347 ER PT J AU Anshu Herbert, A Cochand-Priollet, B Cross, P Desai, M Dina, R Duskova, J Evered, A Farnsworth, A Gray, W Gupta, SS Kapila, K Kardum-Skelin, I Kloboves-Prevodnik, V Kobayashi, TK Koutselini, H Olszewski, W Onal, B Pitman, MB Marinsek, Z Sauer, T Schenck, U Schmitt, F Shabalova, I Smith, JHF Tani, E Vass, L Vielh, P Wiener, H AF Anshu Herbert, A. Cochand-Priollet, B. Cross, P. Desai, M. Dina, R. Duskova, J. Evered, A. Farnsworth, A. Gray, W. Gupta, S. S. Kapila, K. Kardum-Skelin, I. Kloboves-Prevodnik, V. Kobayashi, T. K. Koutselini, H. Olszewski, W. Onal, B. Pitman, M. B. Marinsek, Z. Sauer, T. Schenck, U. Schmitt, F. Shabalova, I. Smith, J. H. F. Tani, E. Vass, L. Vielh, P. Wiener, H. TI Survey of medical training in cytopathology carried out by the journal Cytopathology SO CYTOPATHOLOGY LA English DT Article DE medical training in cytopathology; international survey; accreditation; postgraduate training; cytopathology examinations ID CYTOLOGY AB This report of the Editorial Advisory Board of Cytopathology gives the results of a survey of medical practitioners in cytopathology, which aimed to find out their views on the current situation in undergraduate and postgraduate training in their institutions and countries. The results show that training in cytopathology and histopathology are largely carried out at postgraduate level and tend to be organized nationally rather than locally. Histopathology was regarded as essential for training in cytopathology by 89.5% of respondents and was mandatory according to 83.1%. Mandatory cytopathology sections of histopathology were reported by 67.3% and specific examinations in cytopathology by 55.4%. The main deficiencies in training were due to its variability; there were insufficient numbers of pathologists interested in cytology and a consequent lack of training to a high level of competence. Pathologists without specific training in cytopathology signed out cytology reports according to 54.7% of responses, more often in centres where training was 3-6 months or less duration. Although 92.2% of respondents thought that specialist cytology should not be reported by pathologists without experience in general cytopathology, that practice was reported by 30.9%, more often in centres with small workloads. The survey report recommends that 6-12 months should be dedicated to cytopathology during histopathology training, with optional additional training for those wanting to carry out independent practice in cytopathology. Formal accreditation should be mandatory for independent practice in cytopathology. When necessary, temporary placements to centres of good practice should be available for trainees intending to practise independently in cytopathology. There should be adequate numbers of pathologists trained in cytopathology to a high level of competence; some of their time could be released by training cytotechnologists and trainee pathologists to prescreen cytology slides and assess adequacy of fine-needle aspiration samples when immediate diagnosis was not required. The survey demonstrated a clear need for European and international guidelines for training in cytopathology. C1 [Herbert, A.] St Thomas Hosp, Dept Cellular Pathol, Guys & St Thomas NHS Fdn Trust, London, England. [Anshu] Mahatma Gandhi Inst Med Sci, Sevagram, India. [Cochand-Priollet, B.] Hop Lariboisiere, Serv Anat & Cytol Pathol, F-75475 Paris, France. [Cross, P.] Queen Elizabeth Hosp, Dept Pathol, Gateshead, England. [Desai, M.] Manchester Royal Infirm, Manchester Cytol Ctr, Manchester M13 9WL, Lancs, England. [Dina, R.] Hammersmith Hosp, Dept Histopathol, Imperial Coll NHS Trust, London W12 0HS, England. [Duskova, J.] Charles Univ Prague, Inst Pathol, Fac Med 1, Prague, Czech Republic. [Evered, A.] Cerv Screening Wales, Cardiff, S Glam, Wales. [Evered, A.] Univ Wales Inst, Cardiff, S Glam, Wales. [Farnsworth, A.] Douglass Hanly Moir Pathol Cytol, Macquarie Pk, NSW, Australia. [Gray, W.] John Radcliffe Hosp, Oxford OX3 9DU, England. [Gupta, S. S.] Mahatma Gandhi Inst Med Sci, Dept Community Med, Sevagram, India. [Kapila, K.] Kuwait Univ, Fac Med, Dept Pathol, Cytopathol Unit, Kuwait, Kuwait. [Kardum-Skelin, I.] Univ Zagreb, Merkur Univ Hosp, Lab Cytol & Haematol, HR-10002 Zagreb, Croatia. [Kloboves-Prevodnik, V.; Marinsek, Z.] Inst Oncol, Dept Cytopathol, Ljubljana, Slovenia. [Kobayashi, T. K.] Saiseikai Shiga Hosp, Imperial Gift Fdn Inc, Dept Pathol, Shiga, Japan. [Koutselini, H.] Univ Athens, Sch Med, Aretaieion Univ Hosp, Dept Cytopathol, GR-11527 Athens, Greece. [Olszewski, W.] Inst Oncol, Dept Pathol, Warsaw, Poland. [Onal, B.] Ankara Diskapi Training & Res Hosp, Dept Cytol & Pathol, Ankara, Turkey. [Pitman, M. B.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sauer, T.] Ullevaal Univ Hosp, Dept Pathol, Oslo, Norway. [Schenck, U.] Tech Univ Munich, Inst Pathol, D-8000 Munich, Germany. [Schmitt, F.] Univ Porto, IPATIMUP, P-4100 Oporto, Portugal. [Schmitt, F.] Univ Porto, Fac Med, P-4100 Oporto, Portugal. [Shabalova, I.] Gen Inst Adv Med Studies, Moscow, Russia. [Smith, J. H. F.] Royal Hallamshire Hosp, Dept Histopathol & Cytol, Sheffield S10 2JF, S Yorkshire, England. [Tani, E.] Karolinska Univ Hosp, Dept Pathol & Cytol, Stockholm, Sweden. [Vass, L.] Flor F Univ Hosp Pest Cty, Dept Pathol Cytopathol, Kistarcsa, Hungary. [Vielh, P.] Inst Gustave Roussy, Dept Pathol, Villejuif, France. [Wiener, H.] Med Univ Vienna, Dept Clin Pathol, Vienna, Austria. RP Herbert, A (reprint author), St Thomas Hosp, Dept Cellular Pathol, Guys & St Thomas NHS Fdn Trust, 2nd Floor N Wing, London, England. EM amanda.herbert@kcl.ac.uk OI Schmitt, Fernando/0000-0002-3711-8681 NR 8 TC 10 Z9 10 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0956-5507 J9 CYTOPATHOLOGY JI Cytopathology PD JUN PY 2010 VL 21 IS 3 BP 147 EP 156 DI 10.1111/j.1365-2303.2010.00761.x PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 592TI UT WOS:000277402800004 PM 20482722 ER PT J AU Phillips, KA Stein, DJ Rauch, SL Hollander, E Fallon, BA Barsky, A Fineberg, N Mataix-Cols, D Ferrao, YA Saxena, S Wilhelm, S Kelly, MM Clark, LA Pinto, A Bienvenu, OJ Farrow, J Leckman, J AF Phillips, Katharine A. Stein, Dan J. Rauch, Scott L. Hollander, Eric Fallon, Brian A. Barsky, Arthur Fineberg, Naomi Mataix-Cols, David Ferrao, Ygor Arzeno Saxena, Sanjaya Wilhelm, Sabine Kelly, Megan M. Clark, Lee Anna Pinto, Anthony Bienvenu, O. Joseph Farrow, Joanne Leckman, James TI SHOULD AN OBSESSIVE-COMPULSIVE SPECTRUM GROUPING OF DISORDERS BE INCLUDED IN DSM-V? SO DEPRESSION AND ANXIETY LA English DT Review DE obsessive compulsive spectrum; obsessive compulsive disorder; classification; DSM-V ID BODY DYSMORPHIC DISORDER; COGNITIVE-BEHAVIORAL THERAPY; CEREBRAL GLUCOSE-METABOLISM; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; SOCIAL ANXIETY DISORDER; LA-TOURETTE-SYNDROME; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; COMORBIDITY SURVEY REPLICATION; OCD COLLABORATIVE GENETICS AB The obsessive compulsive (OC) spectrum has been discussed in the literature for two decades. Proponents of this concept propose that certain disorders characterized by repetitive thoughts and/or behaviors are related to obsessive compulsive disorder (OCD), and suggest that such disorders be grouped together in the same category (i.e. grouping, or "chapter') in DSM. This article addresses this topic and presents options and preliminary recommendations to be considered for DSM-V The article builds upon and extends prior reviews of this topic that were prepared for and discussed at a DSM-V Research Planning Conference on Obsessive Compulsive Spectrum Disorders held in 2006. Our preliminary recommendation is that an OC-spectrum grouping of disorders he included in DSM-V Furthermore, we preliminarily recommend that consideration be given to including this group of disorders within a larger supraordinate category of "Anxiety and Obsessive Compulsive Spectrum Disorders." These preliminary recommendations must be evaluated in light of recommendations for, and constraints upon, the overall structure of DSM-V Depression and Anxiety 27:528-555, 2010. (C)Wiley-Liss, Inc. C1 [Phillips, Katharine A.] Rhode Isl Hosp, Coro Ctr W, Butler Hosp, Providence, RI 02903 USA. [Phillips, Katharine A.; Kelly, Megan M.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Stein, Dan J.] Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa. [Rauch, Scott L.; Barsky, Arthur; Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA USA. [Rauch, Scott L.] McLean Hosp, Boston, MA USA. [Hollander, Eric] Albert Einstein Coll Med, New York, NY USA. [Hollander, Eric] Montefiore Med Ctr, New York, NY USA. [Fallon, Brian A.; Pinto, Anthony] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Fallon, Brian A.; Pinto, Anthony] Columbia Univ, New York, NY USA. [Barsky, Arthur] Brigham & Womens Hosp, Boston, MA 02115 USA. [Fineberg, Naomi; Farrow, Joanne] Univ Hertfordshire, Hatfield AL10 9AB, Herts, England. [Mataix-Cols, David] Kings Coll London, London WC2R 2LS, England. [Ferrao, Ygor Arzeno] Porto Alegre Hlth Sci Fed Univ, Porto Alegre, RS, Brazil. [Ferrao, Ygor Arzeno] Presidente Vargas Hosp, Psychiat Serv, Outpatient Program Anxiety Disorders, Porto Alegre, RS, Brazil. [Saxena, Sanjaya] Univ Calif San Diego, San Diego, CA 92103 USA. [Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kelly, Megan M.] Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Clark, Lee Anna] Univ Iowa, Iowa City, IA USA. [Bienvenu, O. Joseph] Johns Hopkins Sch Med, Baltimore, MD USA. [Leckman, James] Yale Univ, Sch Med, New Haven, CT USA. RP Phillips, KA (reprint author), Rhode Isl Hosp, Coro Ctr W, Butler Hosp, 1 Hoppin St, Providence, RI 02903 USA. EM Katharine_Phillips@Brown.edu RI Mataix-Cols, David/G-3843-2010; Ferrao, Ygor/N-8058-2013; Stein, Dan/A-1752-2008; Pinto, Anthony/D-2718-2017 OI Mataix-Cols, David/0000-0002-4545-0924; Ferrao, Ygor/0000-0003-3770-5912; Stein, Dan/0000-0001-7218-7810; Pinto, Anthony/0000-0002-6078-7242 FU NIMH NIH HHS [K24 MH063975, R01 MH060241] NR 416 TC 102 Z9 104 U1 17 U2 43 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUN PY 2010 VL 27 IS 6 BP 528 EP 555 DI 10.1002/da.20705 PG 28 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 608GY UT WOS:000278572700003 PM 20533367 ER PT J AU Mataix-Cols, D Frost, RO Pertusa, A Clark, LA Saxena, S Leckman, JF Stein, DJ Matsunaga, H Wilhelm, S AF Mataix-Cols, David Frost, Randy O. Pertusa, Alberto Clark, Lee Anna Saxena, Sanjaya Leckman, James F. Stein, Dan J. Matsunaga, Hisato Wilhelm, Sabine TI HOARDING DISORDER: A NEW DIAGNOSIS FOR DSM-V? SO DEPRESSION AND ANXIETY LA English DT Review DE boarding; obsessive-compulsive disorder; obsessive-compulsive personality disorder; Anankastic personality disorder; DSM-V; classification; nosology ID OBSESSIVE-COMPULSIVE DISORDER; OCD COLLABORATIVE GENETICS; FACTOR-ANALYZED SYMPTOM; BINGE-EATING DISORDER; PERSONALITY-DISORDER; CLINICAL-FEATURES; COGNITIVE ASPECTS; YOUNG-CHILDREN; NEURAL BASIS; CRITERIA AB This article provides a focused review of the literature on compulsive hoarding and presents a number of options and preliminary recommendations to be considered for DSM-V In DSM-IV-TR, hoarding is listed as one of the diagnostic criteria for obsessive compulsive personality disorder (OCPD). According to DSM-IV-TR, when hoarding is extreme, clinicians should consider a diagnosis of obsessive compulsive disorder (OCD) and may diagnose both OCPD and OCD if the criteria for both are met. However, compulsive hoarding seems to frequently be independent from other neurological and psychiatric disorders, including OCD and OCPD. In this review, we first address whether hoarding should be considered a symptom of OCD and/or a criterion of OCPD. Second, we address whether compulsive boarding should be classified as a separate disorder in DSM-V weighing the advantages and disadvantages of doing so. Finally, we discuss where compulsive hoarding should be classified in DSM-V if included as a separate disorder. We conclude that there is sufficient evidence to recommend the creation of a new disorder, provisionally called hoarding disorder. Given the historical link between hoarding and OCD/OCPD, and the conservative approach adopted by DSM-V; it may make sense to provisionally list it as an obsessive compulsive spectrum disorder. An alternative to our recommendation would be to include it in an Appendix of Criteria Sets Provided for Further Study. The creation of a new diagnosis in DSM-V would likely increase public awareness, improve identification of cases, and stimulate both research and the development of specific treatments for hoarding disorder. Depression and Anxiety 27:556-572, 2010. (C) 2010 Wilty-Liss, Inc. C1 [Mataix-Cols, David; Pertusa, Alberto] Kings Coll London, Inst Psychiat, London SE5 8AF, England. [Frost, Randy O.] Smith Coll, Dept Psychol, Northampton, MA 01063 USA. [Clark, Lee Anna] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Saxena, Sanjaya] Univ Calif San Diego, Obsess Compuls Disorders Program, San Diego, CA 92103 USA. [Leckman, James F.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. [Stein, Dan J.] Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa. [Matsunaga, Hisato] Osaka City Univ, Grad Sch Med, Dept Neuropsychiat, Osaka 558, Japan. [Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Obsess Compuls Disorder Clin, Boston, MA 02114 USA. RP Mataix-Cols, D (reprint author), Kings Coll London, Inst Psychiat, PO 69,Crespigny Pk, London SE5 8AF, England. EM david.mataix-cols@kcl.ac.uk RI Mataix-Cols, David/G-3843-2010; Stein, Dan/A-1752-2008; OI Mataix-Cols, David/0000-0002-4545-0924; Stein, Dan/0000-0001-7218-7810; Pertusa, Alberto/0000-0002-8664-8582 NR 106 TC 210 Z9 219 U1 9 U2 41 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUN PY 2010 VL 27 IS 6 BP 556 EP 572 DI 10.1002/da.20693 PG 17 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 608GY UT WOS:000278572700004 PM 20336805 ER PT J AU Phillips, KA Wilhelm, S Koran, LM Didie, ER Fallon, BA Feusner, J Stein, DJ AF Phillips, Katharine A. Wilhelm, Sabine Koran, Lorrin M. Didie, Elizabeth R. Fallon, Brian A. Feusner, Jamie Stein, Dan J. TI BODY DYSMORPHIC DISORDER: SOME KEY ISSUES FOR DSM-V SO DEPRESSION AND ANXIETY LA English DT Review DE body dysmorphic disorder; dysmorphophobia; delusional disorder; classification; DSM-V ID OBSESSIVE-COMPULSIVE DISORDER; NONPSYCHIATRIC MEDICAL-TREATMENT; GENERALIZED ANXIETY DISORDER; QUALITY-OF-LIFE; EATING-DISORDERS; CLINICAL-FEATURES; MUSCLE DYSMORPHIA; IMAGINED UGLINESS; ANOREXIA-NERVOSA; PSYCHIATRIC-INPATIENTS AB Body dysmorphic disorder (BDD), a distressing or impairing preoccupation with an imagined or slight defect in appearance, has been described for more than a century and increasingly studied over the past several decades. This article provides a focused review of issues pertaining to BDD that are relevant to DSM-V The review presents a number of options and preliminary recommendations to be considered for DSM-V: (1) Criterion A may benefit from some rewording, without changing its focus or meaning; (2) There are both advantages and disadvantages to adding a new criterion to reflect compulsive BDD behaviors; this possible addition requires further consideration; (3) A clinical significance criterion seems necessary for BDD to differentiate it from normal appearance concerns; (4) BDD and eating disorders have some overlapping features and need to be differentiated; some minor changes to DSM-IV's criterion C are suggested; (5) BDD should not be broadened to include body integrity identity disorder (apotemnophilia) or olfactory reference syndrome; (6) There is no compelling evidence for including diagnostic features or subtypes that are specific to gender-related, age-related, or cultural manifestations of BDD; (7) Adding muscle dysmorphia as a specifier may have clinical utility; and (8) The ICD-10 criteria for hypochondriacal disorder are not suitable for BDD, and there is no empirical evidence that BDD and hypochondriasis are the same disorder. The issue of how BDD's delusional variant should be classified in DSM-V is briefly discussed and will be addressed more extensively in a separate article. Depression and Anxiety 27:573-591, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Phillips, Katharine A.] Brown Univ, Rhode Isl Hosp, Coro Ctr W, Butler Hosp, Providence, RI 02903 USA. [Phillips, Katharine A.; Didie, Elizabeth R.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02903 USA. [Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA USA. [Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koran, Lorrin M.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Fallon, Brian A.] Columbia Univ, New York, NY USA. [Fallon, Brian A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Feusner, Jamie] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Stein, Dan J.] Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa. RP Phillips, KA (reprint author), Brown Univ, Rhode Isl Hosp, Coro Ctr W, Butler Hosp, 1 Hoppin St, Providence, RI 02903 USA. EM Katharine_Phillips@Brown.edu RI Feusner, Jamie/K-2312-2012; Stein, Dan/A-1752-2008 OI Feusner, Jamie/0000-0002-0391-345X; Stein, Dan/0000-0001-7218-7810 FU NIMH NIH HHS [K23 MH079212, K23 MH079212-05, K24 MH063975] NR 160 TC 66 Z9 69 U1 8 U2 46 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JUN PY 2010 VL 27 IS 6 BP 573 EP 591 DI 10.1002/da.20709 PG 19 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 608GY UT WOS:000278572700005 PM 20533368 ER PT J AU Deacon, DC Nevis, KR Cashman, TJ Zhou, Y Zhao, L Washko, D Guner-Ataman, B Burns, CG Burns, CE AF Deacon, Dekker C. Nevis, Kathleen R. Cashman, Timothy J. Zhou, Yong Zhao, Long Washko, Daniel Guner-Ataman, Burcu Burns, C. Geoffrey Burns, Caroline E. TI The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis SO DEVELOPMENT LA English DT Article DE microRNA; miR-143 (mir143); Adducin; Zebrafish; Heart development; Organogenesis ID MUSCLE-CELL FATE; CHICK-EMBRYO; DEVELOPING ZEBRAFISH; ACTIN BUNDLES; HEART TUBE; MICRORNAS; GROWTH; SPECIFICATION; EXPRESSION; MECHANISM AB Discovering the genetic and cellular mechanisms that drive cardiac morphogenesis remains a fundamental goal, as three-dimensional architecture greatly impacts functional capacity. During development, accurately contoured chambers balloon from a primitive tube in a process characterized by regional changes in myocardial cell size and shape. How these localized changes are achieved remains elusive. Here, we show in zebrafish that microRNA-143 (miR-143) is required for chamber morphogenesis through direct repression of adducin3 (add3), which encodes an F-actin capping protein. Knockdown of miR-143 or disruption of the miR-143-add3 interaction inhibits ventricular cardiomyocyte F-actin remodeling, which blocks their normal growth and elongation and leads to ventricular collapse and decreased contractility. Using mosaic analyses, we find that miR-143 and add3 act cell-autonomously to control F-actin dynamics and cell morphology. As proper chamber emergence relies on precise control of cytoskeletal polymerization, Add3 represents an attractive target to be fine-tuned by both uniform signals, such as miR-143, and undiscovered localized signals. Together, our data uncover the miR-143-add3 genetic pathway as essential for cardiac chamber formation and function through active adjustment of myocardial cell morphology. C1 [Deacon, Dekker C.; Nevis, Kathleen R.; Cashman, Timothy J.; Zhou, Yong; Zhao, Long; Washko, Daniel; Guner-Ataman, Burcu; Burns, C. Geoffrey; Burns, Caroline E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Burns, Caroline E.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Burns, CG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM gburns@cvrc.mgh.harvard.edu; cburns6@partners.org RI Zhao, Long/A-6439-2014 FU NIDDK NIH HHS [DK43351, DK57521] NR 54 TC 36 Z9 38 U1 0 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN 1 PY 2010 VL 137 IS 11 BP 1887 EP 1896 DI 10.1242/dev.050526 PG 10 WC Developmental Biology SC Developmental Biology GA 594SN UT WOS:000277557900012 PM 20460367 ER PT J AU Lizarraga, SB Margossian, SP Harris, MH Campagna, DR Han, AP Blevins, S Mudbhary, R Barker, JE Walsh, CA Fleming, MD AF Lizarraga, Sofia B. Margossian, Steven P. Harris, Marian H. Campagna, Dean R. Han, An-Ping Blevins, Sherika Mudbhary, Raksha Barker, Jane E. Walsh, Christopher A. Fleming, Mark D. TI Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors SO DEVELOPMENT LA English DT Article DE CDK5RAP2; Centrosome; Neurogenesis; Mouse ID CEREBRAL CORTICAL SIZE; TUBULIN RING COMPLEX; RADIAL GLIAL-CELLS; GAMMA-TUBULIN; HERTWIGS ANEMIA; ASYMMETRIC INHERITANCE; DEVELOPING NEOCORTEX; SPINDLE ORIENTATION; NEURAL PRECURSORS; BRAIN SIZE AB Microcephaly affects similar to 1% of the population and is associated with mental retardation, motor defects and, in some cases, seizures. We analyzed the mechanisms underlying brain size determination in a mouse model of human microcephaly. The Hertwig's anemia (an) mutant shows peripheral blood cytopenias, spontaneous aneuploidy and a predisposition to hematopoietic tumors. We found that the an mutation is a genomic inversion of exon 4 of Cdk5rap2, resulting in an in-frame deletion of exon 4 from the mRNA. The finding that CDK5RAP2 human mutations cause microcephaly prompted further analysis of Cdk5rap2(an/an) mice and we demonstrated that these mice exhibit microcephaly comparable to that of the human disease, resulting from striking neurogenic defects that include proliferative and survival defects in neuronal progenitors. Cdk5rap2(an/an) neuronal precursors exit the cell cycle prematurely and many undergo apoptosis. These defects are associated with impaired mitotic progression coupled with abnormal mitotic spindle pole number and mitotic orientation. Our findings suggest that the reduction in brain size observed in humans with mutations in CDK5RAP2 is associated with impaired centrosomal function and with changes in mitotic spindle orientation during progenitor proliferation. C1 [Lizarraga, Sofia B.; Mudbhary, Raksha; Walsh, Christopher A.] Childrens Hosp, Howard Hughes Med Inst, Beth Israel Deaconess Med Ctr, Div Genet, Boston, MA 02115 USA. [Lizarraga, Sofia B.; Mudbhary, Raksha; Walsh, Christopher A.] Childrens Hosp, Howard Hughes Med Inst, Beth Israel Deaconess Med Ctr, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Lizarraga, Sofia B.; Mudbhary, Raksha; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Lizarraga, Sofia B.; Mudbhary, Raksha; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Margossian, Steven P.; Harris, Marian H.; Campagna, Dean R.; Han, An-Ping; Blevins, Sherika; Fleming, Mark D.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Margossian, Steven P.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Margossian, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Harris, Marian H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Barker, Jane E.] Jackson Lab, Bar Harbor, ME 04609 USA. RP Walsh, CA (reprint author), Childrens Hosp, Howard Hughes Med Inst, Beth Israel Deaconess Med Ctr, Div Genet, 3 Blackfan Circle, Boston, MA 02115 USA. EM christopher.walsh@childrens.harvard.edu; mark.fleming@childrens.harvard.edu FU Howard Hughes Medical Institute; NHLBI NIH HHS [K08 HL077157, T32 HL 076115-03, T32 HL076115]; NIA NIH HHS [T32 AG000222, T32AG0222-13]; NIDDK NIH HHS [P30 DK049216]; NINDS NIH HHS [R01 NS032457, R01 NS32456] NR 64 TC 92 Z9 93 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN 1 PY 2010 VL 137 IS 11 BP 1907 EP 1917 DI 10.1242/dev.040410 PG 11 WC Developmental Biology SC Developmental Biology GA 594SN UT WOS:000277557900014 PM 20460369 ER PT J AU Wang, WD Ni, LJ Yu, QM Xiong, JW Liu, HC Rosenwaks, Z AF Wang, Weidong Ni, Lujuan Yu, Qingming Xiong, Jingwei Liu, Hung-Ching Rosenwaks, Zev TI Expression of the Lycat Gene in the Mouse Cardiovascular and Female Reproductive Systems SO DEVELOPMENTAL DYNAMICS LA English DT Article DE acyltransferase; BAC transgenesis; ET-cloning; vascular smooth muscle; female reproductive organs ID TRISOMY 2P SYNDROME; HOMEOBOX GENE; ACYLTRANSFERASE CONTROLS; ENDOTHELIAL LINEAGES; SONIC HEDGEHOG; BARTH-SYNDROME; MICE LACKING; CARDIOLIPIN; HYBRIDIZATION; MITOCHONDRIA AB The Lycat homologue in zebrafish maps to the deletion interval of the cloche mutant in which hematopoietic and endothelial cell lineages are affected. However, its definitive relationship to cloche is inconclusive, partly due to inadequate expression data of Lycat from any organisms. We precisely examined the temporal and spatial expression patterns of Lycat in mouse using RNA in situ hybridization, immunostaining, and BAC transgenesis. Lycat is initially expressed in developing heart, lung, and somites, and later becomes progressively restricted to all vascular smooth muscle cells. In adult ovaries, Lycat turns on in oocytes during the transition from primary to secondary follicles. Expression of the Lycat/reporter transgene in the extraembryonic mesoderm, cardiogenic mesoderm, and primitive streak, but not extraembryonic endoderm at E7.5, suggests its potential roles in regulating cardiac, smooth muscle, hematopoietic and endothelial lineages. Promoter mapping assay by transient transgenesis identifies a novel cardiac-specific regulatory region in the Lycat locus. Developmental Dynamics 239:1827-1837, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Wang, Weidong; Ni, Lujuan; Liu, Hung-Ching; Rosenwaks, Zev] Cornell Univ, Weill Med Coll, Ronald O Perelman & Claudia Cohen Ctr Reprod Med, New York, NY 10065 USA. [Yu, Qingming; Xiong, Jingwei] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Charlestown, MA USA. [Yu, Qingming; Xiong, Jingwei] Harvard Univ, Sch Med, Charlestown, MA USA. RP Wang, WD (reprint author), Cornell Univ, Weill Med Coll, Ronald O Perelman & Claudia Cohen Ctr Reprod Med, New York, NY 10065 USA. EM wew2004@med.cornell.edu RI Xiong, Jing-Wei/A-7113-2011 FU The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University FX Grant sponsor: The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University. NR 37 TC 4 Z9 4 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 2010 VL 239 IS 6 BP 1827 EP 1837 DI 10.1002/dvdy.22300 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 610UB UT WOS:000278761700024 PM 20503378 ER PT J AU An, D Toyoda, T Taylor, EB Yu, HY Fujii, N Hirshman, MF Goodyear, LJ AF An, Ding Toyoda, Taro Taylor, Eric B. Yu, Haiyan Fujii, Nobuharu Hirshman, Michael F. Goodyear, Laurie J. TI TBC1D1 Regulates Insulin- and Contraction-Induced Glucose Transport in Mouse Skeletal Muscle SO DIABETES LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; GLUT4 TRANSLOCATION; AKT SUBSTRATE; STIMULATED PHOSPHORYLATION; AS160 PHOSPHORYLATION; RECEPTOR SUBSTRATE-1; BINDING DOMAIN; PROTEIN; RAT; OBESITY AB OBJECTIVE-TBC1D1 is a member of the TBC1 Rab-GTPase family of proteins and is highly expressed in skeletal muscle. Insulin and contraction increase TBC1D1 phosphorylation on phospho-Akt substrate motifs (PASs), but the function of TBC1D1 in muscle is not known. Genetic linkage analyses show a TBC1D1 R125W missense variant confers risk for severe obesity in humans. The objective of this study was to determine whether TBC1D1 regulates glucose transport in skeletal muscle. RESEARCH DESIGN AND METHODS-In vivo gene injection and electroporation were used to overexpress wild-type and several mutant TBC1D1 proteins in mouse tibialis anterior muscles, and glucose transport was measured in vivo. RESULTS-Expression of the obesity-associated R125W mutant significantly decreased insulin-stimulated glucose transport in the absence of changes in TBC1D1 PAS phosphorylation. Simultaneous expression of an inactive Rab-GTPase (GAP) domain of TBC1D1 in the R125W mutant reversed this decrease in glucose transport caused by the R125W mutant. Surprisingly, expression of TBC1D1 mutated to Ala on four conserved Akt and/or AMP-activated protein kinase predicted phosphorylation sites (4P) had no effect on insulin-stimulated glucose transport. In contrast, expression of the TBC1D1 4P mutant decreased contraction-stimulated glucose transport, an effect prevented by concomitant disruption of TBC1D1 Rab-GAP activity. There was no effect of the R125W mutation on contraction-stimulated glucose transport. CONCLUSIONS-TBC1D1 regulates both insulin- and contraction-stimulated glucose transport, and this occurs via distinct mechanisms. The R125W mutation of TBC1D1 impairs skeletal muscle glucose transport, which could be a mechanism for the obesity associated with this mutation. Diabetes 59:1358-1365, 2010 C1 [An, Ding; Toyoda, Taro; Taylor, Eric B.; Yu, Haiyan; Fujii, Nobuharu; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Goodyear, Laurie J.] Harvard Univ, Sch Med, Boston, MA USA. [Goodyear, Laurie J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU National Institutes of Health [R01 AR-42238, R01 AR-45670]; Joslin Diabetes Center [P30 DK-36836]; American Diabetes Association; Canadian Institute for Health [MFE-83802]; Canadian Diabetes Association [PF-3-07-2255-DA]; Japan Society for the Promotion of Science KAICENHI [21240063]; Nakatomi Foundation and the Naito Foundation; Individual Kirschstein National Research [F32 DK-075851] FX This work was supported by funding from the National Institutes of Health R01 AR-42238 and R01 AR-45670 (L.J.G.), the Graetz Challenge Grant from the Joslin Diabetes Center (L.J.G.), the American Diabetes Association Mentor-based Award (L.J.G.), and DERC Grant P30 DK-36836 (Joslin Diabetes Center). D.A. was supported by fellowships from the Canadian Institute for Health Research MFE-83802 and Canadian Diabetes Association Incentive Award PF-3-07-2255-DA; N.F., by a grant from the Japan Society for the Promotion of Science KAICENHI 21240063; T.T., by a fellowship from the Nakatomi Foundation and the Naito Foundation; and E.B.T., by the Individual Kirschstein National Research Service Award F32 DK-075851. NR 33 TC 67 Z9 67 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2010 VL 59 IS 6 BP 1358 EP 1365 DI 10.2337/db09-1266 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 611TC UT WOS:000278844700009 PM 20299473 ER PT J AU Redmon, JB Bertoni, AG Connelly, S Feeney, PA Glasser, SP Glick, H Greenway, F Hesson, LA Lawlor, MS Montez, M Montgomery, B AF Redmon, J. Bruce Bertoni, Alain G. Connelly, Stephanie Feeney, Patricia A. Glasser, Stephen P. Glick, Henry Greenway, Frank Hesson, Louise A. Lawlor, Michael S. Montez, Maria Montgomery, Brenda CA Look AHEAD Res Grp TI Effect of the Look AHEAD Study Intervention on Medication Use and Related Cost to Treat Cardiovascular Disease Risk Factors in Individuals With Type 2 Diabetes SO DIABETES CARE LA English DT Article ID LIFE EXPECTANCY; WEIGHT-LOSS; MELLITUS; INSULIN; PREVENTION; THERAPY; TRIAL AB OBJECTIVE-To examine the effect of a lifestyle intervention to produce weight loss and increased physical fitness on use and cost of medications to treat cardiovascular disease (CVD) risk factors in people with type 2 diabetes. RESEARCH DESIGN AND METHODS-Look AHEAD is a multicenter randomized controlled trial of 5,145 overweight or obese individuals with type 2 diabetes, aged 45-76 years. An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition. Medications prescribed to treat diabetes, hypertension, and hyperlipidemia were compared at baseline and 1 year. Medication costs were conservatively estimated using prices from a national online pharmacy. RESULTS-Participants randomized to an ILI had significantly greater improvements in CVD risk parameters and reduced medication use and cost compared with those assigned to DSE. At 1 year, average number of medications prescribed to treat CVD risk factors was 3.1 +/- 1.8 for the ILI group and 3.6 +/- 1.8 for the DSE group (P < 0.0001), with estimated total monthly medication costs of $143 and $173, respectively (P < 0.0001). DSE participants meeting optimal care goals at 1 year were taking an average of 3.8 +/- 1.6 medications at an estimated cost of $194/month. ILL participants at optimal care required fewer medications (3.2 +/- 1.7) at lower cost ($1.54/month) (P < 0.001). CONCLUSIONS-At 1 year, ILI significantly improved CVD risk factors, while at the same time reduced medication use and cost. Continued intervention and follow-up will determine whether these changes are maintained and reduce cardiovascular risk. C1 [Redmon, J. Bruce] Univ Minnesota, Sch Med, Dept Med, Div Endocrinol, Minneapolis, MN 55455 USA. [Bertoni, Alain G.] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Connelly, Stephanie] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Feeney, Patricia A.] Wake Forest Univ, Dept Biostat, Winston Salem, NC 27109 USA. [Glasser, Stephen P.] Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Glick, Henry] Univ Penn, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Greenway, Frank] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Hesson, Louise A.] Univ Penn, Weight & Eating Disorders Program, Philadelphia, PA 19104 USA. [Lawlor, Michael S.] Wake Forest Univ, Dept Econ, Winston Salem, NC 27109 USA. [Montez, Maria] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. [Montgomery, Brenda] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Montgomery, Brenda] Univ Washington, Seattle, WA 98195 USA. RP Redmon, JB (reprint author), Univ Minnesota, Sch Med, Dept Med, Div Endocrinol, Minneapolis, MN 55455 USA. EM redmo001@umn.edu OI Redmon, J. Bruce/0000-0002-1883-9467; Glasser, Stephen/0000-0001-9620-6406 FU National Institutes of Health (NIH) [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992, DK046204]; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; Centers for Disease Control and Prevention; Johns Hopkins Medical Institution Bayview General Clinical Research Center [M01RR02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center [M01RR01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University of Tennessee [M01RR0021140]; University of Pittsburgh [M01RR000056 44]; VA Puget Sound HealthCare Sysrem Medical Research Service, Department of Veterans Affairs; Frederic C. Banter General Clinical Research Center [M01RR01346] FX This study is supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health (NIH): DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The following federal agencies have contributed support: the National Institute of Diabetes and Digestive and Kidney Diseases; the National Heart, Lung, and Blood Institute; the National Institute of Nursing Research; the National Center on Minority Health and Health Disparities; the Office of Research on Women's Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (IHS) provided personnel, medical oversight, and use of facilities. Additional support was received from the Johns Hopkins Medical Institution Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (M01RR000056 44); NIH Grant DK046204; the VA Puget Sound HealthCare Sysrem Medical Research Service, Department of Veterans Affairs; and the Frederic C. Banter General Clinical Research Center (M01RR01346). The following organizations have committed to make major contributions to the Look AHEAD study: Federal Express; Health Management Resources; Life Scan, a Johnson & Johnson Company; Optifast of Nestle Health Care Nutrition; Hoffmann-La Roche; Abbott Nutrition; and Slim-Fast Brand of Unilever North America. NR 24 TC 37 Z9 38 U1 0 U2 2 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 JUN PY 2010 VL 33 IS 6 BP 1153 EP 1158 DI 10.2337/dc09-2090 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 617TI UT WOS:000279304300001 PM 20332353 ER PT J AU Chisholm, JW Goldfine, AB Dhalla, AK Braunwald, E Morrow, DA Karwatowska-Prokopczuk, E Belardinelli, L AF Chisholm, Jeffrey W. Goldfine, Allison B. Dhalla, Arvinder K. Braunwald, Eugene Morrow, David A. Karwatowska-Prokopczuk, Ewa Belardinelli, Luiz TI Effect of Ranolazine on A1C and Glucose Levels in Hyperglycemic Patients With Non-ST Elevation Acute Coronary Syndrome SO DIABETES CARE LA English DT Article ID LATE SODIUM CURRENT; RANDOMIZED CONTROLLED-TRIAL; DIABETES-MELLITUS; CHRONIC ANGINA; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; EUROPEAN-ASSOCIATION; EXERCISE TOLERANCE; RISK-FACTORS; INHIBITION AB OBJECTIVE - We determined the relationships between glycemia at randomization, concurrent antidiabetic therapy, and change in A1C and fasting plasma glucose (FPG) in patients with diabetes receiving standard treatment for diabetes and randomized to ranolazine or placebo within the MERLIN-TIMI-36 (MERLIN) study. Ranolazine is a novel first-in-class drug approved for treating angina pectoris. RESEARCH DESIGN AND METHODS - Randomization and 4-month glycemic and antidiabetes drug usage data from MERLIN were analyzed using Spotfire and SAS version 9.1 software. RESULTS - In patients with diabetes and A1C of >= 8-1.0% at randomization (n = 171), there was an absolute A1C reduction in the ranolazine group of 1.2% (95% CI -1.4 to -1.0), and the placebo-adjusted (n = 182) decrease in A1C by ranolazine was 0.59% (95% CI -0.99 to -0.20, P < 0.001). In patients with FPG of 150 400 mg/dl at randomization, ranolazine (n = 131) compared with placebo (n = 147) reduced EPG by 25.7 mg/dl (95% CI -43.3 to -8.1, P = 0.001.). When changes in either A1C or FPG were correlated to A1C or FPG at randomization, the slopes were significantly steeper for ranolazine than placebo (A1C, P = 0.046; EPG, P < 0.001), indicating that lowering of A1C and PPG by ranolazine is related to hyperglycemia at randomization. Ranolazine, compared with placebo, was not associated with serious hypoglycemic events, associated with significant changes in concurrent antidiabetic therapy, or dependent on a history of angina. CONCLUSIONS - Ranolazine, when added to concurrent antidiabetes treatment, lowers PPG and A1C in patients with cardiovascular disease and poorly controlled diabetes. C1 [Chisholm, Jeffrey W.; Dhalla, Arvinder K.; Karwatowska-Prokopczuk, Ewa] Gilead Sci Inc, Div Cardiovasc Therapeut, Palo Alto, CA USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Braunwald, Eugene; Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Braunwald, Eugene; Morrow, David A.] Dept Med, Boston, MA USA. [Belardinelli, Luiz] Gilead Sci Inc, Div Cardiovasc Therapeut, Foster City, CA 94404 USA. RP Chisholm, JW (reprint author), Gilead Sci Inc, Div Cardiovasc Therapeut, Palo Alto, CA USA. EM jeff.chisholm@gilead.com FU CV Therapeutics Inc. (Gilead Sciences Inc.) FX J.W.C., A.K.D., E.K.P., and L.B. are employees and shareholders of Gilead Sciences Inc., and D.M. and E.B. have received grant support from CV Therapeutics Inc. (Gilead Sciences Inc.). NR 22 TC 35 Z9 35 U1 0 U2 2 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 JUN PY 2010 VL 33 IS 6 BP 1163 EP 1168 DI 10.2337/dc09-2334 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 617TI UT WOS:000279304300003 PM 20357382 ER PT J AU Ausk, KJ Boyko, EJ Ioannou, GN AF Ausk, Karlee J. Boyko, Edward J. Ioannou, George N. TI Insulin Resistance Predicts Mortality in Nondiabetic Individuals in the US SO DIABETES CARE LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; TYPE-2 DIABETES-MELLITUS; CARDIOVASCULAR EVENTS; HEART-FAILURE; DISEASE; RISK; INFLAMMATION; ASSOCIATION; GLUCOSE; OBESITY AB OBJECTIVE - Insulin resistance is a suspected causative factor in a wide variety of diseases. We aimed to determine whether insulin resistance, estimated by the homeostasis model assessment for insulin resistance (HOMA-IR), is associated with all-cause or disease-specific mortality among nondiabetic persons in the U.S. RESEARCH DESIGN AND METHODS - We determined the association between HOMA-IR and death certificate based mortality among 5,511 nondiabetic, adult participants of the third U.S. National Health and Nutrition Examination Survey (1988-1994) during up to 12 years of follow-up, after adjustment for potential confounders (age, sex, BM!, waist-to-hip ratio, alcohol consumption, race/ethnicity, educational attainment, smoking status, physical activity, C-reactive protein, systolic and diastolic blood pressure, plasma total and HDL cholesterol, and triglycerides). RESULTS - HOMA-IR was significantly associated with all-cause mortality (adjusted hazard ratio 1.16[95% CI 1.01-1.3], comparing successive quartiles of HOMA-IR in a linear model and 1.64 [1.1-2.5], comparing the top [HOMA-IR >2.8] to the bottom [HOMA-IR 1.4] quartile). HOMA-IR was significantly associated with all-cause mortality only in subjects with BMI <25.2 kg/m(2) (the median value) but not in subjects with BMI 25.2 kg/m(2). Subjects in the second, third, and fourth quartile of HOMA-IR appeared to have higher cardiovascular mortality than subjects in the lowest quartile of HOMA-IR. HOMA-IR was not associated with cancer-related mortality. CONCLUSIONS - HOMA-IR is associated with all-cause mortality in the nondiabetic U.S. population but only among persons with normal BMI HOMA-IR is a readily available measure that can be used in the future to predict mortality in clinical or epidemiological settings. C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA. [Ausk, Karlee J.; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA USA. [Ausk, Karlee J.; Boyko, Edward J.; Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Internal Med, Seattle, WA USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA. EM georgei@medicine.washington.edu FU American Liver Foundation; American Association for the Study of Liver Diseases Jan Albrecht Award; Veterans Affairs Research Enhancement Award Program FX This work is supported by the American Liver Foundation and the American Association for the Study of Liver Diseases Jan Albrecht Award and Veterans Affairs Research Enhancement Award Program. NR 25 TC 32 Z9 35 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 JUN PY 2010 VL 33 IS 6 BP 1179 EP 1185 DI 10.2337/dc09-2110 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 617TI UT WOS:000279304300007 PM 20200308 ER PT J AU Ficociello, LH Rosolowsky, ET Niewczas, MA Maselli, NJ Weinberg, JM Aschengrau, A Eckfeldt, JH Stanton, RC Galecki, AT Doria, A Warram, JH Krolewski, AS AF Ficociello, Linda H. Rosolowsky, Elizabeth T. Niewczas, Monika A. Maselli, Nicholas J. Weinberg, Janice M. Aschengrau, Ann Eckfeldt, John H. Stanton, Robert C. Galecki, Andrzej T. Doria, Alessandro Warram, James H. Krolewski, Andrzej S. TI High-Normal Serum Uric Acid Increases Risk of Early Progressive Renal Function Loss in Type 1 Diabetes Results of a 6-year follow-up SO DIABETES CARE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CYSTATIN-C; ENDOTHELIAL DYSFUNCTION; SERIAL MEASUREMENTS; FUNCTION DECLINE; BLOOD-PRESSURE; ALLOPURINOL; HYPERURICEMIA; NEPHROPATHY; CREATININE AB OBJECTIVE - We previously described a cross-sectional association between serum uric acid and reduced glomerular filtration rate (GFR) in nonproteinuric patients with type 1 diabetes. Here, we prospectively investigated whether baseline uric acid impacts the risk of early progressive renal function loss (early GFR loss) in these patients. RESEARCH DESIGN AND METHODS - Patients with elevated urinary albumin excretion (n = 355) were followed for 4-6 years for changes in urinary albumin excretion and GFR. The changes were estimated by multiple determinations of albumin-to-creatinine ratios (ACRs) and scrum cystatin C (GFRcystatin). RESULTS At baseline, the medians (25th-75th percentiles) for uric acid. ACR, and GFRcystatin values were 4.6 mg/dl (3.8-5.4), 26.2 mg/g (15.1-56.0), and 129 ml/min per 1.73 m(2) (111-145), respectively. During the 6-year follow-up, significant association (P < 0.0002) was observed between serum uric acid and development of early GFR loss, defined as GFRcystatin decline exceeding 3.3% per year. In baseline uric acid concentration categories (in mg/dl: <3.0, 3.0-3.9, 4.0-4.9, 5.0-5.9, and >= 6) the risk of early GFR loss increased linearly (9, 13, 20, 29, and 36%, respectively). This linear increase corresponds to odds ratio 1.4 (95% Cl 1.1-1.8) per 1 mg/dl increase of uric acid. The progression and regression of urinary albumin excretion were not associated with uric acid. CONCLUSIONS - We found a clear dose-response relation between serum tine acid and risk of early GFR loss in patients with type 1 diabetes. Clinical trials are warranted to determine whether uric acid-lowering drugs can halt renal function decline before it becomes clinically significant. C1 [Ficociello, Linda H.; Rosolowsky, Elizabeth T.; Niewczas, Monika A.; Maselli, Nicholas J.; Stanton, Robert C.; Doria, Alessandro; Warram, James H.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Ficociello, Linda H.; Weinberg, Janice M.; Aschengrau, Ann] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Rosolowsky, Elizabeth T.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Rosolowsky, Elizabeth T.; Niewczas, Monika A.; Stanton, Robert C.; Doria, Alessandro; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Boston, MA USA. [Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Galecki, Andrzej T.] Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu OI Aschengrau, Ann/0000-0001-8153-7712 FU National Institutes of Health [DK 041526]; Claude Pepper Center [AG08808, AG024824] FX This research was supported by National Institutes of Health Grant DK 041526 (to ASK.) and Claude Pepper Center Grants AG08808 and AG024824 (to A.T.G.). NR 25 TC 73 Z9 79 U1 0 U2 2 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 JUN PY 2010 VL 33 IS 6 BP 1337 EP 1343 DI 10.2337/dc10-0227 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 617TI UT WOS:000279304300037 PM 20332356 ER PT J AU Alish, CJ Garvey, WT Maki, KC Sacks, GS Hustead, DS Hegazi, RA Mustad, VA AF Alish, Carolyn J. Garvey, W. Timothy Maki, Kevin C. Sacks, Gordon S. Hustead, Deborah S. Hegazi, Refaat A. Mustad, Vikkie A. TI A Diabetes-Specific Enteral Formula Improves Glycemic Variability in Patients with Type 2 Diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID CRITICALLY-ILL PATIENTS; BLOOD-GLUCOSE; HOSPITAL MORTALITY; HYPERGLYCEMIA; CARBOHYDRATE; PALATINOSE; INSULIN; TRIAL; ASSOCIATION; FAT AB Background: Well-controlled studies have demonstrated that inpatient hyperglycemia is an indicator of poor clinical outcomes, but the use of diabetes-specific enteral formulas in hospitalized patients remains a topic of great debate. Methods: In two different protocols, postprandial glycemia and insulinemia were measured in 22 subjects with diabetes fed a diabetes-specific or standard formula (protocol 1). Continuous glucose monitoring was used to assess glucose levels in 12 enterally fed patients with diabetes receiving the standard formula followed by the diabetes-specific formula continuously for 5 days each (protocol 2). End points included postprandial glycemia and insulinemia, glycemic variability (mean amplitude of glycemic excursions [MAGE]), mean glucose, and insulin use. Results: In the postprandial response protocol, the diabetes-specific formula resulted in lower positive areas under the postprandial curve (P < 0.001) and peak glucose (P < 0.001) and insulin (P = 0.017) levels. In the protocol using continuous glucose monitoring, glycemic variability (as measured by MAGE) was lower with continuous administration of the diabetes-specific than the standard formula (64.6 +/- 6.8mg/dL vs. 110.6 +/- 15.3mg/dL, P = 0.003). Also, administration of the diabetes-specific formula resulted in lower mean glucose concentrations during feeding (171.1 +/- 16.1 vs. 202.1 +/- 17.4mg/dL, P = 0.024) and insulin requirements (7.8 +/- 2.3 vs. 10.9 +/- 3.3 units/day, P = 0.039) than the standard formula. Conclusions: Relative to the standard formula, the diabetes-specific formula reduced postprandial glycemia, mean glucose, glycemic variability, and short-acting insulin requirements. These results suggest potential clinical usefulness of a diabetes-specific enteral formula for minimizing glycemic excursions in hospitalized patients. C1 [Alish, Carolyn J.; Hustead, Deborah S.; Hegazi, Refaat A.; Mustad, Vikkie A.] Abbott Labs, Columbus, OH 43215 USA. [Garvey, W. Timothy] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. [Maki, Kevin C.] Provident Clin Res, Glen Ellyn, IL USA. [Sacks, Gordon S.] Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA. RP Alish, CJ (reprint author), Abbott Labs, 625 Cleveland Ave, Columbus, OH 43215 USA. EM carolyn.alish@abbott.com NR 26 TC 21 Z9 21 U1 1 U2 3 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 JUN PY 2010 VL 12 IS 6 BP 419 EP 425 DI 10.1089/dia.2009.0185 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 597EB UT WOS:000277738000001 PM 20470226 ER PT J AU Lynch, CP Strom, JL Egede, LE AF Lynch, Cheryl P. Strom, Joni L. Egede, Leonard E. TI Effect of Veterans Administration Use on Indicators of Diabetes Care in a National Sample of Veterans SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID AFFAIRS HEALTH-CARE; QUALITY-OF-CARE; ADULTS; SYSTEM AB Background: Diabetes poses a serious health burden, of which veterans have a disproportionate share. Few data exist regarding differences in self-care behaviors and provider-based quality of care indicators among a large sample of veterans. The objective of this study was to determine the effect of Veterans Affairs (VA) use on diabetes quality of care indicators among veterans. Methods: A cross-sectional analysis was done on data from 36,525 veterans in the 2003 Behavioral Risk Factor Surveillance Survey. VA use was defined as receiving some or all health care from a VA facility in the previous 12 months. Diabetes quality indicators such as two or more provider visits, two or more hemoglobin A1c tests, and flu and pneumonia shots were compared between VA users and non-VA users. The independent effect of VA use on each quality indicator was analyzed with multiple regression using STATA version 10 (Stata Press, College Station, TX) to account for the complex survey design and yield population estimates. Results: Among veterans with diabetes, 26.8% were VA users. The only significant difference between VA users and non-VA users was that VA users were significantly more likely to check their feet one or more times daily (75.7% vs. 68.5%, P = 0.015). In final adjusted models, VA users were at least twice as likely as non-VA users to have foot exams by a provider (odds ratio 2.59) and receive flu and pneumonia shots (odds ratio 2.30 and 2.05, respectively). VA users were also more likely to have two or more provider visits, dilated eye exams, and two or more hemoglobin A1c tests than non-VA users. Conclusions: Key quality indicators for diabetes care were better among veterans getting some or all of their care from VA facilities, suggesting more effective care strategies. However, interventions should identify and perpetuate excellent self-care behaviors to more substantially impact adverse diabetes-related outcomes. C1 [Lynch, Cheryl P.] Med Univ S Carolina, Ctr Hlth Dispar Res, Ralph H Johnson VA Med Ctr, Charleston VA Res Enhancement Award Program, Charleston, SC 29456 USA. RP Lynch, CP (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Ralph H Johnson VA Med Ctr, Charleston VA Res Enhancement Award Program, 135 Rutledge Ave,MSC 250593, Charleston, SC 29456 USA. EM lynchcp@musc.edu FU NIDDK NIH HHS [R01 DK081121] NR 22 TC 4 Z9 4 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 JUN PY 2010 VL 12 IS 6 BP 427 EP 433 DI 10.1089/dia.2009.0171 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 597EB UT WOS:000277738000002 PM 20470227 ER PT J AU Shetty, G Wolpert, H AF Shetty, Greeshma Wolpert, Howard TI Insulin Pump Use in Adults with Type 1 Diabetes-Practical Issues SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID QUALITY-OF-LIFE; MULTIPLE DAILY INJECTIONS; INFUSION CSII THERAPY; GLYCEMIC CONTROL; SEVERE HYPOGLYCEMIA; DAWN PHENOMENON; METAANALYSIS; MELLITUS; TRIAL; BOLUS AB In recent years continuous subcutaneous insulin infusion pumps have become widely adopted in many parts of the world in the treatment of type 1 diabetes in adults. A comprehensive summary of all aspects of pump therapy is beyond the scope of this article, and in this review we will focus on several practical issues that in our experience are of clinical importance in the care of patients using insulin pumps. These include: benefits and risks of pump therapy, including the use of pumps to limit hypoglycemia; individual patient considerations in choosing between pump therapy and multiple daily injections; common pump-specific etiologies of erratic glucose control, including routine clinical practices that can assist with the detection of these problems; and the use of different pump bolus types for prandial insulin coverage. C1 [Shetty, Greeshma; Wolpert, Howard] Joslin Diabet Ctr, Sect Adult Diabet, Boston, MA 02215 USA. RP Wolpert, H (reprint author), Joslin Diabet Ctr, Sect Adult Diabet, 1 Joslin Pl, Boston, MA 02215 USA. EM howard.wolpert@joslin.harvard.edu NR 42 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JUN PY 2010 VL 12 SU 1 BP S11 EP S16 DI 10.1089/dia.2010.0002 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 603MI UT WOS:000278212300003 PM 20515299 ER PT J AU Zraika, S Hull, RL Verchere, CB Clark, A Potter, KJ Fraser, PE Raleigh, DP Kahn, SE AF Zraika, S. Hull, R. L. Verchere, C. B. Clark, A. Potter, K. J. Fraser, P. E. Raleigh, D. P. Kahn, S. E. TI Toxic oligomers and islet beta cell death: guilty by association or convicted by circumstantial evidence? SO DIABETOLOGIA LA English DT Article ID AMYLOID FIBRIL FORMATION; ALZHEIMERS-DISEASE BRAIN; HUMAN AMYLIN; DIABETES-MELLITUS; TRANSGENIC MICE; APOLIPOPROTEIN-E; NONDIABETIC INDIVIDUALS; PROTEIN AGGREGATION; PEPTIDE DEPOSITION; MOUSE MODEL AB Type 2 diabetes is a progressive disease characterised by islet amyloid deposits in the majority of patients. Amyloid formation is considered a significant factor in deterioration of islet function and reduction in beta cell mass, and involves aggregation of monomers of the normally soluble beta cell peptide, human islet amyloid polypeptide (hIAPP) into oligomers, fibrils and, ultimately, mature amyloid deposits. Despite extensive in vitro studies, the process of hIAPP aggregation in vivo is poorly understood, though it is widely reported to promote cytotoxicity. Recently, studies have suggested that only the early stages of fibril assembly, and in particular small hIAPP oligomers, are responsible for beta cell cytotoxicity. This challenges the prior concept that newly formed fibrils and/or mature fibrillar amyloid are cytotoxic. Herein, evidence both for and against the toxic hIAPP oligomer hypothesis is presented; from this, it is apparent that what exactly causes beta cell death when hIAPP aggregates remains debatable. Moreover, substantially more work with more specific reagents and techniques than are currently available will be required to identify conclusively the toxic species resulting from hIAPP aggregation. Keeping an open mind on the nature of the cytotoxic insult has implications for therapeutic developments and clinical care in type 2 diabetes. C1 [Zraika, S.; Hull, R. L.; Kahn, S. E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Zraika, S.; Hull, R. L.; Kahn, S. E.] Univ Washington, Seattle, WA 98108 USA. [Verchere, C. B.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Verchere, C. B.] Univ British Columbia, Dept Surg, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada. [Clark, A.] Churchill Hosp, Diabet Res Labs, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [Potter, K. J.] Univ British Columbia, Child & Family Res Inst, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Fraser, P. E.] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. [Fraser, P. E.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Raleigh, D. P.] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA. RP Zraika, S (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way 151, Seattle, WA 98108 USA. EM zraikas@u.washington.edu OI Verchere, Bruce/0000-0002-9262-0586; Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU Department of Veterans Affairs; Canadian Diabetes Association; Canadian Institutes of Health Research; Alzheimer Society of Ontario; NIH [DK-075998, DK-074404, DK-080945, GM-078114]; Canadian Institutes of Health Research [MOP-14682]; Juvenile Diabetes Research Foundation; Canadian Institutes of Health Research RD Studentship; Michael Smith Foundation for Health Research FX The authors are supported by the Medical Research Service of the Department of Veterans Affairs (S. Zraika, R. L. Hull, S. E. Kahn), the Canadian Diabetes Association (C. B. Verchere), the Canadian Institutes of Health Research (P. E. Fraser) and the Alzheimer Society of Ontario (P. E. Fraser). They are also in receipt of the following grants: NIH grants DK-075998 to S. E. Kahn, DK-074404 to R. L. Hull, DK-080945 to S. Zraika and GM-078114 to D. P. Raleigh; a Canadian Institutes of Health Research grant MOP-14682 to C. B. Verchere; a Juvenile Diabetes Research Foundation Postdoctoral Fellowship grant to S. Zraika; and a Canadian Institutes of Health Research R&D Studentship to K. J. Potter. C. B. Verchere is a Senior Scholar of the Michael Smith Foundation for Health Research. NR 83 TC 80 Z9 80 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 2010 VL 53 IS 6 BP 1046 EP 1056 DI 10.1007/s00125-010-1671-6 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 589HP UT WOS:000277138100005 PM 20182863 ER PT J AU Sawhney, MS McDougall, H Nelson, DB Bond, JH AF Sawhney, Mandeep S. McDougall, Heather Nelson, Douglas B. Bond, John H. TI Fecal Occult Blood Test in Patients on Low-Dose Aspirin, Warfarin, Clopidogrel, or Non-steroidal Anti-inflammatory Drugs SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Colon cancer; FOBT; Occult blood; Screening; Fecal occult blood test ID COLORECTAL-CANCER; HEMOCCULT; VETERANS AB To determine the effect of anticoagulants and antiplatelet medications on the positive-predictive-value of fecal occult blood test (FOBT). All patients who underwent a colonoscopy at our institution from 1995 to 2006 for a positive FOBT were identified. Medical records were searched, and patients were stratified into five groups selected a priori: low-dose aspirin, NSAIDs, warfarin, clopidogrel, or controls. The positive-predictive-value of FOBT for advanced colonic neoplasia was computed for each group. During the study period, 1,126 patients underwent colonoscopy for a positive FOBT and met entry criteria. The average age of study participants was 69 years and most were men. The positive-predictive-value of FOBT for advanced colon neoplasia was significantly higher in the control group (30.5%) when compared to those on low-dose aspirin (20.5%; p = 0.003), NSAIDs (19.7%; p = 0.003), clopidogrel (7.3%; p = 0.002), or warfarin (20%; p = 0.05). The positive-predictive-value of FOBT was significantly lower for those on clopidogrel than those on low-dose aspirin (p = 0.04) and NSAIDs (p = 0.05), but not warfarin (p = 0.08). The positive-predictive-value for FOBT was similar for those on aspirin, NSAIDs, and warfarin. There was a linear trend between the number of number of positive FOBT cards and prevalence of advanced colon neoplasia (p = 0.01). Anticoagulants and antiplatelet medications lower the positive-predictive-value of FOBT for advance colonic neoplasia and should be stopped if clinically feasible prior to stool collection. C1 [Sawhney, Mandeep S.] Beth Israel Deaconess Med Ctr RABB ROSE 101, Div Gastroenterol, Boston, MA 02215 USA. [Sawhney, Mandeep S.; McDougall, Heather; Nelson, Douglas B.; Bond, John H.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Sawhney, Mandeep S.; McDougall, Heather; Nelson, Douglas B.; Bond, John H.] Minneapolis Vet Affairs Med Ctr, Div Gastroenterol, Minneapolis, MN USA. RP Sawhney, MS (reprint author), Beth Israel Deaconess Med Ctr RABB ROSE 101, Div Gastroenterol, 330 Brookline Ave, Boston, MA 02215 USA. EM msawhney@bidmc.harvard.edu NR 20 TC 25 Z9 28 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 JUN PY 2010 VL 55 IS 6 BP 1637 EP 1642 DI 10.1007/s10620-010-1150-4 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 608JC UT WOS:000278578800020 PM 20195757 ER PT J AU Hawkins, EJ Lapham, GT Kivlahan, DR Bradley, KA AF Hawkins, Eric J. Lapham, Gwendolyn T. Kivlahan, Daniel R. Bradley, Katharine A. TI Recognition and management of alcohol misuse in OEF/OIF and other veterans in the VA: A cross-sectional study SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Alcohol misuse; OEF/OIF; Brief alcohol interventions; Referral to treatment; Alcohol screening ID IDENTIFICATION TEST AUDIT; SUBSTANCE USE DISORDERS; MENTAL-HEALTH PROBLEMS; BRIEF PHYSICIAN ADVICE; BENEFIT-COST-ANALYSIS; PRIMARY-CARE PATIENTS; PROBLEM DRINKING; US-VETERANS; BRIEF INTERVENTIONS; PROBLEM DRINKERS AB Background: Mental health problems have been identified among soldiers serving in Operations Enduring Freedom and Iraqi Freedom (OEF/OIF), but little is known about the prevalence and management of alcohol misuse in OEF/OIF veterans seen in the Veterans Administration health care system (VA). Methods: We identified 12,092 veterans (n = 2009 women) 55 and younger and screened for alcohol misuse in FY2007 from a cross-sectional national sample of VA outpatients randomly selected for standardized medical record review for quality monitoring. Alcohol misuse was assessed with the Alcohol Use Disorders Identification Test Consumption questions (AUDIT-C >= 5). Based on medical record reviews, brief alcohol interventions (BI) were defined as documented (1) advice to abstain or drink within recommended limits or (2) feedback about health risks associated with drinking. Results: Adjusted prevalence of alcohol misuse was higher in OEF/OIF men than non-OEF/OIF men [21.8% vs. 10.5%, adjusted odds ratio (AOR) = 2.37(95% CI: 1.88-2.99)], but did not differ reliably between OEF/OIF and non-OEF/OIF women [4.7% vs. 2.9%, AOR = 1.68 (0.74-3.79)]. Adjusted rates of documented advice or feedback [31.6% vs. 34.6%, AOR =0.87 (0.58-1.21)] and referral [24.1% vs. 28.9%, AOR = 0.78 (0.47-1.30)] were not significantly different between OEF/OIF and non-OEF/OIF men who screened positive for alcohol misuse. Conclusion: OEF/OIF men were more likely to screen positive for alcohol misuse than non-OEF/OIF men. Overall, approximately half of those with alcohol misuse had documented BI and/or referral to alcohol treatment suggesting a need for improvement in addressing alcohol misuse in OEF/OIF and other veterans. Published by Elsevier Ireland Ltd. C1 [Hawkins, Eric J.] VA Puget Sound Hlth Care Syst, Seattle Div S116ATC, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care, Seattle, WA 98108 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Hawkins, EJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div S116ATC, Hlth Serv Res & Dev, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Eric.Hawkins@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service; Veteran Affairs' Substance Use Disorders Quality Enhancement Research Initiative [SUB 98-000] FX The research reported here was supported by Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service. The manuscript was specifically produced with support from the Veteran Affairs' Substance Use Disorders Quality Enhancement Research Initiative (SUB 98-000). Dr. Kivlahan and Dr. Bradley presently serve as the Clinical Coordinator and Co-Clinical Coordinator of the Substance Use Disorders Quality Enhancement Research Initiative. Supporting organizations had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the University of Washington. NR 42 TC 49 Z9 49 U1 3 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 1 PY 2010 VL 109 IS 1-3 BP 147 EP 153 DI 10.1016/j.drugalcdep.2009.12.025 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 609MF UT WOS:000278660000023 PM 20167440 ER PT J AU Chen, YT Slaugenhaupt, SA AF Chen, Y-T Slaugenhaupt, S. A. TI FAMILIAL DYSAUTONOMIA SO DRUGS OF THE FUTURE LA English DT Article ID B KINASE COMPLEX; MESSENGER-RNA; ELONGATOR COMPLEX; TRANSCRIPTIONAL ELONGATION; SPINAL DEFORMITY; CELL-MIGRATION; ASHKENAZI JEWS; KINETIN; PROTEIN; IKAP AB Familial dysoutonomia (FD), also known as Riley-Day syndrome or recessive hereditary sensory and autonomic neuropathy type III (HSAN Ill), is caused by a single-base noncoding mutation in intron 20 (IVS20+6T > C) of the IKBKAP/ELP1 gene. This mutation results in variable skipping of exon 20 in IKBKAP/ELP1 transcripts, which leads to tissue-specific reduction of ELP1(IKBKAP) protein, particularly in the nervous system. FD is a devastating disorder with a high mortality rate due primarily to autonomic dysfunction. The identification of the gene and the disease-causing mutation has promised the development of potential treatments that directly target mRNA splicing to increase normal mRNA and protein. FD is a developmental disease with diagnostic symptoms present at birth, whereas patients show progressive neurodegeneration throughout life. Drugs that con increase ELP1 protein may slow this degeneration and improve the quality of life in aging patients. Since these compounds target the mRNA splicing mechanism and not a specific gene, it is likely that they will prove useful in other disorders with similar splice-site mutations. Given that 20-30% of human mutations are predicted to alter mRNA splicing, direct modification of splicing efficiency poses an important target for the design of therapeutics in the future. C1 [Slaugenhaupt, S. A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Slaugenhaupt, SA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, CPZN-5254,185 Cambridge St, Boston, MA 02114 USA. EM Slaugenhaupt@chgr.mgh.harvard.edu NR 75 TC 0 Z9 0 U1 1 U2 7 PU PROUS SCIENCE, SA-THOMSON REUTERS PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD JUN PY 2010 VL 35 IS 6 BP 489 EP 494 DI 10.1358/dof.2010.35.6.1488338 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 637RG UT WOS:000280835800006 ER PT J AU Livingston, D AF Livingston, D. TI Intricacies of BRCA1 genome integrity control and cancer suppression functions SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Livingston, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Livingston, D.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 336 BP 87 EP 87 PG 1 WC Oncology SC Oncology GA 737XF UT WOS:000288603100326 ER PT J AU Schrader, A Bentink, S Spang, R Lenze, D Hummel, M Kuo, M Murray, P Trumper, L Kube, D Vockerodt, M AF Schrader, A. Bentink, S. Spang, R. Lenze, D. Hummel, M. Kuo, M. Murray, P. Truemper, L. Kube, D. Vockerodt, M. TI A c-Myc induced gene expression signature in human germinal center B cells predicts subtypes of aggressive non-Hodgkin Lymphoma SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Schrader, A.; Truemper, L.; Kube, D.] Univ Gottingen, Gottingen, Germany. [Bentink, S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Spang, R.] Univ Regensburg, Inst Funct Genom, Regensburg, Germany. [Lenze, D.; Hummel, M.] Charite, Inst Pathol, Berlin, Germany. [Kuo, M.] Birmingham Childrens Hosp, Dept Paediat Otolaryngol, Birmingham, W Midlands, England. [Murray, P.; Vockerodt, M.] Univ Birmingham, Canc Res UK Div Canc Studies, Birmingham, W Midlands, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 417 BP 107 EP 107 PG 1 WC Oncology SC Oncology GA 737XF UT WOS:000288603100400 ER PT J AU Sprauten, M Darrah, T Hannigan, R Beard, C Haugnes, H Cvancarova, M Peterson, D Travis, L Fossa, S Oldenburg, J AF Sprauten, M. Darrah, T. Hannigan, R. Beard, C. Haugnes, H. Cvancarova, M. Peterson, D. Travis, L. Fossa, S. Oldenburg, J. TI Long-term accumulation of platinum (Pt) and its impact on self-reported neuro-and ototoxicity in cisplatin-treated testicular cancer survivors (TCSs) SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Sprauten, M.; Cvancarova, M.; Fossa, S.; Oldenburg, J.] Oslo Univ Hosp, Oslo, Norway. [Darrah, T.; Hannigan, R.] Univ Massachusetts, Boston, MA 02125 USA. [Beard, C.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Haugnes, H.] Inst Clin Med, Tromso, Norway. [Peterson, D.; Travis, L.] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. RI Hannigan, Robyn /F-8628-2010 OI Hannigan, Robyn /0000-0003-4782-1124 NR 0 TC 0 Z9 0 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 603 BP 153 EP 154 PG 3 WC Oncology SC Oncology GA 737XF UT WOS:000288603100586 ER PT J AU Sadow, PM Heinrich, MC Corless, CL Fletcher, JA Nose, V AF Sadow, Peter M. Heinrich, Michael C. Corless, Christopher L. Fletcher, Jonathan A. Nose, Vania TI Absence of BRAF, NRAS, KRAS, HRAS Mutations, and RET/PTC Gene Rearrangements Distinguishes Dominant Nodules in Hashimoto Thyroiditis from Papillary Thyroid Carcinomas SO ENDOCRINE PATHOLOGY LA English DT Article DE Hashimoto thyroiditis; Papillary thyroid carcinoma; BRAF; NRAS; KRAS; HRAS; RET-PTC; Dominant nodule ID FINE-NEEDLE-ASPIRATION; CHRONIC LYMPHOCYTIC THYROIDITIS; FOLLICULAR CELLS; CANCER; EXPRESSION; MALIGNANCY; RAS; THYROCYTES; FEATURES; TUMORS AB Dominant nodules within Hashimoto thyroiditis (HT) may present with unique morphological features that overlap with but are not diagnostic of papillary thyroid carcinoma (PTC). Activating BRAF point mutations, RAS aberrations, and RET rearrangements are mutually exclusive events in the oncogenesis of papillary thyroid carcinoma, and RET rearrangements have been previously described in dominant nodules of HT. We identified 28 cases of Hashimoto thyroiditis with a dominant nodule, from 345 consecutive HT thyroidectomies. Screening for BRAF, RET, KRAS, NRAS, and HRAS mutations, as well as RET-PTC1 and RET-PTC3 rearrangements, was performed on paraffin-embedded material from 17 of these dominant nodules. Patients ranged in age from 29 to 76 years and were predominantly female, and the nodules ranged from 1.5 to 6.2 cm. No BRAF or RAS mutations or RET-PTC rearrangements were identified in a dominant nodule, including those with atypical, worrisome histopathologic features. Of ten cases with diagnostic concomitant or incidental papillary carcinoma, three had a V600E point mutation in BRAF, and one case had a BRAF exon 15 deletion (600-604E), while the dominant nodules were negative for mutation, supporting the notion that dominant nodules are neither malignant nor precursor lesions, and strict histological, clinical, and molecular criteria must be met for the diagnosis of papillary thyroid carcinoma. C1 [Sadow, Peter M.; Fletcher, Jonathan A.; Nose, Vania] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Dept Med, Portland, OR 97239 USA. [Heinrich, Michael C.; Corless, Christopher L.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Corless, Christopher L.] Portland VA Med Ctr, Dept Pathol, Portland, OR 97239 USA. [Fletcher, Jonathan A.; Nose, Vania] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Sadow, PM (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM psadow@partners.org FU VA Merit Review Grant FX The BRAF data were presented, in part, at the United States and Canadian Academy of Pathology Annual Meeting in Atlanta, GA, February 11-16, 2006. The authors wish to acknowledge prior input from Dr. Kimberly Springer and Victoria Derr in the original presentation, as well as technical assistance from Amy Harlow and Andrea Warrick. This study is supported in part from funding from a VA Merit Review Grant (MCH). Dr. Heinrich has an equity interest in MolecularMD and serves as a consultant for MolecularMD. NR 35 TC 15 Z9 17 U1 1 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD JUN PY 2010 VL 21 IS 2 BP 73 EP 79 DI 10.1007/s12022-009-9101-3 PG 7 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 589HW UT WOS:000277138800001 PM 20012784 ER PT J AU Sozopoulos, E Litsiou, H Voutsinas, G Mitsiades, N Anagnostakis, N Tseva, T Patsouris, E Tseleni-Balafouta, S AF Sozopoulos, Elias Litsiou, Helen Voutsinas, Gerassimos Mitsiades, Nikolaos Anagnostakis, Nikolaos Tseva, Thomais Patsouris, Efstratios Tseleni-Balafouta, Sofia TI Mutational and Immunohistochemical Study of the PI3K/Akt Pathway in Papillary Thyroid Carcinoma in Greece SO ENDOCRINE PATHOLOGY LA English DT Article DE PI3K/Akt pathway; Thyroid cancer; Papillary carcinoma; Mutational analysis ID GROWTH-FACTOR-I; HORMONE-INDEPENDENT PROLIFERATION; EPITHELIAL-CELLS; IGF-I; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; ENDOMETRIAL CARCINOMAS; RET/PTC REARRANGEMENTS; PHOSPHATASE-ACTIVITY; GENETIC ALTERATIONS; GERMLINE MUTATIONS AB PI3K/Akt signaling pathway plays critical role in many cell processes. There is indication that enhanced activation of PI3K/Akt cascade is implicated in thyroid tumors. Aim of this study was to evaluate the mutational status and expression of PI3K/Akt pathway mediators in papillary thyroid carcinoma in Greece. We evaluated the presence of mutations in PIK3CA (exons 9 and 20), AKT1 (exons 6-11), AKT2 (exons 6-11), AKT3 (exons 5-10), PTEN (exons 3-8), and PDPK1 (exons 4-10) genes in 83 papillary thyroid carcinomas by DNA sequencing. The expression levels of phospho-Akt and insulin-like growth factor I receptor (IGF-IR) were evaluated by immunohistochemistry. PIK3CA mutations were found in three samples. The analysis of AKT1 revealed one silent mutation in exon 9 (G726A) in 16 samples. One specimen carried an AKT3 mutation. One missense mutation was found in one sample in PTEN. No mutations were found in AKT2 and PDPK1. Increased levels of phosphorylated total Akt and IGF-IR were identified in some papillary cancers. Our findings indicate that PI3K/Akt signaling pathway is activated in some papillary tumors. However, mutations in genes coding most mediators of the pathway have not been proven to be the major modus of enhanced activation. These data suggest a potential role for PI3K/Akt-mediated signaling in papillary thyroid tumors. C1 [Sozopoulos, Elias; Litsiou, Helen; Anagnostakis, Nikolaos; Tseva, Thomais; Patsouris, Efstratios; Tseleni-Balafouta, Sofia] Univ Athens, Sch Med, Dept Pathol 1, GR-11527 Athens, Greece. [Voutsinas, Gerassimos] Natl Ctr Sci Res Demokritos, Lab Environm Mutagenesis & Carcinogenesis, Inst Biol, Athens, Greece. [Mitsiades, Nikolaos] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sozopoulos, E (reprint author), Univ Athens, Sch Med, Dept Pathol 1, M Asias 75, GR-11527 Athens, Greece. EM elsozopoulos@yahoo.gr; stseleni@cc.uoa.gr FU National and Community Funds; EU-European Social Fund; Greek Ministry of Development, General Secretariat of Research and Technology FX This study is part of the 03ED375 research project, implemented within the framework of (PENED) and cofinanced by National and Community Funds (EU-European Social Fund and Greek Ministry of Development, General Secretariat of Research and Technology). The authors have no conflict of interest to declare. NR 67 TC 10 Z9 10 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD JUN PY 2010 VL 21 IS 2 BP 90 EP 100 DI 10.1007/s12022-010-9112-0 PG 11 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 589HW UT WOS:000277138800003 PM 20186503 ER PT J AU Patti, ME Corvera, S AF Patti, Mary-Elizabeth Corvera, Silvia TI The Role of Mitochondria in the Pathogenesis of Type 2 Diabetes SO ENDOCRINE REVIEWS LA English DT Review ID BROWN ADIPOSE-TISSUE; HUMAN SKELETAL-MUSCLE; TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; RECEPTOR-GAMMA COACTIVATOR-1-ALPHA; SEVERE INSULIN-RESISTANCE; ACTIVATED PROTEIN-KINASE; FREE FATTY-ACIDS; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; MESSENGER-RNA EXPRESSION; BETA-CELL FUNCTION AB The pathophysiology of type 2 diabetes mellitus (DM) is varied and complex. However, the association of DM with obesity and inactivity indicates an important, and potentially pathogenic, link between fuel and energy homeostasis and the emergence of metabolic disease. Given the central role for mitochondria in fuel utilization and energy production, disordered mitochondrial function at the cellular level can impact whole-body metabolic homeostasis. Thus, the hypothesis that defective or insufficient mitochondrial function might play a potentially pathogenic role in mediating risk of type 2 DM has emerged in recent years. Here, we summarize current literature on risk factors for diabetes pathogenesis, on the specific role(s) of mitochondria in tissues involved in its pathophysiology, and on evidence pointing to alterations in mitochondrial function in these tissues that could contribute to the development of DM. We also review literature on metabolic phenotypes of existing animal models of impaired mitochondrial function. We conclude that, whereas the association between impaired mitochondrial function and DM is strong, a causal pathogenic relationship remains uncertain. However, we hypothesize that genetically determined and/or inactivity-mediated alterations in mitochondrial oxidative activity may directly impact adaptive responses to overnutrition, causing an imbalance between oxidative activity and nutrient load. This imbalance may lead in turn to chronic accumulation of lipid oxidative metabolites that can mediate insulin resistance and secretory dysfunction. More refined experimental strategies that accurately mimic potential reductions in mitochondrial functional capacity in humans at risk for diabetes will be required to determine the potential pathogenic role in human insulin resistance and type 2 DM. (Endocrine Reviews 31: 364-395, 2010) C1 [Patti, Mary-Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Patti, Mary-Elizabeth] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Corvera, Silvia] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl,Room 620, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu; silvia.corvera@umassmed.edu FU National Institutes of Health [DK062948, DK080366]; Graetz Foundation [LM008748, DK060837, M01 RR001032, DK36836, DK32520] FX The authors gratefully acknowledge research support from National Institutes of Health Grants DK062948 (to M.-E.P.), DK080366 (to S.C.), the Graetz Foundation (to M.-E.P.), LM008748 (to M.-E.P.), DK060837 (Diabetes Genome Anatomy Project, to M.-E.P., and S.C.), M01 RR001032 (General Clinical Research Center), DK36836 (Diabetes and Endocrinology Research Center, Joslin Diabetes Center), and DK32520 (Diabetes Endocrinology Research Center, University of Massachusetts Medical School). NR 287 TC 181 Z9 186 U1 4 U2 40 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 BP 364 EP 395 DI 10.1210/er.2009-0027 PG 32 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 608PA UT WOS:000278596500004 PM 20156986 ER PT J AU Ahn, J Ko, S Kim, S Knapczyk-Stwora, K Song, CS Chatterjee, B AF Ahn, J. Ko, S. Kim, S. Knapczyk-Stwora, K. Song, C. S. Chatterjee, B. TI Methylation of Androgen Receptor by Set9 Histone Methyltransferase and Its Functional Impact SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Ahn, J.; Ko, S.; Kim, S.; Knapczyk-Stwora, K.; Song, C. S.; Chatterjee, B.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Song, C. S.; Chatterjee, B.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S4 EP S4 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400005 ER PT J AU Chan, YM Pinnell, N Seminara, SB AF Chan, Y-M Pinnell, N. Seminara, S. B. TI Interrogating the Human GnRH Neuron In Vivo: Effects of Exogenous Kisspeptin on GnRH Neuroendocrine Dynamics. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Chan, Y-M; Pinnell, N.; Seminara, S. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chan, Y-M] Childrens Hosp Boston, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S2476 EP S2476 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400183 ER PT J AU Falutz, J Mamputu, J Potvin, D Moyle, G Soulban, G Loughrey, H Marsolais, C Turner, R Grinspoon, S AF Falutz, J. Mamputu, J. Potvin, D. Moyle, G. Soulban, G. Loughrey, H. Marsolais, C. Turner, R. Grinspoon, S. TI Effects of Tesamorelin, a Growth Hormone Releasing Analogue, over 52 Weeks in HIV-Infected Patients with Excess Abdominal Fat: A Pooled Analysis of 2 Multicenter, Randomized, Placebo-Controlled Phase III Trials SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Falutz, J.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Mamputu, J.; Potvin, D.; Soulban, G.; Loughrey, H.; Marsolais, C.] Theratechnologies, Montreal, PQ, Canada. [Moyle, G.] Chelsea & Westminster Hosp, London, England. [Turner, R.] Phase V Technol, Wellesley, MA USA. [Grinspoon, S.] Mass Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S1697 EP S1697 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400150 ER PT J AU George, JT Anderson, RA Seminara, SB Millar, RP AF George, J. T. Anderson, R. A. Seminara, S. B. Millar, R. P. TI Kisspeptin 10 Rapidly and Potently Stimulates LH Secretion in Men. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [George, J. T.; Anderson, R. A.; Millar, R. P.] Ctr Reprod Biol, Edinburgh, Midlothian, Scotland. [Anderson, R. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Seminara, S. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Millar, R. P.] Univ Cape Town, ZA-7925 Cape Town, South Africa. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S2477 EP S2477 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400184 ER PT J AU Hirano, LA Page, ST Dighe, M Marck, BT Matsumoto, AM AF Hirano, L. A. Page, S. T. Dighe, M. Marck, B. T. Matsumoto, A. M. TI Dutasteride Reduces Prostate Size and Prostate Specific Antigen in Hypogonadal Men with Benign Prostatic Hyperplasia Undergoing Testosterone Replacement Therapy. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Hirano, L. A.; Page, S. T.; Dighe, M.; Matsumoto, A. M.] Univ Washington, Seattle, WA 98195 USA. [Hirano, L. A.; Marck, B. T.; Matsumoto, A. M.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S861 EP S861 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400101 ER PT J AU Kawamori, D Liew, CW Hu, J Kurpad, AJ Shadrach, JL Katsuta, H Qian, W Wagers, AJ Kulkarni, RN AF Kawamori, D. Liew, C. W. Hu, J. Kurpad, A. J. Shadrach, J. L. Katsuta, H. Qian, W. Wagers, A. J. Kulkarni, R. N. TI Systemic Signals Promote Enhanced beta-Cell Mitosis in Insulin Resistant Mice. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Kawamori, D.; Liew, C. W.; Hu, J.; Kurpad, A. J.; Shadrach, J. L.; Katsuta, H.; Wagers, A. J.; Kulkarni, R. N.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kawamori, D.; Liew, C. W.; Hu, J.; Kurpad, A. J.; Shadrach, J. L.; Katsuta, H.; Wagers, A. J.; Kulkarni, R. N.] Harvard Univ, Sch Med, Boston, MA USA. [Qian, W.] Pacific NW Natl Lab, Richland, WA 99352 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S2485 EP S2485 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400192 ER PT J AU Koncarevic, A Burton, R Cornwall-Brady, M Davies, M Sako, D Liu, J Kumar, R Tomkinson, K Baker, T Umiker, B Monnell, T Grinberg, A Liharska, K Underwood, K Ucran, J Howard, B Barberio, J Spaits, M Spiegelman, BM Seehra, J Lachey, J AF Koncarevic, A. Burton, R. Cornwall-Brady, M. Davies, M. Sako, D. Liu, J. Kumar, R. Tomkinson, K. Baker, T. Umiker, B. Monnell, T. Grinberg, A. Liharska, K. Underwood, K. Ucran, J. Howard, B. Barberio, J. Spaits, M. Spiegelman, B. M. Seehra, J. Lachey, J. TI Treatment with a Soluble ActRIIB Prevents Obese Phenotype and Promotes Favorable Thermogenic Program in White Adipose Tissue in Mice Fed a High-Fat Diet SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Koncarevic, A.; Burton, R.; Cornwall-Brady, M.; Davies, M.; Sako, D.; Liu, J.; Kumar, R.; Tomkinson, K.; Baker, T.; Umiker, B.; Monnell, T.; Grinberg, A.; Liharska, K.; Underwood, K.; Ucran, J.; Howard, B.; Barberio, J.; Spaits, M.; Seehra, J.; Lachey, J.] Acceleron Pharma Inc, Cambridge, MA USA. [Spiegelman, B. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S838 EP S838 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400078 ER PT J AU Lee, KY Gesta, S Boucher, J Wang, X Gonzalez, FJ Kahn, CR AF Lee, K. Y. Gesta, S. Boucher, J. Wang, X. Gonzalez, F. J. Kahn, C. R. TI Adipose Specific Ablation of Hif1b/Arnt and the Role of Hypoxia in Obesity and Adipose Vascular Function SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Lee, K. Y.; Gesta, S.; Boucher, J.; Wang, X.; Kahn, C. R.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Gonzalez, F. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S836 EP S836 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400076 ER PT J AU Makimura, H Fleischman, A Hrovat, M Systrom, DM Grinspoon, SK AF Makimura, H. Fleischman, A. Hrovat, M. Systrom, D. M. Grinspoon, S. K. TI Skeletal Muscle Mitochondrial Function in Children, Young and Middle Age Adults SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Makimura, H.; Fleischman, A.; Hrovat, M.; Systrom, D. M.; Grinspoon, S. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hrovat, M.] Mirtech Inc, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S2558 EP S2558 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400259 ER PT J AU Misra, M Le Clair, M Mendes, N Miller, KK Lawson, EA Meenaghan, E Weigel, T Ebrahimi, S Herzog, D Klibanski, A AF Misra, M. Le Clair, M. Mendes, N. Miller, K. K. Lawson, E. A. Meenaghan, E. Weigel, T. Ebrahimi, S. Herzog, D. Klibanski, A. TI Use of SSRIs May Impact Bone Density in Adolescents and Young Women with Anorexia Nervosa. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Misra, M.; Le Clair, M.; Mendes, N.; Miller, K. K.; Lawson, E. A.; Meenaghan, E.; Herzog, D.; Klibanski, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Misra, M.; Le Clair, M.; Mendes, N.; Miller, K. K.; Lawson, E. A.; Meenaghan, E.; Herzog, D.; Klibanski, A.] Harvard Univ, Sch Med, Boston, MA USA. [Misra, M.] MassGen Hosp, Boston, MA USA. [Weigel, T.] McLean Hosp, Belmont, MA 02178 USA. [Ebrahimi, S.] Cambridge Eating Disorders Ctr, Cambridge, MA USA. RI Mendes Estella, Nara/A-1469-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S46 EP S46 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400046 ER PT J AU Qin, Y Yao, L King, E Buddavarapu, K Chocron, E Lechleiter, J Aronin, N Sass, M Schiavi, F Opocher, G Toledo, R Toledo, S Stiles, C Aguiar, R Dahia, P AF Qin, Y. Yao, L. King, E. Buddavarapu, K. Chocron, E. Lechleiter, J. Aronin, N. Sass, M. Schiavi, F. Opocher, G. Toledo, R. Toledo, S. Stiles, C. Aguiar, R. Dahia, P. TI FP/TMEM127 is a Novel Pheochromocytoma Susceptibility Gene. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Qin, Y.; Yao, L.; King, E.; Buddavarapu, K.; Chocron, E.; Lechleiter, J.; Aguiar, R.; Dahia, P.] UTHSCSA, San Antonio, TX USA. [Aronin, N.; Sass, M.] UMass, Worcester, MA USA. [Schiavi, F.; Opocher, G.] Veneto Inst Oncol, Padua, Italy. [Toledo, R.; Toledo, S.] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Stiles, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Opocher, Giuseppe/F-3950-2014; Toledo, Rodrigo/N-4078-2013 OI Opocher, Giuseppe/0000-0002-9845-9623; Toledo, Rodrigo/0000-0003-3070-6795 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S1666 EP S1666 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400121 ER PT J AU Rao, RH Cunningham, CA Perreiah, PL AF Rao, R. H. Cunningham, C. A. Perreiah, P. L. TI Achieving Tight Glycemic Control in Critical Care without Precipitating Life-Threatening Hypoglycemia: The VA Pittsburgh Experience SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Rao, R. H.; Cunningham, C. A.; Perreiah, P. L.] VA Pittsburgh Healthcare Syst, Univ Dr Div, Pittsburgh, PA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S1685 EP S1685 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400140 ER PT J AU Shaw, ND Welt, CK Seminara, SB Martin, KA Au, MG Plummer, LC Hughes, VA Pitteloud, N Crowley, WF Hall, JE AF Shaw, N. D. Welt, C. K. Seminara, S. B. Martin, K. A. Au, M. G. Plummer, L. C. Hughes, V. A. Pitteloud, N. Crowley, W. F., Jr. Hall, J. E. TI Variability of the Reproductive Phenotype in Women with Congenital GnRH Deficiency. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Shaw, N. D.; Welt, C. K.; Seminara, S. B.; Martin, K. A.; Au, M. G.; Plummer, L. C.; Hughes, V. A.; Pitteloud, N.; Crowley, W. F., Jr.; Hall, J. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shaw, N. D.] Childrens Hosp Boston, Boston, MA USA. RI PITTELOUD, Nelly/K-2709-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S43 EP S43 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400043 ER PT J AU Stylopoulos, N Zhang, XB Brownell, AL Kaplan, LM AF Stylopoulos, N. Zhang, X. B. Brownell, A-L Kaplan, L. M. TI Melanocortin 4 Receptor Signaling Is Required for Weight Loss and Thermogenesis after Roux-En-Y Gastric Bypass in the Mouse SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Stylopoulos, N.; Zhang, X. B.; Brownell, A-L; Kaplan, L. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S2535 EP S2535 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400238 ER PT J AU Xu, J Jiang, J Lobie, PE Fuchs, SY Frank, SJ AF Xu, Jie Jiang, Jing Lobie, Peter E. Fuchs, Serge Y. Frank, Stuart J. TI Role of Prolactin Receptor in Growth Hormone Signaling in Human Breast Cancer Cells. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Xu, Jie; Jiang, Jing; Frank, Stuart J.] Univ Alabama, Birmingham, AL USA. [Lobie, Peter E.] Univ Auckland, Auckland 1, New Zealand. [Fuchs, Serge Y.] Univ Penn, Philadelphia, PA 19104 USA. [Frank, Stuart J.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S2492 EP S2492 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400199 ER PT J AU Yuen, KCJ Biller, BMK Legg, SE Rhoads, SA Dillard, TH Gurel, MH Chu, O Uwaifo, GI Koch, C Katznelson, L Cook, DM AF Yuen, K. C. J. Biller, B. M. K. Legg, S. E. Rhoads, S. A. Dillard, T. H. Gurel, M. H. Chu, O. Uwaifo, G. I. Koch, C. Katznelson, L. Cook, D. M. TI Clinical Characteristics of the Glucagon Stimulation Test (GST) in the Evaluation of Growth Hormone (GH) Reserve and Hypothalamic-Pituitary-Adrenal (HPA) Axis in Adults: A Multi-Centered US Experience SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Yuen, K. C. J.; Legg, S. E.; Rhoads, S. A.; Dillard, T. H.; Cook, D. M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Biller, B. M. K.; Gurel, M. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chu, O.; Katznelson, L.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Uwaifo, G. I.; Koch, C.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. RI Koch, Christian/A-4699-2008; Uwaifo, Gabriel/M-2361-2016 OI Koch, Christian/0000-0003-3127-5739; Uwaifo, Gabriel/0000-0002-6962-9304 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S1694 EP S1694 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400147 ER PT J AU Abreu, AP Noel, SD Xu, S Trarbach, EB Martin, C Sidis, Y Pitteloud, N Carroll, RS Mendonca, BB Latronico, AC Kaiser, UB AF Abreu, A. P. Noel, S. D. Xu, S. Trarbach, E. B. Martin, C. Sidis, Y. Pitteloud, N. Carroll, R. S. Mendonca, B. B. Latronico, A. C. Kaiser, U. B. TI The Functional Role of the First Intracellular Loop of Prokineticin Receptor 2. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Abreu, A. P.; Noel, S. D.; Xu, S.; Carroll, R. S.; Kaiser, U. B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Abreu, A. P.; Noel, S. D.; Xu, S.; Martin, C.; Sidis, Y.; Pitteloud, N.; Carroll, R. S.; Kaiser, U. B.] Harvard Univ, Sch Med, Boston, MA USA. [Abreu, A. P.; Trarbach, E. B.; Mendonca, B. B.; Latronico, A. C.] Univ Sao Paulo, BR-09500900 Sao Paulo, Brazil. [Martin, C.; Sidis, Y.; Pitteloud, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Mendonca, Berenice/C-2827-2012; Latronico, Ana Claudia/E-1198-2012; PITTELOUD, Nelly/K-2709-2014; Trarbach, Ericka/I-5395-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402281 ER PT J AU Ackerman, KE Davis, B Jacoby, L Tappen, M Misra, M AF Ackerman, K. E. Davis, B. Jacoby, L. Tappen, M. Misra, M. TI Total and Site-Specific Fat and Lean Mass as Predictors of Bone Density in Female Adolescent Athletes. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Ackerman, K. E.; Davis, B.; Jacoby, L.; Tappen, M.; Misra, M.] Harvard Univ, Sch Med, Boston, MA USA. [Ackerman, K. E.; Davis, B.; Jacoby, L.; Tappen, M.; Misra, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Misra, M.] MassGen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402739 ER PT J AU Anawalt, BD Hirano, L Hotaling, JM Walsh, TJ Shields, A Matsumoto, AM AF Anawalt, B. D. Hirano, L. Hotaling, J. M. Walsh, T. J. Shields, A. Matsumoto, A. M. TI Total Testosterone (TT) Measurement Is a Good Screening Test for Male Hypogonadism, but Should Not Be Used To Make a Definitive Biochemical Diagnosis. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Soc C1 [Anawalt, B. D.; Hirano, L.; Hotaling, J. M.; Walsh, T. J.; Shields, A.; Matsumoto, A. M.] Univ Washington, Seattle, WA 98195 USA. [Hirano, L.; Walsh, T. J.; Matsumoto, A. M.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402458 ER PT J AU Balasubramanian, R Hoang, X Dwyer, AA Sykiotis, GP Seminara, SB Pitteloud, N Crowley, WF AF Balasubramanian, R. Hoang, X. Dwyer, A. A. Sykiotis, G. P. Seminara, S. B. Pitteloud, N. Crowley, W. F., Jr. TI The "Fertile Eunuch Syndrome": Genetics and Natural History. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Soc C1 [Balasubramanian, R.; Hoang, X.; Dwyer, A. A.; Sykiotis, G. P.; Seminara, S. B.; Pitteloud, N.; Crowley, W. F., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402460 ER PT J AU Biller, BMK Ji, HJ Lee, S Savoy, C Popovic, V Coculescu, M Roemmler, J Popa, M Cook, DM Strasburger, CJ AF Biller, Beverly M. K. Ji, Hyi-Jeong Lee, Songmi Savoy, Conrad Popovic, Vera Coculescu, Mihail Roemmler, Josefine Popa, Mircea Cook, David M. Strasburger, Christian J. TI Twelve Months Efficacy and Safety of a Novel Once-a-Week Sustained Release rhGH (LB03002): A Phase III Study in Adults with GHD. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Biller, Beverly M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ji, Hyi-Jeong; Lee, Songmi] LG Life Scis Ltd, Seoul, South Korea. [Savoy, Conrad] BioPartners GmbH, Baar, Switzerland. [Popovic, Vera] Inst Endocrinol, Belgrade, Serbia. [Coculescu, Mihail; Popa, Mircea] CI Parhon, Bucharest, Romania. [Roemmler, Josefine] Univ Munich, Munich, Germany. [Cook, David M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402352 ER PT J AU Blincko, S Doran, EJ Weerakoon, A Ramp, JM Doss, RC Keevil, BG Wong, PY Sluss, PM AF Blincko, S. Doran, E. J. Weerakoon, A. Ramp, J. M. Doss, R. C. Keevil, B. G. Wong, P-Y Sluss, P. M. TI ARCHITECT (R) 2(nd) Generation Testosterone Assay, a Direct Immunoassay Capable of Accurate and Precise Measurements for Both Male and Female Specimens. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Soc ID MASS-SPECTROMETRY; HUMAN SERUM C1 [Blincko, S.] Abbott Diagnost, Wiesbaden, Germany. [Doran, E. J.; Weerakoon, A.] Abbott Diagnost, Dartford, Germany. [Ramp, J. M.; Doss, R. C.] Abbott Diagnost, Abbott Pk, IL USA. [Keevil, B. G.] Univ S Manchester Hosp, Manchester M20 8LR, Lancs, England. [Wong, P-Y] Toronto Gen Hosp, Toronto, ON, Canada. [Sluss, P. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403401 ER PT J AU Brar, M Knaub, L Watson, PA Reusch, JEB AF Brar, M. Knaub, L. Watson, P. A. Reusch, J. E. B. TI Oxidized LDL-Induced CREB Down-Regulation and Protein Oxidation in Vascular Smooth Muscle Cells. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Brar, M.; Knaub, L.; Watson, P. A.; Reusch, J. E. B.] Univ Colorado Denver, Aurora, CO USA. [Brar, M.; Watson, P. A.; Reusch, J. E. B.] Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403137 ER PT J AU Cardozo, CP Pan, J Wu, Y Bauman, WA Qin, W AF Cardozo, C. P. Pan, J. Wu, Y. Bauman, W. A. Qin, W. TI Anabolic Steroids Activate Calcineurin- NFAT Signaling in Denervated Muscle, and by This Mechanism Reduce Denervation Atrophy. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Cardozo, C. P.; Pan, J.; Wu, Y.; Bauman, W. A.; Qin, W.] James J Peters VA Med Ctr, Bronx, NY USA. [Cardozo, C. P.; Bauman, W. A.; Qin, W.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402005 ER PT J AU Chavan, NR Dwyer, AA Butler, PW Collins, MT Sykiotis, GP Keefe, KW Seminara, SB Plummer, L Crowley, WF Pitteloud, N AF Chavan, N. R. Dwyer, A. A. Butler, P. W. Collins, M. T. Sykiotis, G. P. Keefe, K. W. Seminara, S. B. Plummer, L. Crowley, W. F. Pitteloud, N. TI Male Functional Hypogonadotropic Hypogonadism (MFHH): A Distinct Clinical Entity?. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society ID AMENORRHEA C1 [Chavan, N. R.; Dwyer, A. A.; Sykiotis, G. P.; Keefe, K. W.; Seminara, S. B.; Plummer, L.; Crowley, W. F.; Pitteloud, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Butler, P. W.; Collins, M. T.] NIH, Bethesda, MD 20892 USA. RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; NR 4 TC 0 Z9 0 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402462 ER PT J AU Deng, LQ Jiang, J Yang, N Waters, MJ Hwa, V Frank, SJ AF Deng, Luqin Jiang, Jing Yang, Ning Waters, Michael J. Hwa, Vivian Frank, Stuart J. TI Evaluation of GH Receptor Dimerization Interface Mutants. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Deng, Luqin; Jiang, Jing; Frank, Stuart J.] Univ Alabama, Birmingham, AL USA. [Yang, Ning] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Waters, Michael J.] Univ Queensland, Brisbane, Qld, Australia. [Hwa, Vivian] Oregon Hlth & Scis Univ, Portland, OR USA. [Frank, Stuart J.] Birmingham VA Med Ctr, Birmingham, AL USA. RI waters, michael/C-9582-2014 NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403230 ER PT J AU Desai, NS Welt, CK AF Desai, N. S. Welt, C. K. TI Ovulatory Menstrual Cycles and Delayed Increase in Testosterone Levels in Women with PCOS Who Discontinue Hormonal Contraception. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Desai, N. S.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Welt, C. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402413 ER PT J AU Echchgadda, I Chang, TH Sabbah, A Bakri, I Chatterjee, B Bose, S AF Echchgadda, Ibtissam Chang, Te-Hung Sabbah, Ahmed Bakri, Imad Chatterjee, Bandana Bose, Santanu TI Growth Inhibition of Androgen-Dependent and Androgen-Refractive Prostate Tumor by the Oncolytic Respiratory Syncytial Virus. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Echchgadda, Ibtissam; Chang, Te-Hung; Sabbah, Ahmed; Bakri, Imad; Chatterjee, Bandana; Bose, Santanu] UTHSCSA, San Antonio, TX USA. [Chatterjee, Bandana] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402035 ER PT J AU Emanuelli, B Tseng, YH Macotela, Y Kahn, CR AF Emanuelli, B. Tseng, Y. H. Macotela, Y. Kahn, C. R. TI Unique Properties of the Insulin Receptor Substrates (IRS)-1 and IRS-2 To Mediate IGF-1 Signaling. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Emanuelli, B.; Tseng, Y. H.; Macotela, Y.; Kahn, C. R.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402134 ER PT J AU Gianetti, E Tusset, C Noel, S Au, MG Dwyer, AA Hughes, VA Abreu, AP Carroll, J Trarbach, E Silveira, LFG Costa, EMF De Mendonca, BB Castro, M Lofrano, A Hall, JE Bolu, E Ozata, M Quinton, R Amory, JK Stewart, SE Arlt, W Cole, TR Crowley, WF Kaiser, UB Latronico, AC Seminara, SB AF Gianetti, E. Tusset, C. Noel, S. Au, M. G. Dwyer, A. A. Hughes, V. A. Abreu, A. P. Carroll, J. Trarbach, E. Silveira, L. F. G. Costa, E. M. F. de Mendonca, B. B. de Castro, M. Lofrano, A. Hall, J. E. Bolu, E. Ozata, M. Quinton, R. Amory, J. K. Stewart, S. E. Arlt, W. Cole, T. R. Crowley, W. F. Kaiser, U. B. Latronico, A. C. Seminara, S. B. TI TAC3/TACR3 Mutations Reveal Preferential Activation of GnRH Release by Neurokinin B in Neonatal Life Followed by Reversal in Adulthood. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Gianetti, E.; Au, M. G.; Dwyer, A. A.; Hughes, V. A.; Hall, J. E.; Crowley, W. F.; Seminara, S. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tusset, C.; Trarbach, E.; Silveira, L. F. G.; Costa, E. M. F.; de Mendonca, B. B.; Latronico, A. C.] HCFMUSP, Sao Paulo, Brazil. [Noel, S.; Abreu, A. P.; Carroll, J.; Kaiser, U. B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [de Castro, M.] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, Brazil. [Lofrano, A.] Hosp Univ Brasilia, Brasilia, DF, Brazil. [Bolu, E.; Ozata, M.] Gulhane Mil Med Acad, Ankara, Turkey. [Quinton, R.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Amory, J. K.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Stewart, S. E.; Cole, T. R.] Birmingham Womens Hosp NHS Fdn Trust Edgbaston, Edgbaston, England. [Arlt, W.] Univ Birmingham, Birmingham, W Midlands, England. RI Mendonca, Berenice/C-2827-2012; Dwyer, Andrew/D-8099-2012; Latronico, Ana Claudia/E-1198-2012; Silveira, Leticia/D-3975-2014; Trarbach, Ericka/I-5395-2012 OI Dwyer, Andrew/0000-0002-7023-6794; NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401324 ER PT J AU Kaur, V Wood, J Hall, JL Thomas, MK AF Kaur, V. Wood, J. Hall, J. L. Thomas, M. K. TI Metabolic Consequences of TCF7L2 Deficiency in Mice. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Kaur, V.; Wood, J.; Thomas, M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wood, J.] Univ Minnesota, Minneapolis, MN USA. [Thomas, M. K.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401464 ER PT J AU Kawamori, D Liew, CW Kulkarni, RN AF Kawamori, D. Liew, C. W. Kulkarni, R. N. TI GLP-1 Compensates for Poor Proliferation of beta-Cells Lacking Insulin Receptors. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Kawamori, D.; Liew, C. W.; Kulkarni, R. N.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kawamori, D.; Liew, C. W.; Kulkarni, R. N.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402493 ER PT J AU Keefe, KW Hoang, XH Plummer, L Dwyer, AA Au, MG Sykiotis, GP Thambundit, A Raivio, T Jacobson-Dickman, E Quinton, R Hughes, VA Seminara, SB Hayes, FJ Hall, JE Crowley, WF Pitteloud, N AF Keefe, K. W. Hoang, X. H. Plummer, L. Dwyer, A. A. Au, M. G. Sykiotis, G. P. Thambundit, A. Raivio, T. Jacobson-Dickman, E. Quinton, R. Hughes, V. A. Seminara, S. B. Hayes, F. J. Hall, J. E. Crowley, W. F. Pitteloud, N. TI Genotype Prediction Based on Clinical Features of GnRH Deficiency. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society ID KALLMANN-SYNDROME; REPRODUCTIVE PHENOTYPES; MUTATIONS; KAL1 C1 [Keefe, K. W.; Hoang, X. H.; Plummer, L.; Dwyer, A. A.; Au, M. G.; Sykiotis, G. P.; Thambundit, A.; Raivio, T.; Jacobson-Dickman, E.; Hughes, V. A.; Seminara, S. B.; Hayes, F. J.; Hall, J. E.; Crowley, W. F.; Pitteloud, N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Quinton, R.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; NR 5 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402283 ER PT J AU Liew, CW Lock, JH Maas, RL Kulkarni, RN AF Liew, C. W. Lock, J. H. Maas, R. L. Kulkarni, R. N. TI Deciphering Protein Codes That Are Essential for Maturation of Pancreatic Islets. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Liew, C. W.; Lock, J. H.; Kulkarni, R. N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Maas, R. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401462 ER PT J AU Liu, XH Pan, JP Wu, Y Qin, WP Bauman, WA Cardozo, C AF Liu, Xin-Hua Pan, Jiangping Wu, Yong Qin, Weiping Bauman, William A. Cardozo, Christopher TI Nandrolone-Induced Nuclear Translocation of Myo-D in Denervated Rat Skeletal Muscle Associated with Induction of Wnt- and Inhibition of Notch-Signaling Pathways SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Liu, Xin-Hua; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher] James J Peter VA Med Ctr, Bronx, NY USA. [Liu, Xin-Hua; Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401040 ER PT J AU Liu, ZJ Bastepe, M AF Liu, Z. J. Bastepe, M. TI The alpha-Subunit of the Stimulatory G Protein (Gs alpha) and Its Imprinted Variants XL alpha s/XXL alpha s Are Trafficked into Distinct Subcellular Compartments upon Activation. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Liu, Z. J.; Bastepe, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401116 ER PT J AU Lo, J Abbara, S Rocha-Filho, JA Shturman, L Wei, J Grinspoon, SK AF Lo, J. Abbara, S. Rocha-Filho, J. A. Shturman, L. Wei, J. Grinspoon, S. K. TI Increased Epicardial Fat Volume in HIV-Infected Men and Relationships to Body Composition and Metabolic Parameters. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Lo, J.; Abbara, S.; Rocha-Filho, J. A.; Shturman, L.; Wei, J.; Grinspoon, S. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401427 ER PT J AU Lodish, MB Kim, SY Janeway, K Ball, ER Raygada, M Huynh, T Faucz, F Horvath, A Pacak, K Carney, JA Gaal, J Rustin, P Gimenez-Roqueplo, A Helman, L Stratakis, CA AF Lodish, M. B. Kim, S. Y. Janeway, K. Ball, E. R. Raygada, M. Huynh, T. Faucz, F. Horvath, A. Pacak, K. Carney, J. A. Gaal, J. Rustin, P. Gimenez-Roqueplo, A. Helman, L. Stratakis, C. A. TI Succinate Dehydrogenase (SDH) Mutations in Patients with "Wild-Type" (Non-KIT, Non-PDGFRA-Mutated) Gastrointestinal Sarcomas. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society ID STROMAL TUMORS C1 [Lodish, M. B.; Kim, S. Y.; Ball, E. R.; Raygada, M.; Huynh, T.; Faucz, F.; Horvath, A.; Pacak, K.; Helman, L.; Stratakis, C. A.] NIH, Bethesda, MD 20892 USA. [Janeway, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Carney, J. A.] Mayo Clin, Rochester, MN USA. [Gaal, J.] Univ Med Ctr, Rotterdam, Netherlands. [Rustin, P.] Hosp Robert Debre, Paris, France. [Gimenez-Roqueplo, A.] Paris Descartes Univ, Paris, France. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402094 ER PT J AU Luque, RM Cordoba-Chacon, J Lin, Q Kahn, CR Koch, L Bruning, JC Kineman, RD AF Luque, R. M. Cordoba-Chacon, J. Lin, Q. Kahn, C. R. Koch, L. Bruning, J. C. Kineman, R. D. TI Use of the Cre-loxP System To Dissect out the Individual Roles IGF-I Receptors (IGFIR) and Insulin Receptors (INSR) Play in Mediating Somatotrope Function, In Vitro and In Vivo. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society ID GROWTH C1 [Luque, R. M.; Lin, Q.; Kineman, R. D.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Luque, R. M.; Cordoba-Chacon, J.; Lin, Q.; Kineman, R. D.] Univ Illinois, Chicago, IL USA. [Luque, R. M.; Cordoba-Chacon, J.] Univ Cordoba, Cordoba, Spain. [Luque, R. M.; Cordoba-Chacon, J.] Inst Maimonides Invest Biomed Cordoba, Cordoba, Spain. [Luque, R. M.; Cordoba-Chacon, J.] CIBER Fisiopatol Obesidad & Nutr, Cordoba, Spain. [Kahn, C. R.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Koch, L.; Bruning, J. C.] Ctr Mol Med, Cologne, Germany. [Koch, L.; Bruning, J. C.] Univ Cologne, Inst Genet, D-5000 Cologne, Germany. RI Kineman, Rhonda/H-2221-2011 OI Kineman, Rhonda/0000-0001-7322-1152 NR 4 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403240 ER PT J AU Mediwala, SN Sun, H Marcelli, M AF Mediwala, S. N. Sun, H. Marcelli, M. TI Truncated Androgen Receptor Gene Expression Is Regulated by Androgen. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Mediwala, S. N.; Sun, H.; Marcelli, M.] Baylor Coll Med, Houston, TX 77030 USA. Michael DeBakey Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402009 ER PT J AU Mody, K Kogai, T Brent, G AF Mody, K. Kogai, T. Brent, G. TI Retinoic Acid Regulation of the Thyroid Hormone Transporter, Monocarboxylate Transporter 8 (Mct8), in Neural Differentiation. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Mody, K.; Kogai, T.; Brent, G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Mody, K.; Kogai, T.; Brent, G.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402581 ER PT J AU Noel, SD Abreu, AP Xu, S Gianetti, E Tusset, C Latronica, AC Seminara, SB Carroll, R Kaiser, UB AF Noel, S. D. Abreu, A. P. Xu, S. Gianetti, E. Tusset, C. Latronica, A. C. Seminara, S. B. Carroll, R. Kaiser, U. B. TI TACR3 Mutations Identified in Patients with Idiopathic Hypogonadotropic Hypogonadism Interfere with NK3R Function through Several Distinct Mechanisms. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Noel, S. D.; Abreu, A. P.; Xu, S.; Carroll, R.; Kaiser, U. B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Noel, S. D.; Abreu, A. P.; Xu, S.; Carroll, R.; Kaiser, U. B.] Harvard Univ, Sch Med, Boston, MA USA. [Gianetti, E.; Seminara, S. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tusset, C.; Latronica, A. C.] Univ Sao Paulo, BR-09500900 Sao Paulo, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402282 ER PT J AU Ooi, M McMillin, DW Kotoula, V Negri, J Delmore, J Mitsiades, CS Anderson, KC Mitsiades, N AF Ooi, Melissa McMillin, Douglas W. Kotoula, Vassiliki Negri, Joseph Delmore, Jake Mitsiades, Constantine S. Anderson, Kenneth C. Mitsiades, Nicholas TI In Vitro and In Vivo Anticancer Effects of Metformin and the AMP-Activated Protein Kinase (AMPK) Activator 5-Aminoimidazole-4-Carboxamide-1-beta-D-Ribofuranoside (AICAR): Enhanced Activity in the Presence of the Local Microenvironment, Activated Akt/mTOR Pathway and Exposure to Glycolysis Inhibitors. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Ooi, Melissa; McMillin, Douglas W.; Negri, Joseph; Delmore, Jake; Mitsiades, Constantine S.; Anderson, Kenneth C.; Mitsiades, Nicholas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kotoula, Vassiliki] Aristotle Univ Thessaloniki, Sch Med, GR-54006 Thessaloniki, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401523 ER PT J AU Page, ST Lin, DW Mostaghel, EA Marck, B Wright, JL Amory, JK Matsumoto, AM AF Page, S. T. Lin, D. W. Mostaghel, E. A. Marck, B. Wright, J. L. Amory, J. K. Matsumoto, A. M. TI Exogenous Dihydrotestosterone Does Not Increase Intraprostatic Dihydrotestosterone Concentrations in Healthy Men. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Page, S. T.; Lin, D. W.; Mostaghel, E. A.; Wright, J. L.; Amory, J. K.; Matsumoto, A. M.] Univ Washington, Sch Med, Seattle, WA USA. [Marck, B.; Matsumoto, A. M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401387 ER PT J AU Pallais, JC Kemp, EH Bergwitz, C Slovik, DM Weetman, AP Brown, EM AF Pallais, J. C. Kemp, E. H. Bergwitz, C. Slovik, D. M. Weetman, A. P. Brown, E. M. TI Acquired Hypocalciuric Hypercalcemia Unresponsive to Glucocorticoid Therapy in a Patient with Autoantibodies Against the Calcium-Sensing Receptor. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Pallais, J. C.; Bergwitz, C.; Slovik, D. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kemp, E. H.; Weetman, A. P.] Univ Sheffield, Sch Med, Sheffield, S Yorkshire, England. [Brown, E. M.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403181 ER PT J AU Petersenn, S Newell-Price, J Findling, JW Gu, F Maldonado, M Sen, K Salgado, LR Colao, A Biller, BMK AF Petersenn, S. Newell-Price, J. Findling, J. W. Gu, F. Maldonado, M. Sen, K. Salgado, L. R. Colao, A. Biller, B. M. K. TI Baseline Characteristics and Urine Free Cortisol (UFC) Variability of 162 Patients Enrolled in a Randomized, Double-Blind Phase III Study Assessing the Efficacy and Safety of Pasireotide (SOM230) in Patients with Cushing's Disease. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Petersenn, S.] ENDOC Ctr Endocrine Tumors, Hamburg, Germany. [Newell-Price, J.] Univ Sheffield, Sheffield, S Yorkshire, England. [Findling, J. W.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gu, F.] Beijing Union Med Coll Hosp, Beijing, Peoples R China. [Maldonado, M.] Novartis Pharma AG, Basel, Switzerland. [Sen, K.] Novartis Pharma Corp, Florham Pk, NJ USA. [Salgado, L. R.] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Colao, A.] Univ Naples Federico 2, Naples, Italy. [Biller, B. M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401272 ER PT J AU Pham, AN Datta, SK Weber, TJ Walter, LC Colon-Emeric, CS AF Pham, A. N. Datta, S. K. Weber, T. J. Walter, L. C. Colon-Emeric, C. S. TI Cost-Effectiveness of Oral Bisphosphonates for Osteoporosis at Different Ages and Levels of Life Expectancy. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Pham, A. N.; Weber, T. J.] Duke Univ, Med Ctr, Durham, NC USA. [Datta, S. K.; Colon-Emeric, C. S.] Durham VA Med Ctr, Durham, NC USA. [Walter, L. C.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403170 ER PT J AU Plant, TM Seminara, SB Ramaswwamy, S AF Plant, T. M. Seminara, S. B. Ramaswwamy, S. TI Neurokinin B Receptor (NK3R) Activation Stimulates Acute GnRH Dependent LH Release in the Juvenile Male Rhesus Monkey (Macaca Mulatta) but, in Contrast to Repetitive Kisspeptin Receptor Activation, Does Not Sustain LH Secretion. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Plant, T. M.; Ramaswwamy, S.] Univ Pittsburgh, Pittsburgh, PA USA. [Seminara, S. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402271 ER PT J AU Qian, WJ Zhou, JY Liew, CW Petyuk, VA Moore, RJ Camp, DG Kulkarni, RN Smith, RD AF Qian, W. J. Zhou, J. Y. Liew, C. W. Petyuk, V. A. Moore, R. J. Camp, D. G. Kulkarni, R. N. Smith, R. D. TI Proteomics Profiling of Putative Growth Factors in Mouse Plasma and Pancreatic Islets by Mass Spectrometry. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Qian, W. J.; Zhou, J. Y.; Petyuk, V. A.; Moore, R. J.; Camp, D. G.; Smith, R. D.] Pacific NW Natl Lab, Richland, WA 99352 USA. [Liew, C. W.; Kulkarni, R. N.] Joslin Diabet Ctr, Boston, MA 02215 USA. RI Zhou, Jian-Ying/D-1308-2012; Smith, Richard/J-3664-2012 OI Smith, Richard/0000-0002-2381-2349 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402136 ER PT J AU Qin, WP Peng, YZ Sun, L Pan, JP Liu, XA Wu, Y Zaidi, M Bauman, WA Cardozo, C AF Qin, Weiping Peng, Yuanzhen Sun, Li Pan, Jiangping Liu, Xuan Wu, Yong Zaidi, Mone Bauman, William A. Cardozo, Christopher TI Anabolic Steroids Slow Hindlimb Bone Loss in a Rat Model of Osteoporosis Due to Spinal Cord Injury: The Role of Wnt Signaling Pathway. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Qin, Weiping; Pan, Jiangping; Wu, Yong; Bauman, William A.; Cardozo, Christopher] James J Peters VA Med Ctr, Bronx, NY USA. [Qin, Weiping; Peng, Yuanzhen; Sun, Li; Liu, Xuan; Zaidi, Mone; Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, New York, NY USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402196 ER PT J AU Shaw, ND Seminara, SB Welt, CK Martin, KA Au, MG Plummer, L Hughes, VA Crowley, WF Pittelloud, N Hall, JE AF Shaw, N. D. Seminara, S. B. Welt, C. K. Martin, K. A. Au, M. G. Plummer, L. Hughes, V. A. Crowley, W. F., Jr. Pittelloud, N. Hall, J. E. TI Genetic Profile of a Large Cohort of Women with GnRH Deficiency Reveals Genetic Heterogeneity and a Role for KAL-1.. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Shaw, N. D.; Seminara, S. B.; Welt, C. K.; Martin, K. A.; Au, M. G.; Plummer, L.; Hughes, V. A.; Crowley, W. F., Jr.; Pittelloud, N.; Hall, J. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shaw, N. D.] Childrens Hosp Boston, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402277 ER PT J AU Swearingen, B Boulanger, L Wu, N Chen, S Pulgar, S Biller, BMK AF Swearingen, B. Boulanger, L. Wu, N. Chen, S. Pulgar, S. Biller, B. M. K. TI Healthcare Costs of Cushing's Disease from the US Commercially-Insured Perspective. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Swearingen, B.; Biller, B. M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boulanger, L.; Wu, N.; Chen, S.] Abt Biopharma Solut, Lexington, MA USA. [Pulgar, S.] Novartis Pharm, Florham Pk, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401285 ER PT J AU Tritos, NA Greenspan, SL King, D Hamrahian, AH Cook, DM Jonsson, PJ Wajnrajch, MP Koltowska-Haggstrom, M Biller, BMK AF Tritos, N. A. Greenspan, S. L. King, D. Hamrahian, A. H. Cook, D. M. Jonsson, P. J. Wajnrajch, M. P. Koltowska-Haggstrom, M. Biller, B. M. K. TI Predictors of Bone Mineral Density (BMD) Response to Growth Hormone (GH) Replacement in Adults with GH Deficiency (GHD) - A KIMS (Pfizer International Metabolic Database) Analysis. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Tritos, N. A.; Biller, B. M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenspan, S. L.] Univ Pittsburgh, Pittsburgh, PA USA. [King, D.; Wajnrajch, M. P.] Pfizer Inc, New York, NY USA. [Jonsson, P. J.; Koltowska-Haggstrom, M.] Pfizer Endocrine Care, Sollentuna, Sweden. [Cook, D. M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Hamrahian, A. H.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402331 ER PT J AU Tusset, C Gianetti, E Trarbach, EB Silveira, LFG Cukier, P Kaiser, UB Mendonca, BB Seminara, SB Latronico, AC AF Tusset, C. Gianetti, E. Trarbach, E. B. Silveira, L. F. G. Cukier, P. Kaiser, U. B. Mendonca, B. B. Seminara, S. B. Latronico, A. C. TI Mutational Analysis of TAC3 and TACR3 Genes in Children with Idiopathic Central Precocious Puberty. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Tusset, C.; Trarbach, E. B.; Silveira, L. F. G.; Cukier, P.; Mendonca, B. B.; Latronico, A. C.] Univ Sao Paulo, Fac Med, Hosp Clins, Sao Paulo, Brazil. [Gianetti, E.; Seminara, S. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kaiser, U. B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kaiser, U. B.] Harvard Univ, Sch Med, Boston, MA USA. RI Mendonca, Berenice/C-2827-2012; Latronico, Ana Claudia/E-1198-2012; Silveira, Leticia/D-3975-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401691 ER PT J AU Wu, Y Bauman, WA Blitzer, R Cardozo, C AF Wu, Y. Bauman, W. A. Blitzer, R. Cardozo, C. TI Testosterone-Induced Hypertrophy of L6 Myoblasts Is Dependent upon mTOR and Erk 1/2 SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Wu, Y.; Bauman, W. A.; Cardozo, C.] James J Peters VA Med Ctr, Bronx, NY USA. [Bauman, W. A.; Blitzer, R.; Cardozo, C.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401039 ER PT J AU Yang, JJ DeGuillebon, AME Seminara, SB AF Yang, J. J. DeGuillebon, A. M. E. Seminara, S. B. TI Differences in Reproductive Phenotypes between C57BL/6 and Sv129 Mice Carrying Mutations in Kiss1 and Gpr54: Evidence for Modifier Genes Affecting Reproduction. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Yang, J. J.; DeGuillebon, A. M. E.; Seminara, S. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401321 ER PT J AU Zhang, Y Gan, YJ Huang, Y Jiang, J Frank, SJ AF Zhang, Yue Gan, Yujun Huang, Yao Jiang, Jing Frank, Stuart J. TI Deletion of IGF-1 Receptor in a Human Prostate Cancer Cell Line Reduces GH-Induced JAK2 and STAT5 Phosphorylation. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Zhang, Yue; Gan, Yujun; Huang, Yao; Jiang, Jing; Frank, Stuart J.] Univ Alabama, Birmingham, AL USA. St Josephs Hosp, Phoenix, AZ USA. Med Ctr, Phoenix, AZ USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403233 ER PT J AU Gordon, FE Nutt, CL Cheunsuchon, P Nakayama, Y Provencher, KA Rice, KA Zhou, YL Zhang, X Klibanski, A AF Gordon, Francesca E. Nutt, Catherine L. Cheunsuchon, Pornsuk Nakayama, Yuki Provencher, Katelyn A. Rice, Kimberley A. Zhou, Yunli Zhang, Xun Klibanski, Anne TI Increased Expression of Angiogenic Genes in the Brains of Mouse Meg3-Null Embryos SO ENDOCRINOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NONFUNCTIONING PITUITARY-ADENOMAS; RECEPTOR TYROSINE KINASE; FOCAL ADHESION KINASE; IMPRINTED GENE; PROMOTER REGION; NONCODING RNA; HES GENES; VEGF; MEG3 AB Maternally expressed gene 3 (MEG3) is a noncoding RNA highly expressed in the normal human brain and pituitary. Expression of MEG3 is lost in gonadotroph-derived clinically nonfunctioning pituitary adenomas. Meg3 knockout mice were generated to identify targets and potential functions of this gene in embryonic development and tumorigenesis. Gene expression profiles were compared in the brains of Meg3-null embryos and wild-type littermate controls using microarray analysis. Microarray data were analyzed with GeneSifter, which uses Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology classifications to identify signaling cascades and functional categories of interest within the dataset. Differences were found in signaling pathways and ontologies related to angiogenesis between wild-type and knockout embryos. Quantitative RTPCR and immunohistological staining showed increased expression of some Vascular Endothelial Growth Factor pathway genes and increased cortical microvessel density in the Meg3-null embryos. In conclusion, Meg3 may play an important role in control of vascularization in the brain and may function as a tumor suppressor in part by inhibiting angiogenesis. (Endocrinology 151: 2443-2452, 2010) C1 [Gordon, Francesca E.; Cheunsuchon, Pornsuk; Nakayama, Yuki; Provencher, Katelyn A.; Zhou, Yunli; Zhang, Xun; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Nutt, Catherine L.; Provencher, Katelyn A.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org RI Nutt, Catherine/K-8794-2012; Cheunsuchon, Pornsuk/O-7915-2015 OI Cheunsuchon, Pornsuk/0000-0001-8851-3553 FU National Institutes of Health [DK40947, UL1 RR025758, F32DK09218]; Guthart Family Foundation; Jarislowsky Foundation FX This work was supported in part by National Institutes of Health Grants DK40947, UL1 RR025758, and F32DK09218, the Guthart Family Foundation, and the Jarislowsky Foundation. NR 54 TC 54 Z9 58 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 JUN PY 2010 VL 151 IS 6 BP 2443 EP 2452 DI 10.1210/en.2009-1151 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 599XY UT WOS:000277948800007 PM 20392836 ER PT J AU Liu, PF Demple, B AF Liu, Pingfang Demple, Bruce TI DNA Repair in Mammalian Mitochondria: Much More Than We Thought? SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE oxidative DNA damage; nucleases; base excision repair; mismatch repair; recombination ID BASE EXCISION-REPAIR; DIFFERENTIAL INTRACELLULAR-LOCALIZATION; MTDNA CONTROL-REGION; DOUBLE-STRAND BREAKS; MUTY HOMOLOG HMYH; ENDONUCLEASE-G; POLYMERASE-GAMMA; OXIDATIVE STRESS; IRRADIATED DNA; HUMAN-CELLS AB For many years, the repair of most damage in mitochondrial DNA (mtDNA) was thought limited to short-patch base excision repair (SP-BER), which replaces a single nucleotide by the sequential action of DNA glycosylases, an apurinic/apyrimidinic (AP) endonuclease, the mitochondrial DNA polymerase gamma, an abasic lyase activity, and mitochondria! DNA ligase. However, the likely array of lesions inflicted on mtDNA by oxygen radicals and the possibility of replication errors and disruptions indicated that such a restricted repair repertoire would be inadequate. Recent studies have considerably expanded our knowledge of mtDNA repair to include long-patch base excision repair (LP-BER), mismatch repair, and homologous recombination and nonhomologous end-joining. In addition, elimination of mutagenic 8-oxodeoxyguanosine triphosphate (8-oxodGTP) helps prevent cell death due to the accumulation of this oxidation product in mtDNA. Although it was suspected for many years that irreparably damaged mtDNA might be targeted for degradation, only recently was clear evidence provided for this hypothesis. Therefore, multiple DNA repair pathways and controlled degradation of mtDNA function together to maintain the integrity of mitochondrial genome. Environ. Mol. Mutagen. 51:417-426, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Demple, Bruce] SUNY Stony Brook, Hlth Sci Ctr, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. [Liu, Pingfang] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Demple, B (reprint author), SUNY Stony Brook, Hlth Sci Ctr, Dept Pharmacol Sci, BST8-140, Stony Brook, NY 11794 USA. EM bruce@pharm.stonybrook.edu FU NIH [R01 GM040000]; NCI [T32 CA009078] FX Work in the author's laboratory was supported by NIH grant R01 GM040000 (to B.D.); P.L. was supported by an NCI training grant in Radiation Biology (T32 CA009078). The authors are grateful to Dr. William C. Copeland for generously supplying Figure 2 to be reprinted here. NR 103 TC 89 Z9 93 U1 3 U2 17 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUN PY 2010 VL 51 IS 5 BP 417 EP 426 DI 10.1002/em.20576 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 614GI UT WOS:000279043000007 PM 20544882 ER PT J AU Wright, RO Schwartz, J Wright, RJ Bollati, V Tarantini, L Park, SK Hu, H Sparrow, D Vokonas, P Baccarelli, A AF Wright, Robert O. Schwartz, Joel Wright, Rosalind J. Bollati, Valentina Tarantini, Letizia Park, Sung Kyun Hu, Howard Sparrow, David Vokonas, Pantel Baccarelli, Andrea TI Biomarkers of Lead Exposure and DNA Methylation within Retrotransposons SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE aging; DNA methylation; epigenetics; lead; metals ID X-RAY-FLUORESCENCE; OXIDATIVE STRESS; LEUKOCYTE DNA; BONE LEAD; IN-VIVO; TOXICITY; HYPOMETHYLATION; PROMOTER; DISEASE; WOMEN AB BACKGROUND: DNA methylation is an epigenetic mark that regulates gene expression. Changes in DNA methylation within white blood cells may result from cumulative exposure to environmental metals such as lead. Bone lead, a marker of cumulative exposure, may therefore better predict DNA methylation than does blood lead. OBJECTIVE: In this study we compared associations between lead biomarkers and DNA methylation. METHODS: We measured global methylation in participants of the Normative Aging Study (all men) who had archived DNA samples. We measured patella and tibia lead levels by K-X-Ray fluorescence and blood lead by atomic absorption spectrophotometry. DNA samples from blood were used to determine global methylation averages within CpG islands of long interspersed nuclear elements-1 (LINE-1) and Mu retrotransposons. A mixed-effects model using repeated measures of Mu or LINE-1 as the dependent variable and blood/bone lead (tibia or patella in separate models) as the primary exposure marker was fit to the data. RESULTS: Overall mean global methylation (+/- SD) was 26.3 +/- 1.0 as measured by Alu and 76.8 +/- 1.9 as measured by LINE-1. In the mixed-effects model, patella lead levels were inversely associated with LINE-1 (beta = -0.25; p < 0.01) but not Alu (beta = -0.03; p = 0.4). Tibia lead and blood lead did not predict global methylation for either Alu or LINE-1. CONCLUSION: Patella lead levels predicted reduced global DNA methylation within LINE-1 elements. The association between lead exposure and LINE-1 DNA methylation may have implications for the mechanisms of action of lead on health outcomes, and also suggests that changes in DNA methylation may represent a biomarker of past lead exposure. C1 [Wright, Robert O.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr, Boston, MA 02215 USA. [Wright, Robert O.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pediat, Boston, MA 02215 USA. [Wright, Rosalind J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02215 USA. [Bollati, Valentina; Tarantini, Letizia; Baccarelli, Andrea] Mangiagalli & Regina Elena Fdn, IRCCS Maggiore Policlin Hosp, Dept Occupat & Environm Hlth, Lab Environm Epigenet, Milan, Italy. [Bollati, Valentina; Tarantini, Letizia; Baccarelli, Andrea] Univ Milan, Milan, Italy. [Park, Sung Kyun; Hu, Howard] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Sparrow, David; Vokonas, Pantel] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Sparrow, David; Vokonas, Pantel] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. RP Wright, RO (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr, 3rd Floor E,401 Pk Dr, Boston, MA 02215 USA. EM rowright@hsph.harvard.edu OI Baccarelli, Andrea/0000-0002-3436-0640; Hu, Howard/0000-0002-3676-2707; Bollati, Valentina/0000-0002-0370-9598 FU U.S. Department of Veterans Affairs; National Institutes of Health [R01ES015172, ES014663, R01ES005257, R01ES013744, K23ES000381]; Grass Foundation, Newton, MA, USA FX The Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Boston, MA, USA. This study was also supported by grants R01ES015172, ES014663, R01ES005257, R01ES013744, K23ES000381, and P30ES00002 from the National Institutes of Health; and by the Leaves of Grass Foundation, Newton, MA, USA. NR 51 TC 91 Z9 95 U1 1 U2 21 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2010 VL 118 IS 6 BP 790 EP 795 DI 10.1289/ehp.0901429 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 608NP UT WOS:000278591300023 PM 20064768 ER PT J AU Weuve, J Hauser, R Calafat, AM Missmer, SA Wise, LA AF Weuve, Jennifer Hauser, Russ Calafat, Antonia M. Missmer, Stacey A. Wise, Lauren A. TI Association of Exposure to Phthalates with Endometriosis and Uterine Leiomyomata: Findings from NHANES, 1999-2004 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE dibutyl phthalate; di(2-ethylhexyl) phthalate; endometriosis; leiomyomata; monobenzyl phthalate; monobutyl phthalate; monoethyl phthalate; mono(2-ethyl-5-hydroxyhexyl) phthalate; mono(2-ethyl-5-oxohexyl) phthalate; mono(2-ethylhexyl) phthalate ID TANDEM MASS-SPECTROMETRY; BUTYL BENZYL PHTHALATE; RAT GRANULOSA-CELLS; UNITED-STATES; QUANTITATIVE DETECTION; PREMENOPAUSAL WOMEN; CYCLING RATS; DI-(2-ETHYLHEXYL) PHTHALATE; SUPPRESSES ESTRADIOL; PSEUDOPREGNANT RATS AB BACKGROUND: Phthalates are ubiquitous chemicals used in consumer products. Some phthalates are reproductive toxicants in experimental animals, but human data are limited. OBJECTIVE: We conducted a cross-sectional study of urinary phthalate metabolite concentrations in relation to self-reported history of endometriosis and uterine leiomyomata among 1,227 women 20-54 years of age from three cycles of the National Health and Nutrition Examination Survey (NHANES), 1999-2004. METHODS: We examined four phthalate metabolites: mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monobenzyl phthalate (MBzP). From the last two NHANES cycles, we also examined mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: Eighty-seven (7%) and 151 (12%) women reported diagnoses of endometriosis and leiomyomata, respectively. The ORs comparing the highest versus lowest three quartiles of urinary MBP were 1.36 (95% CI, 0.77-2.41) for endometriosis, 1.56 (95% CI, 0.93-2.61) for leiomyomata, and 1.71 (95% CI, 1.07-2.75) for both conditions combined. The corresponding ORs for MEHP were 0.44 (95% CI, 0.19-1.02) for endometriosis, 0.63 (95% CI, 0.35-1.12) for leiomyomata, and 0.59 (95% CI, 0.37-0.95) for both conditions combined. Findings for MEHHP and MEOHP agreed with findings for MEHP with respect to endometriosis only. We observed Mill associations for MEP and MBzP. Associations were similar when we excluded women diagnosed > 7 years before their NHANES evaluation. CONCLUSION: The positive associations for MBP and inverse associations for MEHP in relation to endometriosis and leiomyomata warrant investigation in prospective studies. C1 [Weuve, Jennifer] Rush Univ, Med Ctr, Dept Internal Med, Rush Inst Healthy Aging, Chicago, IL 60612 USA. [Weuve, Jennifer; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Androl Lab, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. [Hauser, Russ] Massachusetts Gen Hosp, Vitro Fertilizat Unit, Boston, MA 02114 USA. [Calafat, Antonia M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Missmer, Stacey A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Med, Boston, MA 02115 USA. [Missmer, Stacey A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. [Missmer, Stacey A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wise, Lauren A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. RP Weuve, J (reprint author), Rush Univ, Med Ctr, Dept Internal Med, Rush Inst Healthy Aging, 645 W Jackson Blvd,Suite 675, Chicago, IL 60612 USA. EM Jennifer_Weuve@rush.edu OI Wise, Lauren/0000-0003-2138-3752 NR 67 TC 62 Z9 64 U1 2 U2 18 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2010 VL 118 IS 6 BP 825 EP 832 DI 10.1289/ehp.0901543 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 608NP UT WOS:000278591300028 PM 20185384 ER PT J AU Karakis, I Cole, AJ Montouris, GD Tsiakiri, A Piperidou, C AF Karakis, I Cole, A. J. Montouris, G. D. Tsiakiri, A. Piperidou, C. TI THE BURDEN AMONG CAREGIVERS OF PATIENTS WITH EPILEPSY: IMPACT AND PREDICTORS SO EPILEPSIA LA English DT Meeting Abstract CT 9th European Congress on Epileptology CY JUN 27-JUL 01, 2010 CL Rhodes, GREECE C1 [Karakis, I; Cole, A. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Montouris, G. D.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02215 USA. [Tsiakiri, A.; Piperidou, C.] Democritus Univ, Univ Hosp Alexandroupolis, Alexandroupolis, Greece. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2010 VL 51 SU 4 SI SI BP 20 EP 20 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 619BW UT WOS:000279404600063 ER PT J AU Paul, E Conant, KD Dunne, IE Pfeifer, HH Lyczkowski, DA Linshaw, MA Thiele, EA AF Paul, Elahna Conant, Kerry D. Dunne, Irie E. Pfeifer, Heidi H. Lyczkowski, David A. Linshaw, Michael A. Thiele, Elizabeth A. TI Urolithiasis on the ketogenic diet with concurrent topiramate or zonisamide therapy SO EPILEPSY RESEARCH LA English DT Article DE Ketogenic diet; Topiramate; Zonisamide; Kidney stones; Epilepsy ID METABOLIC-ACIDOSIS; PEDIATRIC EPILEPSY; POTASSIUM CITRATE; SODIUM-CITRATE; KIDNEY-STONES; RISK-FACTORS; CHILDREN; EFFICACY; NEPHROLITHIASIS; SAFETY AB Children with refractory epilepsy who are co-treated with the ketogenic diet (KD) and carbonic anhydrase inhibitor (CA-I) anti-epileptic medications including topiramate (TPM) and zonisamide (ZNS) are at risk for urolithiasis. Retrospective chart review of all children treated with ketogenic therapy at our institution was performed in order to estimate the minimal risk of developing signs or symptoms of stone disease. Children (N=93) were classified into groups according to KD +/- CA-I co-therapy. Fourteen patients had occult hematuria or worse, including 6 with radiologically confirmed stones. Three of 6 calculi developed in the KD + ZNS group of 17 patients who were co-treated for a cumulative total of 97 months (3.1 stones per 100 patient months). One confirmed stone was in the KD + TPM group of 22 children who were co-treated for a cumulative total of 263 months (0.4 stones per 100 patient months). All six patients had at least three of five biochemical risk factors including metabolic acidosis, concentrated urine, acid urine, hypercalciuria and hypocitraturia. Standard of care interventions to minimize hypercalciuria, crystalluria and stone formation used routinely by pediatric nephrologists should also be prescribed by neurologists treating patients with combination anti-epileptic therapy. Non-fasting KD initiation, fluid liberalization, potassium citrate prophylaxis as well as regular laboratory surveillance are indicated in this high risk population. (C) 2010 Elsevier B.V. All rights reserved. C1 [Paul, Elahna; Linshaw, Michael A.] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Conant, Kerry D.; Dunne, Irie E.; Pfeifer, Heidi H.; Lyczkowski, David A.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. [Conant, Kerry D.; Dunne, Irie E.; Pfeifer, Heidi H.; Lyczkowski, David A.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Ketogen Diet Clin, Dept Neurol, Boston, MA 02114 USA. [Conant, Kerry D.; Dunne, Irie E.; Pfeifer, Heidi H.; Lyczkowski, David A.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Pediat, Ketogen Diet Clin, Boston, MA 02114 USA. RP Paul, E (reprint author), Massachusetts Gen Hosp Children, YAW 6C,55 Fruit St, Boston, MA 02114 USA. EM epaul@partners.org FU NINDS NIH HHS [P01 NS024279, P01 NS024279-23] NR 36 TC 16 Z9 16 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD JUN PY 2010 VL 90 IS 1-2 BP 151 EP 156 DI 10.1016/j.eplepsyres.2010.04.005 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 621FK UT WOS:000279560700019 PM 20466520 ER PT J AU Sasada, T Komatsu, N Suekane, S Yamada, A Noguchi, M Itoh, K AF Sasada, Tetsuro Komatsu, Nobukazu Suekane, Shigetaka Yamada, Akira Noguchi, Masanori Itoh, Kyogo TI Overcoming the hurdles of randomised clinical trials of therapeutic cancer vaccines SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE Cancer vaccine; Randomised clinical trial; Immune response; Personalisation ID PERSONALIZED PEPTIDE VACCINATION; PROSTATE-CANCER; IMMUNOLOGICAL EVALUATION; T-CELLS; SURVIVAL; IMMUNOTHERAPY; LYMPHOCYTES; RESPONSES; PARADIGM; ASSAYS AB Most of the recent randomised clinical trials of therapeutic cancer vaccines have failed to demonstrate a meaningful therapeutic benefit to patients over existing treatments. Furthermore, some clinical trials have demonstrated a detrimental effect on patients, resulting in poorer outcomes. These unexpected results have shed light on several important issues to be solved for further development of cancer vaccines. As has been discussed with respect to the use of granulocyte-macrophage colony-stimulating factor (GM-SCF) as an adjuvant, the failures of clinical trials may be explained, in part, by a vaccine-specific adverse event, i.e. the induction of an 'inconvenient immune response' that inhibits preexisting host immunity. This hypothesis may be supported by the fact that randomised trials of personalised peptide vaccines that were selected in consideration of pre-existing host immunities in individual patients resulted in clear benefit to patients. The development of reliable biomarkers for the selection of appropriate patients and vaccine antigens would thus be pivotal to prevent such vaccine-specific adverse events. This article discusses possible ways to overcome the hurdles of randomised clinical trials of therapeutic cancer vaccines based on a review of recently conducted clinical trials. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Sasada, Tetsuro; Suekane, Shigetaka] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Sasada, Tetsuro; Komatsu, Nobukazu; Yamada, Akira; Itoh, Kyogo] Kurume Univ, Sch Med, Dept Immunol & Immunotherapy, Fukuoka, Japan. [Komatsu, Nobukazu; Yamada, Akira; Noguchi, Masanori; Itoh, Kyogo] Kurume Univ, Sch Med, Div Canc Vaccine, Res Ctr Innovat Canc Therapy, Fukuoka, Japan. [Suekane, Shigetaka; Noguchi, Masanori] Kurume Univ, Sch Med, Dept Urol, Fukuoka, Japan. RP Sasada, T (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, 77 Ave Louis Pasteur,HIM 442, Boston, MA 02115 USA. EM Tetsuro_Sasada@dfci.harvard.edu FU KAKENHI [12213134]; Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan FX This study was supported in part by Grants-in-Aid (KAKENHI) (no. 12213134 to KI), 'TOSHI aria jigyo to Kurume City' and 'High-Tech Research Center' Project for Private Universities: matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. NR 37 TC 23 Z9 25 U1 0 U2 3 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 JUN PY 2010 VL 46 IS 9 BP 1514 EP 1519 DI 10.1016/j.ejca.2010.03.013 PG 6 WC Oncology SC Oncology GA 618WV UT WOS:000279387700014 PM 20413296 ER PT J AU Honings, J Gaissert, HA Weinberg, AC Mark, EJ Wright, CD Wain, JC Mathisen, DJ AF Honings, Jimmie Gaissert, Henning A. Weinberg, Alissa C. Mark, Eugene J. Wright, Cameron D. Wain, John C. Mathisen, Douglas J. TI Prognostic value of pathologic characteristics and resection margins in tracheal adenoid cystic carcinoma SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article DE Trachea; Adenoid cystic carcinoma; Airway resection; Resection margins; Survival analysis ID TUMORS AB Objective: We investigate the influence of tumour and resection characteristics on survival in adenoid cystic carcinoma (ACC) of the trachea. Methods: A retrospective study of 12 laryngotracheal, 58 tracheal and 38 carinal resections for primary ACC in 108 consecutive operative survivors between 1962 and 2007 was conducted. Postoperative radiotherapy was administered to 82% of patients (89/108). Depth of invasion, extramural extent, organ invasion, perineural growth, margin status and lymph node involvement were described. Results: The tumour was intramural in 15% (16/108), extramural in 85% (92/108) and invaded adjacent organs in 20% (22/108). Airway margins were grossly positive in 9 (8%), microscopically positive in 59 (55%) and negative in 40 (37%) of 108 resections. Adventitial (radial) margins of transmural sections were grossly positive in 3 (3%), microscopically positive in 95 (88%) and negative in 10 (9%) cases. Perineural growth was present in 37 (34%) and absent in 12 (11%); it was not observed in 59 (55%) cases. Lymph nodes were positive in 16 (15%) and negative in 45 (42%) cases; it was not sampled in 47 (44%) cases. Median overall survival (OS) and disease-free survival (DFS) for the entire group were 17.7 and 10.2 years, respectively. OS was longer after resection with: negative airway margins (20.4 vs 13.3 years, P = 0.028) and negative radial margins (21.7 vs 13.3 years, P = 0.050); absence of extramural disease (21.7 vs 13.3 years, P = 0.007), perineural growth (22.8 vs 7.5 years, P = 0.011) or lymph node metastases (16.8 vs 6.1 years, P = 0.017). DFS was longer after resection with: negative airway margins (16.6 vs 9.3, P = 0.005) and absence of extramural disease (17.9 vs 9.3 years, P = 0.008), perineural growth (17.9 vs 6.6 years, P = 0.033) or lymph node metastases (10.2 vs 3.0 years, P = 0.005). Conclusions: After tracheal resection for ACC, limited tumour extent and complete resection are associated with longer overall and disease-free survival. Long-term survival (>10 years), however, is also observed after tracheal resection of locally advanced ACC. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. C1 [Honings, Jimmie; Gaissert, Henning A.; Weinberg, Alissa C.; Wright, Cameron D.; Wain, John C.; Mathisen, Douglas J.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Honings, Jimmie; Gaissert, Henning A.; Weinberg, Alissa C.; Mark, Eugene J.; Wright, Cameron D.; Wain, John C.; Mathisen, Douglas J.] Harvard Univ, Sch Med, Boston, MA USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,32 Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org RI Honings, Jimmie/B-3639-2016 OI Honings, Jimmie/0000-0001-5077-3472 NR 8 TC 17 Z9 19 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD JUN PY 2010 VL 37 IS 6 BP 1438 EP 1444 DI 10.1016/j.ejcts.2010.01.005 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 614UY UT WOS:000279086500032 PM 20356756 ER PT J AU Sarhan, AAO Al-Dhfyan, A Al-Mozaini, MA Adra, CN Aboul-Fadl, T AF Sarhan, Abdelwareth A. O. Al-Dhfyan, Abdullah Al-Mozaini, Maha A. Adra, Chaker N. Aboul-Fadl, Tarek TI Cell cycle disruption and apoptotic activity of 3-aminothiazolo[3,2a]benzimidazole-2-carbonitrile and its homologues SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE 3-Aminothiazolo[3,2-a]benzimidazole-2-carbonitrile; Cytotoxic activity; Cell cycle disruption; G2/M phase; Apoptosis ID FLOW-CYTOMETRIC DETECTION; CARCINOMA DU145 CELLS; ANNEXIN-V; PHOSPHATIDYLSERINE EXPRESSION; GROWTH-INHIBITION; CANCER CELLS; DERIVATIVES; ARREST; PROGRESSION; MODULATION AB 3-Aminothiazolo[3,2-a]benzimidazole-2-carbonitrile (2) was prepared and upon hydrolysis using concentrated sulfuric acid or phosphoric acid resulted in the corresponding 3-aminothiazolo[3,2-a] benzimidazole-2-carboxamide derivative (3). Cyclization of the 2 using acetic anhydride or formic acid gave the corresponding pyrimido[4',5' 4,5]thiazolo[3,2-a]benzimidazol-4(3H)-one (5) in good yields. Acetylation of 2 with acetic anhydride in pyridine afforded N-acetylaminothiazolo[3,2-a]benzimidazole-2-carbonitrile (6). In vitro annproliferative activities of synthesized compounds were investigated at The National Cancer Institute (NCI), USA, according to their applied protocol. Compound 6 revealed significant annproliferative activity, however, weak activity was shown by the other derivatives. Cell cycle disruption and apoptotic activity of 6 were studied, interestingly, 6 has the ability to arrest G2/M phase and it can induce apoptosis in time dependant manner. C1 [Aboul-Fadl, Tarek] King Saud Univ, Coll Pharm, Dept Pharmaceut Chem, Riyadh 11451, Saudi Arabia. [Sarhan, Abdelwareth A. O.] Assiut Univ, Fac Sci, Dept Chem, Assiut 71516, Egypt. [Al-Dhfyan, Abdullah; Al-Mozaini, Maha A.; Adra, Chaker N.] King Faisal Specialized Hosp & Res Ctr, Stem Cell Therapy Program, Riyadh 11211, Saudi Arabia. [Al-Mozaini, Maha A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Adra, Chaker N.] Harvard Univ, Sch Med, TRC, Brigham & Womens Hosp, Boston, MA USA. [Adra, Chaker N.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Aboul-Fadl, Tarek] Assiut Univ, Fac Pharm, Dept Med Chem, Assiut 71526, Egypt. RP Aboul-Fadl, T (reprint author), King Saud Univ, Coll Pharm, Dept Pharmaceut Chem, POB 2457, Riyadh 11451, Saudi Arabia. FU Assiut University, Egypt FX Assiut University, Egypt is deeply acknowledged for supporting this work National Cancer Institute (NCI), USA is also appreciated for antiproliferative screening of our compounds. NR 38 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD JUN PY 2010 VL 45 IS 6 BP 2689 EP 2694 DI 10.1016/j.ejmech.2010.02.025 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 601JU UT WOS:000278056000071 PM 20226574 ER PT J AU MacLeod, JB Ustin, JS Kim, JT Lewis, F Rozycki, GS Feliciano, DV AF MacLeod, Jana B. Ustin, Jeffrey S. Kim, Joseph T. Lewis, Fran Rozycki, Grace S. Feliciano, David V. TI The Epidemiology of Traumatic Hemothorax in a Level I Trauma Center: Case for Early Video-assisted Thoracoscopic Surgery SO EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY LA English DT Article DE Thoracic trauma; Epidemiology; Patient outcomes; Chest trauma ID TUBE THORACOSTOMY; EARLY EVACUATION; POSTTRAUMATIC HEMOTHORAX; COMPLICATIONS; MANAGEMENT AB Objective: Hemothorax is a common sequela of chest trauma. Complications after chest trauma include retained hemothorax and empyema requiring multiple interventions. We studied the epidemiology of hemothorax and its complications at a level I trauma center. Methods: The trauma registry was reviewed from Jan 1995 to May 2005. All patients >= 16 years of age who were admitted with hemothorax, an AIS chest score of >= 3, and did not receive an immediate thoracotomy were entered in the study cohort. The patient demographics, details of the injury event, treatments, hospital length of stay (LOS), complications and outcome were analyzed. Results: The study cohort of 522 patients with a hemothorax were treated with 685 chest thoracostomy tubes. Overall, the median ISS was 18 and 62% were penetrating injuries. log patients (21%) had a retained hemothorax and required placement of >= 2 chest tubes with a median LOS of 15 days longer than patients with no retained hemothorax (p < 0.0001). The overall complication rate was 5% (26/522). Of these, 20 patients had empyema (3.8%), 8 patients required decortication, and 6 patients received streptokinase treatment. Conclusions: More than 1 out of every 5 patients undergoing intervention for trauma-induced hemothorax develops a complication. The development of retained hemothorax is associated with empyema in 15.6% of cases and a 2-week median increase in length of stay. Future research into interventions such as Video-assisted thoracoscopic surgery (VATS) on the day of admission to completely evacuate hemothorax is warranted to reduce complication rates, length of stay and cost. C1 [MacLeod, Jana B.; Rozycki, Grace S.; Feliciano, David V.] Emory Univ, Sch Med, Dept Surg, Div Trauma & Crit Care, Atlanta, GA 30322 USA. [Ustin, Jeffrey S.] Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kim, Joseph T.] Indiana Univ Sch Med, Indianapolis, IN USA. [Lewis, Fran] Grady Mem Hosp, Grady Hlth Syst, Atlanta, GA USA. RP MacLeod, JB (reprint author), Emory Univ, Sch Med, Dept Surg, Div Trauma & Crit Care, Atlanta, GA 30322 USA. EM jmacleo@emory.edu NR 20 TC 1 Z9 2 U1 0 U2 1 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 1863-9933 J9 EUR J TRAUMA EMERG S JI Eur. J. Trauma Emerg. Surg. PD JUN PY 2010 VL 36 IS 3 BP 240 EP 246 DI 10.1007/s00068-009-9119-8 PG 7 WC Emergency Medicine SC Emergency Medicine GA 612NT UT WOS:000278907000008 PM 26815867 ER PT J AU Choi, JK Jenkins, BG Carreras, I Kaymakcalan, S Cormier, K Kowall, NW Dedeoglu, A AF Choi, Ji-Kyung Jenkins, Bruce G. Carreras, Isabel Kaymakcalan, Sukru Cormier, Kerry Kowall, Neil W. Dedeoglu, Alpaslan TI Anti-inflammatory treatment in AD mice protects against neuronal pathology SO EXPERIMENTAL NEUROLOGY LA English DT Article DE A-Beta; Alzheimer's disease; Amyloid; Celecoxib; Ibuprofen; Magnetic resonance spectroscopy; Mice; Plaques; Presenilin ID MAGNETIC-RESONANCE SPECTROSCOPY; ALZHEIMERS-DISEASE; TRANSGENIC MICE; MEMORY DEFICITS; MOUSE MODELS; BETA; AGGREGATION; METABOLISM; PROFILE; NSAIDS AB Prior studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may lower the incidence of Alzheimer's disease (AD) and delay onset or slow progression of symptoms in mouse models of AD. We examined the effects of chronic NSAID treatment in order to determine which elements of the pathological features might be ameliorated. We compared the effects of the NSAIDs ibuprofen and celecoxib on immunohistological and neurochemical markers at two different ages in APPxPS1 mice using measurements of amyloid plaque deposition, A beta peptide levels, and neurochemical profiles using magnetic resonance spectroscopy (MRS). At 6 months of age, few neurochemical changes were observed between PSAPP mice and WT mice using MRS. Ibuprofen, but not celecoxib, treatment significantly decreased the A beta(42/40) ratio in frontal cortex at 6 months, but overall amyloid plaque burden was unchanged. Consistent with prior findings in mouse models, at 17 months of age, there was a decrease in the neuronal markers NAA and glutamate and an increase in the astrocytic markers glutamine and myo-inositol in AD mice compared to WT. Ibuprofen provided significant protection against NAA and glutamate loss. Neither of the drugs significantly affected myo-inositol or glutamine levels. Both ibuprofen and celecoxib lowered plaque burden without a significant effect on A beta(1-42) levels. NAA levels significantly correlated with plaque burden. These results suggest that selective NSAIDs (ibuprofen and possibly celecoxib) treatment can protect against the neuronal pathology. Published by Elsevier Inc. C1 [Choi, Ji-Kyung; Jenkins, Bruce G.; Dedeoglu, Alpaslan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Choi, Ji-Kyung; Jenkins, Bruce G.; Dedeoglu, Alpaslan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Carreras, Isabel; Kaymakcalan, Sukru; Cormier, Kerry; Kowall, Neil W.; Dedeoglu, Alpaslan] VA Boston Healthcare Syst, Dept Vet Affairs, Boston, MA 02130 USA. [Carreras, Isabel] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Kaymakcalan, Sukru; Cormier, Kerry; Kowall, Neil W.; Dedeoglu, Alpaslan] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Dedeoglu, A (reprint author), Bedford Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Unit 182B, 200 Springs Rd, Bedford, MA 01730 USA. EM dedeoglu@bu.edu RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Dedeoglu, Alpaslan/0000-0003-1156-0874 FU Department of Veterans Affairs; NIH [AG13846-NWK]; Alzheimer Association [NIRG 02 3563-AD] FX This work was supported by Merit Review grants from the Department of Veterans Affairs (AD) and by the NIH (grants AG13846-NWK and AD) and Alzheimer Association New Investigator Award (NIRG 02 3563-AD). NR 22 TC 32 Z9 34 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 2010 VL 223 IS 2 SI SI BP 377 EP 384 DI 10.1016/j.expneurol.2009.07.032 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 597GD UT WOS:000277743700017 PM 19679126 ER PT J AU George, RE Diller, L Bernstein, ML AF George, Rani E. Diller, Lisa Bernstein, Mark L. TI Pharmacotherapy of neuroblastoma SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE ALK tyrosine kinase; anti-angiogenic agents; apoptosis inducers; epigenetic modifiers; heat shock proteins; high-risk neuroblastoma; immunotherapy; MIBG; retinoids; targeted therapy ID CHILDRENS ONCOLOGY GROUP; HIGH-RISK NEUROBLASTOMA; REFRACTORY SOLID TUMORS; ENDOTHELIAL GROWTH-FACTOR; PHASE-I TRIAL; HISTONE DEACETYLASE INHIBITORS; CHEMOTHERAPY-INDUCED APOPTOSIS; BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; STAGE 4 NEUROBLASTOMA AB Importance of the field: Neuroblastoma, a tumor of the sympathetic nervous system, is the most common extracranial solid tumor of early life. High risk disease in older children remains a therapeutic challenge, despite high-intensity therapy with correspondingly significant short- and long-term toxicities. Areas covered in this review: We have reviewed therapy for neuroblastoma over the last three decades. This includes cytotoxic chemotherapy, immunotherapy, radionuclides, antiangiogenic compounds, and molecularly targeted agents. We provide a perspective on the incorporation of these drugs into therapy for neuroblastoma. What the reader will gain: The reader will gain a better understanding of these novel agents and their targets in neuroblastoma. The reader will also gain insight into the need to define through sequential, carefully designed clinical trials, the roles and toxicities of these therapies, especially if the combination of targeted and conventional cytotoxic agents is used. Take home message: Advanced-stage neuroblastoma in older infants and children remains a disease that is difficult to cure. New, targeted agents may improve both the therapeutic index and the outcome, but are, for the most part, in early development and present a challenge for clinical trial design given both the rarity of this disease and its responsiveness (albeit incomplete) to currently used cytotoxic agents. C1 [Bernstein, Mark L.] IWK Hlth Ctr, Halifax, NS B3K 6R8, Canada. [George, Rani E.; Diller, Lisa] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [George, Rani E.; Diller, Lisa] Harvard Univ, Childrens Hosp Boston, Sch Med, Boston, MA 02115 USA. RP Bernstein, ML (reprint author), IWK Hlth Ctr, 5850-5980 Univ Ave, Halifax, NS B3K 6R8, Canada. EM mark.bernstein@iwk.nshealth.ca NR 118 TC 10 Z9 11 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD JUN PY 2010 VL 11 IS 9 BP 1467 EP 1478 DI 10.1517/14656566.2010.482100 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 613BL UT WOS:000278950900004 PM 20408767 ER PT J AU Mejia, NI Jankovic, J AF Mejia, Nicte I. Jankovic, Joseph TI Tardive dyskinesia and withdrawal emergent syndrome in children SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE antiemetic; antipsychotic; children; dopamine; metoclopramide; neuroleptic; pediatric; tardive; tardive dyskinesia; tetrabenazine; withdrawal emergent syndrome ID NEUROLEPTIC-RELATED DYSKINESIAS; HYPERKINETIC MOVEMENT-DISORDERS; DISRUPTIVE BEHAVIOR DISORDERS; AUTISTIC-CHILDREN; LONG-TERM; EXTRAPYRAMIDAL DYSFUNCTION; MOTOR STEREOTYPIES; 2ND-GENERATION ANTIPSYCHOTICS; GENETIC ASSOCIATION; TOURETTES-SYNDROME AB Tardive dyskinesia (TD) is a well-recognized and sometimes permanent adverse effect of treatment with dopamine receptor-blocking drugs (DRBDs), also referred to as neuroleptics. This iatrogenic disorder has been well characterized in adults, but not extensively studied in children. Withdrawal emergent syndrome (WES) is another pediatric movement disorder related to the use of DRBDs. TD and WES are among the most feared adverse effects of DRBD treatment, and have important medical and legal implications. We review published studies of children under the age of 18 years who were exposed to DRBD to determine the clinical spectrum and estimate the possible prevalence of TD and WES. We particularly wish to draw attention to the phenomenology, clinical course and treatment of these childhood-onset disorders. Although avoiding DRBDs is the best strategy for minimizing the risk of TD and WES, physicians who evaluate children exposed to DRBDs must be vigilant and recognize the early symptoms and signs of these syndromes to provide appropriate clinical management. C1 [Jankovic, Joseph] Baylor Coll Med, Parkinsons Dis Ctr, Dept Neurol, Houston, TX 77030 USA. [Jankovic, Joseph] Baylor Coll Med, Movement Disorders Clin, Dept Neurol, Houston, TX 77030 USA. [Mejia, Nicte I.] Harvard Univ, Sch Med, Boston, MA USA. [Mejia, Nicte I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jankovic, J (reprint author), Baylor Coll Med, Parkinsons Dis Ctr, Dept Neurol, 6550 Fannin,Suite 1801, Houston, TX 77030 USA. EM josephj@bcm.tmc.edu FU Biovail; Lundbeck, Inc. FX Joseph Jankovic has received research grants and serves as a consultant to Biovail and Lundbeck, Inc. 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 91 TC 15 Z9 15 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD JUN PY 2010 VL 10 IS 6 BP 893 EP 901 DI 10.1586/ERN.10.58 PG 9 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 612QO UT WOS:000278916800016 PM 20518606 ER PT J AU Pomerantz, AS Sayers, SL AF Pomerantz, Andrew S. Sayers, Steven L. TI Primary Care-Mental Health Integration in Healthcare in the Department of Veterans Affairs SO FAMILIES SYSTEMS & HEALTH LA English DT Article DE primary care-mental health integration; primary care; mental health services; military veterans ID COLLABORATIVE CARE; MEDICAL HOME; MODEL AB The U.S. Department of Veterans Affairs (VA) has been undergoing tremendous transformation in the past 15 years with regard to the delivery of health care. This special issue describes one aspect of this transformation of the largest health system in the U.S.; the system-wide efforts to integrate mental health treatment into the primary care setting in VA. This primary care-mental health integration (PC-MHI) is being accomplished through the central VA system support and implementation of three primary models developed in the field: the White River Colocated models, the Behavioral Health Laboratory, and TIDES (Translating Initiatives in Depression into Effective Solutions). The papers in this special issue describe the development of these models, local and regional efforts to prepare medical centers to adapt and implement PC-MHI, and the impact of the integration on mental health care in these settings. These efforts could represent a national model of PC-MHI implementation for health care systems throughout the U.S. C1 [Pomerantz, Andrew S.] White River Junction VA Med Ctr, VA Med Ctr, White River Jct, VT 05009 USA. [Pomerantz, Andrew S.] Dartmouth Med Sch, Dept Psychiat, Hanover, NH USA. [Sayers, Steven L.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Sayers, Steven L.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Pomerantz, AS (reprint author), White River Junction VA Med Ctr, VA Med Ctr, 215 N Main St,116-D, White River Jct, VT 05009 USA. EM Andrew.Pomerantz@va.gov FU VA Medical Center of White River Junction; Mental Illness, Research, Education and Clinical Center; VISN 4; Philadelphia VA Medical Center FX This paper does not necessarily represent the position or opinions of the Department of Veterans Affairs, and those expressed are the sole responsibility of the authors. The preparation of this paper was in part supported by the VA Medical Center of White River Junction, the Mental Illness, Research, Education and Clinical Center, VISN 4, and the Philadelphia VA Medical Center. NR 16 TC 25 Z9 25 U1 1 U2 6 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1091-7527 J9 FAM SYST HEALTH JI Fam. Syst. Health PD JUN PY 2010 VL 28 IS 2 SI SI BP 78 EP 82 DI 10.1037/a0020341 PG 5 WC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health GA 829AP UT WOS:000295547200002 PM 20695667 ER PT J AU Rubenstein, LV Chaney, EF Ober, S Felker, B Sherman, SE Lanto, A Vivell, S AF Rubenstein, Lisa V. Chaney, Edmund F. Ober, Scott Felker, Bradford Sherman, Scott E. Lanto, Andy Vivell, Susan TI Using Evidence-Based Quality Improvement Methods for Translating Depression Collaborative Care Research Into Practice SO FAMILIES SYSTEMS & HEALTH LA English DT Article DE depression; quality improvement; evaluation; implementation; collaborative care ID AFFAIRS PRIMARY-CARE; MANAGED PRIMARY-CARE; DIABETES-MELLITUS; CHRONIC ILLNESS; QUERI SERIES; HEALTH; IMPACT; VETERANS; INTERVENTIONS; LESSONS AB Objective: Translating Initiatives in Depression into Effective Solution (TIDES) aimed to translate research-based collaborative care for depression into an approach for the Veterans Health Administration (VA). Sites: Three multistate administrative regions and seven of their medium-sized primary care practices. Intervention: Researchers assisted regional leaders in adapting research-based depression care models using evidence-based quality improvement (EBQI) methods. Evaluation: We evaluated model fidelity and impacts on patients. Trained nurse depression care managers collected data on patient adherence and outcomes. Results: Among 72% (128) of the 178 patients followed in primary care with depression care manager assistance during the 3-year study period, mean PHQ-9 scores dropped from 15.1 to 4.7 (p < .001). A total of 87% of patients achieved a PHQ-9 score lower than 10 (no major depression). 62% achieved a score lower than six (symptom resolution). Care managers referred 28% (50) TIDES patients to mental health specialty (MHS). In the MHS-referred group, mean PHQ-9 scores dropped from 16.4 to 9.0 (p < .001). A total of 58% of MHS-referred patients achieved a PHQ-9 score lower than 10, and 40%, a score less than 6. Over the 2 years following the initial development phase reported here, national policymakers endorsed TIDES through national directives and financial support. Conclusions: TIDES developed an evidence-based depression collaborative care prototype for a large health care organization (VA) using EBQI methods. As expected, care managers referred sicker patients to mental health specialists; these patients also improved. Overall, TIDES achieved excellent overall patient outcomes, and the program is undergoing national spread. C1 [Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Rubenstein, Lisa V.] RAND Hlth Program, Santa Monica, CA USA. [Chaney, Edmund F.; Felker, Bradford] VA Puget Sound Healthcare Syst, Mental Hlth Serv, Seattle, WA USA. [Chaney, Edmund F.; Felker, Bradford] VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Chaney, Edmund F.; Felker, Bradford] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Ober, Scott] Cleveland VA Med Ctr, Dept Med, Cleveland, OH USA. [Sherman, Scott E.] VA New York Harbor Healthcare Syst, Dept Med, New York, NY USA. [Sherman, Scott E.] NYU, Dept Med, Sch Med, New York, NY 10003 USA. [Rubenstein, Lisa V.; Lanto, Andy; Vivell, Susan] VA Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence, Los Angeles, CA USA. [Ober, Scott] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. RP Rubenstein, LV (reprint author), VA Greater Los Angeles Sepulveda, 16111 Plummer St,152, North Hills, CA 91343 USA. EM lisa.rubenstein@va.gov OI Sherman, Scott/0000-0003-1752-7303 NR 49 TC 45 Z9 46 U1 3 U2 6 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1091-7527 J9 FAM SYST HEALTH JI Fam. Syst. Health PD JUN PY 2010 VL 28 IS 2 SI SI BP 91 EP 113 DI 10.1037/a0020302 PG 23 WC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health GA 829AP UT WOS:000295547200004 PM 20695669 ER PT J AU Tew, J Klaus, J Oslin, DW AF Tew, James Klaus, Johanna Oslin, David W. TI The Behavioral Health Laboratory: Building a Stronger Foundation for the Patient-Centered Medical Home SO FAMILIES SYSTEMS & HEALTH LA English DT Article DE care management; collaborative care; primary care-mental health integration; patient-centered medical home ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE; TREATMENT ENGAGEMENT; COLLABORATIVE CARE; FAMILY PHYSICIANS; ALCOHOL-PROBLEMS; REFERRAL CARE; MENTAL-HEALTH; LATE-LIFE; DEPRESSION AB The Veterans Health Affairs is in the process of implementing a new model for the delivery of primary care: The Patient-Centered Medical Home (PCMH). One critical challenge of any PCMH model will be the integration of basic mental health treatment into primary care. Such a mental health integration program must be flexible enough to incorporate new evidence-based treatments as patient demographics and health care needs evolve over time. This paper summarizes the Behavioral Health Laboratory (BHL) care management model, a program already in place in more than 20 Veterans Affairs facilities along with private sector insurance providers, as ideally suited to fill this role in the PCMH. The BHL uses a platform of standardized, software-aided mental health assessments and clinical care managers to deliver evidence-based treatments for depression, anxiety, and substance abuse in primary care settings. The authors review this comprehensive program of screening, assessment, treatment, and referral to specialty care when needed. The BHL program is consistent with the guiding principles of the Patient-Centered Medical Home: applying chronic illness disease management principles to provide more continuous, coordinated, and efficient primary care services to patients with diverse needs. Just as importantly, the authors review how this standardized platform for delivering integrated mental health services provides the flexibility to incorporate novel interventions for a changing population. C1 [Tew, James; Klaus, Johanna; Oslin, David W.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Tew, James; Klaus, Johanna; Oslin, David W.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. RP Klaus, J (reprint author), Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Johanna.Klaus@va.gov NR 30 TC 29 Z9 29 U1 1 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1091-7527 J9 FAM SYST HEALTH JI Fam. Syst. Health PD JUN PY 2010 VL 28 IS 2 SI SI BP 130 EP 145 DI 10.1037/a0020249 PG 16 WC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health GA 829AP UT WOS:000295547200006 PM 20695671 ER PT J AU Markuns, JF Fraser, B Orlander, JD AF Markuns, Jeffrey F. Fraser, Bruce Orlander, Jay D. TI The Path to Physician Leadership in Community Health Centers: Implications for Training SO FAMILY MEDICINE LA English DT Article ID WORKFORCE; SHORTAGES; EXPANSION AB Background and Objectives: Community health centers are facing a shortage of primary care physicians at a time when government plans have called for an expansion of community health center programs. To succeed with this expansion, community health centers require additional well-trained physician leadership. Our objective was to ascertain how medical directors obtain leadership skills in an attempt to identify the best methods and venues for providing future leadership training programs. Methods: Using recorded interviews and locus group data with community health center medical directors, we identified patterns and themes through cross-case content analysis to determine leadership training needs in underserved settings. Results: Medical directors often enter positions unprepared and can quickly become frustrated by an inability to make system improvements. Medical directors seek multiple ways to obtain the leadership skills necessary, including conferences, peer networking, mentorship, and formal degree training. Many directors express a desire for additional training, preferring flexibility in curriculum and hands-on components. Conclusions: Additional leadership training opportunities for active and future medical directors are needed. Academic medical centers and other training sponsors should consider innovative ways to develop effective physician leadership to provide quality care to underserved communities. C1 [Markuns, Jeffrey F.] Boston Univ, Dept Family Med, Boston, MA 02118 USA. [Fraser, Bruce] Boston Univ, Sch Educ, Boston, MA 02118 USA. [Orlander, Jay D.] Boston Univ, Evans Dept Med, Boston, MA 02118 USA. [Orlander, Jay D.] VA Boston HealthCare Syst, W Roxbury, MA USA. RP Markuns, JF (reprint author), Boston Univ, Dept Family Med, Dowling 5 S,1 Boston Med Ctr Pl, Boston, MA 02118 USA. EM jeffrey.markuns@bmc.org OI Markuns, Jeffrey/0000-0002-8044-2575 FU HRSA Faculty Development [D55HP00215] FX This study was financed by HRSA Faculty Development grant D55HP00215. NR 18 TC 3 Z9 3 U1 1 U2 3 PU SOC TEACHERS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, STE 540, LEAWOOD, KS 66207 USA SN 0742-3225 J9 FAM MED JI Fam. Med. PD JUN PY 2010 VL 42 IS 6 BP 403 EP 407 PG 5 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 607NT UT WOS:000278511500008 PM 20526907 ER PT J AU Hendrickson, WA Xie, H Le-Khac, M Korkut, A Ng, D Courter, JR Kwon, YD Schon, A Madani, N LaLonde, JM Chaiken, IM Freire, E Sodroski, J Kwong, PD Smith, AB AF Hendrickson, W. A. Xie, H. Le-Khac, M. Korkut, A. Ng, D. Courter, J. R. Kwon, Y. D. Schoen, A. Madani, N. LaLonde, J. M. Chaiken, I. M. Freire, E. Sodroski, J. Kwong, P. D. Smith, A. B. TI Ligand recognition and plasticity in HIV envelope glycoprotein gp120 SO FEBS JOURNAL LA English DT Meeting Abstract CT 35th Congress of the Federation-of-European-Biochemical-Societies CY JUN 26-JUL 01, 2010 CL Gothenburg, SWEDEN C1 [Hendrickson, W. A.] Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Xie, H.; Le-Khac, M.] Columbia Univ, Dept Pharmacol, New York, NY USA. [Ng, D.; Courter, J. R.; Smith, A. B.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Kwon, Y. D.; Kwong, P. D.] Vaccine Res Ctr, NIH, Bethesda, MD USA. [Schoen, A.; Freire, E.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Madani, N.; Sodroski, J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [LaLonde, J. M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. [Chaiken, I. M.] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2010 VL 277 SU 1 BP 15 EP 15 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 608EI UT WOS:000278565100054 ER PT J AU Boudsocq, M Willmann, M McCormack, M Lee, H Shan, L He, P Bush, J Cheng, SH Sheen, J AF Boudsocq, M. Willmann, M. McCormack, M. Lee, H. Shan, L. He, P. Bush, J. Cheng, S-H. Sheen, J. TI Differential innate immune signalling via Ca2+ sensor protein kinases in plants SO FEBS JOURNAL LA English DT Meeting Abstract CT 35th Congress of the Federation-of-European-Biochemical-Societies CY JUN 26-JUL 01, 2010 CL Gothenburg, SWEDEN C1 [Boudsocq, M.; Willmann, M.; McCormack, M.; Lee, H.; Shan, L.; He, P.; Bush, J.; Cheng, S-H.; Sheen, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2010 VL 277 SU 1 BP 29 EP 29 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 608EI UT WOS:000278565100114 ER PT J AU Vidal, M AF Vidal, M. TI Interactome networks and human disease SO FEBS JOURNAL LA English DT Meeting Abstract CT 35th Congress of the Federation-of-European-Biochemical-Societies CY JUN 26-JUL 01, 2010 CL Gothenburg, SWEDEN C1 [Vidal, M.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2010 VL 277 SU 1 BP 33 EP 33 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 608EI UT WOS:000278565100131 ER PT J AU Kwon, JY Myerson, MS AF Kwon, John Y. Myerson, Mark S. TI Management of the Flexible Flat Foot in the Child: A Focus on the Use of Osteotomies for Correction SO FOOT AND ANKLE CLINICS LA English DT Article DE Pes planus; Flat foot deformity; Pediatric; Osteotomy ID POSTERIOR TIBIAL TENDON; PREVALENCE; TALUS; ARCH AB The flexible flat foot is treated according to the location of the deformity, ie, hindfoot valgus, midfoot abduction, and forefoot supination. There is generally a contracture of the gastrocnemius requiring treatment, which is performed in conjunction with osteotomy of the calcaneus and cuneiform as required. C1 [Kwon, John Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Myerson, Mark S.] Mercy Med Ctr, Inst Foot & Ankle Reconstruct Mercy, Baltimore, MD 21201 USA. RP Kwon, JY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. EM johnkwonmd@gmail.com NR 22 TC 5 Z9 6 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1083-7515 J9 FOOT ANKLE CLIN JI Foot Ankle Clin. PD JUN PY 2010 VL 15 IS 2 BP 309 EP 322 DI 10.1016/j.fcl.2010.02.001 PG 14 WC Orthopedics SC Orthopedics GA 746ED UT WOS:000289224600007 PM 20534358 ER PT J AU Wu, MR Deng, LF Zhu, GC Li, YP AF Wu, Mengrui Deng, Lianfu Zhu, Guochun Li, Yi-Ping TI G protein and its signaling pathway in bone development and disease SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE Osteoblasts; Osteoclasts; Bone; Heterometric G protein; G alpha s; G alpha q/11; G alpha i/o; G alpha 12/13; G protein coupled receptor; PTH; PTHrP; Cation Sensing Receptor; Calcitonin; Cannabinoid; Relaxin Family Peptide; Regulator of G Protein Signaling; Review ID OSTEOBLAST-LIKE CELLS; CALCIUM-SENSING RECEPTOR; MESSENGER-RNA EXPRESSION; PARATHYROID-HORMONE PTH; GENE-RELATED PEPTIDE; GROWTH-FACTOR-I; PASTEURELLA-MULTOCIDA TOXIN; HEMATOPOIETIC STEM-CELLS; MCCUNE-ALBRIGHT-SYNDROME; NECROSIS-FACTOR-ALPHA AB G protein signaling is comprised of G protein coupled receptors (GPCRs) that detect ligands or sense cations, heterotrimeric G proteins, and downstream effectors and regulators. G protein signaling plays important roles in bone development, remodeling, and disease. In human cases, mutations of certain GPCRs and G proteins impair bone development and metabolism, resulting in bone diseases. This review focuses on the functions of G proteins and GPCRs in osteoblasts and osteoclasts, their signaling pathways, and their gene mutations in mouse models and human diseases. We have discussed the roles of all four types of G proteins (i.e. Gs, Gq/11, Gi/o, and G12/13) and assessed the roles of the GPCRs, such as type 1 Parathyroid hormone receptor (PTH1R), calcitonin receptor, cation sensing receptor (CaSR), relaxin family peptides, cannabinoid receptor, frizzleds, and proton sensing receptor in normal bone formation and remodeling. The roles of regulators of G protein signaling (RGS) and GTPase-activating proteins (GAP) in G-protein signaling pathways are also reviewed. Lastly, we give perspective for the research of G protein signaling in bone development and disease. C1 [Li, Yi-Ping] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Wu, Mengrui; Li, Yi-Ping] Zhejiang Univ, Life Sci Coll, Hangzhou 310058, Peoples R China. [Wu, Mengrui; Deng, Lianfu; Zhu, Guochun; Li, Yi-Ping] Jiao Tong Univ, Shanghai Inst Traumatol & Orthopaed, Ruijin Hosp, Sch Med, Shanghai 200025, Peoples R China. [Li, Yi-Ping] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM ypli@forsyth.org FU NIH [AR44741, AR-48133-01] FX We thank Christie Taylor for excellent assistance with the manuscript. We apologize to the many researchers whose work could not be cited due to space limitations. The work was supported by NIH grant AR44741 (Y.-P.Li.) and AR-48133-01 (Y.-P.Li.). NR 269 TC 13 Z9 13 U1 1 U2 19 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JUN 1 PY 2010 VL 15 BP 957 EP 985 DI 10.2741/3656 PG 29 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 660DR UT WOS:000282620300010 PM 20515736 ER PT J AU Sweet, RA Fish, KN Lewis, DA AF Sweet, Robert A. Fish, Kenneth N. Lewis, David A. TI Mapping synaptic pathology within cerebral cortical circuits in subjects with schizophrenia SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE schizophrenia; synapse; cerebral cortex; postmortem; immunofluorescence ID PRIMARY AUDITORY-CORTEX; MISMATCH NEGATIVITY GENERATION; DENDRITIC SPINE DENSITY; DORSOLATERAL PREFRONTAL CORTEX; MESSENGER-RNA EXPRESSION; FLUORESCENCE MICROSCOPY; PYRAMIDAL NEURONS; BIPOLAR DISORDER; ARBITRARY PARTICLES; GENE-EXPRESSION AB Converging lines of evidence indicate that schizophrenia is characterized by impairments of synaptic machinery within cerebral cortical circuits. Efforts to localize these alterations in brain tissue from subjects with schizophrenia have frequently been limited to the quantification of structures that are non-selectively identified (e. g., dendritic spines labeled in Golgi preparations, axon boutons labeled with synaptophysin), or to quantification of proteins using methods unable to resolve relevant cellular compartments. Multiple label fluorescence confocal microscopy represents a means to circumvent many of these limitations, by concurrently extracting information regarding the number, morphology, and relative protein content of synaptic structures. An important adaptation required for studies of human disease is coupling this approach to stereologic methods for systematic random sampling of relevant brain regions. In this review article we consider the application of multiple label fluorescence confocal microscopy to the mapping of synaptic alterations in subjects with schizophrenia and describe the application of a novel, readily automated, iterative intensity/morphological segmentation algorithm for the extraction of information regarding synaptic structure number, size, and relative protein level from tissue sections obtained using unbiased stereological principles of sampling. In this context, we provide examples of the examination of pre- and post-synaptic structures within excitatory and inhibitory circuits of the cerebral cortex. C1 [Sweet, Robert A.; Fish, Kenneth N.; Lewis, David A.] Univ Pittsburgh, Translat Neurosci Program, Dept Psychiat, Pittsburgh, PA USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. [Lewis, David A.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA. RP Sweet, RA (reprint author), Biomed Sci Tower,Rm W-1645,3811 OHara St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu RI Lewis, David/G-4053-2014 OI Lewis, David/0000-0002-3225-6778 FU USPHS [MH 071533, MH 084053] FX This work was supported by USPHS grants MH 071533 and MH 084053. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. The authors would like to thank Mrs. Mary Brady and Caitlin Moyer for assistance with the figures, and Dr. Karl-Anton Dorph-Petersen for his comments on the manuscript. The authors gratefully acknowledge the efforts of the research staff of the Translational Neuroscience Program and the Conte Center for Neuroscience of Mental Disorders at the University of Pittsburgh. NR 85 TC 16 Z9 16 U1 3 U2 6 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD JUN PY 2010 VL 4 AR 44 DI 10.3389/fnhum.2010.00044 PG 14 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 662QU UT WOS:000282827200001 PM 20631852 ER PT J AU Chan, AT Giovannucci, EL AF Chan, Andrew T. Giovannucci, Edward L. TI Primary Prevention of Colorectal Cancer SO GASTROENTEROLOGY LA English DT Article DE Colorectal Cancer; Diet; Lifestyle; Epidemiology ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HORMONE REPLACEMENT THERAPY; VITAMIN-D-RECEPTOR; LARGE-BOWEL-CANCER; N-3 FATTY-ACIDS; FAMILIAL ADENOMATOUS POLYPOSIS; RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; DIETARY GLYCEMIC LOAD; LOW-DOSE ASPIRIN AB Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and nonsteroidal anti-inflammatory drugs and postmenopausal hormones for women are associated with substantial reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence. C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chan, Andrew T.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 722, Boston, MA 02114 USA. EM achan@partners.org FU NCI NIH HHS [CA107412, CA087969, CA133891, CA137178, K07 CA107412, K07 CA107412-05, CA 055075, K07 CA107412-05S1, P01 CA055075, P01 CA055075-120001, P01 CA087969, P01 CA087969-100006, P50 CA127003, P50 CA127003-01, R01 CA133891, R01 CA137178, R01 CA137178-02] NR 418 TC 202 Z9 208 U1 13 U2 85 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 JUN PY 2010 VL 138 IS 6 BP 2029 EP U40 DI 10.1053/j.gastro.2010.01.057 PG 25 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 587LJ UT WOS:000276993600002 PM 20420944 ER PT J AU Pino, MS Chung, DC AF Pino, Maria S. Chung, Daniel C. TI The Chromosomal Instability Pathway in Colon Cancer SO GASTROENTEROLOGY LA English DT Article DE Genomic Instability; Chromosomal Instability; Colorectal Cancer ID HUMAN COLORECTAL CANCERS; ABERRANT CRYPT FOCI; FAMILIAL ADENOMATOUS POLYPOSIS; KIRSTEN RAS MUTATIONS; BETA-CATENIN; MICROSATELLITE INSTABILITY; GENOMIC INSTABILITY; STEM-CELLS; TELOMERASE ACTIVITY; TUMOR-SUPPRESSOR AB The acquisition of genomic instability is a crucial feature in tumor development and there are at least 3 distinct pathways in colorectal cancer pathogenesis: the chromosomal instability (CIN), microsatellite instability, and CpG island methylator phenotype pathways. Most cases of colorectal cancer arise through the CIN pathway, which is characterized by widespread imbalances in chromosome number (aneuploidy) and loss of heterozygosity. It can result from defects in chromosomal segregation, telomere stability, and the DNA damage response, although the full complement of genes underlying CIN remains incompletely described. Coupled with the karyotypic abnormalities observed in CIN tumors are the accumulation of a characteristic set of mutations in specific tumor suppressor genes and oncogenes that activate pathways critical for colorectal cancer initiation and progression. Whether CIN creates the appropriate milieu for the accumulation of these mutations or vice versa remains a provocative and unanswered question. The goal of this review is to provide an updated perspective on the mechanisms that lead to CIN and the key mutations that are acquired in this pathway. C1 [Pino, Maria S.; Chung, Daniel C.] Harvard Univ, Gastrointestinal Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Chung, DC (reprint author), Harvard Univ, Gastrointestinal Unit, Massachusetts Gen Hosp, Sch Med, 50 Blossom St, Boston, MA 02114 USA. EM dchung@partners.org FU NCI NIH HHS [P50 CA127003, CA92594, R01 CA092594] NR 130 TC 177 Z9 186 U1 7 U2 20 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 JUN PY 2010 VL 138 IS 6 BP 2059 EP 2072 DI 10.1053/j.gastro.2009.12.065 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 587LJ UT WOS:000276993600004 PM 20420946 ER PT J AU Bordeianou, L Rattner, D AF Bordeianou, Liliana Rattner, David TI Is Laparoscopic Sigmoid Colectomy for Diverticulitis the New Gold Standard? SO GASTROENTEROLOGY LA English DT Editorial Material ID IN-HOSPITAL-MORTALITY; COST STUDY-GROUP; LEARNING-CURVE; COLORECTAL SURGERY; MULTICENTER; RESECTION; CANCER; DISEASE; QUALITY; TRIAL C1 [Rattner, David] Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Colorectal Surg Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rattner, D (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Colorectal Surg Program, 15 Parkman St, Boston, MA 02114 USA. EM drattner@partners.org NR 27 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2010 VL 138 IS 7 BP 2213 EP 2216 DI 10.1053/j.gastro.2010.04.027 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 602KB UT WOS:000278136900008 PM 20435008 ER PT J AU Nguyen, DM Richardson, P El-Serag, HB AF Nguyen, Dang M. Richardson, Peter El-Serag, Hashem B. TI Medications (NSAIDs, Statins, Proton Pump Inhibitors) and the Risk of Esophageal Adenocarcinoma in Patients With Barrett's Esophagus SO GASTROENTEROLOGY LA English DT Article DE Epidemiology; Chemoprevention; Gastroesophageal Reflux Disease; VA ID CANCER; DYSPLASIA; METAPLASIA; PREVALENCE; HISTORY AB BACKGROUND & AIMS: Limited evidence suggests that proton pump inhibitors (PPI), nonsteroidal anti-inflammatory drugs (NSAID)/aspirin, and statins may be associated with a low risk of esophageal neoplasia. However, the possible effect these medications may have on the risk of esophageal adenocarcinoma (EAC) in patients with existing Barrett's esophagus (BE) is unclear. METHODS: We conducted a nested case-control study in a cohort of patients with BE identified in the national Department of Veterans' Affairs computerized databases. Cases with incident EAC were matched by incidence density sampling to controls with BE who remained without EAC at the date of the EAC diagnosis for the corresponding case. We identified prescriptions for PPI, NSAIDs/aspirin, and statins that were filled between BE diagnosis and EAC diagnosis. Incidence density ratios were calculated using conditional logistic regression models that adjusted for race, outpatient encounters, a disease comorbidity index, and socioeconomic status. RESULTS: In a cohort of 11,823 patients with first-time BE diagnosis, we examined 116 EAC cases and 696 matched controls. Most cases and controls had at least one filled PPI prescription (95% vs 94%; P = .5). In this setting of almost universal PPI use, filled NSAID/aspirin prescriptions were associated with a reduced risk of EAC (adjusted incidence density ratio, 0.64; 95% confidence interval, 0.42-0.97). Filled statin prescriptions also were associated with a reduction in EAC risk (0.55; 95% confidence interval, 0.36 - 0.86), with a significant trend toward greater risk reduction with longer duration of statin use. However, the strong inverse associations with even short periods of use raise concerns of uncontrolled confounding. CONCLUSIONS: This observational study indicates that in patients with BE using PPI, NSAID/aspirin, or statin therapy might reduce the risk of developing EAC. C1 Houston Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Houston Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU National Institutes of Health [K24DK07815403]; Texas Gulf Coast Digestive Diseases Center, National Institutes of Health [P50 DK56338]; Houston VA HSR&D Center of Excellence [HFP90-020] FX Supported by National Institutes of Health grant K24DK07815403 and The Texas Gulf Coast Digestive Diseases Center (National Institutes of Health grant P50 DK56338) (H.B.E.-S.). Partly funded by Houston VA HSR&D Center of Excellence (HFP90-020). NR 22 TC 91 Z9 92 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2010 VL 138 IS 7 BP 2260 EP 2266 DI 10.1053/j.gastro.2010.02.045 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 602KB UT WOS:000278136900016 PM 20188100 ER PT J AU Fontana, RJ Sanyal, AJ Ghany, MG Lee, WM Reid, AE Naishadham, D Everson, GT Kahn, JA Di Bisceglie, AM Szabo, G Morgan, TR Everhart, JE AF Fontana, Robert J. Sanyal, Arun J. Ghany, Marc G. Lee, William M. Reid, Andrea E. Naishadham, Deepa Everson, Gregory T. Kahn, Jeffrey A. Di Bisceglie, Adrian M. Szabo, Gyongyi Morgan, Timothy R. Everhart, James E. CA HALT-C Trial Grp TI Factors That Determine the Development and Progression of Gastroesophageal Varices in Patients With Chronic Hepatitis C SO GASTROENTEROLOGY LA English DT Article DE Cirrhosis; Portal Hypertension; Esophagogastroduodenoscopy; Hyaluronic Acid ID VENOUS-PRESSURE GRADIENT; ESOPHAGEAL-VARICES; ADVANCED FIBROSIS; NATURAL-HISTORY; CIRRHOSIS; THERAPY; TRIAL; PEGINTERFERON; PREVALENCE; VALIDATION AB BACKGROUND & AIMS: We aimed to identify the incidence and predictors of de novo gastroesophageal variceal formation and progression in a large cohort of patients with chronic hepatitis C and advanced fibrosis. METHODS: All participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial were offered an endoscopy before treatment and again after 4 years. Patients with varices at baseline also had an endoscopy at 2 years. Baseline laboratory and clinical parameters were analyzed as predictors of de novo variceal formation and variceal progression. RESULTS: De novo varices developed in 157 of the 598 (26.2%) patients. Most of the new varices were small (76.4%) and only 1% of patients developed variceal hemorrhage. The likelihood of developing varices was associated with subject race (Hispanic > Caucasian > African American; P = .0005), lower baseline levels of albumin (P = .051), and higher levels of hyaluronic acid (P < .001) with an area under the receiver operating characteristic curve = .70. Among 210 patients with existing gastroesophageal varices, 74 (35.2%) had variceal progression or bleeding during follow-up. Patients with higher baseline ratios of serum aspartate/alanine aminotransferase (P = .028) and lower platelet counts (P = .0002) were at greatest risk of variceal progression (area under the receiver operating characteristic = .72). Prolonged, low-dose peginterferon-alpha 2a therapy and beta-blockers did not influence the risk of developing new or enlarging varices. CONCLUSION: Development of varices in patients with chronic hepatitis C is associated with patient race/ethnicity and laboratory markers of disease severity. Prolonged low-dose peginterferon-alpha 2a therapy and beta-blockers do not reduce the risk of variceal development or progression. C1 [Fontana, Robert J.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Sch Med, Ann Arbor, MI 48109 USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA. [Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Reid, Andrea E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA. [Everson, Gregory T.] Univ Colorado Denver, Sect Hepatol, Div Gastroenterol & Hepatol, Sch Med, Aurora, CO USA. [Kahn, Jeffrey A.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Szabo, Gyongyi] Univ Massachusetts, Sch Med, Dept Med, Hepatol & Liver Ctr,Div Gastroenterol, Worcester, MA USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Irvine, CA USA. RP Fontana, RJ (reprint author), Univ Michigan, Dept Internal Med, Div Gastroenterol, Sch Med, 3912 Taubman Ctr, Ann Arbor, MI 48109 USA. EM rfontana@med.umich.edu FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources, National Institutes of Health; Hoffmann-La Roche, Inc; University of Massachusetts Medical Center, Worcester, MA [N01-DK-9-2326]; University of Connecticut Health Center, Farmington, CT [M01RR-06192]; Saint Louis University School of Medicine, St Louis, MO [N01-DK-9-2324]; Massachusetts General Hospital, Boston, MA [N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; University of Colorado School of Medicine, Denver, CO [N01-DK-9-2327, M01RR-00051, 1 UL1 RR 025780-01]; Carol McKinley, RN University of California-Irvine, Irvine, CA [N01-DK-9-2320, M01RR-00827]; University of Texas Southwestern Medical Center, Dallas, TX [N01-DK-9-2321, M01RR-00633, 1 UL1 RR024982-01]; University of Southern California, Los Angeles, CA [N01-DK-9-232, M01RR-00043]; University of Michigan Medical Center, Ann Arbor, MI [N01-DK-9-2323, M01RR-00042, 1 UL1 RR024986]; Virginia Commonwealth University Health System, Richmond, VA [N01-DK-9-2322, M01RR-00065]; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD; University of Washington, Seattle, WA [N01-DK-9-2318] FX In addition to the authors of this article, the following individuals were instrumental in the planning, conduct and/or care of patients enrolled in this study at each of the participating institutions as follows: University of Massachusetts Medical Center, Worcester, MA: (Contract N01-DK-9-2326) Gyongyi Szabo, MD, Barbara F. Banner, MD, Maureen Cormier, RN, Donna Giansiracusa, RN; University of Connecticut Health Center, Farmington, CT: (Grant M01RR-06192) Herbert L. Bonkovsky, MD, Gloria Borders, RN, Michelle Kelley, RN, ANP; Saint Louis University School of Medicine, St Louis, MO: (Contract N01-DK-9-2324) Adrian M. Di Bisceglie, MD, Bruce Bacon, MD, Brent Neuschwander-Tetri, MD, Elizabeth M. Brunt, MD, Debra King, RN; Massachusetts General Hospital, Boston, MA: (Contract N01-DK-9-2319, Grant M01RR-01066; Grant 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center) Jules L. Dienstag, MD, Raymond T. Chung, MD, Atul K. Bhan, MD, Wallis A. Molchen, Cara C. Gooch; University of Colorado School of Medicine, Denver, CO: (Contract N01-DK-9-2327, Grant M01RR-00051, Grant 1 UL1 RR 025780-01) Gregory T. Everson, MD, S. Russell Nash, MD, Jennifer DeSanto, RN, Carol McKinley, RN University of California-Irvine, Irvine, CA: (Contract N01-DK-9-2320, Grant M01RR-00827) Timothy R. Morgan, MD, John C. Hoefs, MD, John R. Craig, MD, M. Mazen Jamal, MD, MPH, Muhammad Sheikh, MD, Choon Park, RN; University of Texas Southwestern Medical Center, Dallas, TX: (Contract N01-DK-9-2321, Grant M01RR-00633, Grant 1 UL1 RR024982-01, North and Central Texas Clinical and Translational Science Initiative) Thomas E. Rogers, MD, Peter F. Malet, MD, Janel Shelton, Nicole Crowder, LVN, Rivka Elbein, RN, BSN, Nancy Liston, MPH; University of Southern California, Los Angeles, CA: (Contract N01-DK-9-2325, Grant M01RR-00043) Karen L. Lindsay, MD, MMM, Sugantha Govindarajan, MD, Carol B. Jones, RN, Susan L. Milstein, RN; University of Michigan Medical Center, Ann Arbor, MI: (Contract N01-DK-9-2323, Grant M01RR-00042, Grant 1 UL1 RR024986, Michigan Center for Clinical and Health Research) Anna S. Lok, MD, Joel K. Greenson, MD, Pamela A. Richtmyer, LPN, CCRC, R. Tess Bonham, BS; Virginia Commonwealth University Health System, Richmond, VA: (Contract N01-DK-9-2322, Grant M01RR-00065) Mitchell L. Shiffman, MD, Richard K. Sterling, MD, Melissa J. Contos, MD, A. Scott Mills, MD, Charlotte Hofmann, RN, Paula Smith, RN; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD: T. Jake Liang, MD, David Kleiner, MD, PhD, Yoon Park, RN, Elenita Rivera, RN, Vanessa Haynes-Williams, RN; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD: James E. Everhart, MD, Leonard B. Seeff, MD, Patricia R. Robuck, PhD, Jay H. Hoofnagle, MD, Elizabeth C. Wright, PhD; University of Washington, Seattle, WA: (Contract N01-DK-9-2318) Chihiro Morishima, MD, David R. Gretch, MD, PhD, Minjun Chung Apodaca, BS, ASCP; New England Research Institutes, Watertown, MA: (Contract N01-DK-9-2328) Kristin K. Snow, MSc, ScD, Anne M. Stoddard, ScD, Teresa M. Curto, MSW, MPH; Armed Forces Institute of Pathology, Washington, DC: Zachary D. Goodman, MD, PhD; Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, MD, Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD, Robert P. Perrillo, MD. This is publication #48 from the HALT-C Trial Group. The HALT-C Trial was registered with clinicaltrials.gov (#NCT00006164).; This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc, through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. NR 28 TC 21 Z9 21 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2010 VL 138 IS 7 BP 2321 EP U176 DI 10.1053/j.gastro.2010.02.058 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 602KB UT WOS:000278136900024 PM 20211180 ER PT J AU Lin, WY Tsai, WL Shao, RX Wu, GY Peng, LF Barlow, LL Chung, WJ Zhang, LL Zhao, H Jang, JY Chung, RT AF Lin, Wenyu Tsai, Wei-Lun Shao, Run-Xuan Wu, Guoyang Peng, Lee F. Barlow, Lydia L. Chung, Woo Jin Zhang, Leiliang Zhao, Hong Jang, Jae-Young Chung, Raymond T. TI Hepatitis C Virus Regulates Transforming Growth Factor beta 1 Production Through the Generation of Reactive Oxygen Species in a Nuclear Factor kappa B-Dependent Manner SO GASTROENTEROLOGY LA English DT Article DE Hepatitis C Virus; Reactive Oxygen Species; Nuclear Factor kappa B; Transforming Growth Factor beta 1 ID EPITHELIAL-MESENCHYMAL TRANSITION; OXIDATIVE STRESS; STELLATE CELLS; CORE PROTEIN; MITOCHONDRIAL INJURY; ACTIVATION; EXPRESSION; PATHWAYS; REPLICATION; INFECTION AB BACKGROUND & AIMS: The generation of oxidative stress and transforming growth factor beta 1 (TGF-beta 1) production play important roles in liver fibrogenesis. We have previously shown that hepatitis C virus (HCV) increases hepatocyte TGF-beta 1 expression. However, the mechanisms by which this induction occurs have not been well studied. We explored the possibility that HCV infection regulates TGF-beta 1 expression through the generation of reactive oxygen species (ROS), which act through >= 1 of the p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa B (NF kappa B) signaling pathways to induce TGF-beta 1 expression. METHODS: We used small molecule inhibitors and short interfering RNAs to knock down these pathways to study the mechanism by which HCV regulates TGF-beta 1 production in the infectious JFH1 model. RESULTS: We demonstrated that HCV induces ROS and TGF-beta 1 expression. We further found that JFH1 induces the phosphorylation of p38MAPK, JNK, ERK, and NF kappa B. We also found that HCV-mediated TGF-beta 1 enhancement occurs through a ROS-induced and p38 MAPK, JNK, ERK1/2, NF kappa B-dependent pathway. CONCLUSIONS: These findings provide further evidence to support the hypothesis that HCV enhances hepatic fibrosis progression through the generation of ROS and induction of TGF-beta 1. Strategies to limit the viral induction of oxidative stress appear to be warranted to inhibit fibrogenesis. C1 [Lin, Wenyu; Tsai, Wei-Lun; Shao, Run-Xuan; Wu, Guoyang; Peng, Lee F.; Barlow, Lydia L.; Chung, Woo Jin; Zhang, Leiliang; Zhao, Hong; Jang, Jae-Young; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Gastrointestinal Unit, Sch Med,Dept Med, Boston, MA 02114 USA. RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Gastrointestinal Unit, Sch Med,Dept Med, Warren 1007, Boston, MA 02114 USA. EM rtchung@partners.org FU NIH [R01 AI069939, U19 AI082630] FX This work was supported in part by NIH grants R01 AI069939 and U19 AI082630 (R.T.C.). NR 33 TC 84 Z9 89 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2010 VL 138 IS 7 BP 2509 EP U391 DI 10.1053/j.gastro.2010.03.008 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 602KB UT WOS:000278136900043 PM 20230822 ER PT J AU Horiuchi, A Nakayama, Y Kajiyama, M Kato, N Kamijima, T Graham, DY Tanaka, N AF Horiuchi, Akira Nakayama, Yoshiko Kajiyama, Masashi Kato, Naoyuki Kamijima, Tetsuya Graham, David Y. Tanaka, Naoki TI Biliary stenting in the management of large or multiple common bile duct stones SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID SHOCK-WAVE LITHOTRIPSY; ELECTROHYDRAULIC LITHOTRIPSY; ENDOSCOPIC SPHINCTEROTOMY; URSODEOXYCHOLIC ACID; DIFFICULT; MULTICENTER; CLEARANCE AB Background: Endoscopic biliary stenting with a plastic stent is often performed to prevent impaction of common bile duct (CBD) stones. The therapeutic effect of a plastic stent placement in terms of reduction in stone size and number has not been established. Objective: The aim of this study was to study the effect of biliary stenting as therapy for CBD stones. Design: Retrospective study. Setting: Municipal hospital outpatients. Interventions: Patients with large (>= 20 mm) and/or multiple (>= 3) stones had placement of a 7F double-pigtail plastic stent without stone extraction at the initial ERCP. Approximately 2 months later, stone removal was attempted. The number and size of CBD stones before and after stent placement, stone clearance, complications, and 180-day mortality were evaluated. Results: Forty patients were studied. Stent placement averaged 65 days (range, 50-82 days). The median number (interquartile range) of stones per patient fell after stent placement (4.0 [3.0] before vs. 2.0 [1.0] after; P < .0001). Characteristically, larger stones became smaller and small stones disappeared (ie, the median stone index decreased from 4.6 [3.0] to 2.0 [1.5]; P < .0001). Stone clearance at the second ERCP was achieved in 37 out of 40 patients (93%). Complications included cholangitis (13%) and pancreatitis (5%) after the second ERCP. No 180-day mortality occurred. Limitations: A retrospective, single-center study. Conclusions: Stent placement for 2 months was associated with large and/or multiple CBI) stones becoming smaller and/or disappearing without any complications. Stenting followed by a wait period may assist in difficult CBD stone removal. (Gastrointest Endosc 2010;71:1200-3.) C1 [Horiuchi, Akira; Nakayama, Yoshiko; Kajiyama, Masashi; Kato, Naoyuki; Kamijima, Tetsuya; Tanaka, Naoki] Showa Inan Gen Hosp, Ctr Digest Dis, Komagane 3994191, Japan. [Nakayama, Yoshiko] Shinshu Univ, Sch Med, Dept Pediat, Matsumoto, Nagano 390, Japan. [Tanaka, Naoki] Shinshu Univ, Grad Sch Med, Dept Metab Regulat, Matsumoto, Nagano 390, Japan. [Graham, David Y.] Michael E Debakey Vet Adm Med Ctr, Houston, TX USA. RP Horiuchi, A (reprint author), Showa Inan Gen Hosp, Ctr Digest Dis, Komagane 3994191, Japan. NR 18 TC 30 Z9 31 U1 0 U2 5 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 JUN PY 2010 VL 71 IS 7 BP 1200 EP 1203 DI 10.1016/j.gie.2009.12.055 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 608KL UT WOS:000278582700016 PM 20400079 ER PT J AU Shergill, AK McQuaid, KR Rempel, D AF Shergill, Amandeep K. McQuaid, Kenneth R. Rempel, David TI Call for guidelines on ergonomics in GI endoscopy Response SO GASTROINTESTINAL ENDOSCOPY LA English DT Letter C1 [Shergill, Amandeep K.; McQuaid, Kenneth R.] San Francisco VA Med Ctr, Div Gastroenterol, San Francisco, CA USA. [Rempel, David] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. [Rempel, David] Univ Calif San Francisco, Div Occupat Med, San Francisco, CA 94143 USA. RP Shergill, AK (reprint author), San Francisco VA Med Ctr, Div Gastroenterol, San Francisco, CA USA. RI Rempel, David/E-8424-2013 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 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUN PY 2010 VL 71 IS 7 BP 1333 EP 1333 DI 10.1016/j.gie.2009.11.039 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 608KL UT WOS:000278582700046 ER PT J AU Castelo-Branco, P Passer, BJ Buhrman, JS Antoszczyk, S Marinelli, M Zaupa, C Rabkin, SD Martuza, RL AF Castelo-Branco, P. Passer, B. J. Buhrman, J. S. Antoszczyk, S. Marinelli, M. Zaupa, C. Rabkin, S. D. Martuza, R. L. TI Oncolytic herpes simplex virus armed with xenogeneic homologue of prostatic acid phosphatase enhances antitumor efficacy in prostate cancer SO GENE THERAPY LA English DT Article DE HSV; TRAMP; virotherapy; cancer therapy ID CELL-LINES; THERAPY; ANTIGEN; GROWTH; IMMUNOTHERAPY; IMMUNIZATION; VACCINATION; VIROTHERAPY; INDUCTION; IMMUNITY AB Prostate cancer is one of the most prevalent cancers in men. Replication-competent oncolytic herpes simplex virus (oHSV) vectors are a powerful antitumor therapy that can exert at least two effects: direct cytocidal activity that selectively kills cancer cells and induction of antitumor immunity. In addition, oHSV vectors can also function as a platform to deliver transgenes of interest. In these studies, we have examined the expression of a xenogeneic homologue of the prostate cancer antigen, prostatic acid phosphatase (PAP), with the goal of enhancing virotherapy against PAP-expressing tumors. PAP has already been used for cancer vaccination in patients with prostate cancer. Here we show that treatment with oHSV bP Delta 6 expressing xenogeneic human PAP (hPAP) significantly reduces tumor growth and increases survival of C57/BL6 mice bearing mouse TRAMP-C2 prostate tumors, whereas expression of syngeneic mouse PAP (mPAP) from the same oHSV vector did not enhance antitumor activity. Treatment of mice bearing metastatic TRAMP-C2 lung tumors with oHSV-expressing hPAP resulted in fewer tumor nodules. To our knowledge, this is the first report of oncolytic viruses being used to express xenoantigens. These data lend support to the concept of combining oncolytic and immunogenic therapies as a way to improve therapy of metastatic prostate cancer. Gene Therapy (2010) 17, 805-810; doi: 10.1038/gt.2010.20; published online 11 March 2010 C1 [Castelo-Branco, P.; Passer, B. J.; Buhrman, J. S.; Antoszczyk, S.; Marinelli, M.; Zaupa, C.; Rabkin, S. D.; Martuza, R. L.] Massachusetts Gen Hosp, Mol Neurosurg Lab, Dept Neurosurg, Boston, MA 02114 USA. [Castelo-Branco, P.; Passer, B. J.; Antoszczyk, S.; Zaupa, C.; Rabkin, S. D.; Martuza, R. L.] Harvard Univ, Sch Med, Boston, MA USA. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, Mol Neurosurg Lab, Dept Neurosurg, MGH Simches Res Bldg,185 Cambridge St,CPZN-3800, Boston, MA 02114 USA. RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU DOD [W81XWH-04-1-0254]; NIH [R01 CA102139] FX We thank Dr M Crew for providing the mPAP cDNA and Dr Timothy C. Thompson for providing RM-1 cells. This work was supported in part by grants to RLM from the DOD (W81XWH-04-1-0254) and the NIH (R01 CA102139). NR 38 TC 16 Z9 17 U1 1 U2 6 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 JUN PY 2010 VL 17 IS 6 BP 805 EP 810 DI 10.1038/gt.2010.20 PG 6 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 608GL UT WOS:000278571400014 PM 20220784 ER PT J AU Shay, K Yoshikawa, TT AF Shay, Kenneth Yoshikawa, Thomas T. TI Overview of VA Healthcare for Older Veterans: Lessons Learned and Policy Implications SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID LONG-TERM-CARE; GERIATRICS C1 [Yoshikawa, Thomas T.] VA Greater Los Angeles Healthcare Syst, Staff Geriatr & Extended Care & Special Projects, Los Angeles, CA USA. NR 14 TC 2 Z9 2 U1 0 U2 4 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD SUM PY 2010 VL 34 IS 2 BP 20 EP 28 PG 9 WC Gerontology SC Geriatrics & Gerontology GA 685VJ UT WOS:000284655900004 ER PT J AU Cooley, SG Asthana, S AF Cooley, Susan G. Asthana, Sanjay TI Dementia Care for Veterans: Enhancing Comprehensive, Coordinated Services SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID CONTROLLED-TRIAL; HEALTH-CARE; DISEASE; INTERVENTION; PREVALENCE; CAREGIVERS; OUTCOMES; QUALITY; SYSTEM; COSTS C1 [Cooley, Susan G.] US Dept Vet Affairs, Off Geriatr & Extended Care, Washington, DC USA. [Asthana, Sanjay] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Cooley, SG (reprint author), US Dept Vet Affairs, Off Geriatr & Extended Care, Washington, DC USA. NR 14 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD SUM PY 2010 VL 34 IS 2 BP 57 EP 63 PG 7 WC Gerontology SC Geriatrics & Gerontology GA 685VJ UT WOS:000284655900009 ER PT J AU Braun, M Moye, J AF Braun, Michelle Moye, Jennifer TI Decisional Capacity Assessment: Optimizing Safety and Autonomy for Older Adults SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article C1 [Braun, Michelle] Boston VA Healthcare Syst, Boston, MA USA. [Moye, Jennifer] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Moye, Jennifer] VA Boston, Boston, MA USA. RP Braun, M (reprint author), Boston VA Healthcare Syst, Boston, MA USA. NR 6 TC 2 Z9 2 U1 2 U2 2 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD SUM PY 2010 VL 34 IS 2 BP 102 EP 105 PG 4 WC Gerontology SC Geriatrics & Gerontology GA 685VJ UT WOS:000284655900015 ER PT J AU Vage, J Wade, C Biagi, T Fatjo, J Amat, M Lindblad-Toh, K Lingaas, F AF Vage, J. Wade, C. Biagi, T. Fatjo, J. Amat, M. Lindblad-Toh, K. Lingaas, F. TI Association of dopamine- and serotonin-related genes with canine aggression SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Aggression; candidate genes; canine; dopamine; serotonin; SNP association ID ENGLISH COCKER-SPANIELS; GOLDEN-RETRIEVER DOGS; BEHAVIOR; SYSTEM; POLYMORPHISMS; DISORDERS; TARGETS; TRAITS AB Human-directed canine aggression was studied using 50 aggressive and 81 non-aggressive dogs. We examined 62 single nucleotide polymorphisms (SNPs) occurring in or in the close vicinity of 16 neurotransmitter-related genes. Allelic associations with aggression were identified for DRD1, HTR1D, HTR2C and SLC6A1. Risk or protective haplotypes for aggressive behaviour based on 2-5 SNPs were identified. The frequency of aggressive dogs varied significantly between the haplotypes within loci and the odds ratios of aggression in dogs with risk haplotypes compared with protective haplotypes varied from 4.4 (HTR2C) to 9.0 (SLC6A1). A risk haplotype across the neurotransmitter receptor gene HTR1D harboured a non-synonymous SNP with a potential effect on protein function. We identified no haplotypes in complete association with the recorded phenotypes, supporting a complex inheritance of aggression. C1 [Vage, J.; Lingaas, F.] Norwegian Sch Vet Sci, Dept Basic Sci & Aquat Med, Div Genet, Oslo, Norway. [Wade, C.; Biagi, T.; Lindblad-Toh, K.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Wade, C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Wade, C.] Univ Sydney, Fac Vet Sci, Sydney, NSW 2006, Australia. [Fatjo, J.; Amat, M.] Univ Autonoma Barcelona, Fac Vet Barcelona, Dept Biol Cellular Fisiol & Immunol, E-08193 Barcelona, Spain. [Lindblad-Toh, K.] Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden. RP Lingaas, F (reprint author), Norwegian Sch Vet Sci, Dept Basic Sci & Aquat Med, Div Genet, Oslo, Norway. EM frode.lingaas@veths.no RI Amat, Marta/L-5902-2014 OI Amat, Marta/0000-0002-6017-1341 FU European Commission (LUPA) [GA-201370] FX This work was partly funded by the European Commission (LUPA, GA-201370). NR 29 TC 21 Z9 22 U1 8 U2 51 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD JUN PY 2010 VL 9 IS 4 BP 372 EP 378 DI 10.1111/j.1601-183X.2010.00568.x PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 605AA UT WOS:000278318400003 PM 20132314 ER PT J AU Araldi, E Schipani, E AF Araldi, Elisa Schipani, Ernestina TI MicroRNA-140 and the silencing of osteoarthritis SO GENES & DEVELOPMENT LA English DT Article DE MicroRNA; miR-140; osteoarthritis; cartilage; Adamts-5 ID JOINT FORMATION; SMALL RNAS; CAENORHABDITIS-ELEGANS; ARTICULAR-CARTILAGE; GROWTH-PLATE; DIFFERENTIATION; DICER; MORPHOGENESIS; SKELETON; TARGETS AB MicroRNAs (miRNAs) have emerged as important modulators in development, tissue homeostasis, and diseases. In this issue of Genes & Development, Miyaki and colleagues (pp. 1173-1185) report that miR-140 is involved in the pathogenesis of osteoarthritis by regulating, at least in part, ADAMTS5. Moreover, mice lacking miR-140 are dwarf as a consequence of impaired chondrocyte proliferation. This study is the first in vivo demonstration that miR-140 has a critical and nonredundant role in cartilage development and homeostasis. C1 [Araldi, Elisa; Schipani, Ernestina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Schipani, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu FU NIH [RO1 AR048191-06] FX We thank Dr. Tatsuya Kobayashi for helpful discussions. This paper was supported by NIH RO1 AR048191-06 to E.S. NR 49 TC 23 Z9 33 U1 2 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 2010 VL 24 IS 11 BP 1075 EP 1080 DI 10.1101/gad.1939310 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 604GJ UT WOS:000278267200002 PM 20516192 ER PT J AU Johnson, AD Bhimavarapu, A Benjamin, EJ Fox, C Levy, D Jarvik, GP O'Donnell, CJ AF Johnson, Andrew D. Bhimavarapu, Anupama Benjamin, Emelia J. Fox, Caroline Levy, Daniel Jarvik, Gail P. O'Donnell, Christopher J. TI CLIA-tested genetic variants on commercial SNP arrays: Potential for incidental findings in genome-wide association studies SO GENETICS IN MEDICINE LA English DT Article DE SNP; GWAS; incidental finding; return of results; genetic ID RECURRENT VENOUS THROMBOEMBOLISM; FAMILIAL MEDITERRANEAN FEVER; HEREDITARY HEMOCHROMATOSIS; LONG-TERM; FRAMINGHAM; RECOMMENDATIONS; PANCREATITIS; POPULATION; MUTATIONS; DIAGNOSIS AB Purpose: Increases in throughput and affordability of genotyping products have led to large sample sizes in genetic studies, increasing the likelihood that incidental genetic findings may occur. We set out to survey potential notifiable variants on arrays used in genome-wide association studies and in direct-to-consumer genetic services. Methods: We used multiple bioinformatics strategies to identify, and map variants tested for genetic disorders in >= 2 CLIA-approved laboratories (based on the GeneTests database). We subsequently surveyed 18 commercial single nucleotide polymorphism arrays and HapMap for these variants. Results: Of 1,362 genes tested according to GeneTests, we identified 298 specific targeted mutations measured in more than or equal to two laboratories, encompassing 56 disorders. Only 88 of 298 mutations could be identified as known single nucleotide polymorphisms in genomic databases. We found 18 of 88 single nucleotide polymorphisms present in HapMap or on commercial single nucleotide polymorphism arrays. Homozygotes for rare alleles of some variants were identified in the Framingham Heart Study, an active genome-wide association studies cohort (n = 8,410). Conclusions: Variants in genes including APOE, F5, HFE, CYP21A2, MEFV, SPINK1, BTD, GALT, and G6PD were found on single nucleotide polymorphism arrays or in the HapMap. Some of these variants may warrant further review to determine their likelihood to trigger incidental findings in the course of genome-wide association studies or direct-to- consumer testing. Genet Med 2010:12(6):355-363. C1 [Johnson, Andrew D.; Bhimavarapu, Anupama; Benjamin, Emelia J.; Fox, Caroline; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Johnson, Andrew D.; Bhimavarapu, Anupama; Fox, Caroline; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Johnson, Andrew D.; Bhimavarapu, Anupama; Fox, Caroline; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Benjamin, Emelia J.; Levy, Daniel] Boston Univ, Div Cardiol, Sch Med & Publ Hlth, Boston, MA 02215 USA. [Jarvik, Gail P.] Univ Washington, Med Ctr, Div Med Genet, Seattle, WA 98195 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov RI Johnson, Andrew/G-6520-2013; Jarvik, Gail/N-6476-2014; OI Jarvik, Gail/0000-0002-6710-8708; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; NHLBI; NIH; State of Washington Life Sciences Discovery Fund FX Supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195). ADJ was supported by an NHLBI IRTA fellowship award. AB was supported by the NIH Summer Internship Program in Biomedical Research. GPJ was supported by a State of Washington Life Sciences Discovery Fund. NR 37 TC 13 Z9 13 U1 0 U2 4 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 JUN PY 2010 VL 12 IS 6 BP 355 EP 363 DI 10.1097/GIM.0b013e3181e1e2a9 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 609EO UT WOS:000278638400005 PM 20556870 ER PT J AU Xie, D Chen, CC Ptaszek, LM Xiao, S Cao, XY Fang, F Ng, HH Lewin, HA Cowan, C Zhong, S AF Xie, Dan Chen, Chieh-Chun Ptaszek, Leon M. Xiao, Shu Cao, Xiaoyi Fang, Fang Ng, Huck H. Lewin, Harris A. Cowan, Chad Zhong, Sheng TI Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species SO GENOME RESEARCH LA English DT Article ID STEM-CELLS; RNA INTERFERENCE; TRANSCRIPTIONAL REGULATION; SIGNALING PATHWAYS; GENOME-WIDE; MOUSE; EXPRESSION; EVOLUTION; REVEALS; BOVINE AB Mammalian preimplantation embryonic development (PED) is thought to be governed by highly conserved processes. While it had been suggested that some plasticity of conserved signaling networks exists among different mammalian species, it was not known to what extent modulation of the genomes and the regulatory proteins could "rewire" the gene regulatory networks (GRN) that control PED. We therefore generated global transcriptional profiles from three mammalian species (human, mouse, and bovine) at representative stages of PED, including: zygote, two-cell, four-cell, eight-cell, 16-cell, morula and blastocyst. Coexpression network analysis suggested that 40.2% orthologous gene triplets exhibited different expression patterns among these species. Combining the expression data with genomic sequences and the ChIP-seq data of 16 transcription regulators, we observed two classes of genomic changes that contributed to interspecies expression difference, including single nucleotide mutations leading to turnover of transcription factor binding sites, and insertion of cis-regulatory modules (CRMs) by transposons. About 10% of transposons are estimated to carry CRMs, which may drive species-specific gene expression. The two classes of genomic changes act in concert to drive mouse-specific expression of MTF2, which links POU5F1/NANOG to NOTCH signaling. We reconstructed the transition of the GRN structures as a function of time during PED. A comparison of the GRN transition processes among the three species suggested that in the bovine system, POU5F1's interacting partner SOX2 may be replaced by HMGB1 (a TF sharing the same DNA binding domain with SOX2), resulting in rewiring of GRN by a trans change. C1 [Xie, Dan; Chen, Chieh-Chun; Xiao, Shu; Zhong, Sheng] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Ptaszek, Leon M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ptaszek, Leon M.; Cowan, Chad] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ptaszek, Leon M.; Cowan, Chad] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Ptaszek, Leon M.; Cowan, Chad] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Cao, Xiaoyi] Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA. [Fang, Fang; Ng, Huck H.] Genome Inst Singapore, Gene Regulat Lab, Singapore 138672, Singapore. [Lewin, Harris A.; Zhong, Sheng] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA. [Zhong, Sheng] Univ Illinois, Dept Stat, Urbana, IL 61801 USA. RP Zhong, S (reprint author), Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. EM szhong@illinois.edu RI Ng, Huck Hui/A-1135-2009; Xiao, Shu/H-1007-2014; Fang, Fang/G-7679-2016; Cao, Xiaoyi/D-4646-2017 OI Cao, Xiaoyi/0000-0001-7222-5450 FU NSF [DBI 08-45823]; USDA Agricultural Research Service [AG 58-12657-317] FX We thank the Douglas Melton lab for initiating this collaboration by supplying human IVF embryos, all duly obtained by full review of an ESCRO committee and IRB with certified consent forms. We thank Carole Wilson and Mark Band for microarray experiments. We thank Tetsuya Tanaka, Yanen Li, and Wei Huang for useful discussions. This work is partially supported by NSF DBI 08-45823 (S.Z.) and USDA Agricultural Research Service AG 58-12657-317 (H.A.L.). NR 45 TC 102 Z9 104 U1 1 U2 8 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 JUN PY 2010 VL 20 IS 6 BP 804 EP 815 DI 10.1101/gr.100594.109 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 604HF UT WOS:000278269400011 PM 20219939 ER PT J AU Hayakawa, K Arai, K Lo, EH AF Hayakawa, Kazuhide Arai, Ken Lo, Eng H. TI Role of ERK MAP Kinase and CRM1 in IL-1 beta-Stimulated Release of HMGB1 from Cortical Astrocytes SO GLIA LA English DT Article DE reactive astrocytes; high-mobility group box1; IL-1 beta; ERK signaling; CRM1/exportin1 ID GROUP BOX-1 PROTEIN; ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; DEPENDENT MECHANISM; BRAIN ISCHEMIA; RAT-BRAIN; CELLS; INFLAMMATION; ACTIVATION; MEDIATOR AB Reactive astrocytes are traditionally thought to impede brain plasticity after stroke. However, we previously showed that reactive astrocytes may also contribute to stroke recovery, partly via the release of a nuclear protein called high-mobility group box 1. (HMGB1). Here, we investigate the mechanisms that allow stimulated astrocytes to release HMGB1. Exposure of rat primary astrocytes to IL-1 beta for 24 h elicited a dose-dependent HMGB1 response. Immunostaining and western blots of cell lysates showed increased intracellular levels of HMGB1. Western blots confirmed that IL-1 beta induced a release of HMGB1 into astrocyte conditioned media. MAP kinase signaling was involved. Levels of phospho-ERK were increased by IL-1 beta, and the MEK/ERK inhibitor U0126 decreased HMGB1 up-regulation in the stimulated astrocytes. Since HMGB1. is a nuclear protein, the role of the nuclear protein exporter, chromosome region maintenance 1 (CRM1), was assessed as a candidate mechanism for linking MAP kinase signaling to HMGB1 release. IL-1 beta increased CRM1 expression in concert with a translocation of HMGB1 from nucleus into cytoplasm. Blockade of IL-1 beta-stimulated HMGB1 release with the ERK inhibitor U0126 was accompanied by a downregulation of CRM1. Our findings reveal that IL-1 beta stimulates the release of HMGB1 from activated astrocytes via ERK MAP kinase and CRM1 signaling. These data suggest a novel pathway by which inflammatory cytokines may enhance the ability of reactive astrocytes to release prorecovery mediators after stroke. (C) 2010 Wiley-Liss, Inc. C1 [Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, MGH East 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU NIH [P01-NS55104, R37-NS37074, R01-NS48422, R01-NS53560]; American Heart Association; Deane Institute; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Japan Society for the Promotion of Science FX Grant sponsor: NIH; Grant numbers: P01-NS55104, R37-NS37074, R01-NS48422, R01-NS53560; Grant sponsors: American Heart Association, Deane Institute, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Japan Society for the Promotion of Science (Postdoctoral Fellowship for Research Abroad) NR 44 TC 33 Z9 35 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD JUN PY 2010 VL 58 IS 8 BP 1007 EP 1015 DI 10.1002/glia.20982 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 596RO UT WOS:000277703100011 PM 20222144 ER PT J AU Schernhammer, ES Giovannucci, E Kawasaki, T Rosner, B Fuchs, CS Ogino, S AF Schernhammer, Eva S. Giovannucci, Edward Kawasaki, Takako Rosner, Bernard Fuchs, Charles S. Ogino, Shuji TI Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer SO GUT LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; DNA DEMETHYLATION; CHROMOSOMAL INSTABILITY; METHYLATION LEVEL; MULTIVITAMIN USE; COMPETING RISKS; NURSES HEALTH; LIFE-STYLE AB Background and aims Although critical for methylation reactions, how dietary folate and B vitamins affect global DNA methylation level in colorectal cancers is currently unknown. Long interspersed nucleotide element-1 (LINE-1) is an emerging indicator of genome-wide DNA methylation level that has previously been linked to colon cancer survival. Methods We examined the association between dietary intake of folate, alcohol and B vitamins and LINE-1 hypomethylation in 609 incident colon cancers, utilising the database of two independent prospective cohort studies. Results Participants with >= 400 mg folate intake per day were significantly less likely to develop LINE-1 hypomethylated colon cancers than those reporting <200 mu g of folate intake per day (RR=0.57, 95% CI=0.36 to 0.91 for <55% LINE-1 methylated colon tumours; RR=0.74, 95% CI=0.51 to 1.06 for 55-64% LINE-1 methylated colon tumours; and RR=1.08, 95% CI=0.66 to 1.75 for >= 65% LINE-1 methylated tumours; P(interaction)=0.01). By contrast, high alcohol consumption conferred a higher risk of LINE-1 hypomethylated cancers (>= 15 g alcohol per day versus none, RR=1.67, 95% CI=1.04 to 2.67 for <55% LINE-1 methylated tumours; and RR=1.55, 95% CI=1.10 to 2.18 for 55-64% LINE-1 methylated tumours) but had no association with >= 65% LINE-1 methylated tumours (RR=1.06, 95% CI=0.69 to 1.62). High intakes of vitamin B(6), B(12) or methionine were not significantly associated with colon cancers, regardless of LINE-1 methylation level. Conclusion The influence of dietary folate intake and alcohol consumption on colon cancer risk differs significantly according to tumoral LINE-1 methylation level. C1 [Schernhammer, Eva S.; Rosner, Bernard; Fuchs, Charles S.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Schernhammer, Eva S.; Rosner, Bernard; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Schernhammer, Eva S.; Giovannucci, Edward; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Schernhammer, Eva S.] KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. [Schernhammer, Eva S.] ACR ITR Vienna, Vienna, Austria. [Kawasaki, Takako; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Schernhammer, ES (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM schernhammer@channing.harvard.edu FU National Institutes of Health [CA70817, CA87969, CA55075, CA42812, CA58684, CA90598, CA122826]; Entertainment Industry Foundation National Colorectal Cancer Research Alliance (NCCRA); Bennett Family Fund and Entertainment Industry Foundation FX This work is supported by National Institutes of Health research grants CA70817, CA87969, CA55075, CA42812, CA58684, CA90598, CA122826, the Bennett Family Fund and Entertainment Industry Foundation, and the Entertainment Industry Foundation National Colorectal Cancer Research Alliance (NCCRA). NR 41 TC 72 Z9 74 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUN PY 2010 VL 59 IS 6 BP 794 EP 799 DI 10.1136/gut.2009.183707 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 605ZB UT WOS:000278387700017 PM 19828464 ER PT J AU Darcy, KM Birrer, MJ AF Darcy, Kathleen M. Birrer, Michael J. TI Translational research in the Gynecologic Oncology Group: Evaluation of ovarian cancer markers, profiles, and novel therapies SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Markers; Profiles; Tumor biology; Novel therapies; Translational research ID PHASE-III TRIAL; PRIMARY PERITONEAL CARCINOMA; MAMMARY EPITHELIAL-CELLS; PLATINUM-BASED TREATMENT; STAGE-III; INTRAPERITONEAL CISPLATIN; INTRAVENOUS CISPLATIN; PROGNOSTIC RELEVANCE; RECEPTOR EXPRESSION; DISEASE PROGRESSION AB Objectives. To review the translational research (TR) performed in the Gynecologic Oncology Group (COG) to evaluate ovarian cancer markers, profiles and novel therapies. Methods. Prospective trials with stand alone or embedded TR objectives involving patient and specimen accrual as well as retrospective studies using banked specimens and resources were and continue to be performed in the COG. Appropriate statistical methods are employed to evaluate associations with clinical characteristics and outcomes including tumor response, adverse events, progression free survival and overall survival. Results. Highlights are presented for some of the collaborative and multidisciplinary TR conducted with the COG to evaluate markers, pathway and novel therapeutics in epithelial ovarian, primary peritoneal and/or fallopian tube cancer. For example, in COG 111, high immunohistochemical (IHC) expression of cyclin E was associated with a shorter median survival (29 versus 35 months) and an increased risk of death (hazard ratio [HR]=1.4, 95% confidence interval [CI]=1.0-2.1, p=0.05). In COG 114/132, non-detectable immunoblot expression of maspin was associated with debulking status (p=0.034) and an increased risk of disease progression (HR=1.89, 95% CI=1.04-3.45, p=0.038) and death (HR=1.99, 95% CI=1.07-3.69, p=0.030) while high CD105-microvessel density (MVD), but not CD31-MVD in tumor was associated with increased risk of disease progression (HR=1.873, 95% CI=1.102-3.184, p=0.020) but not death. In COG 172, low IHC expression of BRCA1 was associated with advanced stage (p<0.001), serous histology (p<0.001) and a reduced risk of disease progression (HR=0.64, 95% CI=0.42-0.96) and death (HR=0.51, 95% CI-=0.32-0.83) while the CA/AA versus CC genotypes in C8092A in ERCC1 were associated with an increased risk of disease progression (HR=1.44, 95% CI=1.06-1.94, p=0.018) and death (HR=1.50, 95% CI=1.07-2.09, p=0.018). Conclusions. The COG has an extensive TR program that provides clues regarding the molecular and biochemical mechanisms of disease, treatments and outcomes in women with or at risk for a gynecologic malignancy. (C) 2010 Elsevier Inc. All rights reserved.5 C1 [Darcy, Kathleen M.] Roswell Pk Canc Inst, GOG Stat & Data Ctr, Res Studies Ctr, Buffalo, NY 14263 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Darcy, KM (reprint author), Roswell Pk Canc Inst, GOG Stat & Data Ctr, Res Studies Ctr, Rm 516,Carlton & Elm St, Buffalo, NY 14263 USA. EM darcy@gogstats.org FU National Cancer Institute (NCI) [CA 27469, CA 37517] FX This review was supported by National Cancer Institute (NCI) grants to the Gynecologic Oncology Group (COG) Administrative Office (CA 27469) and the COG Statistical and Data Center (CA 37517). NR 56 TC 20 Z9 22 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 2010 VL 117 IS 3 BP 429 EP 439 DI 10.1016/j.ygyno.2010.01.048 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 607NI UT WOS:000278510400006 PM 20233625 ER PT J AU Stuart, R Ravandi, F Cripe, L Maris, M Cooper, M Dakhil, S Stone, R Turturro, F Fox, J Michelson, G AF Stuart, R. Ravandi, F. Cripe, L. Maris, M. Cooper, M. Dakhil, S. Stone, R. Turturro, F. Fox, J. Michelson, G. TI VORELOXIN SINGLE-AGENT TREATMENT OF OLDER PATIENTS (AT LEAST 60 YEARS) WITH PREVIOUSLY UNTREATED ACUTE MYELOID LEUKEMIA: FINAL RESULTS FROM A PHASE 2 STUDY WITH 3 SCHEDULES SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Stuart, R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Ravandi, F.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cripe, L.] Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. [Maris, M.] Rocky Mt Blood & Marrow Transplant Program, Denver, CO USA. [Cooper, M.] St Francis Hosp, Indianapolis, IN USA. [Dakhil, S.] Canc Ctr Kansas, Wichita, KS USA. [Stone, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Turturro, F.] LSUHSC, Feist Weiller Canc Ctr, Shreveport, LA USA. [Fox, J.; Michelson, G.] Sunesis Pharmaceut Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0070 BP 28 EP 28 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300071 ER PT J AU Kuter, J Newland, A Bussel, J Wasser, J Nie, K Jun, S AF Kuter, J. Newland, A. Bussel, J. Wasser, J. Nie, K. Jun, S. TI EVALUATION OF EFFICACY AND SAFETY OF LONG-TERM ROMIPLOSTIM TREATMENT FOR PATIENTS WITH IMMUNE THROMBOCYTOPENIA (ITP) ENROLLED IN AN OPEN-LABEL EXTENSION STUDY: A PATIENT COHORT-ANALYSIS SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Kuter, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Newland, A.] Royal London Hosp, Dept Haematol, London E1 1BB, England. [Bussel, J.] New York Presbyterian Hosp, Dept Pediat, New York, NY USA. [Bussel, J.] New York Presbyterian Hosp, Dept Med, New York, NY USA. [Wasser, J.] Manchester Mem Hosp, Manchester, NH USA. [Nie, K.; Jun, S.] Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0189 BP 76 EP 76 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300189 ER PT J AU Wilson, H O'Connor, A Czuczman, S LaCasce, S Gerecitano, F Leonard, P Tulpule, A Xiong, H Chiu, YL Busman, T Enschede, H Krivoshik, P Humerickhouse, H AF Wilson, H. O'Connor, A. Czuczman, S. LaCasce, S. Gerecitano, F. Leonard, P. Tulpule, A. Xiong, H. Chiu, Y. L. Busman, T. Enschede, H. Krivoshik, P. Humerickhouse, H. TI PHASE 1/2A STUDY OF NAVITOCLAX (ABT-263) IN RELAPSED OR REFRACTORY LYMPHOID MALIGNANCIES SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Wilson, H.] NCI, Bethesda, MD 20892 USA. [O'Connor, A.] NYU, Inst Canc, New York, NY USA. [Czuczman, S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [LaCasce, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gerecitano, F.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Leonard, P.] Weill Cornell Med Coll, New York, NY USA. [Tulpule, A.] USC Kenneth Norris Canc Hosp, Canc Hosp & Res Inst, Los Angeles, CA USA. [Xiong, H.; Chiu, Y. L.; Busman, T.; Enschede, H.; Krivoshik, P.; Humerickhouse, H.] Abbott Labs, Abbott Pk, IL 60064 USA. RI Jones, Jeffrey/E-9827-2013 NR 0 TC 1 Z9 1 U1 1 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 JUN PY 2010 VL 95 SU 2 MA 0292 BP 116 EP 117 PG 2 WC Hematology SC Hematology GA 614IY UT WOS:000279051300292 ER PT J AU Grass, S Preuss, KD Wikowicz, A Terpos, E Dimopoulos, M Treon, S Hunter, Z Iida, S Inagaki, A Ueda, R Pfreundschuh, M AF Grass, S. Preuss, K. D. Wikowicz, A. Terpos, E. Dimopoulos, M. Treon, S. Hunter, Z. Iida, S. Inagaki, A. Ueda, R. Pfreundschuh, M. TI THE ROLE OF HYPERPHOSPHORYLATED PARATARG-7-THE FIRST AUTOSOMAL-DOMINANTLY INHERITED RISK FACTOR FOR HEMATOLOGICAL NEOPLASMS - IN MGUS, MULTIPLE MYELOMA AND LYMPHOMAS IN DIFFERENT ETHNICS GROUPS SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Grass, S.; Preuss, K. D.; Wikowicz, A.; Pfreundschuh, M.] Jose Carreras Ctr Immuno & Gene Therapy, Homburg, Germany. [Terpos, E.; Dimopoulos, M.] Univ Athens, Sch Med, Dept Clin Therapeut, GR-11527 Athens, Greece. [Treon, S.; Hunter, Z.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Iida, S.; Inagaki, A.; Ueda, R.] Nagoya City Univ, Dept Hematol, Nagoya, Aichi, Japan. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0341 BP 138 EP 138 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300341 ER PT J AU Maiso, P Azab, A Roccaro, A Rommel, C Azab, F Sacco, A Ngo, H Liu, Y Quang, P Zhang, Y Liu, Y Morgan, B Anderson, K Ghobrial, I AF Maiso, P. Azab, A. Roccaro, A. Rommel, C. Azab, F. Sacco, A. Ngo, H. Liu, Y. Quang, P. Zhang, Y. Liu, Y. Morgan, B. Anderson, K. Ghobrial, I. TI INHIBITION OF-TORC1 AND-TORC2 REPRESENTS A NEW APPROACH IN THE TREATMENT OF MULTIPLE MYELOMA SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Maiso, P.; Azab, A.; Roccaro, A.; Azab, F.; Sacco, A.; Ngo, H.; Quang, P.; Zhang, Y.; Liu, Y.; Morgan, B.; Anderson, K.; Ghobrial, I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rommel, C.; Liu, Y.] Intellikine, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0343 BP 138 EP 139 PG 2 WC Hematology SC Hematology GA 614IY UT WOS:000279051300343 ER PT J AU Fulciniti, M Nanjappa, P Amin, S Hideshima, T Rodig, S Tassone, P Anderson, K Munshi, N AF Fulciniti, M. Nanjappa, P. Amin, S. Hideshima, T. Rodig, S. Tassone, P. Anderson, K. Munshi, N. TI TETRA-O-METHYL NORDIHYDROGUAIARETIC ACID (TERAMEPROCOL) INDUCES MYELOMA GROWTH ARREST AND APOPTOSIS BY INHIBITING SP1 ACTIVITY SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Fulciniti, M.; Nanjappa, P.; Amin, S.; Hideshima, T.; Rodig, S.; Anderson, K.; Munshi, N.] DFCI, Boston, MA USA. [Tassone, P.] UNICZ, Catanzaro, Italy. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JUN PY 2010 VL 95 SU 2 MA 0346 BP 140 EP 140 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300346 ER PT J AU Perrone, G Calabrese, E Gorgun, G Cristea, D Santo, L Cavo, M Hideshima, T Anderson, K AF Perrone, G. Calabrese, E. Gorgun, G. Cristea, D. Santo, L. Cavo, M. Hideshima, T. Anderson, K. TI JAK2/STAT3 PATHWAY: A NEW TARGET OF PANOBINOSTAT IN MULTIPLE MYELOMA SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Perrone, G.; Cavo, M.] Inst Hematol & Med Oncol Seragnoli, Bologna, Italy. [Calabrese, E.] Univ studi La Sapienza, Inst Hematol, Rome, Italy. [Gorgun, G.; Cristea, D.; Santo, L.; Hideshima, T.; Anderson, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 JUN PY 2010 VL 95 SU 2 MA 0347 BP 140 EP 140 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300347 ER PT J AU Sedlak, J Pastorek, M Balaz, P Cholujova, D Hunakova, L Duraj, J Jakubikova, J AF Sedlak, J. Pastorek, M. Balaz, P. Cholujova, D. Hunakova, L. Duraj, J. Jakubikova, J. TI SYNERGISTIC CYTOTOXIC EFFECT OF COMBINED TREATMENT WITH NANOSIZED REALGAR PARTICLES AND SULFORAPHANE IN MULTIPLE MYELOMA CELLS IN VITRO SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Sedlak, J.; Pastorek, M.; Cholujova, D.; Hunakova, L.; Duraj, J.] Canc Res Inst SAS, Bratislava, Slovakia. [Balaz, P.] Inst Geotechn SAS, Kosice, Slovakia. [Jakubikova, J.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2010 VL 95 SU 2 MA 0353 BP 142 EP 142 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300353 ER PT J AU Jakubowiak, J Benson, D Bensinger, W Siegel, DD Zimmerman, T Mohrbacher, A Richardson, P Afar, D Singhal, A Anderson, K AF Jakubowiak, J. Benson, D. Bensinger, W. Siegel, D. DiCapua Zimmerman, T. Mohrbacher, A. Richardson, P. Afar, D. Singhal, A. Anderson, K. TI ELOTUZUMAB IN COMBINATION WITH BORTEZOMIB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA WITH ONE TO THREE PRIOR THERAPIES: A PHASE 1 STUDY SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Jakubowiak, J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Benson, D.] Ohio State Univ, Columbus, OH 43210 USA. [Bensinger, W.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Siegel, D. DiCapua] Hackensack Univ Med Ctr, Hackensack, NJ USA. [Zimmerman, T.] Univ Chicago, Chicago, IL 60637 USA. [Mohrbacher, A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Richardson, P.; Anderson, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Afar, D.; Singhal, A.] Facet Biotech Corp, Redwood City, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0374 BP 151 EP 151 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300372 ER PT J AU Kumar, K Blade, J Crowley, J Goldschmidt, H Hoering, A Jagannath, S Klein, S Lahuerta, J Laubach, J Lee, J Moreau, P Morgan, G Orlowski, R Palumbo, A Richardson, P San Miguel, J Sezer, O Siegel, D Sonneveld, P Szymonifka, J Rajkumar, V Durie, B AF Kumar, K. Blade, J. Crowley, J. Goldschmidt, H. Hoering, A. Jagannath, S. Klein, S. Lahuerta, J. Laubach, J. Lee, J. Moreau, P. Morgan, G. Orlowski, R. Palumbo, A. Richardson, P. San Miguel, J. Sezer, O. Siegel, D. Sonneveld, P. Szymonifka, J. Rajkumar, V. Durie, B. TI OUTCOME OF PATIENTS WITH MYELOMA RELAPSING AFTER IMID AND BORTEZOMIB THERAPY: A MULTICENTER STUDY FROM THE INTERNATIONAL MYELOMA FOUNDATION WORKING GROUP SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Kumar, K.] Mayo Clin, Rochester, MN USA. [Blade, J.] Hosp Clin Barcelona, Barcelona, Spain. [Crowley, J.; Hoering, A.] Canc Res & Biostat, Seattle, WA USA. [Goldschmidt, H.] Univ Heidelberg, Heidelberg, Germany. [Jagannath, S.] St Vincent Catholic Med Ctr, New York, NY USA. [Klein, S.] Erasmus MC, Rotterdam, Netherlands. [Lahuerta, J.] Univ Hosp, Madrid, Spain. [Laubach, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lee, J.] Gachon Univ, Sch Med, Inchon, South Korea. [Moreau, P.] Univ Hosp Hotel Dieu, Nantes, France. [Morgan, G.] Royal Marsden Hosp, Sutton, Surrey, England. [Orlowski, R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Palumbo, A.] Univ Turin, Turin, Italy. [San Miguel, J.] Univ Salamanca, Hosp Clin Univ, E-37008 Salamanca, Spain. [Sezer, O.] Univ Wurzburg, Wurzburg, Germany. [Siegel, D.] Hackensack Univ Med Ctr, Ctr Canc, Hackensack, NJ USA. [Szymonifka, J.; Durie, B.] Cedars Sinai Outpatient Canc Ctr, Los Angeles, CA USA. RI richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 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 JUN PY 2010 VL 95 SU 2 MA 0376 BP 151 EP 152 PG 2 WC Hematology SC Hematology GA 614IY UT WOS:000279051300374 ER PT J AU Richardson, P Weber, D Mitsiades, C Dimopoulos, M Harousseau, JL Howe, J Graef, T Gause, C Byrne, C Anderson, K Siegel, D AF Richardson, P. Weber, D. Mitsiades, C. Dimopoulos, M. Harousseau, J. L. Howe, J. Graef, T. Gause, C. Byrne, C. Anderson, K. Siegel, D. TI A PHASE I STUDY OF VORINOSTAT, LENALIDOMIDE, AND DEXAMETHASONE FOR RELAPSED AND REFRACTORY MULTPLE MYELOMA SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Richardson, P.; Mitsiades, C.; Anderson, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weber, D.] MD Anderson Canc Ctr, Houston, TX USA. [Dimopoulos, M.] Univ Athens, Sch Med, Athens, Greece. [Harousseau, J. L.] Ctr Rene Gauducheau, St Herblain, France. [Howe, J.; Graef, T.; Gause, C.] Merck & Co Inc, Upper Gwynedd, NJ USA. [Byrne, C.] Celgene Corp, Summit, NJ USA. [Siegel, D.] Hackensack Univ, Ctr Med, Hackensack, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0385 BP 155 EP 156 PG 2 WC Hematology SC Hematology GA 614IY UT WOS:000279051300383 ER PT J AU San Miguel, J Sezer, O Siegel, D Guenther, A Blade, J Prosser, I Hazell, K Bengoudifa, R Klebsattel, M Bourquelot, P Cavo, M Goebeler, M Niederweiser, D Milder, M Boccadoro, M Anderson, K AF San Miguel, J. Sezer, O. Siegel, D. Guenther, A. Blade, J. Prosser, I. Hazell, K. Bengoudifa, R. Klebsattel, M. Bourquelot, P. Cavo, M. Goebeler, M. Niederweiser, D. Milder, M. Boccadoro, M. Anderson, K. TI A PHASE IB DOSE-ESCALATION STUDY OF ORAL PANOBINOSTAT (LBH589) AND IV BORTEZOMIB IN PATIENTS WITH RELAPSED OR RELAPSED AND REFRACTORY MULTIPLE MYELOMA SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [San Miguel, J.] Hosp Univ Salamanca, Salamanca, Spain. [Sezer, O.; Goebeler, M.] Univ Wurzburg, D-97070 Wurzburg, Germany. [Siegel, D.] Hackensack Univ, Ctr Med, Hackensack, NJ USA. [Guenther, A.] Div Stem Cell Transplantat & Immunotherapy, Kiel, Germany. [Guenther, A.] Dept Med, Kiel, Germany. [Blade, J.] Hosp & Clin, Barcelona, Spain. [Prosser, I.] Canberra Hosp, Canberra, ACT, Australia. [Hazell, K.; Bengoudifa, R.; Klebsattel, M.; Bourquelot, P.] Novartis Pharma AG, Basel, Switzerland. [Cavo, M.] Univ Studi, Policlin S Orsola Malpighi, Az Osp Bologna, Bologna, Italy. [Niederweiser, D.] Univ Klinikum Leipzig, Leipzig, Germany. [Milder, M.] Swedish Med Ctr, Seattle, WA USA. [Boccadoro, M.] AO Univ S Giovanni Battista, Torino Univ Studi, Turin, Italy. [Anderson, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0384 BP 155 EP 155 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300382 ER PT J AU Jagannath, S Siegel, D Hajek, R Dimopoulos, M Yoon, SS Lonial, S Graef, T Lupinacci, L Reiser, D Anderson, K AF Jagannath, S. Siegel, D. Hajek, R. Dimopoulos, M. Yoon, S. S. Lonial, S. Graef, T. Lupinacci, L. Reiser, D. Anderson, K. TI INTERIM ANALYSIS OF A PHASE III RANDOMIZED, DOUBLE-BLIND STUDY OF VORINOSTAT OR PLACEBO COMBINED WITH BORTEZOMIB IN RELAPSED MULTPLE MYELOMA SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Jagannath, S.] St Vincent Catholic Med Ctr, New York, NY USA. [Siegel, D.] Hackensack Univ, Ctr Med, Hackensack, NJ 07604 USA. [Hajek, R.] Univ Hosp Brno, Brno, Czech Republic. [Hajek, R.] Fac Med MU, Brno, Czech Republic. [Dimopoulos, M.] Univ Athens, Dept Therapeut, Athens, Greece. [Yoon, S. S.] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Lonial, S.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA. [Graef, T.; Lupinacci, L.; Reiser, D.] Merck & Co Inc, Upper Gwynedd, NJ USA. [Anderson, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0386 BP 156 EP 156 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300384 ER PT J AU Siegel, D Jagannath, S Lonial, S Dimopoulos, M Yoon, SS Graef, T Pitrangelo, D Lupinacci, L Reiser, D Anderson, K AF Siegel, D. Jagannath, S. Lonial, S. Dimopoulos, M. Yoon, S. S. Graef, T. Pitrangelo, D. Lupinacci, L. Reiser, D. Anderson, K. TI COMBINED VORINOSTAT AND BORTEZOMIB IN BORTEZOMIB-REFRACTORY PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INTERIM ANALYSIS OF A PHASE IIB STUDY SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Siegel, D.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Jagannath, S.] St Vincent Catholic Med Ctr, New York, NY USA. [Lonial, S.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA. [Dimopoulos, M.] Univ Athens, Dept Therapeut, Athens, Greece. [Yoon, S. S.] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Graef, T.; Pitrangelo, D.; Lupinacci, L.; Reiser, D.] Merck & Co Inc, Upper Gwynedd, NJ USA. [Anderson, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0387 BP 156 EP 157 PG 2 WC Hematology SC Hematology GA 614IY UT WOS:000279051300385 ER PT J AU Schrader, A Bentink, S Spang, R Lenze, D Hummel, M Kuo, M Arrand, J Murray, P Trumper, L Kube, D Vockerodt, M AF Schrader, A. Bentink, S. Spang, R. Lenze, D. Hummel, M. Kuo, M. Arrand, J. Murray, P. Truemper, L. Kube, D. Vockerodt, M. TI A C-MYC INDUCED GENE EXPRESSION SIGNATURE IN HUMAN GERMINAL CENTER B CELLS PREDICTS SUBTYPES OF AGGRESSIVE NON-HODGKIN LYMPHOMA SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Schrader, A.; Truemper, L.; Kube, D.] Georg August Univ, Gottingen, Germany. [Bentink, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Spang, R.] Univ Regensburg, Regensburg, Germany. [Lenze, D.; Hummel, M.] Charite, Berlin, Germany. [Kuo, M.] Birmingham Childrens Hosp, Birmingham, W Midlands, England. [Arrand, J.; Murray, P.; Vockerodt, M.] Univ Birmingham, Birmingham, W Midlands, England. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0415 BP 168 EP 169 PG 2 WC Hematology SC Hematology GA 614IY UT WOS:000279051300413 ER PT J AU Roccaro, A Sacco, A Aujay, M Ngo, T Azab, F Azab, A Quang, P Maiso, P Demo, S Rossi, G Ghobrial, M AF Roccaro, A. Sacco, A. Aujay, M. Ngo, T. Azab, F. Azab, A. Quang, P. Maiso, P. Demo, S. Rossi, G. Ghobrial, M. TI SELECTIVE INHIBITION OF THE CHYMOTRYPSIN-LIKE ACTIVITY OF IMMUNOPROTEASOME AND CONSTITUTIVE PROTEASOME REPRESENTS A VALID ANTI-TUMOR STRATEGY IN WALDENSTROM MACROGLOBULINEMIA (WM) SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Roccaro, A.; Rossi, G.] Spedali Civil Brescia, I-25125 Brescia, Italy. [Sacco, A.; Ngo, T.; Azab, F.; Azab, A.; Quang, P.; Maiso, P.; Ghobrial, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Aujay, M.; Demo, S.] Onyx Pharmaceut, Fineryville, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0454 BP 185 EP 185 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300453 ER PT J AU Roccaro, A Sacco, A Azab, A Azab, F Ngo, T Quang, P Maiso, P Rossi, G Ghobrial, M AF Roccaro, A. Sacco, A. Azab, A. Azab, F. Ngo, T. Quang, P. Maiso, P. Rossi, G. Ghobrial, M. TI MICRORNAS CHANGES OCCUR IN MULTIPLE MYELOMA CELLS IN THE CONTEXT OF BONE MARROW MILIEU SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Roccaro, A.; Rossi, G.] Spedali Civil Brescia, I-25125 Brescia, Italy. [Sacco, A.; Azab, A.; Azab, F.; Ngo, T.; Quang, P.; Maiso, P.; Ghobrial, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Rossi, Giuseppe/K-3376-2016 OI Rossi, Giuseppe/0000-0001-8377-2898 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0526 BP 214 EP 215 PG 2 WC Hematology SC Hematology GA 614IY UT WOS:000279051300526 ER PT J AU Roccaro, A Sacco, A Azab, A Azab, F Ngo, T Maiso, P Rossi, G Ghobrial, M AF Roccaro, A. Sacco, A. Azab, A. Azab, F. Ngo, T. Maiso, P. Rossi, G. Ghobrial, M. TI MICRORNA-DEPENDENT MODULATION OF HISTONE ACETYLATION IN WALDENSTROM'S MACROGLOBULINEMIA SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Roccaro, A.; Rossi, G.] Spedali Civil Brescia, I-25125 Brescia, Italy. [Sacco, A.; Azab, A.; Azab, F.; Ngo, T.; Maiso, P.; Ghobrial, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JUN PY 2010 VL 95 SU 2 MA 0555 BP 228 EP 228 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300555 ER PT J AU Krivtsov, V Stubbs, C Sinha, U Wang, J Bullinger, L Kung, L Armstrong, A AF Krivtsov, V. Stubbs, C. Sinha, U. Wang, J. Bullinger, L. Kung, L. Armstrong, A. TI CELL OF ORIGIN INFLUENCES LEUKEMIA STEM CELL PHENOTYPE SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Krivtsov, V.; Stubbs, C.; Sinha, U.; Wang, J.; Bullinger, L.; Armstrong, A.] Childrens Hosp, Boston, MA 02115 USA. [Kung, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0576 BP 240 EP 240 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300577 ER PT J AU Bolli, N Payne, E Johnston, A Grabher, C Falini, B Kanki, J Look, T AF Bolli, N. Payne, E. Johnston, A. Grabher, C. Falini, B. Kanki, J. Look, T. TI EXPRESSION OF THE CYTOPLASMIC NPM1 MUTANT (NPMC plus ) CAUSES THE EXPANSION OF HEMATOPOIETIC CELLS IN ZEBRAFISH SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Bolli, N.; Payne, E.; Johnston, A.; Kanki, J.; Look, T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Grabher, C.] KIT, Karlsruhe, Germany. [Falini, B.] Univ Perugia, Ist Ematol, I-06100 Perugia, Italy. NR 0 TC 0 Z9 0 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 JUN PY 2010 VL 95 SU 2 MA 0580 BP 242 EP 242 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300581 ER PT J AU Chiaretti, S Messina, M Iacobucci, I Tavolaro, S Piciocchi, A Elia, L Vitale, A Negulici, A Vignetti, M Weinstock, D Yoda, A Guarini, A Martinelli, G Foa, R AF Chiaretti, S. Messina, M. Iacobucci, I. Tavolaro, S. Piciocchi, A. Elia, L. Vitale, A. Negulici, A. Vignetti, M. Weinstock, D. Yoda, A. Guarini, A. Martinelli, G. Foa, R. TI IDENTIFICATION OF A FAVORABLE PROGNOSIS GROUP OF ADULT B-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA WITHOUT MOLECULAR ABERRATIONS BY COMBINING GENE EXPRESSION AND SINGLE NUCLEOTIDE POLYMORPHISM ARRAYS SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Messina, M.; Tavolaro, S.; Elia, L.; Vitale, A.; Negulici, A.; Guarini, A.; Foa, R.] Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, Rome, Italy. [Iacobucci, I.; Martinelli, G.] Univ Bologna, Dept Hematol Oncol L & A Seragnoli, Bologna, Italy. [Piciocchi, A.; Vignetti, M.] GIMEMA Data Ctr, Rome, Italy. [Weinstock, D.; Yoda, A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0608 BP 256 EP 256 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051300609 ER PT J AU Jakubikova, J Cervi, D Daley, J Cholujova, D Ooi, M Klippel, S Blotta, S Leiba, M Delmore, J McMillin, D Kastritis, E Laubach, J Richardson, P Anderson, K Sedlak, J Mitsiades, C AF Jakubikova, J. Cervi, D. Daley, J. Cholujova, D. Ooi, M. Klippel, S. Blotta, S. Leiba, M. Delmore, J. McMillin, D. Kastritis, E. Laubach, J. Richardson, P. Anderson, K. Sedlak, J. Mitsiades, C. TI PATHOPHYSIOLOGICAL IMPLICATIONS OF POMALIDOMIDE IN TARGETING THE CLONOGENIC MULTIPLE MYELOMA SIDE POPULATION IN THE CONTEXT OF THE BONE MARROW MILIEU SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Jakubikova, J.; Cervi, D.; Daley, J.; Klippel, S.; Blotta, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cholujova, D.] Canc Res Inst, Bratislava, Slovakia. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 0928 BP 385 EP 385 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051301249 ER PT J AU Brown, J Byrd, J Furman, R Flinn, I Benson, D Coutre, S Kahl, B Wagner-Johnston, N Spurgeon, S Pratz, K Giese, N Yu, OA AF Brown, J. Byrd, J. Furman, R. Flinn, I. Benson, D. Coutre, S. Kahl, B. Wagner-Johnston, N. Spurgeon, S. Pratz, K. Giese, N. Yu, O. A. TI CLINICAL ACTIVITY IN A PHASE 1 STUDY OF CAL-101, AN ISOFORM-SELECTIVE INHIBITOR OF PHOSPHATIDYLINOSITOL 3-KINASE P110DELTA, IN PATIENTS WITH B-CELL MALIGNANCIES SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Brown, J.; Giese, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Byrd, J.; Benson, D.] Ohio State Univ, Columbus, OH 43210 USA. [Furman, R.] Weill Cornell Med Coll, New York, NY USA. [Flinn, I.] Sarah Cannon Res Inst, Nashville, TN USA. [Coutre, S.] Stanford Univ, Stanford, CA 94305 USA. [Kahl, B.] Univ Wisconsin, Madison, WI USA. [Wagner-Johnston, N.] Washington Univ, St Louis, MO USA. [Spurgeon, S.] Oregon Hlth & Sci Univ, Portland, OR USA. [Pratz, K.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Yu, O. A.] Calistoga Pharmaceut, Seattle, WA USA. NR 0 TC 5 Z9 5 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 1130 BP 466 EP 466 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051301451 ER PT J AU Barteneva, N Sotnikov, I Konopleva, M O'Brien, S Andreeff, M Bortakur, G Jaron, S Hillabrant, J Ketman, K Potashnikova, D Kaplanov, K Kalashnikova, O Tregubova, L Klitochenko, T Demidenko, K Matveeva, I Davidova, N Biderman, B Sudarikov, A Vorobjev, I AF Barteneva, N. Sotnikov, I. Konopleva, M. O'Brien, S. Andreeff, M. Bortakur, G. Jaron, S. Hillabrant, J. Ketman, K. Potashnikova, D. Kaplanov, K. Kalashnikova, O. Tregubova, L. Klitochenko, T. Demidenko, K. Matveeva, I. Davidova, N. Biderman, B. Sudarikov, A. Vorobjev, I. TI DEVELOPMENT OF MULTI-COLOR INTRACELLULAR PANELS IN CHRONIC LYMPHOID LEUKEMIA (CLL) USING ZAP-70 QUANTUM DOT-CONJUGATED ANTIBODIES SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 15th Annual Meeting of the European-Hematology-Association CY JUN 10-13, 2010 CL Barcelona, SPAIN SP European Hematol Assoc C1 [Barteneva, N.; Sotnikov, I.; Hillabrant, J.; Ketman, K.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Konopleva, M.; O'Brien, S.; Andreeff, M.; Bortakur, G.] MD Anderson Canc Ctr, Houston, TX USA. [Potashnikova, D.; Biderman, B.; Sudarikov, A.; Vorobjev, I.] Hematol Res Ctr, Moscow, Russia. [Kaplanov, K.; Kalashnikova, O.; Tregubova, L.; Klitochenko, T.; Demidenko, K.; Matveeva, I.; Davidova, N.] GUZ Volgograd Regional, Clin Oncol Ctr, Volgograd, Russia. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2010 VL 95 SU 2 MA 1262 BP 514 EP 514 PG 1 WC Hematology SC Hematology GA 614IY UT WOS:000279051301581 ER PT J AU Woo, TUW Spencer, K McCarley, RW AF Woo, Tsung-Ung W. Spencer, Kevin McCarley, Robert W. TI Gamma Oscillation Deficits and the Onset and Early Progression of Schizophrenia SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE adolescent development; GABA; NMDA; parvalbumin; synaptic pruning ID MONKEY PREFRONTAL CORTEX; INTERNEURON DIVERSITY SERIES; ASPARTATE RECEPTOR SUBUNIT; CB1 CANNABINOID RECEPTORS; MESSENGER-RNA EXPRESSION; RAT FRONTAL-CORTEX; METABOTROPIC GLUTAMATE RECEPTORS; SCHIZOTYPAL PERSONALITY-DISORDER; PARVALBUMIN-CONTAINING NEURONS; CULTURED HIPPOCAMPAL-NEURONS AB A fascinating convergence of evidence in recent years has implicated the disturbances of neural synchrony in the gamma frequency band (30-100 Hz) as a major pathophysiologic feature of schizophrenia. Evidence suggests that reduced glutamatergic neurotransmission via the N-methyl-D-aspartate (NMDA) receptors that are localized to inhibitory interneurons, perhaps especially the fast-spiking cells that contain the calcium-binding protein parvalbumin (PV), may contribute to gamma band synchrony deficits. These deficits may underlie the brain's failure to integrate information and hence the manifestations of many symptoms and deficits of schizophrenia. Furthermore, because gamma oscillations are thought to provide the temporal structure that is necessary for synaptic plasticity, gamma oscillation deficits may disturb the developmental synaptic reorganization process that is occurring during the period of late adolescence and early adulthood. This disturbance may contribute to the onset of schizophrenia and the functional deterioration that is characteristic of the early stage of the illness. Finally, reduced NMDA neurotransmission on inhibitory interneurons, including the PV-containing cells, may inflict excitotoxic or oxidative injury to downstream pyramidal neurons, leading to further loss of synapses and dendritic branchings. Hence, a key element in the conceptualization of rational early-intervention and prevention strategies for schizophrenia may involve correcting the abnormal NMDA neurotransmission on inhibitory interneurons-possibly that on the PV-containing neurons, in particular-thereby normalizing gamma oscillation deficits and attenuating downstream neuronal pathology. 0.05). Conclusion: Fatty liver is a prevalent condition and is characterized by dysglycemia and dyslipidemia independent of visceral adipose tissue and other obesity measures. This work begins to dissect the specific links between fat depots and metabolic disease. (HEPATOLOGY 2010;51:1979-1987) C1 [Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Hoffmann, Udo; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Gen Med, Boston, MA 02114 USA. [Speliotes, Elizabeth K.; Hirschhorn, Joel N.] Broad Inst Harvard, Dept Med & Populat Genet, Cambridge, MA USA. [Speliotes, Elizabeth K.; Hirschhorn, Joel N.] MIT, Cambridge, MA 02139 USA. [Massaro, Joseph M.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Childrens Hosp, Dept Genet, Boston, MA 02115 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 OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU National Institutes of Health [T32 DK07191-32, F32 DK079466-01, K23 DK080145-01]; core contract [N01-HC25195]; American Diabetes Association; General Clinical Research Centers Program [M01-RR-01066]; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140] FX E. K S. was supported by National Institutes of Health Grants T32 DK07191-32 (to Daniel K Podolsky in the Department of Gastroenterology at Massachusetts General Hospital), F32 DK079466-01, and K23 DK080145-01. The Framingham Heart Study is supported by core contract N01-HC25195. Additional research support was provided by an American Diabetes Association Career Development Award (to J. B. M.), the General Clinical Research Centers Program (Grant No. M01-RR-01066), and National Institute of Diabetes and Digestive and Kidney Diseases Grant K24 DK080140 (to J. B. M.). NR 34 TC 150 Z9 157 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2010 VL 51 IS 6 BP 1979 EP 1987 DI 10.1002/hep.23593 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 604FB UT WOS:000278261600015 PM 20336705 ER PT J AU Baggish, AL Fulco, CS Muza, S Rock, PB Beidleman, B Cymerman, A Yared, K Fagenholz, P Systrom, D Wood, MJ Weyman, AE Picard, MH Harris, NS AF Baggish, Aaron L. Fulco, Charles S. Muza, Stephen Rock, Paul B. Beidleman, Beth Cymerman, Allen Yared, Kibar Fagenholz, Peter Systrom, David Wood, Malissa J. Weyman, Arthur E. Picard, Michael H. Harris, N. Stuart TI The Impact of Moderate-Altitude Staging on Pulmonary Arterial Hemodynamics after Ascent to High Altitude SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE pulmonary circulation; pulmonary hypertension; pulmonary arterial pressure; high altitude; moderate altitude ID ACUTE MOUNTAIN-SICKNESS; VASCULAR-RESPONSE; CHRONIC HYPOXIA; CARDIAC-OUTPUT; RAT LUNG; EDEMA; HYPERTENSION; PRESSURE; OXYGEN; VASOCONSTRICTION AB Baggish, Aaron L., Charles S. Fulco, Stephen Muza, Paul B. Rock, Beth Beidleman, Allen Cymerman, Kibar Yared, Peter Fagenholz, David Systrom, Malissa J. Wood, Arthur E. Weyman, Michael H. Picard, and N. Stuart Harris The impact of moderate altitude on pulmonary arterial hemodynamics after ascent to high altitude. High Alt. Med. Biol. 11:139-145, 2010.-Staged ascent ( SA), temporary residence at moderate altitude en route to high altitude, reduces the incidence and severity of noncardiopulmonary altitude illness such as acute mountain sickness. To date, the impact of SA on pulmonary arterial pressure ( PAP) is unknown. We tested the hypothesis that SA would attenuate the PAP increase that occurs during rapid, direct ascent ( DA). Transthoracic echocardiography was used to estimate mean PAP in 10 healthy males at sea level (SL, P(B) approximate to 760 torr), after DA to simulated high altitude ( hypobaric chamber, PB approximate to 460 torr), and at 2 times points ( 90min and 4 days) during exposure to terrestrial high altitude ( PB approximate to 460 torr) after SA ( 7 days, moderate altitude, PB approximate to 548 torr). Alveolar oxygen pressure ( Pao(2)) and arterial oxygenation saturation ( Sao(2)) were measured at each time point. Compared to mean PAP at SL ( mean +/- SD, 14 +/- 3mmHg), mean PAP increased after DA to 37 +/- 8mmHg (Delta=24 +/- 10mmHg, p< 0.001) and was negatively correlated with both Pao(2) (r(2)=0.57, p=0.011) and Sao(2) (r(2)=0.64, p=0.005). In comparison, estimated mean PAP after SA increased to only 25 +/- 4mmHg (Delta=11 +/- 6mmHg, p< 0.001), remained unchanged after 4 days of high altitude residence (24 +/- 5mmHg, p not significant, or NS), and did not correlate with either parameter of oxygenation. SA significantly attenuated the PAP increase associated with continuous direct ascent to high altitude and appeared to uncouple PAP from both alveolar hypoxia and arterial hypoxemia. C1 [Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Fulco, Charles S.; Muza, Stephen; Beidleman, Beth; Cymerman, Allen] USA, Environm Med Res Inst, Natick, MA 01760 USA. [Rock, Paul B.] Oklahoma State Univ, Ctr Hlth Serv, Tulsa, OK USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey Bldg,Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org OI Systrom, David/0000-0002-9610-6330; Picard, Michael/0000-0002-9264-3243 FU Center for Integration of Medicine and Innovative Technology (CIMIT), Boston, Massachusetts; U.S. Army Medical Research and Material Command [ATO IV.MD.2006.01] FX The study was supported in part by a project grant from the Center for Integration of Medicine and Innovative Technology (CIMIT), Boston, Massachusetts, and funding provided by the U.S. Army Medical Research and Material Command ATO IV.MD.2006.01. NR 30 TC 9 Z9 9 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD JUN PY 2010 VL 11 IS 2 BP 139 EP 145 DI 10.1089/ham.2009.1073 PG 7 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA 618BQ UT WOS:000279326600008 PM 20586598 ER PT J AU Burak, KW Thomas, MB Zhu, AX AF Burak, Kelly W. Thomas, Melanie B. Zhu, Andrew X. TI Nonoperative therapies for combined modality treatment of hepatocellular cancer: expert consensus conference SO HPB LA English DT Editorial Material ID RANDOMIZED CONTROLLED TRIAL; PORTAL-VEIN THROMBOSIS; CARCINOMA; CHEMOEMBOLIZATION; EFFICACY; SAFETY C1 [Burak, Kelly W.] Univ Calgary, Dept Med, Div Gastroenterol, Liver Unit, Calgary, AB T2N 4Z6, Canada. [Thomas, Melanie B.] Med Univ S Carolina, Dept Med, Hollings Canc Ctr, Charleston, SC 29425 USA. [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Burak, KW (reprint author), Univ Calgary, Dept Med, Div Gastroenterol, Liver Unit, 3280 Hosp Dr NW, Calgary, AB T2N 4Z6, Canada. EM kwburak@ucalgary.ca; azhu@partners.org NR 13 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1365-182X J9 HPB JI HPB PD JUN PY 2010 VL 12 IS 5 BP 321 EP 322 DI 10.1111/j.1477-2574.2010.00186.x PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 709KI UT WOS:000286436500007 PM 20590906 ER PT J AU Lisovsky, M Dresser, K Woda, B Mino-Kenudson, M AF Lisovsky, Mikhail Dresser, Karen Woda, Bruce Mino-Kenudson, Mari TI Immunohistochemistry for cell polarity protein lethal giant larvae 2 differentiates pancreatic intraepithelial neoplasia-3 and ductal adenocarcinoma of the pancreas from lower-grade pancreatic intraepithelial neoplasias SO HUMAN PATHOLOGY LA English DT Article DE Pancreatic intraepithelial neoplasia; PanIN; Ductal adenocarcinoma of the pancreas; Lgl2 ID PAPILLARY-MUCINOUS NEOPLASMS; PROGRESSION; CANCER; EXPRESSION; LESIONS; LGL; INACTIVATION; CARCINOMA; COMPLEX; BENIGN AB Pancreatic intraepithelial neoplasia is a precursor to ductal adenocarcinoma of the pancreas that shows gastric differentiation. Pancreatic intraepithelial neoplasia-3 has the highest potential to progress to adenocarcinoma, and its distinction from lower-grade pancreatic intraepithelial neoplasias is important for clinical management. However, morphologic grading of pancreatic intraepithelial neoplasia suffers from significant interobserver variability. A product of cell polarity gene lethal giant larvae 2 is a marker of gastric foveolar epithelium expressed in a basolateral fashion, which is lost or mislocalized in gastric epithelial dysplasia and adenocarcinoma. In this study, we investigated a role of lethal giant larvae 2 expression in differentiating low-grade pancreatic intraepithelial neoplasias, that is, pancreatic intraepithelial neoplasia-1 and pancreatic intraepithelial neoplasia-2, from pancreatic intraepithelial neoplasia-3 and pancreatic ductal adenocarcinoma. The immunohistochemical patterns of lethal giant larvae 2 expression were examined in normal pancreatic ducts, 48 pancreatic intraepithelial neoplasia lesions of all histologic grades, and 91 adenocarcinomas on a tissue microarray or conventional sections. The expression pattern was recorded as basolateral, cytoplasmic, negative, or combinations of any of them. Whereas normal duct epithelia did not exhibit lethal giant larvae immunoreactivity, all but one lesion of low-grade pancreatic intraepithelial neoplasia showed basolateral lethal giant larvae staining. Conversely, all lesions of pancreatic intraepithelial neoplasia-3 and adenocarcinoma showed loss of lethal giant larvae 2 staining and/or its cytoplasmic localization. Interestingly, a basolateral expression was focally seen in 4 adenocarcinomas with a foamy gland pattern and was always admixed with negatively stained areas. In conclusion, our results show that low-grade pancreatic intraepithelial neoplasias express lethal giant larvae 2 in a basolateral fashion recapitulating expression in normal gastric epithelium. Loss or abnormal lethal giant larvae 2 expression is seen in pancreatic intraepithelial neoplasia-3 and adenocareinoma and might be useful in separating them from lower-grade pancreatic intraepithelial neoplasias. (C) 2010 Elsevier Inc. All rights reserved. C1 [Mino-Kenudson, Mari] Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, James Homer Wright Pathol Labs,Med Sch, Boston, MA 02114 USA. [Dresser, Karen; Woda, Bruce] Univ Massachusetts, Sch Med, UMass Mem Med Ctr, Dept Pathol, Worcester, MA 02114 USA. RP Mino-Kenudson, M (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, James Homer Wright Pathol Labs,Med Sch, Boston, MA 02114 USA. EM mminokenudson@partners.org NR 35 TC 6 Z9 6 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUN PY 2010 VL 41 IS 6 BP 902 EP 909 DI 10.1016/j.humpath.2009.12.004 PG 8 WC Pathology SC Pathology GA 599BM UT WOS:000277885200015 PM 20233622 ER PT J AU Sarma, SV Eden, UT Cheng, ML Williams, ZM Hu, R Eskandar, E Brown, EN AF Sarma, Sridevi V. Eden, Uri T. Cheng, Ming L. Williams, Ziv M. Hu, Rollin Eskandar, Emad Brown, Emery N. TI Using Point Process Models to Compare Neural Spiking Activity in the Subthalamic Nucleus of Parkinsons Patients and a Healthy Primate SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Deep brain stimulation (DBS); Parkinson's disease (PD); point processes; spike trains ID TRAIN DATA-ANALYSIS; GLOBUS-PALLIDUS; BASAL GANGLIA; NEURONAL-ACTIVITY; CELL DISCHARGE; ARM MOVEMENTS; SINGLE CELL; DISEASE; DIRECTION; PATHOPHYSIOLOGY AB Placement of deep brain stimulating electrodes in the subthalamic nucleus (STN) to treat Parkinson's disease (PD) also allows the recording of single neuron spiking activity. Analyses of these unique data offer an important opportunity to better understand the pathophysiology of PD. Despite the point process nature of PD neural spiking activity, point process methods are rarely used to analyze these recordings. We develop a point process representation of PD neural spiking activity using a generalized linear model to describe long- and short-term temporal dependencies in the spiking activity of 28 STN neurons from seven PD patients and 35 neurons from one healthy primate (surrogate control) recorded, while the subjects executed a directed-hand movement task. We used the point process model to characterize each neuron's bursting, oscillatory, and directional tuning properties during key periods in the task trial. Relative to the control neurons, the PD neurons showed increased bursting, increased 10-30 Hz oscillations, and increased fluctuations in directional tuning. These features, which traditional methods failed to capture accurately, were efficiently summarized in a single model in the point process analysis of each neuron. The point process framework suggests a useful approach for developing quantitative neural correlates that may be related directly to the movement and behavioral disorders characteristic of PD. C1 [Sarma, Sridevi V.; Brown, Emery N.] MIT, Cambridge, MA 02139 USA. [Eden, Uri T.] Boston Univ, Dept Math & Stat, Boston, MA 02115 USA. [Cheng, Ming L.] Brown Univ, Dept Clin Neurosci, Providence, RI 02912 USA. [Williams, Ziv M.; Hu, Rollin; Eskandar, Emad] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sarma, SV (reprint author), Johns Hopkins Univ, Dept Biomed Engn, Inst Computat Med, Baltimore, MD 21218 USA. EM sree@mit.edu FU Burrough's Wellcome Fund; L'Oreal FWIS; NIH-National Eye Institute [1R01EY017658]; NIH-National Institute Drug Addiction [1R01NS063249]; National Science Foundation [IOB 0645886]; HHMI and Klingenstein Foundation; [R01 DA015644]; [DP1 OD003646] FX Manuscript received March 2, 2009; revised September 20, 2009; accepted November 17, 2009. Date of publication February 17, 2010; date of current version May 14, 2010. The work of S. V. Sarma was supported by Burrough's Wellcome Fund and a L'Oreal FWIS Fellowship. The work of E. Eskandar was supported in part by NIH-National Eye Institute under Grant 1R01EY017658, in part by NIH-National Institute Drug Addiction under Grant 1R01NS063249, in part by National Science Foundation under Grant IOB 0645886, and in part by HHMI and Klingenstein Foundation. The work of E. N. Brown was supported under Grants R01 DA015644 and DP1 OD003646. Asterisk indicates corresponding author. NR 44 TC 32 Z9 32 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUN PY 2010 VL 57 IS 6 BP 1297 EP 1305 DI 10.1109/TBME.2009.2039213 PG 9 WC Engineering, Biomedical SC Engineering GA 597PL UT WOS:000277770600005 PM 20172804 ER PT J AU Chen, Z Brown, EN Barbieri, R AF Chen, Zhe Brown, Emery N. Barbieri, Riccardo TI Characterizing Nonlinear Heartbeat Dynamics Within a Point Process Framework SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article; Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn DE Adaptive filters; approximate entropy (ApEn); heart rate variability (HRV); nonlinearity test; point processes; scaling exponent; Volterra series expansion ID RATE-VARIABILITY; TIME-SERIES; ENTROPY ANALYSIS; IDENTIFICATION; FAILURE; SPECTRA; COMPLEXITY; PHYSIOLOGY; DISEASE; SYSTEMS AB Human heartbeat intervals are known to have nonlinear and nonstationary dynamics. In this paper, we propose a model of R-R interval dynamics based on a nonlinear Volterra-Wiener expansion within a point process framework. Inclusion of second-order nonlinearities into the heartbeat model allows us to estimate instantaneous heart rate (HR) and heart rate variability (HRV) indexes, as well as the dynamic bispectrum characterizing higher order statistics of the nonstationary non-Gaussian time series. The proposed point process probability heartbeat interval model was tested with synthetic simulations and two experimental heartbeat interval datasets. Results show that our model is useful in characterizing and tracking the inherent nonlinearity of heartbeat dynamics. As a feature, the fine temporal resolution allows us to compute instantaneous nonlinearity indexes, thus sidestepping the uneven spacing problem. In comparison to other nonlinear modeling approaches, the point process probabilitymodel is useful in revealing nonlinear heartbeat dynamics at a fine timescale and with only short duration recordings. C1 [Chen, Zhe; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Chen, Zhe; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Chen, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM zhechen@neurostat.mit.edu; enb@neurostat.mit.edu; barbieri@neurostat.mit.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Chen, Zhe/0000-0002-6483-6056 FU NCRR NIH HHS [RR-79]; NHLBI NIH HHS [R01-HL084502, R01 HL084502-04, R01 HL084502]; NIA NIH HHS [AG-9550]; NIDA NIH HHS [R01 DA015644, R01-DA015644]; NIGMS NIH HHS [GM-26691]; NIH HHS [DP1 OD003646, DP1-OD003646] NR 62 TC 24 Z9 25 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUN PY 2010 VL 57 IS 6 BP 1335 EP 1347 DI 10.1109/TBME.2010.2041002 PG 13 WC Engineering, Biomedical SC Engineering GA 597PL UT WOS:000277770600009 PM 20172783 ER PT J AU Qiu, AQ Brown, T Fischl, B Ma, J Miller, MI AF Qiu, Anqi Brown, Timothy Fischl, Bruce Ma, Jun Miller, Michael I. TI Atlas Generation for Subcortical and Ventricular Structures With Its Applications in Shape Analysis SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article DE Brain atlas; diffeomorphic mapping; shape classification; shape comparison; subcortical structures ID MILD COGNITIVE IMPAIRMENT; COMPUTATIONAL ANATOMY; HIPPOCAMPAL ATROPHY; TEMPLATE ESTIMATION; ALZHEIMERS-DISEASE; HUMAN BRAIN; MAPS; DIFFEOMORPHISMS; REGISTRATION; VOLUME AB Atlas-driven morphometric analysis has received great attention for studying anatomical shape variation across clinical populations in neuroimaging research as it provides a local coordinate representation for understanding the family of anatomic observations. We present a procedure for generating atlas of subcortical and ventricular structures, including amygdala, hippocampus, caudate, putamen, globus pallidus, thalamus, and lateral ventricles, using the large deformation diffeomorphic metric atlas generation algorithm. The atlas was built based on manually labeled volumes of 41 subjects randomly selected from the database of Open Access Series of Imaging Studies (OASIS, 10 young adults, 10 middle-age adults, 10 healthy elders, and 11 patients with dementia). We show that the estimated atlas is representative of the population in terms of its metric distance to each individual subject in the population. In the application of detecting shape variations, using the estimated atlas may potentially increase statistical power in identifying group shape difference when comparing with using a single subject atlas. In shape-based classification, the metric distances between subjects and each of within-class estimated atlases construct a shape feature space, which allows for performing a variety of classification algorithms to distinguish anatomies. C1 [Qiu, Anqi] Natl Univ Singapore, Div Bioengn, Singapore 117576, Singapore. [Qiu, Anqi; Miller, Michael I.] Agcy Sci Technol & Res, Singapore Inst Clin Sci, Singapore 117574, Singapore. [Qiu, Anqi] Natl Univ Singapore, Clin Imaging Res Ctr, Singapore 117576, Singapore. [Brown, Timothy] Johns Hopkins Univ, Ctr Imaging Sci, Baltimore, MD 21218 USA. [Fischl, Bruce; Miller, Michael I.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Ma, Jun] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. RP Qiu, AQ (reprint author), Natl Univ Singapore, Div Bioengn, Singapore 117576, Singapore. EM bieqa@nus.edu.sg RI Miller, Michael I./A-3213-2010; Qiu, Anqi/H-2267-2011 FU National University of Singapore [R-397-000-058-133]; A*STAR [SERC 082 101 0025, SICS 09/1/1/001]; National Center for Research Resources [P41 RR15241, P41-RR14075, R01 RR16594-01A1, BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01 EB001550, R01EB006758]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; National Institutes of Health [U54 EB005149] FX Manuscript received January 28, 2009; revised January 06, 2010. First published February 02, 2010; current version published May 14, 2010. This work was supported by National University of Singapore Start-Up Grant R-397-000-058-133, A*STAR SERC 082 101 0025, and A*STAR SICS 09/1/1/001. Support of this work was also provided in part by the National Center for Research Resources (P41 RR15241, P41-RR14075, R01 RR16594-01A1, and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01 EB001550, R01EB006758), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01) as well as the Mental Illness and Neuroscience Discovery (MIND) Institute, and is part of the National Alliance for Medical Image Computing (NAMIC), funded by the National Institutes of Health through the NIH Roadmap for Medical Research, under Grant U54 EB005149. The associate editor coordinating the review of this manuscript and approving it for publication was Dr. John Kerekes. NR 50 TC 28 Z9 28 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1057-7149 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD JUN PY 2010 VL 19 IS 6 BP 1539 EP 1547 DI 10.1109/TIP.2010.2042099 PG 9 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 597QG UT WOS:000277773200013 PM 20129863 ER PT J AU Stepp, CE Hillman, RE Heaton, JT AF Stepp, Cara E. Hillman, Robert E. Heaton, James T. TI Use of Neck Strap Muscle Intermuscular Coherence as an Indicator of Vocal Hyperfunction SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Motor drives; surface electromyography; vocal system ID TENSION DYSPHONIA; ISOMETRIC CONTRACTION; OSCILLATORY INTERACTION; PHYSIOLOGICAL TREMOR; MUSCULAR TENSION; VOICE DISORDERS; SURFACE EMG; EEG-EMG; FREQUENCY; SPEECH AB Intermuscular coherence in the beta band was explored as a possible indicator of vocal hyperfunction, a common condition associated with many voice disorders. Surface electromyography (sEMG) was measured from two electrodes on the anterior neck surface of 18 individuals with vocal nodules and 18 individuals with healthy normal voice. Coherence was calculated from sEMG activity gathered while participants produced both read and spontaneous speech. There was no significant effect of speech type on average coherence. Individuals with vocal nodules showed significantly lower mean coherence in the beta band (15-35 Hz) when compared to controls. Results suggest that bilateral EMG-EMG beta coherence in neck strap muscle during speech production shows promise as an indicator of vocal hyperfunction. C1 [Stepp, Cara E.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Hillman, Robert E.] Harvard Univ, Sch Med, Dept Surg & Hlth Sci, Boston, MA 02115 USA. [Hillman, Robert E.] Harvard Univ, Sch Med, Dept Technol, Boston, MA 02115 USA. [Hillman, Robert E.; Heaton, James T.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Heaton, James T.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Stepp, CE (reprint author), Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. EM cstepp@alum.mit.edu; hillman.robert@mgh.harvard.edu; james.heaton@mgh.harvard.edu FU National Institute on Deafness and Other Communication Disorders [5T32DC000038-17] FX This work was supported by the National Institute on Deafness and Other Communication Disorders under Grant 5T32DC000038-17. NR 48 TC 6 Z9 7 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD JUN PY 2010 VL 18 IS 3 BP 329 EP 335 DI 10.1109/TNSRE.2009.2039605 PG 7 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 649OP UT WOS:000281782000013 PM 20083462 ER PT J AU Archer, KA Ader, F Kobayashi, KS Flavell, RA Roy, CR AF Archer, Kristina A. Ader, Florence Kobayashi, Koichi S. Flavell, Richard A. Roy, Craig R. TI Cooperation between Multiple Microbial Pattern Recognition Systems Is Important for Host Protection against the Intracellular Pathogen Legionella pneumophila SO INFECTION AND IMMUNITY LA English DT Article ID LEGIONNAIRES-DISEASE; HUMAN-MONOCYTES; KAPPA-B; BACTERIAL PEPTIDOGLYCAN; ENDOPLASMIC-RETICULUM; ALVEOLAR MACROPHAGES; SIGNALING PATHWAYS; BONE-MARROW; NK CELLS; INFECTION AB Multiple pattern recognition systems have been shown to initiate innate immune responses to microbial pathogens. The degree to which these detection systems cooperate with each other to provide host protection is unknown. Here, we investigated the importance of several immune surveillance pathways in protecting mice against lethal infection by the intracellular pathogen Legionella pneumophila, the causative agent of a severe pneumonia called Legionnaires' disease. Rip2 and Naip5/NLRC4 signaling was found to contribute to the innate immune response generated against L. pneumophila in the lung. Elimination of Rip2 or Naip5/NLRC4 signaling in MyD88-deficient mice resulted in increased replication and dissemination of L. pneumophila and higher rates of mortality. Irradiated wild-type mice receiving bone marrow cells from pattern recognition receptor-deficient mice displayed L. pneumophila infection phenotypes similar to those of donor mice. Rip2 and Naip5/NLRC4 signaling provided additive effects in protecting MyD88-deficient mice from lethal infection by L. pneumophila, with the contribution of Naip5/NLRC4 being slightly greater than that of Rip2. Thus, activation of the Rip2, MyD88, and Naip5/NLRC4 signaling pathways triggers a coordinated and synergistic response that protects the host against lethal infection by L. pneumophila. These data provide new insight into how different pattern recognition systems interact functionally to generate innate immune responses that protect the host from lethal infection by activating cellular pathways that restrict intracellular replication of L. pneumophila and by recruiting to the site of infection additional phagocytes that eliminate extracellular bacteria. C1 [Archer, Kristina A.; Ader, Florence; Roy, Craig R.] Yale Univ, Sch Med, Sect Microbial Pathogenesis, Boyer Ctr Mol Med, New Haven, CT 06536 USA. [Ader, Florence] Univ Lyon 1, INSERM, Natl Reference Ctr Legionella, U851, F-69008 Lyon, France. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Flavell, Richard A.] Yale Univ, Howard Hughes Med Inst, Dept Immunobiol, Sch Med, New Haven, CT 06536 USA. RP Roy, CR (reprint author), Yale Univ, Sch Med, Sect Microbial Pathogenesis, Boyer Ctr Mol Med, 295 Congress Ave, New Haven, CT 06536 USA. EM craig.roy@yale.edu RI ADER, Florence/M-7619-2014; OI Roy, Craig/0000-0003-4490-440X FU NIH [R01-AI048770] FX This work was supported by NIH grant R01-AI048770 to C. R. R. NR 57 TC 33 Z9 35 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2010 VL 78 IS 6 BP 2477 EP 2487 DI 10.1128/IAI.00243-10 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 598ML UT WOS:000277841300013 PM 20351139 ER PT J AU McCoy, MW Marre, ML Lesser, CF Mecsas, J AF McCoy, Melissa W. Marre, Meghan L. Lesser, Cammie F. Mecsas, Joan TI The C-Terminal Tail of Yersinia pseudotuberculosis YopM Is Critical for Interacting with RSK1 and for Virulence SO INFECTION AND IMMUNITY LA English DT Article ID E3 UBIQUITIN LIGASES; SIGNATURE-TAGGED MUTAGENESIS; MOUSE INFECTION MODEL; RIBOSOMAL S6 KINASE; PROTEIN-KINASE; OUTER PROTEINS; LISTERIA-MONOCYTOGENES; GEL ELECTROPHORESIS; POTENTIAL EFFECTOR; SYSTEMIC PLAGUE AB Yersinia spp. undermine the immune responses of infected animals by translocating Yops directly into host cells with a type III secretion system. YopM, a leucine-rich repeat protein, is a critical virulence factor in infection. YopM localizes to both the nucleus and the cytoplasm in cultured cells, interacts with mammalian p90 ribosomal S6 kinase 1 (RSK1), and causes a decrease in NK cell populations in spleens. Little is known about the molecular interaction between YopM and RSK1 and its significance in pathogenesis. We performed a systematic deletion analysis of YopM in Yersinia pseudotuberculosis to determine which regions are required for RSK1 interactions, nuclear localization, virulence, and changes in immune cell populations during infection of mice. Full-length YopM associated with RSK1 in at least two protein complexes in infected cells, and deletion of its C-terminal tail abrogated all RSK1 interactions. The C-terminal tail was required for tissue colonization, as yopM mutants that failed to interact with RSK1 were as defective for tissue colonization as was a Delta yopM mutant; however, nuclear localization of YopM was not dependent on its RSK1 interaction. Mutants expressing YopM proteins which do not interact with RSK1 caused more pathology than did the Delta yopM mutant, suggesting that there are other RSK1-independent functions of YopM. Histopathological and flow cytometric analyses of spleens showed that infection with wild-type Y. pseudotuberculosis caused an influx of neutrophils, while mice infected with yopM mutants had increased numbers of macrophages. Decreases in NK cells after Y. pseudotuberculosis infection did not correlate with YopM expression. In conclusion, the C terminus of YopM is essential for RSK1 interactions and for virulence. C1 [McCoy, Melissa W.; Mecsas, Joan] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Marre, Meghan L.] Tufts Univ, Program Immunol, Boston, MA 02111 USA. [Lesser, Cammie F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis,Dept Med, Cambridge, MA 02139 USA. [Lesser, Cammie F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Microbiol & Mol Genet,Div Infect Dis, Cambridge, MA 02139 USA. RP Mecsas, J (reprint author), Tufts Univ, Dept Mol Biol & Microbiol, 136 Harrison Ave, Boston, MA 02111 USA. EM joan.mecsas@tufts.edu FU NIH [A1056058, AI073759]; [T32GM07310]; [T32AI007077] FX This work was supported by NIH A1056058 and AI073759 awarded to J.M. M. W. M. was supported by T32GM07310; M. L. M. was supported by T32AI007077. NR 65 TC 31 Z9 32 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2010 VL 78 IS 6 BP 2584 EP 2598 DI 10.1128/IAI.00141-10 PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 598ML UT WOS:000277841300023 PM 20368345 ER PT J AU Herbold, W Maus, R Hahn, I Ding, N Srivastava, M Christman, JW Mack, M Reutershan, J Briles, DE Paton, JC Winter, C Welte, T Maus, UA AF Herbold, Wiebke Maus, Regina Hahn, Ines Ding, Nadine Srivastava, Mrigank Christman, John W. Mack, Matthias Reutershan, Joerg Briles, David E. Paton, James C. Winter, Christine Welte, Tobias Maus, Ulrich A. TI Importance of CXC Chemokine Receptor 2 in Alveolar Neutrophil and Exudate Macrophage Recruitment in Response to Pneumococcal Lung Infection SO INFECTION AND IMMUNITY LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE INFECTION; PULMONARY INFECTION; MONOCYTE MIGRATION; CCL2-CCR2 AXIS; HOST-DEFENSE; MURINE MODEL; MICE; CC; INJURY; INFLAMMATION AB Sustained neutrophilic infiltration is known to contribute to organ damage, such as acute lung injury. CXC chemokine receptor 2 (CXCR2) is the major receptor regulating inflammatory neutrophil recruitment in acute and chronic inflamed tissues. Whether or not the abundant neutrophil recruitment observed in severe pneumonia is essential for protective immunity against Streptococcus pneumoniae infections is incompletely defined. Here we show that CXCR2 deficiency severely perturbs the recruitment of both neutrophils and exudate macrophages associated with a massive bacterial outgrowth in distal airspaces after infection with S. pneumoniae, resulting in 100% mortality in knockout (KO) mice within 3 days. Moreover, irradiated wild-type mice reconstituted with increasing amounts of CXCR2 KO bone marrow (10, 25, 50, and 75% KO) have correspondingly decreased numbers of both neutrophils and exudate macrophages, which is associated with a stepwise increase in bacterial burden and a reciprocal stepwise decrease in survival in S. pneumoniae-induced pulmonary infection. Finally, application of the CXCR2 antagonist SB-225002 resulted in decreased alveolar neutrophil and exudate macrophage recruitment in mice along with increased lung bacterial loads after infection with S. pneumoniae. Together, these data show that CXC chemokine receptor 2 serves a previously unrecognized nonredundant role in the regulation of both neutrophil and exudate macrophage recruitment to the lung in response to S. pneumoniae infection. In addition, we demonstrate that a threshold level of 10 to 25% of reduced neutrophil recruitment is sufficient to cause increased mortality in mice infected with S. pneumoniae. C1 [Herbold, Wiebke; Maus, Regina; Hahn, Ines; Ding, Nadine; Winter, Christine; Welte, Tobias; Maus, Ulrich A.] Hannover Med Sch, Dept Pulm Med, Lab Expt Lung Res, D-30625 Hannover, Germany. [Srivastava, Mrigank] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Christman, John W.] Univ Illinois, Ctr Lung & Vasc Biol, Chicago, IL USA. [Mack, Matthias] Univ Regensburg, Dept Nephrol, Regensburg, Germany. [Reutershan, Joerg] Univ Tubingen, Dept Anaesthesiol & Intens Care Med, Tubingen, Germany. [Briles, David E.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Paton, James C.] Univ Adelaide, Sch Mol & Biomed Sci, Res Ctr Infect Dis, Adelaide, SA, Australia. RP Maus, UA (reprint author), Hannover Med Sch, Dept Pulm Med, Lab Expt Lung Res, D-30625 Hannover, Germany. EM Maus.Ulrich@mh-hannover.de RI Paton, James/A-9920-2008 FU German Research Foundation [SFB 587] FX This study was supported by the German Research Foundation, grant SFB 587 to U. A. M. and T. W. NR 32 TC 44 Z9 46 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2010 VL 78 IS 6 BP 2620 EP 2630 DI 10.1128/IAI.01169-09 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 598ML UT WOS:000277841300026 PM 20368349 ER PT J AU Jabbar, U Leischner, J Kasper, D Gerber, R Sambol, SP Parada, JP Johnson, S Gerding, DN AF Jabbar, Umair Leischner, Julie Kasper, Douglas Gerber, Robert Sambol, Susan P. Parada, Jorge P. Johnson, Stuart Gerding, Dale N. TI Effectiveness of Alcohol-Based Hand Rubs for Removal of Clostridium difficile Spores from Hands SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID DISEASE; INFECTION; HOSPITALS; HYGIENE; AGENTS AB BACKGROUND. Alcohol-based hand rubs (ABHRs) are an effective means of decreasing the transmission of bacterial pathogens. Alcohol is not effective against Clostridium difficile spores. We examined the retention of C. difficile spores on the hands of volunteers after ABHR use and the subsequent transfer of these spores through physical contact. METHODS. Nontoxigenic C. difficile spores were spread on the bare palms of 10 volunteers. Use of 3 ABHRs and chlorhexidine soap-and-water washing were compared with plain water rubbing alone for removal of C. difficile spores. Palmar cultures were performed before and after hand decontamination by means of a plate stamping method. Transferability of C. difficile after application of ABHR was tested by having each volunteer shake hands with an uninoculated volunteer. RESULTS. Plain water rubbing reduced palmar culture counts by a mean (+/- standard deviation [SD]) of 1.57 +/- 0.11 log(10) colony-forming units (CFU) per cm(2), and this value was set as the zero point for the other products. Compared with water washing, chlorhexidine soap washing reduced spore counts by a mean (+/- SD) of 0.89 +/- 0.34 log(10) CFU per cm2; among the ABHRs, Isagel accounted for a reduction of 0.11 +/- 0.20 log(10) CFU per cm(2) (P = .005), Endure for a reduction of 0.37 +/- 0.42 log(10) CFU per cm(2) (P = .010), and Purell for a reduction of 0.14 +/- 0.33 log(10) CFU per cm(2) (P = .005). There were no statistically significant differences between the reductions achieved by the ABHRs; only Endure had a reduction statistically different from that for water control rubbing (P = .040). After ABHR use, handshaking transferred a mean of 30% of the residual C. difficile spores to the hands of recipients. CONCLUSIONS. Hand washing with soap and water is significantly more effective at removing C. difficile spores from the hands of volunteers than are ABHRs. Residual spores are readily transferred by a handshake after use of ABHR. Infect Control Hosp Epidemiol 2010; 31(6): 565-570 C1 [Jabbar, Umair; Leischner, Julie; Kasper, Douglas; Gerber, Robert; Sambol, Susan P.; Parada, Jorge P.; Johnson, Stuart; Gerding, Dale N.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Parada, Jorge P.; Johnson, Stuart; Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Gerding, DN (reprint author), Hines VA Hosp, Res Serv 151, 5000 S 5th Ave,Bldg 1,Rm C344, Hines, IL 60141 USA. EM dale.gerding2@va.gov FU US Department of Veterans Affairs Research Service [1I01BX000515-01]; Loyola Stritch School of Medicine; Massachusetts Biological Laboratories; ViroPharma; Gojo; Cepheid; Optimer; Merck FX Financial support. The US Department of Veterans Affairs Research Service (to J.P.P. and S.J. and grant 1I01BX000515-01 to D.N.G.); and the Loyola Stritch School of Medicine (Student Approaches to Research grant to U.J.).; Potential conflicts of interest. D.N.G. holds patents for the prevention and treatment of C. difficile-associated disease licensed to ViroPharma; has received research funding from Massachusetts Biological Laboratories, ViroPharma, Gojo, Cepheid, Optimer, and Merck; and is a consultant for Optimer, Actelion, Gojo, Schering-Plough, Cepheid, BD GeneOhm, Cubist, and ViroPharma. S.J. is a consultant for Genzyme, Salix, Optimer, ViroPharma, and BD GeneOhm. J.P.P. has received honoraria for services as a consultant and/or as a member of the speakers bureau for ViroPharma, Merck, Cepheid, and Pfizer. All other authors report no potential conflicts of interest relevant to this article. NR 21 TC 48 Z9 48 U1 4 U2 44 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUN PY 2010 VL 31 IS 6 BP 565 EP 570 DI 10.1086/652772 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 590EX UT WOS:000277208400001 PM 20429659 ER PT J AU Lee, BY Bailey, RR Smith, KJ Muder, RR Strotmeyer, ES Lewis, GJ Ufberg, PJ Song, YH Harrison, LH AF Lee, Bruce Y. Bailey, Rachel R. Smith, Kenneth J. Muder, Robert R. Strotmeyer, Elsa S. Lewis, G. Jonathan Ufberg, Paul J. Song, Yeohan Harrison, Lee H. TI Universal Methicillin-Resistant Staphylococcus aureus (MRSA) Surveillance for Adults at Hospital Admission: An Economic Model and Analysis SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID COST-EFFECTIVENESS; ACQUIRED INFECTION; CARE; ENTEROCOCCUS; VANCOMYCIN; CARRIAGE; BURDEN AB BACKGROUND. Methicillin-resistant Staphylococcus aureus (MRSA) transmission and infections are a continuing problem in hospitals. Although some have recommended universal surveillance for MRSA at hospital admission to identify and to isolate MRSA-colonized patients, there is a need for formal economic studies to determine the cost-effectiveness of such a strategy. METHODS. We developed a stochastic computer simulation model to determine the potential economic impact of performing MRSA surveillance (ie, single culture of an anterior nares specimen) for all hospital admissions at different MRSA prevalences and basic reproductive rate thresholds from the societal and third party-payor perspectives. Patients with positive surveillance culture results were placed under isolation precautions to prevent transmission by way of respiratory droplets. MRSA-colonized patients who were not isolated could transmit MRSA to other hospital patients. RESULTS. The performance of universal MRSA surveillance was cost-effective (defined as an incremental cost-effectiveness ratio of less than $50,000 per quality-adjusted life-year) when the basic reproductive rate was 0.25 or greater and the prevalence was 1% or greater. In fact, surveillance was the dominant strategy when the basic reproductive rate was 1.5 or greater and the prevalence was 15% or greater, the basic reproductive rate was 2.0 or greater and the prevalence was 10% or greater, and the basic reproductive rate was 2.5 or greater and the prevalence was 5% or greater. CONCLUSIONS. Universal MRSA surveillance of adults at hospital admission appears to be cost-effective at a wide range of prevalence and basic reproductive rate values. Individual hospitals and healthcare systems could compare their prevailing conditions (eg, the prevalence of MRSA colonization and MRSA transmission dynamics) with the benchmarks in our model to help determine their optimal local strategies. Infect Control Hosp Epidemiol 2010; 31(6): 598-606 C1 [Lee, Bruce Y.; Harrison, Lee H.] Univ Pittsburgh, Infect Dis Epidemiol Res Unit, Sch Med, Pittsburgh, PA 15213 USA. [Harrison, Lee H.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Lee, Bruce Y.; Bailey, Rachel R.; Smith, Kenneth J.; Lewis, G. Jonathan; Ufberg, Paul J.; Song, Yeohan] Vet Affairs Pittsburgh Hlth Care Syst, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA USA. [Bailey, Rachel R.; Lewis, G. Jonathan; Ufberg, Paul J.; Song, Yeohan] Vet Affairs Pittsburgh Hlth Care Syst, Dept Biomed Informat, Pittsburgh, PA USA. [Bailey, Rachel R.; Strotmeyer, Elsa S.; Lewis, G. Jonathan; Ufberg, Paul J.; Song, Yeohan] Vet Affairs Pittsburgh Hlth Care Syst, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Muder, Robert R.] Vet Affairs Pittsburgh Hlth Care Syst, Div Infect Dis, Pittsburgh, PA USA. RP Lee, BY (reprint author), Univ Pittsburgh, Infect Dis Epidemiol Res Unit, Sch Med, 200 Meyran Ave,Rm 217, Pittsburgh, PA 15213 USA. EM BYL1@pitt.edu RI Strotmeyer, Elsa/F-3015-2014; OI Smith, Kenneth J/0000-0001-8088-566X; Strotmeyer, Elsa/0000-0002-4093-6036; Slayton, Rachel/0000-0003-4699-8040 FU National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) [5U01GM070708-05] FX Financial support. National Institute of General Medical Sciences Models of Infectious Disease Agent Study (MIDAS) (grant 5U01GM070708-05). NR 30 TC 34 Z9 35 U1 0 U2 11 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUN PY 2010 VL 31 IS 6 BP 598 EP 606 DI 10.1086/652524 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 590EX UT WOS:000277208400007 PM 20402588 ER PT J AU Fishman, JA Issa, NC AF Fishman, Jay A. Issa, Nicolas C. TI Infection in Organ Transplantation: Risk Factors and Evolving Patterns of Infection SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE Solid-organ transplantation; Infection; Viral infection; Epidemiology ID WEST-NILE-VIRUS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; RENAL-ALLOGRAFT RECIPIENTS; T-CELL DEPLETION; LIVER-TRANSPLANTATION; BK VIRUS; CYTOMEGALOVIRUS INFECTIONS; KIDNEY-TRANSPLANTATION; ANTITHYMOCYTE GLOBULIN; LUNG TRANSPLANTATION AB The nature of infections after solid-organ transplantation has changed with increasingly potent immunosuppressive regimens, routine use of antimicrobial prophylaxis, and improved microbiologic diagnostic tools. New pathogens have been identified in this population including many with significant antimicrobial resistance. Intensification of immunosuppressive regimens, including the use of T- and B-lymphocyte depleting agents, presents an increased risk for infection and requires linkage to microbiologic monitoring and prophylaxis against opportunistic infections. The effect of these regimens is reflected in the increased recognition of viral and fungal infections beyond 1 year after transplantation. Donor-derived infections represent a challenge to organ transplantation in terms of microbiologic screening of donors and the need for communication among clinical centers, organ procurement organizations, and public health authorities. New approaches to microbiologic assessment of organ donors and recipients are needed. In the future, improved assays for microbiologic and immunologic monitoring will allow individualization of prophylactic strategies to reduce the risk of infection in this highly susceptible population. C1 [Fishman, Jay A.] Harvard Univ, Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Sch Med,Div Infect Dis, Boston, MA 02114 USA. [Fishman, Jay A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Sch Med,Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org NR 71 TC 54 Z9 56 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 2010 VL 24 IS 2 BP 273 EP + DI 10.1016/j.idc.2010.01.005 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 606ZB UT WOS:000278466600003 PM 20466270 ER PT J AU Koo, S Marty, FM Baden, LR AF Koo, Sophia Marty, Francisco M. Baden, Lindsey R. TI Infectious Complications Associated with Immunomodulating Biologic Agents SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article DE Monoclonal antibodies; Biologic therapies; Infectious complications ID NECROSIS-FACTOR-ALPHA; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; NON-HODGKINS-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; STEM-CELL TRANSPLANTATION; ACTIVE RHEUMATOID-ARTHRITIS; VISCERAL LEISHMANIASIS INFECTION; RANDOMIZED CONTROLLED-TRIALS; LISTERIA-MONOCYTOGENES INFECTION; PNEUMOCYSTIS-JIROVECII PNEUMONIA AB The armamentarium of biologic therapies targeting specific elements of the immune system is rapidly expanding. This review describes the spectrum of infectious complications associated to date with each of the immunomodulating biologic therapies approved by the US Food and Drug Administration. C1 [Koo, Sophia; Marty, Francisco M.; Baden, Lindsey R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Koo, Sophia; Marty, Francisco M.; Baden, Lindsey R.] Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. [Koo, Sophia; Marty, Francisco M.; Baden, Lindsey R.] Harvard Univ, Sch Med, Boston, MA USA. RP Koo, S (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM skoo@partners.org OI Koo, Sophia/0000-0002-4973-7439 NR 163 TC 16 Z9 16 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 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 2010 VL 24 IS 2 BP 285 EP + DI 10.1016/j.idc.2010.01.006 PG 23 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 606ZB UT WOS:000278466600004 PM 20466271 ER PT J AU Dean-Clower, E Doherty-Gilman, AM Keshaviah, A Baker, F Kaw, C Lu, WD Manola, J Penson, RT Matulonis, UA Rosenthal, DS AF Dean-Clower, Elizabeth Doherty-Gilman, Anne M. Keshaviah, Aparna Baker, Frank Kaw, Chiewkwei Lu, Weidong Manola, Judith Penson, Richard T. Matulonis, Ursula A. Rosenthal, David S. TI Acupuncture as Palliative Therapy for Physical Symptoms and Quality of Life for Advanced Cancer Patients SO INTEGRATIVE CANCER THERAPIES LA English DT Article DE acupuncture; palliative care; symptom management; ovarian cancer; breast cancer ID ALTERNATIVE MEDICINE USE; RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER; GYNECOLOGIC CANCER; MOOD STATES; SHORT-FORM; COMPLEMENTARY; PAIN; ELECTROACUPUNCTURE; SURVIVORS AB Background. Acupuncture is underutilized as an adjunct cancer therapy. The main study objectives were to determine the feasibility of administering acupuncture as palliative therapy to patients with advanced ovarian or breast cancer and to assess the effect on symptoms and quality of life (QOL). Methods. This study was a pilot, single-armed prospective clinical trial for patients with advanced cancer to receive 12 acupuncture sessions over 8 weeks with follow-up at weeks 9 and 12. Ambulatory patients with advanced ovarian or breast cancer were enrolled to receive treatments at an outpatient academic oncology center. Symptom severity was measured before and after each acupuncture session. A composite QOL assessment tool, consisting of validated instruments, was completed at 5 time points. Results. Forty patients enrolled in the study. Twenty-eight patients (70%; 95% confidence interval [CI] = 53%-83%) completed 4 weeks of treatment, and 26 patients (65%; 95% CI = 48%-79%) completed 8 weeks. Eight patients (20%) withdrew before receiving acupuncture, and 6 patients (15%) discontinued treatment early because of disease progression or scheduling demands. Among all 32 assessed patients, there was self-reported improvement immediately post-treatment in anxiety, fatigue, pain, and depression and significant improvement over time for patients with anxiety (P=.001) and depression (P=.02). Among patients experiencing baseline symptoms, there was improvement in anxiety (P=.001), fatigue (P=.0002), pain (P=.0002), and depression (P=.003). QOL measures of pain severity and interference, physical and psychological distress, life satisfaction, and mood states showed improved scores during treatment, with sustained benefit at 12 weeks. Conclusions. This pilot study demonstrates that an 8-week outpatient acupuncture course is feasible for advanced cancer patients and produces a measurable benefit that should be evaluated in controlled trials. C1 [Rosenthal, David S.] Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, Boston, MA 02115 USA. [Baker, Frank] New York Med Coll, Ctr Med Outcomes Res, Sch Hlth Sci & Practice, Valhalla, NY 10595 USA. [Kaw, Chiewkwei] Amer Canc Soc, Atlanta, GA 30329 USA. [Keshaviah, Aparna; Penson, Richard T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dean-Clower, Elizabeth; Lu, Weidong; Penson, Richard T.; Matulonis, Ursula A.; Rosenthal, David S.] Harvard Univ, Sch Med, Boston, MA USA. RP Rosenthal, DS (reprint author), Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, 44 Binney St, Boston, MA 02115 USA. EM drose@uhs.harvard.edu RI choi, gaeun/F-5707-2014; Lu, Weidong/C-3844-2008 OI Lu, Weidong/0000-0003-2838-6307 FU National Center for Complementary and Alternative Medicine (NCCAM) [5 R21 AT01010-02] FX This study was supported by the National Center for Complementary and Alternative Medicine (NCCAM) [grant # 5 R21 AT01010-02]. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM or the National Institutes of Health. NR 45 TC 24 Z9 24 U1 1 U2 14 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 JUN PY 2010 VL 9 IS 2 BP 158 EP 167 DI 10.1177/1534735409360666 PG 10 WC Oncology; Integrative & Complementary Medicine SC Oncology; Integrative & Complementary Medicine GA 617HW UT WOS:000279272600004 PM 20483875 ER PT J AU Sheu, CC Gong, MN Zhai, RH Bajwa, EK Chen, F Thompson, BT Christiani, DC AF Sheu, Chau-Chyun Gong, Michelle N. Zhai, Rihong Bajwa, Ednan K. Chen, Feng Thompson, B. Taylor Christiani, David C. TI The influence of infection sites on development and mortality of ARDS SO INTENSIVE CARE MEDICINE LA English DT Article DE Acute respiratory distress syndrome; Epidemiology; Infection; Pneumonia; Mortality; Risk factors ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; BLOOD-STREAM INFECTION; INTENSIVE-CARE UNITS; SEVERE SEPSIS; SEPTIC SHOCK; RISK-FACTORS; EPIDEMIOLOGY; PNEUMONIA; COMMUNITY AB Infection is the most frequent cause of acute respiratory distress syndrome (ARDS). However, little is known about the influence of infection sites on ARDS. This study aimed to assess the associations of infection sites with ARDS development and mortality in critically ill infected patients. Prospective observational study. Adult intensive care units (ICUs) of an academic medical center. Study population included 1,973 consecutive patients admitted to ICUs with bacteremia, pneumonia or sepsis. During follow-up, 549 patients developed ARDS and 212 of them died within 60 days. The distribution of infection sites in ARDS patients was: lung (77.2%), abdomen (19.3%), skin/soft tissues (6.0%), urinary tract (4.7%), unknown (2.6%), and multiple sites (17.7%). On multivariate analysis, lung was the only infection site associated with increased ARDS risk [adjusted odds ratio (OR) 3.49]. Urinary tract (adjusted OR 0.43), skin/soft tissue (adjusted OR 0.64), and unknown-site infections (adjusted OR 0.38) were associated with decreased risk. No association was found between individual infection site and ARDS mortality. However, unknown-site [adjusted hazard ratio (HR) 3.08] and multiple-site infections (adjusted HR 1.63) were associated with increased ARDS mortality. When grouping patients into pulmonary, nonpulmonary, and combined infections, nonpulmonary infection was associated with decreased ARDS risk (adjusted OR 0.28) and combined infections was associated with increased ARDS mortality (adjusted HR 1.69), compared with pulmonary infection. In critically ill infected patients, pulmonary infection is associated with higher risk of ARDS development than are infections at other sites. Pulmonary versus nonpulmonary infection significantly affects ARDS development but not mortality. C1 [Sheu, Chau-Chyun; Zhai, Rihong; Chen, Feng] 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, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02115 USA. [Gong, Michelle N.] Montefiore Med Ctr, Div Crit Care Med, Bronx, NY 10461 USA. [Gong, Michelle N.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Sheu, Chau-Chyun] Kaohsiung Med Univ Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Kaohsiung 807, Taiwan. [Sheu, Chau-Chyun] Kaohsiung Med Univ, Coll Med, Fac Resp Therapy, Kaohsiung 807, Taiwan. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Institutes of Health, USA [ES00002, HL60710, HL087934] FX This study was supported by grants ES00002, HL60710, and HL087934 from National Institutes of Health, USA. The authors would like to thank Thomas McCabe, Julia Shin, Hanae Fujii-Rios, Ian Taggart, and Kezia Ellison for patient recruitment; Andrea Shafer and Starr Sumpter for research support; Janna Frelich, Marcia Chertok, and Julie DelPrato for data management; and the patients and staff of ICUs at Massachusetts General Hospital. NR 30 TC 15 Z9 17 U1 0 U2 1 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 JUN PY 2010 VL 36 IS 6 BP 963 EP 970 DI 10.1007/s00134-010-1851-3 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 592II UT WOS:000277371600008 PM 20229040 ER PT J AU Villar, J Cabrera, N Casula, M Flores, C Valladares, F Muros, M Blanch, L Slutsky, AS Kacmarek, RM AF Villar, Jesus Cabrera, Nuria Casula, Milena Flores, Carlos Valladares, Francisco Muros, Mercedes Blanch, Lluis Slutsky, Arthur S. Kacmarek, Robert M. TI Mechanical ventilation modulates Toll-like receptor signaling pathway in a sepsis-induced lung injury model SO INTENSIVE CARE MEDICINE LA English DT Article DE Acute lung injury; Sepsis; Positive-pressure ventilation; Cytokine; Toll-like receptor ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; TIDAL-VOLUME; IRAK-M; ALVEOLAR MACROPHAGES; CYTOKINE RELEASE; PULMONARY-EDEMA; EXPRESSION AB Experimental and clinical studies on sepsis have demonstrated activation of the innate immune response following the initial host-bacterial interaction. In addition, mechanical ventilation (MV) can induce a pulmonary inflammatory response. How these two responses interact when present simultaneously remains to be elucidated. We hypothesized that MV modulates innate host response during sepsis by influencing Toll-like receptor (TLR) signaling. Prospective, randomized, controlled animal study. Male, septic Sprague-Dawley rats. Sepsis was induced by cecal ligation and perforation. At 18 h, surviving animals had the cecum removed and were randomized to spontaneous breathing or two strategies of MV for 4 h: high (20 ml/kg) tidal volume (V (T)) with no positive end-expiratory pressure (PEEP) versus low V (T) (6 ml/kg) plus 10 cmH(2)O PEEP. Histological evaluation, TLR-2, TLR-4, inhibitory kappaB alpha (I kappa B alpha), interleukin-1 receptor-associated kinase-3 (IRAK-3) gene expression, protein levels and immunohistochemical lung localization, inflammatory cytokines gene expression, and protein serum concentrations were analyzed. MV with low V (T) plus PEEP attenuated sepsis-associated TLR-4 activation, and produced a significant decrease of IRAK-3 gene expression and protein levels, a significant increase of I kappa B alpha, and a decrease in lung gene expression and serum levels of cytokines. High-V (T) MV caused a significant increase of TLR-4 and IRAK-3 protein levels, lung and systemic cytokines, and mortality, and a significant decrease of I kappa B alpha. Our findings suggest a novel mechanism that could partially explain how MV modulates the innate immune response in the lung by interfering with cellular signaling pathways that are activated in response to pathogens. C1 [Villar, Jesus; Cabrera, Nuria; Casula, Milena] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, South Wing, Las Palmas Gran Canaria 35010, Spain. [Villar, Jesus; Cabrera, Nuria; Casula, Milena; Flores, Carlos; Valladares, Francisco; Muros, Mercedes; Blanch, Lluis] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus; Slutsky, Arthur S.] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Flores, Carlos] Hosp Univ NS Candelaria, Res Unit, Tenerife, Spain. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Slutsky, Arthur S.] King Saud Univ, Riyadh, Saudi Arabia. [Slutsky, Arthur S.] Univ Toronto, Interdepartmental Div Crit Care Med, Toronto, ON, Canada. [Blanch, Lluis] Corp Sanit, Crit Care Ctr, Sabadell, Spain. [Muros, Mercedes] Hosp Univ NS Candelaria, Dept Clin Biochem, Tenerife, Spain. [Valladares, Francisco] Univ La Laguna, Dept Anat Pathol & Histol, Tenerife, Canary Islands, Spain. RP Villar, J (reprint author), Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, South Wing, Barranco Ballena S-N 4th Floor, Las Palmas Gran Canaria 35010, Spain. EM jesus.villar54@gmail.com FU Ministerio de Ciencia of Spain [SAF 2004-06833]; FUNCIS [53/04]; Instituto de Salud Carlos III and FUNCIS [EMER07/001] FX Supported by grants from Ministerio de Ciencia of Spain (SAF 2004-06833), FUNCIS (53/04), and by a specific agreement between Instituto de Salud Carlos III and FUNCIS (EMER07/001) under the ENCYT 2015 framework. NR 49 TC 31 Z9 32 U1 0 U2 8 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 JUN PY 2010 VL 36 IS 6 BP 1049 EP 1057 DI 10.1007/s00134-010-1799-3 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 592II UT WOS:000277371600020 PM 20397011 ER PT J AU Giraud, R Siegenthaler, N Park, C Beutler, S Bendjelid, K AF Giraud, Raphael Siegenthaler, Nils Park, Chan Beutler, Sascha Bendjelid, Karim TI Transpulmonary thermodilution curves for detection of shunt SO INTENSIVE CARE MEDICINE LA English DT Article DE Pulmonary edema; Interventricular shunt ID INTRATHORACIC BLOOD-VOLUME; EXTRAVASCULAR LUNG WATER; DILUTION TECHNIQUE AB Monitoring using transpulmonary thermodilution (TPTD) via a single thermal indicator technique allows measurement of cardiac output, extravascular lung water (EVLW) and volumetric variables. This report describes two cases of systemic-venous circulation shunt generating early recirculation of thermal indicator with overestimation of EVLW. In the case of recirculation of thermal indicator, the observed overestimated EVLW in absence of gas exchanges abnormality could be an indicator suggesting the search for a circulatory shunt. C1 [Giraud, Raphael; Siegenthaler, Nils; Bendjelid, Karim] Univ Hosp Geneva, Intens Care Unit, CH-1205 Geneva, Switzerland. [Beutler, Sascha] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Park, Chan] Univ Hosp Geneva, Dept Internal Med, Div Cardiol, Geneva, Switzerland. RP Bendjelid, K (reprint author), Univ Hosp Geneva, Intens Care Unit, Rue Micheli du Crest 24, CH-1205 Geneva, Switzerland. EM Karim.Bendjelid@hcuge.ch NR 6 TC 26 Z9 27 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 JUN PY 2010 VL 36 IS 6 BP 1083 EP 1086 DI 10.1007/s00134-010-1876-7 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 592II UT WOS:000277371600024 PM 20397008 ER PT J AU Pena, A Virk, SS Shewchuk, RM Allison, JJ Williams, OD Kiefe, CI AF Pena, Adolfo Virk, Sandeep S. Shewchuk, Richard M. Allison, Jeroan J. Williams, O. Dale Kiefe, Catarina I. TI Validity versus feasibility for quality of care indicators: expert panel results from the MI-Plus study SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE clinical guidelines; feasibility; myocardial infarction; quality indicators; quality of health care; validity ID MYOCARDIAL-INFARCTION; HEALTH; MANAGEMENT AB In the choice and definition of quality of care indicators, there may be an inherent tension between feasibility, generally enhanced by simplicity, and validity, generally enhanced by accounting for clinical complexity. To study the process of developing quality indicators using an expert panel and analyze the tension between feasibility and validity. A multidisciplinary panel of 12 expert physicians was engaged in two rounds of modified Delphi process to refine and choose a smaller subset from 36 indicators; these were developed by a research team studying the quality of care in ambulatory post-myocardial infarction patients with co-morbidities. We studied the correlation between validity/feasibility ranks provided by the expert panel. The correlation between the quality indicators ranks on validity and feasibility scale and variance of experts' responses was also individually studied. Ten of 36 indicators were ranked in both the highest validity and feasibility groups. The strength of association between validity and feasibility of indicators measured by Kendall tau-b was 0.65. In terms of validity, a strong negative correlation was observed between the ranks of indicators and the variability in expert panel responses (Spearman's rho, r = -0.85). A weak correlation was found between the ranks of feasibility and the variability of expert panel responses (Spearman's rho, r = 0.23). There was an unexpectedly strong association between the validity and feasibility of quality indicators, with a high level of consensus among experts regarding both feasibility and validity for indicators rated highly on each of these attributes. C1 [Pena, Adolfo] Birmingham VA Med Ctr, C SMART Ctr Surg Med Acute Care Res & Transit, Birmingham, AL 35233 USA. [Pena, Adolfo] Univ Alabama, Vet Affairs Natl Qual Scholars Fellowship Program, Birmingham VA Med Ctr, Birmingham, AL USA. [Virk, Sandeep S.] Univ Alabama, Montgomery Internal Med Residency Program, Birmingham, AL USA. [Shewchuk, Richard M.] Univ Alabama, Sch Hlth Related Profess, Dept Hlth Serv Adm, Birmingham, AL USA. [Shewchuk, Richard M.; Williams, O. Dale] Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. [Allison, Jeroan J.; Kiefe, Catarina I.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Williams, O. Dale] Univ Alabama, Sch Med, Dept Med, Birmingham, AL USA. RP Pena, A (reprint author), Birmingham VA Med Ctr, C SMART Ctr Surg Med Acute Care Res & Transit, 151 REAP,700 S 19th St, Birmingham, AL 35233 USA. EM adolfope@uab.edu OI Allison, Jeroan/0000-0003-4472-2112 FU National Heart, Lung and Blood Institute [R01 HL70786] FX This project was funded in part by grant number R01 HL70786 from the National Heart, Lung and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung and Blood Institute or the National Institutes of Health. NR 22 TC 8 Z9 8 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD JUN PY 2010 VL 22 IS 3 BP 201 EP 209 DI 10.1093/intqhc/mzq018 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 597CR UT WOS:000277734100007 PM 20382663 ER PT J AU Karp, JF Weiner, DK Dew, MA Begley, A Miller, MD Reynolds, CF AF Karp, Jordan F. Weiner, Debra K. Dew, Mary A. Begley, Amy Miller, Mark D. Reynolds, Charles F., III TI Duloxetine and care management treatment of older adults with comorbid major depressive disorder and chronic low back pain: results of an open-label pilot study SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE depression; pain; geriatric; back pain; clinical trial ID LATE-LIFE DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; MEDICAL ILLNESS BURDEN; SELF-RATED HEALTH; TREATMENT RESPONSE; DOUBLE-BLIND; EFFICACY; SYMPTOMS; QUESTIONNAIRE AB Objective: In older adults, major depressive disorder (MDD) and chronic low back pain (CLEW) are common and mutually exacerbating. We predicted that duloxetine pharmacotherapy and Depression and Pain Care Management (DPCM) would result in (1) significant improvement in NI DD and CLBP and (2) significant improvements in health-related quality of life, anxiety, disability, self-efficacy, and sleep quality. Design and Intervention: Twelve week open-label study using duloxetine up to 120 mg/day + DPCM. Setting: Outpatient late-life depression research clinic. Patients: Thirty community-dwelling adults >60 years old. Outcome Measures: Montgomery Asberg Depression Rating Scale (MADRS) and McGill Pain Questionnaire-Short Form (MPQ-SF). Results: 46.7% (n = 14) of the sample had a depression remission. All subjects who met criteria for the depression remission also had a pain response. 93.3% (n = 28) had a significant pain response. Of the subjects who met criteria for a low back pain response, 50% (n = 14) also met criteria for the depression remission. The mean time to depression remission was 7.6 (SE = 0.6) weeks. The mean time to pain response was 2.8 (SE = 0.5) weeks. There were significant improvements in mental health-related quality of life, anxiety, sleep quality, somatic complaints, and both self-efficacy for pain management and for coping with symptoms. Physical health-related quality of life, back pain-related disability, and self-efficacy for physical functioning did not improve. Conclusions: Serotonin and norepinephrine reuptake inhibitors like duloxetine delivered with DPCM may be a good choice to treat these linked conditions in older adults. Treatments that target low self-efficacy for physical function and improving disability may further increase response rates. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Karp, Jordan F.; Dew, Mary A.; Begley, Amy; Miller, Mark D.; Reynolds, Charles F., III] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Adv Ctr Intervent & Serv Res Late Life Mood Disor, Pittsburgh, PA 15261 USA. [Karp, Jordan F.; Reynolds, Charles F., III] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, John A Hartford Ctr Excellence Geriatr Psychiat, Pittsburgh, PA 15261 USA. [Karp, Jordan F.; Weiner, Debra K.; Dew, Mary A.; Begley, Amy; Miller, Mark D.; Reynolds, Charles F., III] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Weiner, Debra K.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA. [Dew, Mary A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Karp, JF (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Adv Ctr Intervent & Serv Res Late Life Mood Disor, Pittsburgh, PA 15261 USA. EM karpjf@upmc.edu FU John A. Hartford Center of Excellence in Geriatric Psychiatry [P30 MH71944]; UPMC Endowment in Geriatric Psychiatry; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [KL2 RR-024154-03]; NIH Roadmap for Medical Research FX Supported in part by: P30 MH71944 and The John A. Hartford Center of Excellence in Geriatric Psychiatry, and the UPMC Endowment in Geriatric Psychiatry. This publication was also made possible by grant number KL2 RR-024154-03 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Eli Lilly and Company provided medication supplies for this investigator-initiated trial. NR 70 TC 14 Z9 15 U1 4 U2 14 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JUN PY 2010 VL 25 IS 6 BP 633 EP 642 DI 10.1002/gps.2386 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 605KP UT WOS:000278346800011 PM 19750557 ER PT J AU Lauwers, GY AF Lauwers, Gregory Y. TI Gastritis: Beyond Helicobacter pylori SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Pathology Meeting 2010 CY MAY 21-29, 2010 CL Santiago, CHILE C1 [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Gastrointestinal Pathol Serv, WRN 256,55 Fruit St, Boston, MA 02114 USA. EM glauwers@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JUN PY 2010 VL 18 IS 3 SU S BP 28S EP 32S DI 10.1177/1066896910366462 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 595IZ UT WOS:000277605200003 PM 20484257 ER PT J AU Lauwers, GY AF Lauwers, Gregory Y. TI Biopsy Diagnosis of Non-IBD Colitis SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Pathology Meeting 2010 CY MAY 21-29, 2010 CL Santiago, CHILE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Pathol Serv, Boston, MA 02115 USA. RP Lauwers, GY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Pathol Serv, Boston, MA 02115 USA. EM glauwers@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JUN PY 2010 VL 18 IS 3 SU S BP 48S EP 52S DI 10.1177/1066896910368590 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 595IZ UT WOS:000277605200007 PM 20484261 ER PT J AU Young, RH AF Young, Robert H. TI Pseudotumors of the Urinary Bladder SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Pathology Meeting 2010 CY MAY 21-29, 2010 CL Santiago, CHILE ID PSEUDOSARCOMATOUS MYOFIBROBLASTIC PROLIFERATIONS; SPINDLE-CELL PROLIFERATIONS; NEPHROGENIC ADENOMA; INFLAMMATORY PSEUDOTUMOR; GENITOURINARY TRACT; ADENOCARCINOMA; CYSTITIS; CHEMOTHERAPY; EXPRESSION; CARCINOMA C1 [Young, Robert H.] Massachusetts Gen Hosp, Pathol Serv WRN 2, Boston, MA 02114 USA. [Young, Robert H.] Harvard Univ, Sch Med, Boston, MA USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, Pathol Serv WRN 2, 55 Fruit St, Boston, MA 02114 USA. EM rhyoung@partners.org NR 29 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 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JUN PY 2010 VL 18 IS 3 SU S BP 101S EP 105S DI 10.1177/1066896910370470 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 595IZ UT WOS:000277605200018 PM 20484272 ER PT J AU Young, RH AF Young, Robert H. TI The Problematic Testicular Tumor SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Pathology Meeting 2010 CY MAY 21-29, 2010 CL Santiago, CHILE ID SERTOLI-CELL TUMOR; JUVENILE GRANULOSA-CELL; CORD-STROMAL TUMORS; YOLK-SAC TUMOR; CLINICOPATHOLOGICAL ANALYSIS; SPERMATOCYTIC SEMINOMA; METASTATIC CARCINOMA; INFANTILE TESTIS; INCLUDING 3; FEATURES C1 [Young, Robert H.] Massachusetts Gen Hosp, Pathol Serv WRN 2, Boston, MA 02114 USA. [Young, Robert H.] Harvard Univ, Sch Med, Boston, MA USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, Pathol Serv WRN 2, 55 Fruit St, Boston, MA 02114 USA. EM rhyoung@partners.org NR 43 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JUN PY 2010 VL 18 IS 3 SU S BP 149S EP 155S DI 10.1177/1066896910370769 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 595IZ UT WOS:000277605200027 PM 20484281 ER PT J AU Young, RH AF Young, Robert H. TI Ovarian Tumors of the Young SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Pathology Meeting 2010 CY MAY 21-29, 2010 CL Santiago, CHILE ID SERTOLI-LEYDIG CELL; CLINICOPATHOLOGICAL ANALYSIS; GRANULOSA-CELL; CHILDREN; CHILDHOOD; INFANCY; ADOLESCENCE; NEOPLASMS; MALIGNANCY; PATTERN C1 [Young, Robert H.] Massachusetts Gen Hosp, Pathol Serv WRN 2, Boston, MA 02114 USA. [Young, Robert H.] Harvard Univ, Sch Med, Boston, MA USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, Pathol Serv WRN 2, 55 Fruit St, Boston, MA 02114 USA. EM rhyoung@partners.org NR 29 TC 2 Z9 2 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JUN PY 2010 VL 18 IS 3 SU S BP 156S EP 161S DI 10.1177/1066896910370770 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 595IZ UT WOS:000277605200028 PM 20484282 ER PT J AU Koplin, SA Nielsen, GP Hornicek, FJ Rosenberg, AE AF Koplin, Stephanie A. Nielsen, G. Petur Hornicek, Francis J. Rosenberg, Andrew E. TI Epithelioid Sarcoma With Heterotopic Bone: A Morphologic Review of 4 Cases SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Review DE epithelioid sarcoma; heterotopic bone ID IMMUNOHISTOCHEMICAL ANALYSIS; OSSIFICATION; CARCINOMA; DIAGNOSIS AB Epithelioid sarcoma is an uncommon malignancy that usually arises in the superficial soft tissues of the extremities. Classically, epithelioid sarcoma grows as nodules of mild to moderately atypical epithelioid cells, frequently with central necrosis. The stroma is variably fibrous and may rarely contain heterotopic bone. The presence of bone within epithelioid sarcoma raises a variety of lesions in the differential diagnosis, including reactive processes as well as benign and malignant neoplasms. This morphological variant of epithelioid sarcoma and its associated diagnostic pitfalls has received little attention in the literature. The authors report herein 4 cases of epithelioid sarcoma with heterotopic bone and highlight the morphological characteristics of the bone and how such variants can be distinguished from other bone-forming lesions of the soft tissues. C1 [Koplin, Stephanie A.; Nielsen, G. Petur; Hornicek, Francis J.; Rosenberg, Andrew E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Koplin, SA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM stephaniekoplin@hotmail.com NR 10 TC 8 Z9 8 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JUN PY 2010 VL 18 IS 3 BP 207 EP 212 DI 10.1177/1066896909352862 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 594KN UT WOS:000277536600007 PM 20034988 ER PT J AU Lewinsohn, D AF Lewinsohn, David TI Rethinking the natural history of infection with M. tuberculosis SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article; Proceedings Paper CT 2nd Global Symposium on Interferon-Gamma Release Assays CY MAY 30-JUN 01, 2009 CL Dubrovnik, CROATIA SP Fdn Innovat New Diagnost, Cellestis Ltd AB The tuberculin skin test is associated with exposure to TB, and conversion of a TST is associated with the risk of disease. A consistent number of TB cases occur over the years in persons with positive TSTs. The question is: How much of this is reactivation vs. re-exposure in an endemic setting? The actual case rate is really quite low, even among those with positive TSTs, so either only a minority of those infected with M. tuberculosis develop disease, i.e., the M. tuberculosis organism really does a poor job, or it is possible that there are exposures that do not reflect infection. In either case, we need to do a better job of identifying those at risk for developing TB. IFN-gamma is associated with TB exposure, and it is quantitative, with natural variations over time. Dr Lewinsohn offered some food for thought. He expects to see rising amounts of IFN-gamma with exposure, and this rise will indicate either a recent exposure to M. tuberculosis or a reactivation. Another prediction is that a negative IFN-gamma may not distinguish remote exposure from no exposure. Some will be transiently exposed, and will develop TEM/TDC (like tetanus). The duration of these responses will depend upon the environment. T-cells reflect immunologic history, and his prediction is that some will vet a memory response just like tetanus, but he would predict these would be at low risk. What about understanding T-cell memory and persistent infection? In guinea pigs, conversion of the TST is associated with exposure to M. tuberculosis, but many of the animals will have skin test reversions in which no bacteria can be detected either pathologically or microbiologically. These data challenge the notion of 'once infected, always infected'. In humans, we do not yet have reliable tools to distinguish exposure from infection. However, post-mortem series of those with a positive TST often fail to reveal mycobacteria, and if present it is often found in areas of normal lung. CD8 T-cells are present at high frequency in both active and latent TB infection. CD8 T-cells preferentially recognize heavily infected cells, and may be a surrogate for bacterial burden and/or disease progression. D8 cells recognize MHCII-negative cells and may play a unique role in chronic/persistent phases of infection. They may be a good surrogate for intercellular infection. CD8 T-cell responses to ESAT-6 and CFP-10 were measured in young children with pulmonary TB, or in the setting of household exposure. Here, CD8 responses were associated with pulmonary TB, but not residence in a household. In contrast, the CD4 response was present in both groups. These data were consistent with the hypothesis that exposure to M. tuberculosis and infection could be immunologically differentiated. Dr Lewinsohn's prediction is that a CD8 response will identify those at risk for progression but additional antigens will be needed to improve sensitivity. We know what we do not know, and what we need is a way to find out who are at greatest risk. Who are the acutely infected? We need to think next about what kind of studies need to be done and where, and whom we study. C1 [Lewinsohn, David] Portland VA Med Ctr, Portland, OR USA. [Lewinsohn, David] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Lewinsohn, D (reprint author), Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD JUN PY 2010 VL 14 IS 6 SU 1 BP S7 EP S10 PG 4 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 602BS UT WOS:000278113700003 ER PT J AU Tan-Kim, J Weinstein, MM Nager, CW AF Tan-Kim, Jasmine Weinstein, Milena M. Nager, Charles W. TI Urethral sleeve sensor: a non-withdrawal method to measure maximum urethral pressure SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Profilometry; Sleeve sensor; Urethral pressure; Urodynamics ID URINARY-INCONTINENCE; SPHINCTER PRESSURE; WOMEN; REPRODUCIBILITY; PROFILOMETRY; STRENGTH; PROFILE; DEVICE AB This study seeks to evaluate axial variation, comparisons with current technology, performance during dynamic conditions, and patient tolerability of the urethral sleeve sensor (USS) for maximal urethral closure pressure (MUCP) measurements. Eighteen continent and seven stress incontinent women underwent assessments with USS and urethral pressure profilometry (UPP) in random order. Intravesical (p (ves)) and urethral (p (ura)) pressure signals were collected and urethral closure pressure (p (clo)) was calculated. A visual analog scale (VAS) was used to evaluate subject discomfort. The correlation coefficient between MUCP obtained by UPP and USS techniques was 0.86 (p < 0.001). Higher USS pressures were obtained with catheter oriented to 12 o'clock. Continent subjects demonstrated higher values of p (clo). MUCP became < 0 cm H(2)O in subjects with clinical leakage during Valsalva, but not in continent subjects. Subjects tolerated the USS technique better than the UPP technique on VAS (p < 0.001). USS technology can be used to evaluate the urethra in both static and dynamic conditions and is better tolerated than withdrawal techniques. C1 [Nager, Charles W.] UCSD Womens Pelv Med Ctr, La Jolla, CA 92037 USA. [Weinstein, Milena M.] Massachusetts Gen Hosp, Div Urogynecol & Reconstruct Pelv Surg, Boston, MA 02114 USA. [Tan-Kim, Jasmine; Nager, Charles W.] Univ Calif San Diego, Dept Reprod Med, Div Female Pelv Med & Reconstruct Surg, La Jolla, CA 92093 USA. RP Nager, CW (reprint author), UCSD Womens Pelv Med Ctr, 9350 Campus Point Dr,Suite 2A, La Jolla, CA 92037 USA. EM cnager@ucsd.edu NR 16 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD JUN PY 2010 VL 21 IS 6 BP 685 EP 691 DI 10.1007/s00192-009-1084-6 PG 7 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 587CF UT WOS:000276964000011 PM 20076949 ER PT J AU Huang, W Fileta, J Rawe, I Qu, J Grosskreutz, CL AF Huang, Wei Fileta, John Rawe, Ian Qu, Juan Grosskreutz, Cynthia L. TI Calpain Activation in Experimental Glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GANGLION-CELL DEATH; RAT MODEL; RETINAL DEGENERATION; OCULAR HYPERTENSION; CASPASE ACTIVATION; APOPTOSIS; CALCINEURIN; CLEAVAGE; PRESSURE; PROTEOLYSIS AB PURPOSE. Glaucoma is a neurodegenerative disease in which elevated intraocular pressure (IOP) leads to progressive loss of retinal ganglion cells (RGCs) and blindness. Calcium dyshomeostasis has been suggested to play a role in the pathologic events that lead to RGC loss, though the details of these events are not well understood. Calcium-induced activation of calpain has been shown to contribute to neuronal death in a wide variety of neurodegenerative diseases. The authors hypothesize that similar events occur in glaucoma. METHODS. The authors used a well-established rat model of experimental glaucoma. Retinal tissues were harvested after 5 or 10 days of elevated IOP and were subjected to immunoblot analysis, immunoprecipitation, and MALDI-ProTOF/MS peptide fingerprint mapping. Immunohistochemistry was used to localize calpain activation. RESULTS. The authors present four independent lines of evidence that calpain is activated in experimental glaucoma. First, they showed that a 55-kDa autocatalytic active form of calpain is detected on immunoblot analysis. Second, they demonstrated the cleavage of two well-established calpain substrates, spectrin and calcineurin, only in eyes with elevated IOP. Third, they used MALDI-ProTOF to analyze cleaved calcineurin and immunoblot analysis of spectrin cleavage products and showed that both substrates were cleaved by calpain in experimental glaucoma. Fourth, they used immunohistochemistry to show that calpain-mediated spectrin cleavage occurs in RGCs under conditions of elevated IOP. CONCLUSIONS. These data support the hypothesis that calpain is activated under conditions of elevated intraocular pressure and provide further details of the pathologic events leading to RGC loss in glaucoma. (Invest Ophthalmol Vis Sci. 2010; 51:3049-3054) DOI: 10.1167/iovs.09-4364 C1 [Huang, Wei; Fileta, John; Qu, Juan; Grosskreutz, Cynthia L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, Boston, MA 02114 USA. [Rawe, Ian] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM grosskreutz@meei.harvard.edu FU National Institutes of Health [R01EY1339, P30EY0141049]; Research to Prevent Blindness; Massachusetts Lions Eye Research Fund FX Supported by National Institutes of Health Grant R01EY13399 and Core Grant P30EY014104, Research to Prevent Blindness, and the Massachusetts Lions Eye Research Fund. NR 36 TC 27 Z9 29 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2010 VL 51 IS 6 BP 3049 EP 3054 DI 10.1167/iovs.09-4364 PG 6 WC Ophthalmology SC Ophthalmology GA 598OC UT WOS:000277846500031 PM 20107181 ER PT J AU Li, HK Hubbard, LD Danis, RP Esquivel, A Florez-Arango, JF Krupinski, EA AF Li, Helen K. Hubbard, Larry D. Danis, Ronald P. Esquivel, Adol Florez-Arango, Jose F. Krupinski, Elizabeth A. TI Monoscopic versus Stereoscopic Retinal Photography for Grading Diabetic Retinopathy Severity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID DIGITAL PHOTOGRAPHY; COMPLICATIONS; METHODOLOGY; DIAGNOSIS; COHORT AB PURPOSE. To assess agreement between monoscopic and stereoscopic photography for research classification of the severity of diabetic retinopathy (DR). METHODS. Monoscopic digital (MD) images were compared with stereo digital (SD) and film (SF) photographs from a 152-eye cohort with full-spectrum Early Treatment Diabetic Retinopathy Study (ETDRS) severity levels for agreement on severity level, DR presence with ascending severity threshold, presence of DR index lesions, and repeatability of grading. RESULTS. There was substantial agreement classifying ETDRS DR severity levels between MD and SF (kappa = 0.65, kappa(w) [linear weighted] = 0.87), MD and SD (kappa = 0.66, kappa(w) = 0.87), and SD and SF (kappa = 0.62, kappa(w) = 0.86) images. Marginal homogeneity analyses found no significant difference between MD and SF images (P = 0.53, Bhapkar test). The kappa agreement between MD and SF ranged from 0.80 to 0.94 for the presence or absence of eight ascending DR severity thresholds. Repeatability between the readers of the MD images was equal to or better than that of the readers of SD or SF images. Severity threshold grading repeatability between readers was similar with the MD and SF images. The kappa agreement between MD and SF for identifying diabetic retinopathy lesions ranged from moderate to almost perfect. The kappa comparisons showed that performance of grading new vessels on the disc in MD images was slightly lower than that with the SF images. CONCLUSIONS. Monoscopic photography can equal the reliability of stereo photography for full ETDRS DR severity scale grading. (Invest Ophthalmol Vis Sci. 2010;51:3184-3192) DOI: 10.1167/iovs.09-4886 C1 [Li, Helen K.] Univ Texas Med Branch, Dept Ophthalmol & Visual Sci, Galveston, TX 77555 USA. [Li, Helen K.; Florez-Arango, Jose F.] Univ Texas Hlth Sci Ctr, Sch Hlth Informat Sci, Houston, TX USA. [Hubbard, Larry D.; Danis, Ronald P.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Esquivel, Adol] Houston Vet Affairs Med Ctr, Houston, TX USA. [Esquivel, Adol] Baylor Coll Med, Houston, TX 77030 USA. [Florez-Arango, Jose F.] Univ De Antioquia, Medellin, Colombia. [Krupinski, Elizabeth A.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. RP Li, HK (reprint author), Univ Texas Med Branch, Dept Ophthalmol & Visual Sci, 301 Univ Blvd, Galveston, TX 77555 USA. EM hlimed@mac.com OI Florez-Arango, Jose F/0000-0001-9083-0195 FU Juvenile Diabetes Foundation Research International, New York, NY; Research to Prevent Blindness (Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch); Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health FX Supported by a grant from Juvenile Diabetes Foundation Research International, New York, NY (HKL), and by unrestricted grants from Research to Prevent Blindness (Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, and the Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health). NR 31 TC 7 Z9 7 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2010 VL 51 IS 6 BP 3184 EP 3192 DI 10.1167/iovs.09-4886 PG 9 WC Ophthalmology SC Ophthalmology GA 598OC UT WOS:000277846500049 PM 20053978 ER PT J AU Fink, C Alkadhi, H Boll, DT Johnson, T Kachelriess, M AF Fink, Christian Alkadhi, Hatem Boll, Daniel T. Johnson, Thorsten Kachelriess, Marc TI Advances in CT Technology SO INVESTIGATIVE RADIOLOGY LA English DT Editorial Material C1 [Fink, Christian] Univ Hosp Mannheim, Dept Clin Radiol, D-68167 Mannheim, Germany. [Alkadhi, Hatem] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boll, Daniel T.] Duke Univ, Durham, NC USA. [Johnson, Thorsten] Univ Munich, Munich, Germany. [Kachelriess, Marc] Univ Erlangen Nurnberg, Erlangen, Germany. RP Fink, C (reprint author), Univ Hosp Mannheim, Dept Clin Radiol, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. EM christian.fink@rad.ma.uni-heidelberg.de NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 2010 VL 45 IS 6 BP 289 EP 289 DI 10.1097/RLI.0b013e3181e03045 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 600PU UT WOS:000278000200001 PM 20479613 ER PT J AU Goetti, R Leschka, S Baumuller, S Plass, A Wieser, M Desbiolles, L Stolzmann, P Falk, V Marincek, B Alkadhi, H Feuchtner, G AF Goetti, Robert Leschka, Sebastian Baumueller, Stephan Plass, Andre Wieser, Monika Desbiolles, Lotus Stolzmann, Paul Falk, Volkmar Marincek, Borut Alkadhi, Hatem Feuchtner, Gudrun TI Low Dose High-Pitch Spiral Acquisition 128-Slice Dual-Source Computed Tomography for the Evaluation of Coronary Artery Bypass Graft Patency SO INVESTIGATIVE RADIOLOGY LA English DT Article DE dual-source computed tomography; coronary artery bypass graft; radiation dose; high-pitch spiral acquisition mode ID 64-SLICE CT; NONINVASIVE VISUALIZATION; DIAGNOSTIC PERFORMANCE; ANGIOGRAPHY; SURGERY AB Objectives: To prospectively assess electrocardiography (ECG)-synchronized dual-source computed tomography (CT) in high-pitch spiral acquisition mode for the evaluation of coronary artery bypass graft (CABG) patency regarding image quality and radiation dose. Materials and Methods: Fifty consecutive patients (47 men, age 69.6 +/- 9.6 years, body mass index 26.6 +/- 3.5 kg/m(2)) underwent clinically indicated 128-slice dual-source CT angiography of the entire thorax for the evaluation of graft patency after CABG surgery using a prospectively ECG-synchronized high-pitch spiral acquisition mode (pitch 3.2; 100 kV tube voltage, 0.28 seconds gantry rotation time). Heart rates (HR) were noted. Image quality of the proximal anastomosis, graft body, distal anastomosis, and postanastomotic coronary artery were graded by 2 independent readers on a 3-point scale (1 = excellent, 2 = moderate, and 3 = poor/nondiagnostic). Quantitative image quality parameters (noise, contrast-to-noise ratio) were measured. Effective radiation doses were calculated. Results: Mean HR was 76 +/- 19 bpm (range, 45-135 bpm). Median scan time was 0.9 seconds (range, 0.76-1.17 seconds), mean scan length was 349 +/- 38 mm (range, 294-452 mm). A total of 125 CABG (54% arterial grafts) and 465 vessel sections were analyzed. Twelve grafts were proximally occluded. Diagnostic image quality was obtained in 462 (99.4%) sections. Of those, image quality was excellent in 397 (85.4%) and moderate in 65 (14.0%). All 3 (0.6%) nondiagnostic sections affected the distal anastomosis due to motion artifacts caused by high HR. Separating the study population by the median HR of 71 bpm, image quality of the distal anastomosis regarding motion artifacts was significantly lower at high HR (P < 0.05). Interobserver agreement in grading image quality of graft segments was good (kappa = 0.77). Image noise in the aorta was 36.9 +/- 8.1, contrast-to-noise ratio was 13.1 +/- 4.2. Effective radiation dose was 2.3 +/- 0.3 mSv. Conclusions: The patency of coronary artery bypass grafts can be assessed with decreasing image quality at high HR in high-pitch prospectively ECG-synchronized thoracic 128-slice dual-source CT angiography at a low radiation dose. C1 [Goetti, Robert; Leschka, Sebastian; Baumueller, Stephan; Desbiolles, Lotus; Stolzmann, Paul; Marincek, Borut; Alkadhi, Hatem; Feuchtner, Gudrun] Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. [Plass, Andre; Wieser, Monika; Falk, Volkmar] Univ Zurich Hosp, Div Cardiac & Vasc Surg, CH-8091 Zurich, Switzerland. [Alkadhi, Hatem] Massachusetts Gen Hosp, Cardiac MR PET CT Grp, Boston, MA 02114 USA. [Alkadhi, Hatem] Harvard Univ, Sch Med, Boston, MA USA. RP Leschka, S (reprint author), Univ Zurich Hosp, Inst Diagnost Radiol, Raemistr 100, CH-8091 Zurich, Switzerland. EM sebastian.leschka@usz.ch RI Goetti, Robert/I-8961-2012 NR 25 TC 31 Z9 34 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 2010 VL 45 IS 6 BP 324 EP 330 DI 10.1097/RLI.0b013e3181dfa47e PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 600PU UT WOS:000278000200006 PM 20404735 ER PT J AU Yared, K Baggish, AL Picard, MH Hoffmann, U Hung, J AF Yared, Kibar Baggish, Aaron L. Picard, Michael H. Hoffmann, Udo Hung, Judy TI Multimodality Imaging of Pericardial Diseases SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE pericarditis; echocardiography; cardiac computed tomography; cardiac magnetic resonance ID EFFUSIVE-CONSTRICTIVE PERICARDITIS; EXPERIMENTAL CARDIAC-TAMPONADE; RESTRICTIVE CARDIOMYOPATHY; MAGNETIC-RESONANCE; COMPUTED-TOMOGRAPHY; DOPPLER-ECHOCARDIOGRAPHY; HEART-DISEASE; DIAGNOSIS; CT; FEATURES AB Pericardial disease is an important cause of morbidity and mortality in patients with cardiovascular disease. Inflammatory diseases of the pericardium constitute a spectrum ranging from acute pericarditis to chronic constrictive pericarditis. Other important entities that involve the pericardium include benign and malignant pericardial masses, pericardial cysts, and diverticula, as well as congenital absence of the pericardium. Recent advances in multimodality noninvasive cardiac imaging have solidified its role in the management of patients with suspected pericardial disease. The physiologic and structural information obtained from transthoracic echocardiography and the anatomic detail provided by cardiac computed tomography and magnetic resonance have led to growing interest in the complementary use of these techniques. Optimal management of the patient with suspected pericardial disease requires familiarity with the key imaging modalities and the ability to choose the appropriate imaging tests for each patient. This report reviews the imaging modalities most useful in the assessment of patients with pericardial disease, with an emphasis on the complementary value of multimodality cardiac imaging. (J Am Coll Cardiol Img 2010; 3: 650-60) (C) 2010 by the American College of Cardiology Foundation C1 [Hung, Judy] Harvard Univ, Ultrasound Lab, Massachusetts Gen Hosp, Sch Med,Div Cardiol, Boston, MA 02114 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Yared, Kibar] Scarborough Gen Hosp, Div Cardiol, Toronto, ON, Canada. RP Hung, J (reprint author), Harvard Univ, Ultrasound Lab, Massachusetts Gen Hosp, Sch Med,Div Cardiol, Blake 256,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 55 TC 48 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JUN PY 2010 VL 3 IS 6 BP 650 EP 660 DI 10.1016/j.jcmg.2010.04.009 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 647NY UT WOS:000281626400012 PM 20541720 ER PT J AU Desai, NR Bhatt, DL AF Desai, Nihar R. Bhatt, Deepak L. TI The State of Periprocedural Antiplatelet Therapy After Recent Trials SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE antiplatelet; periprocedural; therapy; trials ID ACUTE CORONARY SYNDROMES; ST-SEGMENT-ELEVATION; ACUTE MYOCARDIAL-INFARCTION; PLATELET GLYCOPROTEIN IIB/IIIA; RANDOMIZED-TRIALS; CLOPIDOGREL RESISTANCE; STENT IMPLANTATION; CLINICAL-OUTCOMES; ISCHEMIC EVENTS; UNSTABLE ANGINA AB The ability to mechanically dilate and treat stenoses in the coronary arteries opened a new chapter in cardiovascular medicine. Percutaneous coronary intervention (PCI) has been shown to improve outcomes among patients with acute coronary syndromes as well as improve symptoms among patients with stable coronary artery disease. Adjunctive antiplatelet therapy plays a critical role both in the periprocedural setting as well as in the long-term management of atherothrombosis. Over the past several years, clinical trials of novel compounds and treatment strategies have further refined our pharmacotherapeutic approach. Aspirin remains the cornerstone for antiplatelet therapy across the spectrum of ischemic heart disease. In contrast, studies of glycoprotein IIb/IIIa inhibitors suggest a more limited role, particularly when used in addition to contemporary dual antiplatelet therapy. Clopidogrel, the most widely used P2Y(12) adenosine diphosphate receptor blocker although having demonstrated efficacy in patients with ST-segment elevation myocardial infarction, non-ST-segment elevation acute coronary syndrome, and stable coronary artery disease undergoing PCI has several limitations, including delay in onset, variability in response, and modest potency. The third-generation thienopyridine, prasugrel, as well as nonthienopyridine inhibitors of the P2Y(12) receptor such as ticagrelor and cangrelor address these shortcomings, offering more potent, consistent, and rapid platelet inhibition. Prasugrel and ticagrelor led to significant reductions in adverse cardiovascular events, including cardiovascular mortality for the latter, whereas cangrelor met noninferiority compared with 600 mg of clopidogrel in patients with ACS undergoing PCI. There are myriad novel compounds at varying stages of development, including thrombin receptor antagonists whose role in the periprocedural and long-term setting will be defined through further study. Significant questions regarding antiplatelet therapy remain unanswered, including the role of genetic and platelet function testing to "tailor therapy"; the optimal duration of therapy; and the optimal mechanism to deliver high-quality, cost-effective antiplatelet therapy to all patients. (J Am Coll Cardiol Intv 2010; 3:571-83) (C) 2010 by the American College of Cardiology Foundation C1 [Desai, Nihar R.; Bhatt, Deepak L.] Harvard Univ, Dept Med, Div Cardiovasc, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. RP Bhatt, DL (reprint author), Harvard Univ, Dept Med, Div Cardiovasc, Brigham & Womens Hosp,Med Sch, 75 Francis St,PBB 146, Boston, MA 02115 USA. EM dlbhattmd@post.harvard.edu FU AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Heartscape; Sanofi-Aventis; Medicines Company FX Dr. Bhatt receives research grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi-Aventis, and The Medicines Company. NR 74 TC 26 Z9 28 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JUN PY 2010 VL 3 IS 6 BP 571 EP 583 DI 10.1016/j.jcin.2010.04.008 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 621QC UT WOS:000279595700001 PM 20630450 ER PT J AU Lopes, RD Peterson, ED Chen, AY Roe, MT Wang, TY Ohman, EM Magid, DJ Ho, PM Wiviott, SD Scirica, BM Alexander, KP AF Lopes, Renato D. Peterson, Eric D. Chen, Anita Y. Roe, Matthew T. Wang, Tracy Y. Ohman, E. Magnus Magid, David J. Ho, P. Michael Wiviott, Stephen D. Scirica, Benjamin M. Alexander, Karen P. TI Antithrombotic Strategy in Non-ST-Segment Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention Insights From the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE antithrombotic therapy; in-hospital major bleeding; mortality; non-ST-segment elevation myocardial infarction; percutaneous coronary intervention ID POSTINFARCTION ANGINA; BIVALIRUDIN; HEPARIN; TRIAL; ANGIOPLASTY; CRUSADE AB Objectives The aim of this study was to examine the use of and outcomes associated with antithrombotic strategies in patients with non-ST-segment elevation myocardial infarction (NSTEMI) who undergo percutaneous coronary intervention (PCI). Background A variety of antithrombotic strategies have been tested in clinical trials for NSTEMI patients treated with PCI. Methods Antithrombotic strategies for NSTEMI patients undergoing PCI at 217 ACTION (Acute Coronary Treatment and Intervention Outcomes Network) hospitals from January 1, 2007, to December 31, 2007, (n = 11,085) were classified into commonly observed antithrombotic groups: heparin alone (Hep alone; low-molecular-weight heparin or unfractionated heparin), bivalirudin alone (Bival alone), heparin with glycoprotein IIb/IIIa inhibitors (Hep/GPI), and bivalirudin with GPI (Bival/GPI). Baseline characteristics are shown across treatment groups. In addition, unadjusted and adjusted rates of in-hospital major bleeding and death are shown. Results The standard strategy used was Hep/GPI (64%), followed by Hep or Bival alone (28%), and Bival/GPI (8%). Patients who received Hep or Bival alone were older with more comorbidities, higher baseline bleeding and mortality risk, and lower peak troponin. Compared with patients who received Hep/GPI, those who received Hep alone and Bival alone had lower rates of major bleeding (adjusted odds ratio [OR] 0.52; 95% confidence interval [CI]: 0.42 to 0.65; adjusted OR: 0.48; 95% CI: 039 to 0.60; respectively), yet only patients who received Bival alone had lower mortality (adjusted OR: 0.39; 95% CI: 021 to 0.71). Conclusions NSTEMI patients undergoing PCI are more likely to receive Bival or Hep alone when at higher baseline bleeding risk than when at lower baseline bleeding risk. Despite higher baseline risk, those receiving Bival or Hep alone had less bleeding. (J Am Coll Cardiol Intv 2010;3:669-77) (C) 2010 by the American College of Cardiology Foundation C1 [Lopes, Renato D.; Peterson, Eric D.; Chen, Anita Y.; Roe, Matthew T.; Wang, Tracy Y.; Ohman, E. Magnus; Alexander, Karen P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. [Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Magid, David J.] Univ Colorado, Hlth Sci Ctr, Dept Emergency Med, Denver, CO USA. [Magid, David J.] Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. [Ho, P. Michael] Denver VA Med Ctr, Cardiol Sect, Denver, CO USA. [Wiviott, Stephen D.; Scirica, Benjamin M.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Lopes, RD (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Box 3850,2400 Pratt St,Room 0311, Durham, NC 27705 USA. EM renato.lopes@duke.edu FU Bristol-Myers Squibb/Sanofi Pharmaceuticals; Genentech FX The National Cardiovascular Dam Registry ACTION Registry is administered by the American College of Cardiology Foundation (ACCF) and sponsored by Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Genentech, and Schering-Plough Corporation, who provide material support for the operation of the dam collection and infrastructure. The sponsors had no additional role in this project, including the selection of topic, analysis of data, decision to publish, or approval of the manuscript before publication. Data analysis was performed independently by a statistician (Dr. Chen) from the Duke Clinical Research Institute. NR 19 TC 17 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JUN PY 2010 VL 3 IS 6 BP 669 EP 677 DI 10.1016/j.jcin.2010.03.015 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 621QC UT WOS:000279595700012 PM 20630461 ER PT J AU Howard, AA Hoover, DR Anastos, K Wu, X Shi, QH Strickler, HD Cole, SR Cohen, MH Kovacs, A Augenbraun, M Latham, PS Tien, PC AF Howard, Andrea A. Hoover, Donald R. Anastos, Kathryn Wu, Xi Shi, Qiuhu Strickler, Howard D. Cole, Stephen R. Cohen, Mardge H. Kovacs, Andrea Augenbraun, Michael Latham, Patricia S. Tien, Phyllis C. TI The Effects of Opiate Use and Hepatitis C Virus Infection on Risk of Diabetes Mellitus in the Women's Interagency HIV Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE diabetes mellitus; fasting glucose; Hepatitis C virus; HIV; opiate use; women ID ACTIVE ANTIRETROVIRAL THERAPY; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MULTICENTER AIDS COHORT; GLUCOSE-METABOLISM; INSULIN-RESISTANCE; PREVALENCE; HCV; HEROIN; LOPINAVIR/RITONAVIR; COINFECTION AB Background: Opiate use is common in HIV-infected and hepatitis C virus (HCV)-infected individuals, however, its contribution to the risk of diabetes mellitus is not well understood. Methods: Prospective study of 1713 HIV-infected and 652 HIV-uninfected participants from the Women's Interagency HIV Study between October 2000 and March 2006. Diabetes defined as fasting glucose >= 126 mg/dL, self report of diabetes medication use, or confirmed diabetes diagnosis. Opiate use determined using an interviewer-administered questionnaire. Detectable plasma HCV RNA confirmed HCV infection. Results: Current opiate users had a higher prevalence of diabetes (15%) than nonusers (10%, P = 0.03), and a higher risk of incident diabetes (adjusted relative hazard: 1.58, 95% confidence interval: 1.01 to 2.46), after controlling for HCV infection, HIV/antiretroviral therapy status, and diabetes risk factors including age, race/ethnicity, family history of diabetes, and body mass index. HCV infection was also an independent risk factor for diabetes (adjusted relative hazard: 1.61, 95% confidence interval: 1.02 to 2.52). HCV-infected women reporting current opiate use had the highest diabetes incidence (4.83 cases per 100 person-years). Conclusions: Among women with or at-risk for HIV, opiate use is associated with increased diabetes risk independently of HCV infection. Diabetic screening should be part of care for opiate users and those infected with HCV. C1 [Howard, Andrea A.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA. [Hoover, Donald R.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA. [Anastos, Kathryn] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. [Anastos, Kathryn; Strickler, Howard D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Wu, Xi] Data Solut LLC, Bronx, NY USA. [Shi, Qiuhu] New York Med Coll, Sch Hlth Sci & Practice, Dept Epidemiol & Community Hlth, Valhalla, NY 10595 USA. [Cole, Stephen R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Cole, Stephen R.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Cohen, Mardge H.] John H Stroger Jr Hosp Cook Cty, CORE Ctr, Chicago, IL USA. [Kovacs, Andrea] Univ So Calif, Keck Sch Med, Dept Pediat & Pathol, Los Angeles, CA 90033 USA. [Kovacs, Andrea] Univ So Calif, Keck Sch Med, Maternal Child & Adolescent Ctr Infect Dis & Viro, Los Angeles, CA 90033 USA. [Augenbraun, Michael] SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA. [Latham, Patricia S.] George Washington Univ, Med Ctr, Dept Pathol & Med, Washington, DC 20037 USA. [Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Howard, AA (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St,Room 709, New York, NY 10032 USA. EM aah2138@columbia.edu OI Latham, Patricia/0000-0003-2782-9444 FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590, R01-AI-052065, R01-AI-057006, P30-AI-51519, K23-AI-66943]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources [UL1 RR024131]; National Institute on Drug Abuse [K23-DA-15003] FX The Women's Interagency HIV Study is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). Hepatitis C virus testing was supported by grants from the National Institute of Allergy and Infectious Diseases (R01-AI-052065 and R01-AI-057006). This work was also supported in part by the Center for AIDS Research at the Albert Einstein College of Medicine and Montefiore Medical Center funded by the National Institutes of Allergy and Infectious Diseases (P30-AI-51519). Dr. A. A. H. received support from the National Institute on Drug Abuse (K23-DA-15003). Dr. P. C. T. received support from the National Institute of Allergy and Infectious Diseases (K23-AI-66943). NR 38 TC 12 Z9 12 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUN PY 2010 VL 54 IS 2 BP 152 EP 159 DI 10.1097/QAI.0b013e3181d0c911 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 601XK UT WOS:000278100600007 PM 20190642 ER PT J AU Dau, B Ayers, D Singer, J Harrigan, PR Brown, S Kyriakides, T Cameron, DW Angus, B Holodniy, M AF Dau, Birgitt Ayers, Dieter Singer, Joel Harrigan, P. Richard Brown, Sheldon Kyriakides, Tassos Cameron, D. William Angus, Brian Holodniy, Mark TI Connection Domain Mutations in Treatment-Experienced Patients in the OPTIMA Trial SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral; clinical trial; HIV; resistance; veterans ID HIV-1 REVERSE-TRANSCRIPTASE; RNASE-H ACTIVITY; CONFERS ZIDOVUDINE; CLINICAL-TRIAL; RESISTANCE; 3'-AZIDO-3'-DEOXYTHYMIDINE; MECHANISM; INHIBITOR; EXCISION; THERAPY AB Objectives: To determine the frequency of mutations in the connection domain (CD) of HIV reverse transcriptase in treatment-experienced patients in the Options in Management with Antiretrovirals trial, their impact on susceptibility to antiretroviral (ARV) drugs, and their impact on virologic outcomes. Methods: Baseline plasma ARV genotypes and inferred resistance phenotypes were obtained. Frequencies of E312Q, Y318F, G333D, G333E, G335C, G335D, N348I, A360I, A360V, V365I, A371V, A376S, and E399G were compared with a treatment-naive population. The association of CD mutations with inferred IC(50) fold changes to nucleos(t)ide reverse transcriptase inhibitors was evaluated. Univariate and multivariate analyses examined the association of CD mutations with a>1 log(10) per milliliter decrease in HIV viral load after 24 weeks on a new ARV regimen. Results: Higher CD mutation rates were seen in Options in Management with Antiretrovirals patients (n = 345) compared with a treatment-naive population. CD mutations were associated with increased inferred IC50 fold changes to abacavir, stavudine, tenofovir, and zidovudine. On univariate analysis, A371V was associated with lack of virologic response, as was having any CD mutation on multivariate analysis. Conclusions: CD mutations are frequent in treatment-experienced populations. They are associated with reduced susceptibility to some nucleos(t)ide reverse transcriptase inhibitors and with a diminished response to ARV therapy. C1 [Dau, Birgitt] VA Palo Alto Hlth Care Syst, AIDS Res Ctr, Palo Alto, CA 94304 USA. [Ayers, Dieter; Singer, Joel] Canadian HIV Trials Network, Canadian Inst Hlth Res, Vancouver, BC, Canada. [Harrigan, P. Richard] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Brown, Sheldon] Bronx Vet Affairs Med Ctr, Div Infect Dis, New York, NY USA. [Kyriakides, Tassos] Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Cameron, D. William] Ottawa Gen Hosp, Dept Med, Div Infect Dis, Ottawa, ON K1H 8L6, Canada. [Angus, Brian] Univ Oxford, Dept Med, Oxford, England. [Holodniy, Mark] Stanford Univ, Dept Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA. RP Dau, B (reprint author), VA Palo Alto Hlth Care Syst, AIDS Res Ctr, 3801 Miranda Ave 132, Palo Alto, CA 94304 USA. EM birgitt.dau@gmail.com OI Angus, Brian/0000-0003-3598-7784; Cameron, Bill/0000-0002-0090-3539 FU US Department of Veterans Affairs Office of Research and Development; Canadian Institutes for Health Research; Canadian HIV Trials Network; UK Medical Research Council; Veterans Affairs FX The Options in Management with Antiretrovirals study was funded in part by the Cooperative Studies Program of the US Department of Veterans Affairs Office of Research and Development, the Canadian Institutes for Health Research, the Canadian HIV Trials Network, and the UK Medical Research Council. This substudy was funded in part by a Veterans Affairs grant to M. H. and by the Canadian HIV Trials Network. NR 28 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUN PY 2010 VL 54 IS 2 BP 160 EP 166 DI 10.1097/QAI.0b013e3181cbd235 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 601XK UT WOS:000278100600008 PM 20130473 ER PT J AU Daniels, AB Jakobiec, FA Westerfeld, CB Hagiwara, A Michaud, N Mukai, S AF Daniels, Anthony B. Jakobiec, Frederick A. Westerfeld, Corey B. Hagiwara, Akira Michaud, Norman Mukai, Shizuo TI Idiopathic subfoveal choroidal neovascular membrane in a 21-month-old child: Ultrastructural features and implication for membranogenesis SO JOURNAL OF AAPOS LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; INTRAVITREAL BEVACIZUMAB; PHOTODYNAMIC THERAPY; PEDIATRIC-PATIENTS; SURGICAL REMOVAL; EXPRESSION; CELLS; VEGF AB PURPOSE To report the clinical and pathologic features of an idiopathic choroidal neovascular membrane (CNVM) in a 21-month-old child and to discuss the unique findings of infantile CNVM in the context of understanding the mechanism of membrane formation. METHODS The CNVM was removed by submacular surgery. Light and electron microscopic tissue analyses were used to elucidate the structure and constituents of the CNVM. RESULTS Postoperative vision was 20/60 at 10 months without evidence of recurrence. Endothelium-lined vascular channels were observed within a membrane composed entirely of retinal pigment epithelial (RPE) cells with an associated fibrocollagenous and amorphous matrix. No inflammatory cells were identified. The RPE cells toward the inner (photoreceptor) side of the membrane exhibited a less-differentiated appearance, having lost their polarity and most of their cytoplasmic melanin granules. They secreted more prominent fibrils and mucopolysaccharides. Fenestrated endothelial cells surrounded by pericytes were present between the proliferating RPE cells. CONCLUSIONS Submacular surgery can be beneficial for idiopathic CNVM in pediatric patients, even at this early age. Proliferating RPE cells in the current membrane appear to be capable of performing all of the necessary functions associated with membranogenesis, even in the absence of inflammatory cells. (J AAPOS 2010;14:244-250) C1 [Westerfeld, Corey B.; Hagiwara, Akira; Mukai, Shizuo] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. [Daniels, Anthony B.; Jakobiec, Frederick A.; Westerfeld, Corey B.; Hagiwara, Akira; Michaud, Norman; Mukai, Shizuo] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Daniels, Anthony B.; Jakobiec, Frederick A.; Westerfeld, Corey B.; Hagiwara, Akira; Michaud, Norman; Mukai, Shizuo] Harvard Univ, Sch Med, Boston, MA USA. [Jakobiec, Frederick A.; Michaud, Norman] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Hagiwara, Akira] Chiba Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Chiba, Japan. RP Mukai, S (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM shizuo_mukai@meei.harvard.edu NR 26 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD JUN PY 2010 VL 14 IS 3 BP 244 EP 250 DI 10.1016/j.jaapos.2010.01.010 PG 7 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 626JU UT WOS:000279963100012 PM 20417139 ER PT J AU McLean, CP Hope, DA AF McLean, Carmen P. Hope, Debra A. TI Subjective anxiety and behavioral avoidance: Gender, gender role, and perceived confirmability of self-report SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Gender role; Anxiety; Gender differences; Behavioral avoidance ID SEX-ROLE ORIENTATION; FEAR QUESTIONNAIRES; ROLE IDENTITY; CHILDREN; ADOLESCENTS; FEARFULNESS; ATTRIBUTES; ATTITUDES; DISGUST; SPIDERS AB Commonly reported gender effects for differential vulnerability for anxiety may relate to gender socialization processes The present study examined the relationship between gender role and fear under experimental conditions designed to elicit accurate fear reporting Undergraduate students (N=119) completed several self-report measures and a behavioral avoidance task (BAT) with a tarantula while wearing a heart rate monitor Gender roles were operationalized as instrumentality and expressiveness, as measured by the Personal Attributes Questionnaire (Spence, Helmreich, & Stapp, 1975) As expected, women reported greater subjective anxiety and were more avoidant of the tarantula than men Regardless of gender, low levels of instrumentality were associated with greater avoidance of the tarantula. The hypothesis that men underreport fear compared to women and that gender role differences underlie this reporting bias was not supported In spite of a ceiling effect on the BAT, results of this study confirm the relevance of gender role in understanding gender effects in fear and anxiety (C) 2010 Elsevier Ltd All rights reserved C1 [McLean, Carmen P.; Hope, Debra A.] Univ Nebraska, Dept Psychol, Lincoln, NE 68588 USA. RP McLean, CP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B-5, Boston, MA 02130 USA. NR 45 TC 16 Z9 16 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JUN PY 2010 VL 24 IS 5 BP 494 EP 502 DI 10.1016/j.janxdis.2010.03.006 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 599YW UT WOS:000277951300007 PM 20381303 ER PT J AU Wannomae, KK Christensen, SD Micheli, BR Rowell, SL Schroeder, DW Muratoglu, OK AF Wannomae, Keith K. Christensen, Steven D. Micheli, Brad R. Rowell, Shannon L. Schroeder, Dave W. Muratoglu, Orhun K. TI Delamination and Adhesive Wear Behavior of alpha-Tocopherol-Stabilized Irradiated Ultrahigh-Molecular-Weight Polyethylene SO JOURNAL OF ARTHROPLASTY LA English DT Article DE polyethylene; delamination; oxidation; vitamin E ID CROSS-LINKED POLYETHYLENE; TOTAL KNEE REPLACEMENTS; TIBIAL COMPONENTS; SURFACE DAMAGE; MECHANICAL-PROPERTIES; OXIDATION; RESISTANCE; UHMWPE; ARTHROPLASTIES; PERFORMANCE AB Wear and delamination of conventional ultrahigh-molecular-weight polyethylene (UHMWPE) components used in total knee arthroplasty can compromise long-term performance. Radiation cross-linking and melt-annealing reduced wear and increased delamination resistance of UHMWPE. An alternative material is the alpha-tocopherol stabilized irradiated UHMWPE (alpha TPE), with improved mechanical and fatigue properties vs irradiated and melted UHMWPE. We studied the wear and delamination resistance of alpha TPE and conventional UHMWPE (direct compression molded GUR 1050 and Himont 1900) under reciprocating unidirectional motion. Wear resistance was improved, and no delamination was observed in alpha TPE. Accelerated aging did not alter the wear and delamination behavior of alpha TPE. The GUR 1050 UHMWPE showed delamination and pitting when subjected to unidirectional reciprocating motion after accelerated aging. Himont 1900 UHMWPE showed no delamination when subjected to unidirectional reciprocating motion after accelerated aging. alpha-Tocopherol stabilized irradiated UHMWPE is advanced for use in total knee arthroplasty due to its high resistance to wear, delamination, and oxidation. C1 [Wannomae, Keith K.; Christensen, Steven D.; Micheli, Brad R.; Rowell, Shannon L.; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthoped Biomat & Biomech Lab, Boston, MA 02114 USA. [Schroeder, Dave W.] Biomet Inc, Warsaw, IN USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Harris Orthoped Biomat & Biomech Lab, 55 Fruit St,GRJ-1206, Boston, MA 02114 USA. FU Biomet Inc. (Warsaw, Ind) FX This work was funded by a research grant from Biomet Inc. (Warsaw, Ind). NR 33 TC 15 Z9 17 U1 1 U2 8 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUN PY 2010 VL 25 IS 4 BP 635 EP 643 DI 10.1016/j.arth.2009.04.005 PG 9 WC Orthopedics SC Orthopedics GA 612NF UT WOS:000278905300022 PM 19493652 ER PT J AU Kuhlthau, K Orlich, F Hall, TA Sikora, D Kovacs, EA Delahaye, J Clemons, TE AF Kuhlthau, Karen Orlich, Felice Hall, Trevor A. Sikora, Darryn Kovacs, Erica A. Delahaye, Jennifer Clemons, Traci E. TI Health-Related Quality of Life in Children with Autism Spectrum Disorders: Results from the Autism Treatment Network SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Quality of life; Behavior; Adaptive behavior ID HIGH-FUNCTIONING CHILDREN; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; GENERIC CORE SCALES; INTELLECTUAL DISABILITY; PSYCHOMETRIC PROPERTIES; MATERNAL PERCEPTIONS; SLEEP PROBLEMS; ADOLESCENTS; POPULATION; PEDSQL(TM)-4.0 AB We examined data collected as a part of the Autism Treatment Network, a group of 15 autism centers across the United States and Canada. Mean Health-Related Quality of Life (HRQoL) scores of the 286 children assessed were significantly lower than those of healthy populations (according to published norms). When compared to normative data from children with chronic conditions, children with ASD demonstrated worse HRQoL for total, psychosocial, emotional and social functioning, but did not demonstrate differing scores for physical and school functioning. HRQoL was not consistently related to ASD diagnosis or intellectual ability. However, it was consistently related to internalizing and externalizing problems as well as repetitive behaviors, social responsiveness, and adaptive behaviors. Associations among HRQoL and behavioral characteristics suggest that treatments aimed at improvements in these behaviors may improve HRQoL. C1 [Kuhlthau, Karen; Delahaye, Jennifer] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Kuhlthau, Karen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Orlich, Felice] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Orlich, Felice] Seattle Childrens Hosp, Autism Program, Seattle, WA USA. [Hall, Trevor A.] Warm Springs Autism Diagnost & Treatment Ctr, Portland, OR USA. [Hall, Trevor A.; Sikora, Darryn] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kovacs, Erica A.] Columbia Univ, Med Ctr, Columbia Dev Neuropsychiat Program, Div Child & Adolescent Psychiat, New York, NY USA. [Clemons, Traci E.] EMMES Corp, Potomac, MD USA. RP Kuhlthau, K (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. EM kkuhlthau@partners.org FU Autism Speaks [AS1954] NR 42 TC 62 Z9 63 U1 4 U2 25 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 JUN PY 2010 VL 40 IS 6 BP 721 EP 729 DI 10.1007/s10803-009-0921-2 PG 9 WC Psychology, Developmental SC Psychology GA 592IL UT WOS:000277372000007 PM 20033762 ER PT J AU Orban, T Farkas, K Jalahej, H Kis, J Treszl, A Falk, B Reijonen, H Wolfsdorf, J Ricker, A Matthews, JB Tchao, N Sayre, P Bianchine, P AF Orban, Tihamer Farkas, Klara Jalahej, Heyam Kis, Janos Treszl, Andras Falk, Ben Reijonen, Helena Wolfsdorf, Joseph Ricker, Alyne Matthews, Jeffrey B. Tchao, Nadio Sayre, Peter Bianchine, Pete TI Autoantigen-specific regulatory T cells induced in patients with type 1 diabetes mellitus by insulin B-chain immunotherapy SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Type 1 diabetes mellitus; Insulin B-chain immunotherapy; Clinical trial; Autoantigen-specific regulatory T cells ID GLUTAMIC-ACID DECARBOXYLASE; PRIMARY IMMUNE-RESPONSE; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; DOUBLE-BLIND; NOD MICE; TGF-BETA; VACCINATION; PEPTIDE; TRIAL AB There is a growing body of evidence to suggest that the autoimmunity observed in type 1 diabetes mellitus (T1DM) is the result of an imbalance between autoaggressive and regulatory cell subsets. Therapeutics that supplement or enhance the existing regulatory subset are therefore a much sought after goal in this indication. Here, we report the results of a double blind, placebo controlled, phase I clinical trial of a novel antigen-specific therapeutic in 12 subjects with recently diagnosed T1DM. Our primary objective was to test its safety. The study drug, human insulin B-chain in incomplete Freund's adjuvant (IFA) was administered as a single intramuscular injection, with subjects followed for 2 years. All subjects completed therapy and all follow-up visits. The therapy was generally safe and well-tolerated. Mixed meal stimulated C-peptide responses, measured every 6 months, showed no statistical differences between arms. All patients vaccinated with the autoantigen, but none who received placebo, developed robust insulin-specific humoral and T cell responses. Up to two years following the single injection, in peripheral blood from subjects in the experimental arm, but not the control arm, insulin B-chain-specific CD4+ T cells could be isolated and cloned that showed phenotypic and functional characteristics of regulatory T cells. The induction of a lasting, robust immune response generating autoantigen-specific regulatory T cells provides strong justification for further testing of this therapy in type 1 diabetes. (clinicaltrials.gov identifier NCT00057499). (C) 2009 Elsevier Ltd. All rights reserved. C1 [Orban, Tihamer; Farkas, Klara; Jalahej, Heyam; Kis, Janos; Treszl, Andras; Ricker, Alyne] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kis, Janos] Polyclin Hosp Bros, Budapest, Hungary. [Treszl, Andras] Inst Med Biometrie & Epidemiol, Zentrum Expt Med, Hamburg, Germany. [Falk, Ben; Reijonen, Helena] Benaroya Res Inst Virginia Mason, Seattle, WA USA. [Wolfsdorf, Joseph] Childrens Hosp Boston, Boston, MA USA. [Matthews, Jeffrey B.; Tchao, Nadio; Sayre, Peter] UCSF, Immune Tolerance Network, San Francisco, CA USA. [Bianchine, Pete] NIAID, Bethesda, MD 20892 USA. RP Orban, T (reprint author), Joslin Diabet Ctr, Room 433,1 Joslin Pl, Boston, MA 02215 USA. EM torban@joslin.harvard.edu FU National Institute of Allergy and Infectious Diseases; National Institute of Diabetes, and Digestive and Kidney Disease [N01-A1-15416]; Juvenile Diabetes Research Foundation FX This research was performed as a project of the Immune Tolerance Network, a collaborative clinical research project head-quartered at the University of California San Francisco and supported by the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes, and Digestive and Kidney Disease "(NIH contract #N01-A1-15416 NIH/NIAID)" and the Juvenile Diabetes Research Foundation. NR 50 TC 52 Z9 56 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 2010 VL 34 IS 4 BP 408 EP 415 DI 10.1016/j.jaut.2009.10.005 PG 8 WC Immunology SC Immunology GA 598WF UT WOS:000277869500009 PM 19931408 ER PT J AU Takada, Y Ono, Y Sagusa, J Mitsiades, C Mitsiades, N Tsai, J He, Y Maningding, E Coleman, A Ramirez-Maverakis, D Rodriquez, R Takada, Y Maverakis, E AF Takada, Yoshikazu Ono, Yoko Sagusa, Jun Mitsiades, Constantine Mitsiades, Nicholas Tsai, Jean He, Yong Maningding, Ernest Coleman, Annie Ramirez-Maverakis, Dalila Rodriquez, Raphael Takada, Yoko Maverakis, Emanual TI A T cell-binding fragment of fibrinogen can prevent autoimmunity SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Autoimmunity; Experimental autoimmune encephalomyelitis (EAE); MOG; Multiple sclerosis ID CONTROLLED TRIAL; GAMMA-CHAIN; INTEGRIN; ENCEPHALOMYELITIS; DISEASE; IDENTIFICATION; ANTIBODY; MODEL; EAE AB The C-terminal domain of the fibrinogen gamma chain (gamma C) has been shown to bind to the integrins alpha IIb beta 3, alpha M beta 2 and alpha V beta 3. It has also been reported that a peptide derived from the alpha M beta 2-binding site of gamma C can suppress an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Here we have truncated gamma C at position 399 to remove the prothrombotic alpha IIb beta 3-binding site. We show that this truncated version of gamma C, termed gamma C399tr, can bind to activated T cells. In addition, T cells incubated with gamma C399tr secreted less IFN-gamma when stimulated with antigen and APC; however, cytokine secretion was unaltered when T cells were stimulated non-specifically with a mixture of anti-CD3 and anti-CD28 antibodies. Thus, only antigen-dependent T cell activation is inhibited by gamma C399tr. When administered intraperitoneally, gamma C399tr potently inhibited actively induced EAE and reversed ongoing disease. We hypothesize that the ability of gamma C399tr to inhibit autoreactive immune responses is a result of its ability to bind integrins. This activity was not solely dependent on the alpha M beta 2 integrin-binding site. When polyalanine was substituted for the alpha M beta 2-binding site, the resulting gamma C390polyA was still able to inhibit EAE. To our knowledge, this is the first demonstration that T cells can bind to fibrin (ogen), an important extracellular matrix protein that is deposited at sites of inflammation. Our results also identify gamma C399tr as a novel therapeutic molecule. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Takada, Yoshikazu; Ono, Yoko; Sagusa, Jun; Tsai, Jean; He, Yong; Maningding, Ernest; Coleman, Annie; Ramirez-Maverakis, Dalila; Takada, Yoko; Maverakis, Emanual] Univ Calif Davis, Dept Dermatol, Sch Med, Sacramento, CA 95816 USA. [Mitsiades, Constantine; Mitsiades, Nicholas] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Maverakis, Emanual] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Rodriquez, Raphael] Univ Calif Davis, Dept Pathol, Sacramento, CA 95817 USA. [Maverakis, Emanual] Dept Vet Affairs No Calif Hlth Care Syst, Sacramento, CA 95655 USA. RP Takada, Y (reprint author), Univ Calif Davis, Dept Dermatol, Sch Med, 3301 C St,Suite 1400, Sacramento, CA 95816 USA. EM ytakada@ucdavis.edu RI Maverakis, Emanual/E-1185-2013; OI takada, yoshikazu/0000-0001-5481-9589; Maverakis, Emanual/0000-0002-6294-6294 FU Burroughs Wellcome Fund; Howard Hughes Medical Institute; NIH [A1075029, CA131015] FX EM is a recipient of a Career Award for Medical Scientists from the Burroughs Wellcome Fund and a Howard Hughes Medical Institute Physician Scientist Early Career Award. This work was supported by the NIH (A1075029 awarded to EM and CA131015 to YT). NR 15 TC 6 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 2010 VL 34 IS 4 BP 453 EP 459 DI 10.1016/j.jaut.2009.11.017 PG 7 WC Immunology SC Immunology GA 598WF UT WOS:000277869500014 PM 20036106 ER PT J AU Kuohung, W Burnett, M Mukhtyar, D Schuman, E Ni, J Crowley, WF Glicksman, MA Kaiser, UB AF Kuohung, Wendy Burnett, Maria Mukhtyar, Deepa Schuman, Eli Ni, Jake Crowley, William F. Glicksman, Marcie A. Kaiser, Ursula B. TI A High-Throughput Small-Molecule Ligand Screen Targeted to Agonists and Antagonists of the G-Protein-Coupled Receptor GPR54 SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE GPR54; kisspeptin; agonist; antagonist; high-throughput screening ID METASTASIS-SUPPRESSOR GENE; HORMONE-RELEASING ACTIVITY; POTENTIAL MECHANISM; KISS-1 PEPTIDE; EXPRESSION; CELLS; KISSPEPTINS; PUBERTY; MOUSE; ACTIVATION AB Recent data have shown that the G-protein-coupled receptor GPR54 (also known as KiSS-1 receptor) regulates GnRH release from the hypothalamus. This essential role of GPR54 in controlling the hypothalamic-pituitary-gonadal axis makes it an attractive target for therapeutic intervention in reproductive and cancer medicine. Currently, there are no small-molecule modulators of GPR54 function for experimental or clinical use. To identify small-molecule compounds that modify GPR54 signal transduction, the authors have adapted a cell-based functional assay for high-throughput screening (HTS) using a commercially available homogeneous time-resolved fluorescence assay for inositol phosphate accumulation. They generated stable Chinese hamster ovary cell transfectants that express human GPR54 for use in this assay. After optimization in an automated HTS environment, they screened a library of 110,000 small-molecule compounds using 2 protocols, one to identify agonists and one to identify antagonists. Hits obtained in the primary screen were confirmed to be active in secondary in vitro assays. Compounds identified as agonists or antagonists from HTS and secondary screening will be characterized to identify agents with the potential to be developed as novel orally active agents to treat hormone-dependent disorders such as abnormal puberty, infertility, endometriosis, and sex steroid-dependent tumors. (Journal of Biomolecular Screening 2010:508-517) C1 [Kuohung, Wendy; Burnett, Maria; Mukhtyar, Deepa; Kaiser, Ursula B.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Kuohung, Wendy] Boston Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA 02118 USA. [Schuman, Eli; Ni, Jake; Glicksman, Marcie A.] Brigham & Womens Hosp, Lab Drug Discovery Neurodegenerat, Boston, MA 02115 USA. [Crowley, William F.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Kaiser, UB (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM ukaiser@partners.org FU National Institutes of Health SCPRR [U54-HD28138]; ASRM/Ortho-McNeil Research Grant; Reproductive Scientist Development Program (ASRM-NICHD) [5K12-HD00849]; NICHD [1K08HD053706]; Partners Center for Drug Discovery FX This work was supported by National Institutes of Health SCPRR Grant U54-HD28138 (to WFC and UBK), the ASRM/Ortho-McNeil Research Grant, Reproductive Scientist Development Program (ASRM-NICHD 5K12-HD00849 Phase I, ACOG Phase II), NICHD Grant 1K08HD053706 (to ), and the Partners Center for Drug Discovery. NR 30 TC 11 Z9 11 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD JUN PY 2010 VL 15 IS 5 BP 508 EP 517 DI 10.1177/1087057110369701 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 602MJ UT WOS:000278143100005 PM 20460252 ER PT J AU Latorre-Esteves, E Akilov, OE Rai, P Beverley, SM Hasan, T AF Latorre-Esteves, Elena Akilov, Oleg E. Rai, Prakash Beverley, Stephen M. Hasan, Tayyaba TI Monitoring the efficacy of antimicrobial photodynamic therapy in a murine model of cutaneous leishmaniasis using L. major expressing GFP SO JOURNAL OF BIOPHOTONICS LA English DT Article DE Leishmania; photodynamic therapy; murine model; green fluorescent protein ID GREEN FLUORESCENT PROTEIN; FLUENCE RATE; IN-VIVO; TUMOR AB A murine model of cutaneous leishmaniasis with green fluorescent protein positive (GFP+) L. major enables the monitoring of parasitic load via measurements of GFP fluorescence intensity, allowing for a faster and more efficient way of monitoring the clinical outcome of photodynamic therapy (PDT). This model may provide new insights on the phototoxic aspects in PDT. Although PDT regimens may be somewhat different in humans, it is expected that the developed model will facilitate the optimization and clinical translation of PDT as a therapy for cutaneous leishmaniasis and the eventual development of topical PDT treatments for other granulomatous infections. [GRAPHICS] Green fluorescence from GFP+ L. major in cutaneous leishmaniasis lesions on the ear of BALB/c mouse. C1 [Latorre-Esteves, Elena; Akilov, Oleg E.; Rai, Prakash; Beverley, Stephen M.; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Ctr Photomed, Boston, MA 02114 USA. [Latorre-Esteves, Elena] Univ Puerto Rico, Mayaguez, PR 00681 USA. [Akilov, Oleg E.] Univ Pittsburgh, Dept Dermatol, Pittsburgh, PA 15213 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@partners.org RI Rinaldi2, Carlos/D-4479-2011; OI Beverley, Stephen/0000-0001-5319-0811 FU Department of Defense [FA9550-04-1-0079]; NIH [AI029646] FX This work was supported by the Department of Defense Medical Free Electron Laser Program Grant No. FA9550-04-1-0079 (to T. Hasan) and NIH AI029646 (to S. Beverley). We thank Andreas Hubel for providing constructs and transfected L. major. For this work, Elena Latorre-Esteves was presented with an outstanding poster presentation award at the 2008 Annual Biomedical Research Conference for Minority Students (ABRCMS) in Orlando, Florida. NR 29 TC 12 Z9 12 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1864-063X J9 J BIOPHOTONICS JI J. Biophotonics PD JUN PY 2010 VL 3 IS 5-6 BP 328 EP 335 DI 10.1002/jbio.201000008 PG 8 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA 612HF UT WOS:000278886700009 PM 20376860 ER PT J AU Suryakumar, G Kasiganesan, H Balasubramanian, S Kuppuswamy, D AF Suryakumar, Geetha Kasiganesan, Harinath Balasubramanian, Sundaravadivel Kuppuswamy, Dhandapani TI Lack of beta 3 Integrin Signaling Contributes to Calpain-Mediated Myocardial Cell Loss in Pressure-Overloaded Myocardium SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE cardiac hypertrophy; beta 3 integrin knockout mice; pressure-overload; programmed cell death ID ENDOPLASMIC-RETICULUM STRESS; CARDIAC MYOCYTE APOPTOSIS; SMOOTH-MUSCLE-CELLS; FACTOR-KAPPA-B; HEART-FAILURE; DEGRADED COLLAGEN; CARDIOMYOCYTE APOPTOSIS; CROSS-TALK; ACTIVATION; HYPERTROPHY AB Although cardiac hypertrophy initially ensues as a compensatory mechanism, it often culminates in congestive heart failure. Based on our earlier studies that calpain and beta 3 integrin play cell death and survival roles, respectively, during pressure-overload (PO) hypertrophy, we investigated if the loss of beta 3 integrin signaling is a potential mechanism for calpain-mediated cardiomyocyte death during PO. beta 3 Integrin knockout (beta 3(-/-)) and wild-type mice were used to induce either moderate or severe PO in vivo for short-term (72-hour) and long-term (4-week) transverse aortic constriction. Whereas wild-type mice showed no changes during moderate PO at both time points, beta 3(-/-) mice exhibited both enrichment of the m-calpain isoform and programmed cell death of cardiomyocytes after 4-week PO. However, with severe PO that caused increased mortality in both mice groups, cell death was observed in wild-type mice also. To study calpain's role, calpeptin, a specific inhibitor of calpain, was administered through an osmotic mini-pump at 2.5 mg/kg per day beginning 3 days before moderate transverse aortic constriction or sham surgery. Calpeptin administration blocked both calpain enrichment and myocardial cell death in the 4-week PO beta 3(-/-) mice. Because beta 3 integrin contributes to cardioprotective signaling, these studies indicate that the loss of specific integrin function could be a key mechanism for calpain-mediated programmed cell death of cardiomyocytes in PO myocardium. C1 [Suryakumar, Geetha; Kasiganesan, Harinath; Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. [Kuppuswamy, Dhandapani] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Kuppuswamy, D (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, 114 Doughty St, Charleston, SC 29425 USA. EM kuppusd@musc.edu FU National Institutes of Health (NIH) [HL-48788, RHL092124A]; Research Service of the Department of Veterans Affairs; Department of Science and Technology, India FX This study was supported by National Institutes of Health (NIH) grant PPG HL-48788, by NIH grant RHL092124A (to D. K), by a Merit award from the Research Service of the Department of Veterans Affairs, and by a BOYSCAST fellowship from the Department of Science and Technology, India (to G. S.). NR 36 TC 15 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD JUN PY 2010 VL 55 IS 6 BP 567 EP 573 DI 10.1097/FJC.0b013e3181d9f5d4 PG 7 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 612EQ UT WOS:000278880000006 PM 20224428 ER PT J AU Ren, SP Liu, SH Howell, PM Zhang, GY Pannell, L Samant, R Shevde-Samant, L Tucker, JA Fodstad, O Riker, AI AF Ren, Suping Liu, Suhu Howell, Paul M., Jr. Zhang, Guangyu Pannell, Lewis Samant, Rajeev Shevde-Samant, Lalita Tucker, J. Allan Fodstad, Oystein Riker, Adam I. TI Functional characterization of the progestagen-associated endometrial protein gene in human melanoma SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE melanoma; progestagen-associated endometrial protein; oncogene; RNA interference ID HUMAN PLACENTAL PROTEIN-14; BREAST-CANCER; METASTATIC MELANOMA; GLYCODELIN-A; EXPRESSION; SUPPRESSION; PROGRESSION; GROWTH; CELLS; RNA AB Utilizing gene microarray profiling of melanoma samples, we have recently identified a novel gene overexpressed in both thick primary and metastatic melanomas. This gene, progestagen-associated endometrial protein (PAEP), has never before been implicated in the oncogenic processes of melanoma, with its true function in oncogenesis and tumour progression relatively unknown. Overexpression of the PAEP gene in freshly procured thick primary and metastatic melanoma samples (58%) and daughter cell lines (77%) is confirmed by quantitative RT-PCR, immunohistochemistry, Western blotting and mass spectrometric analysis. We suggest that PAEP gene overexpression is involved with melanoma tumour progression as well as an aggressive phenotype. Transfection of melanoma cells with PAEP small interfering RNA (siRNA) reveals a significant decrease in soft agar colony formation and a marked inhibition of both cell migration and cell invasion. Furthermore, we establish stable melanoma transfectants via PAEP lentiviral small hairpin RNA (shRNA), examine their growth characteristics in a murine xenograft model and reveal that tumour growth is significantly inhibited in two separate melanoma cell lines. Our data strongly implicate the PAEP gene as a tumour growth promoter with oncogenic properties and a potential therapeutic target for patients with advanced melanoma. C1 [Riker, Adam I.] Ochsner Hlth Syst, Ochsner Canc Inst, Dept Surg, New Orleans, LA 70121 USA. [Ren, Suping; Howell, Paul M., Jr.; Zhang, Guangyu; Pannell, Lewis; Samant, Rajeev; Shevde-Samant, Lalita; Fodstad, Oystein] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA. [Liu, Suhu] Harvard Univ, Dana Farber Canc Inst, Boston, MD USA. [Tucker, J. Allan] Univ S Alabama, Dept Pathol, Mobile, AL 36688 USA. [Fodstad, Oystein] Norwegian Radium Hosp, Inst Canc Res, Dept Tumor Biol, Oslo, Norway. RP Riker, AI (reprint author), Ochsner Hlth Syst, Ochsner Canc Inst, Dept Surg, 1514 Jefferson Hwy,BH 334, New Orleans, LA 70121 USA. EM ariker@ochsner.org NR 40 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD JUN PY 2010 VL 14 IS 6B BP 1432 EP 1442 DI 10.1111/j.1582-4934.2009.00922.x PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 782QA UT WOS:000292023100006 PM 19799645 ER PT J AU Cai, J Yi, FF Bian, ZY Shen, DF Yang, L Yan, L Tang, QZ Yang, XC Li, HL AF Cai, Jun Yi, Fang-Fang Bian, Zhou-Yan Shen, Di-Fei Yang, Long Yan, Ling Tang, Qi-Zhu Yang, Xin-Chun Li, Hongliang TI Crocetin protects against cardiac hypertrophy by blocking MEK-ERK1/2 signalling pathway (vol 13, pg 909, 2009) SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Correction C1 [Cai, Jun] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Cai, Jun] Harvard Univ, Sch Med, Boston, MA USA. [Cai, Jun; Yi, Fang-Fang; Yang, Long] Capital Med Univ, Beijing Chaoyang Hosp, Dept Cardiol, Beijing, Peoples R China. [Bian, Zhou-Yan; Shen, Di-Fei; Yan, Ling; Tang, Qi-Zhu; Yang, Xin-Chun; Li, Hongliang] Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China. [Bian, Zhou-Yan; Shen, Di-Fei; Yan, Ling; Tang, Qi-Zhu; Yang, Xin-Chun; Li, Hongliang] Wuhan Univ, Cardiovasc Res Inst, Wuhan 430060, Peoples R China. RP Li, HL (reprint author), Wuhan Univ, Cardiovasc Res Inst, JieFang Rd 238, Wuhan 430060, Peoples R China. EM hongliang.li@ymail.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD JUN PY 2010 VL 14 IS 6B BP 1868 EP 1868 DI 10.1111/j.1582-4934.2010.01108.x PG 1 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 782QA UT WOS:000292023100042 ER PT J AU Chen, JJ Pike, GB AF Chen, J. Jean Pike, G. Bruce TI Global cerebral oxidative metabolism during hypercapnia and hypocapnia in humans: implications for BOLD fMRI SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE BOLD; hypercapnia; CMRO(2); fMRI; CO(2); CBF ID BLOOD-FLOW; OXYGEN-CONSUMPTION; FUNCTIONAL MRI; TESLA; FLUCTUATIONS; RESPONSES; SIGNAL; BRAIN; CO2 AB The effect of carbon dioxide (CO(2)) on cerebral metabolism is of tremendous interest to functional imaging. In particular, mild-to-moderate hypercapnia is routinely used in calibrated blood oxygen-level dependent (BOLD)-functional magnetic resonance imaging (fMRI)-based quantification of cerebral oxidative metabolism changes (Delta CMRO(2)), and relies on the assumption of a stable CMRO(2) during CO(2) challenges. However, this assumption has been challenged by certain animal studies, necessitating its verification in humans and under conditions customary to fMRI. We report, for the first time, on global Delta CMRO(2) measurements made noninvasively in humans during graded hypercapnia and hypocapnia. We used computerized end-tidal CO(2) modulation to minimize undesired concurrent changes in oxygen pressure, and our findings suggest that no significant change in global CMRO(2) is expected at the levels of end-tidal CO(2) changes customary to calibrated BOLD. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1094-1099; doi: 10.1038/jcbfm.2010.42; published online 7 April 2010 C1 [Chen, J. Jean; Pike, G. Bruce] Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. RP Chen, JJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM jjchen@nmr.mgh.harvard.edu RI Chen, J. Jean/A-2846-2013; Pike, Bruce/K-5562-2014 OI Chen, J. Jean/0000-0001-5469-7542; Pike, Bruce/0000-0001-8924-683X FU Natural Sciences and Engineering Research Council of Canada (NSERC); Canadian Institutes of Health Research (CIHR); Fonds de la Recherche en Sante du Quebec FX This research was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) (to JJC), the Canadian Institutes of Health Research (CIHR) and Fonds de la Recherche en Sante du Quebec (to GBP). NR 26 TC 65 Z9 65 U1 1 U2 5 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 JUN PY 2010 VL 30 IS 6 BP 1094 EP 1099 DI 10.1038/jcbfm.2010.42 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 604GH UT WOS:000278267000002 PM 20372169 ER PT J AU Zhu, HH Fan, X Yu, ZY Liu, JX Murata, Y Lu, J Zhao, S Hajjar, KA Lo, EH Wang, XY AF Zhu, Haihao Fan, Xiang Yu, Zhanyang Liu, Jianxiang Murata, Yoshihiro Lu, Jie Zhao, Song Hajjar, Katherine A. Lo, Eng H. Wang, Xiaoying TI Annexin A2 combined with low-dose tPA improves thrombolytic therapy in a rat model of focal embolic stroke SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE annexin A2; cerebral ischemia; combination therapy; thrombolysis; tPA ID TISSUE-PLASMINOGEN ACTIVATOR; BLOOD-BRAIN-BARRIER; ACUTE ISCHEMIC-STROKE; CEREBRAL-ISCHEMIA; HEMORRHAGIC TRANSFORMATION; MATRIX-METALLOPROTEINASE; NEUROVASCULAR UNIT; IN-VITRO; REPERFUSION; INJURY AB Recent studies showed that soluble annexin A2 dramatically increases tissue plasminogen activator (tPA)-mediated plasmin generation in vitro, and reduces thrombus formation in vivo. Here, we hypothesize that combining annexin A2 with tPA can significantly enhance thrombolysis efficacy, so that lower doses of tPA can be applied in ischemic stroke to avoid neurotoxic and hemorrhagic complications. In vitro activity assays confirmed tPA-specific amplification of plasmin generation by recombinant annexin A2. In a rat focal embolic stroke model, combination therapy with tPA and recombinant annexin A2 protein at 2 h post-ischemia decreased the effective dose required for tPA by four-fold and reduced brain infarction. Combining annexin A2 with tPA also lengthened the time window for thrombolysis. Compared with tPA (10 mg/kg) alone, the combination of annexin A2 (5 mg/kg) plus low-dose tPA (2.5 mg/kg) significantly enhanced fibrinolysis, attenuated mortality, brain infarction, and hemorrhagic transformation, even when administered at 4 h post-ischemia. Combination with recombinant annexin A2, the effective thrombolytic dose of tPA can be decreased. As a result, brain hemorrhage and infarction are reduced, and the time window for stroke reperfusion prolonged. Our present findings provide a promising new approach for enhancing tPA-based thrombolytic stroke therapy. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1137-1146; doi: 10.1038/jcbfm.2009.279; published online 13 January 2010 C1 [Zhu, Haihao; Fan, Xiang; Yu, Zhanyang; Liu, Jianxiang; Murata, Yoshihiro; Lu, Jie; Zhao, Song; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Neuroprotect Res Lab, Dept Neurol, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA. [Zhu, Haihao; Fan, Xiang; Yu, Zhanyang; Liu, Jianxiang; Murata, Yoshihiro; Lu, Jie; Zhao, Song; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Neuroprotect Res Lab, Dept Radiol, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA. [Zhu, Haihao; Fan, Xiang; Yu, Zhanyang; Liu, Jianxiang; Murata, Yoshihiro; Lu, Jie; Zhao, Song; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02129 USA. [Hajjar, Katherine A.] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY USA. RP Wang, XY (reprint author), Harvard Univ, Neuroprotect Res Lab, Dept Neurol, Massachusetts Gen Hosp,Sch Med, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. EM wangxi@helix.mgh.harvard.edu FU American Heart Association [0435087N]; National Institute of Health [R01-NS049476, R01-HL042493, P01-046403, R01-NS37074, R01-NS48422, R01-NS53560, P50-NS10828] FX This work was supported in part by Scientist Development Grant 0435087N from the American Heart Association, National Institute of Health grant R01-NS049476 (to XW), National Institute of Health grants R01-HL042493 and P01-046403 (to KAH), National Institute of Health grants R01-NS37074, R01-NS48422, R01-NS53560, and P50-NS10828 (to EHL). NR 45 TC 41 Z9 43 U1 0 U2 4 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 JUN PY 2010 VL 30 IS 6 BP 1137 EP 1146 DI 10.1038/jcbfm.2009.279 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 604GH UT WOS:000278267000007 PM 20068577 ER PT J AU Pallast, S Arai, K Pekcec, A Yigitkanli, K Yu, ZY Wang, XY Lo, EH van Leyen, K AF Pallast, Stefanie Arai, Ken Pekcec, Anton Yigitkanli, Kazim Yu, Zhanyang Wang, Xiaoying Lo, Eng H. van Leyen, Klaus TI Increased nuclear apoptosis-inducing factor after transient focal ischemia: a 12/15-lipoxygenase-dependent organelle damage pathway SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apoptosis; apoptosis-inducing factor; lipoxygenase; mitochondria; oxidative stress; stroke ID OXYGEN-GLUCOSE DEPRIVATION; CELL-DEATH; CEREBRAL-ISCHEMIA; POLY(ADP-RIBOSE) POLYMERASE; GLUTAMATE TOXICITY; OXIDATIVE STRESS; TRANSLOCATION; BAICALEIN; LIPOXYGENASES; INHIBITION AB 12/15-lipoxygenase (12/15-LOX) contributes to acute neuronal injury and edema formation in mouse models of middle cerebral artery occlusion (MCAO). The apoptosis-inducing factor (AIF) is implicated in caspase-independent forms of apoptosis, and has been linked to ischemic neuronal cell death. We show here that increased AIF in the peri-ischemic cortex of mouse colocalizes with 12/15-LOX after 2 h of MCAO. The 12/15-LOX inhibitor baicalein prevents the increase and nuclear localization of AIF, suggesting this pathway may be partially responsible for the neuroprotective qualities of baicalein. Using an established cell line model of neuronal oxidative stress, we show that 12/15-LOX activated after glutathione depletion leads to AIF translocation to the nucleus, which is abrogated by the 12/15-LOX inhibitor baicalein (control: 19.3%+/- 6.8% versus Glutamate: 64.0%+/- 8.2% versus glutamate plus baicalein: 11.4%+/- 2.2%). Concomitantly, resident proteins of the ER are dispersed throughout the cell (control: 31.0%+/- 8.4% versus glutamate: 70.0%+/- 5.5% versus glutamate plus baicalein: 8.0%+/- 2.7%), suggesting cell death through organelle damage. Taken together, these findings show that 12/15-LOX and AIF are sequential actors in a common cell death pathway that may contribute to stroke-induced brain damage. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1157-1167; doi: 10.1038/jcbfm.2009.281; published online 13 January 2010 C1 [Pallast, Stefanie; Arai, Ken; Pekcec, Anton; Yigitkanli, Kazim; Yu, Zhanyang; Wang, Xiaoying; Lo, Eng H.; van Leyen, Klaus] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. RP van Leyen, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, 149 13th St,Room 2401, Charlestown, MA 02129 USA. EM klaus_vanleyen@hms.harvard.edu RI van Leyen, Klaus/C-9126-2013 FU NIH [R01NS049430, R01NS53560, P01NS555104]; American Heart Association FX We thank I Bagayev for help with confocal microscopy and H-Y Kim for ischemic brain sections. Support through grants from the NIH (R01NS049430 to KvL, R01NS53560 and P01NS555104 to EHL), and a Scientist Development grant from the American Heart Association (to KvL.), is gratefully acknowledged. NR 25 TC 41 Z9 49 U1 0 U2 0 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 JUN PY 2010 VL 30 IS 6 BP 1157 EP 1167 DI 10.1038/jcbfm.2009.281 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 604GH UT WOS:000278267000009 PM 20068575 ER PT J AU Bhasin, S Cunningham, GR Hayes, FJ Matsumoto, AM Snyder, PJ Swerdloff, RS Montori, VM AF Bhasin, Shalender Cunningham, Glenn R. Hayes, Frances J. Matsumoto, Alvin M. Snyder, Peter J. Swerdloff, Ronald S. Montori, Victor M. TI Testosterone Therapy in Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; PLACEBO-CONTROLLED TRIALS; LOW SERUM TESTOSTERONE; BONE-MINERAL DENSITY; NOCTURNAL PENILE TUMESCENCE; RANDOMIZED CONTROLLED-TRIAL; DIGITAL RECTAL EXAMINATION; VISUAL EROTIC STIMULI; MIDDLE-AGED MEN; VIRUS-INFECTED MEN AB Objective: Our objective was to update the guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men published previously in 2006. Participants: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Conclusions: We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and, in some men in whom total testosterone is near the lower limit of normal or in whom SHBG abnormality is suspected by measurement of free or bioavailable testosterone level, using validated assays. We recommend testosterone therapy for men with symptomatic androgen deficiency to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. We recommend against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 4 ng/ml or greater than 3 ng/ml in men at high risk for prostate cancer such as African-Americans or men with first-degree relatives with prostate cancer without further urological evaluation, hematocrit greater than 50%, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate Symptom Score above 19, or uncontrolled or poorly controlled heart failure. When testosterone therapy is instituted, we suggest aiming at achieving testosterone levels during treatment in the mid-normal range with any of the approved formulations, chosen on the basis of the patient's preference, consideration of pharmacokinetics, treatment burden, and cost. Men receiving testosterone therapy should be monitored using a standardized plan. (J Clin Endocrinol Metab 95: 2536-2559, 2010) C1 [Bhasin, Shalender] Boston Univ, Sch Med, Boston, MA 02118 USA. [Cunningham, Glenn R.] Baylor Coll Med, Vet Affairs Med Ctr, Houston, TX 77030 USA. [Hayes, Frances J.] St Vincents Univ Hosp, Dublin 4, Ireland. [Matsumoto, Alvin M.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Snyder, Peter J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Swerdloff, Ronald S.] Harbor Univ Calif, Los Angeles Med Ctr, Torrance, CA 90502 USA. [Montori, Victor M.] Mayo Clin, Rochester, MN 55905 USA. RP Bhasin, S (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. EM govt-prof@endo-society.org RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Montori, Victor/0000-0003-0595-2898 NR 152 TC 796 Z9 819 U1 11 U2 57 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 JUN PY 2010 VL 95 IS 6 BP 2536 EP 2559 DI 10.1210/jc.2009-2354 PG 24 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 606RD UT WOS:000278444000004 PM 20525905 ER PT J AU Robinson, BG Paz-Ares, L Krebs, A Vasselli, J Haddad, R AF Robinson, Bruce G. Paz-Ares, Luis Krebs, Annetta Vasselli, James Haddad, Robert TI Vandetanib (100 mg) in Patients with Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CELL LUNG-CANCER; PHASE-II; JAPANESE PATIENTS; MALIGNANT-TUMORS; EGF-RECEPTOR; CARCINOMA; ZD6474; INHIBITORS; HYPOTHYROIDISM; ANGIOGENESIS AB Purpose: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC. Patients and Methods: Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors. Results: The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients(53%); the disease control rate was therefore 68%(95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies. Conclusions: Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile. (J Clin Endocrinol Metab 95: 2664-2671, 2010) C1 [Robinson, Bruce G.] Univ Sydney, Sydney Med Sch, Kolling Inst Med Res, Sydney, NSW 2006, Australia. [Paz-Ares, Luis] Inst Biomed Sevilla, Seville 41013, Spain. [Paz-Ares, Luis] Hosp Univ Virgen de Rocio, Seville 41013, Spain. [Krebs, Annetta; Vasselli, James] AstraZeneca, Wilmington, DE 19850 USA. [Haddad, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Robinson, BG (reprint author), Univ Sydney, Sydney Med Sch, Kolling Inst Med Res, Sydney, NSW 2006, Australia. EM b.robinson@usyd.edu.au RI IBIS, NUEVAS TERAPIA/P-3415-2015 FU AstraZeneca FX This study, including editorial assistance provided by Chris Watson (Mudskipper Bioscience), was supported financially by AstraZeneca. NR 29 TC 126 Z9 131 U1 0 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 JUN PY 2010 VL 95 IS 6 BP 2664 EP 2671 DI 10.1210/jc.2009-2461 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 606RD UT WOS:000278444000020 PM 20371662 ER PT J AU Wesseling-Perry, K Harkins, GC Wang, HJ Elashoff, R Gales, B Horwitz, MJ Stewart, AF Juppner, H Salusky, IB AF Wesseling-Perry, Katherine Harkins, G. Chris Wang, He-jing Elashoff, Robert Gales, Barbara Horwitz, Mara J. Stewart, Andrew F. Jueppner, Harald Salusky, Isidro B. TI The Calcemic Response to Continuous Parathyroid Hormone (PTH)(1-34) Infusion in End-Stage Kidney Disease Varies According to Bone Turnover: A Potential Role for PTH(7-84) SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FIBROBLAST GROWTH FACTOR-23; VITAMIN-D METABOLISM; INTERMITTENT CALCITRIOL THERAPY; IMMUNOMETRIC PTH ASSAYS; RENAL-FAILURE; SECONDARY HYPERPARATHYROIDISM; SKELETAL RESISTANCE; PTH/PTHRP RECEPTOR; DIALYSIS PATIENTS; PHOSPHATE HOMEOSTASIS AB Context: Factors contributing to PTH resistance in dialysis patients remain elusive. Objectives: The study assessed the skeletal and biochemical response to 46 h of PTH(1-34) infusion in dialysis patients. Design: The study was a prospective, controlled assessment of response to PTH(1-34). Setting: The study was performed at the University of California, Los Angeles, General Clinical Research Center. Participants: Nineteen dialysis patients and 17 healthy volunteers were studied. Intervention: PTH(1-34) was infused at a rate of 8 pmol/kg.h for 46 h. Bone biopsy was performed in all dialysis patients. Main Outcome Measures: Serum calcium, phosphorus, 1,25-dihydroxyvitamin D, PTH (four separate assays), and FGF-23 were determined at baseline and h 7, 23, 35, and 46 of the infusion. Results: Serum calcium levels rose in healthy volunteers (9.2 +/- 0.1 to 11.9 +/- 0.3 mg/dl; P < 0.01) and in dialysis patients with adynamic/normal bone turnover (9.0 +/- 0.3 to 10.7 +/- 0.7 mg/dl; P < 0.05) but did not change in dialysis patients with high bone turnover. Serum phosphorus levels declined in healthy volunteers (3.9 +/- 0.1 to 3.5 +/- 0.1 mg/dl; P < 0.05) but increased in all dialysis patients (6.7 +/- 0.4 to 8.0 +/- 0.3 mg/dl; P < 0.05). Full-length PTH(1-84) declined in all subjects; however, PTH(7-84) fragments declined only in healthy subjects and in dialysis patients with normal/adynamic bone but remained unchanged in dialysis patients with high bone turnover. Conclusions: The skeleton of dialysis patients with high bone turnover is resistant to the calcemic actions of PTH. PTH(7-84) may contribute to this phenomenon. (J Clin Endocrinol Metab 95: 2772-2780, 2010) C1 [Wesseling-Perry, Katherine] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Nephrol, Los Angeles, CA 90095 USA. [Harkins, G. Chris] Immutop Int, San Clemente, CA 92673 USA. [Horwitz, Mara J.; Stewart, Andrew F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wesseling-Perry, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Nephrol, A2-383 MDCC,10833 LeConte Blvd, Los Angeles, CA 90095 USA. EM kwesseling@mednet.ucla.edu FU U.S. Public Health Service [DK-67563, DK-35423, DK-51081, DK-073039, RR-00865]; Casey Lee Ball Foundation; National Kidney Foundation FX This work was supported by U.S. Public Health Service Grants DK-67563, DK-35423, DK-51081, DK-073039, and RR-00865 and funds from the Casey Lee Ball Foundation. K.W.-P. was a recipient of a fellowship award from the National Kidney Foundation. NR 52 TC 32 Z9 32 U1 0 U2 10 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 JUN PY 2010 VL 95 IS 6 BP 2772 EP 2780 DI 10.1210/jc.2009-1909 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 606RD UT WOS:000278444000031 PM 20382692 ER PT J AU Petersenn, S Schopohl, J Barkan, A Mohideen, P Colao, A Abs, R Buchelt, A Ho, YY Hu, K Farrall, AJ Melmed, S Biller, BMK AF Petersenn, S. Schopohl, J. Barkan, A. Mohideen, P. Colao, A. Abs, R. Buchelt, A. Ho, Y. -Y. Hu, K. Farrall, A. J. Melmed, S. Biller, B. M. K. CA Pasireotide Acromegaly Study Grp TI Pasireotide (SOM230) Demonstrates Efficacy and Safety in Patients with Acromegaly: A Randomized, Multicenter, Phase II Trial SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SOMATOSTATIN ANALOGS; OCTREOTIDE LAR; MANAGEMENT; SURGERY; THERAPY AB Context: Pasireotide (SOM230) is a novel multireceptor ligand somatostatin analog with affinity for somatostatin receptor subtypes sst(1-3) and sst(5). Because most GH-secreting pituitary adenomas express sst(2) and sst(5), pasireotide has the potential to be more effective than the sst(2)-preferential somatostatin analogs octreotide and lanreotide. Objective: Our objective was to evaluate the efficacy and safety of three different doses of pasireotide in patients with acromegaly. Design: We conducted a phase II, randomized, multicenter, open-label, three-way, crossover study. Patients: Sixty patients with acromegaly, defined by a 2-h five-point mean GH level higher than 5 mu g/liter, lack of suppression of GH to less than 1 mu g/liter after oral glucose tolerance test, and elevated IGF-I for age-and sex-matched controls. Patients could have had previous surgery, radiotherapy, and/or medical therapy or no previous treatment. Intervention: After treatment with octreotide 100 mu g sc three times daily for 28 d, each patient received pasireotide 200, 400, and 600 mu g sc twice daily in random order for 28 d. Main Outcome Measure: A biochemical response was defined as a reduction in GH to no more than 2.5 mu g/liter and normalization of IGF-I to age-and sex-matched controls. Results: After 4 wk of octreotide, 9% of patients achieved a biochemical response. After 4 wk of pasireotide 200-600 mu g sc bid, 19% of patients achieved a biochemical response, which increased to 27% after 3 months of pasireotide; 39% of patients had a more than 20% reduction in pituitary tumor volume. Pasireotide was generally well tolerated. Conclusions: Pasireotide is a promising treatment for acromegaly. Larger studies of longer duration evaluating the efficacy and safety of pasireotide in patients with acromegaly are ongoing. (J Clin Endocrinol Metab 95: 2781-2789, 2010) C1 [Petersenn, S.] Univ Duisburg Essen, Div Endocrinol, Med Ctr, D-45122 Essen, Germany. [Schopohl, J.] Univ Munich, Med Klin Innenstadt, D-80336 Munich, Germany. [Barkan, A.] Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. [Mohideen, P.; Ho, Y. -Y.; Hu, K.] Novartis Pharmaceut, E Hanover, NJ 07936 USA. [Colao, A.] Univ Naples Federico 2, Dept Mol & Clin Endocrinol & Oncol, I-80125 Naples, Italy. [Abs, R.] Univ Antwerp, Dept Endocrinol, BE-2000 Antwerp, Belgium. [Buchelt, A.] Novartis Pharma AG, CH-4056 Basel, Switzerland. [Farrall, A. J.] Univ Edinburgh, Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. [Melmed, S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Biller, B. M. K.] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. RP Petersenn, S (reprint author), Univ Duisburg Essen, Div Endocrinol, Med Ctr, Hufelandstr 55, D-45122 Essen, Germany. EM stephan.petersenn@uni-due.de OI Brue, Thierry/0000-0001-8482-6691; Trainer, Peter/0000-0003-0146-3835 FU Novartis Pharmaceuticals Corp.; Novartis; IPSEN; Pfizer; Italfarmaco FX This study was funded by Novartis Pharmaceuticals Corp. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corp.; This study has been registered in the clinical trials database www.clinicaltrials.gov with the ID number NCT00088582.; Disclosure Summary: R. A. has received research grant support from Novartis and IPSEN and has served on an advisory board for Novartis. A. B. has received research grant support from Novartis and has served on a speaker's bureau for IPSEN. B. M. K. B. has received research grant support from Novartis and Pfizer and has served on advisory boards for Novartis, IPSEN, and Pfizer. A. C. has received research grant support from IPSEN, Italfarmaco, Novartis, and Pfizer; has received speaker fees from IPSEN, Italfarmaco, and Novartis; and has served on advisory boards for IPSEN and Novartis. A. F. has received honoraria from Novartis. S. M. has received research grant support from Novartis and has served on an advisory board for Novartis. S. P. has served on advisory boards for Novartis and IPSEN and has received lecture fees from Novartis and IPSEN. J.S. has received research grant support from Novartis, has received consultancy fees from Novartis and IPSEN, and has received honoraria from Novartis, IPSEN, and Pfizer. A. B., Y.-Y.H., K. H., and P. M. are employed by Novartis. Y.-Y.H. and P. M. have equity interests in Novartis. NR 18 TC 108 Z9 111 U1 1 U2 2 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 JUN PY 2010 VL 95 IS 6 BP 2781 EP 2789 DI 10.1210/jc.2009-2272 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 606RD UT WOS:000278444000032 PM 20410233 ER PT J AU Gianetti, E Tusset, C Noel, SD Au, MG Dwyer, AA Hughes, VA Abreu, AP Carroll, J Trarbach, E Silveira, LFG Costa, EMF de Mendonca, BB de Castro, M Lofrano, A Hall, JE Bolu, E Ozata, M Quinton, R Amory, JK Stewart, SE Arlt, W Cole, TR Crowley, WF Kaiser, UB Latronico, AC Seminara, SB AF Gianetti, Elena Tusset, Cintia Noel, Sekoni D. Au, Margaret G. Dwyer, Andrew A. Hughes, Virginia A. Abreu, Ana Paula Carroll, Jessica Trarbach, Ericka Silveira, Leticia F. G. Costa, Elaine M. F. de Mendonca, Berenice Bilharinho de Castro, Margaret Lofrano, Adriana Hall, Janet E. Bolu, Erol Ozata, Metin Quinton, Richard Amory, John K. Stewart, Susan E. Arlt, Wiebke Cole, Trevor R. Crowley, William F. Kaiser, Ursula B. Latronico, Ana Claudia Seminara, Stephanie B. TI TAC3/TACR3 Mutations Reveal Preferential Activation of Gonadotropin-Releasing Hormone Release by Neurokinin B in Neonatal Life Followed by Reversal in Adulthood SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; KALLMANN-SYNDROME; RAT HYPOTHALAMUS; ARCUATE NUCLEUS; RECEPTOR; GENE; DEFICIENCY; SECRETION; PUBERTY; GPR54 AB Context: Mutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established. Objective: A broad cohort of normosmic IHH probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships. Design and Setting: The study consisted of sequencing of TAC3/TACR3, in vitro functional assays, and neuroendocrine phenotyping conducted in tertiary care centers worldwide. Patients or Other Participants: 345 probands, 18 family members, and 292 controls were studied. Intervention: Reproductive phenotypes throughout reproductive life and before and after therapy were examined. Main Outcome Measure: Rare sequence variants in TAC3/TACR3 were detected. Results: In TACR3, 19 probands harbored 13 distinct coding sequence rare nucleotide variants [three nonsense mutations, six nonsynonymous, four synonymous (one predicted to affect splicing)]. In TAC3, one homozygous single base pair deletion was identified, resulting in complete loss of the neurokinin B decapeptide. Phenotypic information was available on 16 males and seven females with coding sequence variants in TACR3/TAC3. Of the 16 males, 15 had microphallus; none of the females had spontaneous thelarche. Seven of the 16 males and five of the seven females were assessed after discontinuation of therapy; six of the seven males and four of the five females demonstrated evidence for reversibility of their hypogonadotropism. Conclusions: Mutations in the neurokinin B pathway are relatively common as causes of hypogonadism. Although the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time. (J Clin Endocrinol Metab 95: 2857-2867, 2010) C1 [Gianetti, Elena; Au, Margaret G.; Dwyer, Andrew A.; Hughes, Virginia A.; Hall, Janet E.; Crowley, William F.; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Harvard Ctr Reprod Sci, Boston, MA 02114 USA. [Gianetti, Elena; Au, Margaret G.; Dwyer, Andrew A.; Hughes, Virginia A.; Hall, Janet E.; Crowley, William F.; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Tusset, Cintia; Trarbach, Ericka; Costa, Elaine M. F.; de Mendonca, Berenice Bilharinho; Latronico, Ana Claudia] Univ Sao Paulo, Lab Hormonios & Genet Mol, Serv Endocrinol, Div Clin Med 1,Hosp Clin,Fac Med, BR-05403900 Sao Paulo, Brazil. [Noel, Sekoni D.; Abreu, Ana Paula; Carroll, Jessica; Kaiser, Ursula B.] Brigham & Womens Hosp, Harvard Ctr Reprod Sci, Boston, MA 02115 USA. [Noel, Sekoni D.; Abreu, Ana Paula; Carroll, Jessica; Kaiser, Ursula B.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Noel, Sekoni D.; Abreu, Ana Paula; Carroll, Jessica; Kaiser, Ursula B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [de Castro, Margaret] Univ Sao Paulo, Dept Clin Med, Fac Med Ribeirao Preto, BR-14049900 Sao Paulo, Brazil. [Lofrano, Adriana] Univ Hosp Brasilia, Endocrinol Sect, BR-70910900 Brasilia, DF, Brazil. [Lofrano, Adriana] Univ Brasilia, Mol Pharmacol Lab, Fac Hlth Sci, BR-70910900 Brasilia, DF, Brazil. [Bolu, Erol; Ozata, Metin] Gulhane Mil Med Acad, Dept Endocrinol, TR-06018 Ankara, Turkey. [Quinton, Richard] Newcastle Univ, Inst Human Genet, Endocrinol Res Grp, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Amory, John K.] Univ Washington, Med Ctr, Div Gen Internal Med, Seattle, WA 98195 USA. [Stewart, Susan E.; Cole, Trevor R.] Birmingham Womens Hosp Natl Hlth Serv Fdn Trust, Genet Unit, Birmingham B15 2TG, W Midlands, England. [Crowley, William F.] Univ Birmingham, Sch Clin & Expt Med, Ctr Endocrinol Diabet & Metab, Birmingham B15 2TT, W Midlands, England. RP Seminara, SB (reprint author), 55 Fruit St,BHX 511, Boston, MA 02114 USA. EM sseminara@partners.org RI Arlt, Wiebke/B-6310-2009; Mendonca, Berenice/C-2827-2012; Castro, Margaret/A-4918-2009; Latronico, Ana Claudia/E-1198-2012; Trarbach, Ericka/I-5395-2012; Silveira, Leticia/D-3975-2014; Lofrano Porto, Adriana/H-8348-2012; Dwyer, Andrew/D-8099-2012; OI Arlt, Wiebke/0000-0001-5106-9719; Lofrano Porto, Adriana/0000-0002-9590-1631; Dwyer, Andrew/0000-0002-7023-6794; Latronico Xavier, Ana Claudia/0000-0001-6782-693X FU National Center for Research Resources (Harvard Clinical and Translational Science Center) [M01-RR-01066]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [05/04726-0]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [300209/2008-8]; Medical Research Council UK (MRC) [G0900567]; European Commission; Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health [U545U54HD028138]; National Institutes of Health [R01-HD-42708] FX S. B. S. and J.E.H. received grant support from the National Center for Research Resources (M01-RR-01066, Harvard Clinical and Translational Science Center). The Brazilian work was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP-Grant 05/04726-0) (to A. C. L.) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq Grant 300209/2008-8) (to A. C. L.). W. A. is supported by the Medical Research Council UK (MRC Program Grant G0900567) and the European Commission (FP7 Collaborative Project EuroDSD). S. B. S., U. B. K., and W. F. C. received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health through a cooperative agreement(U545U54HD028138) as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research. J.E.H. received grant support from National Institutes of Health R01-HD-42708. NR 36 TC 109 Z9 110 U1 0 U2 9 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 JUN PY 2010 VL 95 IS 6 BP 2857 EP 2867 DI 10.1210/jc.2009-2320 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 606RD UT WOS:000278444000043 PM 20332248 ER PT J AU Lloyd, B Ravi, P Mendes, N Klibanski, A Misra, M AF Lloyd, Benjamin Ravi, Praful Mendes, Nara Klibanski, Anne Misra, Madhusmita TI Peptide YY Levels across Pubertal Stages and Associations with Growth Hormone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ORAL GLUCOSE-LOAD; LUTEINIZING-HORMONE; ANOREXIA-NERVOSA; ADOLESCENT GIRLS; BODY-COMPOSITION; FOOD-INTAKE; SECRETION; GHRELIN; BOYS; POLYPEPTIDE AB Context: Changes in appetite-regulating peptides may impact food intake during puberty and facilitate the pubertal growth spurt. Peptide YY (PYY) is an anorexigenic hormone that is high in anorexia nervosa and low in obesity, inhibits GnRH secretion, and is suppressed by GH administration. The relationship between PYY and GH has not been examined across puberty. Objectives: We hypothesized that PYY would be inversely associated with GH in adolescents and would be lowest when GH is highest. Design and Setting: We conducted a cross-sectional study at a Clinical Research Center. Subjects: We studied 87 children, 46 boys and 41 girls ages 9-17 yr at Tanner stages 1-5 of puberty (10th-90th percentiles for body mass index). Outcome Measures: We measured fasting PYY and nadir GH levels after administration of an oral glucose load. Leptin levels were also measured. Results: Fasting PYY was lowest and nadir GH highest in boys in Tanner stages 3-4 (P = 0.02) and in girls in Tanner stages 2-3 (P = 0.02). Leptin levels were highest in early pubertal boys and late pubertal girls. For the group as a whole and within genders, even after controlling for body mass index, log nadir GH correlated inversely with log PYY (P = 0.003, 0.07, and 0.02). PYY levels did not correlate with leptin levels. Conclusions: Duringmid-puberty, at a time when GH levels are the highest, PYY is at a nadir, and these low PYY levels may facilitate pubertal progression and growth. (J Clin Endocrinol Metab 95: 2957-2962, 2010) C1 [Lloyd, Benjamin; Ravi, Praful; Mendes, Nara; Klibanski, Anne; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Misra, Madhusmita] Mass Gen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, Boston, MA 02114 USA. EM mmisra@partners.org RI Mendes Estella, Nara/E-4682-2013; Mendes Estella, Nara/A-1469-2015 FU National Institutes of Health [1 UL1 RR025758-01, R01 DK 062249, 1 R01 HD060827-01A1] FX This work was supported by National Institutes of Health Grants 1 UL1 RR025758-01, R01 DK 062249, and 1 R01 HD060827-01A1. NR 24 TC 13 Z9 13 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 JUN PY 2010 VL 95 IS 6 BP 2957 EP 2962 DI 10.1210/jc.2009-2496 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 606RD UT WOS:000278444000056 PM 20375207 ER PT J AU Sykiotis, GP Hoang, XH Avbelj, M Hayes, FJ Thambundit, A Dwyer, A Au, M Plummer, L Crowley, WF Pitteloud, N AF Sykiotis, Gerasimos P. Hoang, Xuan-Huong Avbelj, Magdalena Hayes, Frances J. Thambundit, Apisadaporn Dwyer, Andrew Au, Margaret Plummer, Lacey Crowley, William F., Jr. Pitteloud, Nelly TI Congenital Idiopathic Hypogonadotropic Hypogonadism: Evidence of Defects in the Hypothalamus, Pituitary, and Testes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; CAT-EYE SYNDROME; LUTEINIZING-HORMONE; KALLMANN-SYNDROME; GNRH; DEFICIENCY; INDUCTION; MEN; RESPONSIVENESS; ORGANOGENESIS AB Context: Idiopathic hypogonadotropic hypogonadism (IHH) with normal smell (normosmic IHH) or anosmia (Kallmann syndrome) is associated with defects in the production or action of GnRH. Accordingly, most IHH patients respond to physiological pulsatile GnRH replacement by normalizing serum LH, FSH, and testosterone (T) levels and achieving gametogenesis; some patients, however, show atypical responses. Interestingly, several IHH-associated genes are expressed in multiple compartments of the hypothalamic-pituitary-gonadal axis. Objective: The aim of the study was to investigate whether the clinical, biochemical, or genetic characteristics of IHH men with atypical responses to GnRH indicate alternative or additional defects in the hypothalamic-pituitary-gonadal axis. Subjects: We studied 90 IHH men undergoing long-term pulsatile GnRH treatment over 30 yr. Design and Setting: We conducted a retrospective study of response to GnRH at a Clinical Research Center. Interventions: Physiological regimens of pulsatile sc GnRH were administered for at least 12 months. Dose-response studies using iv GnRH pulses assessed the pituitary LH response. Main Outcome Measures: We measured serum T, LH, FSH, and inhibin B levels, sperm in ejaculate, and determined the sequence of IHH-associated genes. Results: Twenty-six percent of subjects displayed atypical responses to GnRH: 1) 10 remained hypogonadotropic and hypogonadal, demonstrating pituitary and testicular defects; 2) eight achieved spermatogenesis and normal T but only with hypergonadotropism, indicating impaired testicular responsiveness to gonadotropins; and 3) five remained azoospermic despite achieving adult testicular volumes and normal hormonal profiles, suggesting primary defects in spermatogenesis. Mutations were identified only in KAL1 across groups. Conclusion: In addition to hypothalamic GnRH deficiency, IHH men can have primary pituitary and/or testicular defects, which are unmasked by GnRH replacement. (J Clin Endocrinol Metab 95: 3019-3027, 2010) C1 [Pitteloud, Nelly] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM npitteloud@partners.org RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Dwyer, Andrew/0000-0002-7023-6794; Avbelj Stefanija, Magdalena/0000-0002-0836-5114; Sykiotis, Gerasimos/0000-0002-9565-4941 FU National Institutes of Health (NIH) [HD15788]; RO1 [HD015788, HD056264]; Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH [U54 HD028138]; American Recovery and Reinvestment Act Supplement [U54 HD028138-19S1]; NIH National Center for Research Resources [M01-RR-01066] FX This work was supported by National Institutes of Health (NIH) Grant HD15788 and RO1 Grants HD015788 and HD056264; the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH, through cooperative agreement U54 HD028138 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research, American Recovery and Reinvestment Act Supplement U54 HD028138-19S1; and M01-RR-01066 NIH National Center for Research Resources, General Clinical Research Centers Program. NR 36 TC 36 Z9 42 U1 0 U2 1 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 JUN PY 2010 VL 95 IS 6 BP 3019 EP 3027 DI 10.1210/jc.2009-2582 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 606RD UT WOS:000278444000064 PM 20382682 ER PT J AU Jiang, DH Liang, JR Campanella, GS Guo, RS Yu, S Xie, T Liu, NS Jung, Y Homer, R Meltzer, EB Li, YJ Tager, AM Goetinck, PF Luster, AD Noble, PW AF Jiang, Dianhua Liang, Jiurong Campanella, Gabriele S. Guo, Rishu Yu, Shuang Xie, Ting Liu, Ningshan Jung, Yoosun Homer, Robert Meltzer, Eric B. Li, Yuejuan Tager, Andrew M. Goetinck, Paul F. Luster, Andrew D. Noble, Paul W. TI Inhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACUTE ALLOGRAFT-REJECTION; CHEMOKINE RECEPTOR CXCR3; INDUCED LUNG INJURY; GROWTH-FACTOR; MESENCHYMAL TRANSITION; EXTRACELLULAR-MATRIX; CELL PROLIFERATION; EPITHELIAL-CELLS; PROGENITOR CELLS; HEPARAN-SULFATE AB Pulmonary fibrosis is a progressive, dysregulated response to injury culminating in compromised lung function due to excess extracellular matrix production. The heparan sulfate proteoglycan syndecan-4 is important in mediating fibroblast-matrix interactions, but its role in pulmonary fibrosis has not been explored. To investigate this issue, we used intratracheal instillation of bleomycin as a model of acute lung injury and fibrosis. We found that bleomycin treatment increased syndecan-4 expression. Moreover, we observed a marked decrease in neutrophil recruitment and an increase in both myofibroblast recruitment and interstitial fibrosis in bleomycin-treated syndecan-4-null (Sdc4(-/-)) mice. Subsequently, we identified a direct interaction between CXCL10, an antifibrotic chemokine, and syndecan-4 that inhibited primary lung fibroblast migration during fibrosis; mutation of the heparin-binding domain, but not the CXCR3 domain, of CXCL10 diminished this effect. Similarly, migration of fibroblasts from patients with pulmonary fibrosis was inhibited in the presence of CXCL10 protein defective in CXCR3 binding. Furthermore, administration of recombinant CXCL10 protein inhibited fibrosis in WT mice, but not in Sdc4(-/-) mice. Collectively, these data suggest that the direct interaction of syndecan-4 and CXCL10 in the lung interstitial compartment serves to inhibit fibroblast recruitment and subsequent fibrosis. Thus, administration of CXCL10 protein defective in CXCR3 binding may represent a novel therapy for pulmonary fibrosis. C1 [Jiang, Dianhua; Liang, Jiurong; Guo, Rishu; Xie, Ting; Liu, Ningshan; Jung, Yoosun; Meltzer, Eric B.; Li, Yuejuan; Noble, Paul W.] Duke Univ, Dept Med, Div Pulm Allergy & Crit Care Med, Sch Med, Durham, NC 27710 USA. [Campanella, Gabriele S.; Tager, Andrew M.; Luster, Andrew D.] Harvard Univ, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Med Sch, Charlestown, MA USA. [Yu, Shuang] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Xie, Ting] Beijing Univ Chinese Med, Beijing, Peoples R China. [Homer, Robert] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Goetinck, Paul F.] Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Sch Med, Charlestown, MA USA. RP Noble, PW (reprint author), Duke Univ, Dept Med, Div Pulm Allergy & Crit Care Med, Sch Med, 106 Res Dr, Durham, NC 27710 USA. EM dianhua.jiang@duke.edu; paul.noble@duke.edu RI Jiang, Dianhua/B-1421-2009; Xie, Ting/B-8531-2013; OI Jiang, Dianhua/0000-0002-4508-3829; Homer, Robert/0000-0002-2055-5885 FU NIH [AI052201, HL06539, HL77291] FX We thank P. Kincade for providing anti-syndecan-4 antibody and C. Gerard for providing Cxcr3-/- mice. This study was supported by NIH grants AI052201, HL06539, and HL77291 to P.W. Noble. NR 66 TC 64 Z9 66 U1 1 U2 6 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 JUN PY 2010 VL 120 IS 6 BP 2049 EP 2057 DI 10.1172/JCI38644 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 605CH UT WOS:000278324400028 PM 20484822 ER PT J AU Cheng, K Ho, K Stokes, R Scott, C Lau, SM Hawthorne, WJ O'Connell, PJ Loudovaris, T Kay, TW Kulkarni, RN Okada, T Wang, XHL Yim, SH Shah, Y Grey, ST Biankin, AV Kench, JG Laybutt, DR Gonzalez, FJ Kahn, CR Gunton, JE AF Cheng, Kim Ho, Kenneth Stokes, Rebecca Scott, Christopher Lau, Sue Mei Hawthorne, Wayne J. O'Connell, Philip J. Loudovaris, Thomas Kay, Thomas W. Kulkarni, Rohit N. Okada, Terumasa Wang, Xiaohui L. Yim, Sun Hee Shah, Yatrik Grey, Shane T. Biankin, Andrew V. Kench, James G. Laybutt, D. Ross Gonzalez, Frank J. Kahn, C. Ronald Gunton, Jenny E. TI Hypoxia-inducible factor-1 alpha regulates beta cell function in mouse and human islets SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HIPPEL-LINDAU-DISEASE; INSULIN-RESISTANCE SYNDROME; CORONARY-HEART-DISEASE; FACTOR 1-ALPHA; PANCREATIC-ISLETS; SERUM FERRITIN; IRON STORES; PROLYL HYDROXYLATION; EMBRYONIC LETHALITY AB Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a transcription factor that regulates cellular stress responses. While the levels of HIF-1 alpha protein are tightly regulated, recent studies suggest that it can be active under normoxic conditions. We hypothesized that HIF-1 alpha is required for normal beta cell function and reserve and that dysregulation may contribute to the pathogenesis of type 2 diabetes (T2D). Here we show that HIF-1 alpha protein is present at low levels in mouse and human normoxic beta cells and islets. Decreased levels of HIF-1 alpha impaired glucose-stimulated ATP generation and beta cell function. C57BL/6 mice with beta cell-specific Hif1a disruption (referred to herein as beta-Hif1a-null mice) exhibited glucose intolerance, beta cell dysfunction, and developed severe glucose intolerance on a high-fat diet. Increasing HIP-1 alpha levels by inhibiting its degradation through iron chelation markedly improved insulin secretion and glucose tolerance in control mice fed a high-fat diet but not in beta-Hif1a-null mice. Increasing HIF-1 alpha levels markedly increased expression of ARNT and other genes in human T2D islets and improved their function. Further analysis indicated that HIF-1 alpha was bound to the Arnt promoter in a mouse beta cell line, suggesting direct regulation. Taken together, these findings suggest an important role for HIF-1 alpha in beta cell reserve and regulation of ARNT expression and demonstrate that HIF-1 alpha is a potential therapeutic target for the beta cell dysfunction of T2D. C1 [Cheng, Kim; Ho, Kenneth; Stokes, Rebecca; Scott, Christopher; Lau, Sue Mei; Gunton, Jenny E.] Garvan Inst Med Res, Diabet & Transcript Factors Grp, Sydney, NSW 2010, Australia. [Hawthorne, Wayne J.; O'Connell, Philip J.] Univ Sydney, Ctr Transplantat & Renal Res, Westmead Res Inst, Westmead Hosp, Sydney, NSW 2006, Australia. [Loudovaris, Thomas; Kay, Thomas W.] St Vincents Inst, Melbourne, Vic, Australia. [Kulkarni, Rohit N.; Okada, Terumasa; Wang, Xiaohui L.; Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kulkarni, Rohit N.; Okada, Terumasa; Wang, Xiaohui L.; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA USA. [Yim, Sun Hee; Shah, Yatrik; Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. [Shah, Yatrik] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Grey, Shane T.] GIMR, Gene Therapy & Autoimmun Grp, Sydney, NSW, Australia. [Biankin, Andrew V.; Kench, James G.] GIMR, Canc Res Program, Sydney, NSW, Australia. [Biankin, Andrew V.] Bankstown Hosp, Dept Surg, Sydney, NSW, Australia. [Laybutt, D. Ross] GIMR, Diabet & Obes Res Program, Sydney, NSW, Australia. [Gunton, Jenny E.] Univ Sydney, Fac Med, Sydney, NSW 2006, Australia. [Gunton, Jenny E.] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW, Australia. [Gunton, Jenny E.] Westmead Hosp, Dept Endocrinol & Diabet, Sydney, NSW, Australia. RP Gunton, JE (reprint author), Garvan Inst Med Res, Diabet & Transcript Factors Grp, 384 Victoria St, Sydney, NSW 2010, Australia. EM j.gunton@garvan.org.au RI Grey, Shane/B-3020-2008; Ho, Ken/E-5832-2011; OI Grey, Shane/0000-0003-2160-1625; Biankin, Andrew/0000-0002-0362-5597 FU National Health and Medical Research Council of Australia (NHMRC); Diabetes Australia Research Trust; Juvenile Diabetes Research Foundation (JDRF); Royal Australasian College of Physicians Pfizer and Servier; L'Oreal Australian For Women in Science; NIH [RO1 DK33201, DK60837-02, K08, DK02885, RO1 DK67536]; Cancer Institute New South Wales FX J.E. Gunton was funded by the National Health and Medical Research Council of Australia (NHMRC), Diabetes Australia Research Trust, Juvenile Diabetes Research Foundation (JDRF), the Royal Australasian College of Physicians Pfizer and Servier postdoctoral fellowships, and the L'Oreal Australian For Women in Science fellowship. W.J. Hawthorne, P.J. O'Connell, T. Loudovaris, and T.W. Kay were funded by JDRF and NHMRC. C.R. Kahn was supported by the Mary K. Iacocca Professorship and NIH grants RO1 DK33201 and DK60837-02. RN. Kulkarni was supported by NIH grants K08, DK02885, and RO1 DK67536. A.V. Biankin is supported by a Cancer Institute New South Wales fellowship. A.V. Biankin and J.G. Kench are supported by an NHMRC program grant. We would like to thank Andrew Dwyer, Sof Andrikopoulos, Cecile King, James Cantley, and Don Chisholm for helpful comments; Amber Johns for assistance with the human pancreatic slides; Alice Boulghourjian from the Garvan histology-core; Will Hughes from the Garvan microscope-core; Ed Feener from the Joslin Proteomics Core Facility DERC; staff at BTF for maintaining the mice; and Tina Patel and Lindy Williams from Westmead and Lina Mariana from St. Vincent's Melbourne for human islet isolations. NR 79 TC 85 Z9 87 U1 0 U2 10 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 JUN PY 2010 VL 120 IS 6 BP 2171 EP 2183 DI 10.1172/JCI35846 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 605CH UT WOS:000278324400038 PM 20440072 ER PT J AU Siekmeier, PJ Stufflebeam, SM AF Siekmeier, Peter J. Stufflebeam, Steven M. TI Patterns of Spontaneous Magnetoencephalographic Activity in Patients With Schizophrenia SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Magnetoencephalography; Schizophrenia; Resting state networks; Oscillations; Positive symptoms; Antipsychotic agents ID SPONTANEOUS BRAIN ACTIVITY; RESTING STATE NETWORKS; SLOW-WAVE ACTIVITY; ELECTRICAL-ACTIVITY; AUDITORY HALLUCINATIONS; QUANTITATIVE EEG; ATYPICAL ANTIPSYCHOTICS; CORTICAL OSCILLATIONS; COMPUTER-SIMULATION; THETA OSCILLATIONS AB Magnetoencephalography noninvasively measures the magnetic fields produced by the brain. Pertinent research articles from 1993 to 2009 that measured spontaneous, whole-head magnetoencephalography activity in patients with schizophrenia were reviewed. Data on localization of oscillatory activity and correlation of these findings with psychotic symptoms are summarized. Although the variety of measures used by different research groups makes a quantitative meta-analysis difficult, it appears that magnetoencephalography activity in patients may exhibit identifiable patterns, defined by topographic organization and frequency band. Specifically, 11 of the 12 studies showed increased theta (4-8 Hz) and delta (1-4 Hz) band oscillations in the temporal lobes of patients; of the 10 studies that examined the relationship between oscillatory activity and symptomatology, 8 found a positive correlation between temporal lobe theta activity and positive schizophrenic symptoms. Abnormally high frontal delta activity was not seen. These findings are analyzed in comparison with the electroencephalogram literature on schizophrenics, and possible confounds (e.g., medication effects) are discussed. In the future, magnetoencephalography might be used to assist in diagnosis or might be fruitfully used in conjunction with new neuroscience research approaches such as computational modeling, which may be able to link oscillatory activity and cellular-level pathology. C1 [Siekmeier, Peter J.] McLean Hosp, Belmont, MA 02478 USA. [Siekmeier, Peter J.] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Stufflebeam, Steven M.] Harvard Univ, Massachusetts Gen Hosp, MIT, Med Sch,Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Siekmeier, PJ (reprint author), McLean Hosp, 115 Mill St,NB 310A, Belmont, MA 02478 USA. EM psiekmeier@mclean.harvard.edu FU National Institute of Health [1K08MH072771, 5K08MH067966]; NIMH Conte Center [5P50MH060450] FX This research was supported by National Institute of Health grants 1K08MH072771 and 5K08MH067966, as well as funding from NIMH Conte Center Grant 5P50MH060450. NR 118 TC 18 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JUN PY 2010 VL 27 IS 3 BP 179 EP 190 DI 10.1097/WNP.0b013e3181e0b20a PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 605UQ UT WOS:000278372900003 PM 20461010 ER PT J AU Newman-Toker, DE Rizzo, JF AF Newman-Toker, David E. Rizzo, Joseph F., III TI Subjectively quantified Maddox rod testing improves diagnostic yield over alternate cover testing alone in patients with diplopia SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Diagnosis; Diplopia; Ocular motility disorders; Physical examination; Sensitivity and specificity; Strabismus ID RELIABILITY; NERVE AB We aimed to assess the added diagnostic value of subjectively-quantified red Maddox rod testing in patients with diplopia or suspected strabismus. Over 9 months we compared measures of ocular alignment (inspection; alternate cover; Maddox rod) with final anatomic and etiologic diagnoses using clinical records in a cross-sectional study in an academic neuro-ophthalmology unit. Seventy-seven consecutive patients (98 visits) met study criteria. Mean age was 54 years (range 11-100 years). Most visits (73%) were for symptomatic diplopia and all three measures of alignment were generally available (92%). Maddox findings prompted additional diagnostic tests for 13 patients, leading to an important new diagnosis (systemic vasculitis; posterior fossa arachnoid cyst with mass effect; cavernous sinus mass) in three patients (4%). Maddox rod testing may add clinically relevant diagnostic information to that obtained by alternate cover testing alone. Its use might help prevent missed diagnoses in the evaluation of patients with diplopia or suspected strabismus. (C) 2009 Published by Elsevier Ltd. C1 [Rizzo, Joseph F., III] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Newman-Toker, David E.] Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Dept Neurol, Baltimore, MD USA. [Newman-Toker, David E.] Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Dept Ophthalmol, Baltimore, MD USA. [Newman-Toker, David E.; Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Rizzo, JF (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. EM joseph_rizzo@meei.harvard.edu FU National Institutes of Health (NIH) [RR17324-01]; Agency for Healthcare Research and Quality (AHRQ) [HS017755-01] FX Preparation of this manuscript was supported by grants from the National Institutes of Health (NIH RR17324-01) and Agency for Healthcare Research and Quality (AHRQ HS017755-01). NR 8 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JUN PY 2010 VL 17 IS 6 BP 727 EP 730 DI 10.1016/j.jocn.2009.10.002 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 601SS UT WOS:000278084900009 PM 20382534 ER PT J AU D'Amico, AV AF D'Amico, Anthony V. TI Statin Use and the Risk of Prostate-Specific Antigen Recurrence After Radiation Therapy With or Without Hormone Therapy for Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RADIOTHERAPY; CELLS; MEN; SURVIVAL; PSA; ATORVASTATIN; PROGRESSION; OUTCOMES C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 24 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2010 VL 28 IS 16 BP 2651 EP 2652 DI 10.1200/JCO.2010.28.5809 PG 2 WC Oncology SC Oncology GA 601ZV UT WOS:000278108800001 PM 20421530 ER PT J AU Krop, IE Beeram, M Modi, S Jones, SF Holden, SN Yu, W Girish, S Tibbitts, J Yi, JH Sliwkowski, MX Jacobson, F Lutzker, SG Burris, HA AF Krop, Ian E. Beeram, Muralidhar Modi, Shanu Jones, Suzanne F. Holden, Scott N. Yu, Wei Girish, Sandhya Tibbitts, Jay Yi, Joo-Hee Sliwkowski, Mark X. Jacobson, Fred Lutzker, Stuart G. Burris, Howard A. TI Phase I Study of Trastuzumab-DM1, an HER2 Antibody-Drug Conjugate, Given Every 3 Weeks to Patients With HER2-Positive Metastatic Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; MAYTANSINE; INHIBITOR; THERAPY; RESISTANCE; MECHANISM; ONCOGENE; SURVIVAL; GROWTH; CELLS AB Purpose Trastuzumab-DM1 (T-DM1) is an antibody-drug conjugate that uses trastuzumab to specifically deliver the maytansinoid antimicrotubule agent DM1 to HER2-positive cells. This first-in-human study of T-DM1 evaluated safety, pharmacokinetics, and preliminary activity of T-DM1 in patients with advanced HER2-positive breast cancer. Patients and Methods Successive cohorts of patients who had progressed on trastuzumab-based therapy received escalating doses of T-DM1. Outcomes were assessed by standard solid-tumor phase I methods. Results Twenty-four patients who had received a median of four prior chemotherapeutic agents for metastatic disease received T-DM1 at 0.3 mg/kg to 4.8 mg/kg on an every-3-weeks schedule. Transient thrombocytopenia was dose-limiting at 4.8 mg/kg; the maximum-tolerated dose (MTD) was 3.6 mg/kg. The half-life of T-DM1 at the MTD was 3.5 days, with peak DM1 levels < 10 ng/mL. Clearance at doses < 1.2 mg/kg was faster than at higher doses. Common drug-related adverse events (AEs) included grade <= 2 thrombocytopenia, elevated transaminases, fatigue, nausea, and anemia. No grade > 1 nausea, vomiting, alopecia, or neuropathy events and no cardiac effects requiring dose modification were reported. The clinical benefit rate ( objective response plus stable disease at 6 months) among 15 patients treated at the MTD was 73%, including five objective responses. The confirmed response rate in patients with measurable disease at the MTD (n = 9) was 44%. Conclusion At the MTD of 3.6 mg/kg every 3 weeks, T-DM1 was associated with mild, reversible toxicity and substantial clinical activity in a heavily pretreated population. Phase II and III trials in patients with advanced HER2-positive breast cancer are under way. J Clin Oncol 28:2698-2704. (C) 2010 by American Society of Clinical Oncology C1 [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Drug Dev, San Antonio, TX USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Sarah Cannon Res Inst, Nashville, TN USA. Genentech Inc, San Francisco, CA USA. RP Krop, IE (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 2, Boston, MA 02115 USA. EM Ian_krop@dfci.harvard.edu OI Modi, Shanu/0000-0001-6427-7373 FU Genentech, South San Francisco, CA FX Supported by Genentech, South San Francisco, CA. NR 30 TC 253 Z9 264 U1 3 U2 35 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2010 VL 28 IS 16 BP 2698 EP 2704 DI 10.1200/JCO.2009.26.2071 PG 7 WC Oncology SC Oncology GA 601ZV UT WOS:000278108800008 PM 20421541 ER PT J AU Freeman, MP Fava, M Lake, J Trivedi, MH Wisner, KL Mischoulon, D AF Freeman, Marlene P. Fava, Maurizio Lake, James Trivedi, Madhukar H. Wisner, Katherine L. Mischoulon, David TI Complementary and Alternative Medicine in Major Depressive Disorder: The American Psychiatric Association Task Force Report SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; ST-JOHNS-WORT; PLACEBO-CONTROLLED TRIAL; ADENOSYL-L-METHIONINE; SEASONAL AFFECTIVE-DISORDER; BRIGHT LIGHT THERAPY; DOUBLE-BLIND; AEROBIC EXERCISE; FISH-OIL; NONSEASONAL DEPRESSION AB Objective: To review selected complementary and alternative medicine (CAM) treatments for major depressive disorder (MDD). Participants: Authors of this report were invited participants in the American Psychiatric Association's Task Force on Complementary and Alternative Medicine. Evidence: The group reviewed the literature on individual CAM treatments for MDD, methodological considerations, and future directions for CAM in psychiatry. Individual CAM treatments were reviewed with regard to efficacy in MDD, as well as risks and benefits. Literature searches included MEDLINE and PsycINFO reviews and manual reference searches; electronic searches were limited to English-language publications from 1965 to January 2010 (but manual searches were not restricted by language). Treatments were selected for this review on the basis of (1) published randomized controlled trials in MDD and (2) widespread use with important clinical safety or public health significance relevant to psychiatric practice. An action plan is presented based on needs pertaining to CAM and psychiatry. Consensus Process: Consensus was reached by group conferences. Written iterations were drafted and sent out among group members prior to discussion, resolution of any differences of interpretation of evidence, and final approval. Conclusions: A review of randomized controlled trials for commonly used CAM treatments such as omega-3 fatty acids, St John's wort (Hypericum), folate, S-adenosyl-L-methionine (SAMe), acupuncture, light therapy exercise, and mindfulness psychotherapies revealed promising results. More rigorous and larger studies are recommended. Each CAM treatment must be evaluated separately in adequately powered controlled trials. At this time, several CAM treatments appear promising and deserve further study The greatest risk of pursuing a CAM therapy is the possible delay of other well-established treatments. Clinical, research, and educational initiatives designed to focus on CAM in psychiatry are clearly warranted due to the widespread use of CAM therapies. J an Psychiatry 2010;71(6):669-681 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Freeman, Marlene P.] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Fava, Maurizio; Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wisner, Katherine L.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Freeman, MP (reprint author), Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, Ctr Womens Mental Hlth, 185 Cambridge St,2nd Floor, Boston, MA 02114 USA. EM mfreeman@partners.org FU American Psychiatric Association FX Funding/support: The American Psychiatric Association convened the Task Force and provided peer review. NR 105 TC 52 Z9 53 U1 1 U2 12 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2010 VL 71 IS 6 BP 669 EP 681 DI 10.4088/JCP.10cs05959blu PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 612DN UT WOS:000278877100002 PM 20573326 ER PT J AU Freeman, MP Mischoulon, D Tedeschini, E Goodness, T Cohen, LS Fava, M Papakostas, GI AF Freeman, Marlene P. Mischoulon, David Tedeschini, Enrico Goodness, Tracie Cohen, Lee S. Fava, Maurizio Papakostas, George I. TI Complementary and Alternative Medicine for Major Depressive Disorder: A Meta-Analysis of Patient Characteristics, Placebo-Response Rates, and Treatment Outcomes Relative to Standard Antidepressants SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; ST-JOHNS-WORT; CLINICAL-TRIALS; UNITED-STATES; DIAGNOSTIC CRITERIA; NATIONAL-SURVEY; PROBABILITY; THERAPIES; SCALE AB Objective: To compare patient characteristics, placebo-response rates, and outcome differences in active treatment compared to placebo in randomized controlled trials (RCTs) of complementary and alternative medicine (CAM) and standard antidepressants for major depressive disorder (MDD). Data Sources: Eligible studies were first identified using searches of PubMed/MEDLINE, restricted to English, by cross-referencing the search term placebo with each of the antidepressants (those that had received letters of approval by the US, Canadian, or EU drug regulatory agencies for the treatment of MDD) and selected CAM agents. These searches were limited to articles published between January 1, 1980, and September 15, 2009 (inclusive). Reference lists from identified studies were also searched for studies eligible for inclusion. Study Selection: We selected RCTs for MDD that included validated diagnostic assessment and baseline/outcome measures of illness severity. Assessment was limited to widely used CAM agents most frequently studied in RCTs with pill placebo: St John's wort, omega-3 fatty acids, and S-adenosyl-L-methionine (SAMe). Data Synthesis: Of eligible publications, 173 reported results of 1 trial, and 5 included > 1 trial, representing a total of 185 RCTs. Patient variables, including illness severity, were similar across CAM and antidepressant RCTs, except for a higher proportion of women in CAM studies (P=.0003). Random-effects meta-analysis indicated that both antidepressant and CAM monotherapy resulted in superior response rates compared with placebo. Placebo-response rates were significantly lower for patients enrolled in CAM versus antidepressant RCTs (P=.002). Meta-regression analyses yielded no significant differences in the relative risk of prematurely discontinuing therapy due to any reason between active treatment and placebo for antidepressant and CAM RCTs, although discontinuation due to adverse events was higher in antidepressant RCTs compared to CAM RCTs (P=.007). Conclusions: Participants in CAM trials were more likely to be female and to have a lower placebo-response rate compared to those in standard antidepressant trials for MDD. Trials of standard antidepressants and CAM therapies were composed of patients with similar depression severity. J Clin Psychiatry 2010;71(6):682-688 Copyright (C) 2010 Physicians Postgraduate Press, Inc. C1 [Freeman, Marlene P.; Cohen, Lee S.] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. [Mischoulon, David; Tedeschini, Enrico; Goodness, Tracie; Fava, Maurizio; Papakostas, George I.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Freeman, Marlene P.; Mischoulon, David; Cohen, Lee S.; Fava, Maurizio; Papakostas, George I.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Freeman, MP (reprint author), Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, 185 Cambridge St,2nd Floor, Boston, MA 02114 USA. EM mfreeman@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Forest; Eli Lilly; GlaxoSmithKline FX Potential conflicts of interest: Dr Freeman has received research support from Forest, Eli Lilly, and GlaxoSmithKline; has been a consultant for and received honoraria for a CME program from PamLab; and has received a stipend for medical editing from DSM Nutritionals. NR 33 TC 24 Z9 24 U1 4 U2 14 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 JUN PY 2010 VL 71 IS 6 BP 682 EP 688 DI 10.4088/JCP.10r05976blu PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 612DN UT WOS:000278877100003 PM 20573327 ER PT J AU Warden, D Trivedi, MH Wisniewski, SR Kurian, B Zisook, S Kornstein, SG Friedman, ES Miyahara, S Leuchter, AF Fava, M Rush, AJ AF Warden, Diane Trivedi, Madhukar H. Wisniewski, Stephen R. Kurian, Benji Zisook, Sidney Kornstein, Susan G. Friedman, Edward S. Miyahara, Sachiko Leuchter, Andrew F. Fava, Maurizio Rush, A. John TI Early Adverse Events and Attrition in Selective Serotonin Reuptake Inhibitor Treatment A Suicide Assessment Methodology Study Report SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE attrition; adherence; adverse events; antidepressant; depression ID MAJOR DEPRESSIVE DISORDER; MEASUREMENT-BASED CARE; STAR-ASTERISK-D; REPORT QIDS-SR; ANTIDEPRESSANT MEDICATION; PSYCHOMETRIC EVALUATION; CLINICAL-PRACTICE; QUICK INVENTORY; SMOOTH-MUSCLE; METAANALYSIS AB Adverse events during selective serotonin reuptake inhibitor (SSRI) treatment are frequent and may lead to premature treatment discontinuation. If attrition is associated with early worsening of adverse effects or the frequency, intensity, or burden of adverse effects, interventions to maximize retention could be focused on patients with these events. Outpatient participants (n = 265) with nonpsychotic major depressive disorder entered an 8-week trial with an SSRI. At baseline and week 2, specific adverse effects were evaluated with the Systematic Assessment for Treatment Emergent Events-Systematic Inquiry, and at week 2, the Frequency, Intensity, and Burden of Side Effects Rating globally assessed adverse effects. Attrition was defined by those participants who left treatment after week 2 but before week 8. No specific week 2 adverse effect, either treatment-emergent or with worsening intensity, was independently associated with attrition. Global ratings of adverse effect frequency, intensity, or burden at week 2 were also not associated with subsequent attrition. Neither global ratings nor specific adverse effects at week 2 were related to patient attrition during SSRI treatment. Other factors seem to contribute to patient decisions about continuing with treatment. C1 [Warden, Diane; Trivedi, Madhukar H.; Kurian, Benji] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wisniewski, Stephen R.; Miyahara, Sachiko] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, San Diego VA Med Ctr, San Diego, CA 92103 USA. [Kornstein, Susan G.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Friedman, Edward S.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Leuchter, Andrew F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. [Rush, A. John] Duke Natl Univ Singapore, Singapore, Singapore. RP Warden, D (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Diane.Warden@UTSouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU National Institute of Mental Health [N01MH90003]; National Alliance for Research on Schizophrenia and Depression; Agency for Healthcare Research and Quality; Corcept Therapeutics, Inc; Cyberonics, Inc; National Alliance for Research in Schizophrenia and Depression; National Institute on Drug Abuse; Novartis; Pharmacia Upjohn; Predix Pharmaceuticals; Solvay Pharmaceuticals, Inc; Targacept, Inc.; Aspect Medical Systems; Pam Lab; Eli Lilly Company; Forest Laboratories; Boehringer-Ingelheim; Pfizer; Takeda; Sanofi-Aventis; Wyeth-Ayerst Laboratories; Northstar; National Center for Complementary and Alternative Medicine; Merck Co; Vivometrics; MedAvante; Abbott Laboratories; Alkermes; AstraZeneca BioResearch; BrainCells, Inc; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions; Forest Pharmaceuticals Inc; Ganeden; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; Organon Inc; Pharmavite; Roche; Synthelabo FX This project was funded by the National Institute of Mental Health under Contract N01MH90003 to University of Texas Southwestern Medical Center at Dallas (principal investigator: Dr Trivedi). This analysis was also supported in part by a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (Dr Warden).; Dr Trivedi has been a consultant/speaker for Abbott Laboratories, Inc; Abdi Ibrahim; Akzo (Organon Pharmaceuticals Inc); AstraZeneca; Bristol-Myers Squibb Company; Cephalon, Inc; Evotek; Fabre-Kramer Pharmaceuticals, Inc Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products, LP; Johnson & Johnson PRD; Eli Lilly & Company; Meade Johnson; Medtronic; Neuronetics; Otsuka Pharmaceuticals; Parke Davis Pharmaceuticals, Inc; Pfizer, Inc; Sepracor; SHIRE Development; VantagePoint; and Wyeth-Ayerst Laboratories. He has also received grant support from the Agency for Healthcare Research and Quality; Corcept Therapeutics, Inc; Cyberonics, Inc; Merck; National Alliance for Research in Schizophrenia and Depression; National Institute of Mental Health; National Institute on Drug Abuse; Novartis; Pharmacia & Upjohn; Predix Pharmaceuticals; Solvay Pharmaceuticals, Inc; and Targacept.; Dr Wisniewski has been a consultant for Cyberonics, Inc (2005-2009), ImaRx Therapeutics, Inc (2006); Bristol-Myers Squibb Company (2007-2008); Organon (2007); Case-Western University (2007); and Singapore Clinical Research Institute (2009).; Dr Kurian has received research support from Targacept, Inc.; Dr Zisook has received grant support from NIMH, Aspect Medical Systems, and Pam Lab. He has received honoraria for speaking from GlaxoSmithKline and AstraZeneca.; Dr Kornstein has received grants/research from the National Institute of Mental Health, Bristol-Myers Squibb, Eli Lilly & Company, Forest Laboratories, Wyeth, Novartis, Boehringer-Ingelheim, Pfizer, and Takeda. She has served on advisory boards for Wyeth, Pfizer, Eli Lilly & Company, Bristol-Myers Squibb, Endo, Takeda, and Forest Laboratories and has received book royalties from Guilford Press.; Dr Friedman has served as a consultant for Pfizer Inc; Cephalon, ApotheCom Associates; Medical Consulting Referral Inc; Innovative Solutions & Services, Inc; Primary Insight/Bear Stearns; and Medscape. He has received research support from Pfizer, Sanofi-Aventis, Wyeth-Ayerst Laboratories, Northstar, Novartis, and Cyberonics. He has served as a speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co, GlaxoSmithKline, Pfizer, Wyeth-Ayerst, and the Neuroscience Education Institute.; Dr Miyahara has no disclosures to report.; Dr Leuchter has provided scientific consultation or served on advisory boards for Aspect Medical Systems, Eli Lilly and Company, Novartis Pharmaceuticals, MEDACorp, AstraZeneca, Takeda Pharmaceuticals, and Merck & Co. He has served on a speaker's bureau for Eli Lilly and Company and Wyeth-Ayerst Pharmaceuticals. He has received research/grant support from the National Institute of Mental Health, the National Center for Complementary and Alternative Medicine, Aspect Medical Systems, Eli Lilly and Company, Novartis Pharmaceuticals, Wyeth-Ayerst Pharmaceuticals, Merck & Co, Pfizer, Vivometrics, and MedAvante. He is also a minor shareholder in Aspect Medical Systems.; Dr Fava has received research support from Abbott Laboratories; Alkermes; Aspect Medical Systems; AstraZeneca BioResearch; BrainCells, Inc; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions; Forest Pharmaceuticals Inc; Ganeden; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Eli Lilly & Company; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Organon Inc; PamLab, LLC; Pfizer Inc; Pharmavite; Roche; Sanofi-Aventis; Solvay Pharmaceuticals, Inc; Synthelabo; and Wyeth-Ayerst Laboratories. He has provided advisory/consulting services to Abbott Laboratories; Amarin; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc; BioMarin Pharmaceuticals, Inc; Biovail Pharmaceuticals, Inc; BrainCells, Inc; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions, LLC; CNS Response; Compellis; Cypress Pharmaceuticals; Dov Pharmaceuticals; Eisai, Inc; EPIX Pharmaceuticals; Euthymics Bioscience, Inc; Fabre-Kramer Pharmaceuticals, Inc; Forest Pharmaceuticals Inc; GlaxoSmithKline; Grunenthal GmBH; J & J Pharmaceuticals; Janssen Pharmaceutica; Jazz Pharmaceuticals; Knoll Pharmaceutical Company; Labopharm; Eli Lilly & Company; Lorex Pharmaceuticals; Lundbeck; MedAvante, Inc; Merck; Methylation Sciences; Neuronetics; Novartis; Nutrition 21; Organon Inc; PamLab, LLC; Pfizer Inc; PharmaStar; Pharmavite; Precision Human Biolaboratory; Psychogenics; Psylin Neurosciences, Inc; Ridge Diagnostics, Inc; Roche; Sanofi-Aventis; Schering Plough; Sepracor; Solvay Pharmaceuticals, Inc; Somaxon; Somerset Pharmaceuticals; Synthelabo; Takeda; Tetragenex; TransForm Pharmaceuticals, Inc; Transcept Pharmaceuticals; Vanda Pharmaceuticals Inc; and Wyeth-Ayerst Laboratories. He has been on speaking bureaus for Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir; Boehringer-Ingelheim; Bristol-Myers Squibb Company; Cephalon; Forest Pharmaceuticals Inc; GlaxoSmithKline; Imedex; Eli Lilly & Company; Novartis; Organon Inc; Pfizer Inc; PharmaStar; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed-Elsevier; UBC; and Wyeth-Ayerst Laboratories. Dr Fava has equity holdings (excluding mutual funds/blinded trusts) with Compellis, patent applications for SPCD and for a combination of azapirones and bupropion in major depressive disorder, and copyright royalties for the MGH CPFQ, SFI, ATRQ, DESS, and SAFER. NR 47 TC 10 Z9 13 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2010 VL 30 IS 3 BP 259 EP 266 DI 10.1097/JCP.0b013e3181dbfd04 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 596JF UT WOS:000277680400007 PM 20473060 ER PT J AU Adler, I Batton, D Betz, B Bezinque, S Ecklund, K Junewick, J McCauley, R Miller, C Seibert, J Specter, B Westra, S Leviton, A AF Adler, Ira Batton, Dan Betz, Bradford Bezinque, Steven Ecklund, Kirsten Junewick, Joseph McCauley, Roy Miller, Cindy Seibert, Joanna Specter, Barbara Westra, Sjirk Leviton, Alan TI Mechanisms of Injury to White Matter Adjacent to a Large Intraventricular Hemorrhage in the Preterm Brain SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Review DE brain; preterm newborn; hemorrhage; white matter damage ID EXPERIMENTAL INTRACEREBRAL HEMORRHAGE; NEONATAL-RATS; PERIVENTRICULAR LEUKOMALACIA; MAGNETIC-RESONANCE; MOUSE-BRAIN; DAMAGE; INFANTS; EXPRESSION; THROMBIN; HYDROCEPHALUS AB The purpose of this article is to investigate the hyperechoic lesion seen adjacent to a lateral ventricle that contains blood but is not distended. The literature on ependymal barrier dysfunction was reviewed in search of mechanisms of injury to the white matter adjacent to an intraventricular hemorrhage. The clinical literature on the clinical diagnosis of periventricular hemorrhagic infarction was also reviewed to find out how frequently this diagnosis was made. Support was found for the possibility that the ventricular wall does not always function as an efficient barrier, allowing ventricular contents to gain access to the white matter where they cause damage. Hemorrhagic infarction may not be the only or the most frequent mechanism of white matter damage adjacent to a large intraventricular hemorrhage. (C) 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:254-258, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jcu.20683 C1 [Leviton, Alan] Childrens Hosp Boston, Dept Neurol, Boston, MA 02215 USA. [Batton, Dan] So Illinois Univ, Dept Pediat, Carol Jo Vecchie Women & Childrens Ctr, Springfield, IL 62701 USA. [Betz, Bradford; Bezinque, Steven; Junewick, Joseph] Helen DeVos Childrens Hosp, Dept Radiol, Grand Rapids, MI 49503 USA. [Ecklund, Kirsten] Childrens Hosp Boston, Dept Radiol, Boston, MA 02115 USA. [McCauley, Roy] Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA 02111 USA. [Miller, Cindy] Yale New Haven Childrens Hosp, Dept Radiol, New Haven, CT 06520 USA. [Seibert, Joanna] Arkansas Childrens Hosp, Dept Radiol, Little Rock, AR 72202 USA. [Specter, Barbara] Baptist Med Ctr, Dept Radiol, Winston Salem, NC 27157 USA. [Westra, Sjirk] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Leviton, A (reprint author), Childrens Hosp Boston, Dept Neurol, Boston, MA 02215 USA. FU National Institute of Neurologic Disorders and Stroke [1 U01 NS 40069-01A2]; National Institute of Child Health and Human Development [NTH-P30-HD-18655] FX This work was funded by a cooperative agreement with the National Institute of Neurologic Disorders and Stroke (1 U01 NS 40069-01A2) and a program project grant from the National Institute of Child Health and Human Development (NTH-P30-HD-18655). NR 45 TC 8 Z9 9 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD JUN PY 2010 VL 38 IS 5 BP 254 EP 258 DI 10.1002/jcu.20683 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 599DV UT WOS:000277891300006 PM 20232402 ER PT J AU Valdiserri, RO Nazi, K McInnes, DK Ross, D Kinsinger, L AF Valdiserri, Ronald O. Nazi, Kim McInnes, D. Keith Ross, David Kinsinger, Linda TI Need to Improve Routine HIV Testing of US Veterans in Care: Results of an Internet Survey SO JOURNAL OF COMMUNITY HEALTH LA English DT Article ID UNITED-STATES; ANTIRETROVIRAL THERAPY; COST-EFFECTIVENESS; INFECTION; PREVALENCE; DIAGNOSIS; CENTERS; LESSONS; VIRUS; ERA AB Late diagnosis of HIV infection contributes to poor medical outcomes and helps sustain continued transmission of virus. Published evidence suggests that despite current public health recommendations, patients receiving care in the Veterans Health Administration (VHA) system are not being routinely tested for HIV infection. Using a sample of computer-literate veterans, we conducted a survey of recent testing experiences. My HealtheVet (MHV) is a secure website allowing registered Veterans to access limited personal VHA health information. Using the American Customer Satisfaction Index (ACSI) Survey, an electronic questionnaire on "health screening" was conducted in late Fall/early winter 2008-2009. A random sample (4%) of MHV users were surveyed; approximately 17% completed the survey and responses ranged from 31,237 to 33,074. Only 9% of the respondents indicated that they had been offered a test for HIV in the last 12 months compared to 83% who had been offered cholesterol screening, 65% blood sugar screening and 19% who had been offered testing for Hepatitis C virus (HCV). Of those who had been offered HIV testing, 91% indicated that they'd had the test performed. Of note, the percentage of respondents who indicated that they would "very likely" accept a test, if offered, was similar for HIV (73%), HCV (79%), cholesterol (75%), and blood sugar (75%). Although these results cannot be generalized to all Veterans in care, they suggest that routine testing for HIV has not been taking place and support recent VHA policy changes to remove barriers to HIV testing. C1 [Valdiserri, Ronald O.; Ross, David] US Dept Vet Affairs, Publ Hlth Strateg Hlth Care Grp 13B, Off Publ Hlth & Environm Hazards, Washington, DC 20420 USA. [Nazi, Kim] US Dept Vet Affairs, Vet & Consumers Hlth Informat Off, Washington, DC 20420 USA. [McInnes, D. Keith] US Dept Vet Affairs, Ctr Hlth Qual Outcomes & Econ Res, Washington, DC 20420 USA. [Kinsinger, Linda] US Dept Vet Affairs, Natl Ctr Hlth Promot & Dis Prevent, Washington, DC 20420 USA. RP Valdiserri, RO (reprint author), US Dept Vet Affairs, Publ Hlth Strateg Hlth Care Grp 13B, Off Publ Hlth & Environm Hazards, 810 Vermont Ave NW, Washington, DC 20420 USA. EM R.Valdiserri@va.gov NR 31 TC 8 Z9 8 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD JUN PY 2010 VL 35 IS 3 BP 215 EP 219 DI 10.1007/s10900-010-9233-x PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 586DA UT WOS:000276880600001 PM 20146092 ER PT J AU Kullgren, JT McLaughlin, CG AF Kullgren, Jeffrey T. McLaughlin, Catherine G. TI Beyond Affordability: The Impact of Nonfinancial Barriers on Access for Uninsured Adults in Three Diverse Communities SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE Uninsured; Access to care; Nonfinancial barriers; Health reform ID HEALTH-INSURANCE; MEDICAL-CARE; UNITED-STATES; SERVICES; SATISFACTION; DEFINITION AB Most proposals to improve access for uninsured adults focus on removing financial barriers to health care. Health services researchers have long recognized, however, that access to care is a multidimensional concept consisting of both financial and nonfinancial dimensions. While financial barriers faced by those without health insurance have been well-documented, it is not known to what degree nonfinancial barriers limit access for those without coverage. In this study we sought to identify the types and frequencies of nonfinancial access barriers faced by low-income uninsured adults, as well as determine how frequently nonfinancial barriers coexist with financial access barriers in this population. We conducted a telephone survey of 1,118 low-income uninsured adults in Alameda, California, Austin, Texas, and Southern Maine who had enrolled in local access programs funded through the Robert Wood Johnson Foundation's Communities in Charge initiative. Financial barriers were the most often cited barrier to access in each of the three groups, though nonfinancial barriers were often cited as well. Across all three populations, one-third to one-half of respondents with financial access barriers also cited one or more nonfinancial barriers as contributing to their problems accessing health care. Our results suggest that many uninsured adults face nonfinancial health care barriers in addition to their well-documented financial challenges. Health reform efforts must address both types of barriers in order to maximally improve access for the uninsured population. C1 [Kullgren, Jeffrey T.] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Kullgren, Jeffrey T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kullgren, Jeffrey T.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [McLaughlin, Catherine G.] Math Policy Res Inc, Ann Arbor, MI USA. [McLaughlin, Catherine G.] Univ Michigan, Dept Hlth Management & Policy, Ann Arbor, MI 48104 USA. [Kullgren, Jeffrey T.] Brigham & Womens Hosp, Residency Program Primary Care & Populat Hlth Har, Boston, MA 02115 USA. [Kullgren, Jeffrey T.] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. RP Kullgren, JT (reprint author), Univ Penn, Robert Wood Johnson Clin Scholars Program, 1303A Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kullgren@mail.med.upenn.edu NR 30 TC 10 Z9 11 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD JUN PY 2010 VL 35 IS 3 BP 240 EP 248 DI 10.1007/s10900-010-9230-0 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 586DA UT WOS:000276880600005 PM 20127505 ER PT J AU Contini, M Lin, B Kobayashi, K Okano, H Masland, RH Raviola, E AF Contini, Massimo Lin, Bin Kobayashi, Kazuto Okano, Hideyuki Masland, Richard H. Raviola, Elio TI Synaptic Input of ON-Bipolar Cells onto the Dopaminergic Neurons of the Mouse Retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE transgenic mice; immunocytochemistry; electron microscopy; GFP; PLAP; amacrine cells ID IMMUNOREACTIVE AMACRINE CELLS; RHESUS-MONKEY RETINA; TYROSINE-HYDROXYLASE; GANGLION-CELLS; RABBIT RETINA; RAT RETINA; CAT RETINA; IMMUNOAFFINITY CHROMATOGRAPHY; EXTRASYNAPTIC RELEASE; INTERPLEXIFORM CELLS AB In the retina, dopamine fulfills a crucial role in neural adaptation to photopic illumination, but the pathway that carries cone signals to the dopaminergic amacrine (DA) cells was controversial. We identified the site of ON-cone bipolar input onto DA cells in transgenic mice in which both types of catecholaminergic amacrine (CA) cells were labeled with green fluorescent protein or human placental alkaline phosphatase (PLAP). In confocal Z series of retinal whole mounts stained with antibodies to tyrosine hydroxylase (TH), DA cells gave rise to varicose processes that descended obliquely through the scleral half of the inner plexiform layer (IPL) and formed a loose, tangential plexus in the middle of this layer. Comparison with the distribution of the dendrites of type 2 CA cells and examination of neurobiotin-injected DA cells proved that their vitreal processes were situated in stratum S3 of the IPL. Electron microscope demonstration of PLAP activity showed that bipolar cell endings in S3 established ribbon synapses onto a postsynaptic dyad in which one or both processes were labeled by a precipitate of lead phosphate and therefore belonged to DA cells. In places, the postsynaptic DA cell processes returned a reciprocal synapse onto the bipolar endings. Confocal images of sections stained with antibodies to TH, kinesin Kif3a, which labels synaptic ribbons, and glutamate or GABA(A) receptors, confirmed that ribbon-containing endings made glutamatergic synapses onto DA cells processes in S3 and received from them GABAergic synapses. The presynaptic ON-bipolar cells most likely belonged to the CB3 (type 5) variety. J. Comp. Neurol. 518:2035-2050, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Contini, Massimo; Raviola, Elio] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Lin, Bin; Masland, Richard H.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Kobayashi, Kazuto] Fukushima Med Univ, Sch Med, Dept Mol Genet, Fukushima 9601295, Japan. [Okano, Hideyuki] Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan. RP Raviola, E (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. EM elio_raviola@hms.harvard.edu RI Hidokano, Hideyuki/J-5973-2013 FU National Institutes of Health [EY01344, EY017169] FX Grant sponsor: National Institutes of Health; Grant numbers: EY01344, EY017169; R.H.M. is a Senior Investigator of Research to Prevent Blindness. NR 58 TC 26 Z9 26 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 1 PY 2010 VL 518 IS 11 BP 2035 EP 2050 DI 10.1002/cne.22320 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 591ID UT WOS:000277292700010 PM 20394057 ER PT J AU Siqueira, WL Margolis, HC Helmerhorst, EJ Mendes, FM Oppenheim, FG AF Siqueira, W. L. Margolis, H. C. Helmerhorst, E. J. Mendes, F. M. Oppenheim, F. G. TI Evidence of Intact Histatins in the in vivo Acquired Enamel Pellicle SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE histatin; proteomics; enamel pellicle; demineralization; saliva ID HISTIDINE-RICH POLYPEPTIDE; HUMAN-PAROTID SECRETION; MASS-SPECTROMETRY; CANDIDA-ALBICANS; PROTEINS; DEMINERALIZATION; HYDROXYAPATITE; IDENTIFICATION; ADSORPTION; PROTEOME AB Understanding the composition and function of the acquired enamel pellicle (AEP) has been a major goal in oral biology. The aim of this study was to test the hypothesis that intact histatins are part of the in vivo AEP and that histatins after adsorption to HA have effects on in vitro enamel demineralization. This is the first study demonstrating the presence of intact histatins in vivo in the AEP. The in vitro experiments show that all naturally occurring histatins in the AEP have the potential to provide some level of protection against acid injury. C1 [Helmerhorst, E. J.; Oppenheim, F. G.] Boston Univ, Henry M Goldman Sch Dent Med, Dept Periodontol & Oral Biol, CABR, Boston, MA 02118 USA. [Siqueira, W. L.] Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON, Canada. [Margolis, H. C.] Forsyth Inst, Dept Biomineralizat, Boston, MA USA. [Mendes, F. M.] Univ Sao Paulo, Fac Dent, Dept Pediat Dent, BR-05508 Sao Paulo, Brazil. RP Oppenheim, FG (reprint author), Boston Univ, Henry M Goldman Sch Dent Med, Dept Periodontol & Oral Biol, CABR, 700 Albany St,Suite W-201, Boston, MA 02118 USA. EM fropp@bu.edu RI Mendes, Fausto/E-7067-2010; OI Mendes, Fausto/0000-0003-1711-4103; Helmerhorst, Eva/0000-0002-4803-3018 FU NIH/NIDCR [DE05672, DE07652, DE15163, DE17788, DE18132] FX This study is supported by NIH/NIDCR Grants DE05672, DE07652, DE15163, DE17788, and DE18132. NR 20 TC 26 Z9 26 U1 0 U2 6 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 JUN PY 2010 VL 89 IS 6 BP 626 EP 630 DI 10.1177/0022034510363384 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 596ND UT WOS:000277691000013 PM 20351356 ER PT J AU Kitada, M Zhang, ZY Mima, A King, GL AF Kitada, Munehiro Zhang, Zhaoyun Mima, Akira King, George L. TI Molecular mechanisms of diabetic vascular complications SO JOURNAL OF DIABETES INVESTIGATION LA English DT Review DE Diabetic complications; Diabetes mellitus; Endogenous protective factors ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; GLYCATION END-PRODUCTS; SMOOTH-MUSCLE-CELLS; FACTOR-KAPPA-B; ALDOSE REDUCTASE INHIBITION; NERVE CONDUCTION-VELOCITY; INDUCED OXIDATIVE STRESS; ALTERED GENE-EXPRESSION; PKC-BETA INHIBITOR AB Diabetic complications are the major causes of morbidity and mortality in patients with diabetes. Microvascular complications include retinopathy, nephropathy and neuropathy, which are leading causes of blindness, end-stage renal disease and various painful neuropathies; whereas macrovascular complications involve atherosclerosis related diseases, such as coronary artery disease, peripheral vascular disease and stroke. Diabetic complications are the result of interactions among systemic metabolic changes, such as hyperglycemia, local tissue responses to toxic metabolites from glucose metabolism, and genetic and epigenetic modulators. Chronic hyperglycemia is recognized as a major initiator of diabetic complications. Multiple molecular mechanisms have been proposed to mediate hyperglycemia's adverse effects on vascular tissues. These include increased polyol pathway, activation of the diacylglycerol/protein kinase C pathway, increased oxidative stress, overproduction and action of advanced glycation end products, and increased hexosamine pathway. In addition, the alterations of signal transduction pathways induced by hyperglycemia or toxic metabolites can also lead to cellular dysfunctions and damage vascular tissues by altering gene expression and protein function. Less studied than the toxic mechanisms, hyperglycemia might also inhibit the endogenous vascular protective factors such as insulin, vascular endothelial growth factor, platelet-derived growth factor and activated protein C, which play important roles in maintaining vascular homeostasis. Thus, effective therapies for diabetic complications need to inhibit mechanisms induced by hyperglycemia's toxic effects and also enhance the endogenous protective factors. The present review summarizes these multiple biochemical pathways activated by hyperglycemia and the potential therapeutic interventions that might prevent diabetic complications. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00018.x, 2010) C1 [Kitada, Munehiro; Zhang, Zhaoyun; Mima, Akira; King, George L.] Joslin Diabet Ctr, Dianne Nunnally Hoppes Lab Diabet Complicat, Boston, MA 02215 USA. RP King, GL (reprint author), Joslin Diabet Ctr, Dianne Nunnally Hoppes Lab Diabet Complicat, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu FU National Institutes of Health [5 R01 DK053105, R01 EY016150]; American Diabetes Association [1-08-RA-93]; Joslin Diabetes Center DERC [P30 DK036836] FX Dr King is supported by National Institutes of Health grants 5 R01 DK053105, R01 EY016150, American Diabetes Association 1-08-RA-93 and by Joslin Diabetes Center DERC P30 DK036836. None of the authors have any financial support or relationships that might pose a conflict of interest. NR 171 TC 33 Z9 34 U1 3 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2040-1116 J9 J DIABETES INVEST JI J. Diabetes Investig. PD JUN PY 2010 VL 1 IS 3 BP 77 EP 89 DI 10.1111/j.2040-1124.2010.00018.x PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 755DG UT WOS:000289906300001 PM 24843412 ER PT J AU Salanitro, A Safford, M Ovalle, F Curry, W Williams, JH Kim, Y Estrada, C Foster, PP Houston, T Allison, J AF Salanitro, Amanda Safford, Monika Ovalle, Fernando Curry, William Williams, Jessica Hillman Kim, Yongin Estrada, Carlos Foster, Pamela Payne Houston, Thomas Allison, Jeroan TI A CLUSTER-RANDOMIZED TRIAL OF A WEB-BASED PHYSICIAN INTERVENTION TO IMPROVE DIABETES CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Salanitro, Amanda] Birmingham VA Med Ctr, Birmingham, AL USA. [Safford, Monika; Ovalle, Fernando; Curry, William; Williams, Jessica Hillman; Kim, Yongin; Estrada, Carlos] Univ Alabama, Birmingham, AL USA. [Foster, Pamela Payne] Univ Alabama, Tuscaloosa, AL USA. [Houston, Thomas; Allison, Jeroan] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. RI Houston, Thomas/F-2469-2013 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 JUN PY 2010 VL 25 SU 3 BP 206 EP 206 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300005 ER PT J AU Steinman, M Goldstein, M AF Steinman, Michael Goldstein, Mary TI A NEW APPROACH TO PERFORMANCE MEASUREMENT FOR HYPERTENSION: PRELIMINARY RESULTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Steinman, Michael] UCSF, San Francisco VAMC, San Francisco, CA USA. [Goldstein, Mary] CHCE, VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 211 EP 211 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300015 ER PT J AU Lasser, K Valley-Shah, L Lisboa, S Casimir, N Murillo, J Emmons, K Ayanian, J Fletcher, R AF Lasser, Karen Valley-Shah, Lisa Lisboa, Sandra Casimir, Naomie Murillo, Jennifer Emmons, Karen Ayanian, John Fletcher, Robert TI A RANDOMIZED CONTROLLED TRIAL OF PATIENT NAVIGATION TO PROMOTE COLORECTAL CANCER SCREENING IN COMMUNITY HEALTH CENTERS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Lasser, Karen] Boston Univ, Sch Med, Chestnut Hill, MA USA. [Valley-Shah, Lisa] Cambridge Hlth Alliance, Cambridge, MA USA. [Lisboa, Sandra] Cambridge Hlth Alliance, Everett, MA USA. [Casimir, Naomie] Cambridge Hlth Alliance, Mattapan, MA USA. [Murillo, Jennifer] Cambridge Hlth Alliance, W Roxbury, MA USA. [Emmons, Karen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ayanian, John] Harvard Med Sch, Boston, MA USA. [Fletcher, Robert] Harvard Med Sch, Chapel Hill, NC USA. NR 0 TC 1 Z9 1 U1 0 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 JUN PY 2010 VL 25 SU 3 BP 213 EP 213 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300020 ER PT J AU Moskowitz, D Smith, CS Zia, J Wipf, J AF Moskowitz, David Smith, C. Scott Zia, Jasmine Wipf, Joyce TI A STRUCTURED MENTORSHIP PROGRAM INCREASES RESIDENTS' SATISFACTION WITH MENTORING: A TWO-YEAR COHORT STUDY AT A MULTI-HOSPITAL INTERNAL MEDICINE RESIDENCY PROGRAM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Moskowitz, David] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Smith, C. Scott] Boise VA Med Ctr, Boise, ID USA. [Wipf, Joyce] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 214 EP 215 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300024 ER PT J AU Chen, GQ Moran, W Egede, L Jia, HG Yu, HJ AF Chen, Guoqing Moran, William Egede, Leonard Jia, Huanguang Yu, Hong-Jen TI ADHERENCE TO GUIDELINE-RECOMMENDED CARE FOR VETERANS WITH CHRONIC KIDNEY DISEASE IN VA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Chen, Guoqing] Baylor Coll Med, Houston, TX 77030 USA. [Chen, Guoqing; Yu, Hong-Jen] VA Houston HSR&D Ctr Excellence, Houston, TX USA. [Moran, William; Egede, Leonard] Med Univ S Carolina, Charleston, SC 29425 USA. [Egede, Leonard] Ralph H Johnson VAMC, Charleston, SC USA. [Jia, Huanguang] RORC, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 219 EP 220 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300034 ER PT J AU Salanitro, A Agee, B Burczyk-Brown, J Funkhouser, E Muntner, P Crenshaw, K Horton, T Halanych, J Richman, J Kaffka, J Safford, M AF Salanitro, Amanda Agee, Bonita Burczyk-Brown, Jennifer Funkhouser, Ellen Muntner, Paul Crenshaw, Katie Horton, Trudi Halanych, Jewell Richman, Joshua Kaffka, Jaimee Safford, Monika TI APPROPRIATE INACTION AND CLINICAL INERTIA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Salanitro, Amanda] Birmingham VA Med Ctr, Birmingham, AL USA. [Agee, Bonita; Burczyk-Brown, Jennifer; Funkhouser, Ellen] C SMART, Birmingham VA Med Ctr, Birmingham, AL USA. [Muntner, Paul] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Crenshaw, Katie; Horton, Trudi] Univ Alabama, Div Continuing Med Educ, Birmingham, AL USA. [Halanych, Jewell; Richman, Joshua; Kaffka, Jaimee] Univ Alabama, Div Prevent Med, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 223 EP 224 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300043 ER PT J AU Green, A Eamranond, PP Mehta, D Renfrew, M Cervantes, M Betancourt, J AF Green, Alexander Eamranond, Pracha Peter Mehta, Darshan Renfrew, Megan Cervantes, Marina Betancourt, Joseph TI ASSESSING MEDICAL STUDENTS' PREPAREDNESS AND SKILLS TO PROVIDE CROSS-CULTURAL CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Green, Alexander; Renfrew, Megan; Cervantes, Marina; Betancourt, Joseph] Massachusetts Gen Hosp, Dispar Solut Ctr, James J Mongan MD Inst Hlth Policy, Boston, MA USA. [Eamranond, Pracha Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mehta, Darshan] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 226 EP 227 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300049 ER PT J AU Schnipper, J Liang, C Carty, M Gandhi, T Hamann, C Karson, A Bhan, I Turchin, A AF Schnipper, Jeffrey Liang, Catherine Carty, Marcy Gandhi, Tejal Hamann, Claus Karson, Andrew Bhan, Ishir Turchin, Alexander TI ASSESSMENT OF IMPROVEMENTS TO IT-BASED MEDICATION RECONCILIATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Schnipper, Jeffrey; Liang, Catherine; Carty, Marcy; Gandhi, Tejal] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hamann, Claus; Karson, Andrew; Bhan, Ishir] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Turchin, Alexander] Partners Healthcare Syst, Wellesley, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 227 EP 228 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300051 ER PT J AU Seal, K McCaslin, S McCamish, N Ren, L Abadjian, L Burt, M Daley, A AF Seal, Karen McCaslin, Shannon McCamish, Nicole Ren, Li Abadjian, Linda Burt, Michelle Daley, Aaron TI CAN MOTIVATIONAL INTERVIEWING ENHANCE MENTAL HEALTH TREATMENT ENGAGEMENT IN IRAQ AND AFGHANISTAN VETERANS: PRELIMINARY RESULTS FROM A RANDOMIZED CONTROLLED TRIAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Seal, Karen] Univ Calif San Francisco, San Francisco, CA 94143 USA. [McCaslin, Shannon; McCamish, Nicole; Ren, Li; Abadjian, Linda; Burt, Michelle; Daley, Aaron] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 235 EP 236 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300070 ER PT J AU Bitton, A Zaslavsky, A Ayanian, J Rigotti, N AF Bitton, Asaf Zaslavsky, Alan Ayanian, John Rigotti, Nancy TI CHANGES IN ADDRESSING TOBACCO USE BY US PHYSICIANS AT AMBULATORY VISITS, 2005-2007 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Bitton, Asaf] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zaslavsky, Alan; Ayanian, John] Harvard Univ, Sch Med, Boston, MA USA. [Rigotti, Nancy] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 236 EP 236 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300072 ER PT J AU Linder, J Schneider, L Brawarsky, P Schnipper, J Middleton, B Haas, J Rigotti, N Kelley, J AF Linder, Jeffrey Schneider, Louise Brawarsky, Phyllis Schnipper, Jeffrey Middleton, Blackford Haas, Jennifer Rigotti, Nancy Kelley, Jennifer TI CLINICIAN CHARACTERISTICS AND UPTAKE OF NOVEL ELECTRONIC HEALTH RECORD FUNCTIONALITY IN PRIMARY CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Linder, Jeffrey; Schneider, Louise; Brawarsky, Phyllis; Schnipper, Jeffrey; Middleton, Blackford; Haas, Jennifer] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rigotti, Nancy; Kelley, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 240 EP 240 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300080 ER PT J AU Laiteerapong, N Karter, A Liu, J Moffet, H Sudore, R Schillinger, D John, P Huang, E AF Laiteerapong, Neda Karter, Andrew Liu, Jennifer Moffet, Howard Sudore, Rebecca Schillinger, Dean John, Priya Huang, Elbert TI DETERMINANTS OF QUALITY OF LIFE IN OLDER ADULTS WITH DIABETES: THE DIABETES & AGING STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Laiteerapong, Neda; John, Priya; Huang, Elbert] Univ Chicago, Chicago, IL 60637 USA. [Karter, Andrew; Liu, Jennifer; Moffet, Howard] Kaiser Permanente No Calif, Oakland, CA USA. [Sudore, Rebecca; Schillinger, Dean] Univ Calif San Francisco, San Francisco, CA USA. [Sudore, Rebecca] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 251 EP 251 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300103 ER PT J AU Grant, R Ashburner, J Atlas, S Liu, L AF Grant, Richard Ashburner, Jeffrey Atlas, Steven Liu, Lulu TI DOMAINS OF COMPLEXITY AMONG PATIENTS IDENTIFIED AS COMPLEX BY THEIR PRIMARY CARE PHYSICIANS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Grant, Richard; Ashburner, Jeffrey; Atlas, Steven; Liu, Lulu] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 261 EP 261 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300124 ER PT J AU Pabon-Nau, L Lopez, L AF Pabon-Nau, Lina Lopez, Lenny TI EFFECT OF ANXIETY OR DEPRESSION ON CANCER SCREENING AMONG HISPANIC IMMIGRANTS BY YEARS IN THE US SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Pabon-Nau, Lina; Lopez, Lenny] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 262 EP 262 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300127 ER PT J AU Yano, E Washington, D Bean-Mayberry, B Canelo, I Rose, D AF Yano, Elizabeth Washington, Donna Bean-Mayberry, Bevanne Canelo, Ismelda Rose, Danielle TI EROSION OF WOMEN'S HEALTH SERVICES IN THE VA: VHA SURVEY OF WOMEN VETERANS HEALTH PROGRAMS AND PRACTICES, 2001-2006 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Yano, Elizabeth; Canelo, Ismelda] VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. [Washington, Donna] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Rose, Danielle] VA HSR&D Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. [Bean-Mayberry, Bevanne] VA Greater Los Angeles HSR&D Ctr, Sherman Oaks, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 270 EP 270 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300145 ER PT J AU True, G Crowley-Matoka, M Bayliss, N AF True, Gala Crowley-Matoka, Megan Bayliss, Nichole TI EXPLORING VARIABILITY IN PRIMARY CARE PROVIDERS' APPROACHES TO NON-CANCER PAIN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [True, Gala] Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Crowley-Matoka, Megan; Bayliss, Nichole] Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 274 EP 274 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300156 ER PT J AU Linsky, A Rudolph, J Hermos, J Lawler, E AF Linsky, Amy Rudolph, James Hermos, John Lawler, Elizabeth TI FACTORS ASSOCIATED WITH PROTON PUMP INHIBITOR DISCONTINUATION IN NURSING HOME RESIDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Linsky, Amy] Boston Med Ctr, Boston, MA USA. [Rudolph, James] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Jamaica Plain, MA USA. [Hermos, John; Lawler, Elizabeth] Massachusetts Vet Epidemiol Res & Informat Ctr, VA Cooperat Studies Program, VA Boston Healthcare Syst, Jamaica Plain, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 276 EP 276 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300161 ER PT J AU John, L Loewenstein, G Volpp, K Norton, L Troxel, A Fassbender, J AF John, Leslie Loewenstein, George Volpp, Kevin Norton, Laurie Troxel, Andrea Fassbender, Jennifer TI FINANCIAL INCENTIVES FOR LONGER-TERM WEIGHT LOSS: A RANDOMIZED CONTROLLED TRIAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [John, Leslie; Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Volpp, Kevin] Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Wharton Sch,Philadelpia VA Med Ctr, Philadelphia, PA 19104 USA. [Norton, Laurie] Philadelphia Vet Adm, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 5 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 JUN PY 2010 VL 25 SU 3 BP 278 EP 279 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300167 ER PT J AU Baggett, T Rigotti, N AF Baggett, Travis Rigotti, Nancy TI FOOD INSUFFICIENCY AND HEALTH SERVICE UTILIZATION IN A NATIONAL SAMPLE OF HOMELESS ADULTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Baggett, Travis; Rigotti, Nancy] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 281 EP 281 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300173 ER PT J AU Steinman, M Sloane, R Schmader, K Hanlon, J AF Steinman, Michael Sloane, Richard Schmader, Kenneth Hanlon, Joseph TI FRAILTY AND RISK OF ADVERSE DRUG REACTIONS IN AMBULATORY ELDERS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Steinman, Michael] UCSF, San Francisco VAMC, San Francisco, CA USA. [Sloane, Richard; Schmader, Kenneth] Duke Univ, Durham, NC USA. [Hanlon, Joseph] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 281 EP 282 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300174 ER PT J AU Zeliadt, S Cresswell, D Etzioni, R Lin, D Ginger, VA AF Zeliadt, Steven Cresswell, Darlene Etzioni, Ruth Lin, Daniel Ginger, Van Anh TI GAPS IN FOLLOW-UP CARE AFTER AN ELEVATED PSA TEST SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Zeliadt, Steven] VA Puget Sound Healthcare Syst, HSR& COE, Seattle, WA USA. [Etzioni, Ruth] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Ginger, Van Anh] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 282 EP 283 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300177 ER PT J AU Korthuis, P Bass, M Berkenblit, G Cofrancesco, J Cook, R Edison, M Bashook, P Sosman, J Asch, S Sullivan, L AF Korthuis, Philip Bass, Michael Berkenblit, Gail Cofrancesco, Joseph, Jr. Cook, Robert Edison, Marcia Bashook, Philip Sosman, James Asch, Steven Sullivan, Lynn TI GENERAL INTERNISTS' BELIEFS AND BEHAVIORS REGARDING ROUTINE HIV SCREENING IN PRIMARY CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Korthuis, Philip] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bass, Michael] Univ Illinois, Jane Addams Coll Social Work, Chicago, IL USA. [Berkenblit, Gail] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Cofrancesco, Joseph, Jr.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Cook, Robert] Univ Florida, Gainesville, FL USA. [Edison, Marcia] Univ Illinois, Chicago Sch Med, Chicago, IL USA. [Bashook, Philip] Univ Illinois, Dept Med Educ, Chicago, IL 60612 USA. [Sosman, James] Univ Wisconsin, Madison Sch Med & Publ Hlth, Madison, WI USA. [Asch, Steven] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Sullivan, Lynn] Yale Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 284 EP 285 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300180 ER PT J AU Bains, S Egede, L Osborn, C AF Bains, Sujeev Egede, Leonard Osborn, Chandra TI HEALTH LITERACY, DEMOGRAPHIC PROXIES, AND DIABETES SELF-CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Egede, Leonard] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. [Osborn, Chandra] Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 292 EP 292 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300191 ER PT J AU Lopez, L Ashburner, J Atlas, S Percac-Lima, S Grant, R AF Lopez, Lenny Ashburner, Jeffrey Atlas, Steven Percac-Lima, Sanja Grant, Richard TI HEMOGLOBIN A1C AND LOW-DENSITY LIPOPROTEIN TESTING FOR LATINOS WITH TYPE 2 DIABETES: DIFFERENCES BETWEEN HIGH PROPORTION VS. LOW PROPORTION LATINO CLINICS IN AN INTEGRATED ACADEMIC HEALTH SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Lopez, Lenny; Ashburner, Jeffrey; Atlas, Steven; Percac-Lima, Sanja; Grant, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 292 EP 293 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300192 ER PT J AU Tetrault, J McGinnis, K Sullivan, L Fiellin, D Justice, A AF Tetrault, Jeanette McGinnis, Kathleen Sullivan, Lynn Fiellin, David Justice, Amy TI HEPATIC SAFETY AND ANTIRETROVIRAL EFFECTIVENESS IN HIV-INFECTED PATIENTS RECEIVING NALTREXONE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Tetrault, Jeanette; Fiellin, David] Yale Univ, Sch Med, New Haven, CT USA. [McGinnis, Kathleen] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sullivan, Lynn] Yale Sch Med, New Haven, CT USA. [Justice, Amy] Yale Univ, Sch Med, West Haven, CT 06516 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 293 EP 293 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300193 ER PT J AU Grant, R Ashburner, J Liu, L Atlas, S AF Grant, Richard Ashburner, Jeffrey Liu, Lulu Atlas, Steven TI HOW DO PRIMARY CARE PHYSICIANS DEFINE PATIENT COMPLEXITY? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Grant, Richard; Ashburner, Jeffrey; Liu, Lulu; Atlas, Steven] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 297 EP 297 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300202 ER PT J AU Caton, C Strom, J Moran, W Lynch, C AF Caton, Cathryn Strom, Joni Moran, William Lynch, Cheryl TI IDENTIFYING FALL RISK FACTORS AMONG NURSING HOME PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Lynch, Cheryl] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 300 EP 300 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300209 ER PT J AU Beach, MC Roter, D Moore, RD Korthuis, PT Saha, S Sharp, V Wilson, IB Cohn, J Eggly, S Sankar, A AF Beach, Mary Catherine Roter, Debra Moore, Richard D. Korthuis, P. Todd Saha, Somnath Sharp, Victoria Wilson, Ira B. Cohn, Jonathon Eggly, Susan Sankar, Andrea TI IMPACT OF A PATIENT AND PROVIDER INTERVENTION TO IMPROVE THE QUALITY OF COMMUNICATION ABOUT MEDICATION ADHERENCE AMONG HIV PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Beach, Mary Catherine; Roter, Debra; Moore, Richard D.] Johns Hopkins Univ, Baltimore, MD USA. [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Sharp, Victoria] St Lukes Roosevelt, New York, NY USA. [Wilson, Ira B.] Tufts Med Ctr, Boston, MA USA. [Cohn, Jonathon; Eggly, Susan; Sankar, Andrea] Wayne State, Detroit, MI USA. RI Roter, Debra/N-8830-2014; Wilson, Ira/F-9190-2016 OI Wilson, Ira/0000-0002-0246-738X NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 301 EP 302 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300213 ER PT J AU Cohen, A Young, A Niv, N Reist, C Hamilton, A AF Cohen, Amy Young, Alexander Niv, Noosha Reist, Christopher Hamilton, Alison TI IMPLEMENTATION OF A PSYCHOSOCIAL WEIGHT MANAGEMENT PROGRAM AT MENTAL HEALTH CLINICS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Cohen, Amy; Young, Alexander] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Niv, Noosha; Reist, Christopher] Long Beach VA Healthcare Ctr, Long Beach, CA USA. [Hamilton, Alison] MIRECC, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 5 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 JUN PY 2010 VL 25 SU 3 BP 305 EP 305 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300219 ER PT J AU Cohen, A Glynn, S Young, A Hamilton, A AF Cohen, Amy Glynn, Shirley Young, Alexander Hamilton, Alison TI IMPLEMENTING FAMILY SERVICES AT MENTAL HEALTH CLINICS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Cohen, Amy; Glynn, Shirley; Young, Alexander] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Hamilton, Alison] MIRECC, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 305 EP 306 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300220 ER PT J AU Dankers, C Crevensten, G Miloslavsky, E Thompson, R Berube, R Turgeon, T Roosevelt, S Kitch, B Jackson, Y Karson, A AF Dankers, Christian Crevensten, Gwen Miloslavsky, Eli Thompson, Ryan Berube, Rhodes Turgeon, Tyler Roosevelt, Suzanne Kitch, Barry Jackson, Yanie Karson, Andrew TI IMPROVING THE QUALITY OF RESIDENT-TO-RESIDENT HANDOFFS: A METHOD FOR DEVELOPING AND EVALUATING HANDOFF IMPROVEMENT INTERVENTIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Dankers, Christian; Crevensten, Gwen; Miloslavsky, Eli] Massachusetts Gen Hosp, Residency Training Program, Dept Med, Boston, MA 02114 USA. [Thompson, Ryan] Mass Gen Physicians Org, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 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 JUN PY 2010 VL 25 SU 3 BP 310 EP 311 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300229 ER PT J AU Ripp, J Katz, JT Bazari, H Babyatsky, M Fallar, R Korenstein, D Bellini, L Pecker, M Kapadia, C AF Ripp, Jonathan Katz, Joel T. Bazari, Hasan Babyatsky, Mark Fallar, Robert Korenstein, Deborah Bellini, Lisa Pecker, Mark Kapadia, Cyrus TI INCIDENCE AND PREDICTORS OF JOB BURNOUT IN FIRST YEAR INTERNAL MEDICINE RESIDENTS: WHAT'S FUELING THIS FIRE? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Ripp, Jonathan; Babyatsky, Mark; Fallar, Robert; Korenstein, Deborah] Mt Sinai Sch Med, New York, NY USA. [Katz, Joel T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bazari, Hasan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bellini, Lisa] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Pecker, Mark] Weill Cornell Med Coll, New York, NY USA. [Kapadia, Cyrus] Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 311 EP 312 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300230 ER PT J AU Mortensen, E Pugh, MJ Copeland, L Restrepo, M Nakashima, B Perry, T Anzueto, A AF Mortensen, Eric Pugh, Mary Jo Copeland, Laurel Restrepo, Marcos Nakashima, Brandy Perry, Theodore Anzueto, Antonio TI INCIDENCE OF CARDIAC ARRHYTHMIA AFTER HOSPITALIZATION FOR PNEUMONIA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Copeland, Laurel] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Nakashima, Brandy; Perry, Theodore; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 312 EP 312 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300231 ER PT J AU Thompson, R Dankers, C Crevensten, G Miloslavsky, E Berube, R Turgeon, T Roosevelt, S Kitch, B Karson, A AF Thompson, Ryan Dankers, Christian Crevensten, Gwen Miloslavsky, Eli Berube, Rhodes Turgeon, Tyler Roosevelt, Suzanne Kitch, Barry Karson, Andy TI JUST HOW PROBLEMATIC ARE PATIENT HANDOFFS? RESULTS FROM A DAILY LONGITUDINAL SURVEY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Thompson, Ryan] Mass Gen Phys Org, Boston, MA USA. [Dankers, Christian; Crevensten, Gwen; Miloslavsky, Eli] Massachusetts Gen Hosp, Dept Med Residency Training Program, Boston, MA 02114 USA. [Berube, Rhodes; Turgeon, Tyler; Roosevelt, Suzanne; Kitch, Barry] MGH, Ctr Qual & Safety, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 321 EP 322 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300252 ER PT J AU Bishop, T Ross, J Federman, A AF Bishop, Tara Ross, Joseph Federman, Alex TI LABORATORY TEST ORDERING AT PHYSICIAN OFFICES WITH AND WITHOUT ON-SITE LABORATORIES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Bishop, Tara] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA. [Ross, Joseph] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, HSR&D Res Enhancement Award Program, New York, NY USA. [Ross, Joseph] James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Federman, Alex] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 322 EP 323 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300255 ER PT J AU Lynch, C Egede, L Gebregziabher, M Mueller, M Zhao, YM Echols, C Gilbert, G AF Lynch, Cheryl Egede, Leonard Gebregziabher, Mulugeta Mueller, Martina Zhao, Yumin Echols, Carrae Gilbert, Gregory TI LONGITUDINAL EFFECTS OF MEDICATION NON-ADHERENCE ON GLYCEMIC CONTROL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Lynch, Cheryl] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 324 EP 324 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300259 ER PT J AU Saha, S Perrin, N Gerrity, M Gatchell, M AF Saha, Somnath Perrin, Nancy Gerrity, Martha Gatchell, Melissa TI MEASURING PHYSICIAN CULTURAL COMPETENCE: RESULTS FROM A NATIONAL SURVEY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Saha, Somnath; Gatchell, Melissa] Portland VA Med Ctr, Portland, OR USA. [Perrin, Nancy] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Gerrity, Martha] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 1 Z9 1 U1 0 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 JUN PY 2010 VL 25 SU 3 BP 329 EP 329 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300269 ER PT J AU Hamilton, A Cohen, A Young, A AF Hamilton, Alison Cohen, Amy Young, Alexander TI ORGANIZATIONAL READINESS IN MENTAL HEALTH CLINICS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Hamilton, Alison] MIRECC, Los Angeles, CA USA. [Cohen, Amy; Young, Alexander] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 339 EP 340 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300291 ER PT J AU Bryson, C Jackson, G Maciejewski, M Au, D Fihn, S Perkins, M Sharp, N Liu, CF Blough, D Piette, J AF Bryson, Christopher Jackson, George Maciejewski, Matthew Au, David Fihn, Stephan Perkins, Mark Sharp, Nancy Liu, Chuan-Fen Blough, David Piette, John TI PATIENT FACTORS DO NOT EXPLAIN LARGE FACILITY VARIATION IN MEDICATION ADHERENCE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Bryson, Christopher; Au, David; Fihn, Stephan; Perkins, Mark; Sharp, Nancy; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Jackson, George; Maciejewski, Matthew] Durham VA Med Ctr, Hlth Serv Res & Dev, Durham, NC USA. [Blough, David] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Piette, John] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 342 EP 342 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300298 ER PT J AU McTigue, K Zickmund, S Simkin-Silverman, L Bryce, C Bhargava, T Conroy, M Fischer, G Meiksin, R AF McTigue, Kathleen Zickmund, Susan Simkin-Silverman, Laurey Bryce, Cindy Bhargava, Tina Conroy, Molly Fischer, Gary Meiksin, Rebecca TI PATIENT PREFERENCES FOR FEATURES OF AN ONLINE INTERACTIVE BEHAVIORAL WEIGHT LOSS PROGRAM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Zickmund, Susan] Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Simkin-Silverman, Laurey] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Bryce, Cindy] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Bhargava, Tina] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Bhargava, Tina] Univ Pittsburgh, Dept Behav Sci & Community Hlth, Pittsburgh, PA USA. [Meiksin, Rebecca] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 342 EP 343 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300299 ER PT J AU Copeland, L Zeber, J MacCarthy, D Lawrence, V AF Copeland, Laurel Zeber, John MacCarthy, Dan Lawrence, Valerie TI PERIOPERATIVE OUTCOMES OF NON-CARDIAC SURGERY FOR SERIOUSLY MENTALLY ILL ELDERLY (POSSE) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Copeland, Laurel; MacCarthy, Dan; Lawrence, Valerie] South Texas Vet Hlth Care Syst, VERDICT Res, San Antonio, TX USA. [Zeber, John] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Lawrence, Valerie] UTHSCSA, Dept Med, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 348 EP 348 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300312 ER PT J AU Saha, S Moore, R Beach, MC Korthuis, T Sharp, V Cohn, J AF Saha, Somnath Moore, Richard Beach, Mary Catherine Korthuis, Todd Sharp, Victoria Cohn, Jonathan TI PHYSICIAN INTERRACIAL ANXIETY, COMMUNICATION, AND SATISFACTION AMONG PATIENTS WITH HIV SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Moore, Richard; Beach, Mary Catherine] Johns Hopkins Univ, Baltimore, MD USA. [Korthuis, Todd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cohn, Jonathan] Wayne State Univ, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 350 EP 350 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300317 ER PT J AU Saha, S Beach, MC AF Saha, Somnath Beach, Mary Catherine TI PHYSICIAN PATIENT-CENTEREDNESS AND PATIENT DECISION-MAKING: A RANDOMIZED STUDY USING VIDEO VIGNETTES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Beach, Mary Catherine] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 351 EP 352 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300321 ER PT J AU Bishop, T Keyhani, S Federman, A AF Bishop, Tara Keyhani, Salomeh Federman, Alex TI PHYSICIAN VIEWS ON DEFENSIVE MEDICINE: A NATIONAL SURVEY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Bishop, Tara; Federman, Alex] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA. [Keyhani, Salomeh] James J Peters Vet Adm Med Ctr, Mt Sinai Sch Med, Dept Hlth Policy, Div Gen Internal Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 352 EP 353 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300323 ER PT J AU Federman, A Keyhani, S Woodward, M AF Federman, Alex Keyhani, Salomeh Woodward, Mark TI PHYSICIANS OPINIONS ABOUT REFORMING REIMBURSEMENT: RESULTS OF A NATIONAL SURVEY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Federman, Alex] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA. [Keyhani, Salomeh] James J Peters Vet Adm Med Ctr, Mt Sinai Sch Med, Dept Hlth Policy, Div Gen Internal Med, New York, NY USA. [Woodward, Mark] George Inst Int Hlth, Sydney, NSW, Australia. RI Woodward, Mark/D-8492-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 353 EP 353 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300324 ER PT J AU Finley, E Pugh, MJ Parchman, M Noel, P Zeber, J Copeland, L Cantu, G AF Finley, Erin Pugh, Mary Jo Parchman, Michael Noel, Polly Zeber, John Copeland, Laurel Cantu, Gabriel TI POST-DEPLOYMENT HEALTHCARE FOR RETURNING OEF/OIF MILITARY PERSONNEL AND THEIR SOCIAL NETWORKS: A QUALITATIVE APPROACH SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Parchman, Michael] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Dept Family & Community Med, San Antonio, TX 78229 USA. [Noel, Polly] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78229 USA. [Zeber, John; Copeland, Laurel] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Dept Psychiat, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 354 EP 354 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300327 ER PT J AU Castiglioni, A Kertesz, S Kim, Y Schumacher, J Snyder, E AF Castiglioni, Analia Kertesz, Stefan Kim, Young Schumacher, Joseph Snyder, Erin TI PRESCRIBING OPIATES FOR CHRONIC PAIN IN RESIDENT CONTINUITY CLINICS- EXPERIENCE MAY NOT ASSURE ADEQUATE KNOWLEDGE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Kertesz, Stefan] Birmingham VA Med Ctr, Birmingham, AL USA. [Kim, Young; Schumacher, Joseph] Univ Alabama, Sch Med, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 360 EP 361 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300338 ER PT J AU Korthuis, P Fleishman, J Gebo, K Cameron, B Hickam, D Hellinger, J Mathews, W AF Korthuis, Philip Fleishman, John Gebo, Kelly Cameron, Bonnie Hickam, David Hellinger, James Mathews, William TI PREVALENCE AND CORRELATES OF NON-RECOMMENDED ANTIRETROVIRAL THERAPY IN A MULTICENTER HIV COHORT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Fleishman, John] Agcy Healthcare Res & Qual, Rockville, MD USA. [Gebo, Kelly] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Cameron, Bonnie] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Hickam, David] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Hellinger, James] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Mathews, William] UCSD, Dept Med, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 361 EP 362 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300340 ER PT J AU Lynch, C Gebregziabher, M Zhao, YM Echols, C Gilbert, G Egede, L AF Lynch, Cheryl Gebregziabher, Mulugeta Zhao, Yumin Echols, Carrae Gilbert, Gregory Egede, Leonard TI RACIAL DISPARITIES IN ALL-CAUSE MORTALITY AMONG VETERANS WITH TYPE 2 DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Lynch, Cheryl; Egede, Leonard] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 376 EP 376 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300370 ER PT J AU Borrero, S Dehlendorf, C Abebe, K Schwarz, E Creinin, M Nikolajski, C Ibrahim, S AF Borrero, Sonya Dehlendorf, Christine Abebe, Kaleab Schwarz, Eleanor Creinin, Mitchell Nikolajski, Cara Ibrahim, Said TI RACIAL VARIATION IN TUBAL STERILIZATION RATES: THE ROLE OF PATIENT-LEVEL FACTORS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Borrero, Sonya; Ibrahim, Said] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Borrero, Sonya] UPMC, Pittsburgh, PA USA. [Dehlendorf, Christine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Abebe, Kaleab; Schwarz, Eleanor; Creinin, Mitchell; Nikolajski, Cara] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 377 EP 377 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300372 ER PT J AU Clair, C Bitton, A Meigs, J Rigotti, N AF Clair, Carole Bitton, Asaf Meigs, James Rigotti, Nancy TI RELATIONSHIP BETWEEN CIGARETTE SMOKING, NICOTINE AND A1C AMONG PEOPLE WITH DIABETES IN THE UNITED STATES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Clair, Carole; Meigs, James; Rigotti, Nancy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bitton, Asaf] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Clair, Carole/D-9786-2014 OI Clair, Carole/0000-0001-5281-0943 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 JUN PY 2010 VL 25 SU 3 BP 382 EP 382 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300385 ER PT J AU Brooks, G Prochazka, A Gopal, R Huang, J Smart, A Bowles, D Yamashita, T Jamieson, D Heist, K AF Brooks, Gabriel Prochazka, Allan Gopal, Ravi Huang, Janice Smart, Alexandra Bowles, Daniel Yamashita, Traci Jamieson, Daniel Heist, Kathleen TI REPORTING OF NEGATIVE RANDOMIZED CONTROLLED TRIALS IN THREE MAJOR MEDICAL JOURNALS: EFFECT OF TRIAL REGISTRATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Brooks, Gabriel; Huang, Janice; Smart, Alexandra; Bowles, Daniel; Yamashita, Traci; Jamieson, Daniel] Univ Colorado Denver, Aurora, CO USA. [Prochazka, Allan; Gopal, Ravi] Denver VA Med Ctr, Denver, CO USA. [Heist, Kathleen] Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 384 EP 385 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300391 ER PT J AU Cordasco, K Schneider, DC Franco, I Sarkisian, C AF Cordasco, Kristina Schneider, Diana C. Franco, Idalid Sarkisian, Catherine TI SENSITIVITIES OF THREE SINGLE-ITEM LITERACY SCREENER (SILS) QUESTIONS IN GERIATRIC MONOLINGUAL SPANISH-SPEAKING PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Cordasco, Kristina; Franco, Idalid] RAND Corp, Santa Monica, CA USA. [Schneider, Diana C.] LAC, USC Med Ctr, Los Angeles, CA USA. [Sarkisian, Catherine] Univ Calif Los Angeles, VA Greater Los Angeles, GRECC, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 389 EP 389 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300404 ER PT J AU Sudore, R Williams, B Castillo, L AF Sudore, Rebecca Williams, Brie Castillo, Leslie TI THE CLASH BETWEEN ADVANCE DIRECTIVE LAW AND CLINICAL CARE: RAMIFICATIONS FOR VULNERABLE POPULATIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Sudore, Rebecca; Williams, Brie; Castillo, Leslie] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sudore, Rebecca] San Francisco VA Med Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 399 EP 399 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300423 ER PT J AU Hong, C Subramanian, S Atlas, S Chang, Y Ashburner, J Barry, M Grant, R AF Hong, Clemens Subramanian, Sv Atlas, Steven Chang, Yuchiao Ashburner, Jeffrey Barry, Michael Grant, Richard TI THE IMPACT OF ADJUSTING FOR PRACTICE SITE, PATIENT CHARACTERISTICS, AND VISIT FREQUENCY ON PHYSICIAN PAY-FOR-PERFORMANCE IN A LARGE, ACADEMIC HEALTH CARE SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Hong, Clemens] Harvard Univ, Massachusetts Gen Hosp, Charlestown, MA USA. [Subramanian, Sv] Harvard Sch Publ Hlth, Boston, MA 02115 USA. [Atlas, Steven; Chang, Yuchiao; Ashburner, Jeffrey; Barry, Michael; Grant, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 405 EP 405 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300437 ER PT J AU Ahluwalia, S Fried, T Gross, C Chaudhry, S AF Ahluwalia, Sangeeta Fried, Terri Gross, Cary Chaudhry, Sarwat TI THE IMPACT OF COMORBIDITY ON MORTALITY AMONG OLDER PERSONS WITH ADVANCED HEART FAILURE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Ahluwalia, Sangeeta] Vet Adm Greater Los Angeles, Los Angeles, CA USA. [Fried, Terri] VA CT Healthcare Syst, West Haven, CT USA. [Gross, Cary] Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 406 EP 406 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300439 ER PT J AU Morone, N Rollman, B Belnap, BH Houck, P Karp, J Mazumdar, S He, F Weiner, D AF Morone, Natalia Rollman, Bruce Belnap, Bea Herbeck Houck, Patricia Karp, Jordan Mazumdar, Sati He, Fanyin Weiner, Debra TI THE IMPACT OF PAIN AND DEPRESSION ON POST-CABG RECOVERY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Morone, Natalia; Rollman, Bruce] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Belnap, Bea Herbeck; Houck, Patricia] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Weiner, Debra] Ctr Geriatr Res Educ & Clin, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 406 EP 406 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300440 ER PT J AU Percac-Lima, S Ashburner, J Grant, R Lopez, L Atlas, S AF Percac-Lima, Sanja Ashburner, Jeffrey Grant, Richard Lopez, Lenny Atlas, Steven TI THE IMPACT OF PATIENT NAVIGATION ON DECREASING DISPARITIES IN CANCER SCREENING IN A LARGE PRIMARY CARE NETWORK SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Percac-Lima, Sanja] Massachusetts Gen Hosp, Chelsea, MA USA. [Ashburner, Jeffrey; Grant, Richard; Lopez, Lenny; Atlas, Steven] Massachusetts Gen Hosp, Boston, MA 02114 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 406 EP 407 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300441 ER PT J AU Volpp, K Silber, J Wang, YL Even-Shoshan, O Halenar, M Bellini, L Romano, P Zhu, JS Press, M Rosen, A Itani, K AF Volpp, Kevin Silber, Jeffrey Wang, Yanli Even-Shoshan, Orit Halenar, Michael Bellini, Lisa Romano, Patrick Zhu, Jingsan Press, Matthew Rosen, Amy Itani, Kamal TI THE IMPACT OF RESIDENT DUTY HOUR REFORM ON HOSPITAL READMISSION RATES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Volpp, Kevin] Univ Penn, Sch Med, Wharton Sch, Leonard Davis Inst Hlth Econ,Philadelphia VA Med, Philadelphia, PA 19104 USA. [Silber, Jeffrey; Wang, Yanli; Even-Shoshan, Orit; Halenar, Michael] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA. [Bellini, Lisa] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Romano, Patrick] Univ Calif Davis, Sacramento, CA 95817 USA. [Rosen, Amy; Itani, Kamal] VA Boston Healthcare Syst, Boston, MA USA. RI Romano, Patrick/N-4225-2014 OI Romano, Patrick/0000-0001-6749-3979 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 407 EP 407 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300442 ER PT J AU Beach, MC Brown, R Hughes, M Saha, S Haywood, C Lanzkron, S Massa, M AF Beach, Mary Catherine Brown, Rochelle Hughes, Mark Saha, Somnath Haywood, Carlton, Jr. Lanzkron, Sophie Massa, Michele TI THE INFLUENCE OF CLINICIAN RACE ON ATTITUDES TOWARD PATIENTS WITH SICKLE CELL DISEASE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Beach, Mary Catherine; Brown, Rochelle; Haywood, Carlton, Jr.; Lanzkron, Sophie; Massa, Michele] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Hughes, Mark] Johns Hopkins Univ, Towson, MD USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 409 EP 410 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300448 ER PT J AU Caines, L Brockmeyer, D Kim, H Tess, A Bates, C Kriegel, G AF Caines, Laurie Brockmeyer, Diane Kim, Hans Tess, Anjala Bates, Carol Kriegel, Gila TI THE REVOLVING DOOR OF RESIDENT CONTINUITY PRACTICE: A QUALITY IMPROVEMENT PROJECT TO ADDRESS TRANSITIONS OF CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Caines, Laurie; Brockmeyer, Diane; Kim, Hans; Tess, Anjala; Bates, Carol] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kriegel, Gila] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 413 EP 413 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300456 ER PT J AU Rosen, A Zhao, S Borzecki, A Shin, M Loveland, S Hanchate, A AF Rosen, Amy Zhao, Shibei Borzecki, Ann Shin, Marlena Loveland, Susan Hanchate, Amresh TI TRENDS IN READMISSION RATES WITHIN THE VETERANS HEALTH ADMINISTRATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Rosen, Amy; Shin, Marlena; Loveland, Susan; Hanchate, Amresh] VA Boston Healthcare Syst, Boston, MA USA. [Zhao, Shibei; Borzecki, Ann] Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 418 EP 418 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300466 ER PT J AU Englander, H Kansagara, D AF Englander, Honora Kansagara, Devan TI UNDERSTANDING AND IMPROVING CARE TRANSITIONS FOR THE UNDERSERVED SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Englander, Honora] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kansagara, Devan] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 419 EP 419 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300469 ER PT J AU Borrero, S McCall-Hosenfeld, J Brandt, C Mattocks, K Nikolajski, C Haskell, S AF Borrero, Sonya McCall-Hosenfeld, Jennifer Brandt, Cynthia Mattocks, Kristin Nikolajski, Cara Haskell, Sally TI UNDERSTANDING WOMEN VETERAN'S PERCEPTIONS OF REPRODUCTIVE HEALTH CARE SERVICES IN THE VETERANS ADMINISTRATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Borrero, Sonya] UPMC, Pittsburgh, PA USA. [McCall-Hosenfeld, Jennifer] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Brandt, Cynthia; Mattocks, Kristin] VA Connecticut Healtcare Syst, West Haven, CT USA. [Nikolajski, Cara] Univ Pittsburgh, Pittsburgh, PA USA. [Haskell, Sally] Yale Univ, Sch Med, West Haven, CT 06516 USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Nikolajski, Cara] VAPHS, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 420 EP 420 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300471 ER PT J AU Chen, G Egede, L Jia, H Yu, HJ AF Chen, Guoqing Egede, Leonard Jia, Huanguang Yu, Hong-Jen TI UNDERUTILIZATION OF NEPHROLOGISTS SERVICES FOR VETERANS WITH CHRONIC KIDNEY DISEASE IN VA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Chen, Guoqing] Baylor Coll Med, Houston, TX 77030 USA. [Chen, Guoqing; Yu, Hong-Jen] VA Houston HSR&D Ctr Excellence, Houston, TX USA. [Egede, Leonard] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. [Jia, Huanguang] RORC, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 420 EP 420 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300472 ER PT J AU Gellad, W Donohue, J Good, CB Lowe, J AF Gellad, Walid Donohue, Julie Good, C. Bernie Lowe, John TI USE OF ANGIOTENSIN RECEPTOR BLOCKERS IN THE VA, 2000-2009: WHY SO MUCH VARIATION? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Gellad, Walid] VA Pittsburgh, RAND Hlth, Pittsburgh, PA USA. [Donohue, Julie] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Good, C. Bernie] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Lowe, John] VHA Pharm Benefits Management Serv, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 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 JUN PY 2010 VL 25 SU 3 BP 421 EP 422 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300475 ER PT J AU Liu, CF Maciejewski, M Bryson, C Perkins, M Sharp, N AF Liu, Chuan-Fen Maciejewski, Matthew Bryson, Christopher Perkins, Mark Sharp, Nancy TI USE OF OUTPATIENT CARE IN VA AND MEDICARE AMONG DISABILITY-ELIGIBLE AND AGE-ELIGIBLE VETERANS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Liu, Chuan-Fen; Bryson, Christopher; Perkins, Mark; Sharp, Nancy] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Maciejewski, Matthew] Durham VA Med Ctr, Hlth Serv Res & Dev, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 423 EP 423 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300478 ER PT J AU Rosen, AK Kaafarani, H Mull, H Itani, K Nebeker, J AF Rosen, Amy K. Kaafarani, Haytham Mull, Hillary Itani, Kamal Nebeker, Jonathan TI USE OF TRIGGER TOOLS TO DETECT ADVERSE EVENTS IN AMBULATORY SURGERY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Rosen, Amy K.; Mull, Hillary] VA Boston Healthcare Syst, Boston, MA USA. [Kaafarani, Haytham] Tufts Med Ctr, Boston, MA USA. [Itani, Kamal] VA Boston Healthcare Syst, W Roxbury, MA USA. [Nebeker, Jonathan] VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 423 EP 424 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300479 ER PT J AU Roy, B Salanitro, A Willett, L Qu, H Shewchuk, R Centor, R Castiglioni, A AF Roy, Brita Salanitro, Amanda Willett, Lisa Qu, Haiyan Shewchuk, Richard Centor, Robert Castiglioni, Analia TI USING COGNITIVE MAPPING TO IDENTIFY ATTRIBUTES CONTRIBUTING TO SUCCESSFUL WARD-ATTENDING ROUNDS - A RESIDENT AND STUDENT PERSPECTIVE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Roy, Brita; Willett, Lisa; Qu, Haiyan; Shewchuk, Richard; Centor, Robert; Castiglioni, Analia] Univ Alabama, Birmingham, AL USA. [Salanitro, Amanda] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 424 EP 425 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300481 ER PT J AU Ayotte, B Manze, M Kressin, N Orner, M AF Ayotte, Brian Manze, Meredith Kressin, Nancy Orner, Michelle TI WHAT IS THE BEST WAY TO MEASURE ADHERENCE TO ANTIHYPERTENSIVE MEDICATIONS? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Ayotte, Brian] VA Boston Healthcare Syst, Boston, MA USA. [Manze, Meredith] Boston Med Ctr, Boston, MA USA. [Kressin, Nancy] Boston Univ, Sch Med, Boston, MA 02118 USA. [Orner, Michelle] Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 430 EP 430 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300491 ER PT J AU Korenstein, D Ross, J Keyhani, S Mendelson, A AF Korenstein, Deborah Ross, Joseph Keyhani, Salomeh Mendelson, Ali TI WHEN THE CAT LOOKS AWAY, WILL THE MICE PLAY? ADHERENCE OF PHARMACEUTICAL ADS IN MEDICAL JOURNALS TO FDA STANDARDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Ross, Joseph] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, HSR&D Res Enhancement Award Program & Geriatr Res, New York, NY USA. [Ross, Joseph] James J Peters Vet Adm Med Ctr, Ctr Clin, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 432 EP 432 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300496 ER PT J AU Bates, C Caines, L Brockmeyer, D Tess, A Yang, J Smith, C Reynolds, E Vanka, A AF Bates, Carol Caines, Laurie Brockmeyer, Diane Tess, Anjala Yang, Julius Smith, Christopher Reynolds, Eileen Vanka, Anita TI ALTERNATING CALL/ELECTIVE SCHEDULE (ACES): RESTRUCTURING THE BIDMC MEDICINE RESIDENCY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Bates, Carol; Caines, Laurie; Brockmeyer, Diane; Tess, Anjala; Yang, Julius; Smith, Christopher; Reynolds, Eileen] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Vanka, Anita] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 438 EP 438 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300510 ER PT J AU Thompson, R Miloslavsky, E Crevensten, G Dankers, C O'Donnell, W AF Thompson, Ryan Miloslavsky, Eli Crevensten, Gwen Dankers, Christian O'Donnell, Walter TI THE RESIDENT QUALITY AND SAFETY FORUM: AN INNOVATIVE SYSTEM TO ENHANCE RESIDENT EDUCATION IN QUALITY AND SAFETY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Thompson, Ryan] Mass Gen Phys Org, Boston, MA USA. [Miloslavsky, Eli; Crevensten, Gwen; Dankers, Christian] Massachusetts Gen Hosp, Dept Med, Residency Training Program, Boston, MA 02114 USA. [O'Donnell, Walter] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 453 EP 453 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300544 ER PT J AU Conde, M Lawrence, V Wathen, P AF Conde, Michelle Lawrence, Val Wathen, Patricia TI USING STANDARDIZED PATIENTS TO TEACH ALCOHOL SCREENING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Conde, Michelle; Lawrence, Val] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. [Wathen, Patricia] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 454 EP 454 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300546 ER PT J AU Jena, A Wright, D AF Jena, Anupam Wright, Douglas TI A 21 YEAR-OLD MAN WITH SYNCOPE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Wright, Douglas] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 475 EP 475 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300596 ER PT J AU Patwardhan, V Lemly, D AF Patwardhan, Vilas Lemly, Diana TI A NINETEEN YEAR OLD FEMALE WITH FEVER AND RASH SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Patwardhan, Vilas; Lemly, Diana] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 482 EP 482 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300615 ER PT J AU Turbett, S Baggett, MV AF Turbett, Sarah Baggett, Meridale Vaught TI A MASS-IVE SURPRISE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Turbett, Sarah; Baggett, Meridale Vaught] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 482 EP 482 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300614 ER PT J AU Patwardhan, V Coley, C AF Patwardhan, Vilas Coley, Christopher TI AN UNSUAL PRESENTATION OF FEVER IN A TWENTY-TWO YEAR OLD FEMALE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Patwardhan, Vilas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Coley, Christopher] Massachusetts Gen Hosp, Chestnut Hill, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 490 EP 490 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300635 ER PT J AU Noel, PH Copeland, LA Pugh, MJ Kahwati, L Tsevat, J Nelson, K Wang, CP Bollinger, MJ Hazuda, HP AF Noel, Polly Hitchcock Copeland, Laurel A. Pugh, Mary Jo Kahwati, Leila Tsevat, Joel Nelson, Karin Wang, Chen-Pin Bollinger, Mary J. Hazuda, Helen P. TI Obesity Diagnosis and Care Practices in the Veterans Health Administration SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE obesity; diagnosis; patient education; health services research; veterans ID WEIGHT MANAGEMENT; NATIONAL TRENDS; ADULTS; OVERWEIGHT AB In response to dramatic increases in obesity prevalence, clinical guidelines urge health care providers to prevent and treat obesity more aggressively. To describe the proportion of obese primary care patients receiving obesity care over a 5-year period and identify factors predicting receipt of care. Retrospective cohort study utilizing VHA administrative data from 6 of 21 VA administrative regions. Veterans seen in primary care in FY2002 with a body mass index (BMI) a parts per thousand yen30 kg/m(2) based on heights and weights recorded in the electronic medical record (EMR), survival through FY2006, and active care (1 or more visits in at least 3 follow-up years FY2003-2006). Receipt of outpatient visits for individual or group education or instruction in nutrition, exercise, or weight management; receipt of prescriptions for any FDA-approved medications for weight reduction; and receipt of bariatric surgery. Of 933,084 (88.6%) of 1,053,228 primary care patients who had recorded heights and weights allowing calculation of BMI, 330,802 (35.5%) met criteria for obesity. Among obese patients who survived and received active care (N = 264,667), 53.5% had a recorded obesity diagnosis, 34.1% received at least one outpatient visit for obesity-related education or counseling, 0.4% received weight-loss medications, and 0.2% had bariatric surgery between FY2002-FY2006. In multivariable analysis, patients older than 65 years (OR = 0.62; 95% CI: 0.60-0.64) were less likely to receive obesity-related education, whereas those prescribed 5-7 or 8 or more medication classes (OR = 1.41; 1.38-1.45; OR = 1.94; 1.88-2.00, respectively) or diagnosed with obesity (OR = 4.0; 3.92-4.08) or diabetes (OR = 2.23; 2.18-2.27) were more likely to receive obesity-related education. Substantial numbers of VHA primary care patients did not have sufficient height or weight data recorded to calculate BMI or have recorded obesity diagnoses when warranted. Receipt of obesity education varied by sociodemographic and clinical factors; providers may need to be cognizant of these when engaging patients in treatment. C1 [Noel, Polly Hitchcock; Copeland, Laurel A.; Pugh, Mary Jo; Wang, Chen-Pin; Bollinger, Mary J.] VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Noel, Polly Hitchcock; Copeland, Laurel A.; Pugh, Mary Jo; Wang, Chen-Pin; Hazuda, Helen P.] UT Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Kahwati, Leila] VHA Natl Ctr Hlth Promot & Dis Prevent, Durham, NC USA. [Tsevat, Joel] Cincinnati VAMC, Cincinnati, OH USA. [Tsevat, Joel] Univ Cincinnati, Cincinnati, OH USA. [Nelson, Karin] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Nelson, Karin] Univ Washington, Dept Med, Seattle, WA USA. RP Noel, PH (reprint author), VERDICT S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM noelp@uthscsa.edu OI Pugh, Mary Jo/0000-0003-4196-7763; Copeland, Laurel/0000-0002-9478-0209 FU Department of Veteran Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 05-121] FX The research reported here was supported by the Department of Veteran Affairs, Veterans Health Administration, Health Services Research and Development Service (project no. IIR 05-121). Dr. Noel is a Research Psychologist at the South Texas Veterans Health Care System. The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs. NR 32 TC 23 Z9 23 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 JUN PY 2010 VL 25 IS 6 BP 510 EP 516 DI 10.1007/s11606-010-1279-z PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 596UY UT WOS:000277712200008 PM 20180155 ER PT J AU Certain, L Bhattacharyya, R Gonzalez, A AF Certain, Laura Bhattacharyya, Roby Gonzalez, Alejandro TI FEVER AND LEUKOPENIA IN A 52-YEAR-OLD CUBAN IMMIGRANT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 18-MAY 01, 2010 CL Minneapolis, MN SP Soc Gen Internal Med C1 [Certain, Laura; Bhattacharyya, Roby] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gonzalez, Alejandro] Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2010 VL 25 SU 3 BP 513 EP 514 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591EO UT WOS:000277282300696 ER PT J AU Guitton, TG van Leerdam, RH Ring, D AF Guitton, Thierry G. van Leerdam, Roderick H. Ring, David TI Necessity of Routine Pathological Examination After Surgical Excision of Wrist Ganglions SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Ganglion; wrist; pathological; examination; excision ID KNEE REPLACEMENT; FEMORAL-HEAD; TOTAL HIP; SPECIMENS; COST; HISTOPATHOLOGY; ARTHROPLASTY; MANAGEMENT; TESTS; TIME AB Purpose The value of routine pathological evaluation of ganglion cysts is questionable considering that the pretest odds of a wrist lesion being a ganglion cyst are usually high based on physical examination and surgical findings alone. This study evaluates the necessity of routine pathological examination of specimens derived from surgical removal of wrist ganglion cysts. Methods We identified 429 consecutive adult patients who underwent surgical excision of a wrist ganglion with routine pathological examination of the specimen between 1997 and 2008. The rates of concordant, discrepant, and discordant diagnoses were reported with 95% confidence intervals. The odds of a discrepant or discordant diagnosis were calculated. Results The prevalence of a concordant diagnosis was 98.6% (424 of 429; 95% confidence interval, 97.3% to 99.6%). The prevalence of a discrepant diagnosis was 1.4% (5 of 429; 95% confidence interval, 0.38% to 2.7%), and the prevalence of a discordant diagnosis was zero. The odds ratio was 0.012 for a discrepant diagnosis and zero for a discordant diagnosis. Conclusions This study suggests that, in patients with the clinical diagnosis of wrist ganglion cyst, quality of care would not be compromised by abandoning the practice of routinely submitting surgical specimens for pathological examination after excision of the ganglion cyst. Discrepant diagnoses are encountered infrequently and discordant diagnoses did not occur. We recommend pathological examination only when the clear gelatinous fluid typical of a ganglion cyst is not encountered at surgery. (J Hand Surg 2010;35A:905-908. (C) 2010 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Guitton, Thierry/0000-0002-2599-1985 NR 24 TC 7 Z9 8 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUN PY 2010 VL 35A IS 6 BP 905 EP 908 DI 10.1016/j.jhsa.2010.03.021 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 608GJ UT WOS:000278571100004 PM 20478665 ER PT J AU Vranceanu, AM Jupiter, JB Mudgal, CS Ring, D AF Vranceanu, Ana-Maria Jupiter, Jesse B. Mudgal, Chaitanya S. Ring, David TI Predictors of Pain Intensity and Disability After Minor Hand Surgery SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Carpal tunnel syndrome; minor hand surgery; local anesthesia; pain intensity; depression ID LOW-BACK-PAIN; PSYCHOLOGICAL DISTRESS; DEPRESSION; HEALTH; EFFICACY; THERAPY AB Purpose To test the null hypothesis that there is no relationship between coping mechanisms and depression measured before surgery, and pain intensity and disability after surgery, as assessed at the time of suture removal. Methods A total of 120 patients (39 electing surgery for carpal tunnel syndrome, 65 for trigger finger, and 16 for a benign tumor) completed questionnaires measuring depression, pain self-efficacy (confidence that one can perform various activities despite pain), pain anxiety (fear and anxiety in response to pain sensations), and pain catastrophizing (maladaptive cognitive activities such as pain-related rumination, magnification, and helplessness) before surgery. Before the surgery and at the time of suture removal (10 to 14 days after surgery) participants completed the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) and a numerical pain intensity rating scale. Results At the time of suture removal, there was a significant correlation between pain intensity and depression (r = 0.45, p<.001), pain catastrophizing (r = 0.41, p<.001), pain anxiety (r = 0.32, p<.01), and self-efficacy (r = -0.29, p<.01). Disability correlated with self-efficacy (r = -0.34; p<.001) and depression (r = 0.49; p<.001), but not with pain anxiety and catastrophizing (p>.05). In multivariate analyses, depression was the sole predictor of both disability and pain intensity and accounted for 26% of the variance in DASH scores and 25% of the variance in pain intensity, after removing the influence of preoperative DASH and diagnosis, which accounted for 14% variance. Conclusions Psychosocial factors, especially. depression, explain a notable proportion of the variation in pain intensity and disability after minor hand surgery. (J Hand Surg 2010;35A: 956-960. (C) 2010 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) Type of study/level of evidence Prognostic I. C1 [Ring, David] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthoped Surg, Yawkey Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Behav Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hand & Orthoped Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthoped Surg, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Acumed; Tornier FX D.R. received unrestricted research grants from Acumed and Tornier. D.R. received royalties from Hand Innovations and is a consultant for Wright Medical, Acumed, and Tomier. NR 35 TC 63 Z9 64 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUN PY 2010 VL 35A IS 6 BP 956 EP 960 DI 10.1016/j.jhsa.2010.02.001 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 608GJ UT WOS:000278571100013 PM 20381981 ER PT J AU Harrod, CC Boykin, RE Jupiter, JB AF Harrod, Christopher C. Boykin, Robert E. Jupiter, Jesse B. TI Pain and Swelling After Radiofrequency Treatment of Proximal Phalanx Osteoid Osteoma: Case Report SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Osteoid osteoma; phalangeal tumors; radiofrequency ablation ID TOMOGRAPHY-GUIDED THERMOCOAGULATION; CONTROL ENERGY DELIVERY; OPERATIVE TREATMENT; UPPER EXTREMITY; COOLED PROBES; ABLATION; BONE; MANAGEMENT; ELECTRODE AB Bony tumors in the hand and wrist are uncommon conditions. The objective of this article was to describe an impressive soft-tissue reaction with pain after radiofrequency ablation was used to treat a proximal phalangeal osteoid osteoma in the hand. We feel radiofrequency ablation should be cautiously used in the treatment of these lesions out of concern for similar complications. (J Hand Surg 2010;35A:990-994. (C) 2010 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Harrod, Christopher C.; Boykin, Robert E.; Jupiter, Jesse B.] Massachusetts Gen Hosp, Orthopaed Associates, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Orthopaed Associates, 55 Fruit St,YAW 2162, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 29 TC 6 Z9 6 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUN PY 2010 VL 35A IS 6 BP 990 EP 994 DI 10.1016/j.jhsa.2010.03.012 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 608GJ UT WOS:000278571100019 PM 20452144 ER PT J AU Lozano-Calderon, SA Brouwer, KM Doornberg, JN Goslings, JC Kloen, P Jupiter, JB AF Lozano-Calderon, S. A. Brouwer, K. M. Doornberg, J. N. Goslings, J. Carel Kloen, P. Jupiter, J. B. TI LONG-TERM OUTCOMES OF CORRECTIVE OSTEOTOMY FOR THE TREATMENT OF DISTAL RADIUS MALUNION SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Article DE corrective; osteotomy; distal radius; malunion; long-term; radiographic outcomes ID ULNAR-SHORTENING OSTEOTOMY; COLLES FRACTURES; CLOSING WEDGE; DEFORMITY; ADULTS; JOINT; COMPLICATIONS; WRIST; END AB Corrective osteotomy is an established but challenging treatment for distal radius malunion. Short- and intermediate-term results have been previously published while long-term results have not. The long-term results of 22 patients treated with corrective osteotomy for symptomatic distal radius malunion are presented (range 6-24 years, mean 13 years). All patients completed the DASH questionnaire and the modified Gartland and Werley, and Green and O'Brien scores postoperatively. Wrist alignment was assessed through standard wrist radiographs. Average wrist flexion-extension was 72.5% of the contralateral limb. Grip strength averaged 71%. The DASH score averaged 16 points corresponding to mild perceived disability. Results were categorized as fair on both the Gartland and Werley score (average 9 points) and the modified Green and O'Brien score (average 67 points). Wrist alignment was maintained over time but 13 patients presented mild to moderate symptomatic wrist arthritis. The outcome presented may be a reflection of the use of stricter evaluation instruments or reflect the development of post-traumatic arthritis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. Univ Amsterdam, Orthotrauma Res Ctr Amsterdam, Dept Trauma Surg, NL-1012 WX Amsterdam, Netherlands. Acad Med Ctr Amsterdam, Dept Orthopaed Surg, Amsterdam, Netherlands. RP Lozano-Calderon, SA (reprint author), New York Med Coll, Westchester Med Ctr, Dept Orthopaed Surg, Macy Pavil,Room 008,95 Grasslands Rd, Valhalla, NY 10595 USA. EM slozanocalderon@partners.org NR 45 TC 14 Z9 14 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-1934 J9 J HAND SURG-EUR VOL JI J. Hand Surg.-Eur. Vol. PD JUN PY 2010 VL 35E IS 5 BP 370 EP 380 DI 10.1177/1753193409357373 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 605CN UT WOS:000278325100004 PM 20031995 ER PT J AU Basile, J Babazadeh, S Lillestol, M Wright, M Laflamme, AK Weitzman, R AF Basile, J. Babazadeh, S. Lillestol, M. Wright, M. Laflamme, A. K. Weitzman, R. TI FIRST-LINE ALISKIREN/HYDROCHLOROTHIAZIDE COMBINATION THERAPY LOWERS BLOOD PRESSURE MORE EFFECTIVELY THAN HYDROCHLOROTHIAZIDE ALONE IN OBESE OLDER PATIENTS WITH STAGE 2 HYPERTENSION SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 20th Annual Meeting of the European-Society-of-Hypertension CY JUN 18-21, 2010 CL Oslo, NORWAY SP European Soc Hypertens C1 [Basile, J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Babazadeh, S.] Crest Clin Trials Inc, Santa Ana, CA USA. [Lillestol, M.] Lillestol Res LLC, Fargo, ND USA. [Wright, M.; Laflamme, A. K.] Novartis Pharma AG, Basel, Switzerland. [Weitzman, R.] Novartis Pharmaceut, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2010 VL 28 SU A BP E563 EP E563 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 665GM UT WOS:000283023405151 ER PT J AU Sullivan, LV Hicks, P Salazar, G Robinson, CK AF Sullivan, Loretta V. Hicks, Paul Salazar, Gilda Robinson, C. Kelet TI Patient Beliefs and Sense of Control Among Spanish-Speaking Patients with Diabetes in Northeast Colorado SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE Diabetes; Self-management; Health disparities; Latino ID AMERICANS EXPLANATORY MODEL; NON-HISPANIC WHITES; MEXICAN-AMERICANS; HEALTH-CARE; ETHNIC-DIFFERENCES; UNITED-STATES; ADULTS; DISEASE AB Purpose Latinos have higher diabetes prevalence and complication rates with lower use of self-management compared to other populations. This study evaluated perceived barriers to diabetes control among Spanish-speaking only patients in rural Colorado. Methods Thirty-five Spanish-speaking patients with diabetes were randomly sampled and interviewed about their attitudes and beliefs concerning diabetes, self-management activities, and the care they received. Results Patients perceived a high level of control over their diabetes. A minority of patients were adherent to recommended dietary changes or levels of exercise. Use of herbal home remedies to maintain glycemic control was common. Almost half of respondents felt that susto played a role in the development of their diabetes. Three fourths of those testing their glucose felt their physician was not interested in reviewing their blood sugar log. Conclusions Diabetes management programs should recognize the barriers patients may have to self-management and help patients incorporate traditional beliefs into a workable treatment regimen. C1 [Hicks, Paul] Univ Arizona, Dept Family & Community Med, Tucson, AZ 85719 USA. [Sullivan, Loretta V.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Sullivan, Loretta V.] Univ Calif Los Angeles, David Geffen Sch Med, Westwood, CA USA. [Salazar, Gilda; Robinson, C. Kelet] Salud Family Hlth Ctr, Ft Lupton, CO 80621 USA. RP Hicks, P (reprint author), Univ Arizona, Dept Family & Community Med, 1450 N Cherry Ave, Tucson, AZ 85719 USA. EM phicks@uph.org NR 20 TC 6 Z9 6 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD JUN PY 2010 VL 12 IS 3 BP 384 EP 389 DI 10.1007/s10903-008-9184-9 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 645ZW UT WOS:000281505700013 PM 19266283 ER PT J AU De Jesus, M AF De Jesus, Maria TI Institutional Barriers and Strategies to Health Promotion: Perspectives and Experiences of Cape Verdean Women Health Promoters SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE Health promotion; Cape Verdean immigrant women; Health promoters; Barriers; Strategies ID COMMUNITY-HEALTH; WORKERS; CARE AB Background Health promoters are critical resources in improving health care access and in providing culturally-responsive health education and interventions to members of medically underserved communities. Little is known about the barriers that impede their health-promoting practices and the strategies used to overcome these barriers. Methods In-depth, semi-structured interviews were conducted with nine Cape Verdean women health promoters to examine their perspectives on barriers and strategies to health promotion. Results Findings revealed how their health promotion practice is influenced by a host of institutional barriers, including insufficient program funding, restrictive institutional policies, and a lack of culturally and linguistically appropriate health resources. Adaptive and resistant strategies used to counterbalance these barriers included forming supportive internal and external alliances, having a good mentor, and "making noise." Discussion A complete and effective model of health promotion must embrace not only individual-level factors, but also macro-level factors, thus emphasizing the need for institutional change to enhance health-promoting practices. C1 [De Jesus, Maria] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [De Jesus, Maria] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP De Jesus, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM Maria_dejesus@dfci.harvard.edu FU NIMHD NIH HHS [L60 MD008329] NR 26 TC 3 Z9 3 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD JUN PY 2010 VL 12 IS 3 BP 398 EP 407 DI 10.1007/s10903-008-9127-5 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 645ZW UT WOS:000281505700015 PM 18307042 ER PT J AU Navarro, F Lieberman, J AF Navarro, Francisco Lieberman, Judy TI Small RNAs Guide Hematopoietic Cell Differentiation and Function SO JOURNAL OF IMMUNOLOGY LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; MICRORNA EXPRESSION; NEGATIVE REGULATOR; MIRNA EXPRESSION; MATURE MICRORNA; TRANSGENIC MICE; T-CELLS; B-CELLS AB MicroRNAs (miRNAs) are key regulators of gene expression that help direct normal differentiation and malignant transformation of hematopoietic cells. This review summarizes our current knowledge of how miRNAs function in normal and malignant hematopoiesis and how miRNAs might be applied for disease treatment. The Journal of Immunology, 2010, 184: 5939-5947. C1 [Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp Boston, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp Boston, Warren Alpert Bldg,Room 255,200 Longwood Ave, Boston, MA 02115 USA. EM lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015 FU GlaxoSmithKline-Immune Disease Institute Alliance FX This work was supported by a GlaxoSmithKline-Immune Disease Institute Alliance research grant and fellowship. NR 78 TC 45 Z9 50 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2010 VL 184 IS 11 BP 5939 EP 5947 DI 10.4049/jimmunol.0902567 PG 9 WC Immunology SC Immunology GA 606PP UT WOS:000278439600003 PM 20483778 ER PT J AU Collington, SJ Hallgren, J Pease, JE Jones, TG Rollins, BJ Westwick, J Austen, KF Williams, TJ Gurish, MF Weller, CL AF Collington, Sarah J. Hallgren, Jenny Pease, James E. Jones, Tatiana G. Rollins, Barrett J. Westwick, John Austen, K. Frank Williams, Timothy J. Gurish, Michael F. Weller, Charlotte L. TI The Role of the CCL2/CCR2 Axis in Mouse Mast Cell Migration In Vitro and In Vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; BONE-MARROW; AIRWAY INFLAMMATION; ALLERGIC RHINITIS; CCR2 EXPRESSION; NASAL-MUCOSA; MIP-1 ALPHA; MICE; PROGENITORS; CHEMOKINE AB Tissue-resident mast cells (MCs) are important in allergic diseases. In a mouse model of allergic airways inflammation, an increase in peribronchiolar MCs was associated with increased concentrations of the chemokine CCL2 in lung lavage. MC progenitors (MCps) arising in bone marrow (BM) are recruited to tissues by transendothelial migration, and we found that CCL2 is chemotactic for MCps in freshly isolated BM in vitro. Immature, but not mature, BM-derived MCs migrated in response to CCL2 when cultured in IL-3+stem cell factor (SCF) but not when cultured in IL-3 alone. However, the cells under both culture conditions expressed mRNA for CCR2, the receptor for CCL2, and bound the radiolabeled chemokine with similar affinities, highlighting SCF as a key mediator in coupling CCR2 to downstream events, culminating in chemotaxis. Immature BM-derived MCs from IL-3+SCF cultures, when administered i.v., accumulated at skin sites injected with CCL2 in vivo. MCp recruitment to the allergen-sensitized/challenged lung was significantly reduced in CCR2(-/-) and CCL2(-/-) mouse strains. However, reconstitution studies of sublethally irradiated and BM-reconstituted mice indicated that BM cells and stromal elements could provide CCL2, whereas the CCR2 function resided with stromal elements rather than BM cells. These experiments revealed a new function of SCF in chemokine receptor coupling, but they suggest a complex role of the CCL2/CCR2 axis in recruiting MCps during pulmonary inflammation. The Journal of Immunology, 2010, 184: 6114-6123. C1 [Collington, Sarah J.; Pease, James E.; Williams, Timothy J.; Weller, Charlotte L.] Univ London Imperial Coll Sci Technol & Med, Leukocyte Biol Sect, Natl Heart & Lung Inst, Fac Med,Med Res Council, London SW7 2AZ, England. [Collington, Sarah J.; Pease, James E.; Williams, Timothy J.; Weller, Charlotte L.] Univ London Imperial Coll Sci Technol & Med, Asthma UK Ctr Allerg Mech Asthma, Natl Heart & Lung Inst, Fac Med, London SW7 2AZ, England. [Westwick, John] Novartis Horsham Res Ctr, Novartis Inst Biomed Res, Horsham, W Sussex, England. [Hallgren, Jenny; Jones, Tatiana G.; Austen, K. Frank; Gurish, Michael F.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Hallgren, Jenny; Jones, Tatiana G.; Rollins, Barrett J.; Austen, K. Frank; Gurish, Michael F.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Rollins, Barrett J.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Weller, CL (reprint author), Univ London Imperial Coll Sci Technol & Med, Leukocyte Biol Sect, Natl Heart & Lung Inst, Fac Med,Med Res Council, London SW7 2AZ, England. EM charlotte.weller@imperial.ac.uk FU Novartis Institutes for Biomedical Research; Asthma UK Centre; Swedish Society for Medical Research; National Institutes of Health (NIH) [R01-AI083516] FX This work was supported by a Ph.D. studentship provided by Novartis Institutes for Biomedical Research, the Asthma UK Centre, the Swedish Society for Medical Research, and the National Institutes of Health (Grant NIH R01-AI083516). NR 48 TC 39 Z9 41 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2010 VL 184 IS 11 BP 6114 EP 6123 DI 10.4049/jimmunol.0904177 PG 10 WC Immunology SC Immunology GA 606PP UT WOS:000278439600024 PM 20427772 ER PT J AU Hubbard, LLN Ballinger, MN Thomas, PE Wilke, CA Standiford, TJ Kobayashi, KS Flavell, RA Moore, BB AF Hubbard, Leah L. N. Ballinger, Megan N. Thomas, Peedikayil E. Wilke, Carol A. Standiford, Theodore J. Kobayashi, Koichi S. Flavell, Richard A. Moore, Bethany B. TI A Role for IL-1 Receptor-Associated Kinase-M in Prostaglandin E-2-Induced Immunosuppression Post-Bone Marrow Transplantation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; TOLL-LIKE RECEPTORS; PNEUMOCOCCAL PNEUMONIA; ALVEOLAR MACROPHAGES; PHAGOSOME MATURATION; SCAVENGER RECEPTORS; HOST-DEFENSE; M EXPRESSION; ACTIVATION; PATHWAY AB Following immune reconstitution, hematopoietic stem cell transplant patients often display reduced immune function and are especially susceptible to lung infections. In a mouse model of syngeneic bone marrow transplantation (BMT), we previously reported that PGE(2) is overproduced in lungs of BMT mice, significantly impairing host defense against Pseudomonas aeruginosa. This impairment in host defense post-BMT is also marked by diminished alveolar macrophage (AM) phagocytosis, bacterial killing, and production of TNF-alpha and cysteinyl leukotrienes. However, a mechanism by which overproduction of PGE(2) suppresses pulmonary host defense post-BMT is unknown. As IL-1R-associated kinase (IRAK)-M is a known inhibitor of MyD88-dependent IL-1R/TLR signaling and macrophage function, we sought to determine whether IRAK-M is involved in PGE(2)-induced immunosuppression post-BMT. We found that IRAK-M expression is elevated 3.5-fold in BMT AMs relative to control AMs, and this is related to AM overproduction of PGE(2). Furthermore, genetic ablation of IRAK-M in the bone marrow of BMT mice restores host defense against P. aeruginosa. Despite AM overproduction of PGE(2) and elevated E prostanoid 2 receptor expression, AM phagocytosis, killing, and production of cysteinyl leukotrienes and TNF-alpha are restored in the absence of IRAK-M post-BMT. Also, treatment with PGE(2) does not inhibit AM phagocytosis in the absence of IRAK-M. These data suggest that the absence of IRAK-M in the hematopoietic compartment post-BMT enhances pulmonary host defense and mitigates AM sensitivity to the inhibitory effects of PGE(2). Therefore, strategies to limit IRAK-M elevation post-BMT may be efficacious in reducing patient susceptibility to infection. The Journal of Immunology, 2010, 184: 6299-6308. C1 [Hubbard, Leah L. N.] Univ Michigan, Grad Program Immunol, Ann Arbor, MI 48109 USA. [Ballinger, Megan N.; Wilke, Carol A.; Standiford, Theodore J.; Moore, Bethany B.] Univ Michigan, Div Pulm & Crit Care Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Thomas, Peedikayil E.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, Howard Hughes Med Inst, New Haven, CT 06520 USA. RP Moore, BB (reprint author), 4053 BSRB,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM bmoore@umich.edu OI Moore, Bethany/0000-0003-3051-745X FU National Institutes of Health [AI065543, P50 HL074024, HL25243]; Howard Hughes Medical Institute FX This work was supported by National Institutes of Health Grants AI065543 (to B. B. M.) and P50 HL074024 and HL25243 (to T.J.S.). R. A. F. is an Investigator of the Howard Hughes Medical Institute. NR 25 TC 25 Z9 25 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 JUN 1 PY 2010 VL 184 IS 11 BP 6299 EP 6308 DI 10.4049/jimmunol.0902828 PG 10 WC Immunology SC Immunology GA 606PP UT WOS:000278439600044 PM 20439918 ER PT J AU Canter, JA Robbins, GK Selph, D Clifford, DB Kallianpur, AR Shafer, R Levy, S Murdock, DG Ritchie, MD Haas, DW Hulgan, T AF Canter, Jeffrey A. Robbins, Gregory K. Selph, Doug Clifford, David B. Kallianpur, Asha R. Shafer, Robert Levy, Shawn Murdock, Deborah G. Ritchie, Marylyn D. Haas, David W. Hulgan, Todd CA Aids Clinical Trials Grp Study 384 New Work Concept Sheet 273 Teams TI African Mitochondrial DNA Subhaplogroups and Peripheral Neuropathy during Antiretroviral Therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID REGION SEQUENCES; HAPLOGROUPS; DISEASE; RISK AB Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse-transcriptase inhibitors was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine whether nucleoside reverse-transcriptase inhibitor-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic black persons with genomic data, 51 (33%) developed peripheral neuropathy. In a multivariate model, African mtDNA subhaplogroup L1c was an independent predictor of peripheral neuropathy (odds ratio, 3.7 [95% confidence interval, 1.1-12.0]). An African mtDNA subhaplogroup is for the first time implicated in susceptibility to nucleoside reverse-transcriptase inhibitor-associated toxicity. C1 [Canter, Jeffrey A.; Murdock, Deborah G.; Ritchie, Marylyn D.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. [Canter, Jeffrey A.; Selph, Doug; Murdock, Deborah G.; Ritchie, Marylyn D.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Dept Med, Nashville, TN 37212 USA. [Kallianpur, Asha R.] Vanderbilt Univ, Sch Med, Div Gen Internal Med & Publ Hlth, Nashville, TN 37212 USA. [Haas, David W.; Hulgan, Todd] Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37212 USA. [Levy, Shawn] Vanderbilt Univ, Sch Med, Microarray Shared Resource Facil, Nashville, TN 37212 USA. [Haas, David W.] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37212 USA. [Robbins, Gregory K.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. [Shafer, Robert] Stanford Univ, Dept Med Infect Dis, Stanford, CA 94305 USA. [Clifford, David B.] Washington Univ, Sch Med, Dept Neurol & Med, St Louis, MO USA. RP Hulgan, T (reprint author), 345 24th Ave N,Suite 105, Nashville, TN 37203 USA. EM todd.hulgan@vanderbilt.edu RI Ritchie, Marylyn/C-1114-2012; Murdock, Deborah/C-3483-2012; Hulgan, Todd/B-3947-2014 OI Hulgan, Todd/0000-0002-3339-067X FU NCRR NIH HHS [RR024975, UL1 RR024975]; NHLBI NIH HHS [HL087726, R21 HL087726]; NIAID NIH HHS [UM1 AI069495, AI062435, AI069415, AI069419, AI069423, AI069424, AI069428, AI069432, AI069434, AI069450, AI069452, AI069465, AI069471, AI069472, AI069474, AI069477, AI069484, AI069495, AI069501, AI069502, AI069511, AI069513, AI069532, AI069556, AI077505, AI25859, AI27661, AI34835, AI34853, AI38844, AI46370, AI54999, AI69467, AI69495, K01 AI062435, P30 AI054999, R01 AI077505, U01 AI025859, U01 AI027661, U01 AI034853, U01 AI038858, U01 AI046370, U01 AI068636, U01 AI069415, U01 AI069419, U01 AI069423, U01 AI069424, U01 AI069428, U01 AI069432, U01 AI069434, U01 AI069450, U01 AI069452, U01 AI069465, U01 AI069467, U01 AI069471, U01 AI069472, U01 AI069474, U01 AI069477, U01 AI069484, U01 AI069495, U01 AI069501, U01 AI069502, U01 AI069511, U01 AI069513, U01 AI069532, U01 AI069556, UM1 AI069415, UM1 AI069419, UM1 AI069423, UM1 AI069424, UM1 AI069428, UM1 AI069432, UM1 AI069434, UM1 AI069450, UM1 AI069452, UM1 AI069465, UM1 AI069467, UM1 AI069471, UM1 AI069472, UM1 AI069474, UM1 AI069477, UM1 AI069484, UM1 AI069501, UM1 AI069502, UM1 AI069511, UM1 AI069513, UM1 AI069532, UM1 AI069556]; NIMH NIH HHS [MH071205, R01 MH071205]; NINDS NIH HHS [NS059330, R21 NS059330, R21 NS059330-01]; PHS HHS [AL32782] NR 16 TC 21 Z9 22 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2010 VL 201 IS 11 BP 1703 EP 1707 DI 10.1086/652419 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 589TH UT WOS:000277176200014 PM 20402593 ER PT J AU Mechtouff, L Touze, E Steg, PG Ohman, EM Goto, S Hirsch, AT Rother, J Aichner, FT Weimar, C Bhatt, DL Alberts, MJ Mas, JL AF Mechtouff, L. Touze, E. Steg, P. G. Ohman, E. M. Goto, S. Hirsch, A. T. Roether, J. Aichner, F. T. Weimar, C. Bhatt, D. L. Alberts, M. J. Mas, J. -L. CA REACH Registry Investigators TI Worse blood pressure control in patients with cerebrovascular or peripheral arterial disease compared with coronary artery disease SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE antihypertensive drugs; blood pressure; cerebrovascular disease; coronary artery disease; peripheral arterial disease ID PROSPECTIVELY-DESIGNED OVERVIEWS; MAJOR CARDIOVASCULAR EVENTS; HYPERTENSION CONTROL; HEART-DISEASE; UNCONTROLLED HYPERTENSION; MYOCARDIAL-INFARCTION; THERAPEUTIC INERTIA; RANDOMIZED-TRIALS; LOWERING REGIMENS; ISCHEMIC-STROKE AB Mechtouff L, Touze E, Steg PG, Ohman EM, Goto S, Hirsch AT, Rother J, Aichner FT, Weimar C, Bhatt DL, Alberts MJ, Mas J-L, on behalf of the REACH Registry Investigators (Paris-Descartes University; Universite Paris 7; Paris, France, Duke University, Durham NC, USA, Tokai University, Isehara, Japan, University of Minnesota, Minneapolis, MN, USA, Academic Teaching Hospital Hannover Medical School, Minden, Germany, Academic Teaching Hospital Wagner-Jauregg, Linz, Austria, University of Duisburg-Essen, Essen, Germany, VA Boston Healthcare System, and Brigham and Women's Hospital, Boston, MA; and Northwestern University Medical School, Chicago, IL; USA). Worse blood pressure control in patients with cerebrovascular or peripheral arterial disease compared with coronary artery disease. J Intern Med 2010; 267:621-633. Objectives. Poor blood pressure (BP) control is common amongst patients with symptomatic atherothrombotic disease. It is unclear whether BP control and management differ across atherothrombotic disease subtypes. Methods. We analysed the baseline data of 44 984 patients with documented coronary artery disease (CAD) only (n = 30 414), cerebrovascular disease (CVD) only (n = 11 359) and peripheral arterial disease (PAD) only (n = 3211) from the international REduction of Atherothrombosis for Continued Health Registry and investigated the impact of atherothrombotic disease subtype on BP control and use of antihypertensive drugs. Results. The proportion of patients with BP controlled (< 140/90 mmHg) was higher in CAD (58.1%) than in CVD (44.8%) or PAD (38.9%) patients (P < 0.001). Amongst patients with treated hypertension, CAD patients were more likely to have BP controlled than were CVD patients [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 1.59-1.75] or PAD (OR = 2.30; 95% CI = 2.10-2.52). These differences were smaller in women than in men and decreased with age. Amongst treated patients, CAD patients were more likely to receive >= 3-drug combination therapies than were CVD (OR = 1.73; 95% CI = 1.64-1.83) or PAD (OR = 1.64; 95% CI = 1.49-1.80) patients. Adjustment for age, gender, waist obesity, diabetes, education level and world region did not alter the results. Conclusions. Coronary artery disease patients are more likely than CVD or PAD patients to have BP controlled and to receive antihypertensive drugs, particularly combination therapies. Promotion of more effective BP control through combination antihypertensive therapies could improve secondary prevention and therefore prevent complications in CVD and PAD patients. C1 [Touze, E.] Univ Paris 05, INSERM, Hop St Anne, U894,Serv Neurol,Dept Neurol, F-75014 Paris, France. [Steg, P. G.] Univ Paris 07, INSERM, U698, AP HP, Paris, France. [Ohman, E. M.] Duke Univ, Div Cardiol, Durham, NC USA. [Goto, S.] Tokai Univ, Dept Med Cardiol, Isehara, Kanagawa, Japan. [Hirsch, A. T.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Roether, J.] Acad Teaching Hosp, Hannover Med Sch, Dept Neurol, Johannes Wesling Klinikum, Minden, Germany. [Aichner, F. T.] Acad Teaching Hosp Wagner Jauregg, Linz, Austria. [Weimar, C.] Univ Duisburg Essen, Dept Neurol, Essen, Germany. [Bhatt, D. L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, D. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Alberts, M. J.] Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. RP Touze, E (reprint author), Univ Paris 05, INSERM, Hop St Anne, U894,Serv Neurol,Dept Neurol, 1 Rue Cabanis, F-75014 Paris, France. EM e.touze@ch-sainte-anne.fr OI Touze, Emmanuel/0000-0002-7254-2162 FU sanofi-aventis, Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan) FX The REACH Registry is sponsored by sanofi-aventis, Bristol-Myers Squibb and the Waksman Foundation (Tokyo, Japan). The REACH Registry is endorsed by the World Heart Federation. A complete list of REACH investigators is accessible online at http://www.reachregistry.org. The REACH Registry enforces a no ghost-writing policy. This manuscript was written and edited by the authors, who take full responsibility for its content. We thank Sophie Rushton-Smith, PhD, for her assistance with coordinating revisions and providing editorial help in preparing this manuscript including editing, checking content and language, formatting, referencing and preparing tables and figures. NR 39 TC 11 Z9 12 U1 5 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JUN PY 2010 VL 267 IS 6 BP 621 EP 633 DI 10.1111/j.1365-2796.2009.02198.x PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 591SF UT WOS:000277322900008 PM 20210837 ER PT J AU Pendse, GV Schwarz, AJ Baumgartner, R Coimbra, A Upadhyay, J Borsook, D Becerra, L AF Pendse, Gautam V. Schwarz, Adam J. Baumgartner, Richard Coimbra, Alexandre Upadhyay, Jaymin Borsook, David Becerra, Lino TI Robust, Unbiased General Linear Model Estimation of phMRI Signal Amplitude in the Presence of Variation in the Temporal Response Profile SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE general linear model (GLM); robust; bias; variance; pharmacological MRI (PhMRI); singular value decomposition (SVD) ID EVENT-RELATED FMRI; CEREBRAL BLOOD-VOLUME; PHARMACOLOGICAL MRI; HUMAN BRAIN; FUNCTIONAL MRI; HEALTHY-VOLUNTEERS; CLUSTER-ANALYSIS; ACUTE COCAINE; RAT-BRAIN; BUPRENORPHINE AB Purpose: To determine a simple yet. robust method to generate parsimonious design matrices that accurately estimate the 'pharmacological MRI" (phMRI) response amplitude in the presence of both confounding signals and variability in temporal profile. Variability in the temporal response profile of phMRI time series data is often observed. If not properly accounted for, this variation can result in inaccurate and unevenly biased signal amplitude estimates when modeled within a general linear model (GLM) framework. Materials and Methods: The approach uses a low-rank singular value decomposition (SVD) approximation to a set of vectors capturing anticipated variations of no interest around the signal model to generate additional regressors for the design matrix. The method is demonstrated for both plateau and bolus type phMRI response profiles In the presence of variation in signal onset and/or shape, and applied to an in vivo blood oxygenation level-dependent (BOLD) phMRI study of buprenorphine in healthy human subjects. Results: In general, 2-3 additional regressors, capturing >75% of the anticipated variance, resulted in robust and unbiased signal amplitude estimates in the presence of substantial variability. Conclusion: This method provides a simple and flexible means to provide robust phMRI amplitude estimates within a GLM framework. C1 [Pendse, Gautam V.; Upadhyay, Jaymin; Borsook, David; Becerra, Lino] Harvard Univ, McLean Hosp, Sch Med, PAIN Grp,Brain Imaging Ctr, Belmont, MA 02478 USA. [Pendse, Gautam V.; Schwarz, Adam J.; Baumgartner, Richard; Coimbra, Alexandre; Upadhyay, Jaymin; Borsook, David; Becerra, Lino] Imaging Consortium Drug Dev ICD, Belmont, MA USA. [Schwarz, Adam J.] Eli Lilly & Co, Translat Imaging Exploratory & Program Med, Indianapolis, IN 46285 USA. [Baumgartner, Richard] Merck & Co Inc, Biometr Res, Rahway, NJ USA. [Coimbra, Alexandre] Merck & Co Inc, Dept Imaging, West Point, PA USA. [Borsook, David; Becerra, Lino] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Borsook, David; Becerra, Lino] Harvard Univ, Sch Med, Boston, MA USA. RP Pendse, GV (reprint author), Harvard Univ, McLean Hosp, Sch Med, PAIN Grp,Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM gpendse@mclean.harvard.edu FU Imaging Consortium for Drug Development (ICD) FX Contract grant sponsor: the Imaging Consortium for Drug Development (ICD). NR 44 TC 8 Z9 8 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2010 VL 31 IS 6 BP 1445 EP 1457 DI 10.1002/jmri.22180 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 602YF UT WOS:000278174300019 PM 20512898 ER PT J AU Stacy, RC Jakobiec, FA Lessell, S Cestari, DM AF Stacy, Rebecca C. Jakobiec, Frederick A. Lessell, Simmons Cestari, Dean M. TI Monocular Nasal Hemianopia From Atypical Sphenoid Wing Meningioma SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Editorial Material ID OPTIC-NERVE; CATARACT AB Neurogenic monocular nasal field defects respecting the vertical midline are quite uncommon. We report a case of a unilateral nasal hemianopia that was caused by compression of the left optic nerve by a sphenoid wing meningioma. Histological examination revealed that the pathology of the meningioma was consistent with that of an atypical meningioma, which carries a guarded prognosis with increased chance of recurrence. The tumor was debulked surgically, and the patient's visual field defect improved. C1 [Stacy, Rebecca C.; Lessell, Simmons; Cestari, Dean M.] Massachusetts Eye & Ear Infirm, Dept Neuroophthalmol, Boston, MA 02114 USA. [Stacy, Rebecca C.; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ocular Pathol, Boston, MA 02114 USA. RP Stacy, RC (reprint author), Suite 321,243 Charles St, Boston, MA 02114 USA. EM Rebecca_Stacy@meei.harvard.edu NR 13 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD JUN PY 2010 VL 30 IS 2 BP 160 EP 163 DI 10.1097/WNO.0b013e3181de8b56 PG 4 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 605UL UT WOS:000278372400012 PM 20431487 ER PT J AU Vanderwerf, S David, L Buck, D Romanelli, R Neve, K AF Vanderwerf, S. David, L. Buck, D. Romanelli, R. Neve, K. TI Methamphetamine-induced alterations in the proteome of striatal lipid rafts SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 4th ISN Special Conference on Membrane Domains in CNS Physiology and Pathology CY MAY 22-26, 2010 CL Erice, ITALY SP ISN C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2010 VL 113 SU 1 MA 101 BP 30 EP 30 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 603SV UT WOS:000278229300102 ER PT J AU Denny, CA Heinecke, KA Kim, YP Baek, RC Loh, KS Butters, TD Bronson, RT Platt, FM Seyfried, TN AF Denny, Christine A. Heinecke, Karie A. Kim, Youngho P. Baek, Rena C. Loh, Katrina S. Butters, Terry D. Bronson, Roderick T. Platt, Frances M. Seyfried, Thomas N. TI Restricted ketogenic diet enhances the therapeutic action of N-butyldeoxynojirimycin towards brain GM2 accumulation in adult Sandhoff disease mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE GA2; ganglioside; GM2; ketogenic diet; lysosomal storage disease; Sandhoff disease ID BONE-MARROW-TRANSPLANTATION; THIN-LAYER CHROMATOGRAPHY; KETONE-BODIES; CALORIC RESTRICTION; AUDIOGENIC-SEIZURES; GANGLIOSIDE CONTENT; CEREBELLAR-ATAXIA; LYSOSOMAL STORAGE; GAUCHERS-DISEASE; MOUSE MODELS AB P>Sandhoff disease is an autosomal recessive, neurodegenerative disease involving the storage of brain ganglioside GM2 and asialo-GM2. Previous studies showed that caloric restriction, which augments longevity, and N-butyldeoxynojirimycin (NB-DNJ, Miglustat), an imino sugar that hinders the glucosyltransferase catalyzing the first step in glycosphingolipid biosynthesis, both increase longevity and improve motor behavior in the beta-hexosaminidase (Hexb) knockout (-/-) murine model of Sandhoff disease. In this study, we used a restricted ketogenic diet (KD-R) and NB-DNJ to combat ganglioside accumulation. Adult Hexb-/- mice were placed into one of the following groups: (i) a standard diet (SD), (ii) a SD with NB-DNJ (SD + NB-DNJ), (iii) a KD-R, and (iv) a KD-R with NB-DNJ (KD-R + NB-DNJ). Forebrain GM2 content (mu g sialic acid/100 mg dry wt) in the four groups was 375 +/- 15, 312 +/- 8, 340 +/- 28, and 279 +/- 26, respectively, indicating an additive interaction between NB-DNJ and the KD-R. Most interestingly, brain NB-DNJ content was 3.5-fold greater in the KD-R + NB-DNJ mice than in the SD + NB-DNJ mice. These data suggest that the KD-R and NB-DNJ may be a potential combinatorial therapy for Sandhoff disease by enhancing NB-DNJ delivery to the brain and may allow lower dosing to achieve the same degree of efficacy as high dose monotherapy. C1 [Denny, Christine A.; Heinecke, Karie A.; Kim, Youngho P.; Baek, Rena C.; Loh, Katrina S.; Seyfried, Thomas N.] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Butters, Terry D.] Univ Oxford, Dept Biochem, Glycobiol Inst, Oxford OX1 3QU, England. [Bronson, Roderick T.] Dana Farber Harvard Comprehens Canc Ctr, Boston, MA USA. [Platt, Frances M.] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England. RP Seyfried, TN (reprint author), Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. EM thomas.seyfried@bc.edu RI Denny, Christine Ann/I-5235-2015; OI Denny, Christine Ann/0000-0002-6926-2020; Seyfried, Thomas/0000-0003-1491-3989 FU NIH [NS055195]; Boston College Research Expense Fund; National Tay-Sachs and Allied Disease Association, Inc. (NTSAD) FX We thank John Mantis and Aurelien Bergmann for excellent technical assistance. This work was supported in part by NIH grant NS055195, Boston College Research Expense Fund, and the National Tay-Sachs and Allied Disease Association, Inc. (NTSAD). NR 50 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2010 VL 113 IS 6 BP 1525 EP 1535 DI 10.1111/j.1471-4159.2010.06733.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 604WT UT WOS:000278309900015 PM 20374428 ER PT J AU Sinha, S Subramanian, S Emerson-Webber, A Lindner, M Burrows, GG Grafe, M Linington, C Vandenbark, AA Bernard, CCA Offner, H AF Sinha, Sushmita Subramanian, Sandhya Emerson-Webber, Ashley Lindner, Maren Burrows, Gregory G. Grafe, Marjorie Linington, Christopher Vandenbark, Arthur A. Bernard, Claude C. A. Offner, Halina TI Recombinant TCR Ligand Reverses Clinical Signs and CNS Damage of EAE Induced by Recombinant Human MOG SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Article DE EAE; MS; recombinant human MOG; CNS damage ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; MULTIPLE-SCLEROSIS; CYTOKINE SWITCH; MICE; PEPTIDE; CELLS; PATTERN; PROTEIN; RAT AB Increasing evidence suggests that in addition to T cell-dependent effector mechanisms, autoantibodies are also involved in the pathogenesis of MS, including demyelinating antibodies specific for myelin oligodendrocyte glycoprotein (MOG). Our previous studies have demonstrated that recombinant T cell receptor ligands (RTLs) are very effective for treating T cell-mediated experimental autoimmune encephalomyelitis (EAE). In order to expand the scope of RTL therapy in MS patients, it was of interest to study RTL treatment of EAE involving a demyelinating antibody component. Therefore, we evaluated the therapeutic effects of RTL551, specific for T cells reactive to mouse (m)MOG-35-55 peptide, on EAE induced with recombinant human (rh)MOG in C57BL/6 mice. We report that RTL551 therapy can reverse disease progression and reduce demyelination and axonal damage induced by rhMOG without suppressing the anti-MOG antibody response. This result suggests that T cell-mediated inflammation and associated blood-brain barrier dysfunction are the central contributors to EAE pathogenesis and that successful regulation of these key players restricts potential damage by demyelinating antibodies. The results of our study lend support for the use of RTL therapy for treatment of MS subjects whose disease includes inflammatory T cells as well as those with an additional antibody component. C1 [Sinha, Sushmita; Subramanian, Sandhya; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. [Sinha, Sushmita; Burrows, Gregory G.; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Emerson-Webber, Ashley; Bernard, Claude C. A.] Monash Univ, Immunol & Stem Cell Labs, Multiple Sclerosis Res Grp, Clayton, Vic 3800, Australia. [Lindner, Maren; Linington, Christopher] Univ Glasgow, Div Clin Neurosci, Glasgow G12 9PP, Lanark, Scotland. [Burrows, Gregory G.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. [Burrows, Gregory G.; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Tykeson Multiple Sclerosis Res Lab, Portland, OR 97239 USA. [Grafe, Marjorie] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu OI Linington, Christopher/0000-0002-0937-9526 FU National Multiple Sclerosis Society [FG1749-A-1, RG3794-A-4, RG3468, RG3844A2/1]; Multiple Sclerosis Society [874/07]; National Institutes of Health [NS47661, AI43960, NS46877]; Nancy Davis Center Without Walls; Biomedical Laboratory R&D Service, Department of Veterans Affairs; National Health and Medical Research Council of Australia; Baker Foundation; Bellberry Ltd Fund FX The authors wish to thank Ms. Eva K. Niehaus for assistance in manuscript preparation. Dr. Sinha is a Postdoctoral Fellow of the National Multiple Sclerosis Society, and this work was supported in part by National Multiple Sclerosis Society Postdoctoral Fellowship FG1749-A-1 and National Multiple Sclerosis Society grants RG3794-A-4, RG3468, and RG3844A2/1; Multiple Sclerosis Society grant 874/07; National Institutes of Health grants NS47661, AI43960, and NS46877; The Nancy Davis Center Without Walls; The Biomedical Laboratory R&D Service, Department of Veterans Affairs; The National Health and Medical Research Council of Australia, The Baker Foundation; and the Bellberry Ltd Fund. NR 22 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD JUN PY 2010 VL 5 IS 2 BP 231 EP 239 DI 10.1007/s11481-009-9175-1 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 593CR UT WOS:000277430100008 PM 19789980 ER PT J AU Albuquerque, F Fiorella, D Hirsch, J Prestigiacomo, C Zaidat, O Tarr, R AF Albuquerque, Felipe Fiorella, David Hirsch, Joshua Prestigiacomo, Charles Zaidat, Osama Tarr, Robert TI CREST: equipoise realized SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID CAROTID STENOSIS; ENDARTERECTOMY C1 [Tarr, Robert] Univ Hosp, Case Med Ctr, Dept Radiol, Cleveland, OH 44106 USA. [Albuquerque, Felipe] Barrow Neurol Inst, Dept Neurosurg, Phoenix, AZ 85013 USA. [Fiorella, David] SUNY Stony Brook, Med Ctr, Dept Neurosurg, New York, NY USA. [Hirsch, Joshua] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Prestigiacomo, Charles] Univ Med & Dent New Jersey, Dept Neurosurg, Newark, NJ 07103 USA. [Zaidat, Osama] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. RP Tarr, R (reprint author), Univ Hosp, Case Med Ctr, Dept Radiol, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM robert.tarr@uhhospitals.org NR 4 TC 1 Z9 1 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUN PY 2010 VL 2 IS 2 BP 97 EP 98 DI 10.1136/jnis.2010.002634 PG 2 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 601ZF UT WOS:000278106200002 PM 21990586 ER PT J AU Natarajan, SK Ogilvy, CS Hopkins, LN Siddiqui, AH Levy, EI AF Natarajan, Sabareesh K. Ogilvy, Christopher S. Hopkins, L. Nelson Siddiqui, Adnan H. Levy, Elad I. TI Initial experience with an everolimus-eluting, second-generation drug-eluting stent for treatment of intracranial atherosclerosis SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID CORONARY-ARTERY LESIONS; CANINE CEREBRAL VASCULATURE; RANDOMIZED CONTROLLED-TRIAL; FOLLOW-UP; SLOW-RELEASE; ISCHEMIC-STROKE; DOUBLE-BLIND; TAXUS-IV; STENOSIS; THROMBOSIS AB Background and purpose High in-stent restenosis (ISR) rates have been reported after treatment of intracranial atherosclerotic stenosis (ICAS). Balloon-mounted drug-luting stent (DES) implantation has led to an ISR reduction in coronary vessels and may provide a solution to overcome this obstacle in the intracranial circulation. We present our initial experience with the everolimus-eluting stent (EES; Abbott Vascular, Abbott Park, Illinois, USA), a second-generation balloon-mounted DES, for ICAS treatment. Methods A retrospective review of prospectively collected endovascular data at our institution resulted in the identification of six patients with ICAS treated with EES. Data collected included patient demographics, presentation, comorbidities and lesion, intervention and follow-up details. Results These six patients had >70% angiographic ICAS and history of stroke or recurrent transient ischemic attacks, despite aspirin therapy and medical management of comorbidities. Lesions were located in the V4-vertebral artery segment (n-2), M1 middle cerebral artery segment (n=1), proximal basilar artery (n=1), supraclinoid internal carotid artery (n=1) and petrous internal carotid artery (n=1). Average stenosis severity was 82.8 +/- 6.6% (median, 80%); average lesion length was 10.2 +/- 2.2 mm. Stent placement was successful in all cases. Average postintervention stenosis was 5.5 +/- 4.4% (median, 7.5%). One patient had postintervention reperfusion hemorrhage that required urgent decompressive craniectomy. None of the five patients with angiographic follow-up (5-6 months) had ISR. The six patients had 4-10 months of clinical follow-up. Only the patient with reperfusion hemorrhage had decreased functional status after treatment (modified Rankin scale score=4) and is making a slow recovery. Conclusion This study confirms feasibility of use of a second-generation DES for ICAS and provides short-term follow-up results. C1 [Natarajan, Sabareesh K.; Ogilvy, Christopher S.; Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Millard Fillmore Gates Hosp, Dept Neurosurg, Buffalo, NY 14209 USA. [Natarajan, Sabareesh K.; Ogilvy, Christopher S.; Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Toshiba Stroke Res Ctr, Buffalo, NY 14209 USA. [Natarajan, Sabareesh K.; Ogilvy, Christopher S.; Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Dept Neurosurg, Buffalo, NY 14209 USA. [Ogilvy, Christopher S.] Massachusetts Gen Hosp, Neurovasc Serv, Boston, MA 02114 USA. [Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Dept Radiol, Sch Med & Biomed Sci, Buffalo, NY 14209 USA. RP Levy, EI (reprint author), SUNY Buffalo, Millard Fillmore Gates Hosp, Dept Neurosurg, 3 Gates Circle, Buffalo, NY 14209 USA. EM elevy@ubns.com FU Toshiba; Abbott; Boston Scientific; Cordis; ev3; Micrus Endovascular; University at Buffalo; National Institutes of Health [NINDS 1R01NS064592-01A1] FX Dr Hopkins receives research support from Toshiba; serves as a consultant to Abbott, Boston Scientific, Cordis, Micrus and W. L. Gore; has a financial interest in AccessClosure, Boston Scientific and Micrus; serves as a board member, trustee, or holds an officer position in AccessClosure and Micrus; receives research support from Abbott, Boston Scientific, Cordis, and ev3; consultant to Lumen Biomedical; financial interest in Cordis, serves as the conference director for Nurcon Conferences/Strategic Medical Seminars LLC; receives honoraria from Bard, Boston Scientific, and Cordis, and serves on the Speakers' Bureau for Abbott Vascular. Dr Levy receives research grant support, other research support (devices) and honoraria from Boston Scientific and research support from Micrus Endovascular and ev3; has ownership interests in Intratech Medical Ltd and Mynx/Access Closure; serves as a consultant on the board of Scientific Advisors to Codman Neurovascular; serves as a consultant per project and/or per hour for Micrus Endovascular, ev3 and TheraSyn Sensors, Inc.; and receives fees for carotid stent training from Abbott Vascular and ev3. Dr Levy receives no consulting salary arrangements. All consulting is per project and/or per hour. Dr Ogilvy serves as a consultant to Mizuho America. Dr Natarajan has no disclosure information to report. Dr Siddiqui has received research grants from the University at Buffalo and from the National Institutes of Health (NINDS 1R01NS064592-01A1) is a consultant to Codman Neurovascular, Concentric Medical, ev3 and Micrus Endovascular; serves on speakers' bureaus for Codman Neurovascular and Genentech; and has received honoraria from Genentech, Neocure Group LLC, American Association of Neurological Surgeons' courses and an Emergency Medicine Conference and from Codman Neurovascular for training other neurointerventionists. Dr Siddiqui receives NR 46 TC 6 Z9 6 U1 0 U2 8 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUN PY 2010 VL 2 IS 2 BP 104 EP 109 DI 10.1136/jnis.2009.001875 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 601ZF UT WOS:000278106200004 PM 21990588 ER PT J AU Wall, C AF Wall, Conrad, III TI Application of Vibrotactile Feedback of Body Motion to Improve Rehabilitation in Individuals With Imbalance SO JOURNAL OF NEUROLOGIC PHYSICAL THERAPY LA English DT Article DE balance rehabilitation; vibrotactile tilt feedback; biofeedback; balance prosthesis AB Background and Purpose: Balance rehabilitation and vestibular or balance prostheses are both emerging fields that have a potential for synergistic interaction. This article reviews vibrotactile prosthetic devices that have been developed to date and ongoing work related to the application of vibrotactile feedback for enhanced postural control. A vibrotactile feedback device developed in the author's laboratory is described. Methods: Twelve subjects with vestibular hypofunction were tested on a platform that moved randomly in a plane, while receiving vibrotactile feedback in the anteroposterior direction. The feedback allowed subjects to significantly decrease their anteroposterior body tilt but did not change mediolateral tilt. A tandem walking task performed by subjects with vestibulopathies demonstrated a reduction in their mediolateral sway due to vibrotactile feedback of mediolateral body tilt, after controlling for the effects of task learning. Published findings from 2 additional experiments conducted in the laboratories of collaborating physical therapists are summarized. Results: The Dynamic Gait Index scores in community-dwelling elderly individuals who were prone to falls were significantly improved with the use of mediolateral body tilt feedback. Discussion and Conclusions: Although more work is needed, these results suggest that vibrotactile tilt feedback of subjects' body motion can be used effectively by physical therapists for balance rehabilitation. A preliminary description of the third-generation device that has been reduced from a vest format to a belt format is described to demonstrate the progressive evolution from research to clinical application. C1 [Wall, Conrad, III] Harvard Univ, Sch Med, Dept Otolol & Laryngol, Boston, MA 02115 USA. [Wall, Conrad, III] Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, Boston, MA 02114 USA. RP Wall, C (reprint author), Harvard Univ, Sch Med, Dept Otolol & Laryngol, Boston, MA 02115 USA. EM cwall@mit.edu FU National Institutes of Health [NIDCD_R01DC0006210]; Keck Foundation FX Supported by the National Institutes of Health (in part).; The author acknowledges the significant contributions of Dr. Fay Horak at Oregon Health Sciences University and Dr. Diane Wrisley at the University of Buffalo, without whom this work would have not been possible. He appreciates the assistance by the members of the Horak and Wrisley Laboratories. Many contributed to the development of the balance vest prototype including Angus Rupert, Lars Oddsson, the seniors of the Mechatronics Department of the Swedish Royal Institute of Technology (KTH), Jimmy Robertson, Robin Karlsson, David Balkwill, and Kathleen Sienko. The anthropomorphic belt design project was done by Therese Zackrisson. Finally, he acknowledges the generous support of the Keck Foundation to the Massachusetts Eye and Ear Infirmary's Neuroprosthesis Research Center, of the National Institutes of Health (NIDCD_R01DC0006210). NR 51 TC 20 Z9 20 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1557-0576 J9 J NEUROL PHYS THER JI J. Neurol. Phys. Ther. PD JUN PY 2010 VL 34 IS 2 BP 98 EP 104 DI 10.1097/NPT.0b013e3181dde6f0 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA V21PD UT WOS:000208218600009 PM 20588096 ER PT J AU Schwarz, T De Meyer, SF Deckmyn, H Denis, CV Nieswandt, B Vanhoorelbeke, K Stoll, G Kleinschnitz, C AF Schwarz, T. De Meyer, S. F. Deckmyn, H. Denis, C. V. Nieswandt, B. Vanhoorelbeke, K. Stoll, G. Kleinschnitz, C. TI Von Willebrand factor binding to collagen and glycoprotein Ib-alpha, but not glycoprotein IIb/IIIa contributes to ischaemic stroke in mice SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 20th Meeting of the European-Neurological-Society CY JUN 19-23, 2010 CL Berlin, GERMANY SP European Neurol Soc C1 Univ Hosp, Wurzburg, Germany. Immune Dis Inst Inc, Boston, MA USA. Katholieke Univ Leuven, Kortrijk, Belgium. Univ Paris 11, Le Kremlin Bicetre, France. Univ Wurzburg, Wurzburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUN PY 2010 VL 257 SU 1 MA O136 BP S43 EP S43 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 600AH UT WOS:000277955200114 ER PT J AU Zhao, SP Aviles, ER Fujikawa, DG AF Zhao, Shuangping Aviles, Ernesto R., Jr. Fujikawa, Denson G. TI Nuclear Translocation of Mitochondrial Cytochrome c, Lysosomal Cathepsins B and D, and Three Other Death-Promoting Proteins Within the First 60 Minutes of Generalized Seizures SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE epilepsy; necrosis; programmed cell death ID PROGRAMMED CELL-DEATH; INDUCED STATUS EPILEPTICUS; INTERNUCLEOSOMAL DNA CLEAVAGE; APOPTOSIS-INDUCING FACTOR; INDUCED NEURONAL NECROSIS; KAINIC ACID; FRAGMENTATION; ACTIVATION; MECHANISMS; CASPASE-3 AB We have shown that generalized seizures produce necrotic neurons with caspase-independent nuclear pyknosis and DNA fragmentation. In this study, we determined the time course of translocation of mitochondrial cytochrome c, apoptosis-inducing factor, endonuclease G, lysosomal cathepsins B and D, and DNase II with respect to signs of irreversible neuronal damage. Adult male Wistar rats underwent lithium-pilocarpine-induced seizures lasting for 60 min, 3 hr, and 3 hr with 6- or 24-hr survival periods, after which the brains were prepared for immunofluorescence microscopic examination of piriform cortex. Contrary to expectation, cytochrome c and cathepsins B and D translocated to neuronal nuclei with DNase II, endonuclease G, and apoptosis-inducing factor within 60 min of seizure onset and persisted for 24 hr after 3-hr seizures. After 60-min seizures, some neurons showed translocation of the death-promoting proteins in normal-appearing neurons, prior to their appearance in irreversibly damaged neurons. Western blots of subcellular fractions of cytochrome c and cathepsins B and D confirmed their nuclear translocation. This is the first evidence of nuclear translocation of cathepsins B and D and the first in vivo evidence of nuclear translocation of cytochrome c. The appearance of these mitochondrial proteins and lysosomal enzymes before signs of irreversible neuronal death suggests that they could contribute to seizure-induced nuclear pyknosis and DNA fragmentation. (C) 2010 Wiley-Liss, Inc.dagger C1 [Zhao, Shuangping; Aviles, Ernesto R., Jr.; Fujikawa, Denson G.] VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab, North Hills, CA 91343 USA. [Fujikawa, Denson G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Fujikawa, Denson G.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Fujikawa, DG (reprint author), VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab 151B4, 16111 Plummer St, North Hills, CA 91343 USA. EM dfujikawa@ucla.edu FU Medical Research Service, Office of Research and Development, Department of Veterans Affairs FX Contract grant sponsor: Medical Research Service, Office of Research and Development, Department of Veterans Affairs. NR 47 TC 14 Z9 15 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN PY 2010 VL 88 IS 8 BP 1727 EP 1737 DI 10.1002/jnr.22338 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 590RQ UT WOS:000277245500011 PM 20077427 ER PT J AU Yang, JS You, ZR Kim, HH Hwang, SK Khuman, J Guo, SZ Lo, EH Whalen, MJ AF Yang, Jinsheng You, Zerong Kim, Hyung-Hwan Hwang, Seo-Kyoung Khuman, Jugta Guo, Shuzhen Lo, Eng H. Whalen, Michael J. TI Genetic Analysis of the Role of Tumor Necrosis Factor Receptors in Functional Outcome after Traumatic Brain Injury in Mice SO JOURNAL OF NEUROTRAUMA LA English DT Article DE controlled cortical impact; gene knockout; inflammation; mice; tumor necrosis factor; traumatic brain injury ID NF-KAPPA-B; CONTROLLED CORTICAL IMPACT; NONAPOPTOTIC CELL-DEATH; LACKING TNF RECEPTORS; FACTOR-ALPHA; ACTIVATION; EXPRESSION; DAMAGE; INHIBITOR; PATHWAY AB We previously reported that tumor necrosis factor-alpha (TNF-alpha) and Fas receptor induce acute cellular injury, tissue damage, and motor and cognitive deficits after controlled cortical impact (CCI) in mice (Bermpohl et al. 2007); however, the TNF receptors (TNFR) involved are unknown. Using a CCI model and novel mutant mice deficient in TNFR1/Fas, TNFR2/Fas, or TNFR1/TNFR2/Fas, we tested the hypothesis that the combination of TNFR2/Fas is protective, whereas TNFR1/Fas is detrimental after CCI. Uninjured knockout (KO) mice showed no differences in baseline physiological variables or motor or cognitive function. Following CCI, mice deficient in TNFR2/Fas had worse post-injury motor and Morris water maze (MWM) performance than wild-type (WT) mice (p < 0.05 group effect for wire grip score and MWM performance by repeated measures ANOVA). No differences in motor or cognitive outcome were observed in TNFR1/Fas KO, or in TNFR2 or TNFR1 single KO mice, versus WT mice. Additionally, no differences in propidium iodide (PI)-positive cells (at 6 h) or lesion size (at 14 days) were observed between WT and TNFR1/Fas or TNFR2/Fas KO mice. Somewhat surprisingly, mice deficient in TNFR1/TNFR2/Fas also had PI-positive cells, lesion size, and motor and MWM deficits similar to those of WT mice. These data suggest a protective role for TNFR2/Fas in the pathogenesis of TBI. Further studies are needed to determine whether direct or indirect effects of TNFR1 deletion in TNFR2/Fas KO mice mediate improved functional outcome in TNFR1/TNFR2/Fas KO mice after CCI. C1 [Yang, Jinsheng; You, Zerong; Khuman, Jugta; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. [Khuman, Jugta; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. [Guo, Shuzhen; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Guo, Shuzhen; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Kim, Hyung-Hwan; Hwang, Seo-Kyoung] Brigham & Womens Hosp, Vasc Med Res Unit, Boston, MA 02115 USA. RP Whalen, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. EM mwhalen@partners.org FU NIH/National Institute of Neurological Diseases and Stroke [RO1NS47447] FX This work was supported by NIH/National Institute of Neurological Diseases and Stroke grant RO1NS47447 to M.J.W. NR 39 TC 22 Z9 22 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN PY 2010 VL 27 IS 6 BP 1037 EP 1046 DI 10.1089/neu.2009.1229 PG 10 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 612VO UT WOS:000278933300007 PM 20205514 ER PT J AU Sozda, CN Hoffman, AN Olsen, AS Cheng, JP Zafonte, RD Kline, AE AF Sozda, Christopher N. Hoffman, Ann N. Olsen, Adam S. Cheng, Jeffrey P. Zafonte, Ross D. Kline, Anthony E. TI Empirical Comparison of Typical and Atypical Environmental Enrichment Paradigms on Functional and Histological Outcome after Experimental Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE behavior; controlled cortical impact; enrichment; recovery; spatial learning; water maze ID CONTROLLED CORTICAL IMPACT; FACTOR MESSENGER-RNA; RECEPTOR AGONIST 8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN; FLUID PERCUSSION INJURY; SPINAL-CORD-INJURY; MORRIS WATER MAZE; COGNITIVE DEFICITS; SPATIAL MEMORY; DENTATE GYRUS; SYNAPTOPHYSIN LEVELS AB Several studies have shown that housing rats in an enriched environment (EE) after traumatic brain injury (TBI) improves functional and histological outcome. The typical EE includes exploratory, sensory, and social components in cages that are often vastly larger than standard (STD) housing. It is uncertain, however, whether a single or specific component is sufficient to confer these benefits after TBI, or if all, perhaps in an additive or synergistic manner, are necessary. To clarify this ambiguity, anesthetized adult male rats were subjected to either a controlled cortical impact or sham injury, and then were randomly assigned to five different housing paradigms: (1) EE (typical), (2) EE (-social), (3) EE (-stimuli), (4) STD (typical), and (5) STD (+stimuli). Motor and cognitive function were assessed using conventional motor (beam-balance/traversal) and cognitive (spatial learning in a Morris water maze) tests on postoperative days 1-5 and 14-19, respectively, and cortical lesion volume and CA1/CA3 cell loss were quantified at 3 weeks. No significant differences were observed among the sham groups in any comparison and thus their data were pooled (i.e., SHAM). In the TBI groups, typical EE improved beam-balance versus both STD (+stimuli) and EE (-social), it facilitated the acquisition of spatial learning and memory retention versus all other housing conditions (p<0.003), and it reduced lesion volume and CA3 cell loss versus STD (typical) housing. While rats in the three atypical EE conditions exhibited slightly better cognitive performance and histological protection versus the typical STD group, the overall effects were not significant. These data suggest that exposing TBI rats to any of the three components individually may be more advantageous than no enrichment, but only exposure to typical EE yields optimal benefits. C1 [Kline, Anthony E.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Rehabil Res, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Kline, Anthony E.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15213 USA. [Kline, Anthony E.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15213 USA. [Kline, Anthony E.] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA. [Zafonte, Ross D.] Harvard Univ, Sch Med, Boston, MA USA. [Zafonte, Ross D.] Spaulding Rehabil Hosp, Boston, MA USA. [Zafonte, Ross D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kline, AE (reprint author), Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Rehabil Res, Dept Phys Med & Rehabil, 3471 5th Ave,Suite 201, Pittsburgh, PA 15213 USA. EM klineae@upmc.edu OI Cheng, Jeffrey/0000-0001-8285-3207 FU National Institutes of Health [HD046700, NS060005] FX This work was supported, in part, by National Institutes of Health grants HD046700 and NS060005, awarded to A.E.K. NR 62 TC 46 Z9 47 U1 4 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN PY 2010 VL 27 IS 6 BP 1047 EP 1057 DI 10.1089/neu.2010.1313 PG 11 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 612VO UT WOS:000278933300008 PM 20334496 ER PT J AU Hage, FG Venkataraman, R Aljaroudi, W Bravo, PE McLarry, J Faulkner, M Heo, J Iskandrian, AE AF Hage, Fadi G. Venkataraman, Rajesh Aljaroudi, Wael Bravo, Paco E. McLarry, Joel Faulkner, Michael Heo, Jaekyeong Iskandrian, Ami E. TI The impact of viability assessment using myocardial perfusion imaging on patient management and outcome SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Viability; coronary revascularization; myocardial perfusion imaging; mortality ID LEFT-VENTRICULAR DYSFUNCTION; CORONARY-ARTERY-BYPASS; ISCHEMIC CARDIOMYOPATHY; HEART-FAILURE; NONVIABLE MYOCARDIUM; EJECTION FRACTION; CONTROLLED-TRIAL; TL-201; REVASCULARIZATION; INFARCTION AB Prior studies show that ischemic cardiomyopathy (ICM) patients with substantial viable myocardium have better survival with coronary revascularization (CR) than medical therapy (MT). When myocardial perfusion imaging (MPI) is used, the analysis is often based on visual scoring. We sought to determine the value of automated quantitative viability analysis in guiding management and predicting outcome. We identified 246 consecutive ICM patients who had rest-redistribution gated SPECT thallium-201 MPI. Size and severity of perfusion defects were assessed by automated method. Regions with < 50% activity vs normal were considered nonviable. Mortality was verified against the social security death index database. Of the 246 patients, 37% underwent CR within 3 months of MPI. The initial images showed a total perfusion defect size of 32 +/- A 17%, redistribution of 3.5 +/- A 4.6% and nonviable myocardium of 13 +/- A 14%LV. Using multivariate logistic regression analysis, independent predictors of CR included chest pains (OR 2.74) and rest-delayed transient ischemic dilatation (OR 4.49), while a prior history of CR or ventricular arrhythmias favored MT. The cohort was followed-up for 41 +/- A 30 m during which 111 patients (45%) died. Survival was better with CR than MT (P < .0001). For CR, survival was better for those with a smaller area of nonviable myocardium (risk of death increased by 5%/1% increase in size of nonviable myocardium, P = .009) but this was not seen in MT. CR had a mortality advantage over MT when the area of nonviable myocardium was a parts per thousand currency sign20%LV but not larger. Automated quantitative analysis of MPI is useful in predicting survival in ICM, but the decision for or against CR is a complex one as it depends on multiple other factors and "viability testing" is just one variable that needs to be incorporated in the decision-making process. C1 [Hage, Fadi G.; Venkataraman, Rajesh; Aljaroudi, Wael; Heo, Jaekyeong; Iskandrian, Ami E.] Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. [Bravo, Paco E.] Johns Hopkins Univ, Div Nucl Med, Baltimore, MD USA. [McLarry, Joel; Faulkner, Michael] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. RP Hage, FG (reprint author), Univ Alabama, Div Cardiovasc Dis, Zeigler Res Bldg 1024,1530 3rd AVE S, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 35 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD JUN PY 2010 VL 17 IS 3 BP 378 EP 389 DI 10.1007/s12350-010-9199-1 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 594PW UT WOS:000277550700008 PM 20186583 ER PT J AU Perciaccante, VJ Carey, JW Susarla, SM Dodson, TB AF Perciaccante, Vincent J. Carey, John W. Susarla, Srinivas M. Dodson, Thomas B. TI Markers for Intimate Partner Violence in the Emergency Department Setting SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DOMESTIC VIOLENCE; INJURY LOCATION; FACIAL INJURIES; WOMEN; ABUSE; HEAD; NECK AB Purpose: Intimate partner violence (IPV) is a serious, under-reported public health problem in the United States. Pilot studies suggested that injury location, that is, head, neck, or face, was a sensitive but nonspecific marker for IPV-related injuries. This study's goal was to determine whether adding a second element to the diagnostic protocol-response to an IPV-screening questionnaire-improved the specificity of the protocol. Materials and Methods: We used a cross-sectional study design and a sample composed of women presenting to the emergency department for evaluation and management of injuries of non-verifiable etiology. The predictor study variables were injury location (head, neck, or face vs other), responses to a verbal questionnaire (Partner Violence Screen or Woman Abuse Screening Tool), and the combination of both elements. By combining both elements, the probability for IPV-related injury was classified as high or low. The outcome variable was self-report of injury etiology (IPV or other etiology). Appropriate univariate and bivariate statistics were computed, including estimates of sensitivity, specificity, positive and negative predictive values, and relative risk. Results: The sample was composed of 300 women with a mean age of 36.5 years. The frequency of self-reported IPV-related injury was 32.3%. The sensitivities and specificities for injury location and the questionnaires combined ranged from 86.5% to 91.8% and 93.1% to 96.1%, respectively. Conclusions: The study findings suggest that combining information regarding injury location and the results of a screening questionnaire was a better predictor of a woman's likelihood to report IPV-related injuries than either modality alone. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:1219-1224, 2010 C1 [Perciaccante, Vincent J.] Emory Univ, Sch Med, Dept Surg, Div Oral & Maxillofacial Surg, Atlanta, GA 30322 USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, 55 Fruit St,WRN1201, Boston, MA 02114 USA. EM tbdodson@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 NR 20 TC 7 Z9 8 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2010 VL 68 IS 6 BP 1219 EP 1224 DI 10.1016/j.joms.2010.02.010 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 604PV UT WOS:000278291900002 PM 20395028 ER PT J AU Loveless, TP Bjornland, T Dodson, TB Keith, DA AF Loveless, Tyman P. Bjornland, Tore Dodson, Thomas B. Keith, David A. TI Efficacy of Temporomandibular Joint Ankylosis Surgical Treatment SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID COSTAL CARTILAGE GRAFT; COSTOCHONDRAL GRAFT; FOLLOW-UP; RECONSTRUCTION; PROSTHESIS; MANAGEMENT; ARTHROPLASTY; OUTCOMES; PATIENT AB Purpose: The purpose of the present study was to answer the following clinical question: of the patients with temporomandibular joint ankylosis, do those treated with ankylosis resection and ramus-condyle unit reconstruction with a prosthetic total joint (total joint replacement [TJR]) have improved jaw function and decreased pain compared with those treated with ankylosis resection and interpositional arthroplasty (IA)? Materials and Methods: Using a retrospective study design, the investigators enrolled a sample derived from the population of patients presenting to the Massachusetts General Hospital (Boston, MA) and the University of Oslo Faculty of Dentistry from 1998 to 2008 for the evaluation and management of temporomandibular joint ankylosis. The primary predictor variable was treatment (ie, TJR or IA). The outcome variables were the maximal interincisal opening and pain. Data analyses were performed using bivariate and multiple regression methods. Results: The final study sample included 36 subjects with a mean age of 40 +/- 13.1 years, and 25 were women (69%). Of the 36 patients, 14 (39%) and 22 (61%) were in the TJR and IA groups, respectively. The changes in the maximal interincisal opening in the TJR and IA groups were 9.4 +/- 6.7 and 18 +/- 9.7 mm (P = .02). After adjusting for institutional location, number of previous operations, laterality (unilateral versus bilateral operation), age, and etiology, the difference in the maximal interincisal opening between the 2 treatment groups was not significant (P = .06). The changes between preoperative and postoperative pain scores were insignificant between the groups (P = .16). Conclusion: Ankylosis resection and ramus-condyle unit reconstruction with a prosthetic total joint and IA produced comparable outcomes in terms of mandibular range of motion and pain. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:1276-1282, 2010 C1 [Dodson, Thomas B.; Keith, David A.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02214 USA. [Loveless, Tyman P.] Case Western Reserve Univ, Sch Dent Med, Cleveland Hts, OH USA. [Bjornland, Tore] Univ Oslo, Dept Oral Surg & Oral Med, Inst Clin Dent, Fac Dent, Oslo, Norway. [Keith, David A.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Keith, David A.] Harvard Vanguard Med Associates, Boston, MA USA. RP Keith, DA (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, 133 Fruit St, Boston, MA 02214 USA. EM david_keith@vmed.org FU Massachusetts General Hospital; Department of Oral and Maxillofacial Surgery Education and Research Fund; University of Oslo; US-Norway Fulbright Foundation for Educational Exchange FX This study was supported by Massachusetts General Hospital, Department of Oral and Maxillofacial Surgery Education and Research Fund (T.P.L.), University of Oslo (T.B.), and the US-Norway Fulbright Foundation for Educational Exchange (TB.). NR 27 TC 17 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2010 VL 68 IS 6 BP 1276 EP 1282 DI 10.1016/j.joms.2009.10.014 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 604PV UT WOS:000278291900010 PM 20304543 ER PT J AU Susarla, SM Sidhu, HK Avery, LL Dodson, TB AF Susarla, Srinivas M. Sidhu, Harlyn K. Avery, Laura L. Dodson, Thomas B. TI Does Computed Tomographic Assessment of Inferior Alveolar Canal Cortical Integrity Predict Nerve Exposure During Third Molar Surgery? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID 3RD-MOLAR EXTRACTION; INJURY; REMOVAL AB Purpose: To evaluate the association between computed tomographic (CT) assessment of inferior alveolar nerve (IAN) canal cortical integrity and intraoperative IAN exposure. Materials and Methods: This was a retrospective cohort study. The study sample included patients considered at high risk for IAN injury based on panoramic findings. The primary predictor variable was IAN canal integrity (intact or interrupted) assessed on coronal CT images. The secondary predictor variable was length of the cortical defect, in millimeters. The primary outcome variable was intraoperative visualization of the IAN. Other variables were demographic and operative parameters. Bivariate and multiple logistic regression analyses were used to evaluate the unadjusted and adjusted associations between the cortical integrity and IAN exposure. Diagnostic test characteristics were computed for cortical integrity and threshold cortical defect size. A P value <= 0.05 was statistically significant. Results: The sample consisted of 51 subjects (57% female) with a mean age of 35.2 +/- 12.8 years. Of the 80 third molars available for evaluation, 52 third molars (64.1%) had evidence of loss of cortical integrity. The mean cortical defect length was 2.9 +/- 2.6 mm. Loss of cortical integrity had a high sensitivity (>= 0.88) but low specificity (<= 0.49) as a diagnostic test for IAN visualization. A cortical defect size mm was associated with an increased risk for intraoperative IAN visualization with a high sensitivity and specificity (>= 0.82). Conclusion: Cortical defect size on a maxillofacial CT has a high sensitivity and specificity for predicting intraoperative IAN exposure during third molar removal. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:1296-1303, 2010 C1 [Susarla, Srinivas M.; Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Susarla, Srinivas M.; Avery, Laura L.] Harvard Univ, Sch Med, Boston, MA USA. [Sidhu, Harlyn K.; Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Avery, Laura L.] Massachusetts Gen Hosp, Div Emergency Radiol, Dept Radiol, Boston, MA 02114 USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, WACC230, Boston, MA 02114 USA. EM ssusarla1@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU Oral and Maxillofacial Surgery Foundation; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Center; Massachusetts General Hospital Physicians' Organization FX The authors would like to acknowledge the support of the Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation, the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Center for Applied Clinical Investigation and Education and Research Fund, and the Massachusetts General Hospital Physicians' Organization. NR 21 TC 14 Z9 15 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2010 VL 68 IS 6 BP 1296 EP 1303 DI 10.1016/j.joms.2010.01.021 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 604PV UT WOS:000278291900013 PM 20356665 ER PT J AU Funakoshi, T Spector, M AF Funakoshi, Tadanao Spector, Myron TI Chondrogenic Differentiation and Lubricin Expression of Caprine lnfraspinatus Tendon Cells SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE tendon; cartilage; lubricin; rotator cuff; mesenchymal stem cells ID SMOOTH-MUSCLE ACTIN; MESENCHYMAL STEM-CELLS; MARROW STROMAL CELLS; COLLAGEN-GLYCOSAMINOGLYCAN MATRIX; ANTERIOR CRUCIATE LIGAMENT; FIBROBLASTS IN-VITRO; HUMAN BONE-MARROW; PROGENITOR CELLS; ROTATOR CUFF; TISSUE AB Reparative strategies for the treatment of injuries to tendons, including those of the rotator cuff of the shoulder, need to address the formation of the cartilage which serves as the attachment apparatus to bone and which forms at regions undergoing compressive loading. Moreover, recent work indicates that cells employed for rotator cuff repair may need to synthesize a lubricating glycoprotein, lubricin, which has recently been found to play a role in tendon tribology. The objective of the present study was to investigate the chondrogenic differentiation and lubricin expression of caprine infraspinatus tendon cells in monolayer and three-dimensional culture, and to compare the behavior with bone marrow-derived mesenchymal stem cells (MSCs). The results demonstrated that while tendon cells in various media, including chondrogenic medium, expressed lubricin, virtually none of the MSCs synthesized this important lubricating molecule. Also of interest was that the cartilage formation capacity of the tendon cells grown in pellet culture in chondrogenic medium was comparable with MSCs. These data inform the use of tendon cells for rotator cuff repair, including for fibrocartilaginous zones. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:716-725, 2010 C1 [Spector, Myron] VA Boston Healthcare Syst, Boston, MA 02130 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,MS 151, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU Department of Veterans Affairs FX Funding was provided in part from the Department of Veterans Affairs. The authors are grateful to T.M. Schmid, Rush University Medical Center, Chicago, IL, for providing the lubricin antibody, and to Mix Weaver, B.S., Tobias Gotterbarm, M.D., and Harmeet Gill, B.S., for their assistance. NR 52 TC 10 Z9 10 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD JUN PY 2010 VL 28 IS 6 BP 716 EP 725 DI 10.1002/jor.21053 PG 10 WC Orthopedics SC Orthopedics GA 592BI UT WOS:000277349400003 PM 20058273 ER PT J AU Duan, ZF Choy, E Nielsen, GP Rosenberg, A Iafrate, J Yang, C Schwab, J Mankin, H Xavier, R Hornicek, FJ AF Duan, Zhenfeng Choy, Edwin Nielsen, G. Petur Rosenberg, Andrew Iafrate, John Yang, Cao Schwab, Joe Mankin, Henry Xavier, Ramnik Hornicek, Francis J. TI Differential Expression of microRNA (miRNA) in Chordoma Reveals a Role for miRNA-1 in Met Expression SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE chordoma; miRNA; Met; RT-PCR ID BREAST-CANCER; OVARIAN-CANCER; CELL-LINES; C-MET; TUMOR; GENE; RESISTANCE; THERAPY; ALPHA; RNA AB Emerging evidence suggests that microRNA (miRNA) expression signatures in cancer may have important diagnostic, prognostic, and therapeutic value, but there is no data on miRNA expression in chordoma. The purpose of this study was to identify the role of miRNAs in human chordoma. We analyzed rniRNA expression in chordoma-derived cell lines and chordoma tissue by using miRNA microarray technology with unsupervised hierarchical clustering analysis. The relative expression levels of these miRNAs were confirmed by real-time quantitative RT-PCR and Northern blot analysis. To characterize the potential role of miRNA-1, miRNA-1 was stably transfected into a chordoma cell line, UCH1. The expression of miRNA-1 targeted gene Met in chordoma tissues was also studied. We observe that human chordoma tissues and cell lines can be distinguished from normal muscle tissue by comparing miRNA expression profiles. Several miRNAs were differentially expressed in chordoma cell lines compared to controls, and similar expression patterns were found in primary chordoma tissues. Importantly, we were able to show for the first time, to our knowledge, that expression of miRNA-1 and miRNA-206, two miRNAs implicated in a number of other cancer types, were markedly decreased in both chordoma tissues and cell lines. When chordoma cell lines were transfected with miRNA-1, downregulation of known miRNA-1 targets was observed. These targets included Met and HDAC4-two genes that were observed to be overexpressed in chordoma. Our results demonstrate that some miRNAs are differentially expressed in chordoma and, in particular, miRNA-1 may have a functional effect on chordoma tumor pathogenesis. (C) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:746-752, 2010 C1 [Duan, Zhenfeng; Choy, Edwin; Yang, Cao; Schwab, Joe; Mankin, Henry; Hornicek, Francis J.] Massachusetts Gen Hosp, Sarcoma Mol Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Nielsen, G. Petur; Rosenberg, Andrew; Iafrate, John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Sarcoma Mol Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, 50 Fruit St,Jackson 1115, Boston, MA 02114 USA. EM zduan@partners.org OI Choy, Edwin/0000-0001-9896-8084 FU Sarcoma Foundation of America (SFA); Gattegno; Wechsler FX This project was supported, in part, by a grant from the Stephan L. Harris Fund. Dr. Duan is supported, in part, through a grant from Sarcoma Foundation of America (SFA). Support has also been provided by the Gattegno and Wechsler funds. In addition, we acknowledge Dr. Christoph Eicken at LC Sciences, LLC for providing useful advice during the analysis of miRNA expression data. NR 26 TC 33 Z9 37 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD JUN PY 2010 VL 28 IS 6 BP 746 EP 752 DI 10.1002/jor.21055 PG 7 WC Orthopedics SC Orthopedics GA 592BI UT WOS:000277349400007 PM 20041488 ER PT J AU Hwang, E Pakdaman, MN Tamilia, M Hier, MP Black, MJ Rochon, L Payne, RJ AF Hwang, Euna Pakdaman, Michael N. Tamilia, Michael Hier, Michael P. Black, Martin J. Rochon, Louise Payne, Richard J. TI Bilateral Papillary Thyroid Cancer and Associated Histopathologic Findings SO JOURNAL OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article DE bilaterality; extrathyroidal extension; multifocality; papillary thyroid cancer; T staging ID COMPLETION THYROIDECTOMY; TNM CLASSIFICATION; RISK GROUPS; CARCINOMA AB Objective: To determine the incidence of bilateral papillary thyroid cancer (PTC) at total thyroidectomy (TT) and compare demographic risk factors (gender and age) and histopathologic findings (tumour size, extrathyroidal extension [ETE], T staging, and multifocality) between patients with PTC in both thyroid lobes and those with PTC limited to the ipsilateral lobe and/or isthmus. Design: Retrospective study. Setting: University teaching hospital. Methods: The pathology results of 1047 consecutive patients who underwent TT between 2002 and 2008 were reviewed. Statistical significance was obtained using the chi-square test. Main Outcome Measures: Incidence of bilateral PTC and its association with demographic risk factors and histopathologic findings. Results: Among 592 patients with PTC, 13.2% had bilateral PTC and 86.8% had unilateral and/or isthmian PTC. Bilaterality was present in 12.4% of women and 16.7% of men (p = .24) and in 12.9% of patients aged >= 45 years and 13.5% < 45 years (p = .83). Bilateral PTC was found in 12.6% of patients with a primary tumour <= 2 cm and 13.5% > 2 cm(p = .75); 23.6% of tumours with ETE demonstrated bilaterality compared to 9.7% without (p < .0001), and 8.7% of pT1 (p = .08), 9.2% of pT2 (p = .02), 23.0% of pT3 (p < .0001), and 12.5% of pT4 (p = .87) tumours were bilateral, respectively. Among bilateral PTC patients, 43.2% had multifoci in at least one lobe compared to 6.4% when nonbilateral (p < .0001). Conclusions: After TT, 13.2% of patients had bilateral PTC. No significant correlation was established between bilaterality and gender, age, and tumour size. Bilaterality was more commonly found in patients with ETE, advanced T stage, and at least one multifocal lobe. C1 [Hwang, Euna; Pakdaman, Michael N.] McGill Univ, Fac Med, Montreal, PQ, Canada. [Hwang, Euna] Univ Ottawa, Dept Otolaryngol Head & Neck Surg, Ottawa, ON, Canada. [Pakdaman, Michael N.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hier, Michael P.; Black, Martin J.; Payne, Richard J.] McGill Univ, Jewish Gen Hosp, Dept Otolaryngol Head & Neck Surg, Montreal, PQ H3T 1E2, Canada. [Tamilia, Michael] McGill Univ, Jewish Gen Hosp, Dept Endocrinol, Montreal, PQ H3T 1E2, Canada. [Rochon, Louise] McGill Univ, Jewish Gen Hosp, Dept Pathol, Montreal, PQ H3T 1E2, Canada. RP Hwang, E (reprint author), Ottawa Gen Hosp, Dept Otolaryngol Head & Neck Surg, Campus S3,501 Smyth Rd, Ottawa, ON K1H 8L6, Canada. EM euna.hwang@mail.mcgill.ca NR 19 TC 6 Z9 8 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1916-0216 J9 J OTOLARYNGOL-HEAD N JI J. Otolaryngol-Head Neck Surg. PD JUN PY 2010 VL 39 IS 3 BP 284 EP 287 DI 10.2310/7070.2010.090019 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 678CA UT WOS:000284045200012 PM 20470673 ER PT J AU Wasan, AD Kong, JA Pham, LD Kaptchuk, TJ Edwards, R Gollub, RL AF Wasan, Ajay Darsh Kong, Jian Pham, Loc-Duyen Kaptchuk, Ted J. Edwards, Robert Gollub, Randy L. TI The Impact of Placebo, Psychopathology, and Expectations on the Response to Acupuncture Needling in Patients With Chronic Low Back Pain SO JOURNAL OF PAIN LA English DT Article DE Psychiatric comorbidity; acupuncture; chronic low back pain; placebo controlled; expectations ID PSYCHOLOGICAL RISK-FACTORS; CONTROLLED-TRIALS; PRIMARY-CARE; ANXIETY; ANALGESIA; PERSONALITY; OUTCOMES; ASSOCIATION; DEPRESSION; EXPECTANCY AB Comorbid psychopathology is a variable not explored in the acupuncture RCTs that could explain whether subgroups of patients with chronic low back pain have differential responses to acupuncture or placebo treatments. This was a controlled, blinded, crossover trial of verum acupuncture and validated sham acupuncture in 40 CLBP patients, with a Low or High level of psychiatric comorbidity. They completed a 0 to 10 rating scale for pain at the beginning and end of each treatment session, and rated their expectations for change in pain. Verum acupuncture was performed at Large Intestine 4 on the dorsal right hand for 30 minutes by a licensed acupuncturist. Data analysis used percent improvement in pain as the primary outcome for each of the treatment sessions. Both groups (21 Low and 19 High) reported significant analgesia with verum acupuncture needling, mean 33%, P = .9 for difference between groups; and with placebo, 26%, P = .09. In both groups, expectations were only a significant predictor of verum acupuncture response, P = .002, such that those with greater expectations had greater pain relief. Psychiatric comorbidity does not significantly impact acupuncture or placebo acupuncture analgesia in CLBP. It does not affect the positive impact of expectations on reported pain relief from real acupuncture. Perspective: Psychiatric comorbidity may predict differences between acupuncture and placebo responses, not otherwise seen in the RCTs for low back pain. Using a blinded, crossover design, we report that it does not predict outcome, nor does it seem to modify the effect of expectancy (a known predictor) on acupuncture response. (C) 2010 by the American Pain Society C1 [Wasan, Ajay Darsh; Pham, Loc-Duyen; Edwards, Robert] Womens Hosp Med Ctr, Dept Anesthesiol, Boston, MA USA. [Kaptchuk, Ted J.] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA USA. [Wasan, Ajay Darsh; Edwards, Robert] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Kong, Jian; Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Wasan, AD (reprint author), Pain Management Ctr, Suite 320,850 Boylston St, Chestnut Hill, MA 02467 USA. EM awasan@partners.org OI Gollub, Randy L./0000-0002-9434-4044 FU NIH, NIDA [1K23DA020681-01A1]; NIH, NCCAM [P01 AT002048-01, KO1AT003883, K24AT004095] FX Supported by NIH grants# NIDA 1K23DA020681-01A1 and NCCAM P01 AT002048-01 (A.D.W.); NCAAM KO1AT003883 (J.K.); NCAAM K24AT004095 (T.K.). NR 62 TC 23 Z9 24 U1 1 U2 12 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JUN PY 2010 VL 11 IS 6 BP 555 EP 563 DI 10.1016/j.jpain.2009.09.013 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 612DF UT WOS:000278876300006 PM 20075014 ER PT J AU Smith, AK Schonberg, MA Fisher, J Pallin, DJ Block, SD Forrow, L McCarthy, EP AF Smith, Alexander K. Schonberg, Mara A. Fisher, Jonathan Pallin, Daniel J. Block, Susan D. Forrow, Lachlan McCarthy, Ellen P. TI Emergency Department Experiences of Acutely Symptomatic Patients With Terminal Illness and Their Family Caregivers SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Emergency department; pain; patient; caregiver; palliative care; qualitative research ID END-OF-LIFE; CARE AB Context. Despite increased focus on improving palliative care in the emergency department (ED), there is little research on how to best address the specific needs of this patient population. Objectives. To better understand the experiences of acutely symptomatic patients seen in the ED. Methods. Using in-person semi-structured interviews, we explored the attitudes, experiences, and beliefs of 14 patients and seven family caregivers on the inpatient palliative care consult service, who had been admitted through the ED at two academic medical centers. We used a grounded theory approach to code responses. Transcripts were coded by a palliative medicine physician, an emergency medicine physician, and a general internist. Discrepancies were resolved by consensus. Coded sections were iteratively reviewed for interpretation, and concepts were collapsed into themes. Results. Five distinct themes emerged: 1) unprepared for managing symptoms at home; 2) uncertainty and anxiety; 3) communication is essential; 4) mixed experiences with symptom management; and 5) conflicting perspectives about the purpose of palliative care clinicians in the ED. Conclusion. Patients and caregivers identified systems, communication, and clinical issues in ED care that should be a focus for future research. J Pain Symptom Manage 2010;39:972-981. (C) 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Smith, Alexander K.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94121 USA. [Smith, Alexander K.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Schonberg, Mara A.; Fisher, Jonathan; Pallin, Daniel J.; Block, Susan D.; Forrow, Lachlan; McCarthy, Ellen P.] Harvard Univ, Sch Med, Boston, MA USA. [Schonberg, Mara A.; Forrow, Lachlan; McCarthy, Ellen P.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Fisher, Jonathan] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Fisher, Jonathan] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Pallin, Daniel J.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Block, Susan D.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Smith, AK (reprint author), Univ Calif San Francisco, Div Geriatr, Dept Med, 4150 Clement St 181G, San Francisco, CA 94121 USA. EM aksmith@ucsf.edu RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 FU Beth Israel Deaconess Hospital; institutional National Research Service [5 T32 HP11001-19]; National Institute on Aging [R01AG028481] FX The authors have no conflicts of interest to report. This study was performed in its entirety while Dr. Smith was a general medicine fellow at Beth Israel Deaconess Medical Center. This research was supported by The Julie Henry Fund at Beth Israel Deaconess Hospital. Dr. Smith was supported by an institutional National Research Service Award, #5 T32 HP11001-19 and a Research Supplement to Promote Diversity in Health Related Research from the National Institute on Aging (R01AG028481). The funding organizations had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. NR 19 TC 39 Z9 41 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUN PY 2010 VL 39 IS 6 BP 972 EP 981 DI 10.1016/j.jpainsymman.2009.10.004 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 619OM UT WOS:000279439500002 PM 20434873 ER PT J AU Parr, JD Zhang, BH Nilsson, ME Wright, A Balboni, T Duthie, E Paulk, E Prigerson, HG AF Parr, John D. Zhang, Baohui Nilsson, Matthew E. Wright, Alexi Balboni, Tracy Duthie, Edmund Paulk, Elizabeth Prigerson, Holly G. TI The Influence of Age on the Likelihood of Receiving End-of-Life Care Consistent with Patient Treatment Preferences SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CANCER-PATIENTS; HOSPITALIZED-PATIENTS; SUSTAINING TREATMENT; TREATMENT DECISIONS; ADVANCED ILLNESS; OLDER PERSONS; OUTCOMES; PHYSICIAN; SUPPORT AB Background: Age differences may help to explain discrepancies in medical care received by cancer patients near death. Objectives: Understanding age differences in advanced cancer patients' end-of-life experiences. Design: NCI and NIMH funded multi-site prospective cohort study. Participants: 396 deceased cancer patients, mean age (58.6 +/- 12.5), in the Coping with Cancer study. Measurements: Baseline interviews (Treatment Preference) and 1 week postmortem chart reviews (Treatment Received). Results: 14.1% of patients were 20-44 years old, 54.0% were 45-64 years old, and 31.8% were >= 65 years old. Compared to younger patients, middle-aged patients wanted less life-prolonging care (OR 0.32; CI 0.16-0.64). In the last week of life, older patients were less likely to undergo ventilation (OR 0.27; CI 0.07-1.00) than younger patients. Middle-aged patients who preferred life-prolonging care were less likely to receive it than younger patients (OR 0.21; CI 0.08-0.54), but were more likely to avoid unwanted life-prolonging care (OR 2.38; CI 1.20-4.75) than younger patients. Older patients were less likely to receive desired life-prolonging care than younger patients (OR 0.23; CI 0.08-0.68), however, they were not more likely to avoid unwanted life-prolonging care than younger patients (OR 1.74; CI 0.87-3.47). Conclusions: Likelihood of a patient's treatment preference being consistent with care differ by age and treatment preferences. Older patients preferring life-prolonging therapies are less likely to receive them than younger patients; middle-aged patients who want to avoid life-prolonging care are more likely to do so than younger patients. Both findings have implications for patients' quality-of-death, indicating a need for further research. C1 [Parr, John D.] Med Coll Wisconsin, Dept Med Educ, Milwoukee, WI USA. [Duthie, Edmund] Med Coll Wisconsin, Dept Gesiatr, Milwoukee, WI USA. [Parr, John D.; Zhang, Baohui; Nilsson, Matthew E.; Wright, Alexi; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Parr, John D.; Zhang, Baohui; Nilsson, Matthew E.; Wright, Alexi; Balboni, Tracy; Prigerson, Holly G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Balboni, Tracy] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Balboni, Tracy] Med Coll Wisconsin, Dept Geriatr, Milwaukee, WI 53226 USA. [Paulk, Elizabeth] Univ Texas Dallas, Palliat Care Serv, Dallas, TX 75230 USA. [Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Parr, JD (reprint author), MCW, Dept Med Educ, 8344A Portland Ave, Wauwatosa, WI 53213 USA. EM jparr@mcw.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA106370]; Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute; NIH [AG026781-04]; American Federation for Aging Research FX This research was supported in part by the following grants to Dr. Prigerson: MH63892 from the National Institute of Mental Health and CA106370 from the National Cancer Institute; the Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute. Research was also supported by NIH Grant AG026781-04 and the American Federation for Aging Research. NR 39 TC 13 Z9 13 U1 3 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2010 VL 13 IS 6 BP 719 EP 726 DI 10.1089/jpm.2009.0337 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 619UM UT WOS:000279455800020 PM 20597704 ER PT J AU Reinke, LF Shannon, SE Engelberg, R Dotolo, D Silvestri, GA Curtis, JR AF Reinke, Lynn F. Shannon, Sarah E. Engelberg, Ruth Dotolo, Danae Silvestri, Gerard A. Curtis, J. Randall TI Nurses' Identification of Important yet Under-Utilized End-of-Life Care Skills for Patients with Life-Limiting or Terminal Illnesses SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PALLIATIVE CARE; NURSING-EDUCATION; COMMUNICATION; PERSPECTIVES; ILL AB Rationale: This study was designed to identify nurses' perspectives on nursing skills that are important yet under-utilized in end-of-life care. Methods: A 45-item survey was administered to nurses (n = 717) in four U. S. states with a response rate of 79%. We identified skills that were endorsed by more than 60% of nurses as extremely important and also endorsed as not currently practiced by more than 25% of nurses. We used Chi square statistics to examine professional characteristics associated with ratings of end-of-life care skills including practice settings, years of experience, and end-of-life care education. Content analysis was used to examine nurses' responses to open-ended questions. Results: Nineteen items were endorsed as extremely important and also ranked as under-utilized. These end-of-life care skills included communication skills, symptom management competencies especially those concerning anxiety and depression, and issues related to patient-centered care systems. Four complementary themes emerged from qualitative analysis of nurses' comments, which supported the quantitative findings. Conclusions: This study provides a summary of skills nurses feel are important and under-utilized in their care of patients with life-limiting illnesses. The findings support the need to target both nursing education and healthcare system interventions to improve the use of practical end-of-life care skills by nurses with a focus on communication and symptom management skills. C1 [Reinke, Lynn F.] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Engelberg, Ruth; Dotolo, Danae; Curtis, J. Randall] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Reinke, Lynn F.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA USA. [Silvestri, Gerard A.] Med Univ S Carolina, Dept Med, Div Pulm & Crit Care Med, Charleston, SC 29425 USA. RP Reinke, LF (reprint author), Univ Washington, Dept Biobehav Nursing & Hlth Syst, 1959 NE Pacific St, Seattle, WA 98195 USA. EM reinkl@u.washington.edu FU Agency for Health Research and Quality [R01 HS11425-02]; National Institute of Nursing Research [1F31NR010055]; VA Health Services R D [TPP-61-021]; VA Puget Sound Health Care System, Seattle, Washington FX Funding was provided by Agency for Health Research and Quality (R01 HS11425-02) and an NRSA from the National Institute of Nursing Research (1F31NR010055) and Post-Doctoral Fellowship, VA Health Services R & D (TPP-61-021).; This material is the result of work supported with resources at the VA Puget Sound Health Care System, Seattle, Washington. NR 29 TC 20 Z9 21 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2010 VL 13 IS 6 BP 753 EP 759 DI 10.1089/jpm.2009.0423 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 619UM UT WOS:000279455800025 PM 20597709 ER PT J AU Feinberg-Zadek, PL Davies, PA AF Feinberg-Zadek, Paula L. Davies, Paul A. TI Ethanol Stabilizes the Open State of Single 5-Hydroxytryptamine(3A)(QDA) Receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NCB-20 NEUROBLASTOMA-CELLS; 5-HT3 RECEPTORS; CHANNEL CONDUCTANCE; DOPAMINE RELEASE; GABA RELEASE; ALCOHOL; SUBUNIT; ANESTHETICS; MODULATION; TRICHLOROETHANOL AB Ethanol enhancement of 5-hydroxytryptamine (5-HT)(3A) receptor-mediated responses may have important consequences in the intoxicating and addictive properties of ethanol. Although the exact mechanism is unknown, ethanol-mediated enhancement of 5-HT3 receptor current has been proposed to occur due to stabilization of the open-channel state. It has not been possible to directly measure the open state of the channel due to the extremely low single-channel conductance of 5-HT3A channels. Recently, three arginine residues within the large intracellular loop of the 5-HT3A subunit were substituted by their equivalent residues (glutamine, aspartate, and alanine) of the 5-HT3B subunit to produce a 5-HT3A(QDA) subunit that forms functional homomeric channels exhibiting a measurable single-channel conductance. Using whole-cell rapid-agonist application techniques and the cell-attached single-channel recording configuration, we examined human 5-HT3A(QDA) receptors expressed in human embryonic kidney 293 cells. The agonist sensitivity, macroscopic kinetics, and modulation by ethanol were similar between mutant and wild-type channels, suggesting the substitutions had not altered these channel structure-function properties. The open time histogram for single-channel events mediated by 5-HT3A(QDA) receptors in the presence of maximal 5-HT was best fit by three exponentials, but in the presence of ethanol a fourth open state was evident. In summary, the QDA substitution greatly enhanced single-channel conductance with little effect on 5-HT3A channel's kinetic properties and ethanol enhances agonist action on 5-HT3A receptors by inducing a new, long-lived open-channel state. Furthermore, the 5-HT3A(QDA) receptor appears to be suitable for pharmacological studies of 5-HT3A receptor modulation at a single-channel level. C1 [Feinberg-Zadek, Paula L.; Davies, Paul A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Davies, PA (reprint author), Tufts Univ, Sch Med, Dept Neurosci, 136 Harrison Ave, Boston, MA 02111 USA. EM paul.davies@tufts.edu OI Davies, Paul/0000-0002-3973-3143 FU National Institutes of Health National Institute of General Medical Sciences [P01-GM58448]; Institutes of Health National Institute of Alcoholism and Alcohol Abuse [R21-AA017938]; Department of Anesthesia and Critical Care, Massachusetts General Hospital (Boston, MA) FX This work was supported in part by the National Institutes of Health National Institute of General Medical Sciences [Grant P01-GM58448]; the National Institutes of Health National Institute of Alcoholism and Alcohol Abuse [Grant R21-AA017938]; and by the Department of Anesthesia and Critical Care, Massachusetts General Hospital (Boston, MA). NR 40 TC 5 Z9 5 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2010 VL 333 IS 3 BP 896 EP 902 DI 10.1124/jpet.109.164863 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 612JZ UT WOS:000278895800028 PM 20200118 ER PT J AU Iwai, LK Benoist, C Mathis, D White, FM AF Iwai, Leo K. Benoist, Christophe Mathis, Diane White, Forest M. TI Quantitative Phosphoproteomic Analysis of T Cell Receptor Signaling in Diabetes Prone and Resistant Mice SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE phosphotyrosine; mass spectrometry; type 1 diabetes; NOD ID TYROSINE PHOSPHORYLATION SITES; TANDEM MASS-SPECTROMETRY; NOD MICE; CENTRAL TOLERANCE; ADAPTER PROTEINS; PEPTIDE SEQUENCE; ACTIVATION; PATHWAYS; REVEALS; COMPLEX AB Type 1 diabetes, in human patients and NOD mice, results from an immune attack on insulin-producing beta-cells of the pancreas by autoreactive T lymphocytes. In NOD mice, genetically controlled perturbations in the signaling pathways downstream of the antigen-specific T cell receptor (TCR) may be instrumental in the altered responses of T cells, manifest as inefficient induction of apoptosis after recognition of self-antigens in the thymus or as perturbed reactivity of mature T cells in peripheral organs. To map this signaling difference(s), we have used mass spectrometry-based quantitative phosphoproteomics to compare the activation of primary CD4(+) T cells of diabetes-prone NOD and -resistant B6.H2g7 mice. Immunoprecipitation and IMAC purification of tyrosine-phosphorylated peptides, combined with a stable-isotope iTRAQ labeling, enabled us to identify and quantify over 77 phosphorylation events in 54 different proteins downstream of TCR stimulation of primary CD4(+) T cells. This analysis showed a generally higher level of phosphotyrosine in activated NOD cells, as well as several phosphorylation sites that appeared to be differentially regulated in these two strains (involving TXK, CD5, PAG1, and ZAP-70). These data highlight the differences in signaling between CD4(+) T cell compartments of NOD and B6g7 mice and may underlie the dysregulation of T cells in NOD mice. C1 [Iwai, Leo K.; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Iwai, Leo K.; Benoist, Christophe; Mathis, Diane] Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. [White, Forest M.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cbdm@hms.harvard.edu RI Iwai, Leo/M-1734-2013 OI Iwai, Leo/0000-0002-1571-7763 FU NIH [R33 AI 065354]; American Diabetes Association FX We thank K. Hattori for assistance with mice and Prof. Andre Veillette for useful discussion. This work was supported by a grant from the NIH (R33 AI 065354) to DM, CB and FW; LKI was supported by a mentor-based postdoctoral fellowship from the American Diabetes Association. NR 42 TC 34 Z9 34 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JUN PY 2010 VL 9 IS 6 BP 3135 EP 3145 DI 10.1021/pr100035b PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 603YF UT WOS:000278243300034 PM 20438120 ER PT J AU Horan, WP Rassovsky, Y Kern, RS Lee, J Wynn, JK Green, MF AF Horan, William P. Rassovsky, Yuri Kern, Robert S. Lee, Junghee Wynn, Jonathan K. Green, Michael F. TI Further support for the role of dysfunctional attitudes in models of real-world functioning in schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; Negative symptoms; Dysfunctional attitudes; Outcome; Structural equation modeling; Recovery ID PSYCHIATRIC RATING-SCALE; NEGATIVE SYMPTOMS; NEUROCOGNITIVE DEFICITS; COGNITIVE IMPAIRMENT; QUALITY-ASSURANCE; SKILLS; PERFORMANCE; MEDIATOR; PEOPLE; PERSPECTIVE AB According to A.T. Beck and colleagues' cognitive formulation of poor functioning in schizophrenia, maladaptive cognitive appraisals play a key role in the expression and persistence of negative symptoms and associated real-world functioning deficits. They provided initial support for this model by showing that dysfunctional attitudes are elevated in schizophrenia and account for significant variance in negative symptoms and subjective quality of life. The current study used structural equation modeling to further evaluate the contribution of dysfunctional attitudes to outcome in schizophrenia. One hundred eleven outpatients and 67 healthy controls completed a Dysfunctional Attitudes Scale, and patients completed a competence measure of functional capacity, clinical ratings of negative symptoms, and interview-based ratings of real-world functioning. Patients reported higher defeatist performance beliefs than controls and these were significantly related to lower functional capacity, higher negative symptoms, and worse community functioning. Consistent with Beck and colleagues' formulation, modeling analyses indicated a significant indirect pathway from functional capacity -> dysfunctional attitudes -> negative symptoms -> real-world functioning. These findings support the value of dysfunctional attitudes for understanding the determinants of outcome in schizophrenia and suggest that therapeutic interventions targeting these attitudes may facilitate functional recovery. Published by Elsevier Ltd. C1 [Horan, William P.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Horan, WP (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 210A, Los Angeles, CA 90073 USA. EM horan@ucla.edu RI Lee, Junghee/C-5226-2014; Wynn, Jonathan/H-3749-2014 OI Lee, Junghee/0000-0001-9567-8700; Wynn, Jonathan/0000-0002-1763-8540 FU National Institute of Mental Health [MH077141, MH43292, MH65707]; Department of Veterans Affairs, Veterans Integrated Service Network 22, Mental Illness Research Education and Clinical Center FX This research was supported by Research Grants MH077141 (to W.P.H.), MH43292 and MH65707 (to M.F.G.) from the National Institute of Mental Health, and by the Department of Veterans Affairs, Veterans Integrated Service Network 22, Mental Illness Research Education and Clinical Center. NR 38 TC 40 Z9 40 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUN PY 2010 VL 44 IS 8 BP 499 EP 505 DI 10.1016/j.jpsychires.2009.11.001 PG 7 WC Psychiatry SC Psychiatry GA 609JW UT WOS:000278653500003 PM 20006849 ER PT J AU Muehlenkamp, JJ Cowles, ML Gutierrez, PM AF Muehlenkamp, Jennifer J. Cowles, Margaret L. Gutierrez, Peter M. TI Validity of the Self-Harm Behavior Questionnaire with Diverse Adolescents SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Self-harm; Adolescents; Assessment; Suicide; Self-injury ID SUICIDAL-BEHAVIOR; INJURIOUS-BEHAVIOR; LIVING INVENTORY; COMMUNITY SAMPLE; RISK; INSTRUMENTS; POPULATION; VALIDATION; IDEATION; REASONS AB Suicide and non-suicidal self-injurious behavior (NSSI) continue to be significant health problems for adolescents. Although there are many instruments available to assess self-harm behaviors, few have been validated for use with adolescents, and even fewer have been validated for use with different racial/ethnic groups. The Self-Harm Behavior Questionnaire (SHBQ) assesses NSSI, suicidal ideation, suicide threats, and past suicide attempts. Data from 1,386 racially/ethnically diverse adolescents (57.5% minority) were collected to examine the validity of the SHBQ in this age group. Analyses supported the four-factor structure, revealed the SHBQ is internally consistent, and provided evidence for convergent validity within Caucasian, African American, and Hispanic adolescents. However, slight differences were noted. Overall, the findings suggest the SHBQ is a useful assessment tool appropriate for use with Caucasian, African American, and Hispanic adolescents. C1 [Muehlenkamp, Jennifer J.; Cowles, Margaret L.] Univ N Dakota, Dept Psychol, Grand Forks, ND 58282 USA. [Gutierrez, Peter M.] Denver VA Med Ctr, Denver, CO USA. RP Muehlenkamp, JJ (reprint author), Univ N Dakota, Dept Psychol, 319 Harvard St,Stop 8380, Grand Forks, ND 58282 USA. EM jennifer.muehlenkamp@und.edu NR 49 TC 12 Z9 12 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD JUN PY 2010 VL 32 IS 2 BP 236 EP 245 DI 10.1007/s10862-009-9131-7 PG 10 WC Psychology, Clinical SC Psychology GA 584AO UT WOS:000276722600009 ER PT J AU Ellis, C Zhao, YM Egede, LE AF Ellis, Charles Zhao, Yumin Egede, Leonard E. TI Depression and increased risk of death in adults with stroke SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Depression; Mortality; Stroke ID POSTSTROKE DEPRESSION; FOLLOW-UP; MAJOR DEPRESSION; MOOD DISORDERS; ALL-CAUSE; MORTALITY; SYMPTOMS; IMPAIRMENT; COMMUNITY; HEALTH AB Objective: Depression is a common condition among individuals with stroke and believed to influence post-stroke mortality. The objective of this study was to evaluate the effect of depression on all-cause mortality among adults with and without a history of stroke. Methods: We studied 10,025 participants in the population-based National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study who were alive and interviewed in 1982 and had complete data for the Center for Epidemiologic Studies Depression Scale. Four groups were created based on history of stroke and depression status in 1982: (1) no stroke, no depression (reference group); (2) no stroke, depression present; (3) history of stroke, no depression; and (4) history of stroke present, depression present. Cox proportional hazards regression models were used to calculate multivariate-adjusted hazard ratios (HRs) of death for each group compared with the reference group. Results: Over 8 years (83,624 person-years of follow-up), 1,925 deaths were documented. Mortality rate per 1,000 person-years of follow-up was highest in the group with both a history of stroke and depression. Compared with the reference group, HRs for all-cause mortality were: no stroke, depression present, 1.23 (95% Cl 1.08-1.40); stroke present, no depression 1.74 (1.06-2.85); and stroke present, depression present, 1.88 (1.27-2.79). Conclusions: The coexistence of stroke and depression increases the risk of death; however, the combined effect is less than additive. (C) 2010 Elsevier Inc. All rights reserved. C1 [Ellis, Charles; Zhao, Yumin; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. [Ellis, Charles; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Ellis, Charles] Med Univ S Carolina, Dept Hlth Profess, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK NIH HHS [R01 DK081121, R01 DK081121-02] NR 35 TC 35 Z9 40 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUN PY 2010 VL 68 IS 6 BP 545 EP 551 DI 10.1016/j.jpsychores.2009.11.006 PG 7 WC Psychiatry SC Psychiatry GA 606ZO UT WOS:000278468200006 PM 20488271 ER PT J AU Hall, DE Koenig, HG Meador, KG AF Hall, Daniel E. Koenig, Harold G. Meador, Keith G. TI Episcopal Measure of Faith Tradition: A Context-Specific Approach to Measuring Religiousness SO JOURNAL OF RELIGION & HEALTH LA English DT Article ID HEALTH RESEARCH; SCALE; SPIRITUALITY; BELIEFS; ORIENTATION; RELIABILITY; DIMENSIONS; INVENTORY; VALIDITY; ILLNESS AB Precise measurement of religiousness remains a vexing problem. In addition to relying almost exclusively on self-report, existing measures of religiousness pay little attention to the specific context of religious belief, and this may override distinctive norms of particular faith traditions and potentially confound the conclusions drawn from such research. To address these limitations, the authors describe a modified form of narrative content analysis that could eventually sort respondents into distinct theological traditions. A pilot test among Episcopalians demonstrates encouraging reliability (kappa 0.74, 95% LCI 0.47, P < 0.0002), and tests for convergent and discriminate validity suggest that the context of religious belief is both relevant and insufficiently assessed by the existing paradigm of religious measurements. If validated in a religiously diverse sample, this approach could be combined with existing, context-free measures of religiousness to generate more meaningful findings. C1 [Hall, Daniel E.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Hall, Daniel E.; Koenig, Harold G.; Meador, Keith G.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Meador, Keith G.] Duke Divin Sch, Durham, NC 27708 USA. [Hall, Daniel E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Hall, DE (reprint author), Univ Pittsburgh, Suite F-1264 Presbyterian,200 Lothrop St, Pittsburgh, PA 15213 USA. EM hallde@upmc.edu RI Koenig, Harold/F-7379-2011; Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 NR 40 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-4197 J9 J RELIG HEALTH JI J. Relig. Health PD JUN PY 2010 VL 49 IS 2 BP 164 EP 178 DI 10.1007/s10943-009-9240-3 PG 15 WC Public, Environmental & Occupational Health; Religion SC Public, Environmental & Occupational Health; Religion GA 590CY UT WOS:000277202800003 PM 19288198 ER PT J AU Singh, JA Noorbaloochi, S Singh, G AF Singh, Jasvinder A. Noorbaloochi, Shahrzad Singh, Gurkirpal TI Golimumab for Rheumatoid Arthritis: A Systematic Review SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE GOLIMUMAB; RHEUMATOID ARTHRITIS; EFFICACY; SAFETY; SYSTEMATIC REVIEW ID COLLEGE-OF-RHEUMATOLOGY; PATIENT-REPORTED OUTCOMES; NECROSIS-FACTOR-ALPHA; MONOCLONAL-ANTIBODY; RESPONSE CRITERIA; WORK DISABILITY; CLINICAL-TRIALS; METHOTREXATE; DISEASE; PROGRESSION AB Objective. To perform a Cochrane systematic review of benefit (American College of Rheumatology 50% improvement criteria; ACR50) and safety (adverse events and withdrawals) of golimumab in patients with rheumatoid arthritis (RA). Methods. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), OVID Medline, CINAHL, Embase, Science Citation Index (Web of Science), and Current Controlled Trials databases for randomized or controlled clinical trials of golimumab compared to placebo or disease-modifying antirheumatic drug in adults with RA. Two authors independently selected appropriate studies and abstracted study characteristics and safety and efficacy data and performed risk-of-bias assessment. We calculated mean differences for continuous measures, and relative risks for categorical measures. Results. Four randomized controlled trials with 1231 golimumab-treated and 483 placebo-treated patients were included. Of these, 436 were treated with golimumab at 50 ma every 4 weeks [a dosage approved by the US Food and Drug Administration (FDA)]. At an average of 4-6 months, compared to patients treated with placebo and methotrexate (MTX), patients treated with the FDA-approved dosage of golimumab and MTX were 2.6 times more likely to reach ACR50 (p = 0.005, 95% CI 1.3, 4.9; absolute percentage, 38% vs 15%) and 0.5 times as likely to have overall withdrawals (p = 0.005, 95% CI 0.3, 0.8; absolute percentage, 5% vs 10%). Golimumab-treated patients were significantly more likely than those taking placebo to achieve remission (22% vs 4%; p<0.00001), and to have improvement in functional ability on the Health Assessment questionnaire 10.2 points lower (p<0.00001, 95% CI 0.25, 0.15); absolute risk difference, 20% (95% CI 25% to 15%); relative percentage difference, 11% (95% CI 14% to 8.3%)]. The studies were too small and short to be powered sufficiently for safety outcomes, but no substantive statistically significant differences were noted between golimumab and placebo regarding adverse events, serious adverse events, infections, serious infections, lung infections, tuberculosis, cancer, withdrawals due to adverse events, and withdrawals due to inefficacy and deaths. Conclusion. At the approved dosage, in patients with active RA taking background MTX, golimumab is significantly more beneficial than placebo. The short-term safety profile is reasonable. Longterm surveillance studies are needed for safety assessment. (First Release May 1 2010; J Rheumatol 2010;37:1096-104: doi: 10.3899/jrheum.091466) C1 [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.; Noorbaloochi, Shahrzad] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Singh, Jasvinder A.; Noorbaloochi, Shahrzad] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Singh, Gurkirpal] Stanford Univ, Sch Med, Div Gastroenterol & Hepatol, Palo Alto, CA 94304 USA. RP Singh, JA (reprint author), Univ Alabama, 820 Fac Off Tower,Room 805B, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Abbott; Takeda; Savient; Wyeth; Amgen; Savietu; URL Pharmaceuticals; Centocor; Johnson Johnson FX Dr. J.A. Singh has received speaker honoraria from Abbott, research and travel grants from Takeda, Savient, Wyeth and Amgen, and consultant fees from Savietu and URL Pharmaceuticals. Dr. G. Singh has received honoraria/consultant/research grants from Centocor, Abbott, Amgen, and Johnson & Johnson. NR 48 TC 11 Z9 11 U1 1 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 2010 VL 37 IS 6 BP 1096 EP 1104 DI 10.3899/jrheum.091466 PG 9 WC Rheumatology SC Rheumatology GA 616FO UT WOS:000279194600005 PM 20436075 ER PT J AU Ogdie, A Schumacher, HR Dai, L Chen, LX Einhorn, E Pessler, F AF Ogdie, Alexis Schumacher, H. Ralph, Jr. Dai, Lie Chen, Lan X. Einhorn, Eugene Pessler, Frank TI Synovial Biopsy Findings in Arthritis Associated with Hepatitis C Virus Infection SO JOURNAL OF RHEUMATOLOGY LA English DT Letter ID WAR-VETERANS-ILLNESS; RHEUMATOID-ARTHRITIS; JOINT PAIN; OSTEOARTHRITIS; ARTHROPATHIES; ANGIOGENESIS C1 [Pessler, Frank] Tech Univ Dresden, Univ Childrens Hosp, Dresden, Germany. [Pessler, Frank] Helmholtz Ctr Infect Res, Braunschweig, Germany. [Ogdie, Alexis] Univ Penn, Sch Med, Dept Internal Med, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.; Dai, Lie; Chen, Lan X.] Philadelphia VA Med Ctr, Div Rheumatol, Philadelphia, PA USA. [Schumacher, H. Ralph, Jr.; Dai, Lie] Sun Yat Sen Univ, Affiliated Hosp 2, Guangzhou 510275, Guangdong, Peoples R China. [Chen, Lan X.] Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Einhorn, Eugene] Philadelphia VA Med Ctr, Dept Pathol, Philadelphia, PA USA. RP Pessler, F (reprint author), Tech Univ Dresden, Univ Childrens Hosp, Dresden, Germany. EM frank.pessler@helmholtz-hzi.de OI Ogdie, Alexis/0000-0002-4639-0775 FU NCI NIH HHS [T32-CA 09140]; NIAMS NIH HHS [T32-AR 007442] NR 14 TC 2 Z9 2 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 2010 VL 37 IS 6 BP 1361 EP 1363 DI 10.3899/jrheum.091309 PG 3 WC Rheumatology SC Rheumatology GA 616FO UT WOS:000279194600283 PM 20516045 ER PT J AU Mohamed, OA Hamed, HA Roaiah, MF Helmy, T Mahran, A Bennett, CJ AF Mohamed, Osama A. Hamed, Hamed A. Roaiah, Mohamed Farid Helmy, Tarek Mahran, Ali Bennett, Carol J. TI Correlation Between the European System for Cardiac Operative Risk Evaluation and Sexual Function After Coronary Artery Bypass Graft Surgery SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Erectile Dysfunction; Vascular Risk Factors; Coronary Artery Bypass Grafting; EuroSCORE ID VASCULOGENIC ERECTILE DYSFUNCTION; OBSTRUCTIVE PULMONARY-DISEASE; EUROSCORE ADDITIVE-MODEL; STRATIFICATION ANALYSIS; SILDENAFIL CITRATE; HEART-SURGERY; PREVALENCE; PREDICTOR; MORTALITY; IMPOTENCE AB Introduction. The published studies discussing the prognostic factors for expected sexual function after coronary artery bypass graft (CABG) are still limited. Aim. Examining the correlation between the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and the abridged form of International Index of Erectile Function questionnaire (IIEF-5), as a quick and inexpensive tool for the cardiologist to predict the sexual function after CABG. Main Outcome Measures. Validated standardized questionnaire commonly used by cardiologists in identifying appropriate weight to various risk factors related to adult cardiac operations. Methods. Preoperatively patients were evaluated as regards to the sexual function by (IIEF-5) and pharmaco-penile duplex ultrasound. Moreover all patients were evaluated bu EuroSCORE. Six months after surgery, the erectile function of all patients was revaluated according to the same preoperative procedures. The patients were categorized with EuroSCORE as follows: The low-risk group (EuroSCORE 0-2), the medium-risk group (EuroSCORE 3-5), and the high-risk group (EuroSCORE 6 plus). Results. The EuroSCORE was negatively correlated with the IIEF-5 score (r = -0.224, P = 0.025 or rs = -0.259, P = 0.009). Moreover, low-risk patients had significantly higher IIEF-5 scores compared with medium-risk patients (mean +/- standard deviation = 15.27 +/- 6.03 vs. 12.18 +/- 6.07, P < 0.05). Conclusions. There is an inverse correlation between the components of EuroSCORE and the IIEF-5 score. Patients with higher EuroSCORE had lower IIEF-5 scores and vice versa.The EuroSCORE is a useful, quick, and inexpensive tool that allows prediction of ED in those patients with coronary artery disease patients who are undergoing CABG. Mohamed OA, Hamed HA, Roaiah MF, Helmy T, Mahran A, and Bennett CJ. Correlation between the European System for Cardiac Operative Risk Evaluation and sexual function after coronary artery bypass graft surgery. J Sex Med 2010;7:2158-2165. C1 [Mohamed, Osama A.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Mohamed, Osama A.; Hamed, Hamed A.; Roaiah, Mohamed Farid] Cairo Univ, Fac Med, Androl & STDS Dept, Cairo, Egypt. [Helmy, Tarek] Cairo Univ, Fac Med, Cardiothorac Dept, Cairo, Egypt. [Mahran, Ali] Asyut Univ, Fac Med, Androl Dept, Asyut, Egypt. [Bennett, Carol J.] Greater Los Angeles VA Med Syst, Urol, Los Angeles, CA USA. [Bennett, Carol J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Mohamed, OA (reprint author), Baylor Coll Med, Scott Dept Urol, 6560 Fannin St, Houston, TX 77030 USA. EM azimusama@gmail.com NR 50 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD JUN PY 2010 VL 7 IS 6 BP 2158 EP 2165 DI 10.1111/j.1743-6109.2010.01727.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 604XF UT WOS:000278311100019 PM 20954293 ER PT J AU Elhassan, B Ozbaydar, M Massimini, D Higgins, L Warner, JJP AF Elhassan, Bassem Ozbaydar, Mehmet Massimini, Daniel Higgins, Laurence Warner, Jon J. P. TI Arthroscopic capsular release for refractory shoulder stiffness: A critical analysis of effectiveness in specific etiologies SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Arthroscopic; capsular; release; post-traumatic; idiopathic; postsurgical ID RESISTANT FROZEN SHOULDER; ADHESIVE CAPSULITIS; MANIPULATION AB Hypothesis: The purpose of this study is to report and compare the outcome of arthroscopic capsular release in patients with shoulder stiffness with post-traumatic, postsurgical, and idiopathic etiologies. We hypothesize that patients with idiopathic or post-traumatic stiffness have better outcomes after arthroscopic capsular release than those with shoulder stiffness with a postsurgical etiology. Materials and Methods: A retrospective review of 115 patients who underwent arthroscopic capsular release for refractory shoulder stiffness was performed. There were 60 men and 55 women with a mean age of 49 years (range, 27 to 81 years). The patients were divided into 3 groups according to the etiology of stiffness: post-traumatic (26 patients), postsurgical (48 patients), and idiopathic (41 patients). Arthroscopic capsular release was performed in all patients after a mean of 9 months of physical therapy (range, 6 to 13 months). Results: At a mean follow-up of 46 months (range, 25 to 89 months), the overall subjective shoulder value in all groups improved from 29% to 73% and the age- and gender-adjusted Constant score improved from 35% to 86%. The mean pain score decreased from 7.5 to 1, and mean active forward flexion, external rotation, and internal rotation increased from 97 degrees, 14 degrees, and the L5 vertebral level, respectively, to 135 degrees, 38, and the Ill vertebral level, respectively (P<.0001). There was no significant difference between the outcomes of idiopathic and post-traumatic stiffness (P=.7). However, the Constant score and subjective shoulder value were significantly lower in the postsurgical group compared with the idiopathic and post-traumatic groups (P=.0001 and P=.006, respectively). Conclusions: Arthroscopic capsular release is an effective treatment for refractory shoulder stiffness. Patients with idiopathic and post-traumatic shoulder stiffness have better outcomes than patients with postsurgical stiffness. C1 [Massimini, Daniel; Warner, Jon J. P.] Massachusetts Gen Hosp, Div Shoulder Surg, Dept Orthoped Surg, MIT, Boston, MA 02114 USA. [Warner, Jon J. P.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Harvard Shoulder Serv, Boston, MA USA. [Elhassan, Bassem] Mayo Clin, Dept Orthoped Surg, Rochester, MN USA. [Ozbaydar, Mehmet] Okmeydani Teaching Hosp, Istanbul, Turkey. [Higgins, Laurence] Harvard Univ, Sch Med, Sports Med & Shoulder Serv, Brigham & Woman Hosp, Boston, MA USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Div Shoulder Surg, Dept Orthoped Surg, MIT, 55 Fruit St, Boston, MA 02114 USA. EM JJPWarner@partners.org RI Ozbaydar, Mehmet/D-7391-2016 NR 32 TC 24 Z9 26 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JUN PY 2010 VL 19 IS 4 BP 580 EP 587 DI 10.1016/j.jse.2009.08.004 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 612MB UT WOS:000278901500016 PM 20004595 ER PT J AU Bauman, WA Kirshblum, S Cirnigliaro, C Forrest, GF Spungen, AM AF Bauman, William A. Kirshblum, Steven Cirnigliaro, Christopher Forrest, Gail F. Spungen, Ann M. TI Underestimation of Bone Loss of the Spine With Posterior-Anterior Dual-Energy X-Ray Absorptiometry in Patients With Spinal Cord Injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Spinal cord injuries; Paraplegia; Tetraplegia; Bone mineral density; Vertebral body; Dual-energy X-ray absorptiometry; Osteoporosis ID QUANTITATIVE COMPUTED-TOMOGRAPHY; LOWER-EXTREMITY FRACTURES; MINERAL DENSITY; LUMBAR SPINE; OSTEOPOROSIS; DENSITOMETRY; DEMINERALIZATION; DISEASE; WOMEN AB Background: Bone mineral density (BMD) of the lumbar spine (L-spine) has been reported to be normal by routine posterior-anterior (PA) bone density imaging in patients with chronic spinal cord injury (SCI). Objective: To determine BMD of the L-spine by PA and lateral (LAT) dual-energy radiographic absorptiometry (DXA) in patients with chronic SCI. Design: Prospective study. Setting: Veterans Affairs Medical Center and a private rehabilitation facility. Methods: Measurements of the PA and LAT L-spine and hip were performed in 15 patients with SCI: 9 with tetraplegia and 6 with paraplegia. The DXA (GE Lunar Advance DXA) images were obtained using standard software. Results are reported as mean +/- SD. Results: The mean age was 35 +/- 15 years (range = 20-62 years), and the duration of injury was 57 +/- 74 months (range = 3-240 months). T- and Z-scores were lower for the LAT L-spine than those for PA L-spine (T-scores L2: -0.7 +/- 1.2 vs 0.0 +/- 1.4, P < 0.01; L3: -0.9 +/- 1.6 vs 0.3 +/- 1.3, P < 0.002; L2-L3: -0.8 +/- 1.3 vs 0.2 +/- 1.3, P < 0.001; Z-scores L2: -0.3 +/- 1.1 vs 0.2 +/- 1.2, P < 0.05; L3: -0.6 +/- 1.3 vs 0.5 +/- 1.3, P < 0.01; L2-L3: -0.4 +/- 1.1 vs 0.4 +/- 1.2, P < 0.005). The T- and Z-scores for the total hip (-1.1 +/- 1.0 and -1.0 +/- 1.0, respectively) and L2-L3 LAT L-spine demonstrated remarkable similarity, whereas the L2-L3 PA L-spine scores were not reduced. Bone mineral density of the LAT L-spine, but not the PA L-spine, was significantly reduced with increasing duration of injury. Conclusions: Individuals with SCI may have bone loss of the L-spine that is evident on LAT DXA that may be misdiagnosed by PA DXA, underestimating the potential risk of fracture. C1 [Bauman, William A.] James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Med Serv, Bronx, NY 10468 USA. [Bauman, William A.; Cirnigliaro, Christopher; Spungen, Ann M.] Vet Affairs Rehabil Res & Dev Ctr Excellence Med, Bronx, NY USA. [Bauman, William A.; Cirnigliaro, Christopher; Spungen, Ann M.] James J Peters Vet Affairs Med Ctr, Spinal Cord Injury Serv, Bronx, NY 10468 USA. [Bauman, William A.; Cirnigliaro, Christopher; Spungen, Ann M.] James J Peters Vet Affairs Med Ctr, Res Serv, Bronx, NY 10468 USA. [Bauman, William A.; Spungen, Ann M.] Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. [Bauman, William A.; Spungen, Ann M.] Mt Sinai Med Ctr, Dept Rehabil Med, New York, NY 10029 USA. [Kirshblum, Steven] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven; Forrest, Gail F.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. [Kirshblum, Steven; Forrest, Gail F.] Kessler Fdn Res Ctr, W Orange, NJ USA. RP Bauman, WA (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Med Serv, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM william.bauman@va.gov FU VA Rehabilitation Research and Development Service Center of Excellence for the Medical Consequences of Spinal Cord Injury [B4162C]; James J. Peters VA Medical Center; Department of Veterans Affairs Rehabilitation Research and Development Service; Kessler Institute for Rehabilitation; Kessler Foundation Research Center; Centers for Disease Control and Prevention; Christopher and Dana Reeve Foundation FX This work was funded by a VA Rehabilitation Research and Development Service Center of Excellence for the Medical Consequences of Spinal Cord Injury grant (B4162C).; We thank the James J. Peters VA Medical Center, Department of Veterans Affairs Rehabilitation Research and Development Service, Kessler Institute for Rehabilitation, Kessler Foundation Research Center, Centers for Disease Control and Prevention, and the Christopher and Dana Reeve Foundation for their support. NR 20 TC 7 Z9 8 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD JUN PY 2010 VL 33 IS 3 BP 214 EP 220 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 639WQ UT WOS:000281007700003 PM 20737794 ER PT J AU Schwartz, B Wetzler, S Swanson, A Sung, SC AF Schwartz, Bruce Wetzler, Scott Swanson, Arthur Sung, Sharon C. TI Subtyping of substance use disorders in a high-risk welfare-to-work sample: A latent class analysis SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Substance abuse; Substance dependence; Subtypes; Co-occurring disorders; Latent class analysis ID NATIONAL EPIDEMIOLOGIC SURVEY; ADDICTION TREATMENT; DRUG-USE; ALCOHOL DEPENDENCE; HEALTH-PROBLEMS; BARRIERS; CARE; SERVICES; ABUSE; COMORBIDITY AB The goals of this study were (a) to investigate the existence of substance abuse/dependence subtypes in a diverse low-income welfare to work sample and (b) to explore subtype differences in rates of comorbid psychiatric and medical conditions. Data for all demographic and clinical variables were extracted from deidentified case records of 4,977 clients enrolled in a comprehensive case management program for welfare recipients with substance use disorders. Latent class analysis supported a five-class model made up of a multiple abuse/dependence class (n = 1,133), a cocaine/alcohol class (n = 2,120), an opioids class (n = 1,346), a cannabis class (a = 362), and a small polysubstance/none primary class (n = 16). Post hoc chi-square analyses revealed several between-class differences, perhaps reflecting differing levels of severity and service needs. All five classes were characterized by high rates of medical and psychiatric comorbidity. (C) 2010 Elsevier Inc. All rights reserved. C1 [Sung, Sharon C.] Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Schwartz, Bruce; Wetzler, Scott; Swanson, Arthur] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA. RP Sung, SC (reprint author), Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, 185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM ssung@partners.org NR 40 TC 11 Z9 11 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUN PY 2010 VL 38 IS 4 BP 366 EP 374 DI 10.1016/j.jsat.2010.03.001 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 595AF UT WOS:000277582400007 PM 20362407 ER PT J AU Ling, W Jacobs, P Hillhouse, M Hasson, A Thomas, C Freese, T Sparenborg, S McCarty, D Weiss, R Saxon, A Cohen, A Straus, M Brigham, G Liu, D McLaughlin, P Tai, B AF Ling, Walter Jacobs, Petra Hillhouse, Maureen Hasson, Albert Thomas, Christie Freese, Thomas Sparenborg, Steven McCarty, Dennis Weiss, Roger Saxon, Andrew Cohen, Allan Straus, Michele Brigham, Gregory Liu, David McLaughlin, Paul Tai, Betty TI From research to the real world: Buprenorphine in the decade of the Clinical Trials Network SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Buprenorphine; CTN; Clinical Trials Network; Opioids; Opiate dependence; Pharmacotherapy ID SUBSTANCE-ABUSE TREATMENT; OPIOID DEPENDENCE; RANDOMIZED-TRIAL; ADOPTION; DETOXIFICATION; NALOXONE; ADDICTION AB The National Institute on Drug Abuse (NIDA) established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to bring researchers and treatment providers together to develop a clinically relevant research agenda. Initial CTN efforts addressed the use of buprenorphine, a mu-opioid partial agonist, as treatment for opioid dependence. Strong evidence of buprenorphine's therapeutic efficacy was demonstrated in clinical trials involving several thousand opioid-dependent participants, and in 2002, the Food and Drug Administration approved buprenorphine for the treatment of opioid dependence. With the advent of a sublingual tablet containing both buprenorphine and naloxone to mitigate abuse and diversion (Suboxone), buprenorphine appeared poised to be the first-line treatment for opioid addiction. Notwithstanding its many attributes, certain implementation barriers remained to be addressed in CTN studies, and these efforts have brought a body of knowledge on buprenorphine to frontline clinicians. The purpose of this article is to review CTN-based buprenorphine research and related efforts to overcome challenges to the implementation of buprenorphine therapy in mainstream practice. Furthermore, this article explores current issues and future challenges that may require additional CTN efforts. (C) 2010 Elsevier Inc. All rights reserved. C1 [Ling, Walter; Hillhouse, Maureen; Hasson, Albert; Thomas, Christie; Freese, Thomas] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Jacobs, Petra; Sparenborg, Steven; Straus, Michele; Liu, David; Tai, Betty] Natl Inst Drug Abuse, NIDA CCTN, Ctr Clin Trials Network, Lexington, KY USA. [McCarty, Dennis] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Weiss, Roger] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Saxon, Andrew] Vet Affairs Puget Sound Hlth Care Syst, Washington Reg Node, Washington, DC USA. RP Hillhouse, M (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90024 USA. EM hillhous@ucla.edu OI Brigham, Gregory/0000-0003-1150-4493 FU NIDA NIH HHS [U10 DA 13036, U10 DA 13045, U10 DA013045, U10 DA013045-09, U10 DA013045-10, U10 DA015831, U10 DA13732, K24 DA022288, U10 DA15831, K24DA022288] NR 30 TC 22 Z9 22 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUN PY 2010 VL 38 IS 4 SU 1 BP S53 EP S60 DI 10.1016/j.jsat.2010.01.009 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 595AG UT WOS:000277582500006 PM 20307796 ER PT J AU Wells, EA Saxon, AJ Calsyn, DA Jackson, TR Donovan, DM AF Wells, Elizabeth A. Saxon, Andrew J. Calsyn, Donald A. Jackson, Thomas R. Donovan, Dennis M. TI Study results from the Clinical Trials Network's first 10 years: Where do they lead? SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Clinical trials; Substance abuse treatment; Effectiveness research ID SUBSTANCE-ABUSE TREATMENT; MOTIVATIONAL ENHANCEMENT THERAPY; ADAPTIVE TREATMENT STRATEGIES; MULTISITE RANDOMIZED-TRIAL; RISK REDUCTION GROUPS; DRUG-ABUSE; TREATMENT PROGRAMS; BUPRENORPHINE-NALOXONE; BEHAVIORAL THERAPIES; SMOKING-CESSATION AB The National Drug Abuse Treatment Clinical Trials Network (CTN) began in 2000 with the goal of "improv[ing] the quality of drug abuse treatment throughout the country using science as the vehicle." Since then, 24 discrete clinical trials were launched, 20 are completed, and 15 have published main outcome papers. Of the latter, 4 tested pharmacological treatment, 8 psychosocial/behavioral treatment, 1 a combination of medication and counseling, and 2 targeted HIV/hepatitis C virus risk behavior. We review main study findings for these trials, including treatment retention, substance use or risk behavior outcomes, and secondary outcomes when analyzed. The purpose of this review is to identify the incremental progress toward improving drug treatment made by these trials and to propose next steps for the CTN and for the field arising from these studies. The CTN provides a unique opportunity to systematically design trials that incorporate treatment improvements from previous trials and to direct efforts toward innovations most likely to be incorporated into practice. (C) 2010 Elsevier Inc. All rights reserved. C1 [Wells, Elizabeth A.; Jackson, Thomas R.] Univ Washington, Sch Social Work, Seattle, WA 98105 USA. [Saxon, Andrew J.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. [Calsyn, Donald A.; Donovan, Dennis M.] Inst Alcohol & Drug Abuse, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. [Jackson, Thomas R.] Evergreen Treatment Serv, Seattle, WA 98134 USA. RP Wells, EA (reprint author), Univ Washington, Sch Social Work, 4101 15th Ave NE, Seattle, WA 98105 USA. EM bwells@u.washington.edu FU NIDA NIH HHS [U10 DA013714-08, U10 DA013714, 5U10 DA013714] NR 52 TC 16 Z9 16 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUN PY 2010 VL 38 IS 4 SU 1 BP S14 EP S30 DI 10.1016/j.jsat.2009.12.009 PG 17 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 595AG UT WOS:000277582500003 PM 20307792 ER PT J AU Landry, J Catalano, PJ Staley, C Harris, W Hoffman, J Talamonti, M Xu, N Cooper, H Benson, AB AF Landry, Jerome Catalano, Paul J. Staley, Charles Harris, Wayne Hoffman, John Talamonti, Mark Xu, Natalie Cooper, Harry Benson, Al B., III TI Randomized Phase II Study of Gemcitabine Plus Radiotherapy Versus Gemcitabine, 5-Fluorouracil, and Cisplatin Followed by Radiotherapy and 5-Fluorouracil for Patients With Locally Advanced, Potentially Resectable Pancreatic Adenocarcinoma SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE radiotherapy; gemcitabine; pancreatic cancer ID PREOPERATIVE CHEMORADIATION PANCREATICODUODENECTOMY; INTRAOPERATIVE RADIATION-THERAPY; TWICE-WEEKLY GEMCITABINE; FULL-DOSE GEMCITABINE; CONCURRENT RADIATION; SOLID TUMORS; CANCER; TRIAL; RESECTION; HEAD AB Purpose: A randomized phase II trial (E1200) was designed to assess toxicities and surgical resection rates in two neoadjuvant gemcitabine-based chemoradiation regimens in patients with borderline resectable pancreatic cancer. The trial was terminated early due to poor accrual. Patients and Methods: Patients with borderline resectable adenocarcinomas of the pancreas were enrolled. Arm A patients (n = 10) received gemcitabine 500 mg/m(2) IV weekly for 6 weeks, with radiation to 50.4 Gy followed by surgical resection. Arm B patients (n = 11) received preoperative gemcitabine 175 mg/m(2) on days 1, 5, 29, and 33, cisplatin 20 mg/m(2) on days 1-5 and 29-32, 5-FU 600 mg/m(2) on days 1-5 and 29-32, followed by radiation with continuous infusion 5-FU 225 mg/m(2) for 6 weeks. All patients received adjuvant gemcitabine 1,000 mg/m(2) weekly x 3 for five cycles. Results: Three patients in arm A. and two patients in arm B were resected. Hematologic toxicity was comparable between the two arms except more patients in arm B developed grade 3 or 4 thrombocytopenia than those in arm A. Arm B had fewer grade 1-2 GI toxicities although more patients (45%) experienced grade 3-4 GI toxicity. Conclusions: This phase II trial showed that both regimens were tolerable, and resectability and survival were comparable to previous studies. J. Surg. Oncol. 2010;101:587-592. (C) 2010 Wiley-Liss, Inc. C1 [Landry, Jerome; Xu, Natalie] Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA. [Catalano, Paul J.] Harvard Univ, Dana Farber Canc Inst, Dept Bisotatist & Computat Biol, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Staley, Charles] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. [Harris, Wayne] Emory Univ, Sch Med, Dept Med Oncol, Atlanta, GA USA. [Hoffman, John; Cooper, Harry] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Talamonti, Mark] Northwestern Univ, Dept Gen Surg, Chicago, IL 60611 USA. [Benson, Al B., III] Northwestern Univ, Dept Med Oncol, Chicago, IL 60611 USA. RP Landry, J (reprint author), Emory Univ, Sch Med, Dept Radiat Oncol, 1365C Clifton Rd, Atlanta, GA 30322 USA. EM jerome@radonc.emory.org FU Public Health Service [CA23318, CA66636, CA21115, CA27525, CA07190, CA21076, CA49957, CA17145]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX Conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA27525, CA07190, CA21076, CA49957, CA17145 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. NR 21 TC 58 Z9 60 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUN 1 PY 2010 VL 101 IS 7 BP 587 EP 592 DI 10.1002/jso.21527 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 604OI UT WOS:000278288000009 PM 20461765 ER PT J AU Earle, CC Weiser, MR Ter Veer, A Skibber, JM Wilson, J Rajput, A Wong, YN Benson, AB Shibata, S Romanus, D Niland, J Schrag, D AF Earle, Craig C. Weiser, Martin R. Ter Veer, Anna Skibber, John M. Wilson, John Rajput, Ashwani Wong, Yu-Ning Benson, Al B. Shibata, S. Romanus, Dorothy Niland, Joyce Schrag, Deborah TI Effect of Lymph Node Retrieval Rates on the Utilization of Adjuvant Chemotherapy in Stage II Colon Cancer SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Letter C1 [Earle, Craig C.] Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada. [Weiser, Martin R.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ter Veer, Anna; Shibata, S.; Schrag, Deborah] City Hope Canc Ctr, Duarte, CA USA. [Skibber, John M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wilson, John] Ohio State Univ, Columbus, OH 43210 USA. [Rajput, Ashwani] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Benson, Al B.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Romanus, Dorothy; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Earle, CC (reprint author), Inst Clin Evaluat Sci, 2075 Bayview Ave,G Wing,Room 106, Toronto, ON M4N 3M5, Canada. EM craig.earle@ices.on.ca 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUN 1 PY 2010 VL 101 IS 7 BP 644 EP 644 DI 10.1002/jso.21549 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 604OI UT WOS:000278288000020 ER PT J AU Dille, MF Konrad-Martin, D Gallun, F Helt, WJ Gordon, JS Reavis, KM Bratt, GW Fausti, SA AF Dille, Marilyn F. Konrad-Martin, Dawn Gallun, Frederick Helt, Wendy J. Gordon, Jane S. Reavis, Kelly M. Bratt, Gene W. Fausti, Stephen A. TI Tinnitus Onset Rates from Chemotherapeutic Agents and Ototoxic Antibiotics: Results of a Large Prospective Study SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Ototoxicity; ototoxicity monitoring; tinnitus; veterans ID CISPLATIN-INDUCED OTOTOXICITY; INDUCED HEARING-LOSS; QUALITY-OF-LIFE; TESTICULAR CANCER; RISK-FACTORS; RANGE AB Background and Purpose: To report on the incidence and relative risk of tinnitus onset from a variety of drug therapies known to be ototoxic. Two main questions were asked: (1) What is the prevalence and incidence of tinnitus among patients treated with cisplatin, carboplatin, or-ototoxic antibiotic therapies? (2) Do commonly reported treatment or subject factors confound or modify the incidence of tinnitus onset? Data Collection and Analysis: A prospective observational study design was used to evaluate occurrence of significant otologic changes in 488 veterans (962 ears) receiving chemotherapeutic agents (cisplatin, carboplatin), ototoxic antibiotics (primarily aminoglycoside), or nonototoxic drugs (control medications). A subset of 260 veterans lacking tinnitus prior to drug exposure was used to compare rates of tinnitus onset. Subjects were tested prior to, during, and following their treatment. Planned comparisons using logistic regression, analysis of variance (ANOVA), and chi(2) statistics were made among groups by the type of medication taken, age, presence of preexisting hearing loss, days on drug, and cumulative dose of drug. Results: Baseline tinnitus rates were high (nearly 47%) relative to the general population of a similar age. Subjects with exposure to ototoxic medications had significantly increased risk for developing tinnitus. Those on chemotherapeutic agents were found to have the greatest risk. Cisplatin elevated the risk by 5.53 times while carboplatin increased the risk by 3.75 over nonototoxic control medications. Ototoxic antibiotics resulted in borderline risk (2.81) for new tinnitus. Contrary to other reports, we did not find that subject factors (increased age or pre-existing hearing loss) or treatment factors (days on drug or cumulative dose) contributed to rates of tinnitus onset during treatment. Conclusions: This large prospective study confirms that new tinnitus during treatment is associated with chemotherapy and with certain ototoxic antibiotic treatment. Cisplatin and carboplatin were found to be the most potent ototoxic agents causing tinnitus at much greater numbers than the other drugs studied. Implications for counseling and audiological resource allocation are discussed. C1 [Dille, Marilyn F.; Konrad-Martin, Dawn; Gallun, Frederick; Helt, Wendy J.; Gordon, Jane S.; Fausti, Stephen A.] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res, Portland, OR USA. [Dille, Marilyn F.; Konrad-Martin, Dawn; Gallun, Frederick; Fausti, Stephen A.] Oregon Hlth & Sci Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Reavis, Kelly M.] Univ Calif Irvine, Dept Otolaryngol, Irvine, CA 92717 USA. [Bratt, Gene W.] Vanderbilt Univ, Dept Otolaryngol, Sch Med, Nashville, TN USA. RP Dille, MF (reprint author), 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM marilyn.dille@va.gov RI Gallun, Frederick/G-3792-2012; OI Gallun, Frederick/0000-0002-4145-2199; Reavis, Kelly/0000-0002-4906-1010 FU Rehabilitation Research and Development Service (RR&D), Department of Veterans Affairs [C4183R, C3213R, C2346R, C4447K] FX This work was supported by grants from the Rehabilitation Research and Development Service (RR&D), Department of Veterans Affairs (C4183R, C3213R, C2346R, and C4447K). NR 24 TC 19 Z9 20 U1 0 U2 4 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD JUN PY 2010 VL 21 IS 6 BP 409 EP 417 DI 10.3766/jaaa.21.6.6 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 637DP UT WOS:000280796300006 PM 20701838 ER PT J AU Weaver, MJ Miller, MA Vrahas, MS AF Weaver, Michael J. Miller, Micah A. Vrahas, Mark S. TI The Orthopaedic Implications of Diphosphonate Therapy SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID BONE-MINERAL DENSITY; FRACTURE INTERVENTION TRIAL; ZOLEDRONIC ACID; POSTMENOPAUSAL OSTEOPOROSIS; MICRODAMAGE ACCUMULATION; BIOMECHANICAL PROPERTIES; NONENZYMATIC GLYCATION; VERTEBRAL FRACTURES; ALENDRONATE THERAPY; RANDOMIZED-TRIAL AB Diphosphonates are among the many commonly prescribed drugs for osteoporosis management. These synthetic analogues of physiologically occurring inorganic pyrophosphate bind to the hydroxyapatite crystals of bone. Diphosphonates act by decreasing the amount of osteoclast-mediated bone resorption by inducing apoptosis and disrupting the mevalonate biosynthetic pathway. Prospective clinical trials have shown that diphosphonates increase bone mineral density and reduce the risk of fracture. Diphosphonates are generally well tolerated, with a low incidence of side effects. They may be administered orally or intravenously; infusions are the most potent. Few studies have directly studied the effect of diphosphonates on the rate of fracture or time to union. Concern exists regarding the long-term safety of diphosphonates, particularly in patients with osteoporosis. New evidence suggests that long-term therapy may increase the risk of fracture of the femoral shaft, with possible morphologic and prodromal warning signs. Further prospective research into the consequences of diphosphonate-mediated suppressed bone turnover is needed to elucidate a safe duration of treatment. C1 [Weaver, Michael J.] Brigham & Womens Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Weaver, MJ (reprint author), Brigham & Womens Hosp, Partners Orthopaed Trauma Serv, 75 Francis St, Boston, MA 02115 USA. FU Synthes; Zimmer; DePuy, a Johnson & Johnson company; AO FX Dr. Weaver or an immediate family member has received research or institutional support from Synthes and Zimmer. Dr. Vrahas or an immediate family member has received research or institutional support from Synthes; DePuy, a Johnson & Johnson company; Zimmer; and AO. Neither Mr. Miller nor any immediate family member has received anything of value from or owns stock in a commercial company or institution related directly or indirectly to the subject of this article. NR 45 TC 7 Z9 11 U1 0 U2 0 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD JUN PY 2010 VL 18 IS 6 BP 367 EP 374 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 603WJ UT WOS:000278238500009 PM 20511442 ER PT J AU Hochholzer, W Trenk, D Fromm, MF Valina, CM Stratz, C Bestehorn, HP Buttner, HJ Neumann, FJ AF Hochholzer, Willibald Trenk, Dietmar Fromm, Martin F. Valina, Christian M. Stratz, Christian Bestehorn, Hans-Peter Buettner, Heinz Joachim Neumann, Franz-Josef TI Impact of Cytochrome P450 2C19 Loss-of-Function Polymorphism and of Major Demographic Characteristics on Residual Platelet Function After Loading and Maintenance Treatment With Clopidogrel in Patients Undergoing Elective Coronary Stent Placement SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE antiplatelet therapy; CYP2C19; platelet function; polymorphism; predictor ID TYPE-2 DIABETES-MELLITUS; ANTIPLATELET; INTERVENTION; REACTIVITY; THROMBOSIS; THERAPY; RESPONSIVENESS; AGGREGATION; DETERMINANT; INHIBITION AB Objectives The aim of this study was to evaluate the relative impact of demographic and clinical variables versus the cytochrome P450 2C19 (CYP2C19) polymorphism on antiplatelet effects of clopidogrel. Background Platelet responses to clopidogrel show a marked interindividual variability with substantial impact on clinical outcome. Several demographic and clinical characteristics as well as a polymorphism of CYP2C19 have been described as predictors for a low response to clopidogrel. Methods This analysis enrolled 760 patients undergoing elective coronary stent implantation after loading with 600 mg of clopidogrel. Residual platelet aggregation was determined by optical aggregometry (adenosine diphosphate 5 mu mol/l) before discharge. We analyzed the predictive value of the CYP2C19*2 polymorphism and baseline variables for an insufficient antiplatelet response by multivariable regression analysis and classification and regression trees analysis and determined the proportion responsible for the antiplatelet response of these predictors by multivariable linear regression analysis. Results Major independent predictors for an insufficient antiplatelet response to clopidogrel were CYP2C19*2 carrier status (odds ratio [OR]: 2.74; 95% confidence interval [CI]: 1.93 to 3.90) together with age (OR: 1.03; 95% CI: 1.01 to 1.05), diabetes mellitus (OR: 1.75; 95% CI: 1.19 to 2.56), and body mass index (OR: 1.06; 95% CI: 1.02 to 1.11). The classification and regression trees analysis demonstrated that CYP2C19*2 carrier status followed by diabetes mellitus was the best discriminator between a sufficient and an insufficient antiplatelet response to clopidogrel. The full linear regression model including all these parameters could only explain 11.5% of the antiplatelet response (5.2% by CYP2C19*2 carrier status alone). Conclusions Thus, our study does not suggest that, in patients critically dependent on adequate platelet inhibition, genotyping alone or in combination with clinical factors can replace phenotyping of platelet function. (Effect of Clopidogrel Loading and Risk of PCI [EXCELSIOR]; NCT00457236). (J Am Coll Cardiol 2010; 55: 2427-34) (C) 2010 by the American College of Cardiology Foundation C1 [Hochholzer, Willibald] Harvard Univ, Div Cardiovasc, TIMI Study Grp,Sch Med,Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Hochholzer, Willibald; Trenk, Dietmar; Valina, Christian M.; Stratz, Christian; Bestehorn, Hans-Peter; Buettner, Heinz Joachim; Neumann, Franz-Josef] Herz Zentrum Bad Krozingen, Bad Krozingen, Germany. [Fromm, Martin F.] Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol & Toxicol, Erlangen, Germany. RP Hochholzer, W (reprint author), Harvard Univ, Div Cardiovasc, TIMI Study Grp,Sch Med,Dept Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM whochholzer@partners.org RI 刘, 李陆/H-8469-2015 FU Herz-Zentrum, Bad Krozingen; German Heart Foundation FX From the *Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany; dagger Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen, Germany; and the double dagger TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts. This study was supported by a grant from the Herz-Zentrum, Bad Krozingen. Dr. Hochholzer was supported by the German Heart Foundation. NR 35 TC 164 Z9 168 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 JUN 1 PY 2010 VL 55 IS 22 BP 2427 EP 2434 DI 10.1016/j.jacc.2010.02.031 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 600ZB UT WOS:000278026600002 PM 20510210 ER PT J AU Thanassoulis, G Massaro, JM Cury, R Manders, E Benjamin, EJ Vasan, RS Cupple, LA Hoffmann, U O'Donnell, CJ Kathiresan, S AF Thanassoulis, George Massaro, Joseph M. Cury, Ricardo Manders, Emily Benjamin, Emelia J. Vasan, Ramachandran S. Cupple, L. Adrienne Hoffmann, Udo O'Donnell, Christopher J. Kathiresan, Sekar TI Associations of Long-Term and Early Adult Atherosclerosis Risk Factors With Aortic and Mitral Valve Calcium SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE aortic valve; atherosclerosis; calcification; mitral valve; stenosis ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; METABOLIC SYNDROME; DIABETES-MELLITUS; CLINICAL FACTORS; ANULAR CALCIUM; EARLY LESION; STENOSIS; PROGRESSION; CALCIFICATION AB Objectives To determine the association of long-term exposure to atherosclerosis risk factors with valvular calcification. Background Traditional atherosclerosis risk factors have been associated with aortic and mitral valve calcium in cross-sectional studies, but long-term prospective data are lacking. Methods This was a prospective, community-based cohort study with 27-year follow-up (median follow-up 26.9 years; range 23.1 to 29.6 years). Participants from the Framingham Offspring Study (n = 1,323, enrolled between 1971 and 1975, mean age at enrollment 34 +/- 9 years; 52% women) underwent cardiac multidetector computed tomography assessment between 2002 and 2005. Associations between the long-term average of each cardiovascular risk factor and valve calcium were estimated using logistic regression. Results Aortic valve calcium was present in 39% of participants and mitral valve calcium in 20%. In multivariable models, the odds ratio for aortic valve calcium associated with every SD increment in long-term mean total cholesterol was 1.74 (p < 0.0001); with every SD increment in high-density lipoprotein cholesterol, it was 0.77 (p = 0.002); and with every 9 cigarettes smoked per day, it was 1.23 (p = 0.002). Associations of similar magnitude were seen for mitral valve calcium. The mean of 3 serum C-reactive protein measurements was associated with mitral valve calcium (odds ratio: 1.29 per SD increment in C-reactive protein levels; p = 0.002). A higher Framingham risk score in early adulthood (40 years age or younger) was associated with increased prevalence and severity of aortic valve calcium measured 3 decades later. Conclusions Exposure to multiple atherosclerotic risk factors starting in early to mid-adulthood is associated with aortic and mitral valve calcium. Studies evaluating early risk factor modification to reduce the burden of valve disease are warranted. (J Am Coll Cardiol 2010; 55: 2491-8) (C) 2010 by the American College of Cardiology Foundation C1 [Kathiresan, Sekar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Cury, Ricardo; Hoffmann, Udo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Radiol, Boston, MA 02114 USA. [Cury, Ricardo; Hoffmann, Udo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Thanassoulis, George; O'Donnell, Christopher J.; Kathiresan, Sekar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Thanassoulis, George; Manders, Emily; Benjamin, Emelia J.; Vasan, Ramachandran S.; Cupple, L. Adrienne; O'Donnell, Christopher J.; Kathiresan, Sekar] NHLBI, Framingham Heart Study, Framingham, MA USA. [Kathiresan, Sekar] Harvard Univ, Cambridge, MA 02138 USA. [Kathiresan, Sekar] MIT, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02139 USA. [Thanassoulis, George] Boston Univ, Sch Med, Boston, MA 02118 USA. [Massaro, Joseph M.; Cupple, L. Adrienne] Boston Univ, Dept Biostat, Boston, MA 02118 USA. [Benjamin, Emelia J.; Cupple, L. Adrienne] Boston Univ, Dept Epidemiol, Boston, MA 02118 USA. [Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Evans Dept Med, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. RP Kathiresan, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA. EM skathiresan@partners.org OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; Canadian Institute of Health Research; Fonds de Recherche en Sante du Quebec; Astellas Pharma; Pfizer; GE Healthcare; American College of Cardiology Foundation/Merck; GlaxoSmithKline Research & Education Foundation; Alnylam Pharmaceuticals FX From the *National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts; dagger Cardiology Division, Cardiovascular Research Center, Center for Human Genetic Research, and parallel to Radiology Division and Cardiac MR PET CT Program, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts; #School of Medicine, Departments of **Biostatistics dagger dagger Epidemiology, Mathematics and Statistics, Evans Department of Medicine; parallel to parallel to Whitaker Cardiovascular Institute, Boston University, Boston, Massachusetts; and the Division of Intramural Research (COD), National Heart, Lung, and Blood Institute, Bethesda, Maryland. This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195). Dr. Thanassoulis is supported by a Research Fellowship by the Canadian Institute of Health Research and the Fonds de Recherche en Sante du Quebec. Dr. Cury has received research grants from Astellas Pharma, Pfizer, and GE Healthcare, and is a consultant for Astellas Pharma. Dr. Kathiresan's efforts were supported by the American College of Cardiology Foundation/Merck Adult Cardiology Research Fellowship Award and the GlaxoSmithKline Research & Education Foundation for Cardiovascular Disease Young Investigator Award. Dr. Kathiresan serves on a scientific advisory board for Merck, Daiichi Sankyo, and Pfizer, and has received research funding from Pfizer and Alnylam Pharmaceuticals. Drs. O'Donnell and Kathiresan contributed equally to this work. NR 43 TC 29 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 1 PY 2010 VL 55 IS 22 BP 2491 EP 2498 DI 10.1016/j.jacc.2010.03.019 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 600ZB UT WOS:000278026600010 PM 20510217 ER PT J AU Patti, JA AF Patti, John A. TI Staying Ahead of the Curve SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM jpatti@partners.org NR 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2010 VL 7 IS 6 BP 389 EP 390 DI 10.1016/j.jacr.2010.04.004 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SP UT WOS:000208362800001 PM 20522387 ER PT J AU Fink, AS Prochazka, AV Henderson, WG Bartenfeld, D Nyirenda, C Webb, A Berger, DH Itani, K Whitehill, T Edwards, J Wilson, M Karsonovich, C Parmelee, P AF Fink, Aaron S. Prochazka, Allan V. Henderson, William G. Bartenfeld, Debra Nyirenda, Carsie Webb, Alexandra Berger, David H. Itani, Kamal Whitehill, Thomas Edwards, James Wilson, Mark Karsonovich, Cynthia Parmelee, Patricia TI Predictors of Comprehension during Surgical Informed Consent SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 95th Annual Clinical Congress of the American-College-of-Surgeons/64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 11-15, 2009 CL Chicago, IL SP Amer Coll Surg ID LITERACY SKILLS; HEALTH LITERACY; PATIENT RECALL; SHORT-FORM; INFORMATION; ANXIETY; TRIALS; INTERVENTIONS; COMMUNICATION; VOLUNTEERS AB BACKGROUND: Patient comprehension during surgical informed consent remains problematic. Using data from our randomized trial of methods to improve informed consent comprehension, we performed an additional analysis to define independent factors associated with improved patient understanding. STUDY DESIGN: Patients scheduled for 1 of 4 elective operations (total hip arthroplasty [n = 137], carotid endarterectomy [n = 178], laparoscopic cholecystectomy [n = 179], or radical prostatectomy [n = 81]) at 7 Department of Veterans Affairs (VA) medical centers were enrolled. All informed consent discussions were performed using iMedConsent (Dialog Medical), the VA's computerized informed consent platform. Using a unique module within iMedConsent, we randomized patients to repeat back (RB), requiring correct reiteration of procedure-specific facts, or standard (STD) iMedConsent. Patient comprehension was tested after the informed consent discussion using procedure-specific questionnaires. Time spent completing the informed consent process was measured using time stamps within iMedConsent. Multiple linear regression identified factors independently associated with improved comprehension. RESULTS: We enrolled 575 patients (276 RB, 299 standard); 93% were male, 74% were Caucasian, and 89% had at least a high school education. Independent factors associated with improved comprehension included race (p < 0.01), ethnicity (p < 0.05), age (p < 0.02), operation type (p < 0.01), group assignment (+/- RB; p < 0.05), and total consent time (p < 0.0001). Patient comprehension was maximized when informed consent took between 15 and 30 minutes. RB's positive impact on patient comprehension was weaker in the analysis including consent time. CONCLUSIONS: Comprehension during informed consent discussions may be limited in individuals with potential language difficulty due to ethnicity or education. Total consent time was the strongest predictor of patient comprehension. Affording adequate time for informed consent discussions and using informed consent adjuncts such as RB may enhance comprehension in such individuals. (J Am Coll Surg 2010;210:919-926. (C) 2010 by the American College of Surgeons) C1 [Fink, Aaron S.; Bartenfeld, Debra; Webb, Alexandra] VAMC Atlanta, Decatur, GA 30033 USA. [Fink, Aaron S.; Webb, Alexandra] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. [Prochazka, Allan V.] Denver VAMC, Denver, CO USA. [Prochazka, Allan V.; Henderson, William G.; Nyirenda, Carsie] Univ Colorado, Hlth Outcomes Program, Denver, CO 80202 USA. [Berger, David H.] Baylor Coll Med, Michael DeBakey VAMC, Houston, TX 77030 USA. [Berger, David H.] Baylor Coll Med, Michael DeBakey Dept Surg, Houston, TX 77030 USA. [Itani, Kamal] Boston Univ, Boston VAMC, Boston, MA 02215 USA. [Itani, Kamal] Boston Univ, Dept Surg, Boston, MA 02215 USA. [Itani, Kamal] Harvard Univ, Sch Med, Boston, MA USA. [Whitehill, Thomas] Univ Colorado, Denver VAMC, Denver, CO 80202 USA. [Whitehill, Thomas] Univ Colorado, Dept Surg, Denver, CO 80202 USA. [Edwards, James] Oregon Hlth & Sci Univ, Portland VAMC, Portland, OR 97201 USA. [Edwards, James] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. [Wilson, Mark] Univ Pittsburgh, Med Ctr, Pittsburgh VAMC, Pittsburgh, PA USA. [Wilson, Mark] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA USA. [Karsonovich, Cynthia] Univ S Florida, Tampa VAMC, Tampa, FL USA. [Karsonovich, Cynthia] Univ S Florida, Dept Surg, Tampa, FL USA. [Parmelee, Patricia] Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA. RP Fink, AS (reprint author), VAMC Atlanta, 112,1670 Clairmont Rd, Decatur, GA 30033 USA. EM aaron.fink@va.gov NR 48 TC 36 Z9 37 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2010 VL 210 IS 6 BP 919 EP 926 DI 10.1016/j.jamcollsurg.2010.02.049 PG 8 WC Surgery SC Surgery GA 609IH UT WOS:000278649100005 PM 20510800 ER PT J AU Kelley, AS Wenger, NS Sarkisian, CA AF Kelley, Amy S. Wenger, Neil S. Sarkisian, Catherine A. TI Opiniones: End-of-Life Care Preferences and Planning of Older Latinos SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE advance care planning; Latino; Hispanic; medical decision-making ID ETHNIC-DIFFERENCES; DECISION-MAKING; HEALTH-CARE; ATTITUDES; ACCULTURATION; COMPLETION; PHYSICIANS; AMERICANS; AUTONOMY; TRIAL AB OBJECTIVES: To measure end-of-life (EOL) care preferences and advance care planning (ACP) in older Latinos and to examine the relationship between culture-based attitudes and extent of ACP. DESIGN: Cross-sectional interview. SETTING: Twenty-two senior centers in greater Los Angeles. PARTICIPANTS: One hundred forty-seven Latinos aged 60 and older. MEASUREMENTS: EOL care preferences, extent of ACP, attitudes regarding patient autonomy, family-centered decision-making, trust in healthcare providers, and health and sociodemographic characteristics. RESULTS: If seriously ill, 84% of participants would prefer medical care focused on comfort rather than care focused on extending life, yet 47% had never discussed such preferences with their family or doctor, and 77% had no advance directive. Most participants favored family-centered decision making (64%) and limited patient autonomy (63%). Greater acculturation, education, and desire for autonomy were associated with having an advance directive (P-values < .03). Controlling for sociodemographic characteristics, greater acculturation (adjusted odds ratio (AOR) 51.6, 95% confidence interval (CI) = 1.1-2.4) and preferring greater autonomy (AOR = 1.6, 95% CI = 1.1-2.3) were independently associated with having an advance directive. CONCLUSIONS: The majority of older Latinos studied preferred less-aggressive, comfort-focused EOL care, yet few had documented or communicated this preference. This discrepancy places older Latinos at risk of receiving high-intensity care inconsistent with their preferences. J Am Geriatr Soc 58: 1109-1116, 2010. C1 [Kelley, Amy S.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Sarkisian, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. [Sarkisian, Catherine A.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. RP Kelley, AS (reprint author), 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM amy.kelley@mssm.edu FU University of California at Los Angeles John A. Hartford Center of Excellence in Geriatric Medicine; HRSA Institutional National Research Service Award [T32HP19001]; National Institute on Aging [RO1-AG02446005] FX Funding support for this project was provided by the University of California at Los Angeles John A. Hartford Center of Excellence in Geriatric Medicine, the HRSA Institutional National Research Service Award T32HP19001, and a grant from the National Institute on Aging (RO1-AG02446005). This research was presented as a poster at the national meeting of the American Geriatrics Society on April 30, 2009, and an oral presentation at the national meeting of the Society for General Internal Medicine on May 15, 2009. NR 30 TC 33 Z9 33 U1 4 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2010 VL 58 IS 6 BP 1109 EP 1116 DI 10.1111/j.1532-5415.2010.02853.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 604WO UT WOS:000278309400013 PM 20487080 ER PT J AU Smith, AL Wang, PC Anger, JT Mangione, CM Trejo, L Rodriguez, LV Sarkisian, CA AF Smith, Ariana L. Wang, Pin-Chieh Anger, Jennifer T. Mangione, Carol M. Trejo, Laura Rodriguez, Larissa V. Sarkisian, Catherine A. TI Correlates of Urinary Incontinence in Community-Dwelling Older Latinos SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE urinary incontinence; epidemiology; Latino; prevalence; aging ID NURSING-HOME RESIDENTS; RISK-FACTORS; CLINICAL RESEARCH; UNITED-STATES; SHORT-FORM; US WOMEN; PREVALENCE; QUESTIONNAIRE; POPULATION; ADULTS AB The prevalence of urinary incontinence (UI) has varied in the literature and is reflective of the definition and sampling methodologies used, as well as the age, ethnicity, and sex being studied. The aim of the current study was to measure the prevalence and correlates of UI in a sample of 572 older Latinos participating in Caminemos, a trial of a behavioral intervention to increase walking. Participants completed an in-person survey and physical performance measures. UI was measured using the International Consultation on Incontinence item: "How often do you leak urine?" Potential correlates of UI included sociodemographic variables, body mass index, smoking, physical activity, medical comorbidity, physical performance, activity of daily living (ADL) impairment, use of assistive ambulatory devices, health-related quality of life (HRQoL), and depressive symptoms. The prevalence of UI in this sample was 26.9%. Women were more likely to report UI, as were those who were less physically active; used assistive ambulatory devices; and had depressive symptoms, greater medical comorbidity, worse physical performance, greater ADL impairment, worse cognitive function, and lower HRQoL. Multivariate logistic regression revealed that medical comorbidity was independently associated with higher rates of UI (odds ratio (OR) = 1.66, 95% confidence interval (CI) = 1.30-2.12), whereas better cognitive function (OR = 0.73, 95% CI = 0.57-0.93) and higher weighted physical activity scores (OR= 0.77, 95% CI = 0.60-0.98) were independently associated with lower rates of UI. UI is highly prevalent but not ubiquitous among community-residing older Latinos, suggesting that UI is not an inevitable consequence of aging. Future studies should examine whether interventions that decrease comorbidity and cognitive decline and increase physical activity improve continence status. J Am Geriatr Soc 58: 1170-1176, 2010. C1 [Smith, Ariana L.] Univ Penn, Div Urol, Sch Med, Philadelphia, PA 19106 USA. [Wang, Pin-Chieh] Univ Calif Los Angeles, David Geffen Sch Med, Dept Epidemiol, Los Angeles, CA 90095 USA. [Anger, Jennifer T.; Rodriguez, Larissa V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Mangione, Carol M.; Sarkisian, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Trejo, Laura] Dept Aging, Los Angeles, CA USA. [Sarkisian, Catherine A.] Geriatr Res Educ Clin Ctr, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Smith, AL (reprint author), Univ Penn, Div Urol, Sch Med, 299 S 8th St, Philadelphia, PA 19106 USA. EM ariana.smith@uphs.upenn.edu FU National Institute on Aging (NIA) [RO1-AG02446005]; Resource Centers for Minority Aging Research/Center for Health Improvement of Minority Elderly (RCMAR/CHIME) [P30 AG021684]; University of California at Los Angeles Older Americans Independence Center [5 P30 AG028748]; Trial to Increase Walking among Sedentary Older Latinos [RO1 AG024460]; National Institutes of Health/NIA FX Drs. Sarkisian and Mangione were supported by the National Institute on Aging (NIA) (RO1-AG02446005). Dr. Mangione received support from the Resource Centers for Minority Aging Research/Center for Health Improvement of Minority Elderly (RCMAR/CHIME) (P30 AG021684), from the University of California at Los Angeles Older Americans Independence Center (5 P30 AG028748), and from the Trial to Increase Walking among Sedentary Older Latinos (RO1 AG024460), all funded by the National Institutes of Health/NIA. NR 39 TC 14 Z9 18 U1 8 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2010 VL 58 IS 6 BP 1170 EP 1176 DI 10.1111/j.1532-5415.2010.02814.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 604WO UT WOS:000278309400022 PM 20406311 ER PT J AU Hutt, E Radcliff, TA Oman, KS Fink, R Ruscin, JM Linnebur, S Fish, D Liebrecht, D Fish, R McNulty, M AF Hutt, Evelyn Radcliff, Tiffany A. Oman, Kathleen S. Fink, Regina Ruscin, J. Mark Linnebur, Sunny Fish, Doug Liebrecht, Debra Fish, Ron McNulty, Monica TI Impact of NHAP Guideline Implementation Intervention on Staff and Resident Vaccination Rates SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Influenza vaccination; nursing home staff vaccination; pneumococcal vaccination ID LONG-TERM-CARE; HOME-ACQUIRED PNEUMONIA; MINIMUM DATA SET; NURSING-HOME; PNEUMOCOCCAL PNEUMONIA; INFLUENZA IMMUNIZATION; INCREASING INFLUENZA; FACILITIES; MORTALITY; ADHERENCE AB Objectives: Determine whether a comprehensive approach to implementing national consensus guidelines for nursing home acquired pneumonia (NHAP), including influenza and pneumococcal vaccination, improves resident subject and staff vaccination rates. Methods: Quasi-experimental, mixed-methods multifaceted intervention trial conducted at 16 nursing homes (NHs) from 1 corporation (8 in metropolitan Denver, Colorado; 8 in Kansas and Missouri) during 3 influenza seasons, October to April 2004 to 2007. Residents with 2 or more signs and symptoms of systemic lower respiratory tract infection (LRTI) and NH staff and physicians were eligible. Subjects' NH records were reviewed for vaccination. Each director of nursing (DON) completed a questionnaire assessing staffing and the number of direct care staff vaccinated against influenza. DONs and study liaison nurses were interviewed after the intervention. Bivariate analysis compared vaccination outcomes and covariates between intervention and control homes, and risk-adjusted models were fit. Qualitative interview transcripts were analyzed using content coding. Results: No statistically significant relationship between the intervention and improved resident vaccination rates was found, so other factors associated with improved rates were explored. Estimated direct patient care staff vaccination rates were better during the baseline and improved more in the intervention NHs. Qualitative results suggested that facility-specific factors and national policy changes impacted vaccination rates. Conclusions: External factors influence staff and resident vaccination rates, diluting the potential impact of a comprehensive program to improve care for NHAP on vaccination. (J Am Med Dir Assoc 2010; 11: 365-370) C1 [Hutt, Evelyn; Radcliff, Tiffany A.] Denver VA Med Ctr, Denver, CO USA. [Hutt, Evelyn; Radcliff, Tiffany A.; Oman, Kathleen S.; Fink, Regina; Ruscin, J. Mark; Linnebur, Sunny; Fish, Doug; Liebrecht, Debra; Fish, Ron; McNulty, Monica] Univ Colorado, Denver, CO 80202 USA. RP Hutt, E (reprint author), Denver VAMC 151, 1055 Clermont St, Denver, CO 80220 USA. EM evelyn.hutt@ucdenver.edu FU Agency for Health Care Research and Quality [RO1-HS13608]; National Institutes of Health [AHRQ R01 HS013618] FX Supported by a grant from the Agency for Health Care Research and Quality, RO1-HS13608.; We thank the residents who graciously participated in the study, and our data collectors: Margie Ahring, RN, Cathleen Brethauer, RN, Karen Cotter-Hoffman, RN, Susan Lucas, RN, Nancy Robertson, RN, Sara Schultz, RN, and Evelyn Shinn, RN for their hard work. The study would not have been possible without the active support of Clarence Acklam, RN, Divisional Director of Nursing, Mountain States Division, Life Care Corporation of America, and the directors of nursing and their staff at the 16 study nursing homes. This work was supported by AHRQ R01 HS013618 from the National Institutes of Health. The views expressed herein are those of the authors and do not necessarily reflect the position or policy of the University of Colorado Denver or the Department of Veterans Affairs. NR 27 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JUN PY 2010 VL 11 IS 5 BP 365 EP 370 DI 10.1016/j.jamda.2009.09.017 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 614AU UT WOS:000279028200012 PM 20511104 ER PT J AU Brezniceanu, ML Lau, CJ Godin, N Chenier, I Duclos, A Ethier, J Filep, JG Ingelfinger, JR Zhang, SL Chan, JSD AF Brezniceanu, Marie-Luise Lau, Cara J. Godin, Nicolas Chenier, Isabelle Duclos, Alain Ethier, Jean Filep, Janos G. Ingelfinger, Julie R. Zhang, Shao-Ling Chan, John S. D. TI Reactive Oxygen Species Promote Caspase-12 Expression and Tubular Apoptosis in Diabetic Nephropathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; ANGIOTENSINOGEN GENE-EXPRESSION; INTERSTITIAL FIBROSIS; EPITHELIAL-CELLS; RAT-KIDNEY; DB/DB MICE; ACTIVATION; GLUCOSE; DEATH; OVEREXPRESSION AB Apoptosis of tubular epithelial cells contributes to the tubular atrophy that accompanies diabetic nephropathy. Reactive oxygen species (ROS) promote tubular apoptosis, but the mechanisms by which this occurs are incompletely understood. Here, we sought proapoptotic genes that ROS differentially upregulate in renal proximal tubular cells of diabetic (db/db) mice. We performed microarray analysis using total RNA from freshly isolated renal proximal tubules of nondiabetic, diabetic, and diabetic transgenic mice overexpressing catalase in the proximal tubule (thereby attenuating ROS). We observed greater expression of caspase-12 in the proximal tubules of the diabetic mice compared with the nondiabetic and diabetic transgenic mice. Quantitative PCR and immunohistochemistry confirmed the enhanced expression of caspase-12, as well as members of the endoplasmic reticulum stress-induced apoptotic pathway. Ex vivo, albumin induced caspase-12 activity and expression (protein and mRNA) and mRNA expression of the CCAT/enhancer-binding protein homologous protein in freshly isolated wildtype proximal tubules but not in catalase-overexpressing proximal tubules. In vitro, albumin stimulated activity of both caspase-12 and caspase-3 as well as expression of caspase-12 and CCAT/enhancer-binding protein homologous protein in a human proximal tubule cell line (HK-2). The free radical scavenger tiron inhibited these effects. Furthermore, knockdown of caspase-12 with small interfering RNA reduced albumin-induced apoptosis in HK-2 cells. Taken together, these studies demonstrate that albuminuria may induce tubular apoptosis through generation of ROS and the subsequent expression and activation of endoplasmic reticulum stress genes in the diabetic kidney. C1 [Brezniceanu, Marie-Luise; Lau, Cara J.; Godin, Nicolas; Chenier, Isabelle; Duclos, Alain; Ethier, Jean; Zhang, Shao-Ling; Chan, John S. D.] Univ Montreal, CHU Montreal, Hotel Dieu Hosp, Ctr Rech, Montreal, PQ H2W 1T8, Canada. [Filep, Janos G.] Univ Montreal, Maisonneuve Rosemont Hosp, Ctr Rech, Montreal, PQ H2W 1T8, Canada. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. RP Chan, JSD (reprint author), Univ Montreal, CHU Montreal, Hotel Dieu Hosp, Ctr Rech, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca FU Kidney Foundation of Canada [KFOC80015]; Canadian Institutes of Health Research [MOP 84363, MT-12573, MOP 86450]; National Institutes of Health [HL-48455]; Office, Centre de recherche du Centre hospitalier de l'Universite de Montreal FX This work was supported by grants from the Kidney Foundation of Canada (KFOC80015), the Canadian Institutes of Health Research (MOP 84363 to J.S.D.C., MT-12573 to J.G.F., and MOP 86450 to S.-L.Z.), and the National Institutes of Health (HL-48455 to J.R.I.).; The editorial assistance of Research Support Office, Centre de recherche du Centre hospitalier de l'Universite de Montreal, is acknowledged. NR 54 TC 40 Z9 45 U1 0 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2010 VL 21 IS 6 BP 943 EP 954 DI 10.1681/ASN.2009030242 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 606FW UT WOS:000278409000012 PM 20299359 ER PT J AU Rhee, EP Souza, A Farrell, L Pollak, MR Lewis, GD Steele, DJR Thadhani, R Clish, CB Greka, A Gerszten, RE AF Rhee, Eugene P. Souza, Amanda Farrell, Laurie Pollak, Martin R. Lewis, Gregory D. Steele, David J. R. Thadhani, Ravi Clish, Clary B. Greka, Anna Gerszten, Robert E. TI Metabolite Profiling Identifies Markers of Uremia SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; KETOTIC DICARBOXYLIC ACIDURIA; MITOCHONDRIAL-DNA; FATTY-ACIDS; OMEGA-OXIDATION; BETA-OXIDATION; MEDIUM-CHAIN; INSULIN-RESISTANCE; URINARY-EXCRETION; BIOLOGICAL ORIGIN AB ESRD is a state of small-molecule disarray. We applied liquid chromatography/tandem mass spectrometry-based metabolite profiling to survey >350 small molecules in 44 fasting subjects with ESRD, before and after hemodialysis, and in 10 age-matched, at-risk fasting control subjects. At baseline, increased levels of polar analytes and decreased levels of lipid analytes characterized uremic plasma. In addition to confirming the elevation of numerous previously identified uremic toxins, we identified several additional markers of ESRD, including dicarboxylic acids (adipate, malonate, methylmalonate, and maleate), biogenic amines, nucleotide derivatives, phenols, and sphingomyelins. The pattern of lipids was notable for a universal decrease in lower-molecular-weight triacylglycerols, and an increase in several intermediate-molecular-weight triacylglycerols in ESRD compared with controls; standard measurement of total triglycerides obscured this heterogeneity. These observations suggest disturbed triglyceride catabolism and/or beta-oxidation in ESRD. As expected, the hemodialysis procedure was associated with significant decreases in most polar analytes. Unexpected increases in several metabolites, however, indicated activation of a broad catabolic program, including glycolysis, lipolysis, ketosis, and nucleotide breakdown. In summary, this study demonstrates the application of metabolite profiling to identify markers of ESRD, provide perspective on uremic dyslipidemia, and broaden our understanding of the biochemical effects of hemodialysis. C1 [Rhee, Eugene P.; Steele, David J. R.; Thadhani, Ravi; Greka, Anna] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Rhee, Eugene P.; Souza, Amanda; Clish, Clary B.; Gerszten, Robert E.] Broad Inst, Cambridge, MA USA. [Farrell, Laurie; Lewis, Gregory D.; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Pollak, Martin R.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, 149 13th St,8th Floor, Charlestown, MA 02129 USA. EM rgerszten@partners.org FU NIH [UL1 RR025758-01, DK00754023]; American Heart Association FX This research was made possible with funding from the Harvard Catalyst Pilot Grant program (NIH UL1 RR025758-01). Dr. Eugene Rhee received support from the National Institutes of Health T32 grant DK00754023. Dr. Robert Gerszten received support from the American Heart Association Established Investigator Grant. The authors thank Dr. Amin Arnaout for his support. NR 55 TC 67 Z9 69 U1 2 U2 12 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2010 VL 21 IS 6 BP 1041 EP 1051 DI 10.1681/ASN.2009111132 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 606FW UT WOS:000278409000022 PM 20378825 ER PT J AU Schwartzman, A Dougherty, RF Taylor, JE AF Schwartzman, Armin Dougherty, Robert F. Taylor, Jonathan E. TI Group Comparison of Eigenvalues and Eigenvectors of Diffusion Tensors SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Diffusion tensor imaging; Likelihood ratio test; Manifold-valued data; Multiple testing; Random matrix; Satterthwaite approximation ID FALSE DISCOVERY RATE; STATISTICAL-ANALYSIS; SYMMETRIC-MATRICES; DIRECTION MAPS; EMPIRICAL NULL; MRI; INFERENCE; VARIABLES; GEOMETRY; CHILDREN AB Diffusion tensor imaging (DID data differ from most medical images in that values at each voxel are not scalars, but 3 x 3 symmetric positive definite matrices called diffusion tensors (DTs). The anatomic characteristics of the tissue at each voxel are reflected by the DT eigenvalues and eigenvectors. In this article we consider the problem of testing whether the means of two groups of DT images are equal at each voxel in terms of the DT's eigenvalues, eigenvectors, or both. Because eigendecompositions are highly nonlinear, existing likelihood ratio statistics (LRTs) for testing differences in eigenvalues or eigenvectors of means of Gaussian symmetric matrices assume an orthogonally invariant covariance structure between the matrix entries. While retaining the form of the LRTs, we derive new approximations to their true distributions when the covariance between the DT entries is arbitrary and possibly different between the two groups. The approximate distributions are those of similar LRT statistics computed on the tangent space to the parameter manifold at the true value of the parameter, but plugging in an estimate for the point of application of the tangent space. The resulting distributions, which are weighted sums of chi-squared distributions, are further approximated by scaled chi-squared distributions by matching the first two moments. For validity of the Gaussian model, the positive definite constraints on the DT are removed via a matrix log transformation, although this is not crucial asymptotically. Voxelwise application of the test statistics leads to a multiple-testing problem, which is solved by false discovery rate inference. The foregoing methods are illustrated in a DTI group comparison of boys versus girls. C1 [Schwartzman, Armin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02155 USA. [Dougherty, Robert F.] Dana Farber Canc Inst, Boston, MA 02155 USA. [Dougherty, Robert F.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Taylor, Jonathan E.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP Schwartzman, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02155 USA. EM armins@hsph.harvard.edu; bobd@stanford.edu; jonathan.taylor@stanford.edu OI Schwartzman, Armin/0000-0001-5335-1611 FU National Institutes of Health [EY015000]; National Science Foundation [DMS-0405970] FX Armin Schwartzman is Assistant Professor, Department of Biostatistics, Harvard School of Public Health and Dana-Farber Cancer Institute, Boston, MA 02115 (E-mail: armins@hsph.harvard.edu). Robert F. Dougherty is Senior Research Scientist, Department of Psychology (E-mail: bobd@stanford.edu) and Jonathan E. Taylor is Associate Professor, Department of Statistics (E-mail: jonathan.taylor@stanford.edu), Stanford University, Stanford, CA 94305. This work was supported in part by National Institutes of Health grant EY015000 and National Science Foundation grant DMS-0405970. NR 38 TC 12 Z9 12 U1 2 U2 5 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 JUN PY 2010 VL 105 IS 490 BP 588 EP 599 DI 10.1198/jasa.2010.ap07291 PG 12 WC Statistics & Probability SC Mathematics GA 629RF UT WOS:000280216700012 ER PT J AU Demetri, GD Antonia, S Benjamin, RS Bui, MM Casper, ES Conrad, EU DeLaney, TF Ganjoo, KN Heslin, MJ Hutchinson, RJ Kane, JM Letson, GD McGarry, SV O'Donnell, RJ Paz, IB Pfeifer, JD Pollock, RE Randall, RL Riedel, RF Schupak, KD Schwartz, HS Thornton, K von Mehren, M Wayne, J AF Demetri, George D. Antonia, Scott Benjamin, Robert S. Bui, Marilyn M. Casper, Ephraim S. Conrad, Ernest U., III DeLaney, Thomas F. Ganjoo, Kristen N. Heslin, Martin J. Hutchinson, Raymond J. Kane, John M., III Letson, G. Douglas McGarry, Sean V. O'Donnell, Richard J. Paz, I. Benjamin Pfeifer, John D. Pollock, Raphael E. Randall, R. Lor Riedel, Richard F. Schupak, Karen D. Schwartz, Herbert S. Thornton, Katherine von Mehren, Margaret Wayne, Jeffrey TI Soft Tissue Sarcoma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; soft tissue sarcoma; soft tissue extremity sarcoma; retroperitoneal sarcomas; gastrointestinal stromal tumors; desmoid tumor; radiation therapy; chemotherapy; surgery ID GASTROINTESTINAL STROMAL TUMORS; PHASE-II TRIAL; POSITRON-EMISSION-TOMOGRAPHY; PRIMARY EXTREMITY SARCOMA; OF-FUNCTION MUTATIONS; LONG-TERM OUTCOMES; IMATINIB MESYLATE; RADIATION-THERAPY; NEOADJUVANT CHEMOTHERAPY; EUROPEAN-ORGANIZATION C1 [Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Demetri, George D.] Harvard Univ, Ctr Canc, Cambridge, MA 02138 USA. [Antonia, Scott; Bui, Marilyn M.; Letson, G. Douglas] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Benjamin, Robert S.; Pollock, Raphael E.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Casper, Ephraim S.; Schupak, Karen D.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Conrad, Ernest U., III] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [DeLaney, Thomas F.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Heslin, Martin J.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Hutchinson, Raymond J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Kane, John M., III] Roswell Pk Canc Inst, Roswell, GA USA. [McGarry, Sean V.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [O'Donnell, Richard J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Paz, I. Benjamin] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Pfeifer, John D.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Pfeifer, John D.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Randall, R. Lor] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [O'Donnell, Richard J.] Duke Comprehens Canc Ctr, Durham, NC USA. [Schwartz, Herbert S.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Thornton, Katherine] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. [von Mehren, Margaret] Fox Chase Canc Ctr, Philadelphia, PA USA. [Wayne, Jeffrey] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [K24 CA128953] NR 154 TC 48 Z9 49 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUN PY 2010 VL 8 IS 6 BP 630 EP 674 PG 45 WC Oncology SC Oncology GA 625XC UT WOS:000279929100002 PM 20581298 ER PT J AU Thomas, DM Wagner, AJ AF Thomas, David M. Wagner, Andrew J. TI Specific Targets in Sarcoma and Developmental Therapeutics SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article DE Sarcoma; therapy; drug targets; mutation ID GIANT-CELL TUMOR; REGULATES OSTEOCLAST DIFFERENTIATION; SOFT PART SARCOMA; DERMATOFIBROSARCOMA PROTUBERANS; GROWTH-FACTOR; IN-VIVO; ALVEOLAR RHABDOMYOSARCOMA; MAMMALIAN TARGET; MTOR INHIBITION; STROMAL TUMOR AB Connective tissue tumors comprise a rich array of subtypes, many of which possess strong pathognomonic phenotypes and genotypes of therapeutic significance. This article describes recent applications of targeted and nontargeted therapeutic agents in connective tissue tumors that illustrate important themes in drug development. Targeted therapy has exploited the paradigms of oncogene and lineage addiction. In other cases, potential targets are more difficult to classify, such as the role of the insulin-like growth factor 1 pathway in Ewing's sarcoma. Understanding why these pathways seem critical in some cancers, and in some individuals but not others, is important in identifying novel therapeutic opportunities in an age of personalized medicine. (JNCCN 2010;8:677-686) C1 [Thomas, David M.] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia. [Wagner, Andrew J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Thomas, DM (reprint author), Peter MacCallum Canc Ctr, St Andrews Pl, Melbourne, Vic 3002, Australia. EM david.thomas@petermac.org FU Amgen Inc. FX Disclosure: David M. Thomas, FRACP, PhD, has disclosed the following relevant financial relationships: participated in unfunded research on and gave a talk for denosumab for a giant-cell tumor trial from Amgen Inc. NR 67 TC 2 Z9 3 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUN PY 2010 VL 8 IS 6 BP 677 EP 686 PG 10 WC Oncology SC Oncology GA 625XC UT WOS:000279929100003 PM 20581299 ER PT J AU Biermann, JS Adkins, DR Benjamin, RS Brigman, B Chow, W Conrad, EU Frassica, DA Frassica, FJ George, S Hande, KR Hornicek, FJ Letson, GD Mayerson, J McGarry, SV McGrath, B Morris, CD O'Donnell, RJ Randall, RL Santana, VM Satcher, RL Siegel, HJ Somaiah, N Yasko, AW AF Biermann, J. Sybil Adkins, Douglas R. Benjamin, Robert S. Brigman, Brian Chow, Warren Conrad, Ernest U., III Frassica, Deborah A. Frassica, Frank J. George, Suzanne Hande, Kenneth R. Hornicek, Francis J. Letson, G. Douglas Mayerson, Joel McGarry, Sean V. McGrath, Brian Morris, Carol D. O'Donnell, Richard J. Randall, R. Lor Santana, Victor M. Satcher, Robert L. Siegel, Herrick J. Somaiah, Neeta Yasko, Alan W. TI Bone Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; bone cancer; sarcoma; chondrosarcomas; osteosarcomas; Ewing's sarcoma; metastasis; surgery; radiation therapy ID PEDIATRIC-ONCOLOGY-GROUP; EUROPEAN-OSTEOSARCOMA-INTERGROUP; POSITRON-EMISSION-TOMOGRAPHY; SLOAN-KETTERING EXPERIENCE; HIGH-DOSE CHEMOTHERAPY; EWINGS-SARCOMA FAMILY; PRIMITIVE NEUROECTODERMAL TUMORS; REFRACTORY SOLID TUMORS; HIGH-GRADE OSTEOSARCOMA; STEM-CELL RESCUE C1 [Biermann, J. Sybil] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Adkins, Douglas R.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Adkins, Douglas R.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Benjamin, Robert S.; Satcher, Robert L.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Brigman, Brian] Duke Comprehens Canc Ctr, Durban, South Africa. [Chow, Warren] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Conrad, Ernest U., III] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Frassica, Deborah A.; Frassica, Frank J.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. [George, Suzanne] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Hande, Kenneth R.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Hornicek, Francis J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Letson, G. Douglas] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Mayerson, Joel] Ohio State Univ, Ctr Comprehens Canc, Solove Res Inst, Columbus, OH 43210 USA. [McGarry, Sean V.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [McGrath, Brian] Roswell Pk Canc Inst, Roswell, GA USA. [Morris, Carol D.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [O'Donnell, Richard J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Randall, R. Lor] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Santana, Victor M.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Siegel, Herrick J.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Somaiah, Neeta] Fox Chase Canc Ctr, Philadelphia, PA USA. [Yasko, Alan W.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. RP Biermann, JS (reprint author), Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RI Mayerson, Joel/E-3616-2011 NR 130 TC 14 Z9 14 U1 0 U2 2 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUN PY 2010 VL 8 IS 6 BP 688 EP 712 PG 25 WC Oncology SC Oncology GA 625XC UT WOS:000279929100004 PM 20581300 ER PT J AU Knight, J Baumuller, S Kurtcuoglu, V Turina, M Turina, J Schurr, U Poulikakos, D Marshall, W Alkadhi, H AF Knight, Joseph Baumueller, Stephan Kurtcuoglu, Vartan Turina, Marko Turina, Juraj Schurr, Ulrich Poulikakos, Dimos Marshall, William, Jr. Alkadhi, Hatem TI Long-term follow-up, computed tomography, and computational fluid dynamics of the Cabrol procedure SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID AORTIC ROOT REPLACEMENT; CORONARY-ANGIOGRAPHY; ASCENDING AORTA; BENTALL PROCEDURE; REIMPLANTATION; ARTERIES; GRAFT AB Objectives: The Cabrol procedure is characterized by insertion of an ascending aortic composite graft with reimplantation of the coronary arteries by the interposition of a graft tube. Our purpose is to report the clinical long-term follow-up and computed tomographic findings in patients having undergone the Cabrol procedure and to determine blood flow in the Cabrol graft using computational fluid dynamics. Methods: Clinical follow-up (76.6 +/- 16.6 months) and dual-source computed tomographic angiography data of 7 patients (all men, mean age 54.9 +/- 9.6 years) with 12 Cabrol grafts (left main coronary artery, n = 7; right coronary artery, n = 5) were reviewed. In 2 patients, the right coronary artery was directly reattached to the aortic graft. Computational fluid dynamics were calculated using computed tomographic data of a patient with the Cabrol procedure and compared with those in a Valsalva graft and a healthy aortic root. Results: Computed tomography showed Cabrol graft occlusions to 1 of 7 (14%) left main and of 2 of 5 (40%) right coronary arteries. Six grafts to the left main and 3 to the right coronary artery were fully patent, similar to the 2 directly reattached right coronary arteries to the aortic graft. Computational fluid dynamics results show similar blood flow parameters into the coronaries for the healthy aortic root and Valsalva graft. In the Cabrol graft, a spiraling flow pattern with low flow into the right coronary artery was found (right coronary artery = 1 mL/min at both systole and diastole). Conclusions: Our study indicates low flow rates particularly in the right Cabrol graft correlating with a higher incidence of occlusions of the right as compared with the left Cabrol graft at long-term follow-up. (J Thorac Cardiovasc Surg 2010;139:1602-8) C1 [Alkadhi, Hatem] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Alkadhi, Hatem] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Knight, Joseph; Kurtcuoglu, Vartan; Poulikakos, Dimos] Swiss Fed Inst Technol, Lab Thermodynam Emerging Technol, Dept Mech & Proc Engn, Zurich, Switzerland. [Baumueller, Stephan] Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. [Turina, Marko; Schurr, Ulrich] Univ Zurich Hosp, Cardiovasc Surg Clin, CH-8091 Zurich, Switzerland. [Turina, Marko] Univ Zurich Hosp, Ctr Cardiovasc, CH-8091 Zurich, Switzerland. [Marshall, William, Jr.] Univ S Florida, Coll Med, Tampa, FL USA. RP Alkadhi, H (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. EM halkadhi@partners.org RI Kurtcuoglu, Vartan/A-8940-2008; poulikakos, dimos/O-2853-2014 OI Kurtcuoglu, Vartan/0000-0003-2665-0995; poulikakos, dimos/0000-0001-5733-6478 FU Swiss National Science Foundation FX Supported by the National Center of Competence in Research, Computer Aided and Image Guided Medical Interventions of the Swiss National Science Foundation. NR 21 TC 16 Z9 17 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 2010 VL 139 IS 6 BP 1602 EP 1608 DI 10.1016/j.jtcvs.2009.09.023 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 599TX UT WOS:000277937500036 PM 19913239 ER PT J AU Miller, YE AF Miller, York E. TI Does Unilateral DIPNECH Provide Clues to Pathogenesis? SO JOURNAL OF THORACIC ONCOLOGY LA English DT Editorial Material ID NEUROENDOCRINE CELL HYPERPLASIA; IDIOPATHIC DIFFUSE HYPERPLASIA; CARCINOID-TUMORS; RESPIRATORY EPITHELIUM; LUNG; MUTATIONS; DISEASE C1 Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Miller, YE (reprint author), Denver Vet Affairs Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM york.miller@uchsc.edu NR 12 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2010 VL 5 IS 6 BP 761 EP 762 DI 10.1097/JTO.0b013e3181dd0ba7 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 601XJ UT WOS:000278100500002 PM 20502267 ER PT J AU Aisner, SC Dahlberg, S Hameed, MR Ettinger, DS Schiller, JH Johnson, DH Aisner, J Loehrer, PJ AF Aisner, Seena C. Dahlberg, Suzanne Hameed, Meera R. Ettinger, David S. Schiller, Joan H. Johnson, David H. Aisner, Joseph Loehrer, Patrick J. TI Epidermal Growth Factor Receptor, C-kit, and Her2/neu Immunostaining in Advanced or Recurrent Thymic Epithelial Neoplasms Staged According to the 2004 World Health Organization in Patients Treated with Octreotide and Prednisone An Eastern Cooperative Oncology Group Study SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Thymoma; 2004 WHO classification of thymoma; Octreotide; Thymic epithelial neoplasms; EGFR; C-kit; Her2/neu ID MUTATIONAL STATUS; THYMOMA; CARCINOMA; CLASSIFICATION; EXPRESSION; TUMORS; EGFR AB Advanced or recurrent nonresectable thymic epithelial tumors show only a modest response to standard chemotherapy. A recent study using octreotide and prednisone in thymic tumors, Eastern Cooperative Oncology Group study E1C97, was conducted to verify the activity of octreotide for thymic tumors. The aim of this study was to determine whether epidermal growth factor receptor (EGFR) immunoreactivity correlated with outcomes and to identify new biologic markers for potential targeted therapy. Three markers, EGFR, C-kit, and Her2/neu, were selected for evaluation in patients with advanced thymic epithelial tumors treated on E1C97. Methods: Of the 42 patients entered onto E1C97, 34 patients (World Health Organization [WHO] categories: type A = 1, type AB = 1, type B1 = 10, type B2 = 11 type B3 = 8, and type C = 3) had sufficient tissue available for immunohistologic study. Each tumor was assessed to have 0, 1+, 2+, or 3+ immunoreactivity in the cytoplasm or membranes of the neoplastic cells for Her2/neu and EGFR and for the presence or absence of C-kit immunoreactivity. Results: EGFR immunoreactivity of 2+ or 3+ was associated with more aggressive thymic tumors (WHO types B2 and B3). However, strong EGFR immunoreactivity was not consistently seen with thymic carcinoma. The presence of EGFR within cells was associated with a significantly improved progression-free survival (PFS) and a trend for overall survival (OS). Twelve patients demonstrated C-kit immunoreactivity; the lack of C-kit immunoreactivity was significantly associated with superior PFS but not OS. Her2/neu immunoreactivity was uniformly negative for all tumors evaluated. There was no association between response and biomarker status. Conclusions: High EGFR immunoreactivity is seen in more aggressive thymic neoplasms as classified according to the 2004 WHO, but regardless of classification, the presence of EGFR in tumor cells (1+, 2+, and 3+) is associated with improved performance free survival (PFS) and a trend for better OS. In contrast, the absence of C-kit immunoreactivity was associated with improved PFS. These data suggest that EGFR and C-kit may be prognostic, and further studies of these markers in subcategories of thymic malignancies is warranted. C1 [Aisner, Seena C.; Hameed, Meera R.] UMDNJ NJMS, Dept Pathol, Newark, NJ USA. [Dahlberg, Suzanne] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ettinger, David S.] Johns Hopkins Univ, Dept Oncol, Div Upper Aerodigest Canc Program, Baltimore, MD USA. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Div Hematol Oncol, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Johnson, David H.] Vanderbilt Univ, Div Hematol Oncol, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Aisner, Joseph] RWJMS UMDNJ, Canc Inst New Jersey, New Brunswick, NJ USA. [Loehrer, Patrick J.] Indiana Univ, Med Ctr, Simon Canc Ctr, Div Hematol Oncol, Indianapolis, IN USA. RP Aisner, SC (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol & Lab Med, 150 Bergen St,UHE 155, Newark, NJ 07103 USA. EM aisnersc@verizon.net FU Public Health Service [CA23318, CA66636, CA21115, CA107868, CA16116, CA49883, CA49957]; National Cancer Institute; National Institutes of Health and the Department of Health and Human Services; Eastern Cooperative Oncology Group FX Supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA107868, CA16116, CA49883, CA49957 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services.; This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD). NR 24 TC 20 Z9 23 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2010 VL 5 IS 6 BP 885 EP 892 DI 10.1097/JTO.0b013e3181d86a30 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 601XJ UT WOS:000278100500022 PM 20421818 ER PT J AU Camidge, DR Christensen, J Bang, YJ Shaw, AT Costa, DB Salgia, R Dezube, BJ Shapiro, GI Janne, PA Maki, RG Solomon, B Kwak, EL Tan, W Shreeve, SM Wilner, K Clark, JW Iafrate, AJ AF Camidge, D. Ross Christensen, James Bang, Yung Jue Shaw, Alice T. Costa, Daniel B. Salgia, Ravi Dezube, Bruce J. Shapiro, Geoffrey I. Janne, Pasi A. Maki, Robert G. Solomon, Benjamin Kwak, Eunice L. Tan, Weiwei Shreeve, S. Martin Wilner, Keith Clark, Jeffrey W. Iafrate, A. John TI Addressing right drug/right target/right patient in phase I studies to accelerate bench to clinical benefit time: ALK gene rearrangements and the development of PF-02341066 in NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Camidge, D. Ross] Univ Colorado, Denver, CO 80202 USA. [Christensen, James; Tan, Weiwei; Shreeve, S. Martin; Wilner, Keith] Pfizer Pharmaceut Inc, La Jolla, CA USA. [Bang, Yung Jue] Seoul Natl Univ, Seoul, South Korea. [Shaw, Alice T.; Kwak, Eunice L.; Clark, Jeffrey W.; Iafrate, A. John] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Salgia, Ravi] Univ Chicago, Chicago, IL 60637 USA. [Shapiro, Geoffrey I.; Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Maki, Robert G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Solomon, Benjamin] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2010 VL 5 IS 6 SU 3 BP S233 EP S233 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 601XW UT WOS:000278102300053 ER PT J AU Foley, KP Proia, D Shimamura, T Borgman, CL Inoue, T Korbut, T Li, D Perera, SA Sang, J Ogawa, LS Smith, D Tatsuta, N Ying, WW Zhang, CH Zhang, HL Shapiro, GI Wong, KK Blackman, RK AF Foley, Kevin P. Proia, David Shimamura, Takeshi Borgman, Christa L. Inoue, Takayo Korbut, Tim Li, Danan Perera, Samanthi A. Sang, Jim Ogawa, Luisa Shin Smith, Don Tatsuta, Noriaki Ying, Weiwen Zhang, Chaohua Zhang, Haili Shapiro, Geoffrey I. Wong, Kwok-Kin Blackman, Ronald K. TI Synergy between the novel Hsp90 inhibitor STA-9090 and taxanes in preclinical models of NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Foley, Kevin P.; Proia, David; Inoue, Takayo; Korbut, Tim; Sang, Jim; Ogawa, Luisa Shin; Smith, Don; Tatsuta, Noriaki; Ying, Weiwen; Zhang, Chaohua; Zhang, Haili; Blackman, Ronald K.] Synta Pharmaceut Corp, Lexington, MA USA. [Shimamura, Takeshi; Borgman, Christa L.; Li, Danan; Perera, Samanthi A.; Shapiro, Geoffrey I.; Wong, Kwok-Kin] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2010 VL 5 IS 6 SU 3 BP S234 EP S234 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 601XW UT WOS:000278102300055 ER PT J AU Haura, EB Camidge, DR Reckamp, K Chiappori, A Johnson, F Herbst, R Wong, K Carbone, D AF Haura, Eric B. Camidge, D. Ross Reckamp, Karen Chiappori, Alberto Johnson, Faye Herbst, Roy Wong, Kwok Carbone, David TI Molecular Origins of Lung Cancer: Prospects for Personalized Prevention and Therapy SO JOURNAL OF THORACIC ONCOLOGY LA English DT Editorial Material ID GROWTH-FACTOR RECEPTOR; EGFR; INHIBITION; GEFITINIB; SRC AB The first Meeting on "Molecular Origins of Lung Cancer - Prospects for Personalized Prevention and Therapy" was held from January 10 to 14, 2010 in San Diego, California. The purpose of the meeting was to discuss important basic, translational, and clinical work aimed at improving lung cancer prevention, detection, and treatment. Topics included drug design, target identification, early detection, cancer stem cells, microRNAs, genome wide approaches to determining risk and outcome, mouse models, and tumor microenvironment. The role of cancer advocates in supporting research was an important component of the meeting. Meeting presentations demonstrated that emerging technologies can molecularly dissect lung cancers that have important relevance for clinical utility. This includes molecular based strategies not only for treatment of established cancers but also individualized and molecularly-based strategies for cancer risk reduction and chemoprevention. C1 [Haura, Eric B.; Chiappori, Alberto] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Thorac Oncol, Tampa, FL 33682 USA. [Camidge, D. Ross] Univ Colorado, Dept Med, Aurora, CO USA. [Reckamp, Karen] City Hope & Beckman Res Inst, Dept Med Oncol & Therapeut Res, Duarte, CA USA. [Reckamp, Karen] City Hope & Beckman Res Inst, Dept Hematol & Hematopoeit Transplantat Med, Duarte, CA USA. [Johnson, Faye; Herbst, Roy] Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac & Head & Neck Oncol, Houston, TX 77030 USA. [Wong, Kwok] Dana Farber Canc Ctr, Dept Canc Biol, Boston, MA USA. [Carbone, David] Vanderbilt Ingram Canc Ctr, Dept Med Oncol, Nashville, TN USA. RP Haura, EB (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, Dept Thorac Oncol, Tampa, FL 33682 USA. OI Reckamp, Karen/0000-0002-9213-0325 NR 20 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2010 VL 5 IS 6 SU 3 BP S207 EP S213 DI 10.1097/JTO.0b013e3181e2f682 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 601XW UT WOS:000278102300001 PM 20502275 ER PT J AU MacDermed, DM Khodarev, NN Pitroda, SP Edwards, DC Pelizzari, CA Huang, L Kufe, DW Weichselbaum, RR AF MacDermed, Dhara M. Khodarev, Nikolai N. Pitroda, Sean P. Edwards, Darrin C. Pelizzari, Charles A. Huang, Lei Kufe, Donald W. Weichselbaum, Ralph R. TI MUC1-associated proliferation signature predicts outcomes in lung adenocarcinoma patients SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [MacDermed, Dhara M.] Scripps Res Inst, La Jolla, CA 92037 USA. [Khodarev, Nikolai N.; Pitroda, Sean P.; Edwards, Darrin C.; Pelizzari, Charles A.; Weichselbaum, Ralph R.] Univ Chicago, Chicago, IL 60637 USA. [Huang, Lei; Kufe, Donald W.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2010 VL 5 IS 6 SU 3 BP S238 EP S238 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 601XW UT WOS:000278102300067 ER PT J AU Pennell, NA Chirieac, LR El Karak, F Lynch, TJ Heist, RS Christiani, DC AF Pennell, Nathan A. Chirieac, Lucian R. El Karak, Fadi Lynch, Thomas J. Heist, Rebecca S. Christiani, David C. TI ERCC1 protein expression is not associated with survival after platinum-based chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Pennell, Nathan A.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Chirieac, Lucian R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [El Karak, Fadi; Heist, Rebecca S.; Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lynch, Thomas J.] Yale Canc Ctr, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2010 VL 5 IS 6 SU 3 BP S238 EP S239 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 601XW UT WOS:000278102300068 ER PT J AU Yeomans, PD Forman, EM Herbert, JD Yuen, E AF Yeomans, Peter D. Forman, Evan M. Herbert, James D. Yuen, Erica TI A Randomized Trial of a Reconciliation Workshop With and Without PTSD Psychoeducation in Burundian Sample SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; HOPKINS SYMPTOM CHECKLIST-25; HARVARD TRAUMA QUESTIONNAIRE; EXPOSURE THERAPY; SRI-LANKA; REFUGEES; GENOCIDE; INTERVENTION; ASSESSMENTS; INSTRUMENT AB Posttraumatic stress disorder (PTSD) psychoeducation is increasingly offered in diverse cultural settings. As the literature offers theoretical arguments for why such information might be normalizing and distress-reducing, or might risk morbid suggestion of greater vulnerability, a two-sided hypothesis was proposed to examine the specific effect of PTSD psychoeducation. Participants of a trauma healing and reconciliation intervention in Burundi were randomized to conditions with and without PTSD psychoeducation, or to a waitlist control. Both interventions reduced symptoms more than the waitlist. Participants in the condition without psychoeducation experienced a greater reduction in PTSD symptoms relative to other conditions. Findings are discussed in relationship to intervention development for traumatic stress in nonindustrialized and culturally diverse settings. C1 [Yeomans, Peter D.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Forman, Evan M.; Herbert, James D.; Yuen, Erica] Drexel Univ, Dept Psychol, Philadelphia, PA USA. RP Yeomans, PD (reprint author), Philadelphia Vet Affairs Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM peter.yeomans@va.gov RI Forman, Evan/I-1042-2012 NR 37 TC 20 Z9 20 U1 4 U2 14 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2010 VL 23 IS 3 BP 305 EP 312 DI 10.1002/jts.20531 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 619HG UT WOS:000279419300001 PM 20564362 ER PT J AU Dickstein, BD Suvak, M Litz, BT Adler, AB AF Dickstein, Benjamin D. Suvak, Michael Litz, Brett T. Adler, Amy B. TI Heterogeneity in the Course of Posttraumatic Stress Disorder: Trajectories of Symptomatology SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID VEHICLE ACCIDENT SURVIVORS; TRAUMA-EXPOSED ADULTS; PSYCHOMETRIC PROPERTIES; RISK-FACTORS; PREDICTORS; METAANALYSIS; CHECKLIST; SYMPTOMS; EVENTS; COMBAT AB Unconditional and conditional trajectories of posttraumatic stress disorder (PTSD) symptomatology were examined using a sample of U.S. soldiers deployed on a NATO-led peacekeeping mission to Kosovo. Data were collected at 4 time points, ranging from the weeks leading up to deployment to 9-months postdeployment. Latent class growth analysis revealed 4 unique symptom trajectories: resilience, recovery, delayed, and unrealized anxiety. Variables identified as significant predictors of trajectory class included previous traumatic events, combat exposure, peacekeeping daily hassles, depression, alcohol use, aggressive behavior, stress reaction); and military rank. Results from this study add to the literature detailing the variability in PTSD course, as well as to the literature pertaining to predictors of PTSD onset and course. C1 [Litz, Brett T.] Boston Univ, Dept Psychol, VA Boston Healthcare Syst, Natl Ctr PTSD,Sch Med, Boston, MA 02215 USA. [Adler, Amy B.] USA, Med Res Unit Europe, Washington, DC USA. [Adler, Amy B.] Walter Reed Inst Res, Silver Spring, MD USA. RP Dickstein, BD (reprint author), Boston Dept Vet Affairs Med Ctr, Natl Ctr Posttraumat Stress Disorder, Behav Sci Div 116 B5, 150 S Huntington Ave, Boston, MA 02130 USA. EM Benjamin.Dickstein@va.gov NR 43 TC 76 Z9 76 U1 3 U2 18 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2010 VL 23 IS 3 BP 331 EP 339 DI 10.1002/jts.20523 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 619HG UT WOS:000279419300004 PM 20564365 ER PT J AU Forbes, D Elhai, JD Miller, MW Creamer, M AF Forbes, David Elhai, Jon D. Miller, Mark W. Creamer, Mark TI Internalizing and Externalizing Classes in Posttraumatic Stress Disorder: A Latent Class Analysis SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID COMMON MENTAL-DISORDERS; COMBAT-RELATED PTSD; PERSONALITY; VETERANS; SUBTYPES; SCALES; PSY-5; PSYCHOPATHOLOGY; COMORBIDITY; SUBGROUPS AB Using latent class analysis (LCA) the typology of personality profiles of veterans with posttraumatic stress disorder (PTSD) was examined based on internalizing/externalizing dimensions of psychopathology. Latent class analysis on Minnesota Multiphasic Personality Inventory-2 (MMPI-2) Personality Psychopathology-5 (PSY-5) scale data from 299 Australian combat veterans with PTSD supported the model, identifying an optimal 4-class solution, with PTSD externalizing class defined by aggressiveness and disconstraint, high and moderate internalizing classes differentiated on the extent of elevations in introversion and negative emotionality and elevation of psychoticism in the high internalizing class and a simple PTSD class with normal range scores. The model was validated using external self-report and psychiatric-interview-derived diagnoses. A second exploratory LA using broader comorbidity indicators (MMPI-2 Restructured Clinical scales) demonstrated some support for, although limitations in, using nonpersonality measures to identify these classes directly. C1 [Forbes, David; Creamer, Mark] Australian Ctr Posttraumat Mental Hlth, Melbourne, Vic 3002, Australia. [Forbes, David; Creamer, Mark] Univ Melbourne, Dept Psychiat, Melbourne, Vic 3010, Australia. [Elhai, Jon D.] Univ Toledo, Dept Psychol, Toledo, OH USA. [Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Dept Psychiat & Psychol, Boston, MA USA. [Miller, Mark W.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Forbes, D (reprint author), Australian Ctr Posttraumat Mental Hlth, Level 1-340 Albert St, Melbourne, Vic 3002, Australia. EM dforbes@unimelb.edu.au RI Miller, Mark/G-7322-2011 OI Miller, Mark/0000-0001-6393-8563 FU CSRD VA [I01 CX000431]; NIMH NIH HHS [MH079806] NR 43 TC 34 Z9 34 U1 2 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2010 VL 23 IS 3 BP 340 EP 349 DI 10.1002/jts.20526 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 619HG UT WOS:000279419300005 PM 20564366 ER PT J AU Saylor, PJ Kaufman, DS Michaelson, MD Lee, RJ Smith, MR AF Saylor, Philip J. Kaufman, Donald S. Michaelson, M. Dror Lee, Richard J. Smith, Matthew R. TI Application of a Fracture Risk Algorithm to Men Treated With Androgen Deprivation Therapy for Prostate Cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; osteoporosis; fractures; bone; androgens ID BONE-MINERAL DENSITY; HORMONE AGONISTS; ZOLEDRONIC ACID; BODY-MASS; OSTEOPOROSIS; METAANALYSIS; HIP; METASTASES; CARCINOMA; PLACEBO AB Purpose: Osteoporosis causes morbidity and mortality in men. The National Osteoporosis Foundation recommends fracture risk assessment with the online WHO/FRAX (R) tool. Although androgen deprivation therapy for prostate cancer increases fracture risk, there is limited information about which men require preventative drug therapy. We applied the WHO/FRAX tool to men treated with androgen deprivation therapy for prostate cancer. Materials and Methods: Information was collected from a practice cohort of men treated with gonadotropin-releasing hormone agonists, and included age, height, weight, history of gonadotropin-releasing hormone agonist treatment, dual energy x-ray absorptiometry results, prior bone targeted therapy and clinical risk factors for fracture. Subjects were evaluated with the WHO/FRAX algorithm (http://www.shef.ac.uk/FRAX/). Results: A total of 363 men treated with androgen deprivation therapy (median age 72 years) were evaluated. By the FRAX algorithm with clinical information (no dual energy x-ray absorptiometry data) the 3% hip fracture risk threshold for treatment was exceeded by 51.2% of the men (median risk 3.1%). When subjects were grouped by age the treatment threshold was reached by 3.3% of those younger than 70 years, 76.6% of those 70 to 79 years old and by 98.8% of those 80 years old or older. Using FRAX with bone mineral density data in the 93 patients who underwent bone mineral density testing the median 10-year hip fracture risk was 0.9% and the treatment threshold was exceeded by 15% of these subjects. Conclusions: In this cohort of men receiving androgen deprivation therapy the prevalence of risk sufficient to necessitate drug therapy was high and was strongly influenced by age. The WHO/FRAX algorithm identifies a greater proportion of men for treatment than the traditional threshold of T score -2.5 or less. C1 [Saylor, Philip J.] Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, Boston, MA 02114 USA. RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, 55 Fruit St,Lawrence House,POB 2, Boston, MA 02114 USA. EM psaylor@partners.org OI Michaelson, Dror/0000-0001-9249-6338 FU National Institutes of Health [5K24CA121990-02]; Prostate Cancer Foundation FX Recipient of a National Institutes of Health K24 Midcareer Investigator Award (5K24CA121990-02) and grants from the Prostate Cancer Foundation. NR 30 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2010 VL 183 IS 6 BP 2200 EP 2205 DI 10.1016/j.juro.2010.02.022 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 595QZ UT WOS:000277628700028 PM 20399451 ER PT J AU Anger, JT Weinberg, A Suttorp, MJ Litwin, MS Shekelle, PG AF Anger, Jennifer T. Weinberg, Aviva Suttorp, Marika J. Litwin, Mark S. Shekelle, Paul G. TI Outcomes of Intravesical Botulinum Toxin for Idiopathic Overactive Bladder Symptoms: A Systematic Review of the Literature SO JOURNAL OF UROLOGY LA English DT Article DE urinary bladder, overactive; urinary incontinence, urge; treatment outcome ID DETRUSOR OVERACTIVITY; CLINICAL-TRIALS; A TOXIN; METAANALYSES; BIAS AB Purpose: We systematically reviewed the evidence for the efficacy and safety of botulinum toxin in the management of overactive bladder. Materials and Methods: We performed a systematic review of the literature to identify articles published between 1985 and March 2009 on intravesical botulinum toxin-A injections for the treatment of refractory idiopathic overactive bladder in men and women. Databases searched included MEDLINE (R), CENTRAL and Embase (R). Data were tabulated from case series and from randomized controlled trials, and data were pooled where appropriate. Results: Our literature search identified 432 titles and 23 full articles were included in the final review. Three randomized placebo controlled trials addressing the use of botulinum toxin-A were identified (99 patients total). The pooled random effects estimate of effect across all 3 studies was 3.88 (95% CI -6.15, -1.62), meaning that patients treated with botulinum toxin-A had 3.88 fewer incontinence episodes per day. Urogenital Distress Inventory data revealed significant improvements in quality of life compared with placebo with a standardized mean difference of -0.62 (CI -1.04, -0.21). Data from case series demonstrated significant improvements in overactive bladder symptoms and quality of life, despite heterogeneity in methodology and case mix. However, based on the randomized controlled trials there was a 9-fold increased odds of increased post-void residual after botulinum toxin-A compared with placebo (8.55; 95% CI 3.22, 22.71). Conclusions: Intravesical injection of botulinum toxin resulted in improvement in medication refractory overactive bladder symptoms. However, the risk of increased post-void residual and symptomatic urinary retention was significant. Several questions remain concerning the optimal administration of botulinum toxin-A for the patient with overactive bladder. C1 [Anger, Jennifer T.; Weinberg, Aviva; Litwin, Mark S.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. [Litwin, Mark S.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. [Suttorp, Marika J.; Shekelle, Paul G.] RAND Corp, Los Angeles, CA USA. [Shekelle, Paul G.] W Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Anger, JT (reprint author), Dept Urol, 1260 15th St,Suite 1200, Santa Monica, CA 90404 USA. EM janger@mednet.ucla.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [1 K23 DK080227-01] FX Supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant 1 K23 DK080227-01. NR 17 TC 42 Z9 43 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2010 VL 183 IS 6 BP 2258 EP 2264 DI 10.1016/j.juro.2010.02.009 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 595QZ UT WOS:000277628700051 PM 20400142 ER PT J AU Morrisroe, SN Su, RR Bae, KT Eisner, BH Hong, C Lahey, S Catalano, OA Sahani, DV Jackman, SV AF Morrisroe, Shelby N. Su, Ruthie R. Bae, Kyongtae T. Eisner, Brian H. Hong, Cheng Lahey, Susan Catalano, Onofrio A. Sahani, Dushyant V. Jackman, Stephen V. TI Differential Renal Function Estimation Using Computerized Tomography Based Renal Parenchymal Volume Measurement SO JOURNAL OF UROLOGY LA English DT Article DE kidney; kidney function tests; tomography; technetium Tc 99m mertiatide; hydronephrosis ID GLOMERULAR-FILTRATION-RATE; KIDNEY DONORS; CT; SESSION AB Purpose: Nuclear renal scan is currently the gold standard imaging study to determine differential renal function. We propose helical computerized tomography as a more efficient way to gain renal function information. Renal parenchymal volume is measured and percent total renal volume is used as a surrogate marker for differential renal function. Materials and Methods: Computerized tomography and diuretic enhanced nuclear renal scan were performed in 33 patients with chronic obstruction. Computerized tomography was contrast enhanced in 23 cases and nonenhanced in 10. Diagnoses included ureteropelvic junction obstruction, ureteral stricture and extrinsic compression. Using semiautomated boundary delineation with manual editing method the parenchymal volume of each kidney was measured and percent renal volume was calculated. Percent renal volume was compared with percent renal function, as determined by nuclear renal scan. Correlations between the 2 measures were evaluated using the Spearman or Pearson coefficient. Results: Strong correlations were observed between percent renal function and percent renal volume in all cases (r = 0.90, p < 0.001), including the enhanced (r = 0.87, p < 0.001) and nonenhanced (r = 0.95, p < 0.001) groups. Moderately strong correlations were noted in the less than 40% (r = 0.76, p < 0.001) and less than 30% (r = 0.64, p = 0.015) renal function subgroups. Conclusions: Differential renal volume measured from computerized tomography strongly correlates with differential renal function on nuclear renal scan for normal and chronically obstructed kidneys. Computerized tomography may serve as a single radiological diagnostic study for anatomical and functional assessment in patients in whom a poorly functioning kidney is suspected. C1 [Morrisroe, Shelby N.; Su, Ruthie R.; Jackman, Stephen V.] Univ Pittsburgh, Dept Urol, Med Ctr, Pittsburgh, PA 15213 USA. [Bae, Kyongtae T.; Hong, Cheng] Univ Pittsburgh, Dept Radiol, Med Ctr, Pittsburgh, PA 15213 USA. [Eisner, Brian H.; Lahey, Susan; Catalano, Onofrio A.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Su, RR (reprint author), Univ Pittsburgh, Dept Urol, Med Ctr, 3471 5th Ave,Suite 700, Pittsburgh, PA 15213 USA. EM surr@upmc.edu FU PercSys; Boston Scientific; Ravine Group FX Financial interest and/or other relationship with PercSys, Boston Scientific and Ravine Group. NR 14 TC 16 Z9 18 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2010 VL 183 IS 6 BP 2289 EP 2293 DI 10.1016/j.juro.2010.02.024 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 595QZ UT WOS:000277628700065 PM 20400144 ER PT J AU Eisner, BH Asplin, JR Goldfarb, DS Ahmad, A Stoller, ML AF Eisner, Brian H. Asplin, John R. Goldfarb, David S. Ahmad, Ardalanejaz Stoller, Marshall L. TI Citrate, Malate and Alkali Content in Commonly Consumed Diet Sodas: Implications for Nephrolithiasis Treatment SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carbonated beverages; nephrolithiasis; malic acid; alkalies ID CALCIUM NEPHROLITHIASIS; POTASSIUM CITRATE; CITRIC-ACID; HYPOCITRATURIC NEPHROLITHIASIS; URINARY LITHOGENICITY; STONE FORMATION; KIDNEY-STONES; LEMON JUICE; RISK; MANAGEMENT AB Purpose: Citrate is a known inhibitor of calcium stone formation. Dietary citrate and alkali intake may have an effect on citraturia. Increasing alkali intake also increases urine pH, which can help prevent uric acid stones. We determined citrate, malate and total alkali concentrations in commonly consumed diet sodas to help direct dietary recommendations in patients with hypocitraturic calcium or uric acid nephrolithiasis. Materials and Methods: Citrate and malate were measured in a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis and in 15 diet sodas. Anions were measured by ion chromatography. The pH of each beverage was measured to allow calculation of the unprotonated anion concentration using the known pK of citric and malic acid. Total alkali equivalents were calculated for each beverage. Statistical analysis was done using Pearson's correlation coefficient. Results: Several sodas contained an amount of citrate equal to or greater than that of alkali and total alkali as a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis (6.30 mEq/l citrate as alkali and 6.30 as total alkali). These sodas were Diet Sunkist (R) Orange, Diet 7Up (R), Sprite Zero (TM), Diet Canada Dry (R) Ginger Ale, Sierra Mist (R) Free, Diet Orange Crush (R), Fresca (R) and Diet Mountain Dew (R). Colas, including Caffeine Free Diet Coke (R), Coke Zero (TM), Caffeine Free Diet Pepsi (R) and Diet Coke with Lime, had the lowest total alkali (less than 1.0 mEq/l). There was no significant correlation between beverage pH and total alkali content. Conclusions: Several commonly consumed diet sodas contain moderate amounts of citrate as alkali and total alkali. This information is helpful for dietary recommendations in patients with calcium nephrolithiasis, specifically those with hypocitraturia. It may also be useful in patients with low urine pH and uric acid stones. Beverage malate content is also important since malate ingestion increases the total alkali delivered, which in turn augments citraturia and increases urine pH. C1 [Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. [Eisner, Brian H.; Ahmad, Ardalanejaz; Stoller, Marshall L.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Asplin, John R.] Litholink Corp, Chicago, IL USA. [Goldfarb, David S.] St Vincents Hosp, New York Harbor Vet Affairs Med Ctr, Dept Urol, Nephrol Sect, New York, NY USA. [Goldfarb, David S.] NYU, Sch Med, New York, NY USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org OI Goldfarb, David/0000-0002-9215-1273 FU Boston Scientific; PercSys; Ravine Group FX Financial interest and/or other relationship with Boston Scientific, PercSys and Ravine Group.; Financial interest and/or other relationship with Ravine Group.; Financial interest and/or other relationship with PercSys and Ravine Group. NR 27 TC 11 Z9 11 U1 9 U2 40 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2010 VL 183 IS 6 BP 2419 EP 2423 DI 10.1016/j.juro.2010.02.2388 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 595QZ UT WOS:000277628700113 PM 20403610 ER PT J AU Cambria, RP Conrad, MF Ergul, EA Patel, VI LaMuraglia, GM Cambria, MR AF Cambria, Richard P. Conrad, Mark F. Ergul, Emel A. Patel, Virendra I. LaMuraglia, Glenn M. Cambria, Matthew R. TI Evolution of Operative Strategies in Open Thoracoabdominal Aneurysm Repair (TAA) SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting/Society-for-Vascular Surgery CY JUN 10-13, 2010 CL Boston, MA SP Soc Vasc Surg C1 [Cambria, Richard P.; Conrad, Mark F.; Ergul, Emel A.; Patel, Virendra I.; LaMuraglia, Glenn M.; Cambria, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 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 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2010 VL 51 SU S BP 4S EP 5S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 601EA UT WOS:000278039700004 ER PT J AU Nguyen, RNH Albadawi, H Crawford, RS Yoo, HJ Conrad, MF Cambria, RP Watkins, MT AF Nguyen, Rao-Ngoc H. Albadawi, Hassan Crawford, Robert S. Yoo, Hyung-Jin Conrad, Mark F. Cambria, Richard P. Watkins, Michael T. TI Ethyl Pyruvate Prevents Delayed Paralysis in a Murine Model of Spinal Cord Ischemic Injury SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting/Society-for-Vascular Surgery CY JUN 10-13, 2010 CL Boston, MA SP Soc Vasc Surg C1 [Nguyen, Rao-Ngoc H.; Albadawi, Hassan; Crawford, Robert S.; Yoo, Hyung-Jin; Conrad, Mark F.; Cambria, Richard P.; Watkins, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endo Vasc Surg, 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 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2010 VL 51 SU S BP 81S EP 81S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 601EA UT WOS:000278039700169 ER PT J AU Patel, VI Ergul, E Conrad, MF Cambria, M Paruchuri, V LaMuraglia, GM Kwolek, CJ Brewster, DC Cambria, RP AF Patel, Virendra I. Ergul, Emel Conrad, Mark F. Cambria, Matthew Paruchuri, Vikram LaMuraglia, Glenn M. Kwolek, Christopher J. Brewster, David C. Cambria, Richard P. TI Continued Favorable Results With Type IV Thoracoabdominal Aortic Aneurysm Repair SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting/Society-for-Vascular Surgery CY JUN 10-13, 2010 CL Boston, MA SP Soc Vasc Surg C1 [Patel, Virendra I.; Ergul, Emel; Conrad, Mark F.; Cambria, Matthew; Paruchuri, Vikram; LaMuraglia, Glenn M.; Kwolek, Christopher J.; Brewster, David C.; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2010 VL 51 SU S BP 89S EP 89S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 601EA UT WOS:000278039700186 ER PT J AU Tsibris, AMN Hirsch, MS AF Tsibris, Athe M. N. Hirsch, Martin S. TI Antiretroviral Therapy in the Clinic SO JOURNAL OF VIROLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITOR; CD4 CELL COUNT; SYNCYTIUM-INDUCING PHENOTYPE; SOCIETY-USA PANEL; PROTEASE INHIBITORS; HIV-1 INFECTION; INSULIN SENSITIVITY; DRUG-RESISTANCE; VIROLOGICAL SUPPRESSION AB Antiretroviral therapy in the developed world has resulted in substantial reductions in HIV-associated morbidity and mortality, changing an HIV diagnosis from a likely death sentence into a manageable chronic infection (F. J. Palella, Jr., K. M. Delaney, A. C. Moorman, M. O. Loveless, J. Fuhrer, G. A. Satten, D. J. Aschman, and S. D. Holmberg, N. Engl. J. Med. 338: 853-860, 1998). Several million years of life have been saved by effective anti-HIV treatment, although these successes should not obscure the magnitude of the ongoing worldwide HIV epidemic (R. P. Walensky, A. D. Paltiel, E. Losina, L. M. Mercincavage, B. R. Schackman, P. E. Sax, M. C. Weinstein, and K. A. Freedberg, J. Infect. Dis. 194: 11-19, 2006). Readers of the Journal of Virology are doubtless aware of the fundamental advances in retrovirology that have made possible the development of potent inhibitors of HIV replication. In this review, we focus on the issues surrounding how these drugs and drug regimens are actually used in clinical settings. Their proper use requires detailed knowledge of the natural history of HIV infection, the pharmacology of the individual drugs, the complexities of drug-drug interactions, and the use of sophisticated molecular tests for monitoring of viral load, immunologic response, and drug resistance. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tsibris, AMN (reprint author), Massachusetts Gen Hosp, 65 Landsdowne St,Room 422, Cambridge, MA 02139 USA. EM atsibris@partners.org NR 74 TC 17 Z9 17 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2010 VL 84 IS 11 BP 5458 EP 5464 DI 10.1128/JVI.02524-09 PG 7 WC Virology SC Virology GA 592NQ UT WOS:000277386700001 PM 20181709 ER PT J AU Shao, RX Zhang, LL Peng, LF Sun, E Chung, WJ Jang, JY Tsai, WL Hyppolite, G Chung, RT AF Shao, Run-Xuan Zhang, Leiliang Peng, Lee F. Sun, Eileen Chung, Woo Jin Jang, Jae Yong Tsai, Wei-Lun Hyppolite, Guibenson Chung, Raymond T. TI Suppressor of Cytokine Signaling 3 Suppresses Hepatitis C Virus Replication in an mTOR-Dependent Manner SO JOURNAL OF VIROLOGY LA English DT Article ID INSULIN-RESISTANCE; GENE-EXPRESSION; CORE PROTEIN; ANTIVIRAL THERAPY; MAMMALIAN TARGET; SOCS3 EXPRESSION; IN-VITRO; ACTIVATION; PATHWAY; CELLS AB We and others have observed that hepatic levels of suppressor of cytokine signaling 3 (SOCS3) are significantly higher in persons with chronic hepatitis C, particularly those who are nonresponders to interferon (IFN) treatment, than in healthy individuals. However, the relationship between SOCS3 and hepatitis C virus (HCV) replication remains unclear. Given its putative role, we hypothesized that SOCS3 is permissive for viral replication. We therefore used the OR6 cell line, which harbors a genotype 1b full-length HCV replicon, and the genotype 2a full-length HCV strain JFH1 infection system to analyze the effects of SOCS3 overexpression and short hairpin RNA (shRNA)-mediated knockdown on HCV replication. We further analyzed the role of mTOR in the effects of SOCS3 by treating selected cells with rapamycin. OR6 cells and JFH1-infected Huh7.5.1 cells expressed significantly less SOCS3 than control cells. Furthermore, inhibition of HCV replication with the HCV protease inhibitor BILN 2061 restored SOCS3 protein levels. SOCS3 overexpression in OR6 cells and JFH1-infected Huh7.5.1 cells resulted in significantly lower HCV replication than that in the control cells, despite SOCS3-related inhibition of STAT1 phosphorylation and type I IFN signaling. In contrast, JFH1-infected cells with stable SOCS3 knockdown expressed higher levels of HCV proteins and RNA than did control cells. SOCS3-targeting shRNA also knocked down mTOR and phospho-mTOR. The mTOR inhibitor rapamycin reversed the inhibitory effects of SOCS3. In independent investigations, SOCS3 unexpectedly suppressed HCV replication in an mTOR-dependent manner. These findings suggest that increased SOCS3 levels consistently observed in chronic IFN nonresponders may reflect a compensatory host antiviral response to persistent infection and that manipulation of SOCS3/mTOR may offer benefit against HCV infection. C1 [Shao, Run-Xuan; Zhang, Leiliang; Peng, Lee F.; Sun, Eileen; Chung, Woo Jin; Jang, Jae Yong; Tsai, Wei-Lun; Hyppolite, Guibenson; Chung, Raymond T.] Harvard Univ, Sch Med, Gastrointestinal Unit, Massachusetts Gen Hosp,GI Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Harvard Univ, Sch Med, Gastrointestinal Unit, Massachusetts Gen Hosp,GI Unit, Warren 1007,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU National Institutes of Health [AI069939-01, DK078772] FX This work was supported by National Institutes of Health grants AI069939-01 (to R. T. C.) and DK078772 (to R. T. C.). NR 28 TC 19 Z9 19 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2010 VL 84 IS 12 BP 6060 EP 6069 DI 10.1128/JVI.02484-09 PG 10 WC Virology SC Virology GA 597CQ UT WOS:000277733900020 PM 20375166 ER PT J AU Wang, GP Sherrill-Mix, SA Chang, KM Quince, C Bushman, FD AF Wang, Gary P. Sherrill-Mix, Scott A. Chang, Kyong-Mi Quince, Chris Bushman, Frederic D. TI Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; RESISTANCE MUTATIONS; MICROBIAL DIVERSITY; GENETIC DIVERSITY; GUT MICROBIOME; INFECTION; EVOLUTION; IMMUNOSUPPRESSION; DETERMINANTS AB Hepatitis C virus (HCV) replication in infected patients produces large and diverse viral populations, which give rise to drug-resistant and immune escape variants. Here, we analyzed HCV populations during transmission and diversification in longitudinal and cross-sectional samples using 454/Roche pyrosequencing, in total analyzing 174,185 sequence reads. To sample diversity, four locations in the HCV genome were analyzed, ranging from high diversity (the envelope hypervariable region 1 [HVR1]) to almost no diversity (the 5' untranslated region [UTR]). For three longitudinal samples for which early time points were available, we found that only 1 to 4 viral variants were present, suggesting that productive infection was initiated by a very small number of HCV particles. Sequence diversity accumulated subsequently, with the 5' UTR showing almost no diversification while the envelope HVR1 showed >100 variants in some subjects. Calculation of the transmission probability for only a single variant, taking into account the measured population structure within patients, confirmed initial infection by one or a few viral particles. These findings provide the most detailed sequence-based analysis of HCV transmission bottlenecks to date. The analytical methods described here are broadly applicable to studies of viral diversity using deep sequencing. C1 [Wang, Gary P.; Sherrill-Mix, Scott A.; Bushman, Frederic D.] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Wang, Gary P.] Univ Florida, Dept Med, Coll Med, Gainesville, FL 32610 USA. [Chang, Kyong-Mi] Philadelphia VA Med Ctr, Dept Med, Philadelphia, PA 19104 USA. [Quince, Chris] Univ Glasgow, Dept Civil Engn, Glasgow G12 8LT, Lanark, Scotland. RP Bushman, FD (reprint author), Univ Penn, Sch Med, Dept Microbiol, 3610 Hamilton Walk, Philadelphia, PA 19104 USA. EM bushman@mail.med.upenn.edu OI Bushman, Frederic/0000-0003-4740-4056 FU Human Microbiome Demonstration Project [UH2DK083981]; NIH [K08 AI077713]; University of Pennsylvania Department of Medicine Measey Basic Science FX This work was supported by a Human Microbiome Demonstration Project Grant to F. D. B., James Lewis, and Gary Wu (UH2DK083981). G.P.W. was supported by NIH K08 AI077713 and a University of Pennsylvania Department of Medicine Measey Basic Science Fellowship Award. NR 47 TC 87 Z9 89 U1 1 U2 12 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 JUN PY 2010 VL 84 IS 12 BP 6218 EP 6228 DI 10.1128/JVI.02271-09 PG 11 WC Virology SC Virology GA 597CQ UT WOS:000277733900034 PM 20375170 ER PT J AU Godin, N Liu, F Lau, GJ Brezniceanu, ML Chenier, I Filep, JG Ingelfinger, JR Zhang, SL Chan, JSD AF Godin, Nicolas Liu, Fang Lau, Garnet J. Brezniceanu, Marie-Luise Chenier, Isabelle Filep, Janos G. Ingelfinger, Julie R. Zhang, Shao-Ling Chan, John S. D. TI Catalase overexpression prevents hypertension and tubular apoptosis in angiotensinogen transgenic mice SO KIDNEY INTERNATIONAL LA English DT Article DE angiotensinogen; catalase; hypertension; oxidative stress; transgenic mice ID RENAL PROXIMAL TUBULE; BLOOD-PRESSURE; RAT-KIDNEY; CONVERTING-ENZYME; NAD(P)H OXIDASE; GENE-EXPRESSION; TYPE-1 RECEPTOR; CHRONIC HYPOXIA; II RECEPTOR; RENIN AB Transgenic mice that overexpress angiotensinogen, the sole precursor of angiotensins, in their renal proximal tubular cells develop hypertension, albuminuria, and tubular apoptosis. These pathological changes are due to enhanced generation of reactive oxygen species in the proximal tubule cells. Here, we determined whether overexpression of catalase to decrease oxidant injury in the proximal tubular cells could reverse these abnormalities. Double-transgenic mice specifically overexpressing angiotensinogen and catalase in their renal proximal tubular cells were created by cross-breeding the single transgenics. Non-transgenic littermates served as controls. Overexpression of catalase prevented hypertension, albuminuria, tubulointerstitial fibrosis, and tubular apoptosis in the angiotensinogen transgenic mice. Furthermore, the double transgenics had lower reactive oxygen species generation and reduced pro-fibrotic and apoptotic gene expression in the renal proximal tubular cells. Renal angiotensin converting enzyme-2 expression and urinary angiotensin 1-7 levels were downregulated in the single but normal in the double-transgenic mice. Thus, we suggest that the intrarenal renin-angiotensin system and reactive oxygen species generation have an important role in the development of hypertension and renal injury. Kidney International (2010) 77, 1086-1097; doi: 10.1038/ki.2010.63; published online 17 March 2010 C1 [Godin, Nicolas; Liu, Fang; Lau, Garnet J.; Brezniceanu, Marie-Luise; Chenier, Isabelle; Zhang, Shao-Ling; Chan, John S. D.] Hop Hotel Dieu, CRCHUM, Montreal, PQ H2W 1T8, Canada. [Filep, Janos G.] Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H1T 2M4, Canada. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. RP Chan, JSD (reprint author), Hop Hotel Dieu, CRCHUM, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca FU Kidney Foundation of Canada; Canadian Institutes of Health Research [MOP-84363, MOP-86450, MOP-12573]; National Institutes of Health of USA [HL-48455]; Foundation of the CHUM FX This work was supported in part by grants from the Kidney Foundation of Canada, the Canadian Institutes of Health Research MOP-84363 to JSDC, MOP-86450 to S-LZ and MOP-12573 to JGF), the National Institutes of Health of USA (HL-48455 to JRI) and the support from the Foundation of the CHUM. We thank Dr Kevin D Burns (University of Ottawa, ON, CA) for the advice on urinary Ang 1-7 measurement. NR 47 TC 41 Z9 41 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2010 VL 77 IS 12 BP 1086 EP 1097 DI 10.1038/ki.2010.63 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 602OX UT WOS:000278149800008 PM 20237455 ER PT J AU Tucker, JD Bu, J Brown, LB Yin, YP Chen, XS Cohen, MS AF Tucker, Joseph D. Bu, Jin Brown, Lillian B. Yin, Yue-Pin Chen, Xiang-Sheng Cohen, Myron S. TI Accelerating worldwide syphilis screening through rapid testing: a systematic review SO LANCET INFECTIOUS DISEASES LA English DT Review ID SEXUALLY-TRANSMITTED INFECTIONS; CONGENITAL-SYPHILIS; PLASMA REAGIN; DIAGNOSTIC-ACCURACY; FIELD-EVALUATION; HIV-INFECTION; METAANALYSIS; PERFORMANCE; GUIDELINES; MANAGEMENT AB Syphilis is a persistent public health issue in many low-income countries that have limited capacity for testing, which traditionally relies on a sensitive non-treponemal test and then a specific treponemal test. However, the development of a new rapid treponemal test provides an opportunity to scale up syphilis screening in many settings where traditional tests are unavailable. This systematic review of immunochromatographic strip (ICS) syphilis tests describes the sensitivity and specificity in two important clinical settings: sexually transmitted infection (STI) clinics and antenatal clinics. Clinical data from more than 22000 whole blood, plasma, or fingerstick ICS tests obtained at STI or antenatal clinics were retrieved from 15 studies. ICS syphilis tests have a high sensitivity (median 0.86, interquartile range 0.75-0.94) and a higher specificity (0.99, 0.98-0.99), both comparable with non-treponemal screening test characteristics. Further research evaluating ICS syphilis tests among primary syphilis cases and among patients infected with HIV will be essential for the effective roll-out of syphilis screening programmes. C1 [Tucker, Joseph D.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Tucker, Joseph D.; Bu, Jin; Yin, Yue-Pin; Chen, Xiang-Sheng] Chinese Acad Med Sci, Inst Dermatol, Natl Ctr STD Control, Nanjing, Peoples R China. [Brown, Lillian B.; Cohen, Myron S.] Univ N Carolina, Inst Global Hlth & Infect Dis, Chapel Hill, NC USA. [Bu, Jin] Journal Nanjing Med Univ, Editorial Dept, Nanjing, Peoples R China. RP Tucker, JD (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jtucker4@partners.org FU China Syphilis Working Group; UNC Fogarty AIDS International Research and Training Program (NIH) [FIC D43 TW01039]; UNC Social Science Research on HIV/AIDS in China (NIH NICHD) [R24 HD056670-01]; UNC Center for AIDS Research; UNC STI Cooperative Grant; WHO Rapid Syphilis Test Project [A70577]; US NIH Fogarty International Center; Harvard Initiative for Global Health; Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene FX Special thanks to David Mabey and Rosanna Peeling, both at the London School of Tropical Medicine and Hygiene, for helpful comments. We acknowledge the China Syphilis Working Group, the UNC Fogarty AIDS International Research and Training Program (NIH FIC D43 TW01039), the UNC Social Science Research on HIV/AIDS in China (NIH NICHD R24 HD056670-01), the UNC Center for AIDS Research, the UNC STI Cooperative Grant, the WHO Rapid Syphilis Test Project (UNICEF/UNDP/World Bank/WHO A70577), the US NIH Fogarty International Center International Clinical Fellowship, the Harvard Initiative for Global Health, and Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Wellcome Postdoctoral Fellowship in Tropical Infectious Diseases. NR 45 TC 60 Z9 63 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD JUN PY 2010 VL 10 IS 6 BP 381 EP 386 PG 6 WC Infectious Diseases SC Infectious Diseases GA 609VL UT WOS:000278685800011 PM 20510278 ER PT J AU Barone, P Poewe, W Albrecht, S Debieuvre, C Massey, D Rascol, O Tolosa, E Weintraub, D AF Barone, Paolo Poewe, Werner Albrecht, Stefan Debieuvre, Catherine Massey, Dan Rascol, Olivier Tolosa, Eduardo Weintraub, Daniel TI Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled trial SO LANCET NEUROLOGY LA English DT Article ID DOPAMINE-RECEPTOR AGONIST; RATING-SCALE; ANTIDEPRESSANT; METAANALYSIS; INVENTORY; VALIDITY AB Background Depression is common in patients with Parkinson's disease, but evidence on the efficacy of antidepressants in this population is lacking. Because depression in patients with Parkinson's disease might be related to dopaminergic dysfunction, we aimed to assess the efficacy of the dopamine agonist pramipexole for treatment of depressive symptoms in patients with Parkinson's disease. Methods We did a 12-week randomised, double-blind, placebo-controlled (1:1 ratio) trial of pramipexole (0.125-1.0 mg three times per day) compared with placebo in patients with mild-to-moderate Parkinson's disease. Patients from 76 centres in 12 European countries and South Africa were included if they were on stable antiparkinsonian therapy without motor fluctuations and had depressive symptoms (15-item geriatric depression scale score >= 5 and unified Parkinson's disease rating scale [UPDRS] part 1 depression item score a 2). Patients were randomly assigned by centre in blocks of four by use of a randomisation number generating system. Clinical monitors, the principal investigator, and patients were masked to treatment allocation. The primary endpoint was change in Beck depression inventory (BDI) score and all treated patients who had at least one post-baseline efficacy assessment were included in the primary analysis. We also did a pre-specified path analysis with regression models to assess the relation between BDI and UPDRS part 3 (motor score) changes. This trial is registered with ClinicalTrials.gov, number NCT00297778, and EudraCT, number 2005-003788-22. Findings Between March, 2006, and February, 2008, we enrolled 323 patients. Of 296 patients randomly assigned to pramipexole or placebo, 287 were induded in the primary analysis: 139 in the pramipexole group and 148 in the placebo group. BDI scores decreased by an adjusted mean 5.9 (SE 0.5) points in the pramipexole group and 4.0 (0.5) points in the placebo group (difference 1.9, 95% CI 0.5-3.4; p=0.01, ANCOVA). The UPDRS motor score decreased by an adjusted mean 4.4 (0.6) points in the pramipexole group and 2.2 (0.5) points in the placebo group (difference 2.2, 95% CI 0-7-3-7; p=0.003, ANCOVA). Path analysis showed the direct effect of pramipexole on depressive symptoms accounted for 80% of total treatment effect (p=0.04). Adverse events were reported in 105 of 144 patients in the pramipexole group and 101 of 152 in the placebo group. Adverse events in the pramipexole group were consistent with the known safety profile of the drug. Interpretation Pramipexole improved depressive symptoms in patients with Parkinson's disease, mainly through a direct antidepressant effect. This effect should be considered in the clinical management of patients with Parkinson's disease. C1 [Barone, Paolo] Univ Naples Federico 2, Dept Neurol Sci, I-80131 Naples, Italy. [Barone, Paolo] IDC Hermitage Capodimonte, Naples, Italy. [Poewe, Werner] Innsbruck Med Univ, Dept Neurol, Innsbruck, Austria. [Albrecht, Stefan] Boehringer Ingelheim GmbH & Co KG, Corp Dept Med Affairs, Ingelheim, Germany. [Debieuvre, Catherine] Boehringer Ingelheim France SAS, Dept Clin Res, Reims, France. [Massey, Dan] Boehringer Ingelheim UK, Bracknell, Berks, England. [Rascol, Olivier] Toulouse Univ Hosp, UMR 825, Toulouse, France. [Rascol, Olivier] Toulouse Univ Hosp, INSERM 9302, Clin Invest Ctr, Dept Clin Pharmacol & Neurosci, Toulouse, France. [Tolosa, Eduardo] Univ Barcelona, Hosp Clin, IDIBAPS, Neurol Serv,CIBERNED, E-08007 Barcelona, Spain. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis & Mental Illness Res Educ & Clin C, Philadelphia, PA USA. RP Barone, P (reprint author), Univ Naples Federico 2, Dept Neurol Sci, Via Pansini 5, I-80131 Naples, Italy. EM barone@unina.it RI TM, Inct/J-8630-2013 FU Boehringer Ingelheim FX This study was funded by Boehringer Ingelheim. E Jay Bienen and Linnea Elliott provided editing assistance. Funding for editing assistance was provided by Boehringer Ingelheim. NR 41 TC 163 Z9 175 U1 2 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD JUN PY 2010 VL 9 IS 6 BP 573 EP 580 DI 10.1016/S1474-4422(10)70106-X PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 607NY UT WOS:000278512000010 PM 20452823 ER PT J AU Rubnitz, JE Inaba, H Dahl, G Ribeiro, RC Bowman, WP Taub, J Pounds, S Razzouk, BI Lacayo, NJ Cao, XY Meshinchi, S Degar, B Airewele, G Raimondi, SC Onciu, M Coustan-Smith, E Downing, JR Leung, W Pui, CH Campana, D AF Rubnitz, Jeffrey E. Inaba, Hiroto Dahl, Gary Ribeiro, Raul C. Bowman, W. Paul Taub, Jeffrey Pounds, Stanley Razzouk, Bassem I. Lacayo, Norman J. Cao, Xueyuan Meshinchi, Soheil Degar, Barbara Airewele, Gladstone Raimondi, Susana C. Onciu, Mihaela Coustan-Smith, Elaine Downing, James R. Leung, Wing Pui, Ching-Hon Campana, Dario TI Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial SO LANCET ONCOLOGY LA English DT Article ID CHILDRENS CANCER GROUP; ACUTE LYMPHOBLASTIC-LEUKEMIA; DOSE CYTOSINE-ARABINOSIDE; CLINICAL-TRIALS; ONCOLOGY-GROUP; PEDIATRIC-PATIENTS; CHEMOTHERAPY; CYTARABINE; INDUCTION; TRANSPLANTATION AB Background We sought to improve outcome in patients with childhood acute myeloid leukaemia (AML) by applying risk-directed therapy that was based on genetic abnormalities of the leukaemic cells and measurements of minimal residual disease (MRD) done by flow cytometry during treatment. Methods From Oct 13, 2002, to June 19, 2008, 232 patients with de-novo AML (n=206), therapy-related or myelodysplasia-related AML (n=12), or mixed-lineage leukaemia (n=14) were enrolled at eight centres. 230 patients were assigned by block, non-blinded randomisation, stratified by cytogenetic or morphological subtype, to high-dose (18 g/m(2), n=113) or low-dose (2 g/m(2), n=117) cytarabine given with daunorubicin and etoposide (ADE; induction 1). The primary aim of the study was to compare the incidence of MRD positivity of the high-dose group and the low-dose group at day 22 of induction 1. Induction 2 consisted of ADE with or without gemtuzumab ozogamicin (GO anti-CD33 monoclonal antibody); consolidation therapy included three additional courses of chemotherapy or haematopoietic stem-cell transplantation (HSCT). Levels of MRD were used to allocate GO and to determine the timing of induction 2. Both MRD and genetic abnormalities at diagnosis were used to determine the final risk classification. Low-risk patients (n=68) received five courses of chemotherapy, whereas high-risk patients (n=79), and standard-risk patients (n=69) with matched sibling donors, were eligible for HSCT (done for 48 high-risk and eight standard-risk patients). All 230 randomised patients were analysed for the primary endpoint. Other analyses were limited to the 216 patients with AML, excluding those with mixed-lineage leukaemia. This trial is closed to accrual and is registered with ClinicalTrials.gov, number NCT00136084. Findings Complete remission was achieved in 80% (173 of 216 patients) after induction 1 and 94% (203 of 216) after induction 2. Induction failures included two deaths from toxic effects and ten cases of resistant leukaemia. The introduction of high-dose versus low-dose cytarabine did not significantly lower the rate of MRD-positivity after induction 1 (34% vs 42%, p=0.17). The 6-month cumulative incidence of grade 3 or higher infection was 79.3% (SE 4.0) for patients in the high-dose group and 75.5% (4.2) for the low-dose group. 3-year event-free survival and overall survival were 63.0% (SE 4.1) and 71.1% (3.8), respectively. 80% (155 of 193) of patients achieved MRD of less than 0.1% after induction 2, and the cumulative incidence of relapse for this group was 17% (SE 3). MRD of 1% or higher after induction 1 was the only significant independent adverse prognostic factor for both event-free (hazard ratio 2 41, 95% CI 1.36-4.26; p=0.003) and overall survival (2.11, 1.09-4.11; p=0.028). Interpretation Our findings suggest that the use of targeted chemotherapy and HSCT, in the context of a comprehensive risk-stratification strategy based on genetic features and MRD findings, can improve outcome in patients with childhood AML. C1 [Rubnitz, Jeffrey E.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Rubnitz, Jeffrey E.; Inaba, Hiroto; Ribeiro, Raul C.; Pounds, Stanley; Razzouk, Bassem I.; Cao, Xueyuan; Raimondi, Susana C.; Onciu, Mihaela; Coustan-Smith, Elaine; Downing, James R.; Leung, Wing; Pui, Ching-Hon; Campana, Dario] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Dahl, Gary; Lacayo, Norman J.] Lucile Packard Childrens Hosp, Palo Alto, CA USA. [Dahl, Gary; Lacayo, Norman J.] Stanford Canc Ctr, Palo Alto, CA USA. [Bowman, W. Paul] Cook Childrens Med Ctr, Ft Worth, TX USA. [Taub, Jeffrey] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Degar, Barbara] Dana Farber Canc Inst, Boston, MA 02115 USA. [Airewele, Gladstone] Texas Childrens Canc Ctr, Houston, TX USA. RP Rubnitz, JE (reprint author), St Jude Childrens Hosp, Dept Oncol, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM jeffrey.rubnitz@stjude.org OI Pounds, Stanley/0000-0002-9167-2114 FU National Institutes of Health [R01 CA115422, P30 CA021765]; American Lebanese Syrian Associated Charities (ALSAC) FX We thank Sheila Shurtleff for doing molecular diagnostic analyses, Shengping Yang for statistical assistance, Kathy Jackson for data collection, and Julie Groff for preparing the figures. This work was supported by R01 CA115422 and Cancer Center Support (CORE) P30 CA021765 grants from the National Institutes of Health, and by the American Lebanese Syrian Associated Charities (ALSAC). NR 36 TC 212 Z9 223 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JUN PY 2010 VL 11 IS 6 BP 543 EP 552 DI 10.1016/S1470-2045(10)70090-5 PG 10 WC Oncology SC Oncology GA 613YA UT WOS:000279019500026 PM 20451454 ER PT J AU Hadlock, T Lindsay, R Edwards, C Smitson, C Weinberg, J Knox, C Heaton, JT AF Hadlock, Tessa Lindsay, Robin Edwards, Cohn Smitson, Christopher Weinberg, Julie Knox, Christopher Heaton, James T. TI The Effect of Electrical and Mechanical Stimulation on the Regenerating Rodent Facial Nerve SO LARYNGOSCOPE LA English DT Article DE Facial nerve; electrical stimulation; mechanical stimulation ID IMPROVES FUNCTIONAL RECOVERY; MANUAL STIMULATION; GUIDANCE CHANNELS; RECONSTRUCTIVE SURGERY; AXONAL REGENERATION; C57BL/OLA MOUSE; GROWTH-FACTOR; ADULT RATS; INJURY; MOTOR AB Objectives/Hypothesis: Investigators have long sought realistic methods to accelerate regeneration following nerve injury. Herein, we investigated the degree to which manual target muscle manipulation and brief electrical stimulation of the facial nerve, alone or in combination, affects recovery following rat facial nerve injury. Study Design: Prospective, randomized animal study. Methods: Sixty rats were randomized to three groups: brief electrical stimulation (BES), mechanical stimulation of the whisker pad (MEC), or both (COMBO). Animals underwent facial nerve transection and immediate microsurgical repair. In BES and COMBO groups, transection was preceded by 1-hour (3 V, 20 Hz square wave) electrical stimulation. Animals were tested weekly, with 5-minute recording sessions of whisker movement. In the MEC and COMBO groups, animals received 5 minutes of daily massage to the left whisker pad throughout the recovery period. Whisking behavior was analyzed for comparisons. Results: The BES and MEC groups demonstrated improved functional recovery in all whisking parameters compared with the COMBO group or historical controls at most time points between postoperative weeks 1 and 7. After 12 weeks, functional recovery remained superior in the BES and MEC groups compared with the COMBO and control groups, although the effect was no longer statistically significant. Conclusions: We observed an accelerative recovery effect of either electrical nerve stimulation or massage of the whisker pad on whisking behavior. The combination of both interventions had a negating effect on the acceleration of recovery. The potential clinical utility of these modalities bears consideration, and their negating interaction warrants further study. C1 [Hadlock, Tessa; Lindsay, Robin; Edwards, Cohn; Smitson, Christopher; Weinberg, Julie; Knox, Christopher] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Heaton, James T.] Massachusetts Eye & Ear Infirm, Dept Surg, Boston, MA 02114 USA. RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu FU National Institutes of Health, National Institute of Dental and Craniofacial Research [NIDCR K-08 DE015665-01A2] FX This work was supported by a National Institutes of Health, National Institute of Dental and Craniofacial Research grant (NIDCR K-08 DE015665-01A2). The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 53 TC 19 Z9 19 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 2010 VL 120 IS 6 BP 1094 EP 1102 DI 10.1002/lary.20903 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 607DS UT WOS:000278479600004 PM 20513023 ER PT J AU Kyle, RA Durie, BGM Rajkumar, SV Landgren, O Blade, J Merlini, G Kroger, N Einsele, H Vesole, DH Dimopoulos, M San Miguel, J Avet-Loiseau, H Hajek, R Chen, WM Anderson, KC Ludwig, H Sonneveld, P Pavlovsky, S Palumbo, A Richardson, PG Barlogie, B Greipp, P Vescio, R Turesson, I Westin, J Boccadoro, M AF Kyle, R. A. Durie, B. G. M. Rajkumar, S. V. Landgren, O. Blade, J. Merlini, G. Kroeger, N. Einsele, H. Vesole, D. H. Dimopoulos, M. San Miguel, J. Avet-Loiseau, H. Hajek, R. Chen, W. M. Anderson, K. C. Ludwig, H. Sonneveld, P. Pavlovsky, S. Palumbo, A. Richardson, P. G. Barlogie, B. Greipp, P. Vescio, R. Turesson, I. Westin, J. Boccadoro, M. CA Int Myeloma Working Grp TI Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management SO LEUKEMIA LA English DT Review DE monoclonal gammopathy of undetermined significance; smoldering multiple myeloma; International Myeloma Working Group; MGUS ID LIGHT-CHAIN RATIO; MALIGNANT-TRANSFORMATION; FLOW-CYTOMETRY; PLASMA-CELLS; LONG-TERM; PREVALENCE; RECOGNITION; PROGNOSIS; CRITERIA; BONE AB Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year. Low-risk MGUS is characterized by having an M protein < 15 g/l, IgG type and a normal free light chain (FLC) ratio. Patients should be followed with serum protein electrophoresis at six months and, if stable, can be followed every 2-3 years or when symptoms suggestive of a plasma cell malignancy arise. Patients with intermediate and high-risk MGUS should be followed in 6 months and then annually for life. The risk of smoldering (asymptomatic) multiple myeloma (SMM) progressing to multiple myeloma or a related disorder is 10% per year for the first 5 years, 3% per year for the next 5 years and 1-2% per year for the next 10 years. Testing should be done 2-3 months after the initial recognition of SMM. If the results are stable, the patient should be followed every 4-6 months for 1 year and, if stable, every 6-12 months. Leukemia (2010) 24, 1121-1127; doi:10.1038/leu.2010.60; published online 22 April 2010 C1 [Kyle, R. A.; Rajkumar, S. V.; Greipp, P.] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Durie, B. G. M.; Vescio, R.] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Aptium Oncol Inc, Los Angeles, CA USA. [Landgren, O.] NCI, NIH, Bethesda, MD 20892 USA. [Blade, J.] Hosp Clin Barcelona, IDIBAPS, Dept Hematol, Barcelona, Spain. [Merlini, G.] Univ Hosp San Matteo, Dept Biochem, Pavia, Italy. [Kroeger, N.] Univ Hamburg Hosp, Dept Stem Cell Transplantat, D-2000 Hamburg, Germany. [Einsele, H.] Univ Wurzburg, Dept Internal Med, Wurzburg, Germany. [Vesole, D. H.] Hackensack Univ Med Ctr, Hackensack Canc Ctr, Hackensack, NJ USA. [Dimopoulos, M.] Univ Athens, Sch Med, Dept Therapeut, GR-11527 Athens, Greece. [San Miguel, J.] Hosp Univ Salamanca, IBMCC USAL CSIC Salamanca, Serv Hematol, Dept Hematol,CIC, Salamanca, Spain. [Avet-Loiseau, H.] Inst Biol, Hematol Lab, Nantes, France. [Hajek, R.] Univ Hosp Brno, Dept Internal Med Hematol, Brno, Czech Republic. [Chen, W. M.] Beijing Chaoyang Hosp, Dept Hematol & Oncol, Beijing, Peoples R China. [Anderson, K. C.; Richardson, P. G.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. [Ludwig, H.] Wilhelminenspital Stadt Wien, Ctr Oncol & Hematol, Dept Med 1, Vienna, Austria. [Sonneveld, P.] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Pavlovsky, S.] Angel Ocampo Hosp, FUNDALEU, Buenos Aires, DF, Argentina. [Palumbo, A.; Boccadoro, M.] Univ Turin, Div Ematol, Turin, Italy. [Barlogie, B.] MIRT UAMS, Dept Hematol, Little Rock, AR USA. [Barlogie, B.] MIRT UAMS, Dept Pathol, Little Rock, AR USA. [Turesson, I.] Malmo Univ Hosp, Dept Hematol, Malmo, Sweden. [Westin, J.] Sahlgrens Univ Hosp, Dept Hematol, Gottenburg, Sweden. RP Kyle, RA (reprint author), Mayo Clin, Div Hematol, 200 1st St SW,Stabile 6-28, Rochester, MN 55905 USA. EM kyle.robert@mayo.edu RI Waage, Anders/D-7705-2013; FACON, THIERRY/M-9736-2014; Garcia-Sanz, Ramon/B-7986-2017; OI FACON, THIERRY/0000-0001-7705-8460; Garcia-Sanz, Ramon/0000-0003-4120-2787; SAN MIGUEL, JESUS/0000-0002-9183-4857; Rajkumar, S. Vincent/0000-0002-5862-1833; Merlini, Giampaolo/0000-0001-7680-3254 NR 23 TC 260 Z9 273 U1 1 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 2010 VL 24 IS 6 BP 1121 EP 1127 DI 10.1038/leu.2010.60 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 608HV UT WOS:000278575400003 PM 20410922 ER PT J AU Radulovic, M Schilero, GJ Wecht, JM La Fountaine, M Rosado-Rivera, D Bauman, WA AF Radulovic, Miroslav Schilero, Gregory J. Wecht, Jill M. La Fountaine, Michael Rosado-Rivera, Dwindally Bauman, William A. TI Exhaled Nitric Oxide Levels Are Elevated in Persons with Tetraplegia and Comparable to that in Mild Asthmatics SO LUNG LA English DT Article DE Spinal cord injury; Tetraplegia; Fraction exhaled nitric oxide; Nitric oxide; Asthma ID SPINAL-CORD-INJURY; AIRWAY HYPERRESPONSIVENESS; LUNG; SYNTHASE AB The role of airway inflammation in mediating airflow obstruction in persons with chronic traumatic tetraplegia is unknown. Measurement of the fraction of exhaled nitric oxide (FeNO) affords a validated noninvasive technique for gauging the airway inflammatory response in asthma, although it has never been assessed in persons with tetraplegia. This study was designed to determine the FeNO in individuals with chronic tetraplegia compared with that in patients with mild asthma and healthy able-bodied individuals. Nine subjects with chronic tetraplegia, seven subjects with mild asthma, and seven matched healthy able-bodied controls were included in this prospective, observational, pilot study. All subjects were nonsmokers and clinically stable at the time of study. Spirometry was performed on all participants at baseline. FENO was determined online by a commercially available closed circuit, chemiluminescence method, using a single-breath technique. Subjects with tetraplegia had significantly higher values of FeNO than controls (17.72 +/- A 3.9 ppb vs. 10.37 +/- A 4.9 ppb; P a parts per thousand currency sign 0.01), as did subjects with asthma (20.23 +/- A 4.64 ppb vs. 10.37 +/- A 4.9 ppb, P a parts per thousand currency sign 0.001). There was no significant difference in FeNO between subjects with tetraplegia and those with asthma (17.72 +/- A 3.9 ppb vs. 20.23 +/- A 4.64 ppb, P a parts per thousand currency sign 0.27). Individuals with chronic tetraplegia have FeNO levels that are comparable to that seen in mild asthmatics and higher than that in healthy able-bodied controls. The clinical relevance of this observation has yet to be determined. C1 [Radulovic, Miroslav; Schilero, Gregory J.; Wecht, Jill M.; La Fountaine, Michael; Rosado-Rivera, Dwindally; Bauman, William A.] James J Peters VA Med Ctr, Rehabil Res & Dev Ctr Excellence Med Consequences, Bronx, NY 10468 USA. [Radulovic, Miroslav; Schilero, Gregory J.; Wecht, Jill M.; Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Radulovic, Miroslav; Schilero, Gregory J.; Wecht, Jill M.; Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Wecht, Jill M.; Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP Radulovic, M (reprint author), James J Peters VA Med Ctr, Rehabil Res & Dev Ctr Excellence Med Consequences, Rm 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Miroslav.Radulovic@va.gov FU Rehabilitation Research and Development (RR&D) Service Career Development award [B4335 V]; RR&D Center of Excellence for the Medical Consequences of Spinal Cord Injury [B4162C]; Department of Veterans Affairs Rehabilitation Research and Development FX This work was funded by a Rehabilitation Research and Development (RR&D) Service Career Development award (B4335 V) & RR&D Center of Excellence for the Medical Consequences of Spinal Cord Injury (B4162C). The authors thank The James J. Peters Medical Center, Bronx, NY, and Department of Veterans Affairs Rehabilitation Research and Development service for their support. NR 17 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2040 J9 LUNG JI Lung PD JUN PY 2010 VL 188 IS 3 BP 259 EP 262 DI 10.1007/s00408-009-9207-x PG 4 WC Respiratory System SC Respiratory System GA 586LM UT WOS:000276910400011 PM 20012982 ER PT J AU Egede, LE Mueller, M Echols, CL Gebregziabher, M AF Egede, Leonard E. Mueller, Martina Echols, Carrae L. Gebregziabher, Mulugeta TI Longitudinal Differences in Glycemic Control by Race/Ethnicity Among Veterans With Type 2 Diabetes SO MEDICAL CARE LA English DT Article DE diabetes; ethnicity; veterans; glycemic control ID AFFAIRS HEALTH-CARE; RACIAL DISPARITIES; UNITED-STATES; RACIAL/ETHNIC DIFFERENCES; INTERMEDIATE OUTCOMES; MEDICATION ADHERENCE; ETHNIC-DIFFERENCES; GLUCOSE CONTROL; ADULTS; QUALITY AB Objective: To examine longitudinal differences in glycemic control between non-Hispanic white and non-Hispanic black veterans with type 2 diabetes. Design: Retrospective cohort study. Setting: VA facility in the Southeastern United States. Participants: A 3-month person-period dataset was created for 8813 veterans with type 2 diabetes between June 1997 and May 2006. Main Outcome Measures: Primary outcome was mean change in hemoglobin A1c (HbA1c) over time. Secondary outcome was the odds of poor glycemic control over time (HbA1c >8%). For the primary outcome, a linear mixed model (LMM) approach was used to model the relationship of HbA1c levels and race/ethnicity over time. For the secondary outcome, generalized LMMs were used to assess whether glycemic control changed over time and whether change in glycemic control varied by racial/ethnic group. Results: Mean age was 66.3 years, 36% were non-Hispanic black (NHB), 98% were male, 65% were married, and 50% were unemployed. Mean follow-up time was 4.4 years. Least square mean HbA1c levels from LMM adjusted for time and relevant confounders showed that NHBs had higher HbA1c values over time (mean difference of 0.54% [P < 0.001]). The final model with poor versus good glycemic control as the dependent variable, race/ethnicity as primary independent variable adjusted for time, and relevant confounders showed that NHBs were likely to have poor control compared with NHWs (OR: 1.8, 95% CI, 1.7; 2.0, P < 0.0001). Conclusions: NHB veterans were more likely to have higher mean HbA1c values and less likely to have good glycemic control over time compared with NHW veterans. C1 [Egede, Leonard E.; Echols, Carrae L.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Egede, Leonard E.; Mueller, Martina; Echols, Carrae L.; Gebregziabher, Mulugeta] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Mueller, Martina] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Biostat, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Bioinformat, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Epidemiol, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU Veterans Health Administration [REA 08-261] FX Supported by the Veterans Health Administration Health Services Research Development program (VA HSRD) grant REA 08-261. All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 40 TC 12 Z9 12 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2010 VL 48 IS 6 BP 527 EP 533 DI 10.1097/MLR.0b013e3181d558dc PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 603ER UT WOS:000278191900006 PM 20473215 ER PT J AU Regan, S Ferris, TG Campbell, EG AF Regan, Susan Ferris, Timothy G. Campbell, Eric G. TI Physician Attitudes Toward Personal Relationships With Patients SO MEDICAL CARE LA English DT Article DE Physician-patient relations; professionalism; professional boundary; medical education ID NATIONAL-SURVEY; SEXUAL CONTACT; PROFESSIONALISM; PREVALENCE AB Background: Maintenance of appropriate boundaries in the doctor-patient relationship is central to medical professionalism. Little is known about physician attitudes toward personal relationships with patients. Objective: To explore physician attitudes toward a range of personal relationships with patients and the connection between them and other facets of professional behavior. Research Design: National survey by mail using a stratified random sample. Subjects: Active physicians specializing in internal medicine, family medicine, pediatrics, cardiology, surgery, and anesthesiology. Measures: Respondents rated the appropriateness of social, business, and sexual contacts with patients and expressed level of agreement with statements regarding other aspects of medical professionalism relating to patient welfare and professional self-regulation. Endorsement of relationships was dichotomized as never versus rarely, sometimes, often, or always appropriate. Results: A total of 1662 eligible physicians responded of 3504 sampled (adjusted response rate: 58%). Support was high for social relations (91%), somewhat less for business relations (65%), and low for sexual contact (9%). Women, nonwhites, and foreign medical school graduates were less likely to support all 3 relationships. Support for sensitive relationships was associated with rejection of the primacy of patient welfare over physician financial interests (P = 0.015), providing care to indigent patients (P = 0.010), reporting medical errors (P = 0.002), and participating in peer evaluations (P = 0.002). Conclusion: Physicians may perceive different types of relations with patients to fall on a continuum of potential for conflict with their professional role. Support for personal relationships was associated with physician demographic characteristics. More permissive interpersonal boundaries may be associated with weaker support for other professional standards. C1 [Regan, Susan] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Ferris, Timothy G.; Campbell, Eric G.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Regan, S (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM sregan@partners.org NR 18 TC 5 Z9 5 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2010 VL 48 IS 6 BP 547 EP 552 DI 10.1097/MLR.0b013e3181d559d0 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 603ER UT WOS:000278191900009 PM 20473214 ER PT J AU Ollendorf, DA Pearson, SD AF Ollendorf, Daniel A. Pearson, Steven D. TI An Integrated Evidence Rating to Frame Comparative Effectiveness Assessments for Decision Makers SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Symposium on Clinical and Comparative Effectiveness Research Methods II CY JUN 01-02, 2009 CL Rockville, MD SP Agcy Healthcare Res & Qual DE comparative effectiveness research; cost-effectiveness; translation; evidence-based decision making ID ADJUSTED LIFE-YEAR; TASK-FORCE; QUALITY; RECOMMENDATIONS; GRADE; MEDICINE; STRENGTH AB Background: An important challenge facing the research community is how to make comparative effectiveness reviews "fit for purpose"-how to translate the results into a format that can provide actionable guidance for all stakeholders trying to improve the quality and value of health care. Methods: To communicate transparently the overall judgments on the findings from a comparative effectiveness review, the Institute for Clinical and Economic Review ( ICER) uses an integrated evidence rating that combines separate ratings of comparative clinical effectiveness and comparative value. These integrated ratings look somewhat like bond ratings, and are suited to foster more direct consideration by all decision makers for potential application to patient information, clinical guidelines, and value-based coverage and payment policies. Results: ICER Integrated Evidence Ratings have supported coverage decision-making processes in a limited number of public and private payers, and demonstration efforts are underway to link reviews to patient information and revised payment policies. Several important challenges to rating have been encountered and addressed. Early feedback has suggested that the rating format helps decision makers understand the key issues underlying judgments about the comparative effectiveness of alternative interventions. Conclusion: Decision makers need comparative effectiveness reviews to be objective and rigorous; they also need key judgments regarding the evidence to be translated so all stakeholders can understand and consider them fully. A rating format that captures key judgments about comparative clinical effectiveness and comparative value could prove an effective method for helping ensure that comparative effectiveness reviews are understandable and useful to all stakeholders. C1 [Ollendorf, Daniel A.; Pearson, Steven D.] Massachusetts Gen Hosp, Inst Technol Assessment, Inst Clin & Econ Review, Boston, MA 02114 USA. RP Pearson, SD (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, Inst Clin & Econ Review, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM spearson@icer-review.org NR 16 TC 6 Z9 6 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2010 VL 48 IS 6 SU 1 BP S145 EP S152 DI 10.1097/MLR.0b013e3181d9913b PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 603SG UT WOS:000278227800022 PM 20473206 ER PT J AU Kozak, L Boynton, L Bentley, J Bezy, E AF Kozak, Leila Boynton, Lorin Bentley, Jacob Bezy, Emma TI Introducing spirituality, religion and culture curricula in the psychiatry residency programme SO MEDICAL HUMANITIES LA English DT Article ID MENTAL-HEALTH; MEDICINE; CARE; EDUCATION AB A growing body of research suggests that religion and spirituality may have a positive effect on mental and physical health. Medical schools have been increasingly offering courses in spirituality and health, particularly about the multi-cultural dimensions of religion and spirituality. There is a trend towards integrating the teaching of cross-cultural issues related to spirituality and religion into medical education. This trend is particularly evident in the field of psychiatry, where an increasing number of residency programmes are developing curriculum in this area. This article describes a specific curriculum in spirituality, religion and culture that was introduced in 2003 at the University of Washington Psychiatry Residency Program in Seattle, Washington. Reflections about the present and future of subject areas such as spirituality and religion in medical education and psychiatry residency are discussed. C1 [Kozak, Leila] Dept Vet Affairs Med Ctr, Hlth Serv R&D Serv, Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. [Kozak, Leila] Univ Washington, Dept Hlth Serv, Sch Publ Hlth, Seattle, WA 98195 USA. [Boynton, Lorin] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Bentley, Jacob] Seattle Pacific Univ, Dept Psychol, Seattle, WA 98119 USA. [Bezy, Emma] Ctr Spirit & Hlth Seattle, Seattle, WA USA. RP Kozak, L (reprint author), Dept Vet Affairs Med Ctr, Hlth Serv R&D Serv, Dept Vet Affairs, VA Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM leila.kozak@va.gov NR 28 TC 4 Z9 4 U1 1 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1468-215X J9 MED HUMANIT JI Med. Humanit. PD JUN PY 2010 VL 36 IS 1 BP 48 EP 51 DI 10.1136/jmh.2010.004267 PG 4 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA 701TE UT WOS:000285845500016 PM 21393277 ER PT J AU Laubach, JP Richardson, PG Anderson, KC AF Laubach, Jacob P. Richardson, Paul G. Anderson, Kenneth C. TI The evolution and impact of therapy in multiple myeloma SO MEDICAL ONCOLOGY LA English DT Article DE Multiple myeloma; Stem cell transplantation; Lenalidomide; Thalidomide; Bortezomib ID STEM-CELL TRANSPLANTATION; LENALIDOMIDE PLUS DEXAMETHASONE; BONE-MARROW-TRANSPLANTATION; DOSE INTRAVENOUS MELPHALAN; COMBINATION CHEMOTHERAPY; MAINTENANCE THERAPY; REFRACTORY MYELOMA; IMPROVES SURVIVAL; RANDOMIZED-TRIAL; ELDERLY-PATIENTS AB Multiple myeloma is a clonal B-cell malignancy characterized by aberrant expression of plasma cells wtihin the bone marrow, and is associated with the well known clinical manifestations anemia, bone disease, renal dysfunction, hypercalcemia, and recurrent infections. For many years, melphalan and prednisone represented the standard of care in multiple myeloma therapy, with stem cell transplantation reserved for selected patients. Treatment of the disease has evolved rapidly over the past decade, however, with the development and utilization of thalidomide, lenalidomide, and bortezomib. As a result of these developments, clinical outcomes have improved significantly. This review highlights important historic landmarks as well as more recent events that have played an important role in the evolution of myeloma therapy. C1 [Laubach, Jacob P.; Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. RP Laubach, JP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. EM jacobp_laubach@dfci.harvard.edu NR 84 TC 16 Z9 16 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1357-0560 J9 MED ONCOL JI Med. Oncol. PD JUN PY 2010 VL 27 SU 1 BP 1 EP 6 DI 10.1007/s12032-010-9442-2 PG 6 WC Oncology SC Oncology GA 636OR UT WOS:000280747900001 ER PT J AU Reske, T Fulciniti, M Munshi, NC AF Reske, Thomas Fulciniti, Mariateresa Munshi, Nikhil C. TI Mechanism of action of immunomodulatory agents in multiple myeloma SO MEDICAL ONCOLOGY LA English DT Article DE Immunomodulatory agents; Bone marrow microenvironment; Multiple myeloma ID NF-KAPPA-B; MARROW STROMAL CELLS; RESISTANCE CAM-DR; THALIDOMIDE ANALOGS; THERAPEUTIC IMPLICATIONS; INDUCED APOPTOSIS; GROWTH-FACTOR; LENALIDOMIDE; ADHESION; TUMOR AB Immunomodulatory agents (IMiD's) have become an important drug category in the treatment of multiple myeloma. The agents have a complex mechanism of action that influence the microenvironment in the bone marrow. The microenvironment is an essential promotor of disease progression and therefore important in targeting the disease. The article reviews mechanism of action and essential pathways of IMiD's that are important in disease treatment. C1 [Fulciniti, Mariateresa; Munshi, Nikhil C.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Reske, Thomas; Munshi, Nikhil C.] VA Boston Healthcare Syst, Boston, MA USA. [Reske, Thomas] Boston Univ, Med Ctr, Boston, MA USA. RP Munshi, NC (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu FU Department of Veterans Affairs; NIH [RO1-124929, P50-100707, PO1-78378] FX This work is supported by Department of Veterans Affairs Merit Review Award (and NIH grant RO1-124929, P50-100707 and PO1-78378 (NCM). NR 44 TC 11 Z9 12 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1357-0560 J9 MED ONCOL JI Med. Oncol. PD JUN PY 2010 VL 27 SU 1 BP 7 EP 13 DI 10.1007/s12032-010-9527-y PG 7 WC Oncology SC Oncology GA 636OR UT WOS:000280747900002 ER PT J AU Zhu, XP Palmer, MR Makrigiorgos, GM Kassis, AI AF Zhu, Xuping Palmer, Matthew R. Makrigiorgos, G. Mike Kassis, Amin I. TI Solid-tumor radionuclide therapy dosimetry: New paradigms in view of tumor microenvironment and angiogenesis SO MEDICAL PHYSICS LA English DT Article DE dosimetry; electron emitter; alpha particle emitter; tumor vascularity; neovasculature targeting; tumor targeting; targeted radionuclide therapy ID RADIOIMMUNOTHERAPY; CANCER; DISTRIBUTIONS; ANTIBODIES; PARTICLES; ELECTRON AB Purpose: The objective of this study is to evaluate requirements for radionuclide-based solid tumor therapy by assessing the radial dose distribution of beta-particle-emitting and alpha-particle-emitting molecules localized either solely within endothelial cells of tumor vasculature or diffusing from the vasculature throughout the adjacent viable tumor cells. Methods: Tumor blood vessels were modeled as a group of microcylindrical layers comprising endothelial cells (one-cell thick, 10 mu m diameter), viable tumor cells (25-cell thick, 250 mu m radius), and necrotic tumor region (>250 mu m from any blood vessel). Sources of radioactivity were assumed to distribute uniformly in either endothelial cells or in concentric cylindrical 10 mu m shells within the viable tumor-cell region. The EGSnrc Monte Carlo simulation code system was used for beta particle dosimetry and a dose-point kernel method for alpha particle dosimetry. The radioactive decays required to deposit cytocidal doses (>= 100 Gy) in the vascular endothelial cells (endothelial cell mean dose) or, alternatively, at the tumor edge [tumor-edge mean dose (TEMD)] of adjacent viable tumor cells were then determined for six beta ((32)P, (33)P, (67)Cu, (90)Y, (131)I, and (188)Re) and two alpha ((211)At and (213)Bi) particle emitters. Results: Contrary to previous modeling in targeted radionuclide therapy dosimetry of solid tumors, the present work restricts the region of tumor viability to 250 mu m around tumor blood vessels for consistency with biological observations. For delivering >= 100 Gy at the viable tumor edge (TEMD) rather than throughout a solid tumor, energetic beta emitters (90)Y, (32)P, and (188)Re can be effective even when the radionuclide is confined to the blood vessel (i.e., no diffusion into the tumor). Furthermore, the increase in tumor-edge dose consequent to beta emitter diffusion is dependent on the energy of the emitted beta particles, being much greater for lower-energy emitters (131)I, (67)Cu, and (33)P relative to higher-energy emitters (90)Y, (32)P, and (188)Re. Compared to alpha particle emitters, a similar to 150-400 times higher number of beta-particle-emitting radioactive atoms is required to deposit the same dose in tumor neovasculature. However, for the alpha particle emitters (211)At and (213)Bi to be effective in irradiating viable tumor-cell regions in addition to the vasculature, the carrier molecules must diffuse substantially from the vasculature into the viable tumor. Conclusion: The presented data enable comparison of radionuclides used for antiangiogenic therapy on the basis of their radioactive decay properties, tumor neovasculature geometry, and tumor-cell viability. For alpha particle emitters or low-energy beta particle emitters, the targeting carrier molecule should be chosen to permit the radiopharmaceutical to diffuse from the endothelial wall of the blood vessel, while for long-range energetic beta particle emitters that target neovasculature, a radiopharmaceutical that binds to newly formed endothelial cells and does not diffuse is preferable. The work is a first approximation to modeling of tumor neovasculature that ignores factors such as pharmacokinetics and targeting capability of carrier molecules. The calculations quantify the interplay between irradiation of neovasculature, the surrounding viable tumor cells, and the physical properties of commonly used radionuclides and can be used to assist estimation of radioactivity to be administered for neovasculature-targeted tumor therapy. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3431999] C1 [Kassis, Amin I.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Zhu, Xuping; Palmer, Matthew R.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Makrigiorgos, G. Mike] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. RP Kassis, AI (reprint author), Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM amin_kassis@hms.harvard.edu FU NIH [5R01 CA 015523, 1R01 CA 89648]; DOD [W81XWH-04-0499, W81XWH-06-1-204, W81XWH-06-1-0043] FX This work was supported in part by NIH Grant Nos. 5R01 CA 015523 and 1R01 CA 89648, DOD Grant No. W81XWH-04-0499, DOD Grant No. W81XWH-06-1-204, and DOD Grant No. W81XWH-06-1-0043 to Amin I. Kassis. NR 35 TC 16 Z9 16 U1 2 U2 8 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2010 VL 37 IS 6 BP 2974 EP 2984 DI 10.1118/1.3431999 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 608HC UT WOS:000278573100062 PM 20632610 ER PT J AU Ueltzhoffer, S Zygmanski, P Hesser, J Hogele, W Wong, J Bellon, JR Lyatskaya, Y AF Ueltzhoeffer, Stefan Zygmanski, Piotr Hesser, Juergen Hoegele, Wolfgang Wong, Julia Bellon, Jennifer R. Lyatskaya, Yulia TI Clinical application of Varian OBI CBCT system and dose reduction techniques in breast cancer patients setup SO MEDICAL PHYSICS LA English DT Article DE CBCT; dose; image quality; OBI; breast ID BEAM COMPUTED-TOMOGRAPHY; IMAGE-GUIDED RADIOTHERAPY; RADIATION-THERAPY; DIGITAL TOMOSYNTHESIS; CONTRALATERAL BREAST; KILOVOLTAGE; CT; VERIFICATION; IRRADIATION; DOSIMETRY AB Purpose: To characterize the standard modes of Varian on board imaging (OBI) v1.4 system and identify techniques to further optimize imaging parameters, in particular, for breast treatment setup. Methods: A male anthropomorphic torso phantom was used for image quality assessment and a simpler thorax phantom for dose measurements. Both phantoms had artificial breasts attached. Doses were measured with an ion chamber in seven locations in the thorax and the breast. Evaluation of image quality was performed in terms of contrast-to-noise ratio (CNR) and in combination with the dose-to-contrast-to-noise (CNRD) parameter. The effect of kVp and mAs on the image quality, dose, and CNRD parameter was analyzed. In addition, image geometry with noncentral isocenter location with start and stop imaging angles adjusted for greater sparing of the contralateral breast was evaluated in terms of image quality and dose. Results: The measurements showed doses between 0.02 and 1.6 cGy for the three full-fan modes and 0.6-3.2 cGy for half-fan modes. This is a reduction of over 80% and 30%-50% compared to OBI v.1.3 modes for full-fan and half-fan modes, respectively. The CNRD is the highest for both low dose modes (low dose thorax and low dose head). Optimal ranges for an averaged sized thorax are tube voltages not higher than 100 kVp and current-time products between 100 and 400 mAs. For the contralateral breast and lung, a dose less than 0.03 cGy per scan was measured for the optimized image geometry with the noncentral isocenter location. Conclusions: The OBI v1.4 system allows for imaging with a larger variety of imaging parameters compared to previous OBI v1.3 systems. The largest doses (up to 4 cGy) were measured in a phantom when OBI v1.4 system was used for imaging with half-fan modes. Using full-fan modes resulted in the doses less than 1.6 cGy. Further decrease in dose may be achieved by reducing mAs while preserving acceptable image quality. Organ specific sparing (e. g., contralateral breast) may be achieved by proper selection of the start and stop angles. For thorax imaging, the use of Low Dose Thorax mode is recommended. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3432617] C1 [Ueltzhoeffer, Stefan; Zygmanski, Piotr; Hoegele, Wolfgang; Wong, Julia; Bellon, Jennifer R.; Lyatskaya, Yulia] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Ueltzhoeffer, Stefan; Hesser, Juergen; Hoegele, Wolfgang] Univ Heidelberg, Med Fac Mannheim, D-68167 Mannheim, Germany. RP Lyatskaya, Y (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. EM ylyatskaya@lroc.harvard.edu RI Hoegele, Wolfgang/A-2575-2013 OI Hoegele, Wolfgang/0000-0002-5303-9334 NR 19 TC 4 Z9 6 U1 1 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2010 VL 37 IS 6 BP 2985 EP 2998 DI 10.1118/1.3432617 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 608HC UT WOS:000278573100063 PM 20632611 ER PT J AU Baggish, AL Yared, K Weiner, RB Wang, F Demes, R Picard, MH Hagerman, F Wood, MJ AF Baggish, Aaron L. Yared, Kibar Weiner, Rory B. Wang, Francis Demes, Robert Picard, Michael H. Hagerman, Fredrick Wood, Malissa J. TI Differences in Cardiac Parameters among Elite Rowers and Subelite Rowers SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE EXERCISE-INDUCED CARDIAC REMODELING; ATHLETE'S HEART; ELITE ATHLETE; MYOCARDIAL FUNCTION; DIASTOLIC FUNCTION ID LEFT-VENTRICULAR HYPERTROPHY; ATHLETES HEART; ENDOTHELIAL FUNCTION; DIASTOLIC FUNCTION; AEROBIC FITNESS; LEFT ATRIAL; EXERCISE; ENDURANCE; DIMENSIONS; MORPHOLOGY AB BAGGISH, A. L., K. YARED, R. B. WEINER, F. WANG, R. DEMES, M. H. PICARD, F. HAGERMAN, and M. J. WOOD. Differences in Cardiac Parameters among Elite Rowers and Subelite Rowers. Med. Sci. Sports Exerc., Vol. 42, No. 6, pp. 1215-1220, 2010. There is significant individual variability in the cardiac adaptation that occurs in response to exercise training. Factors associated with this variability remain incompletely understood. To date, the relationship between the competition level at which athletes participate and their underlying cardiac parameters has not been explored. Purpose: The purpose of this study was to determine whether parameters of cardiac structure and function differ significantly among elite competitive rowers (ER), subelite competitive rowers (SR), and sedentary controls (C). Methods: Cardiac parameters were assessed in ER (n = 20), SR (n = 20), and C (n = 20) using two-dimensional, tissue Doppler, and speckled-tracking echocardiography. Results: Physiologic cardiac remodeling was present in both ER and SR as evidenced by the significant differences in the majority of structural and functional parameters in both rower groups when compared with C. When compared with SR, ER were found to have greater left ventricular (LV) end-diastolic volume (76 +/- 6 vs 71 +/- 8 mL.m(-2), P = 0.02), LV mass (150 +/- 11 vs 134 +/- 16 g.m(-2), P = 0.002), and right ventricular (RV) end-diastolic chamber dimensions (15.6 +/- 0.9 vs 13.9 perpendicular to 1.5 cm(2).m(-2), P < 0.001). Further, ER demonstrated significantly more enhancement of RV systolic function (peak strain = 36% +/- 7% vs 31% +/- 6%, P = 0.008) and late diastolic relaxation in both the LV (A' = 4.2 +/- 1.3 vs 3.2 +/- 0.9 cm.s(-1), P = 0.01) and the RV (A' = 6.6 +/- 1.4 vs 4.3 +/- 1.3 cm.s(-1), P < 0.001). Conclusions: Although cardiac remodeling occurs in both ER and SR, specific aspects of cardiac structure and function differ between rowers who compete at the elite and the subelite levels of sport. C1 [Baggish, Aaron L.; Yared, Kibar; Weiner, Rory B.; Picard, Michael H.; Wood, Malissa J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Wang, Francis] Harvard Univ, Hlth Serv, Cambridge, MA 02138 USA. [Demes, Robert] USA, Environm Med Res Inst, Natick, MA 01760 USA. [Hagerman, Fredrick] Ohio Univ, Dept Biomed Sci, Athens, OH 45701 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey Bldg,Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 40 TC 27 Z9 27 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUN PY 2010 VL 42 IS 6 BP 1215 EP 1220 DI 10.1249/MSS.0b013e3181c81604 PG 6 WC Sport Sciences SC Sport Sciences GA 596ZV UT WOS:000277725700022 PM 19997021 ER PT J AU Fuchs, BB Eby, J Nobile, CJ El Khoury, JB Mitchell, AP Mylonakis, E AF Fuchs, Beth Burgwyn Eby, Josh Nobile, Clarissa J. El Khoury, Joseph B. Mitchell, Aaron P. Mylonakis, Eleftherios TI Role of filamentation in Galleria mellonella killing by Candida albicans SO MICROBES AND INFECTION LA English DT Article DE Candida albicans; Galleria mellonella; Filamentation; Hyphae ID TRANSCRIPTION FACTOR; HYPHAL DEVELOPMENT; GENE DISRUPTION; VIRULENCE; MUTANTS; LARVAE; IDENTIFICATION; PATHOGENICITY; INFECTION; BIOFILMS AB Candida albicans is an important cause of morbidity in hospitalized and immunosuppressed patients. Virulence factors of C. albicans include: filamentation, proteinases, adherence proteins and biofilm formation. The objective of this work was to use Galleria mellonella as a model to study the roles of C. albicans filamentation in virulence. We focused our study to five genes BCR1, FLO8, KEM1, SUV3 and TEC1 that have been shown to play a role in filamentation. Filaments are necessary for biofilm formation and evading interaction with macrophages in mammalian infections. Among the five mutant strain tested, we found that only the flo8/flo8 mutant strain did not form filaments within G. mellonella. This strain also exhibited reduced virulence in the larvae. Another strain that exhibited reduced pathogenicity in the G. mellonella model was tec1/tec1 but by contrast, the tec1/tec1 strain retained the ability to form filaments. Overexpression of TEC1 in the flo8/flo8 mutant restored filamentation but did not restore virulence in the larvae as well as in a mouse model of C. albicans infection. The filamentation phenotype did not affect the ability of hemocytes, the immune cells of G. mellonella, to associate with the various mutant strains of C. albicans. The capacities of the tec1/tec1 mutant and the flo8/flo8 TDH3-TEC1 strains to form filaments with impaired virulence suggest that filamentation alone is not sufficient to kill G. mellonella and suggest other virulence factors may be associated with genes that regulate filamentation. (C) 2010 Elsevier Masson SAS. All rights reserved. C1 [Fuchs, Beth Burgwyn; Eby, Josh; El Khoury, Joseph B.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Nobile, Clarissa J.; Mitchell, Aaron P.] Columbia Univ, Dept Microbiol, New York, NY 10032 USA. [El Khoury, Joseph B.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [El Khoury, Joseph B.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM hfuchs@partners.org; emylonakis@partners.org RI Nobile, Clarissa/C-2407-2015; OI Nobile, Clarissa/0000-0003-0799-6499; Mitchell, Aaron/0000-0002-0868-4000 FU NIH [A1075286, R21A1070569]; Massachusetts General Hospital Executive Committee FX The flo8/flo8 mutants strain CA2 was provided as a gift from Dr. Haoping Liu. CAN14 was provided by Dr. Gerald Fink. This work was supported by a R01 award A1075286 from the NIH and a R21 award R21A1070569 to EM. BBF was supported by a Massachusetts General Hospital Executive Committee on Research Fund for Medical Discovery Fellowship. NR 24 TC 50 Z9 61 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUN PY 2010 VL 12 IS 6 BP 488 EP 496 DI 10.1016/j.micinf.2010.03.001 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 614GY UT WOS:000279044800008 PM 20223293 ER PT J AU Thompson, BT AF Thompson, B. T. TI Corticosteroids for ARDS SO MINERVA ANESTESIOLOGICA LA English DT Review DE Respiratory distress syndrome, adult; Adrenal cortex hormones; Glucocorticoids ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; SURVIVING SEPSIS CAMPAIGN; SEPTIC SHOCK; CORTISOL RESPONSE; CRITICAL ILLNESS; ADRENOCORTICAL RESPONSIVENESS; GLUCOCORTICOID TREATMENT; ILL PATIENTS AB The aim of this study was to describe the role of glucocorticoids in immune modulation during critical illness and to review clinical trials and recent meta-analyses of glucocorticoids in early and late acute respiratory distress syndrome (ARDS). Selected reviews of publications, clinical trials, and meta-analyses were considered for the study. Activation of the adrenal axis is an important component of the compensatory anti-inflammatory response to critical illness. A recent meta-analysis of high doses of corticosteroids in patients with or at risk for ARDS demonstrated a trend for greater risk of the development of ARDS and a final outcome. Additional meta-analyses of four randomized trials and live cohort studies in patients with established ARDS or pneumonia indicated an overall mortality benefit with corticosteroids but this finding was not confirmed in another meta-analysis limited to randomized trials and excluding die trial focused on pneumonia. Lung function is improved and the duration of mechanical ventilation is reduced with prolonged administration flower closes. In conclusion, short-duration, high-dose glucocorticoid therapy is not effective in preventing ARDS and may be harmful. Lower doses for persistent ARDS improve lung function and shorten the duration of mechanical ventilation but the impact on long-term mortality is unclear. Additional trials are needed to determine if corticosteroids improve important clinical outcomes before they can be recommended for the routine use of patients with unresolved ARDS. (Minerva Anestesiol 2010;76:441-7) C1 [Thompson, B. T.] Massachusetts Gen Hosp, Med Intens Care Unit, Boston, MA 02114 USA. [Thompson, B. T.] Harvard Univ, Sch Med, Boston, MA USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Med Intens Care Unit, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM tthompson1@partners.org NR 56 TC 24 Z9 30 U1 0 U2 2 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD JUN PY 2010 VL 76 IS 6 BP 441 EP 447 PG 7 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA 602AR UT WOS:000278111000010 PM 20473257 ER PT J AU Brown, IS Whiteman, DC Lauwers, GY AF Brown, Ian S. Whiteman, David C. Lauwers, Gregory Y. TI Foveolar type dysplasia in Barrett esophagus SO MODERN PATHOLOGY LA English DT Article DE foveolar dysplasia; Barrett esophagus; intestinal metaplasia ID COLUMNAR-LINED ESOPHAGUS; INTESTINAL METAPLASIA; ESOPHAGOGASTRIC JUNCTION; MUSCULARIS MUCOSAE; ADENOCARCINOMA; DIAGNOSIS; CDX2; EXPRESSION; EPITHELIUM; DIFFERENTIATION AB Adenocarcinoma of the lower esophagus and esophagogastric junction is increasing in incidence in Western countries. A metaplasia (Barrett esophagus)-dysplasia-carcinoma sequence induced by gastroesophageal reflux disease is established. Two patterns of Barrett dysplasias have been described-adenomatous (type 1) and non-adenomatous (type 2 or foveolar/hyperplastic type). Interestingly, little is known about non-adenomatous dysplasia. Esophagogastrectomy cases from 41 patients with glandular dysplasia with and without associated invasive adenocarcinoma of the lower esophagus were evaluated for expression of MUC2, MUC5AC, CDX2, villin, Ki67 and p53. Results were correlated with sub-classification of the dysplasia into morphologic patterns of adenomatous vs foveolar vs hybrid type. In addition, clinicopathological parameters including the presence and extent of background intestinal metaplasia were also evaluated. Foveolar type dysplasia was present in 46% of the cases and thus, was more common than adenomatous type or hybrid type (both similar to 27%) dysplasia. Immunohistochemistry confirmed the histological stratification in all cases. Foveolar type dysplasia commonly expressed MUC5AC (P<0.12) but was consistently negative for markers of intestinal differentiation, MUC2, CDX2 and villin (all P<0.01). By contrast, adenomatous type dysplasia frequently displayed intestinal differentiation markers (all P<0.0001) Hybrid-type dysplasia was similar to adenomatous type dysplasia in showing expression of intestinal differentiation markers (P<0.01) and therefore could not be sustained as a separate category. In conclusion, our study provides evidence for a non intestinal pathway to neoplastic development in Barrett esophagus, that is, gastric metaplasia-foveolar dysplasia-adenocarcinoma. Modern Pathology (2010) 23, 834-843; doi:10.1038/modpathol.2010.59; published online 12 March 2010 C1 [Brown, Ian S.] Sullivan Nicolaides Pathol, Brisbane, Qld, Australia. [Brown, Ian S.] Royal Brisbane & Womens Hosp Brisbane, Brisbane, Qld, Australia. [Whiteman, David C.] Queensland Inst Med Res, Div Populat Studies & Human Genet, Brisbane, Qld 4006, Australia. [Whiteman, David C.] Queensland Inst Med Res, Div Canc & Cell Biol, Brisbane, Qld 4006, Australia. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brown, IS (reprint author), Sullivan Nicolaides Pathol, Dept Histopathol, 134 Whitmore St Taringa, Indooroopilly, Qld 4068, Australia. EM ian_brown@snp.com.au RI Whiteman, David/P-2728-2014; Brown, Ian/R-7763-2016 OI Whiteman, David/0000-0003-2563-9559; Brown, Ian/0000-0001-6329-2547 FU Cancer Council Queensland; National Health and Medical Research Council (NHMRC) of Australia [199600]; NHMRC FX This study was supported by grants the Cancer Council Queensland and the National Health and Medical Research Council (NHMRC) of Australia (Program no. 199600). David C Whiteman is a Principal Research Fellow funded by the NHMRC. The funding bodies had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; or preparation, review or approval of the article. The Australian Cancer Study Chief Investigators are David C Whiteman MBBS, PhD, Penelope M Webb MA, D Phil, Adele C Green MBBS, PhD, Nicholas K Hayward PhD, Peter G Parsons PhD, David M Purdie PhD. NR 47 TC 29 Z9 31 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUN PY 2010 VL 23 IS 6 BP 834 EP 843 DI 10.1038/modpathol.2010.59 PG 10 WC Pathology SC Pathology GA 604GG UT WOS:000278266800008 PM 20228780 ER PT J AU Kashiwagi, A Schipani, E Fein, MJ Greer, PA Shimada, M AF Kashiwagi, Aki Schipani, Ernestina Fein, Mikaela J. Greer, Peter A. Shimada, Masako TI Targeted Deletion of Capn4 in Cells of the Chondrocyte Lineage Impairs Chondrocyte Proliferation and Differentiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CALPAIN SMALL-SUBUNIT; HORMONE-RELATED PEPTIDE; PROTEIN-KINASE; PARATHYROID-HORMONE; BONE-DEVELOPMENT; OSTEOBLAST LINEAGE; NUCLEAR EXPORT; CYCLE ARREST; MICE LACKING; MAP KINASE AB Calpains are calcium-dependent intracellular cysteine proteases, which include ubiquitously expressed mu- and m-calpains. Both calpains are heterodimers consisting of a large catalytic subunit and a small regulatory subunit. The calpain small subunit encoded by the gene Capn4 directly binds to the intracellular C-terminal tail of the receptor for the parathyroid hormone (PTH) and PTH-related peptide and modulates cellular functions in cells of the osteoblast lineage in vitro and in vivo. To investigate a physiological role of the calpain small subunit in cells of the chondrocyte lineage, we generated chondrocyte- specific Capn4 knockout mice. Mutant embryos had reduced chondrocyte proliferation and differentiation in embryonic growth plates compared with control littermates. In vitro analysis further revealed that deletion of Capn4 in cells of the chondrocyte lineage correlated with impaired cell cycle progression at the G(1)/S transition, reduced cyclin D gene transcription, and accumulated cell cycle proteins known as calpain substrates. Moreover, silencing of p27(Kip1) rescued an impaired cell growth phenotype in Capn4 knockdown cells, and reintroducing the calpain small subunit partially normalized cell growth and accumulated cyclin D protein levels in a dose-dependent manner. Collectively, our findings suggest that the calpain small subunit is essential for proper chondrocyte functions in embryonic growth plates. C1 [Kashiwagi, Aki; Schipani, Ernestina; Fein, Mikaela J.; Shimada, Masako] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Kashiwagi, Aki; Schipani, Ernestina; Fein, Mikaela J.; Shimada, Masako] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Greer, Peter A.] Queens Univ, Canc Res Inst, Kingston, ON K7L 3N6, Canada. RP Shimada, M (reprint author), 50 Blossom St,Thier 10, Boston, MA 02114 USA. EM shimada@helix.mgh.harvard.edu FU National Institutes of Health [R01DK072102]; Canadian Institute of Health Research [MOP-81189] FX This work was supported by grants from the National Institutes of Health Grant R01DK072102 (M.S.) and the Canadian Institute of Health Research MOP-81189 (P.A.G.). NR 53 TC 19 Z9 21 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2010 VL 30 IS 11 BP 2799 EP 2810 DI 10.1128/MCB.00157-10 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 594SQ UT WOS:000277558300018 PM 20368361 ER PT J AU Yamamura, S Kawakami, K Hirata, H Ueno, K Saini, S Majid, S Dahiya, R AF Yamamura, Soichiro Kawakami, Kazumori Hirata, Hiroshi Ueno, Koji Saini, Sharanjot Majid, Shahana Dahiya, Rajvir TI Oncogenic Functions of Secreted Frizzled-Related Protein 2 in Human Renal Cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID FREQUENT EPIGENETIC INACTIVATION; COLORECTAL-CANCER; BETA-CATENIN; BREAST-CANCER; WNT PROTEINS; BCL2 FAMILY; SFRP2 GENE; FECAL DNA; CYCLIN-E; APOPTOSIS AB The secreted Frizzled-related proteins (sFRP) are modulators of the Wnt signaling pathway, which is involved in embryonic development and tumor progression. The functions of sFRP2 have not been studied in renal cancer. Transient transfection of sFRP2 promoted cell growth in renal carcinoma cells, whereby the largest effect was observed in A498 cells. To further study the functions of sFRP2 gene in renal carcinoma cells, we established A498 renal cancer cell lines, which stably expressed sFRP2. Stably expressed sFRP2 significantly promoted cell proliferation in vitro and in vivo tumor growth. The stably expressed sFRP2 cells were also found to have reduced UV-induced apoptosis and increased G(2) phase of the cell cycle. The phosphorylation level at Ser(33/37)/Thr(41) of beta-catenin was lower in the stable sFRP2 cell lines compared with the control cell line. sFRP2 significantly activated T-cell factor/lymphoid enhancer factor transcriptional activity. In the stable sFRP2 cell line, expression of c-Fos, Bcl2, Bcl-w, cyclin B2, and cyclin E2 genes was significantly increased and p53 expression was decreased. This is the first report documenting that sFRP2 activates the canonical Wnt pathway and promotes cell growth by evoking diverse signaling cascades in renal cancer cells. This study may provide better strategies for the management of renal cancer through regulation of sFRP2 pathways. Mol Cancer Ther; 9(6); 1680-7. (C)2010 AACR. C1 San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Dahiya, R (reprint author), Vet Affairs Med Ctr, Urol Res Ctr 112F, 4150 Clement St, San Francisco, CA 94121 USA. EM rdahiya@urology.ucsf.edu FU NIH [RO1CA130860, T32DK007790]; Veterans Affairs Research Enhancement Award Program; Veterans Affairs Merit Review FX Grant Support; NIH grants RO1CA130860 (S. Yamamura, K. Kawakami, H. Hirata, K. Ueno, and R. Dahiya) and T32DK007790 (S. Saini, S. Majid, and R. Dahiya), Veterans Affairs Research Enhancement Award Program (R. Dahiya), and Veterans Affairs Merit Review (R. Dahiya). NR 37 TC 19 Z9 19 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUN PY 2010 VL 9 IS 6 BP 1680 EP 1687 DI 10.1158/1535-7163.MCT-10-0012 PG 8 WC Oncology SC Oncology GA 608FS UT WOS:000278569200020 PM 20501806 ER PT J AU Mok, GSP Du, Y Wang, YC Frey, EC Tsui, BMW AF Mok, Greta S. P. Du, Yong Wang, Yuchuan Frey, Eric C. Tsui, Benjamin M. W. TI Development and Validation of a Monte Carlo Simulation Tool for Multi-Pinhole SPECT SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Monte Carlo simulation; SPECT; Multi-pinhole; SimSET; MCNP ID SMALL ANIMAL SPECT; GEOMETRIC TRANSFER-FUNCTION; ULTRA-HIGH-RESOLUTION; COMPENSATION METHODS; MYOCARDIAL SPECT; BEAM COLLIMATORS; GATE; PET; OPTIMIZATION; TOMOGRAPHY AB In this work, we developed and validated a Monte Carlo simulation (MCS) tool for investigation and evaluation of multi-pinhole (MPH) SPECT imaging. This tool was based on a combination of the SimSET and MCNP codes. Photon attenuation and scatter in the object, as well as penetration and scatter through the collimator detector, are modeled in this tool. It allows accurate and efficient simulation of MPH SPECT with focused pinhole apertures and user-specified photon energy, aperture material, and imaging geometry. The MCS method was validated by comparing the point response function (PRF), detection efficiency (DE), and image profiles obtained from point sources and phantom experiments. A prototype single-pinhole collimator and focused four- and five-pinhole collimators fitted on a small animal imager were used for the experimental validations. We have also compared computational speed among various simulation tools for MPH SPECT, including SimSET-MCNP, MCNP, SimSET-GATE, and GATE for simulating projections of a hot sphere phantom. We found good agreement between the MCS and experimental results for PRF, DE, and image profiles, indicating the validity of the simulation method. The relative computational speeds for SimSET-MCNP, MCNP, SimSET-GATE, and GATE are 1: 2.73: 3.54: 7.34, respectively, for 120-view simulations. We also demonstrated the application of this MCS tool in small animal imaging by generating a set of low-noise MPH projection data of a 3D digital mouse whole body phantom. The new method is useful for studying MPH collimator designs, data acquisition protocols, image reconstructions, and compensation techniques. It also has great potential to be applied for modeling the collimator-detector response with penetration and scatter effects for MPH in the quantitative reconstruction method. C1 [Mok, Greta S. P.] Chinese Univ Hong Kong, Dept Diagnost Radiol & Organ Imaging, Shatin, Hong Kong, Peoples R China. [Du, Yong; Frey, Eric C.; Tsui, Benjamin M. W.] Johns Hopkins Univ, Div Med Imaging Phys, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Wang, Yuchuan] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mok, GSP (reprint author), Chinese Univ Hong Kong, Dept Diagnost Radiol & Organ Imaging, Shatin, Hong Kong, Peoples R China. EM gretamok@cuhk.edu.hk OI Wang, Yuchuan/0000-0001-5111-6562 FU US Public Health Service [EB001558] FX The authors wish to thank Mr. Si Chen from Division of Medical Imaging Physics at the Johns Hopkins University, and Dr. Chia-Lin Chen from Chung Shan Medical University for their help on the GATE and SimSET-GATE simulations. This work was supported by the US Public Health Service Grant EB001558. NR 35 TC 4 Z9 4 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD JUN PY 2010 VL 12 IS 3 BP 295 EP 304 DI 10.1007/s11307-009-0263-7 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592JO UT WOS:000277375300008 PM 19779896 ER PT J AU Szilagyi, A Banlaki, Z Pozsonyi, E Yunis, EJ Awdeh, ZL Hosso, A Rajczy, K Larsen, CE Fici, DA Alper, CA Fust, G AF Szilagyi, Agnes Banlaki, Zsofia Pozsonyi, Eva Yunis, Edmond J. Awdeh, Zuheir L. Hosso, Adrienn Rajczy, Katalin Larsen, Charles E. Fici, Dolores A. Alper, Chester A. Fuest, George TI Frequent occurrence of conserved extended haplotypes (CEHs) in two Caucasian populations SO MOLECULAR IMMUNOLOGY LA English DT Article DE Conserved extended haplotype; MHC; HLA; Complotype; family study ID MAJOR HISTOCOMPATIBILITY COMPLEX; TUMOR-NECROSIS-FACTOR; LINKAGE-DISEQUILIBRIUM MAP; MHC HAPLOTYPES; HLA HAPLOTYPES; RAGE GENE; DISEASE; POLYMORPHISMS; ASSOCIATION; REGION AB Conserved extended haplotypes (CEHs) are large (>= 1 Mb) regions of identical DNA of the major histocompatibility complex (MHC) region of chromosome 6p in unrelated individuals. They are recognized by family studies and constitute nearly half of MHC haplotypes among European Caucasians. We studied 49 Hungarian Caucasian families in comparison with the previous findings in 2675 normal American Caucasian chromosomes from families in the Boston area. Besides HLA-A, -B and HLA-DRB1/-DQB1 alleles, copy number polymorphism of C4A and C4B genes and several SNPs encoded in the central (class III) MHC region were determined. By comparing 188 Caucasian haplotypes in Hungary to 2675 normal Caucasian chromosomes in Boston, we found that 11 of 12 of the most common CEHs (with a frequency of at least 1%) among the Boston chromosomes also occurred in Hungary. Moreover, there was a significant correlation (R = 0.789: p = 0.0023) in the frequency order of these haplotypes between the two Caucasian populations. Of 10 haplotypes found in >= 2 copies among the Hungarian chromosomes, all but one occurred in one to 14 copies among the Boston haplotypes. These findings indicate that CEHs are commonly shared by distinct European Caucasian populations; however, lower frequency CEHs may differ. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Szilagyi, Agnes; Banlaki, Zsofia; Fuest, George] Semmelweis Univ, Hungarian Acad Sci, Res Grp Inflammat Biol & Immungenom, Budapest, Hungary. [Pozsonyi, Eva; Hosso, Adrienn; Rajczy, Katalin] Natl Blood Transfus Serv, Dept Immunogenet, Budapest, Hungary. [Yunis, Edmond J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Awdeh, Zuheir L.; Larsen, Charles E.; Fici, Dolores A.; Alper, Chester A.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Larsen, Charles E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Alper, Chester A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Awdeh, Zuheir L.; Fici, Dolores A.] Pulsar Clin Technol Inc, Cambridge, MA 02138 USA. RP Fust, G (reprint author), Semmelweis Univ, Hungarian Acad Sci, Res Grp Inflammat Biol & Immungenom, Budapest, Hungary. EM fustge@kut.sote.hu RI Szilagyi, Agnes/F-2337-2010 FU National Office for Research and Technology, Hungary; Hungarian Research Fund [OTKA T049266, OTKA NF72689, OTKA K 73247]; Juvenile Diabetes Research Foundation [1-2008-472]; National Institutes of Health, USA [HL 29583, AM 26844, HD 17461] FX We are greatly indebted to the study participants. This study was supported by the National Office for Research and Technology, Hungary, the OTKA T049266 (GF), the OTKA NF72689 (ZP) and OTKA K 73247 grants of the Hungarian Research Fund (ZP) and a grant from the Juvenile Diabetes Research Foundation (1-2008-472) and former grants HL 29583, AM 26844 and HD 17461 from the National Institutes of Health, USA. NR 29 TC 7 Z9 7 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUN PY 2010 VL 47 IS 10 BP 1899 EP 1904 DI 10.1016/j.molimm.2010.03.013 PG 6 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 609FI UT WOS:000278640800004 PM 20409590 ER PT J AU Lage, K Mollgard, K Greenway, S Wakimoto, H Gorham, JM Workman, CT Bendsen, E Hansen, NT Rigina, O Roque, FS Wiese, C Christoffels, VM Roberts, AE Smoot, LB Pu, WT Donahoe, PK Tommerup, N Brunak, S Seidman, CE Seidman, JG Larsen, LA AF Lage, Kasper Mollgard, Kjeld Greenway, Steven Wakimoto, Hiroko Gorham, Joshua M. Workman, Christopher T. Bendsen, Eske Hansen, Niclas T. Rigina, Olga Roque, Francisco S. Wiese, Cornelia Christoffels, Vincent M. Roberts, Amy E. Smoot, Leslie B. Pu, William T. Donahoe, Patricia K. Tommerup, Niels Brunak, Soren Seidman, Christine E. Seidman, Jonathan G. Larsen, Lars A. TI Dissecting spatio-temporal protein networks driving human heart development and related disorders SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE genetics; organ developmental networks; polygenic common disorders; proteomics; systems biology ID GENE REGULATORY NETWORKS; CAENORHABDITIS-ELEGANS; EXPRESSION; MUTATIONS; EVOLUTION; DISEASE; BIOLOGY; SEGMENTATION; MODULARITY; COMPLEXES AB Aberrant organ development is associated with a wide spectrum of disorders, from schizophrenia to congenital heart disease, but systems-level insight into the underlying processes is very limited. Using heart morphogenesis as general model for dissecting the functional architecture of organ development, we combined detailed phenotype information from deleterious mutations in 255 genes with high-confidence experimental interactome data, and coupled the results to thorough experimental validation. Hereby, we made the first systematic analysis of spatio-temporal protein networks driving many stages of a developing organ identifying several novel signaling modules. Our results show that organ development relies on surprisingly few, extensively recycled, protein modules that integrate into complex higher-order networks. This design allows the formation of a complicated organ using simple building blocks, and suggests how mutations in the same genes can lead to diverse phenotypes. We observe a striking temporal correlation between organ complexity and the number of discrete functional modules coordinating morphogenesis. Our analysis elucidates the organization and composition of spatio-temporal protein networks that drive the formation of organs, which in the future may lay the foundation of novel approaches in treatments, diagnostics, and regenerative medicine. Molecular Systems Biology 6: 381; published online 22 June 2010; doi:10.1038/msb.2010.36 C1 [Lage, Kasper; Donahoe, Patricia K.] Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Surg Res Labs, Boston, MA 02114 USA. [Greenway, Steven; Wakimoto, Hiroko; Gorham, Joshua M.; Seidman, Christine E.; Seidman, Jonathan G.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Lage, Kasper; Donahoe, Patricia K.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Lage, Kasper; Workman, Christopher T.; Hansen, Niclas T.; Rigina, Olga; Roque, Francisco S.; Brunak, Soren] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Lage, Kasper; Roque, Francisco S.; Brunak, Soren] Univ Copenhagen, Ctr Prot Res, Copenhagen, Denmark. [Mollgard, Kjeld] Univ Copenhagen, Dept Cellular & Mol Med, Dev Biol Unit, Copenhagen, Denmark. [Bendsen, Eske] Odense Univ Hosp, Dept Obstet & Gynaecol, Fertil Clin, DK-5000 Odense, Denmark. [Wiese, Cornelia; Christoffels, Vincent M.] Univ Amsterdam, Acad Med Ctr, Ctr Heart Failure Res, NL-1105 AZ Amsterdam, Netherlands. [Roberts, Amy E.] Partners HealthCare Ctr Genet & Genom, Boston, MA USA. [Roberts, Amy E.; Smoot, Leslie B.; Pu, William T.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Pu, William T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Larsen, Lars A.] Univ Copenhagen, Dept Cellular & Mol Med, Wilhelm Johannsen Ctr Funct Genome Res, Copenhagen, Denmark. RP Lage, K (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Lab, 185 Cambridge St, Boston, MA 02114 USA. EM lage.kasper@mgh.harvard.edu; larsal@sund.ku.dk RI Workman, Christopher/K-1066-2015 OI Workman, Christopher/0000-0002-2210-3743 FU Danish Heart Foundation; Villum Kann Rasmussen Foundation; Novo Nordisk Foundation; Forskningsradet for Sundhed og Sygdom; NICHD [HD055150-03] FX We thank Christine Kocks, Barbara Pober, Chris Cotsapas, Josh Korn, Soumya Raychaudhuri, Ben Voight, Gerasimos Sykiotis, and Lars Juhl Jensen for critical discussions. We are also grateful to the Charles Lee laboratory for discussions and input on the project and results. This work was supported by The Danish Heart Foundation, the Villum Kann Rasmussen Foundation, and The Novo Nordisk Foundation. Wilhelm Johannsen Centre for Functional Genome Research is established by the Danish National Research Foundation. KL is supported by a grant from 'Forskningsradet for Sundhed og Sygdom'; and KL and PKD are supported by NICHD RO1 grant HD055150-03. We thank Lillian Rasmussen and Kirsten Winther for technical assistance. NR 37 TC 47 Z9 48 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD JUN PY 2010 VL 6 AR 381 DI 10.1038/msb.2010.36 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622CH UT WOS:000279636000011 PM 20571530 ER EF