FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Podar, K Tai, YT Hideshima, T Vallet, S Richardson, PG Anderson, KC AF Podar, Klaus Tai, Yu-Tzu Hideshima, Teru Vallet, Sonia Richardson, Paul G. Anderson, Kenneth C. TI Emerging therapies for multiple myeloma SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE bone marrow microenvironment; combination therapy; multiple myeloma ID NF-KAPPA-B; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; NEWLY-DIAGNOSED MYELOMA; LENALIDOMIDE PLUS DEXAMETHASONE; HISTONE DEACETYLASE INHIBITOR; PEGYLATED LIPOSOMAL DOXORUBICIN; FARNESYL TRANSFERASE INHIBITOR; OVERCOMES DRUG-RESISTANCE; ENDOTHELIAL GROWTH-FACTOR AB Multiple myeloma (MM) is a clonal plasma cell malignancy clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. There are an estimated 750,000 people diagnosed with MM worldwide, with a median overall survival of 3 - 5 years. Besides chromosomal aberrations, translocations, and mutations in essential growth and tumor-suppressor genes, accumulating data strongly highlight the pathophysiologic role of the bone marrow (BM) microenvironment in MM pathogenesis. Based on this knowledge, several novel agents have been identified, and treatment options in MM have fundamentally changed during the last decade. Thalidomide, bortezomib, and lenalidomide have been incorporated into conventional cytotoxic and transplantation regimens, first in relapsed and refractory and now also in newly diagnosed MM. Despite these significant advances, there remains an urgent need for more efficacious and tolerable drugs. Indeed, a plethora of preclinical agents awaits translation from the bench to the bedside. This article reviews the scientific rationale of new therapy regimens and newly identified therapeutic agents - small molecules as well as therapeutic antibodies - that hold promise to further improve outcome in MM. C1 [Podar, Klaus; Tai, Yu-Tzu; Hideshima, Teru; Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. [Vallet, Sonia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Multiple Myeloma, Boston, MA 02115 USA. RP Podar, K (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu FU Multiple Myeloma Research Foundation; National Institutes of Health [IP50 CA100707, PO-1 78378, RO-1 CA 50947]; Myeloma Research Fund; LeBow Family Fund FX This work was supported by the Multiple Myeloma Research Foundation (IMF) Senior Research Grant Award and Dunkin' Donuts Rising Star Award (KP), International Myeloma Foundation (MMRF) Junior Research Grant Award (SV) as well as National Institutes of Health Grants IP50 CA100707, PO-1 78378, and RO-1 CA 50947; The Myeloma Research Fund; and the LeBow Family Fund to Cure Myeloma (KCA). NR 188 TC 25 Z9 26 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8214 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD MAR PY 2009 VL 14 IS 1 BP 99 EP 127 DI 10.1517/14728210802676278 PG 29 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 426CS UT WOS:000264685900007 PM 19249983 ER PT J AU Webb, TR Slavish, J George, RE Look, AT Xue, LQ Jiang, Q Cui, XL Rentrop, WB Morris, SW AF Webb, Thomas R. Slavish, Jake George, Rani E. Look, A. Thomas Xue, Liquan Jiang, Qin Cui, Xiaoli Rentrop, Walter B. Morris, Stephan W. TI Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE anaplastic large-cell lymphoma; anaplastic lymphoma kinase; esophageal squamous cell carcinoma; glioblastoma; inflammatory myofibroblastic tumor; midkine; neuroblastoma; non-small-cell lung carcinoma; pleiotrophin; targeted cancer therapy; tyrosine kinase inhibitor ID LARGE-CELL LYMPHOMA; INFLAMMATORY MYOFIBROBLASTIC TUMOR; RECEPTOR TYROSINE KINASE; NON-HODGKINS-LYMPHOMA; BINDING GROWTH-FACTOR; CHRONIC MYELOID-LEUKEMIA; CYTOREDUCTIVE ANTITUMOR-ACTIVITY; GASTROINTESTINAL STROMAL TUMORS; ALK PROTEIN EXPRESSION; CENTRAL-NERVOUS-SYSTEM AB Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase in the insulin receptor superfamily, was initially identified in constitutively activated oncogenic fusion forms-the most common being nucleophosmin-ALK - in anaplastic large-cell lymphomas, and subsequent studies have identified ALK fusions in diffuse large B-cell lymphomas, systemic histiocytosis, inflammatory myofibroblastic tumors, esophageal squamous cell carcinomas and non-small-cell lung carcinomas. More recently, genomic DNA amplification and protein overexpression, as well as activating point mutations, of ALK have been described in neuroblastomas. In addition to those cancers for which a causative role for aberrant ALK activity is well validated, more circumstantial links implicate the full-length, normal ALK receptor in the genesis of other malignancies-including glioblastoma and breast cancer-via a mechanism of receptor activation involving autocrine and/or paracrine growth loops with the reported ALK ligands, pleiotrophin and midkine. This review summarizes normal ALK biology, the confirmed and putative roles of ALK in the development of human cancers and efforts to target ALK using small-molecule kinase inhibitors. C1 [Xue, Liquan; Jiang, Qin; Cui, Xiaoli; Rentrop, Walter B.; Morris, Stephan W.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. [Xue, Liquan; Jiang, Qin; Cui, Xiaoli; Rentrop, Walter B.; Morris, Stephan W.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Webb, Thomas R.; Slavish, Jake] St Jude Childrens Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA. [George, Rani E.; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Morris, SW (reprint author), St Jude Childrens Hosp, Dept Pathol, Thomas Tower,Room 4026,Mail Stop 343,262 Danny Th, Memphis, TN 38105 USA. EM steve.morris@stjude.org RI Webb, Thomas/J-4511-2013 FU NIH [R01 CA69129]; Cancer Center CORE [CA21765]; American Lebanese Syrian Associated Charities, St Jude Children's Research Hospital FX Thomas R Webb is a coinventor on patents that describe the synthesis and characterization of anaplastic lymphoma kinase (ALK) small-molecule inhibitors designed by ChemBridge Research Laboratories. A Thomas Look and Stephan W Morris are coinventors on patents concerned with the discovery of ALK, the use of methods to detect ALK for diagnostic purposes, and the targeting of ALK for therapeutic indications. Studies cited in this review performed in the authors' laboratories were supported in part by NIH grants R01 CA69129 (Stephan Morris) and Cancer Center CORE grant CA21765, and by the American Lebanese Syrian Associated Charities, St Jude Children's Research Hospital. 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 230 TC 111 Z9 113 U1 0 U2 12 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD MAR PY 2009 VL 9 IS 3 BP 331 EP 356 DI 10.1586/14737140.9.3.331 PG 26 WC Oncology SC Oncology GA 423JW UT WOS:000264493600013 PM 19275511 ER PT J AU Chowdhury, S Choueiri, TK AF Chowdhury, Simon Choueiri, Toni K. TI Recent advances in the systemic treatment of metastatic papillary renal cancer SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE erlotinib; kinase inhibitor; MET; papillary renal carcinoma; sorafenib; sunitinib; temsirolimus; VEGF ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; TUMOR-SUPPRESSOR GENE; CELL CARCINOMA; CLEAR-CELL; ANTITUMOR-ACTIVITY; HISTOLOGIC SUBTYPES; MET PROTOONCOGENE; INTERFERON-ALPHA; TARGETED THERAPY AB Renal cell carcinoma (RCC) encompasses a heterogeneous group of histological subtypes, of which clear cell RCC (CCRCC) is the most common, comprising more than 70% of all cases. Papillary RCC (PRCC) is the next most common, comprising 10-15% of cases. PRCC is refractory to chemotherapy, immunotherapy and hormonal therapy. Recent improvements in our understanding of the molecular biology of CCRCC have identified multiple pathways associated with the development of this cancer. This has led to drug development targeting these pathways, including the small molecule tyrosine kinase inhibitors sunitinib and sorafenib, the monoclonal antibody bevacizumab and the mTOR inhibitor temsirolimus. These drugs have shown significant clinical benefits in randomized trials of advanced CCRCC and have become the standard of care for most patients. However, since these trials were, on the whole, restricted to patients with clear cell histology, their efficacy in patients with non-clear cell RCC, and particularly PRCC, is unclear. This review will focus on the activity of these targeted agents in the treatment of metastatic PRCC. C1 [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. [Chowdhury, Simon] Guys Hosp, Dept Med Oncol, London SE1 9RT, England. RP Choueiri, TK (reprint author), Harvard Univ, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst,Sch Med, 44 Binney St, Boston, MA 02115 USA. EM toni_choueiri@dfci.harvard.edu NR 49 TC 19 Z9 22 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD MAR PY 2009 VL 9 IS 3 BP 373 EP 379 DI 10.1586/14737140.9.3.373 PG 7 WC Oncology SC Oncology GA 423JW UT WOS:000264493600016 PM 19275514 ER PT J AU Almulki, L Noda, K Amini, R Schering, A Garland, RC Nakao, S Nakazawa, T Hisatomi, T Thomas, KL Masli, S Hafezi-Moghadam, A AF Almulki, Lama Noda, Kousuke Amini, Reza Schering, Alexander Garland, Rebecca C. Nakao, Shintaro Nakazawa, Toru Hisatomi, Toshio Thomas, Kennard L. Masli, Sharmila Hafezi-Moghadam, Ali TI Surprising up-regulation of P-selectin glycoprotein ligand-1 (PSGL-1) in endotoxin-induced uveitis SO FASEB JOURNAL LA English DT Article DE leukocyte rolling velocity; autoperfused micro-flow chamber; lipopolysaccharides; adhesion molecules; acute immune response ID ROLLING IN-VIVO; ISCHEMIA/REPERFUSION INJURY; OCULAR INFLAMMATION; ENDOTHELIAL INTERACTIONS; MONOCLONAL-ANTIBODIES; ADHESION MOLECULES; RAT-KIDNEY; LEUKOCYTE; INHIBITION; NEUTROPHILS AB P-selectin glycoprotein ligand-1 (PSGL-1) is constitutively expressed on leukocytes and was thought to be down-regulated with cell activation. However, this work shows the surprising finding of functional PSGL-1 up-regulation during acute inflammation. PSGL-1 function was studied in our autoperfusion assay, in which blood from a mouse carotid flows through a microchamber coated with a fixed density of P-selectin. Under the inflammatory conditions-uveitis induced by systemic lipopolysaccharide injection-we recorded significantly reduced leukocyte rolling velocity, which suggests PSGL-1 up-regulation; however, flow cytometry showed reduced PSGL-1. When bound leukocytes were released from the vasculature by PSGL-1 blockade, a large peripheral blood leukocyte (PBL) population showed elevated PSGL-1, which could account for the reduced PSGL-1 in the remaining unbound population. In the eye, systemic blockade of PSGL-1 with a monoclonal antibody or recombinant soluble PSGL-1 drastically reduced the severe manifestations of uveitis. Furthermore, PSGL-1 blockade was significantly more effective in reducing retinal leukostasis than was P-selectin blockade. Our results provide surprising evidence for functional PSGL-1 up-regulation in PBLs during acute inflammation. The temporal overlap between PSGL-1 and P-selectin up-regulation reveals an as yet unrecognized collaboration between this receptor-ligand pair, increasing efficiency of the first steps of the leukocyte recruitment cascade.-Almulki, L., Noda, K., Amini, R., Schering, A., Garland, R. C., Nakao, S., Nakazawa, T., Hisatomi, T., Thomas, K. L., Masli, S., Hafezi-Moghadam, A. Surprising up-regulation of P-selectin glycoprotein ligand-1 (PSGL-1) in endotoxin-induced uveitis. FASEB J. 23, 929-939 (2009) C1 [Almulki, Lama; Noda, Kousuke; Amini, Reza; Schering, Alexander; Garland, Rebecca C.; Nakao, Shintaro; Nakazawa, Toru; Hisatomi, Toshio; Thomas, Kennard L.; Hafezi-Moghadam, Ali] Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. [Almulki, Lama; Noda, Kousuke; Amini, Reza; Schering, Alexander; Garland, Rebecca C.; Nakao, Shintaro; Nakazawa, Toru; Hisatomi, Toshio; Thomas, Kennard L.; Masli, Sharmila; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Masli, Sharmila] Schepens Eye Res Inst, Boston, MA USA. RP Hafezi-Moghadam, A (reprint author), Massachusetts Eye & Ear Infirm, Angiogenesis Lab, 325 Cambridge St,3rd Floor, Boston, MA 02114 USA. EM ali_hafezi-moghadam@meei.harvard.edu OI Hisatomi, Toshio/0000-0003-2552-9595; Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU U. S. National Institue of Health [HL086933, AI050775]; National Eye Institute [EY14104] FX We are grateful to Dr. P. Cheung, Director of Preclinical Research and Discovery at Y's Therapeutics for graciously providing research- grade YSPSL (recombinant soluble Pselectin glycoprotein ligand IgG fusion protein, rPSGL-Ig). The authors thank Dr. S. E. Leeman for a critical review of the manuscript and R. Huang for his assistance with flow cytometry. This work was supported by U. S. National Institue of Health grants (HL086933, AI050775) and a National Eye Institute core grant (EY14104). We are indebted to the Massachusetts Lions Foundation for generous funds provided for laboratory equipment used in this project. We thank Research to Prevent Blindness for unrestricted funds awarded to the Department of Ophthalmology at Harvard Medical School. We are grateful to the Marion W. and Edward F. Knight Fund for support of A. H.-M.'s research. NR 43 TC 9 Z9 9 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 2009 VL 23 IS 3 BP 929 EP 939 DI 10.1096/fj.08-118760 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 437SD UT WOS:000265506300028 PM 19050046 ER PT J AU Shimazaki, K Chan, AM Moniz, RJ Wadehra, M Nagy, A Coulam, CP Mareninov, S Lepin, EM Wu, AM Kelly, KA Braun, J Gordon, LK AF Shimazaki, Kaori Chan, Ann M. Moniz, Raymond J. Wadehra, Madhuri Nagy, Agnes Coulam, Catherine P. Mareninov, Sergey Lepin, Eric M. Wu, Anna M. Kelly, Kathleen A. Braun, Jonathan Gordon, Lynn K. TI Blockade of epithelial membrane protein 2 (EMP2) abrogates infection of Chlamydia muridarum murine genital infection model SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE Chlamydia muridarum; epithelial membrane protein 2 (EMP2); infection; antibody therapy ID TRACHOMATIS INFECTION; HEPARAN-SULFATE; TRACT INFECTION; SURFACE EXPRESSION; FIELD TRIAL; CELLS; MICE; VACCINE; MOUSE; GLYCOSAMINOGLYCAN AB New methods are needed to eradicate or prevent Chlamydia trachomatis infections. Blockade of epithelial membrane protein 2 (EMP2) by genetic silencing or neutralizing polyclonal antibody reduced chlamydial infectivity in vitro. This study tests the prediction that recombinant anti-EMP2 diabody could reduce early chlamydial infection of the genital tract in vivo. In a murine infection model, pretreatment with anti-EMP2 diabody, as compared with control diabody, significantly reduced bacterial load, tissue production of inflammatory cytokines, recruitment of polymorphonuclear leukocytes, and local tissue inflammation. These findings support EMP2 as a potential preventative and therapeutic target for genital chlamydial infection. C1 [Gordon, Lynn K.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Shimazaki, Kaori; Braun, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Biol, Los Angeles, CA 90095 USA. [Chan, Ann M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol Sci, Los Angeles, CA 90095 USA. [Moniz, Raymond J.; Wadehra, Madhuri; Nagy, Agnes; Coulam, Catherine P.; Mareninov, Sergey; Kelly, Kathleen A.; Braun, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Lepin, Eric M.; Wu, Anna M.; Braun, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM lgordon@ucla.edu FU NIH [CA86306, CA009120, 2-T32-AI-07323, AI026328, CA016042]; Iris Cantor Foundation; Giannini Family Foundation; Oppenheimer Family Foundation FX This work was supported by NIH CA86306 (A.M.W., J.B.), CA009120 (M.W.), 2-T32-AI-07323 (K.S.), AI026328 (K.K.), and CA016042 (UCLA Jonsson Comprehensive Cancer Center flow cytometry core); Iris Cantor Foundation (M.W.); the Giannini Family Foundation (M.W.); the Oppenheimer Family Foundation Grant - Center for the Prevention of Eye Disease (L.K.G., J.B.); and Richard and Barbara Braun. We are grateful to Dr Harlan Caldwell for gift of reagent (anti-Chlamydia lipopolysaccharide mouse antibody) and also thank Dr Wei Bo for helpful comments. NR 40 TC 4 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD MAR PY 2009 VL 55 IS 2 BP 240 EP 249 DI 10.1111/j.1574-695X.2008.00525.x PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 404EM UT WOS:000263133600016 PM 19159428 ER PT J AU de Jong-Curtain, TA Parslow, AC Trotter, AJ Hall, NE Verkade, H Tabone, T Christie, EL Crowhurst, MO Layton, JE Shepherd, IT Nixon, SJ Parton, RG Zon, LI Stainier, DYR Lieschke, GJ Heath, JK AF de Jong-Curtain, Tanya A. Parslow, Adam C. Trotter, Andrew J. Hall, Nathan E. Verkade, Heather Tabone, Tania Christie, Elizabeth L. Crowhurst, Meredith O. Layton, Judith E. Shepherd, Iain T. Nixon, Susan J. Parton, Robert G. Zon, Leonard I. Stainier, Didier Y. R. Lieschke, Graham J. Heath, Joan K. TI Abnormal Nuclear Pore Formation Triggers Apoptosis in the Intestinal Epithelium of elys-Deficient Zebrafish SO GASTROENTEROLOGY LA English DT Article ID DIGESTIVE ORGANS; TARGETED DISRUPTION; CHROMATIN; EXPRESSION; ENVELOPE; SYSTEM; MORPHOGENESIS; COMPLEX; DIFFERENTIATION; EXPANSION AB Background & Aims: Zebrafish mutants generated by ethylnitrosourea-mutagenesis provide a powerful toot for dissecting the genetic regulation of developmental processes, including organogenesis. One zebrafish mutant, "flotte lotte" (flo), displays striking defects in intestinal, liver, pancreas, and eye formation at 78 hours postfertilization (hpf). In this study, we sought to identify the underlying mutated gene in flo and link the generic lesion to its phenotype. Methods: Positional cloning was employed to map the flo mutation. Subcellular characterization of flo embryos was achieved using histology, immunocytochemistry, bromodeoxyuridine incorporation analysis, and confocal and electron microscopy. Results: The molecular lesion in flo is a nonsense mutation in the elys (embryonic large molecule derived from yolk sac) gene, which encodes a severely truncated protein lacking the Elys C-terminal AT-hook DNA binding domain. Recently, the human ELYS protein has been shown to play a critical, and hitherto unsuspected, role in nuclear pore assembly. Although elys messenger RNA (mRNA) is expressed broadly during early zebrafish development, widespread early defects in flo are circumvented by the persistence of maternally expressed elys mRNA until 24 hpf From 72 hpf, elys mRNA expression is restricted to proliferating tissues, including the intestinal epithelium, pancreas, liver, and eye. Cells in these tissues display disrupted nuclear pore formation; ultimately, intestinal epithelial cells undergo apoptosis. Conclusions: Our results demonstrate that Elys regulates digestive organ formation. C1 [de Jong-Curtain, Tanya A.; Parslow, Adam C.; Trotter, Andrew J.; Hall, Nathan E.; Verkade, Heather; Tabone, Tania; Christie, Elizabeth L.; Crowhurst, Meredith O.; Heath, Joan K.] Royal Melbourne Hosp, Ludwig Inst Canc Res, Parkville, Vic 3050, Australia. [Layton, Judith E.; Lieschke, Graham J.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. [Shepherd, Iain T.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA. [Nixon, Susan J.; Parton, Robert G.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. [Nixon, Susan J.; Parton, Robert G.] Univ Queensland, Ctr Microscopy & Microanal, Brisbane, Qld, Australia. [Zon, Leonard I.] Childrens Hosp, Howard Hughes Med Inst, Dana Farber Canc Inst, Stem Cell Program, Boston, MA 02115 USA. [Zon, Leonard I.] Childrens Hosp, Howard Hughes Med Inst, Dana Farber Canc Inst, Div Hematol & Oncol, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Boston, MA USA. [Stainier, Didier Y. R.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. RP Heath, JK (reprint author), Post Off Royal Melbourne Hosp, Ludwig Inst Canc Res, Colon Mol & Cell Biol Lab, Parkville, Vic 3050, Australia. EM joan.heath@ludwig.edu.au RI Parton, Robert/C-5673-2009; Tabone, Tania/C-1660-2010; Heath, Joan/D-3054-2012; Verkade, Heather/J-2401-2013; OI Parton, Robert/0000-0002-7494-5248; Nixon, Susan/0000-0003-0346-9683; Heath, Joan/0000-0001-6955-232X; Verkade, Heather/0000-0002-2817-0509; Parslow, Adam Chalmers/0000-0002-9868-6914; Christie, Elizabeth/0000-0002-9959-7024 FU NHMRC Australia [280916, 433614]; NHMRC Dora Lush; NHMRC Howard Florey Centenary Fellowship; Australian Research Council [DP0346823]; NIH [DK 067285, K058181, DK060322] FX The authors disclose the following: Supported by NHMRC Australia project grants 280916 and 433614 (to J.K.H.); NHMRC Dora Lush (Biomedical) Scholarship (to T.A.D.J-C.); NHMRC Howard Florey Centenary Fellowship (to H.V.); Australian Research Council grant DP0346823 (to G.J.L.); and NIH grants DK 067285 (to I.T.S.), K058181, and DK060322 (to D.Y.R.S.). NR 31 TC 24 Z9 24 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2009 VL 136 IS 3 BP 902 EP 911 DI 10.1053/j.gastro.2008.11.012 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 412VD UT WOS:000263751400029 PM 19073184 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI How to choose a job after a GI fellowship (weighing family and city life against salary and research) SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material C1 Portland VA Med Ctr, Dept Gastroenterol, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Dept Gastroenterol, Portland, OR USA. NR 1 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 MAR PY 2009 VL 69 IS 3 BP 526 EP 529 DI 10.1016/j.gie.2008.11.053 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 416NF UT WOS:000264012100020 PM 19231493 ER PT J AU El Hajj, II Khalid, A Schoedel, KE Abu-Ehmagd, KM McGrath, KM Fasanella, KE AF El Hajj, Ihab I. Khalid, Asif Schoedel, Karen E. Abu-Ehmagd, Kareem M. McGrath, Kevin M. Fasanella, Kenneth E. TI EUS-guided FNA diagnosis of primary splenic lymphoma SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID FINE-NEEDLE-ASPIRATION; ENDOSCOPIC ULTRASOUND; VEIN-THROMBOSIS; NATURAL-HISTORY; BIOPSY; SPLEEN C1 [El Hajj, Ihab I.; Khalid, Asif; McGrath, Kevin M.; Fasanella, Kenneth E.] Univ Pittsburgh, Dept Med, Med Ctr, Pittsburgh, PA 15213 USA. [Schoedel, Karen E.] Univ Pittsburgh, Dept Pathol, Med Ctr, Pittsburgh, PA 15213 USA. [Abu-Ehmagd, Kareem M.] Univ Pittsburgh, Dept Surg, Med Ctr, Pittsburgh, PA 15213 USA. [Khalid, Asif] VA Pittsburgh Hlth Care Syst, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. RP Fasanella, KE (reprint author), Univ Pittsburgh, Dept Med, Med Ctr, 200 Lothrop St,Mezzanine Level 2,C Wing, Pittsburgh, PA 15213 USA. RI Fasanella, Kenneth/I-2781-2012 NR 12 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 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAR PY 2009 VL 69 IS 3 BP 585 EP 588 DI 10.1016/j.gie.2008.04.058 PN 1 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 416NF UT WOS:000264012100040 PM 19012888 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI How to overbook procedures in the endoscopy unit SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID NON-ATTENDANCE RATE; OUTPATIENT ENDOSCOPY; NONATTENDANCE; APPOINTMENTS; PATIENT AB Background: Because nonattendance of outpatients scheduled for GI endoscopy is unavoidable, a frequently recommended Solution involves overbooking patient appointments. Objective: To provide a set of numerical guidelines of how to overbook patients scheduled for endoscopy. Design: Cost-benefit analysis using stochastic modeling to estimate the total number of endoscopy appointments (including overbooking) that maximize the expected benefit from endoscopy. Patients: Subjects schecluled for GI endoscopy. Main Outcome Measurements: The number of endoscopies that should be scheduled under various scenarios of patient attendance rates, the number of available endoscopy slots, and the cost impact of missed appointments. Results: Overbooking can increase the expected benefit but never quite reaches the benefit that would be achieved, if all patients were perfectly reliable in meeting their scheduled appointments. The expected benefit of overbooking always comes to lie between the low benefit without overbooking and the high benefit associated with perfectly reliable patients. The less reliable the patient population, the more overbooking needs to take place. Overbooking should also expand with a decreasing cost impact of overbooked endoscopies. Overbooking is most beneficial in large endoscopy units. This article provides a table with a large set of numerical examples for different scenarios of overbooking that cover endoscopy units of diverse sizes and patient attendance rates. Limitations: The analysis does not take into account individual patient characteristics that may affect attendance rates. Conclusion: This analysis yields a set of estimates for overbooking that can be readily applied to a large variety of endocscopic units. (Gastrointest Endosc 2009;69:710-5.) C1 Portland VA Med Ctr, Dept Gastroenterol, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Dept Gastroenterol, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 17 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAR PY 2009 VL 69 IS 3 BP 710 EP 715 DI 10.1016/j.gie.2008.09.052 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 416NG UT WOS:000264012200018 PM 19251015 ER PT J AU Braun, MM Gurrera, RJ Karel, MJ Armesto, JC Moye, J AF Braun, Michelle M. Gurrera, Ronald J. Karel, Michele J. Armesto, Jorge C. Moye, Jennifer TI Are Clinicians Ever Biased in Their Judgments of the Capacity of Older Adults to Make Medical Decisions? SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID PHYSICIANS LEGAL STANDARD; MILD ALZHEIMERS-DISEASE; TO-MODERATE DEMENTIA; QUALITY-OF-LIFE; PERSONAL JUDGMENTS; INFORMED-CONSENT; MAKING CAPACITY; COMPETENCE; CONSISTENCY C1 [Braun, Michelle M.; Gurrera, Ronald J.] VA Boston Healthcare Syst, Mental Hlth Serv, Serious Mental Illness Treatment Programs, Boston, MA USA. [Braun, Michelle M.; Gurrera, Ronald J.] VA Boston Healthcare Syst, Mental Hlth Serv, Emergency & Consultat Serv, Boston, MA USA. [Karel, Michele J.; Armesto, Jorge C.; Moye, Jennifer] VA Boston Healthcare Syst, Mental Hlth Serv, Geriatr Mental Hlth, Boston, MA USA. [Karel, Michele J.; Armesto, Jorge C.; Moye, Jennifer] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Armesto, Jorge C.] Latino Psychol Inst Inc, Boston, MA USA. RP Braun, MM (reprint author), VA Boston Healthcare Syst, Mental Hlth Serv, Serious Mental Illness Treatment Programs, Boston, MA USA. EM jennifer.moye@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU NIA NIH HHS [P30 AG028717, P30 AG028717-02] NR 20 TC 6 Z9 6 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 SPR PY 2009 VL 33 IS 1 BP 78 EP 81 PG 4 WC Gerontology SC Geriatrics & Gerontology GA 639QY UT WOS:000280990600013 PM 21037935 ER PT J AU Kee, Y Kim, JM D'Andrea, A AF Kee, Younghoon Kim, Jung Min D'Andrea, Alan TI Regulated degradation of FANCM in the Fanconi anemia pathway during mitosis SO GENES & DEVELOPMENT LA English DT Article DE Fanconi anemia; FANCM; mitosis; beta-TRCP; Plk1; ubiquitin ID SCF-BETA-TRCP; ANAPHASE PROMOTING COMPLEX; UBIQUITIN-LIGASE COMPLEX; F-BOX PROTEINS; CORE COMPLEX; DNA-REPAIR; MONOUBIQUITINATED FANCD2; DEPENDENT DEGRADATION; CELL-CYCLE; S-PHASE AB The 13 Fanconi anemia (FA) proteins cooperate in a common DNA repair pathway. Eight of these proteins are assembled into a multisubunit E3 ligase called the FA core complex. During S phase, the FA core complex is loaded by the FANCM protein into chromatin where it monoubiquitinates its substrates. In mitosis, the FA core complex is released from FANCM by an unknown mechanism. Here we show that FANCM is hyper-phosphorylated and degraded during mitosis. beta-TRCP and Plk1 are the key regulators of FANCM degradation. Nondegradable mutant forms of FANCM retain the FA core complex in the chromatin and disrupt the FA pathway. Our data provide a novel mechanism for the cell cycle-dependent regulation of the FA pathway. C1 [Kee, Younghoon; Kim, Jung Min; D'Andrea, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP D'Andrea, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu FU NIH [RO1-HL52725, RO1-DK43889, PO1-HL54785]; Leukemia and Lymphoma Society Fellowship FX We thank Wade Harper for the beta-TRCP plasmids, Jan-Michael Peters for the Plk1 inhibitor, Stephan Jentsch for the His-ubiquitin-expressing plasmid, and Lisa Moreau for chromosomal breakage analysis. We thank members of the D'Andrea laboratory for helpful discussions. This work was supported by NIH grants RO1-HL52725, RO1-DK43889, and PO1-HL54785 to A. D. Y. K. is a recipient of a Leukemia and Lymphoma Society Fellowship. NR 48 TC 41 Z9 43 U1 1 U2 1 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 MAR 1 PY 2009 VL 23 IS 5 BP 555 EP 560 DI 10.1101/gad.1761309 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 415FA UT WOS:000263918500003 PM 19270156 ER PT J AU Eeckhoute, J Lupien, M Meyer, CA Verzi, MP Shivdasani, RA Liu, XS Brown, M AF Eeckhoute, Jerrome Lupien, Mathieu Meyer, Clifford A. Verzi, Michael P. Shivdasani, Ramesh A. Liu, X. Shirley Brown, Myles TI Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers SO GENOME RESEARCH LA English DT Article ID EMBRYONIC STEM-CELLS; GENOME-WIDE ANALYSIS; TISSUE-SPECIFIC ENHANCERS; ALPHA-BINDING-SITES; ESTROGEN-RECEPTOR; BREAST-CANCER; TRANSCRIPTION FACTORS; ANDROGEN RECEPTOR; GENE-EXPRESSION; CHIP-CHIP AB Selective activity of a specific set of enhancers defines tissue-specific gene transcription. The pioneer factor FOXA1 has been shown to induce functional enhancer competency through chromatin openings. We have previously found that FOXA1 is recruited to thousands of regions across the genome of a given cell type. Here, we monitored the chromatin structure at FOXA1 binding sites on a chromosome-wide scale using formaldehyde assisted isolation of regulatory elements (FAIRE). Surprisingly, we find that a significant fraction of FOXA1-bound sites have a relatively closed chromatin conformation linked to a shift of the epigenetic signature toward repressive histone marks. Importantly, these sites are not correlated with gene expression in a given cell type suggesting that FOXA1 is required, but not sufficient, for the functional activity of bound enhancers. Interestingly, we find that a significant proportion of the inactive FOXA1-bound regulatory sites in one cell type are actually functional in another cellular context. We found that at least half of the FOXA1 binding sites from a given cell type are shared with another cell lineage. Mechanisms that restrict the activity of shared FOXA1-bound enhancers likely play a significant role in defining the cell-type-specific functions of FOXA1. C1 [Lupien, Mathieu; Verzi, Michael P.; Shivdasani, Ramesh A.; Brown, Myles] Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02115 USA. [Eeckhoute, Jerrome] Univ Rennes 1, CNRS, UMR 6026, F-35042 Rennes, France. [Lupien, Mathieu; Verzi, Michael P.; Shivdasani, Ramesh A.; Brown, Myles] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Lupien, Mathieu; Verzi, Michael P.; Shivdasani, Ramesh A.; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Meyer, Clifford A.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Meyer, Clifford A.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu OI Brown, Myles/0000-0002-8213-1658; Eeckhoute, Jerome/0000-0002-7222-9264 FU Centre National de la Recherche Scientifique (CNRS); University of Rennes 1; NIDDK [R01DK074967]; NCI [P01 CA8011105]; DF/HCC Breast Cancer SPORE Grant FX The authors thank members of the SPARTE team for helpful discussions during the preparation of this manuscript. This work was supported by funds from the Centre National de la Recherche Scientifique (CNRS) and the University of Rennes 1 and by grants from the NIDDK (R01DK074967 to M. B.), the NCI (P01 CA8011105 and the DF/HCC Breast Cancer SPORE Grant to M. B.), and the DFCI Women's Cancers Program. NR 63 TC 71 Z9 73 U1 0 U2 2 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 MAR PY 2009 VL 19 IS 3 BP 372 EP 380 DI 10.1101/gr.084582.108 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 414EU UT WOS:000263847500003 PM 19129543 ER PT J AU Odinokova, IV Sung, KF Mareninova, OA Hermann, K Evtodienko, Y Andreyev, A Gukovsky, I Gukovskaya, AS AF Odinokova, I. V. Sung, K-F Mareninova, O. A. Hermann, K. Evtodienko, Y. Andreyev, A. Gukovsky, I. Gukovskaya, A. S. TI Mechanisms regulating cytochrome c release in pancreatic mitochondria SO GUT LA English DT Article ID PERMEABILITY TRANSITION PORE; OXYGEN SPECIES PRODUCTION; CELL-DEATH; ACINAR-CELLS; BRAIN MITOCHONDRIA; OXIDATIVE STRESS; MEMBRANE PERMEABILIZATION; ENZYME ACTIVATION; FREE-RADICALS; APOPTOSIS AB Background: Mechanisms of acinar cell death in pancreatitis are poorly understood. Cytochrome c release is a central event in apoptosis in pancreatitis. Here, we assessed the regulation of pancreatic cytochrome c release by Ca(2+), mitochondrial membrane potential (Delta Psi m), and reactive oxygen species (ROS), the signals involved in acute pancreatitis. We used both isolated rat pancreatic mitochondria and intact acinar cells hyper-stimulated with cholecystokinin-8 (CCK-8; in vitro model of acute pancreatitis). Results: Micromolar amounts of Ca(2+) depolarised isolated pancreatic mitochondria through a mechanism different from the "classical'' (ie, liver) mitochondrial permeability transition pore (mPTP). In contrast with liver, Ca(2+)-induced mPTP opening caused a dramatic decrease in ROS and was not associated with pancreatic mitochondria swelling. Importantly, we found that Ca(2+)-induced depolarisation inhibited cytochrome c release from pancreatic mitochondria, due to blockade of ROS production. As a result, Ca(2+) exerted two opposite effects on cytochrome c release: Ca(2+) per se stimulated the release, whereas Ca(2+)-induced depolarisation inhibited it. This dual effect caused a non-monotonous dose-dependence of cytochrome c release on Ca(2+). In intact acinar cells, cytochrome c release, caspase activation and apoptosis were all stimulated by ROS and Ca(2+), and inhibited by depolarisation, corroborating the findings on isolated pancreatic mitochondria. Conclusions: These data implicate ROS as a key mediator of CCK-induced apoptotic responses. The results indicate a major role for mitochondria in the effects of Ca(2+) and ROS on acinar cell death. They suggest that the extent of apoptosis in pancreatitis is regulated by the interplay between ROS, Delta Psi m and Ca(2+). Stabilising mitochondria against loss of Delta Psi m may represent a strategy to mitigate the severity of pancreatitis. C1 [Gukovskaya, A. S.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Dept Med,David Geffen Sch Med, Los Angeles, CA 90073 USA. [Odinokova, I. V.; Evtodienko, Y.] Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142292, Russia. [Sung, K-F] Chang Gung Mem Hosp, Dept Hepatogastroenterol, Taipei 10591, Taiwan. [Andreyev, A.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. RP Gukovskaya, AS (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Dept Med,David Geffen Sch Med, 11301 Wilshire Blvd,Blg 258,Rm 40, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NIH [DK059936]; Foundation Designated Research Scholar Award in Pancreatitis; Hirshberg Foundation FX This study was supported by NIH grant DK059936 (to ASG), an AGA Foundation Designated Research Scholar Award in Pancreatitis (to OAM) and by the Hirshberg Foundation. NR 66 TC 33 Z9 33 U1 0 U2 3 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 MAR PY 2009 VL 58 IS 3 BP 431 EP 442 DI 10.1136/gut.2007.147207 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 406CZ UT WOS:000263273900022 PM 18596195 ER PT J AU Olawaiye, A Del Carmen, M Tambouret, R Goodman, A Fuller, A Duska, LR AF Olawaiye, Alexander Del Carmen, Marcela Tambouret, Rosemary Goodman, Annekathryn Fuller, Arlan Duska, Linda R. TI Abdominal radical trachelectomy: Success and pitfalls in a general gynecologic oncology practice SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Cervical cancer; Fertility; Radical trachelectomy ID OF-THE-LITERATURE; FERTILITY-PRESERVING OPTION; STAGE CERVICAL-CANCER; LOWER UTERINE SEGMENT; PELVIC LYMPHADENECTOMY; VAGINAL TRACHELECTOMY; FROZEN-SECTION; CARCINOMA; HYSTERECTOMY; PREGNANCY AB Objective. To report Our successes and complications with a series of abdominal radical trachelectomies performed to preserve fertility in young women at the Massachusetts General Hospital (MGH). Methods. Institutional review board (IRB) permission was obtained for retrospective record review. Data were collected regarding patient age and parity, tumor stage and histology, surgical time and complications, post-operative complications. follow-up, and pregnancy. Results. Ten patients underwent radical abdominal trachelectomy, 9 by the same surgeon (LD). Surgery was essentially identical to that of radical hysterectomy with the exception of re-anastomosis of the uterine fundus to the vagina and placement of cerclage. Pre-operative evaluation and post operative follow-up Was for the most part identical for all patients. Two patients achieved pregnancy, with 1 twin delivery and 1 patient had 2 pregnancies. Two patients experienced cervical stenosis with regular menses and the same 2 patients passed their abdominal cerclage vaginally. To date there have been no cancer recurrences. Pap smear follow-up has been complicated by difficulty in reading smears from the lower uterine segment (LUS). Conclusion. Radical abdominal trachelectomy can be Successfully performed by any gynecologic oncologist who is trained in radical pelvic surgery. Pre-operative counseling is crucial in obtaining informed consent. Patients must be aware of potential post-operative complications, including pre-term delivery. Cytology department needs to be aware of potential pitfalls in reading Pap smears from the LUS. (C) 2008 Elsevier Inc. All rights reserved. C1 [Olawaiye, Alexander; Del Carmen, Marcela; Goodman, Annekathryn; Fuller, Arlan; Duska, Linda R.] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. [Tambouret, Rosemary] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Duska, LR (reprint author), Univ Virginia Hlth Syst, Div Gynecol Oncol, POB 800712, Charlottesville, VA 22903 USA. EM lduska@virginia.edu NR 31 TC 23 Z9 27 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2009 VL 112 IS 3 BP 506 EP 510 DI 10.1016/j.ygyno.2008.10.029 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 418QH UT WOS:000264162800014 PM 19131094 ER PT J AU Watts, LA Joseph, N Wallace, M Rauh-Hain, JA Muzikansky, A Growdon, WB del Carmen, MG AF Watts, Luisa A. Joseph, Naima Wallace, Maria Rauh-Hain, Jose A. Muzikansky, Alona Growdon, Whitfield B. del Carmen, Marcela G. TI HPV vaccine: A comparison of attitudes and behavioral perspectives between Latino and non-Latino women SO GYNECOLOGIC ONCOLOGY LA English DT Article DE HPV vaccine; Latino; Acceptance; Survey; Disparity ID HUMAN-PAPILLOMAVIRUS VACCINATION; INVASIVE CERVICAL-CANCER; ACCEPTANCE; KNOWLEDGE AB Objective, Recent scientific advances have lead to the development of a prophylactic, quadrivalent HPV vaccine conferring. We surveyed Latino and non-Latino women directly to examine what motivates them to vaccinate themselves, their daughters, and their sons. Methods. A written survey was administered to 86 Latinas and 141 non-Latinas, ages 18-55, and attending a general medicine, gynecology, or pediatric unit at an academic center. The instrument included questions on demographics, knowledge and attitudes toward the HPV vaccine, attitudes toward HPV vaccination for the respondents' daughters and/or sons, and the effect of vaccine acceptability on women's attitudes towards their sexual behavior and cervical cancer screening practices. Results. Acceptance for the HPV vaccine was high, with 73% of non-vaccinated, eligible women stating that they would vaccinate themselves. Cervical cancer prevention was the primary motivation for seeking vaccination. Most respondents reported that Vaccination should still be accompanied by cervical cancer screening. Seventy-percent of eligible respondent agreed to vaccinate their daughters (97% of Latino and 68.2% of non-Latino mothers, p=0.0078). Eighty-six percent of eligible participants agreed to vaccinate their sons (92.3%, of Latino and 76.9% of non-Latino mothers, p=0.0490). Cervical cancer prevention and anal/penile cancer prevention were the primary motivation reported for accepting the vaccine in their daughters and sons, respectively, Fewer than 20% of eligible respondents cited protection of women against developing cervical cancer as the motivation to vaccinate their son(s). Conclusions, Among vaccine-eligible women, HPV vaccination acceptance for themselves, their daughters, and potentially their sons is high and primarily motivated by cancer prevention for the individual vaccinated. (C) 2008 Elsevier Inc. All rights reserved. C1 [Wallace, Maria; Rauh-Hain, Jose A.; Growdon, Whitfield B.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02115 USA. [Watts, Luisa A.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Joseph, Naima] Univ Connecticut, Sch Med, Farmington, CT USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02115 USA. EM mdelcarmen@partners.org NR 21 TC 67 Z9 67 U1 1 U2 10 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 MAR PY 2009 VL 112 IS 3 BP 577 EP 582 DI 10.1016/j.ygyno.2008.12.010 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 418QH UT WOS:000264162800027 PM 19150120 ER PT J AU Sheth, RA Upadhyay, R Stangenberg, L Sheth, R Weissleder, R Mahmood, U AF Sheth, Rahul Anil Upadhyay, Rabi Stangenberg, Lars Sheth, Rucha Weissleder, Ralph Mahmood, Umar TI Improved detection of ovarian cancer metastases by intraoperative quantitative fluorescence protease imaging in a pre-clinical model SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Molecular imaging; Intraoperative imaging; Fluorescence imaging ID ENZYME-ACTIVITY; CARCINOMA; SURGERY; MICE AB Objectives. Cytoreductive surgery is a cornerstone of therapy in metastatic ovarian cancer, While conventional white light (WL) inspection detects many obvious tumor foci, careful histologic comparison has shown considerable miss rates for smaller foci. The goal of this study was to compare tumor detection using WL versus near infrared (NIR) imaging with a protease activatable probe, as well as to evaluate the ability to quantify NIR fluorescence using a novel quantitative optical imaging system. Methods. A murine model for peritoneal carcinomatosis was generated and metastatic foci were imaged using WL and NIR imaging following the i.v. administration of the protease activatable probe ProSense750. The presence of tumor was confirmed by histology. Additionally, the ability to account for variations in fluorescence signal intensity due to changes in distance between the catheter and target lesion during laparoscopic procedures was evaluated. Results. NIR imaging with a ProSense750 significantly improved upon the target-to-background ratios (TBRs) of tumor foci in comparison to WL imaging (minimum improvement was approximately 3.5 fold), Based on 52 histologically validated samples, the sensitivity for WL imaging was 69%, while the sensitivity for NIR imaging was 100%. The effects of intraoperative distance changes upon fluorescence intensity were corrected in realtime, resulting in a decrease from 89% to 5% in signal variance during fluorescence laparoscopy. Conclusions. With its molecular specificity, low background autofluorescence, high TBRs, and quantitative signal, optical imaging with NIR protease activatable probes greatly improves upon the intraoperative detection of ovarian cancer metastases. (C) 2008 Elsevier Inc. All rights reserved. C1 [Sheth, Rahul Anil; Upadhyay, Rabi; Stangenberg, Lars; Weissleder, Ralph; Mahmood, Umar] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Sheth, Rucha] Cypress Fairbanks Med Ctr, Dept Pathol, Houston, TX USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Simches 8226,185 Cambridge St, Boston, MA 02114 USA. EM mahmood@helix.mgh.harvard.edu FU NIH [R01-EB001872, U24-CA92782] FX This research was supported in part by NIH grant R01-EB001872 and U24-CA92782. NR 17 TC 42 Z9 43 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2009 VL 112 IS 3 BP 616 EP 622 DI 10.1016/j.ygyno.2008.11.018 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 418QH UT WOS:000264162800034 PM 19135233 ER PT J AU Berkowitz, RS Goldstein, DP AF Berkowitz, Ross S. Goldstein, Donald P. TI Current management of gestational trophoblastic diseases SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Gestational trophoblastic disease; Molar pregnancy ID HUMAN CHORIONIC-GONADOTROPIN; COMPLETE HYDATIDIFORM MOLE; CENTRAL-NERVOUS-SYSTEM; GYNECOLOGIC-ONCOLOGY-GROUP; QUALITY-OF-LIFE; RETROSPECTIVE COHORT SURVEY; UNDETECTABLE HCG LEVELS; LOW-RISK; PROGNOSTIC-FACTORS; ACTINOMYCIN-D AB Objectives. This review was undertaken to describe current understanding of the natural history of molar pregnancy and persistent gestational trophoblastic neoplasia (GTN) as well as recent advances in their management. Materials and methods. Recent literature related to molar pregnancy and GTN was thoroughly analyzed to provide a comprehensive review of the current knowledge of their pathogenesis and treatment. Results. Studies in patients with familial recurrent molar pregnancy indicate that dysregulation of parentally imprinted genes is important in the pathogenesis of complete hydatidiform mole (CHM). CHM is now being diagnosed earlier in pregnancy in the first trimester changing the clinical presentation and making the histologic appearance more similar to partial hydatidiform mole (PHM) and hydropic abortion. While the classic presenting symptoms of CHM are less frequent, the risk of developing GTN remains unchanged. Flow cytometry and immunostaining for maternally-expressed genes are helpful in distinguishing early CHM from PHM or hydropic abortion. Patients with molar pregnancy have a low risk of developing persistent GTN after achieving even one non-detectable hCG level (hCG <5 mlU/ml). Patients with persistent low levels of hCG should undergo tests to determine if the hCG is real or phantom. If the hCG is real, then further tests should determine what percentage of the total hCG is hyperglycosylated hCG and free beta subunit to establish a proper diagnosis and institute appropriate management. Patients with non-metastatic GTN have a high remission rate with many different single-agent regimens including methotrexate and actinomycin D. Patients with high-risk metastatic GTN require aggressive combination chemotherapy in conjunction with surgery and radiation therapy to attain remission. After achieving remission, patients can generally expect normal reproduction in the future. Conclusion. Our understanding of the natural history and management of molar pregnancy and GTN has advanced considerably in recent years. While most patients can anticipate a high cure rate, efforts are still necessary to develop effective new second-line therapies for patients with drug-resistant disease. (C) 2008 Elsevier Inc. All rights reserved. C1 [Berkowitz, Ross S.] Brigham & Womens Hosp, Div Gynecol Oncol, New England Trophoblast Dis Ctr, Boston, MA 02115 USA. [Berkowitz, Ross S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goldstein, Donald P.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, New England Trophoblast Dis Ctr, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 149 TC 91 Z9 108 U1 2 U2 10 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 MAR PY 2009 VL 112 IS 3 BP 654 EP 662 DI 10.1016/j.ygyno.2008.09.005 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 418QH UT WOS:000264162800039 PM 18851873 ER PT J AU Bhattacharyya, T Freiberg, AA Mehta, P Katz, JN Ferris, T AF Bhattacharyya, Timothy Freiberg, Andrew A. Mehta, Priyesh Katz, Jeffrey Neil Ferris, Timothy TI Measuring The Report Card: The Validity Of Pay For-Performance Metrics In Orthopedic Surgery SO HEALTH AFFAIRS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL-PERFORMANCE; HOSPITAL QUALITY; KNEE REPLACEMENT; MORTALITY; OUTCOMES; HIP AB To assess the validity of performance measures used in a nationwide pay-forperformance (P4P) project on hip and knee replacement, we analyzed hospital performance data from a Medicare P4P initiative and compared them to publicly available outcomes data. Overall, the ability to measure hospital quality was poor. A hospital's ranking on the composite score was primarily determined by process measures. A higher composite quality score was not associated with lower rates of complications or mortality. The current Medicare P4P quality measure has limited validity because of poor discrimination, lack of measure balance, and lack of correlation with important clinical outcomes. [Health Affairs 28, no. 2 (2009): 526-532; 10.1377/hlthaff.28.2.526] C1 [Bhattacharyya, Timothy] Suburban Hosp, Bethesda, MD USA. [Freiberg, Andrew A.] Massachusetts Gen Hosp, Boston, MA USA. [Mehta, Priyesh] Univ New England, Coll Osteopath Med, Biddeford, ME USA. [Katz, Jeffrey Neil] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bhattacharyya, T (reprint author), Suburban Hosp, Bethesda, MD USA. EM tbhattacharyya@bcc-ortho.com FU Zimmer FX Timothy Bhattacharyya is a consultant for Stryker Orthopaedics and Best Doctors Inc. Andrew Freiberg receives royalties and research support from Zimmer and is a consultant for Biomet. NR 15 TC 22 Z9 22 U1 0 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAR-APR PY 2009 VL 28 IS 2 BP 526 EP 532 DI 10.1377/hlthaff.28.2.526 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 422RJ UT WOS:000264445100028 PM 19276012 ER PT J AU Goldzweig, CL Towfigh, A Maglione, M Shekelle, PG AF Goldzweig, Caroline Lubick Towfigh, Ali Maglione, Margaret Shekelle, Paul G. TI Costs And Benefits Of Health Information Technology: New Trends From The Literature SO HEALTH AFFAIRS LA English DT Article; Proceedings Paper CT 15th Princeton Conference on Can Payment and Other Innovations Improve the Quality and Value of Health Care CY MAY 27-28, 2008 CL Princeton, NJ SP Council Hlth Care Econ & Policy AB To understand what is new in health information technology ( IT), we updated a systematic review of health IT with studies published during 2004-2007. From 4,683 titles, 179 met inclusion criteria. We identified a proliferation of patient-focused applications although little formal evaluation in this area; more descriptions of commercial electronic health records (EHRs) and health IT systems designed to run independently from EHRs; and proportionately fewer relevant studies from the health IT leaders. Accelerating the adoption of health IT will require greater public-private partnerships, new policies to address the misalignment of financial incentives, and a more robust evidence base regarding IT implementation. [Health Affairs 28, no. 2 (2009): w282-w293 (published online 27 January 2009; 10.1377/hlthaff.28.2.w282)] C1 [Goldzweig, Caroline Lubick; Shekelle, Paul G.] VA Greater Los Angeles Healthcare Syst Calif, Los Angeles, CA USA. [Maglione, Margaret; Shekelle, Paul G.] RAND, So Calif Evidence Based Practice Ctr, Santa Monica, CA USA. RP Goldzweig, CL (reprint author), VA Greater Los Angeles Healthcare Syst Calif, Los Angeles, CA USA. EM caroline.goldzweig@va.gov NR 3 TC 123 Z9 125 U1 1 U2 13 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAR-APR PY 2009 VL 28 IS 2 BP W282 EP W293 DI 10.1377/hlthaff.28.2.w282 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 422RJ UT WOS:000264445100083 PM 19174390 ER PT J AU Frakt, AB Pizer, SD Feldman, R AF Frakt, Austin B. Pizer, Steven D. Feldman, Roger TI Payment Reduction and Medicare Private Fee-for-Service Plans SO HEALTH CARE FINANCING REVIEW LA English DT Article AB Medicare private fee-for-service (PFFS) plans are paid like other Medicare Advantage (MA) plans but are exempt from many MA requirements. Recently, Congress set average payments well above the costs of traditional fee-for-service (FFS) Medicare, inducing dramatic increases in PFFS plan enrollment. This has significant implications for Medicare's budget, provoking calls for policy change. We predict the effect of proposals to cut PFFS payments on PFFS plan participation and enrollment. We find that small reductions in payment rates would reduce PFFS participation and enrollment; if Congress reduces payments to traditional FFS levels it would cause the vast majority (85 percent) of PFFS plans to exit the market. C1 [Frakt, Austin B.; Pizer, Steven D.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Feldman, Roger] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. RP Frakt, AB (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 152H, Boston, MA 02130 USA. EM frakt@bu.edu FU Robert Wood Johnson Foundation's Changes in Health Care Financing and Organization Initiative [63744] FX Austin B. Frakt and Steven D. Pizer are with the VA Boston Healthcare System and BU School of Public Health. Roger Feldman is with the University of Minnesota School of Public Health. The research in this article was supported by Grant Number 63744 from the Robert Wood Johnson Foundation's Changes in Health Care Financing and Organization Initiative. The statements expressed in this article are those of the authors and do not necessarily reflect the views or policies of the VA Boston Healthcare System and BU School of Public Health, University of Minnesota School of Public Health, the Robert Wood Johnson Foundation. or the Centers for Medicare &, Medicaid Services (CMS). NR 20 TC 8 Z9 8 U1 0 U2 2 PU CENTERS FOR MEDICARE & MEDICAID SERVICES PI BALTIMORE PA 7500 SECURITY BOULEVARD, BALTIMORE, MD 21244-1850 USA SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SPR PY 2009 VL 30 IS 3 BP 15 EP 24 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 446WR UT WOS:000266152700002 PM 19544932 ER PT J AU Lutfey, KE Link, CL Grant, RW Marceau, LD Mckinlay, JB AF Lutfey, Karen E. Link, Carol L. Grant, Richard W. Marceau, Lisa D. Mckinlay, John B. TI Is certainty more important than diagnosis for understanding race and gender disparities?: An experiment using coronary heart disease and depression case vignettes SO HEALTH POLICY LA English DT Article DE Clinical decision-making; Health disparities; Certainty; CHD; Depression ID MEDICAL DECISION-MAKING; PRIMARY-CARE PHYSICIANS; LATE-LIFE DEPRESSION; HEALTH-CARE; FACTORIAL EXPERIMENT; STATISTICAL DISCRIMINATION; STANDARDIZED PATIENTS; NONMEDICAL INFLUENCES; CLINICAL UNCERTAINTY; SOCIOECONOMIC-STATUS AB Objectives: To (1) examine the influence of patient and provider attributes on physicians' diagnostic certainty and (2) assess the effect of diagnostic certainty on clinical therapeutic actions. Methods: Factorial experiment of 128 generalist physicians using identical clinically authentic videotaped vignettes depicting patients with coronary heart disease (CHD) or depression. Results: For CHD, physicians were least certain for Black patients (p = .003) and for younger female patients (p = .013). For depression, average certainty was higher than for the CHD presentation (74.0 vs. 57.9 on of scale of 0-100, p < .001) and there were no main effects of patient or provider characteristics. Increasing diagnostic certainty was a significant predictor of subsequent clinical actions, and these varied according to physician and patient characteristics across both conditions. Conclusions: Physicians were least certain of their CHD diagnoses for Black patients and for younger women, but patient characteristics alone did not affect physician certainty of depression diagnoses. Physicians responded differentially to diagnostic certainty in terms of their clinical therapeutic actions such as test ordering and writing prescriptions. Physician responses to certainty may be as important as their responses to patient characteristics for understanding variation in clinical decision-making. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Lutfey, Karen E.; Link, Carol L.; Marceau, Lisa D.; Mckinlay, John B.] New England Res Inst, Watertown, MA 02472 USA. [Grant, Richard W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. RP Lutfey, KE (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM klutfey@neriscience.com OI Grant, Richard/0000-0002-6164-8025 FU National Institutes of Health; National Institute on Aging [AG16747]; [R01 AG16747] FX The financial support for this study was provided entirely by a grant from National Institutes of Health, National Institute on Aging (Grant #AG16747). The funding agreement ensured our independence in designing the study interpreting the data, writing, and publishing the report. Funding: This study was supported by R01 AG16747 (PI: John B. McKinlay, Ph.D.). NR 58 TC 20 Z9 20 U1 3 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8510 J9 HEALTH POLICY JI Health Policy PD MAR PY 2009 VL 89 IS 3 BP 279 EP 287 DI 10.1016/j.healthpol.2008.06.007 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 426GE UT WOS:000264695200005 PM 18701185 ER PT J AU Sarkar, U Ali, S Whooley, MA AF Sarkar, Urmimala Ali, Sadia Whooley, Mary A. TI Self-Efficacy as a Marker of Cardiac Function and Predictor of Heart Failure Hospitalization and Mortality in Patients With Stable Coronary Heart Disease: Findings From the Heart and Soul Study SO HEALTH PSYCHOLOGY LA English DT Article DE self-efficacy; heart failure; epidemiology ID HEALTH-CARE UTILIZATION; DEPRESSIVE SYMPTOMS; ARTERY-DISEASE; MEDICATION ADHERENCE; PULMONARY-DISEASE; CONTROLLED-TRIAL; MANAGEMENT; INTERVENTION; ASSOCIATION; BEHAVIORS AB Objective: The authors sought to evaluate the association of self-efficacy with objective measures of cardiac function, subsequent hospitalization for heart failure (HF), and all-cause mortality. Design: Observational cohort of ambulatory patients with stable CHD. The authors measured self-efficacy using a published, validated, 5-item summative scale, the Sullivan Self-Efficacy to Maintain Function Scale. The authors also performed a cardiac assessment, including an exercise treadmill test with stress echocardiography. Main Outcome Measures: Hospitalizations for HF, as determined by blinded review of medical records, and all-cause mortality, with adjustment for demographics, medical history, medication use, depressive symptoms, and social support. Results: Of the 1,024 predominately male, older CHD patients, 1013 (99%) were available for follow-up, 124 (12%) were hospitalized for HF, and 235 (23%) died during 4.3 years of follow-up. Mean cardiac self-efficacy score was 9.7 (SD 4.5, range 0-20), corresponding to responses between "not at all confident" and "somewhat confident" for ability to maintain function. Lower self-efficacy predicted subsequent HF hospitalization (OR per SD decrease = 1.4, p = .0006), and all-cause mortality (OR per SD decrease = 1.4, p < .0001). After adjustment, the association of cardiac self-efficacy with both HF hospitalization and mortality was explained by worse baseline cardiac function. Conclusion: Among patients with CHD, self-efficacy was a reasonable proxy for predicting HF hospitalizations. The increased risk of HF associated with lower baseline self-efficacy was explained by worse cardiac function. These findings indicate that measuring cardiac self-efficacy provides a rapid and potentially useful assessment of cardiac function among outpatients with CHD. C1 [Sarkar, Urmimala; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. [Ali, Sadia; Whooley, Mary A.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. RP Sarkar, U (reprint author), Univ Calif San Francisco, Dept Med, Div Gen Internal Med, Box 1732, San Francisco, CA 94143 USA. EM urmimalasarkar@yahoo.com FU National Research Service Awards [1 T32 HP19025]; Department of Veterans Affairs; Robert Wood Johnson Foundation; American Federation for Aging Research; Ischemia Research and Education Foundation; Nancy Kirwan Heart Research Fund FX Urmimala Sarkar is supported by National Research Service Awards Grant No. 1 T32 HP19025. This work was supported by grants from the Department of Veterans Affairs (Epidemiology Merit Review Program), the Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), the American Federation for Aging Research (Paul Beeson Faculty Scholars in Aging Research Program), the Ischemia Research and Education Foundation, and the Nancy Kirwan Heart Research Fund. None of these funding sources had any role in the collection of data, interpretation of results, or preparation of this article. NR 44 TC 37 Z9 40 U1 0 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAR PY 2009 VL 28 IS 2 BP 166 EP 173 DI 10.1037/a0013146 PG 8 WC Psychology, Clinical; Psychology SC Psychology GA 420YY UT WOS:000264326300004 PM 19290708 ER PT J AU Waters, EA Weinstein, ND Colditz, GA Emmons, K AF Waters, Erika A. Weinstein, Neil D. Colditz, Graham A. Emmons, Karen TI Explanations for Side Effect Aversion in Preventive Medical Treatment Decisions SO HEALTH PSYCHOLOGY LA English DT Article DE decision making; risk perception; risk communication; informed consent; side effects ID AFFECTIVE PSYCHOLOGY; RISK COMMUNICATION; BREAST-CANCER; FORMATS; TAMOXIFEN; PREFERENCES; FREQUENCY; JUDGMENT; MODELS AB Objective: Many laypeople demonstrate excessive sensitivity to negative side effects of medical treatments, which may lead them to refuse beneficial therapies. This Internet-based experiment investigated three possible explanations for such "side effect aversion." One was derived from mental accounting, one examined the mere presence of a side effect, and one focused on computational difficulties. Design: Participants (N = 5,379) were presented with a hypothetical cancer preventive treatment situation that was or was not accompanied by one or two small side effects. The side effects were either beneficial or harmful. In all conditions, the net absolute risk reduction associated with the treatment was 15% Main Outcome Measures: Participants indicated their willingness to accept treatment and their perceptions of the treatment's effects on their overall cancer risk. Results: Data were consistent only with the "mere presence" explanation of side effect aversion, the idea that side effects act as a strong negative cue that directly affects treatment appraisal. The number of negative side effects did not influence treatment willingness. Conclusion: Side effect aversion is a challenge to informed decision making. Specific mechanisms that produce side effect aversion should be identified. C1 [Waters, Erika A.] NCI, HCIRB, BRP, DCCPS, Bethesda, MD 20892 USA. [Waters, Erika A.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA. [Weinstein, Neil D.] Univ Arizona, Coll Med, Dept Family & Community Med, Tucson, AZ USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Colditz, Graham A.] Alvin J Siteman Canc Ctr, St Louis, MO USA. [Emmons, Karen] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Emmons, Karen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Waters, EA (reprint author), NCI, HCIRB, BRP, DCCPS, Execut Plaza N,6130 Execut Blvd MSC 7365, Bethesda, MD 20892 USA. EM erika.a.waters@gmail.com RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Waters, Erika/0000-0001-7402-0133 FU Intramural NIH HHS [NIH0011143336] NR 29 TC 22 Z9 22 U1 3 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAR PY 2009 VL 28 IS 2 BP 201 EP 209 DI 10.1037/a0013608 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 420YY UT WOS:000264326300008 PM 19290712 ER PT J AU Chien, W Rosowski, JJ Ravicz, ME Rauch, SD Smullen, J Merchant, SN AF Chien, Wade Rosowski, John J. Ravicz, Michael E. Rauch, Steven D. Smullen, Jennifer Merchant, Saumil N. TI Measurements of stapes velocity in live human ears SO HEARING RESEARCH LA English DT Article DE Stapes velocity; Middle-ear mechanics; Laser-Doppler vibrometry; Middle-ear output; Umbo velocity; Round-window velocity ID DOPPLER VIBROMETER LDV; HUMAN MIDDLE-EAR; INPUT IMMITTANCE; FOOTPLATE; MOTION; TRANSMISSION; MECHANICS; MOVEMENT; GERBIL AB Sound-induced stapes velocity (Vs) was measured intraoperatively in 14 patients undergoing cochlear implantation. All 14 patients had no history of middle-ear pathology, and their ossicular chains appeared normal on intraoperative inspection and palpation. The magnitude of the mean Vs (normalized by simultaneously-measured ear-canal sound pressure) was stiffness-dominated at frequencies below 1 kHz, increased up to similar to 4 kHz, and then decreased at higher frequencies. The phase of the mean velocity was +0.2 periods at 0.3 kHz, and gradually became a phase lag at higher frequencies. The mean Vs measured in this study was similar to that of seven ears reported in the only other published study of live human measurements (Huber et al., 2001). We also made measurements of Vs in fresh cadaveric temporal bones using a technique identical to that used in live ears, including similar measurement angles and location. The mean Vs measured in the cadaveric ears under these conditions was similar to the mean Vs measurements in the 14 live ears. This indicates that middle-ear mechanics are similar in live and cadaveric ears. In addition, interspecies comparisons were made between our live human Vs and the Vs reported in different animal studies. There were some clear similarities in Vs across species, as well as differences. The primary interspecies differences were in the magnitude of the Vs as well as in the frequency of transitions in the magnitudes' frequency dependence from rising to flat or falling. (C) 2008 Elsevier B.V. All rights reserved. C1 [Chien, Wade; Rosowski, John J.; Ravicz, Michael E.; Merchant, Saumil N.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, Boston, MA 02114 USA. [Chien, Wade; Rosowski, John J.; Rauch, Steven D.; Smullen, Jennifer; Merchant, Saumil N.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Rosowski, John J.; Merchant, Saumil N.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Chien, W (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM wadechien@hotmail.com FU NIDCD [R01 DC047998, R01 DC000194, T32 DC000020]; Silverstein Young Investigator Award FX We thank Diane Jones, William Peake, Jocelyn Songer, and the staff at Eaton-Peabody Lab for their support and inputs. Funded in part by NIDCD (grants R01 DC047998, R01 DC000194, and T32 DC000020), Mr. Axel Eliasen, Mr. Lakshmi Mittal, and the Silverstein Young Investigator Award. NR 27 TC 31 Z9 33 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAR PY 2009 VL 249 IS 1-2 BP 54 EP 61 DI 10.1016/j.heares.2008.11.011 PG 8 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 426XA UT WOS:000264740500006 PM 19111599 ER PT J AU Baggish, A Thompson, PD AF Baggish, Aaron Thompson, Paul D. TI Thick hearts, high stakes, great uncertainties: screening athletes for hypertrophic cardiomyopathy SO HEART LA English DT Editorial Material ID SUDDEN CARDIAC DEATH; PERICARDIAL DISEASES; SPORTS PARTICIPATION; EXERCISE PHYSIOLOGY; EUROPEAN-SOCIETY; OF-CARDIOLOGY; WORKING GROUP; YOUNG-ADULTS; RECOMMENDATIONS; REHABILITATION C1 [Thompson, Paul D.] Hartford Hosp, Henry Low Heart Ctr, Hartford, CT 06102 USA. [Baggish, Aaron] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Thompson, PD (reprint author), Hartford Hosp, Henry Low Heart Ctr, 85 Seymour St, Hartford, CT 06102 USA. EM pthomps@harthosp.org NR 26 TC 5 Z9 5 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD MAR PY 2009 VL 95 IS 5 BP 345 EP 347 DI 10.1136/hrt.2008.158964 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 408KN UT WOS:000263434000001 PM 18977800 ER PT J AU Farmer, SA Kirkpatrick, JN Heidenreich, PA Curtis, JP Wang, YF Groeneveld, PW AF Farmer, Steven A. Kirkpatrick, James N. Heidenreich, Paul A. Curtis, Jeptha P. Wang, Yongfei Groeneveld, Peter W. TI Ethnic and racial disparities in cardiac resynchronization therapy SO HEART RHYTHM LA English DT Article DE Registry; Heart failure; Pacemaker; Epidemiology; Implantable cardioverter-defibrillator ID ACUTE MYOCARDIAL-INFARCTION; CORONARY REVASCULARIZATION PROCEDURES; HEART-FAILURE; SOCIOECONOMIC-STATUS; FUTURE; CARE; UNDERUSE; OUTCOMES; RACE; SEX AB BACKGROUND Racial/ethnic differences in the use of cardiac resynchronization therapy with defibrillator (CRT-D) may result from underprovision or overprovision relative to published guidelines. OBJECTIVE The purpose of this study was to examine the National Cardiovascular Data Registry (NCDR) ICD Registry for ethnic/racial differences in use of CRT-D. METHODS We studied white, black, and Hispanic patients who received either an implantable cardioverter-defibrillator (ICD) or CRT-D between January 2005 and April 2007. Two multivariate Logistic regression models were fit with the following outcome variables: (1) receipt of either ICD or CRT-D and (2) receipt of CRT-D outside of published guidelines. RESULTS Of 108,341 registry participants, 22,205 met inclusion criteria for the first analysis and 27,165 met criteria for the second analysis. Multivariate analysis indicated CRT-eligible black (odds ratio [OR] 0.84; 95% confidence interval [CI], 0.75-0.95; P <.004) and Hispanic (OR 0.83; 95% CI, 0.71-0.99; P <.033) patients were less likely to receive CRT-D than were white patients. A substantial proportion of patients received CRT-D outside of published guidelines, although black (OR 1.18; 95% CI, 1.02-1.36; P = .001) and Hispanic (OR 1.17; 95% CI, 1.02-1.36; P = .03) patients were more likely to meet all. three eligibility criteria. CONCLUSION Black and Hispanic patients who were eligible for CRT-D were less Likely to receive therapy compared with white patients. Conversely, in the context of widespread out-of-guideline use of CRT-D, black and Hispanic patients were more likely to meet established criteria. Our findings suggest systematic racial/ethnic differences in the treatment of patients with advanced heart failure. C1 [Farmer, Steven A.; Kirkpatrick, James N.] Univ Penn, Sch Med, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. [Heidenreich, Paul A.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Heidenreich, Paul A.] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc, Stanford, CA 94305 USA. [Curtis, Jeptha P.; Wang, Yongfei] Yale Univ, Dept Med, Sect Cardiovasc Med, New Haven, CT 06520 USA. [Groeneveld, Peter W.] Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Dept Vet Affairs, Philadelphia, PA USA. RP Farmer, SA (reprint author), Hosp Univ Penn, Div Cardiovasc, 3400 Spruce St,9 Gates, Philadelphia, PA 19104 USA. EM Steven.Farmer@uphs.upenn.edu OI Heidenreich, Paul/0000-0001-7730-8490 FU American College of Cardiology/National Cardiovascular Data Registry; Research Career Development Award FX This research was supported by the American College of Cardiology/National Cardiovascular Data Registry. Dr. Groeneveld was supported by a Research Career Development Award from the Department of Veterans Affairs. NR 33 TC 38 Z9 38 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD MAR PY 2009 VL 6 IS 3 BP 325 EP 331 DI 10.1016/j.hrthm.2008.12.018 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 419OE UT WOS:000264228100007 PM 19251206 ER PT J AU Verrier, RL Kumar, K Nearing, BD AF Verrier, Richard L. Kumar, Kapil Nearing, Bruce D. TI Basis for sudden cardiac death prediction by T-wave alternans from an integrative physiology perspective SO HEART RHYTHM LA English DT Editorial Material DE T-wave alternans; Sudden cardiac death; Cardiac arrest; Ventricular fibrillation; Ventricular tachycardia; Risk stratification ID POSTMYOCARDIAL INFARCTION PATIENTS; LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; HEART-FAILURE; ISCHEMIC CARDIOMYOPATHY; RISK STRATIFICATION; ELECTRICAL INSTABILITY; CALCIUM TRANSIENT; ARRHYTHMIAS; FIBRILLATION AB Detection of microvolt levels of T-wave alternans (TWA) has been shown to be useful in identifying individuals at heightened risk for sudden cardiac death. The mechanistic bases for TWA are complex, at the cellular level involving multiple mechanisms, particularly instabilities in membrane voltage (i.e., steep action potential duration restitution slope) and disruptions in intracellular calcium cycling dynamics. The integrative factors influencing TWA at the systemic Level are also multifold. We focus on three main variables: heart rate, autonomic nervous system activity, and myocardial ischemia. Clinically, there is growing interest in extending TWA testing to include ambulatory ECG monitoring as well as exercise. The former modality permits assessment of the influence of diverse provocative stimuli of daily life, including physical activity, circadian factors, mental stress, and steep-state related disturbances in respiratory and cardiovascular function. Two major emerging concepts in clinical TWA testing are discussed: quantitative analysis of TWA level to complement the current binary classification scheme, and risk stratification of patients with preserved left ventricular function, the population with the largest absolute number of sudden cardiac deaths. C1 [Verrier, Richard L.; Kumar, Kapil; Nearing, Bruce D.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Cardiovasc Inst, Boston, MA USA. RP Verrier, RL (reprint author), Harvard Univ, Inst Med, 77 Ave Louis Pasteur,Room 148, Boston, MA 02115 USA. EM rverrier@bidmc.harvard.edu FU NHLBI NIH HHS [R21 HL085720-02] NR 57 TC 43 Z9 44 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD MAR PY 2009 VL 6 IS 3 BP 416 EP 422 DI 10.1016/j.hrthm.2008.11.019 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 419OE UT WOS:000264228100022 PM 19251221 ER PT J AU Moulton, EA Pendse, G Morris, S Aiello-Lammens, M Becerra, L Borsook, D AF Moulton, Eric A. Pendse, Gautarn Morris, Susie Aiello-Lammens, Matthew Becerra, Lino Borsook, David TI Segmentally Arranged Somatotopy Within the Face Representation of Human Primary Somatosensory Cortex SO HUMAN BRAIN MAPPING LA English DT Article DE innocuous; mechanical; fMRI; trigeminal; brush ID CORTICAL SURFACE; BODY-SURFACE; AREA 3B; FMRI; PAIN; MONKEYS; MACAQUE; SYSTEM; RECONSTRUCTION; ORGANIZATION AB Though somatotypic representation within the face in human primary somatosensory cortex (SI) to innocuous stimuli is controversial; previous work suggests that painful heat is represented based on an "onion-skin" or segmental pattern on the face. The aim of this study was to determine if face somatotopy for brush stimuli in SI also follows this segmental representation model. Twelve healthy subjects (nine men: three women) underwent functional magnetic resonance imaging to measure blood oxygen level dependent signals during brush (1 Hz, 15 s) applied to their faces. Separate functional scans were collected for brush stimuli repetitively applied to each of five separate stimulation sites on the right side of the face. These sites were arranged in a vertical, horizontal, and circular manner encompassing the three divisions of the trigeminal nerve. To minimize inter-individual morphological differences in the post-central gyrus across subjects, cortical surface-based registration was implemented before group statistical image analysis. Based on activation foci, somatotopic activation in the post-central gyrus was detected for brush, consistent with the segmental face representation model. Hum Brain Mapp 30:757-765, 2009. (c) 2008 Wiley-Liss, Inc. C1 [Moulton, Eric A.; Pendse, Gautarn; Morris, Susie; Aiello-Lammens, Matthew; Becerra, Lino; Borsook, David] McLean Hosp, PAIN Grp, Brain Imaging Ctr, Belmont, MA 02478 USA. [Borsook, David] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Moulton, EA (reprint author), McLean Hosp, PAIN Grp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM emoulton@mclean.harvard.edu OI Aiello-Lammens, Matthew/0000-0002-6180-5959 FU NINDS [NS042721] FX Contract grant sponsor: NINDS (NS042721). NR 38 TC 21 Z9 22 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAR PY 2009 VL 30 IS 3 BP 757 EP 765 DI 10.1002/hbm.20541 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 416OR UT WOS:000264015900006 PM 18266215 ER PT J AU Little, J Higgins, JPT Ioannidis, JPA Moher, D Gagnon, F von Elm, E Khoury, MJ Cohen, B Davey-Smith, G Grimshaw, J Scheet, P Gwinn, M Williamson, RE Zou, GY Hutchings, K Johnson, CY Tait, V Wiens, M Golding, J van Duijn, C McLaughlin, J Paterson, A Wells, G Fortier, I Freedman, M Zecevic, M King, R Infante-Rivard, C Stewart, AFR Birkett, N AF Little, Julian Higgins, Julian P. T. Ioannidis, John P. A. Moher, David Gagnon, France von Elm, Erik Khoury, Muin J. Cohen, Barbara Davey-Smith, George Grimshaw, Jeremy Scheet, Paul Gwinn, Marta Williamson, Robin E. Zou, Guang Yong Hutchings, Kim Johnson, Candice Y. Tait, Valerie Wiens, Miriam Golding, Jean van Duijn, Cornelia McLaughlin, John Paterson, Andrew Wells, George Fortier, Isabel Freedman, Matthew Zecevic, Maja King, Richard Infante-Rivard, Claire Stewart, Alex F. R. Birkett, Nick TI Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE Statement SO HUMAN GENETICS LA English DT Review DE Gene-disease associations; Genetics; Gene-environment interaction; Systematic review; Meta-analysis; Reporting recommendations; Epidemiology; Genome-wide association ID GENOME-WIDE ASSOCIATION; HARDY-WEINBERG EQUILIBRIUM; SINGLE-NUCLEOTIDE POLYMORPHISMS; POPULATION STRATIFICATION; RANDOMIZED-TRIALS; DISEASE ASSOCIATIONS; GENOTYPING ERRORS; COMPLEX DISEASES; PROSTATE-CANCER; LINKAGE-DISEQUILIBRIUM AB Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis. C1 [Little, Julian; Moher, David; Hutchings, Kim; Johnson, Candice Y.; Tait, Valerie; Wiens, Miriam; Birkett, Nick] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON K1H 8M5, Canada. [Little, Julian] Canada Res Chair Human Genome Epidemiol, Ottawa, ON, Canada. [Higgins, Julian P. T.] MRC, Biostat Unit, Cambridge CB2 2BW, England. [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Tufts Univ, Ctr Genet Epidemiol & Modeling, Sch Med, Boston, MA 02111 USA. [Gagnon, France] Univ Toronto, CIHR New Investigator & Canada Res Chair Epidemio, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada. [von Elm, Erik] Univ Bern, Inst Social & Prevent Med, CH-3012 Bern, Switzerland. [von Elm, Erik] Univ Med Ctr, Dept Med Biometry & Med Informat, German Cochrane Ctr, Freiburg, Germany. [Khoury, Muin J.; Gwinn, Marta] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA USA. [Cohen, Barbara] Publ Lib Sci, San Francisco, CA USA. [Davey-Smith, George] Univ Bristol, Dept Social Med, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England. [Grimshaw, Jeremy] Univ Ottawa, Dept Med, Canada Res Chair Hlth Knowledge Transfer & Uptake, Clin Epidemiol Program,Ottawa Hlth Res Inst, Ottawa, ON, Canada. [Scheet, Paul] Univ Texas Houston, Dept Epidemiol, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Williamson, Robin E.] Amer Journal Human Genet, Boston, MA 02115 USA. [Zou, Guang Yong] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Golding, Jean] Robarts Res Inst, London, ON N6A 5C1, Canada. [van Duijn, Cornelia] European Journal Epidemiol, Rotterdam, Netherlands. [McLaughlin, John] Canc Care Ontario, Toronto, ON, Canada. [McLaughlin, John] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Paterson, Andrew] Hosp Sick Children, Canada Res Chair Genet Complex Dis, Toronto, ON M5G 1X8, Canada. [Wells, George] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada. [Fortier, Isabel] McGill Univ, Montreal, PQ H3A 1A4, Canada. [Fortier, Isabel] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada. [Freedman, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zecevic, Maja] Lancet, New York, NY USA. [Infante-Rivard, Claire] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Fac Med, Montreal, PQ, Canada. [Stewart, Alex F. R.] Univ Ottawa, Inst Heart, Ottawa, ON K1Y 4W7, Canada. RP Little, J (reprint author), Univ Ottawa, Dept Epidemiol & Community Med, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. EM jlittle@uottawa.ca RI Ioannidis, John/G-9836-2011; Higgins, Julian/H-4008-2011; Stewart, Alexandre/A-5677-2011; Grimshaw, Jeremy/D-8726-2013; McLaughlin, John/E-4577-2013; Zou, Guangyong/K-6408-2013; Paterson, Andrew/A-4088-2011; Davey Smith, George/A-7407-2013; OI Moher , David /0000-0003-2434-4206; Higgins, Julian/0000-0002-8323-2514; Golding, Jean/0000-0003-2826-3307; Paterson, Andrew/0000-0002-9169-118X; Davey Smith, George/0000-0002-1407-8314; von Elm, Erik/0000-0002-7412-0406; Stewart, Alexandre/0000-0003-2673-9164; Grimshaw, Jeremy/0000-0001-8015-8243 NR 154 TC 96 Z9 100 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 2009 VL 125 IS 2 BP 131 EP 151 DI 10.1007/s00439-008-0592-7 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA 409HN UT WOS:000263496900003 PM 19184668 ER PT J AU Scheithauer, BW Swearingen, B Whyte, ETH Auluck, PK Stemmer-Rachamimov, AO AF Scheithauer, Bernd W. Swearingen, Brooke Whyte, E. Tessa Hedley Auluck, Pavan K. Stemmer-Rachamimov, Anat O. TI Ependymoma of the sella turcica: a variant of pituicytoma SO HUMAN PATHOLOGY LA English DT Article DE Ependymoma; Pituicytes; Pituitary; Sella turcica; Immunohistochemistry; Ultrastructure ID MYXOPAPILLARY EPENDYMOMA; HUMAN NEUROHYPOPHYSIS; PITUITARY FOSSA; BROAD LIGAMENT; TUMOR; CELLS AB A broad spectrum of neoplasms affects the sellar region. Among these, gliomas are rare, most being tumors of pituicytes such as granular cell tumor and pituicytoma. Only 4 ependymomas of the human sellar region have been reported to date and all have had classic histologic features. Herein, we describe the clinicopathologic features of a sellar, low-grade ependymoma with unusual histology, but classic ultrastructural features, occurring in an elderly patient and thus expanding the spectrum of reported cases. The literature is reviewed and concepts of histogenesis are explored, particularly an origin in "ependymal pituicytes." The concept that sellar ependymoma is pituicyte-derived is explored. (c) 2009 Elsevier Inc. All rights reserved. C1 [Scheithauer, Bernd W.] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA. [Scheithauer, Bernd W.] Mayo Clin, Lab Med, Rochester, MN 55905 USA. [Swearingen, Brooke] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02101 USA. [Swearingen, Brooke] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02101 USA. [Whyte, E. Tessa Hedley; Auluck, Pavan K.; Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02101 USA. [Whyte, E. Tessa Hedley; Auluck, Pavan K.; Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02101 USA. RP Scheithauer, BW (reprint author), Mayo Clin, Dept Pathol, Rochester, MN 55905 USA. EM scheithauer.bernd@mayo.edu RI Auluck, Pavan/A-1160-2010 NR 36 TC 15 Z9 17 U1 0 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 2009 VL 40 IS 3 BP 435 EP 440 DI 10.1016/j.humpath.2008.08.013 PG 6 WC Pathology SC Pathology GA 411FM UT WOS:000263634400022 PM 18992914 ER PT J AU Cai, J Yi, FF Yang, L Shen, DF Yang, QL Li, AK Ghosh, AK Bian, ZY Yan, L Tang, QZ Li, HL Yang, XC AF Cai, Jun Yi, Fang-Fang Yang, Long Shen, Di-Fei Yang, Qinling Li, Ankang Ghosh, Asish K. Bian, Zhou-Yan Yan, Ling Tang, Qi-Zhu Li, Hongliang Yang, Xin-Chun TI Targeted Expression of Receptor-Associated Late Transducer Inhibits Maladaptive Hypertrophy via Blocking Epidermal Growth Factor Receptor Signaling SO HYPERTENSION LA English DT Article DE RALT; EGFR; ERK1/2; cardiac hypertrophy; heart failure; fibrosis ID LEFT-VENTRICULAR HYPERTROPHY; INDUCED CARDIAC-HYPERTROPHY; ANGIOTENSIN-II; TRANSACTIVATION; PATHWAYS; MICE; OVEREXPRESSION; HYPERTENSION; FIBROBLASTS; ANTISENSE AB Receptor-associated late transducer (RALT) is a feedback inhibitor of epidermal growth factor receptor signaling. RALT has been shown previously to be induced in the ischemic heart and to promote cardiomyocyte apoptosis in vitro. However, the role of RALT in cardiac hypertrophy remains unclear. We hypothesized that forced expression of RALT in the murine heart would protect the heart against cardiac hypertrophy in vivo. We investigated the effect of cardiac overexpression of rat RALT on cardiac hypertrophy induced by angiotensin II and isoproterenol in RALT transgenic mice and wild-type littermates. The extent of cardiac hypertrophy was assessed by 2D and M-mode echocardiography as well as by molecular and pathological analyses of cardiac samples. Constitutive expression of rat RALT in cardiac myocytes of murine heart attenuated both hypertrophic and inflammatory responses and preserved cardiac function. These beneficial effects were associated with the attenuation of the epidermal growth factor receptor-dependent cascade that was triggered by angiotensin II and isoproterenol stimulation. Additional evidence demonstrated that RALT expression blocked fibrosis in vivo and collagen synthesis in vitro. Therefore, cardiac overexpression of RALT improves cardiac function and inhibits maladaptive hypertrophy, inflammation, and fibrosis through attenuating epidermal growth factor receptor-dependent signaling. (Hypertension. 2009;53:539-548.) C1 [Cai, Jun; Yi, Fang-Fang; Yang, Long; Yang, Xin-Chun] Capital Med Univ, Beijing Chaoyang Hosp, Dept Cardiol, Beijing 100020, Peoples R China. [Cai, Jun] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Shen, Di-Fei; Bian, Zhou-Yan; Yan, Ling; Tang, Qi-Zhu; Li, Hongliang] Wuhan Univ, Cardiovasc Res Inst, Wuhan 430072, Peoples R China. [Shen, Di-Fei; Bian, Zhou-Yan; Yan, Ling; Tang, Qi-Zhu; Li, Hongliang] Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430072, Peoples R China. [Yang, Qinling] Univ Alabama, Dept Nutr Sci, Birmingham, AL USA. [Li, Ankang] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA. [Ghosh, Asish K.] Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Chicago, IL 60611 USA. RP Yang, XC (reprint author), Capital Med Univ, Beijing Chaoyang Hosp, Dept Cardiol, 8 Baijiazhuang Rd, Beijing 100020, Peoples R China. EM lihl@whu.edu.cn; yangxc@medmail.com.cn FU National Natural Science Foundation of China [30600337, 30770875] FX This work was supported by grants 30600337 and 30770875 from National Natural Science Foundation of China (X.-C.Y.). NR 30 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2009 VL 53 IS 3 BP 539 EP U228 DI 10.1161/HYPERTENSIONAHA.108.120816 PG 22 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 421EG UT WOS:000264341200020 PM 19204184 ER PT J AU Priolo, C Oh, WK Loda, M AF Priolo, Carmen Oh, William K. Loda, Massimo TI Novel therapeutic strategies in prostate cancer: Establishing a stratification system for patient selection in targeted trials SO IDRUGS LA English DT Review DE Clinical trial; molecular target; personalized therapy; prostate cancer AB Currently, the standard treatment for metastatic hormone-refractory prostate cancer includes a combination regimen with docetaxel and prednisone. Although such therapy has been demonstrated to improve survival compared with previous standards of treatment, the regimen is not curative. In efforts to identify alternative therapeutic strategies that would target single or multiple pathways activated in cancer, many small-molecule inhibitors and recombinant humanized mAbs have been tested in the preclinical setting, and many of these compounds have entered phase I/II clinical trials. However, no guidelines for the use of these drugs are available to date. Results from clinical trials are often difficult to interpret, primarily as a result of the lack of a molecular characterization of prostate tumors; such characterization would help in the search for predictive markers of response to specific drugs. Thus, a molecular classification of human prostate tumors is actively sought to assess predictive models for the stratification of patients with metastatic prostate cancer who are participating in targeted clinical trials. C1 [Priolo, Carmen; Oh, William K.; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Loda, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D1537, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 4 TC 1 Z9 1 U1 0 U2 0 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1369-7056 J9 IDRUGS JI IDrugs PD MAR PY 2009 VL 12 IS 3 BP 165 EP 168 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 419PB UT WOS:000264230500010 PM 19333896 ER PT J AU Tiberi, G Bertini, S Malik, WQ Monorchio, A Edwards, DJ Manara, G AF Tiberi, Gianluigi Bertini, Stefano Malik, Wasim Q. Monorchio, Agostino Edwards, David J. Manara, Giuliano TI Analysis of Realistic Ultrawideband Indoor Communication Channels by Using an Efficient Ray-Tracing Based Method SO IEEE TRANSACTIONS ON ANTENNAS AND PROPAGATION LA English DT Article DE Angle of arrival (AoA); indoor propagation; parallel rays; ray-tracing; ultrawideband (UWB) channel ID PROPAGATION; SYSTEMS AB A fundamental step in ultrawideband (UWB) communication system design involves the characterization of the indoor propagation channel. In this paper, we show that the UWB propagation channel parameters can be accurately predicted by employing ray tracing (RT) simulation carried out at various frequencies over the signal bandwidth. It is important to note that the determination of the rays reaching a given location is made only once, as the RT algorithm is independent of frequency. A parallel ray approximation (PRA) is used to significantly improve the computational efficiency of the RT based method. Moreover the accuracy of the approximation is verified through a measurement campaign. C1 [Tiberi, Gianluigi; Bertini, Stefano; Monorchio, Agostino; Manara, Giuliano] Univ Pisa, Dept Informat Engn, I-56122 Pisa, Italy. [Malik, Wasim Q.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Malik, Wasim Q.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Edwards, David J.] Univ Oxford, Dept Engn Sci, Oxford OX1 3PJ, England. RP Tiberi, G (reprint author), Univ Pisa, Dept Informat Engn, I-56122 Pisa, Italy. EM g.tiberi@iet.unipi.it; stefano.bertini@iet.uni.it; wqm@mit.edu; a.monorchio@iet.unipi.it; david.edwards@eng.ox.ac.uk; g.manara@iet.unipi.it RI Malik, Wasim/C-9982-2011; Tiberi, Gianluigi/K-5995-2016; OI Tiberi, Gianluigi/0000-0001-8787-1295; MONORCHIO, AGOSTINO/0000-0001-6063-4310; Manara, Giuliano/0000-0002-1242-1908 FU Fondazione Cassa di Risparmio di Pisa FX This work was supported in part by the Fondazione Cassa di Risparmio di Pisa. NR 18 TC 22 Z9 26 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-926X J9 IEEE T ANTENN PROPAG JI IEEE Trans. Antennas Propag. PD MAR PY 2009 VL 57 IS 3 BP 777 EP 785 DI 10.1109/TAP.2009.2013432 PG 9 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 431VW UT WOS:000265093500022 ER PT J AU Barley, ME Armoundas, AA Cohen, RJ AF Barley, Maya E. Armoundas, Antonis A. Cohen, Richard J. TI A Method for Guiding Ablation Catheters to Arrhythmogenic Sites Using Body Surface Electrocardiographic Signals SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Catheter ablation; equivalent moving dipole; ventricular tachycardia (VT) ID CORONARY HEART-DISEASE; SUDDEN CARDIAC DEATH; MOVING DIPOLE MODEL; VENTRICULAR-TACHYCARDIA; ELECTRICAL ACTIVATION; DEFIBRILLATORS; APPLICABILITY; ARRHYTHMIAS; ORIGIN; MADIT AB Treatment of hemodynamically unstable ventricular arrhythmias requires rapid and accurate localization of the reentrant circuit. We have previously described an algorithm that uses the single-equivalent moving dipole model to rapidly identify both the location of cardiac sources from body surface electrocardiographic signals and the location of the ablation catheter tip from current pulses delivered at the tip. However, during catheter ablation, in the presence of sources of systematic error, even if the exit site and catheter tip dipole are superposed in real space, their calculated positions may be separated by as much as 5 mm if their orientations are not exactly matched. In this study, we present a method to compensate for the effect of dipole orientation and examine the method's ability to guide a dipole at a catheter tip to an arrhythmogenic dipole corresponding to the exit site. In computer simulations, we show that the new method enables the user to guide the catheter tip to within 1.5 mm of the arrhythmogenic dipole using a realistic number of movements of the ablation catheter. These results suggest that this method has the potential to greatly facilitate RF ablation procedures, especially in the significant patient population with hemodynamically unstable arrhythmias. C1 [Barley, Maya E.; Cohen, Richard J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02139 USA. RP Barley, ME (reprint author), Philips Res Labs, NL-5656 AA Eindhoven, Netherlands. EM mbarley@alum.mit.edu; aarmoundas@partners.org; rjcohen@mit.edu FU National Institutes of Health (NIH) [1 R44 HL079726-01]; American Heart Association (AHA) [0635127N] FX The work of A. A. Armoundas was supported in part by the National Institutes of Health (NIH) under Grant 1 R44 HL079726-01 and in part by the American Heart Association (AHA) under Scientist Development Grant Award 0635127N. NR 23 TC 4 Z9 4 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD MAR PY 2009 VL 56 IS 3 BP 810 EP 819 DI 10.1109/TBME.2008.2006277 PG 10 WC Engineering, Biomedical SC Engineering GA 437KQ UT WOS:000265486800027 PM 19272900 ER PT J AU Barley, ME Choppy, KJ Galea, AM Armoundas, AA Rosbury, TS Hirschman, GB Cohen, RJ AF Barley, Maya E. Choppy, Kristen J. Galea, Anna M. Armoundas, Antonis A. Rosbury, Tamara S. Hirschman, Gordon B. Cohen, Richard J. TI Validation of a Novel Catheter Guiding Method for the Ablative Therapy of Ventricular Tachycardia in a Phantom Model SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Catheter ablation; equivalent moving dipole; ventricular tachycardia (VT) ID CORONARY HEART-DISEASE; MOVING DIPOLE MODEL; ELECTRICAL ACTIVATION; APPLICABILITY; ORIGIN; SITES AB Accurate guidance of an ablation catheter is critical in the RF ablation (RFA) of ventricular tachycardia (VT). With current technologies, it is challenging to rapidly and accurately localize the site of origin of all arrhythmia, often restricting treatment to patients with hemodynamically stable arrhythmias. We investigated the effectiveness of a new guidance method, the inverse solution guidance algorithm (ISGA), which is based on a single-equivalent dipole representation of cardiac electrical activity and is suitable for patients with hemodynamically unstable VT. Imaging was performed in homogeneous and inhomogeneous saline-filled torso phantoms in which a catheter tip was guided toward a stationary electrical dipole source over distances of more than 5 cm. Using ISGA, the moving catheter tip was guided to within 0.61 +/- 0.43 and 0.55 +/- 0.39 mm of the stationary source in the homogeneous and inhomogeneous phantoms, respectively. This accuracy was achieved with less than ten movements of the catheter. These results suggest that ISGA has potential to provide accurate and efficient guidance for RFA procedures in the patient population with hemodynamically unstable arrhythmias. C1 [Barley, Maya E.; Cohen, Richard J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Choppy, Kristen J.; Galea, Anna M.; Hirschman, Gordon B.] Infoscitex Corp, Waltham, MA 02451 USA. [Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02139 USA. [Rosbury, Tamara S.] MIT, Dept Elect Engn, Cambridge, MA 02139 USA. RP Cohen, RJ (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM mbarley@alum.mit.edu; kchoppy@infoscitex.com; agalea@infoscitex.com; aarmoundas@partners.org; tamara@alum.mit.edu; ghirschman@infoscitex.com; rjcohen@mit.edu FU National Institutes of Health (NIH) [1 R44 HL079726-01]; American Heart Association (AHA) [0635127N] FX The work of A.A. ArmoundaS was supported in part by the National Institutes of Health (NIH) under Grant 1 R44 HL079726-01 and in part by the American Heart Association (AHA) under Scientist Development Grant Award 0635127N. NR 10 TC 6 Z9 6 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD MAR PY 2009 VL 56 IS 3 BP 907 EP 910 DI 10.1109/TBME.2008.2006274 PG 4 WC Engineering, Biomedical SC Engineering GA 437KQ UT WOS:000265486800042 PM 19272901 ER PT J AU Zhu, GR Popovic, M Fang, QQ AF Zhu, Guangran Popovic, Milica Fang, Qianqian TI Microwave-Induced Thermoacoustics: Assisting Microwave Tomography SO IEEE TRANSACTIONS ON MAGNETICS LA English DT Article; Proceedings Paper CT 13th Biennial IEEE Conference on Electromagnetic Field Computation CY MAY 11-15, 2008 CL Athens, GREECE SP IEEE DE Electromagnetic scattering inverse problems; finite-difference time domain (FDTD); thermoacoustic process ID TIME-DOMAIN AB One of the applications of microwave tomography, which recovers the dielectric profiles based on the scattered-field data, is the detection of breast cancers. Here, we propose a new method, which aims to collect thermoacoustic signals generated during the period of microwave illumination, and use them for construction of the finite-element mesh for microwave tomography. Our preliminary two-dimensional study carefully links the physical processes that underlies this hybrid detection approach. C1 [Zhu, Guangran; Popovic, Milica] McGill Univ, Dept Elect & Comp Engn, Montreal, PQ H3A 2A7, Canada. [Fang, Qianqian] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Zhu, GR (reprint author), McGill Univ, Dept Elect & Comp Engn, Montreal, PQ H3A 2A7, Canada. EM guangran.zhu@mail.mcgill.ca NR 10 TC 6 Z9 6 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9464 J9 IEEE T MAGN JI IEEE Trans. Magn. PD MAR PY 2009 VL 45 IS 3 BP 1654 EP 1657 DI 10.1109/TMAG.2009.2012768 PG 4 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA 416PW UT WOS:000264019000177 ER PT J AU Chopra, P Diiorio, P Pino, SC Wilson, SB Phillips, NE Mordes, JP Rossini, AA Greiner, DL Shultz, LD Bortell, R AF Chopra, Prerna Diiorio, Philip Pino, Steven C. Wilson, S. Brian Phillips, Nancy E. Mordes, John P. Rossini, Aldo A. Greiner, Dale L. Shultz, Leonard D. Bortell, Rita TI Failure of alpha-Galactosylceramide to Prevent Diabetes in Virus-inducible Models of Type 1 Diabetes in the Rat SO IN VIVO LA English DT Article DE BB rat; type 1 diabetes; alpha-galactosylceramide; iNKT cells; NOD mouse ID KILLER T-CELLS; ANTIGEN-PRESENTING CELLS; ACTIVATED NKT CELLS; DENDRITIC CELLS; NOD MOUSE; BBDR RATS; MICE; GLYCOLIPIDS; RECOGNITION; EXPRESSION AB Background: a-Galactosylceramide (a-GalCer) is an invariant natural killer T (iNKT) cell ligand that prevents type 1 diabetes in NOD mice. However, alpha-GalCer can activate or suppress immune responses, raising concern about its potential use in human diabetes. Materials and Methods: To evaluate this therapeutic issue further, BBDR and LEW.IWRI rats were treated with Kilham rat virus (KRV) plus polyinosinic-polycytidylic acid, with or without alpha-GalCer, and followed for onset of diabetes. Results: alpha-GalCer did not prevent diabetes in inducible rat models. To investigate this discrepancy, we analyzed iNKT cell function. Splenocytes stimulated with alpha-GalCer produced similar levels of IFN gamma in all rat strains, but less than mouse splenocytes. Rat splenocytes stimulated with alpha-GalCer preferentially produced IL-12, whereas mouse splenocytes preferentially produced IL-4. Conclusion: alpha-GalCer elicits species-specific cytokine responses in iNKT cells. In humans with type 1 diabetes, differences in iNKT cell responses to stimulation with alpha-GalCer due to age, genetic variability and other factors may influence its therapeutic potential. C1 [Shultz, Leonard D.] Jackson Lab, Bar Harbor, ME 04609 USA. [Chopra, Prerna; Diiorio, Philip; Pino, Steven C.; Phillips, Nancy E.; Mordes, John P.; Rossini, Aldo A.; Greiner, Dale L.; Bortell, Rita] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. [Rossini, Aldo A.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Wilson, S. Brian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Diabet Unit, Cambridge, MA 02139 USA. RP Shultz, LD (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM lenny.shultz@jax.org FU Juvenile Diabetes Research Foundation; NIH [DK25306]; Diabetes Endocrinology Research Center [DK32520]; NIAID; American Diabetes Association [7-08-RA-106] FX We thank Jean Leif, Linda Leehy, Elaine Norowski, Michael Bates, and Erich Lidstone for technical assistance. Supported in part by grants from the Juvenile Diabetes Research Foundation, NIH research grant DK25306, Diabetes Endocrinology Research Center Grant DK32520, an Autoimmunity Prevention Center grant supported by the NIAID, and grant 7-08-RA-106 from the American Diabetes Association. NR 38 TC 2 Z9 2 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD MAR-APR PY 2009 VL 23 IS 2 BP 195 EP 201 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 430ZA UT WOS:000265029900001 PM 19414403 ER PT J AU Jenkins, TC McCollister, BD Sharma, R McFann, KK Madinger, NE Barron, M Bessesen, M Price, CS Burman, WJ AF Jenkins, Timothy C. McCollister, Bruce D. Sharma, Rohini McFann, Kim K. Madinger, Nancy E. Barron, Michelle Bessesen, Mary Price, Connie S. Burman, William J. TI Epidemiology of Healthcare-Associated Bloodstream Infection Caused by USA300 Strains of Methicillin-Resistant Staphylococcus aureus in 3 Affiliated Hospitals SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID PANTON-VALENTINE LEUKOCIDIN; FIELD GEL-ELECTROPHORESIS; UNITED-STATES; EMERGENCE; PNEUMONIA; CLONE; DISEASE; GENES AB OBJECTIVE. To describe the epidemiology of bloodstream infection caused by USA300 strains of methicillin-resistant Staphylococcus aureus (MRSA), which are traditionally associated with cases of community-acquired infection, in the healthcare setting. DESIGN. Retrospective cohort study. SETTING. Three academically affiliated hospitals in Denver, Colorado. METHODS. Review of cases of S. aureus bloodstream infection during the period from 2003 through 2007. Polymerase chain reaction was used to identify MRSA USA300 isolates. RESULTS. A total of 330 cases of MRSA bloodstream infection occurred during the study period, of which 286 (87%) were healthcare-associated. The rates of methicillin resistance among the S. aureus isolates recovered did not vary during the study period and were similar among the 3 hospitals. However, the percentages of cases of healthcare-associated MRSA bloodstream infection due to USA300 strains varied substantially among the 3 hospitals: 62%, 19%, and 36% (P <.001) for community-onset cases and 33%, 3%, and 33% (P = .005) for hospital-onset cases, in hospitals A, B, and C, respectively. In addition, the number of cases of healthcare-associated MRSA bloodstream infection caused by USA300 strains increased during the study period at 2 of the 3 hospitals. At each hospital, USA300 strains were most common among cases of community-associated infection and were least common among cases of hospital-onset infection. Admission to hospital A (a safety-net hospital), injection drug use, and human immunodeficiency virus infection were independent risk factors for healthcare-associated MRSA bloodstream infection due to USA300 strains. CONCLUSIONS. The prevalence of USA300 strains among cases of healthcare-associated MRSA bloodstream infection varied dramatically among geographically clustered hospitals. USA300 strains are replacing traditional healthcare-related strains of MRSA in some healthcare settings. Our data suggest that the prevalence of USA300 strains in the community is the dominant factor affecting the prevalence of this strain type in the healthcare setting. C1 [Jenkins, Timothy C.; Price, Connie S.; Burman, William J.] Univ Colorado, Div Infect Dis, Denver Hlth, Denver, CO 80202 USA. [Jenkins, Timothy C.; McCollister, Bruce D.; Sharma, Rohini; McFann, Kim K.; Madinger, Nancy E.; Barron, Michelle; Bessesen, Mary; Price, Connie S.; Burman, William J.] Univ Colorado, Dept Med, Div Infect Dis, Denver, CO 80202 USA. [Bessesen, Mary] Denver Vet Affairs Med Ctr, Div Infect Dis, Denver, CO USA. RP Jenkins, TC (reprint author), Denver Hlth Med Ctr, 660 Bannock St, Denver, CO 80204 USA. EM timothy.jenkins@dhha.org OI Bessesen, Mary/0000-0001-9305-1293 FU Division of Infectious Diseases at the University of Colorado Denver FX Financial support. We were supported by the Division of Infectious Diseases at the University of Colorado Denver. NR 21 TC 33 Z9 33 U1 0 U2 3 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 MAR PY 2009 VL 30 IS 3 BP 233 EP 241 DI 10.1086/595963 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 406XL UT WOS:000263328100005 PM 19199535 ER PT J AU McBride, AJA Cerqueira, GM Suchard, MA Moreira, AN Zuerner, RL Reis, MG Haake, DA Ko, AI Dellagostin, OA AF McBride, Alan J. A. Cerqueira, Gustavo M. Suchard, Marc A. Moreira, Angela N. Zuerner, Richard L. Reis, Mitermayer G. Haake, David A. Ko, Albert I. Dellagostin, Odir A. TI Genetic diversity of the Leptospiral immunoglobulin-like (Lig) genes in pathogenic Leptospira spp. SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Leptospirosis; Lig; Pathogenesis; Molecular evolution; Sequence analysis ID SURFACE-EXPOSED LIPOPROTEIN; OUTER-MEMBRANE PROTEIN; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; NUCLEOTIDE-SEQUENCES; MAMMALIAN INFECTION; PROTECTIVE IMMUNITY; BINDING PROTEIN; URBAN EPIDEMIC; HAMSTER MODEL AB Recent serologic, immunoprotection, and pathogenesis studies identified the Lig proteins as key virulence determinants in interactions of leptospiral pathogens with the mammalian host. We examined the sequence variation and recombination patterns of ligA, ligB, and ligC among 10 pathogenic strains from five Leptospira species. All strains were found to have intact ligB genes and genetic drift accounting for most of the ligB genetic diversity observed. The ligA gene was found exclusively in L. interrogans and L. kirschneri strains, and was created from ligB by a two-step partial gene duplication process. The aminoterminal domain of LigB and the LigA paralog were essentially identical (98.5 +/- 0.8% mean identity) in strains with both genes. Like ligB, ligC gene variation also followed phylogenetic patterns, suggesting an early gene duplication event. However, ligC is a pseudogene in several strains, suggesting that LigC is not essential for virulence. Two ligB genes and one ligC gene had mosaic compositions and evidence for recombination events between related Leptospira species was also found for some ligA genes. In conclusion, the results presented here indicate that Lig diversity has important ramifications for the selection of Lig polypeptides for use in diagnosis and as vaccine candidates. This sequence information will aid the identification of highly conserved regions within the Lig proteins and improve upon the performance characteristics of the Lig proteins in diagnostic assays and in subunit vaccine formulations with the potential to confer heterologous protection. (C) 2008 Elsevier B.V. All rights reserved. C1 [McBride, Alan J. A.; Reis, Mitermayer G.; Ko, Albert I.] Fundacao Oswaldo Cruz, Ctr Pesquisa Goncalo Moniz, Salvador, BA, Brazil. [Cerqueira, Gustavo M.; Moreira, Angela N.; Dellagostin, Odir A.] Univ Fed Pelotas, Ctr Biotecnol, Pelotas, RS, Brazil. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Zuerner, Richard L.] USDA ARS, Natl Anim Dis Ctr, Ames, IA 50010 USA. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Ko, Albert I.] Cornell Univ, Weill Med Coll, Div Int Med & Infect Dis, New York, NY 10021 USA. RP Dellagostin, OA (reprint author), Univ Fed Pelotas, Ctr Biotecnol, Pelotas, RS, Brazil. EM odir@ufpel.edu.br RI Ko, Albert/P-2343-2015; McBride, Alan/D-4106-2012; Dellagostin, Odir/C-2331-2009; Vacinas, Inct/J-9431-2013; Cerqueira, Gustavo/B-7180-2015 OI McBride, Alan/0000-0001-9682-540X; Dellagostin, Odir/0000-0003-2803-4088; Cerqueira, Gustavo/0000-0002-3029-6899 FU Bio-Manguinhos; Oswaldo Cruz Foundation; Brazilian Ministry of Health [09224-7]; Brazilian National Research Council [01.06.0298.00 3773/2005, 420067/2005, 554788/2006, 473006/2006-5]; Public Health Service [AI-34431]; National Institute of Allergy and Infectious Diseases [R01 AI034431]; VA Medical Research Funds; Fogarty International Center [D43 TW00919]; National Institutes of Health; Alfred P. Sloane Research Fellowship; John Simon Guggenheim Memorial Fellowship FX This work was supported by Bio-Manguinhos, Oswaldo Cruz Foundation, Brazilian Ministry of Health (grant 09224-7), Brazilian National Research Council (grants 01.06.0298.00 3773/2005, 420067/2005, 554788/2006 and 473006/2006-5); Public Health Service grants AI-34431 (to D.A.H.) and R01 AI034431 (to A.I.K.) from the National Institute of Allergy and Infectious Diseases, the VA Medical Research Funds(to D.A.H.) and grant D43 TW00919 (to A.I.K.) from the Fogarty International Center, National Institutes of Health. M.A.S. is supported by an Alfred P. Sloane Research Fellowship and a John Simon Guggenheim Memorial Fellowship. NR 67 TC 33 Z9 35 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD MAR PY 2009 VL 9 IS 2 BP 196 EP 205 DI 10.1016/j.meegid.2008.10.012 PG 10 WC Infectious Diseases SC Infectious Diseases GA 417BL UT WOS:000264049400006 PM 19028604 ER PT J AU Gerding, DN AF Gerding, Dale N. TI Clostridium difficile 30 years on: what has, or has not, changed and why? SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article; Proceedings Paper CT Conference on New Views on Clostridium Difficile Infections CY SEP 26-27, 2008 CL Leipzig, GERMANY SP Int Soc Chemotherapy DE Clostridium difficile; Pseudomembranous colitis; Antibiotic-associated diarrhoea; Clindamycin colitis; Animal models; Toxins A and B; Binary toxin ID CLINDAMYCIN-ASSOCIATED COLITIS; POLYMERASE-CHAIN-REACTION; PLACEBO-CONTROLLED TRIAL; SERUM ANTIBODY-RESPONSE; TOXIN-A; PSEUDOMEMBRANOUS COLITIS; ORAL VANCOMYCIN; DIARRHEA; HAMSTERS; INFECTION AB The report of clindamycin-associated colitis in 1974 by Tedesco et al. [Ann Intern Med 81: 429 33] stimulated an intense search for the cause of this severe complication of antibiotic use. The search culminated in early 1978 in the publication of a series of papers within 3 months that identified the causative agent as Clostridium difficile and its accompanying toxins. Thirty years later we are in the midst of a resurgence of C. difficile infection (CDI) in North America and Europe that is greater than ever previously reported and for which morbidity and mortality appear to be higher than ever seen in the past. The purpose of this review is to highlight the discoveries of the past 30 years that, in my view, have brought us to our current level of understanding of the pathogenesis, prevention and treatment of CDI, and to suggest why a disease thought to be managed so well 30 years ago could now be causing more morbidity and mortality than ever before. In the 21st century the focus should be on better understanding the relationship between the C. difficile organism and the host at the mucosal level, so that biotherapeutic and vaccine strategies for the prevention of CDI can be developed. (C) 2009 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved. C1 [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. [Gerding, Dale N.] Loyola Univ Chicago, Stritch Sch Med, Div Infect Dis, Maywood, IL USA. RP Gerding, DN (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, 5000 S 5th Ave,Bldg 1,Room C344, Hines, IL 60141 USA. EM dale.gerding2@va.gov NR 91 TC 31 Z9 31 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD MAR PY 2009 VL 33 BP S2 EP S8 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 438OL UT WOS:000265564900002 PM 19303564 ER PT J AU Johnson, S AF Johnson, Stuart TI Recurrent Clostridium difficile infection: causality and therapeutic approaches SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article; Proceedings Paper CT Conference on New Views on Clostridium Difficile Infections CY SEP 26-27, 2008 CL Leipzig, GERMANY SP Int Soc Chemotherapy DE Clostridium difficile; Diarrhoea; Recurrence ID ANTIBODY-RESPONSE; TOXIN-A; GAMMA-GLOBULIN; DIARRHEA; COLITIS; DISEASE; VANCOMYCIN; RIFAXIMIN; METRONIDAZOLE; COLONIZATION AB Recurrent diarrhoea after successful treatment of the primary episode is a common complication of Clostridium difficile infection (CDI) and may be increasing in frequency. Evidence suggests that persistent alterations in the indigenous bowel. ora and failure to mount an effective antibody response to C. difficile toxins are the main mechanisms whereby recurrent CDIs occur. Treatment of the first recurrence with the same agent used for the treatment of the primary episode is reasonable, but a different approach is needed for patients with multiple CDI recurrences. Prolonged, repeated courses of metronidazole are discouraged, but a practical first option in these patients is to use tapered-dose oral vancomycin followed by a pulsed-dose regimen. Other potential options include probiotic approaches, restoration of the normal. ora, immunological approaches, toxin-binding approaches, and serial therapy with vancomycin followed by rifaximin. Randomised studies including a sufficient numbers of patients have not yet been conducted for the treatment of recurrent CDI and are needed to help guide the formulation of effective recommendations. (C) 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. C1 [Johnson, Stuart] Loyola Univ Chicago, Div Infect Dis, Stritch Sch Med, Maywood, IL 60153 USA. [Johnson, Stuart] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Med Serv, Hines, IL 60141 USA. RP Johnson, S (reprint author), Loyola Univ Chicago, Div Infect Dis, Stritch Sch Med, 2160 S 1st Ave,Fahey Ctr Bldg 54,Room 149, Maywood, IL 60153 USA. EM sjohnson@lumc.edu NR 39 TC 26 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD MAR PY 2009 VL 33 BP S33 EP S36 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 438OL UT WOS:000265564900008 PM 19303567 ER PT J AU Merrigan, MM Sambol, SP Johnson, S Gerding, DN AF Merrigan, Michelle M. Sambol, Susan P. Johnson, Stuart Gerding, Dale N. TI New approach to the management of Clostridium difficile infection: colonisation with non-toxigenic C-difficile during daily ampicillin or ceftriaxone administration SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article; Proceedings Paper CT Conference on New Views on Clostridium Difficile Infections CY SEP 26-27, 2008 CL Leipzig, GERMANY SP Int Soc Chemotherapy DE Clostridium difficile; Pseudomembranous colitis; Antibiotic-associated diarrhoea; Ceftriaxone; Hamster model; Ampicillin ID HAMSTERS; CLINDAMYCIN; STRAIN; RISK; PREVENTION; DIARRHEA; DISEASE; TOXIN AB Non-toxigenic strains of Clostridium difficile are highly effective in preventing toxigenic C. difficile infection in hamsters when given following a single dose of an antimicrobial agent. The goal of this study was to determine the ability of non-toxigenic C. difficile to colonise hamsters during administration of an antibiotic to which the organisms are resistant ceftriaxone and an antibiotic to which they are susceptible ampicillin and to determine if non-toxigenic colonisation is protective against toxigenic strain challenge. Groups of four or five hamsters were administered daily ceftriaxone 60 mg/kg/d intraperitoneally or ampicillin 60 mg/kg/d orally for 5 days. Three non-toxigenic strains of C. difficile, M3, M23, and T7 (MICs 96 128 mg/L) were each given orally at a dose of 1 x 10(6) spores to groups of five animals 3 h after the first dose of ceftriaxone. All animals were colonised successfully by day 3 of the study and when challenged with 1 x 10(6) spores of toxigenic strain J9 (MIC > 256 mg/L) on day 3 all animals survived, whereas the control animal given ceftriaxone, but not non-toxigenic C. difficile, died within 48 h of challenge. When groups of four hamsters were given ampicillin, administration of non-toxigenic strain M3 (MIC 2 mg/L) or toxigenic strain J9 (MIC 0.75 mg/L) at 1 x 10(6) spores did not result in any colonisation or infection of the animals until day 8, 3 days after the last ampicillin dose. A protection study was designed by giving M3 spores to groups of five animals daily for 5 days beginning on day 1, 3, or 5 of ampicillin. Toxigenic challenge was given with J9 spores on day 3 of each M3 regimen. M3 colonised all animals by day 8 and none became infected with J9. Colonisation by non-toxigenic C. difficile is an effective prevention strategy during antibiotic administration of ceftriaxone or ampicillin, but multiple-day administration is required for ampicillin and colonisation does not occur until several days after the drug is discontinued. (C) 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. C1 [Merrigan, Michelle M.; Sambol, Susan P.; Johnson, Stuart; Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. [Johnson, Stuart; Gerding, Dale N.] Loyola Univ Chicago, Stritch Sch Med, Div Infect Dis, Maywood, IL USA. RP Gerding, DN (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, 5000 S 5th Ave,Bldg 1,Room C344, Hines, IL 60141 USA. EM dale.gerding2@va.gov NR 12 TC 30 Z9 30 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD MAR PY 2009 VL 33 BP S46 EP S50 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 438OL UT WOS:000265564900011 PM 19303570 ER PT J AU Russo, LM Brown, D Lin, HY AF Russo, Leileata M. Brown, Dennis Lin, Herbert Y. TI The soluble transforming growth factor-beta receptor: Advantages and applications SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Transforming growth factor-beta; Cancer; Diabetic nephropathy; Fibrosis; Albuminuria ID TGF-BETA; HIGH-GLUCOSE; DIABETIC-NEPHROPATHY; GENE-EXPRESSION; III RECEPTOR; I RECEPTOR; CELLS; PROTEIN; CANCER; ANTAGONIST AB Transforming growth factor-beta (TGF-beta) is a cytokine that plays a pivotal role in growth, differentiation, development, immune response and wound healing. TGF-beta is upregulate following wound infliction and inflammation, and plays an important role in the production of extracellular matrix proteins that contribute to tissue repair. However, in some diseases, TGF-beta dysregulation can lead, to tumor formation, organ fibrosis and the disruption of organ function. A number of molecules have been designed to counteract the effects of TGF-beta, including anti-TGF-beta monoclonal antibodies and various small molecules. Here we discuss the design, use and advantages of the highly specific TGF-beta binding molecule, the soluble human TGF-beta receptor (sTGF-beta) as a TGF-beta sequestering agent. (C) 2008 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. RP Russo, LM (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Simches Res Ctr, 185 Cambridge St,Room 8100, Boston, MA 02114 USA. EM leileata.russo@receptor.mgh.harvard.edu FU Juvenile Diabetes Research Foundation International FX L.M. Russo is supported by the Juvenile Diabetes Research Foundation International. NR 26 TC 2 Z9 6 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD MAR PY 2009 VL 41 IS 3 BP 472 EP 476 DI 10.1016/j.biocel.2008.01.026 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 405AZ UT WOS:000263195800007 PM 18339576 ER PT J AU Braithwaite, D Tammemagi, CM Moore, DH Ozanne, EM Hiatt, RA Belkora, J West, DW Satariano, WA Liebman, M Esserman, L AF Braithwaite, Dejana Tammemagi, C. Martin Moore, Dan H. Ozanne, Elissa M. Hiatt, Robert A. Belkora, Jeff West, Dee W. Satariano, William A. Liebman, Michael Esserman, Laura TI Hypertension is an independent predictor of survival disparity between African-American and white breast cancer patients SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE comorbidity; breast cancer; survival; race/ethnicity; cohort ID EPIDEMIOLOGIC ANALYSIS; SOCIOECONOMIC-STATUS; CO-MORBIDITY; COMORBIDITY; VALIDATION; IMPACT; WOMEN; MORTALITY AB The objective of this study was to determine whether comorbidity, or pre-existing conditions, can account for some of the disparity in survival between African-American and white breast cancer patients. A historical cohort study was conducted of 416 African-American and 838 white women diagnosed with breast cancer between 1973 and 1986, and followed through 1999 in the Kaiser Permanente Northern California Medical Care Program. Information on comorbidity, tumor characteristics and breast cancer treatment was obtained from medical records, and Surveillance, Epidemiology and End Results, Northern California Cancer Center Registry, Associations between comorbidity and survival were analyzed with multiple Cox proportional hazards regression. Over a mean follow-up of 9 years, African Americans had higher overall crude mortality than whites: 165 (39.7%) versus 279 (33.3%), respectively. When age, race, tumor characteristics an breast cancer treatment were controlled, the presence of hypertension was associated with all cause survival [hazard ratio (HR) = 1.33, 95% confidence intervals (CI) 1.07-1.67] and it accounted for 30% of racial disparity in this outcome. Hypertension-augmented Charlson Comorbidity Index was a significant predictor of survival from all causes (HR = 1.32, 95%CI 1.18-1.49), competing causes (HR = 1.52, 95%CI 1.32-1.76) and breast cancer specific causes (HR = 1.18, 95%CI 1.03-1.35). In conclusion, hypertension has prognostic significance in relation to survival disparity between African-American and white breast cancer patients. If our findings are replicated in contemporary cohorts, it may be necessary to include hypertension in the Charlson Comorbidity Index and other comorbidity measures. (C) 2008 Wiley-Liss, Inc. C1 [Braithwaite, Dejana] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. [Tammemagi, C. Martin] Brock Univ, Dept Community Hlth Sci, St Catharines, ON L2S 3A1, Canada. [Ozanne, Elissa M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. [West, Dee W.] No Calif Canc Ctr, Fremont, CA USA. [Satariano, William A.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Liebman, Michael] Windber Res Inst, Windber, PA USA. RP Braithwaite, D (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Epidemiol & Biostat, 185 Berry St,Lobby 4,Suite 5700, San Francisco, CA 94107 USA. EM DBraithwaite@psg.ucsf.edu FU Windber Research Institute; US Department of Defense; Division of Research Kaiser Permanente Medical Care Program FX The authors are grateful to Dr. Hyman Muss, for thoughtful comments on an earlier draft of this article. This study was funded by the Windber Research Institute (Executive Director: Dr. Michael Liebman) and US Department of Defense (Center of Excellence in Breast Cancer Care: PI Dr. Laura Esserman). Data were derived from a previous study performed at the Division of Research Kaiser Permanente Medical Care Program in Oakland, California. where Dr. Robert Hiatt was Assistant Director for Epidemiology. The funding sources did not influence the design and conduct of the study. NR 26 TC 45 Z9 45 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 2009 VL 124 IS 5 BP 1213 EP 1219 DI 10.1002/ijc.24054 PG 7 WC Oncology SC Oncology GA 403JC UT WOS:000263077900028 PM 19058216 ER PT J AU Rieber, J Sheth, TN Mooyaart, EAQ Shapiro, MD Butler, J Ferencik, M Brady, TJ Klauss, V Hoffmann, U AF Rieber, Johannes Sheth, Tej N. Mooyaart, Eline A. Q. Shapiro, Michael D. Butler, Javed Ferencik, Maros Brady, Thomas J. Klauss, Volker Hoffmann, Udo TI Assessment of the presence and extent of coronary collateralization by coronary computed tomographic angiography in patients with total occlusions SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Total coronary occlusions; Computed coronary angiography; Coronary collaterals; Coronary artery disease ID ARTERY-DISEASE; INTRAVASCULAR ULTRASOUND; DIAGNOSTIC-ACCURACY; ANGIOPLASTY; HEART; FLOW; EXPERIENCE; SYSTEM; PLAQUE AB Coronary computed tomography angiography (CTA) may be helpful to manage patients with chronic coronary occlusions. The aim of this study was to determine the sensitivity and specificity of CTA to detect the presence and extent of coronary collaterals as compared to invasive coronary angiography (ICA). We retrospectively evaluated 26 patients who underwent both coronary CTA and ICA within 3 weeks and demonstrated a total coronary occlusion (TIMI grade 0) in one of the major coronary arteries. CTA was performed using a 64-slice multidetector CT. The presence, and extent of collateralization was assessed by two blinded observers using the Rentrop classification for ICA. CTA accurately identified the presence and location of all 26 total occlusions. The presence of any collaterals was accurately detected in 21/23 patients [sensitivity 91% (CI: 71-98%)] and the absence in three patients [specificity 100% (CI: 29%-100%)]. The sensitivity of coronary CTA to identify patients with collateralization increased from 91 to 94% (CI: 71-99%) and 100% (CI: 59-100%) for collaterals Rentrop grade 2 and 3 in ICA, respectively. Coronary CTA accurately detects the presence of any coronary collateralization in patients with total occlusions. Although CT technology is currently limited in the assessment of individual collaterals and smaller vessels, it may be helpful in the management of patients with total occlusions. C1 [Rieber, Johannes; Sheth, Tej N.; Mooyaart, Eline A. Q.; Shapiro, Michael D.; Butler, Javed; Ferencik, Maros; Brady, Thomas J.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Rieber, Johannes; Klauss, Volker] Univ Munich, Div Internal Med, Dept Cardiol, Munich, Germany. [Hoffmann, Udo] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 165 Charles River Plaza 400, Boston, MA 02114 USA. EM uhoffman@partners.org FU NHLBI NIH HHS [1 T32 HL076136-02] NR 32 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD MAR PY 2009 VL 25 IS 3 BP 331 EP 337 DI 10.1007/s10554-008-9384-3 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 408EN UT WOS:000263418400017 PM 19020989 ER PT J AU Friedman, ES Thase, ME Wisniewski, SR Trivedi, MH Biggs, MM Fava, M Warden, D Niederehe, G Luther, JF Rush, AJ AF Friedman, Edward S. Thase, Michael E. Wisniewski, Stephen R. Trivedi, Madhukar H. Biggs, Melanie M. Fava, Maurizio Warden, Diane Niederehe, George Luther, James F. Rush, A. John TI Cognitive Therapy Augmentation versus CT Switch Treatment: A STAR*D Report SO INTERNATIONAL JOURNAL OF COGNITIVE THERAPY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; BEHAVIORAL-ANALYSIS SYSTEM; MAJOR DEPRESSIVE DISORDER; ILLNESS RATING-SCALE; REPORT QIDS-SR; QUICK INVENTORY; MOOD DISORDERS; CHRONIC FORMS; PSYCHOMETRIC EVALUATION; PSYCHOTHERAPY AB Objective: This report compares the effectiveness of cognitive therapy (CT) as an augmentation to citalopram vs. CT as a switch from citalopram as a second-step treatment for outpatients with non-psychotic major depressive disorder (MDD) who had received unsatisfactory benefit from an initial trial of citalopram. Methods: 1 Participants who experienced intolerance to or who did not reach remission with an optimal trial of citalopram, and who accepted randomization only to one of the two CT options were randomized to a second-step treatment of either CT switch or CT augmentation of citalopram. Treatment outcomes, side effects, and serious adverse events were compared between the two groups. Results: As a second-step treatment following an optimal trial of citalopram) discontinuing medication and switching to CT (n=32) was as effective as augmenting citalopram with CT (n=26)). Unlike the CT switch subjects, most individuals in the CT augmentation group endorsed mild-to-marked levels of side effect frequency, intensity, and burden. Conclusions: This is the first study to compare CT as a switch or augmentation strategy following unsatisfactory benefit or intolerance to an SSRI antidepressant medication. In these individuals with highly recurrent and chronic depression, there was no apparent benefit to continuing the citalopram and augmenting with CT vs. switching to CT in terms of acute phase treatment features and outcomes, or probability of relapse over one year. Implications for clinical practice arc discussed. C1 [Trivedi, Madhukar H.; Biggs, Melanie M.; Warden, Diane; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15213 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. [Friedman, Edward S.; Thase, Michael E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. [Niederehe, George] NIMH, Bethesda, MD 20892 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Friedman, ES (reprint author), Univ Pittsburgh, Med Ctr, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. EM friedmane@upmc.edu NR 63 TC 1 Z9 1 U1 1 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1937-1209 EI 1937-1217 J9 INT J COGN THER JI Int. J. Cogn. Ther. PD MAR PY 2009 VL 2 IS 1 BP 66 EP 87 PG 22 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 483ZF UT WOS:000269011500006 ER PT J AU Pickel, H Winter, R Young, RH AF Pickel, Hellmuth Winter, Raimund Young, Robert H. TI History of Gynecological Pathology - XXII. Dr. Johann Veit, MD SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Gynecologic pathology; Clinico-pathological collaboration; Carl Ruge; Cervical cancer; Small piece diagnosis; Radiologic treatment; Inoperable cervical cancer; Historical eassy C1 [Pickel, Hellmuth; Winter, Raimund] Med Univ Graz, Dept Gynecol, A-8010 Graz, Austria. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs,Dept Pathol, Boston, MA USA. RP Pickel, H (reprint author), Med Univ Graz, Dept Gynecol, 21 Managettaweg, A-8010 Graz, Austria. EM ulli.pickel@aon.at NR 18 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD MAR PY 2009 VL 28 IS 2 BP 103 EP 106 DI 10.1097/PGP.0b013e3181929290 PG 4 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 411CA UT WOS:000263624200001 PM 19188827 ER PT J AU Munro, EG Jain, M Oliva, E Kamal, N Lele, SM Lynch, MP Guo, L Fu, K Sharma, P Remmenga, S Growdon, WB Davis, JS Rueda, BR Batra, SK AF Munro, Elizabeth G. Jain, Maneesh Oliva, Esther Kamal, Neel Lele, Subodh M. Lynch, Maureen P. Guo, Lankai Fu, Kai Sharma, Poonam Remmenga, Steve Growdon, Whitfield B. Davis, John S. Rueda, Bo R. Batra, Surinder K. TI Upregulation of MUC4 in Cervical Squamous Cell Carcinoma: Pathologic Significance SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE MUC4; Cervical cancer; Squamous cell carcinoma; Adenocarcinoma ID GENE-EXPRESSION; UTERINE CERVIX; PROGNOSTIC-SIGNIFICANCE; DIAGNOSTIC-SIGNIFICANCE; CANCER; MUCINS; ERBB2; METASTASIS; RECEPTOR; THERAPY AB MUC4 is a transmembrane glycoprotein more highly expressed in cervical dysplasia than benign cervical epithelium. We Sought to determine whether MUC4 expression differs between benign and malignant cervical tissue. Fifty-eight patients with benign.. dysplastic, or malignant cervical pathology were identified retrospectively, and representative sections were stained with a mouse monoclonal anti-MUC4 antibody. Semiquantitative analysis was performed on benign, dysplastic, and malignant regions by scoring staining intensity (0: negative, 1: weak, 2: moderate, and 3: strong) and distribution (focal < 10%, multifocal = 10%-60%, diffuse 60%). In samples with benign glycogenated sqamous epithelium, only the parabasal cells had MUC4 staining. and 48.5% had an intensity of 2 or 3. All samples with immature squamous metaplasia were positive through the entire epithelial thickness. Cervical intraepithelial neoplasia (CIN) 1 samples had variable staining with in intensity similar to glycogenated squamous epithelium but distribution similar to squamous metaplasia. All CIN 3 (n = 21) and invasive squamous Cell carcinomas (n = 17) had increased MUC4 staining intensity (P<0.001 and P<0.001) and increased diffuse staining (P<0.001 and P<0.001) compared with the limited staining in glycogenated squamous epithelium. In contrast, no differences in staining were observed between benign endocervical glands, adenocarcinoma in situ, and invasive adenocarcinoma. These expression patterns suggest that MUC4 is a lineage marker in benign cervical tissue that may have aberrant expression in squamous dysplasia and carcinoma, Further studies may elucidate the role or MUC4 in the development of squamous cell cervical cancer. C1 [Jain, Maneesh; Kamal, Neel; Batra, Surinder K.] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. [Munro, Elizabeth G.; Lynch, Maureen P.; Guo, Lankai; Growdon, Whitfield B.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lele, Subodh M.; Fu, Kai] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [Sharma, Poonam] Creighton Univ, Med Ctr, Dept Pathol, Omaha, NE USA. [Remmenga, Steve; Davis, John S.] Univ Nebraska Med Ctr, Dept OB GYN, Eppley Canc Inst, Olson Ctr Womens Hlth, Omaha, NE USA. [Davis, John S.] VA Med Ctr, Omaha, NE USA. RP Batra, SK (reprint author), Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. EM sbatra@unmc.edu FU National Institutes of Health [CA78590]; United States Department of Defence [OC040110] FX This work was supported, in part, by a g-rant CA78590 from the National Institutes of Health and an Idea Award grant OC040110 front the United States Department of Defence. NR 27 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD MAR PY 2009 VL 28 IS 2 BP 127 EP 133 DI 10.1097/PGP.0b013e318184f3e0 PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 411CA UT WOS:000263624200005 PM 19188823 ER PT J AU Pizer, SD Frakt, AB Feldman, R AF Pizer, Steven D. Frakt, Austin B. Feldman, Roger TI Nothing for something? Estimating cost and value for beneficiaries from recent medicare spending increases on HMO payments and drug benefits SO INTERNATIONAL JOURNAL OF HEALTH CARE FINANCE & ECONOMICS LA English DT Article DE Medicare; HMO payment; Choice models; Welfare ID WELFARE ECONOMICS; CHOICE; SELECTION; PROGRAM; RISK AB The Medicare Modernization Act of 2003 added a new outpatient prescription drug benefit to Medicare and increased payments to HMOs. We estimate a nested logit model of plan choice to quantify the welfare benefits from these two expansion paths. We find that the addition of stand-alone prescription drug plans was welfare improving and produced nine times as much value per government dollar as the increase in payments to HMOs. In light of these results, we suggest that HMO bidding procedures should be modified to reduce payments to HMOs by about $67 billion over the next 10 years. C1 [Pizer, Steven D.; Frakt, Austin B.] VA Boston Hlth Care Syst, Dept Vet Affairs Hlth Care Financing & Econ, Boston, MA 02130 USA. [Pizer, Steven D.] Boston Univ, Boston, MA 02215 USA. [Feldman, Roger] Univ Minnesota, Minneapolis, MN USA. RP Pizer, SD (reprint author), VA Boston Hlth Care Syst, Dept Vet Affairs Hlth Care Financing & Econ, 150 S Huntington Ave 152H, Boston, MA 02130 USA. EM pizer@bu.edu NR 26 TC 7 Z9 7 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-6563 J9 INT J HEALTH CARE FI JI Int. J. Health Care Financ. Econ. PD MAR PY 2009 VL 9 IS 1 BP 59 EP 81 DI 10.1007/s10754-008-9047-x PG 23 WC Business, Finance; Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 408EU UT WOS:000263419100004 PM 18821013 ER PT J AU Cloutier, R Horr, S Niemi, JB D'Andrea, S Lima, C Harry, JD Veves, A AF Cloutier, Rachel Horr, Samuel Niemi, James B. D'Andrea, Susan Lima, Christina Harry, Jason D. Veves, Aristidis TI Prolonged Mechanical Noise Restores Tactile Sense in Diabetic Neuropathic Patients SO INTERNATIONAL JOURNAL OF LOWER EXTREMITY WOUNDS LA English DT Article DE diabetes; neuropathy; stochastic resonance AB Acute application of stochastic resonance (SR), defined as a subsensory level of mechanical noise presented directly to sensory neurons, improves the vibration and tactile perception in diabetic patients with mild to moderate neuropathy. This study examined the effect of 1 hour of continuous SR stimulation on sensory nerve function. Twenty diabetic patients were studied. The effect of stimulation was measured at 2 time points, at the beginning and after 60 minutes of continual SR stimulation. This effect was measured using the vibration perception threshold (VPT) at the big toe under 2 conditions: a null (no SR) condition and active SR, defined as mechanical noise below the subject's own threshold of perception. The measurements under null and active conditions were done randomly and the examiner was blinded regarding the type of condition. Immediately after SR application, the VPT with SR in null condition was similar to baseline (32.2 +/- 13.1, P = nonsignificant) but was significantly lower during active SR (27.4 +/- 11.9) compared with both baseline (P = .018) and off position (P = .045). The 60 minutes VPT with active SR (28.7 +/- 11.1) reached significance comparing the baseline when one outlier was removed from the analysis (P = .031). It may be concluded that SR for a continuous 60-minute period can sustain the VPT improvement in diabetic patients with moderate to severe neuropathy. These results permit the conclusion that there is no short-term adaptation to the stimulation signal. Longterm application of this technique, perhaps in the form of a continually vibrating shoe insert, or insole, may result in sustained improvement of nerve function. C1 [Cloutier, Rachel; Horr, Samuel; Lima, Christina; Veves, Aristidis] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. [Cloutier, Rachel; Horr, Samuel; Lima, Christina; Veves, Aristidis] Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. [Horr, Samuel; Niemi, James B.; D'Andrea, Susan; Harry, Jason D.] Afferent Corp, Providence, RI USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Palmer 321A,1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu FU NIH/NIDDK [R44 DK60295] FX This work was supported by a NIH/NIDDK grant (R44 DK60295) awarded to Afferent Corporation with JDH as principal investigator. A subcontract for clinical work was awarded to the Joslin Beth Israel Deaconess Foot Center and Microcirculation Laboratory. NR 11 TC 6 Z9 6 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-7346 J9 INT J LOW EXTR WOUND JI Int. J. Low. Extrem. Wounds PD MAR PY 2009 VL 8 IS 1 BP 6 EP 10 DI 10.1177/1534734608330522 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA V20CY UT WOS:000208119300002 PM 19129201 ER PT J AU Murphy, JM Horton, NJ Burke, JD Monson, RR Laird, NM Lesage, A Sobol, AM AF Murphy, J. M. Horton, N. J. Burke, J. D., Jr. Monson, R. R. Laird, N. M. Lesage, A. Sobol, A. M. TI Obesity and weight gain in relation to depression: findings from the Stirling County Study SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE major depression; overeating; gaining weight; atypical depression ID NATIONAL COMORBIDITY SURVEY; ATYPICAL DEPRESSION; GENERAL-POPULATION; MAJOR DEPRESSION; NEUROVEGETATIVE SYMPTOMS; PSYCHIATRIC-EPIDEMIOLOGY; AFFECTIVE-DISORDERS; MENTAL-HEALTH; UNITED-STATES; COMMUNITY AB Objective: This study concerns the question of whether obese subjects in a community sample experience depression in a different way from the nonobese, especially whether they overeat to the point of gaining weight during periods of depression. Design: A representative sample of adults was interviewed regarding depression and obesity. Subjects: The sample consisted of 1396 subjects whose interviews were studied regarding relationships between obesity and depression and among whom 114 had experienced a major depressive episode at some point in their lives and provided information about the symptoms experienced during the worst or only episode of major depression. Measurements: The Diagnostic Interview Schedule (DIS) was used to identify major depressive episodes. Information was also derived from the section on Depression and Anxiety (DPAX) of the Stirling Study Schedule. Obesity was calculated as a body mass index 430. Logistic regressions were employed to assess relationships, controlling for age and gender, by means of odds ratios and 95% confidence intervals. Results: In the sample as a whole, obesity was not related to depression although it was associated with the symptom of hopelessness. Among those who had ever experienced a major depressive episode, obese persons were 5 times more likely than the nonobese to overeat leading to weight gain during a period of depression (P<0.002). These obese subjects, compared to the nonobese, also experienced longer episodes of depression, a larger number of episodes, and were more preoccupied with death during such episodes. Conclusions: Depression among obese subjects in a community sample tends to be more severe than among the nonobese. Gaining weight while depressed is an important marker of that severity. Further research is needed to understand and possibly prevent the associations, sequences and outcomes among depression, obesity, weight gain and other adversities. C1 [Murphy, J. M.; Sobol, A. M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Murphy, J. M.; Burke, J. D., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Murphy, J. M.; Monson, R. R.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Horton, N. J.] Smith Coll, Dept Math & Stat, Northampton, MA 01063 USA. [Burke, J. D., Jr.] Cambridge Hlth Alliance, Dept Psychiat, Boston, MA USA. [Laird, N. M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lesage, A.] Univ Montreal, Montreal, PQ, Canada. [Lesage, A.] Hop Louis H Lafontaine, Montreal, PQ, Canada. [Lesage, A.] Ctr Rech Fernand Seguin, Montreal, PQ, Canada. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Room 215,5 Longfellow Pl, Boston, MA 02114 USA. EM murphy.jane@mgh.harvard.edu RI Burke, Jack/I-4440-2012; OI Burke, Jack/0000-0001-5868-1695; Horton, Nicholas/0000-0003-3332-4311 FU National Institute of Mental Health of the National Institutes of Health [R01 MH39576-23] FX The research reported here was supported by grant R01 MH39576-23 from the National Institute of Mental Health of the National Institutes of Health (Dr Murphy). Grateful acknowledgement is made to Patricia Merritt, Ellen Krystofik and Julie Burns for field management and data processing and additionally to Julie Burns for help with the literature review. NR 54 TC 26 Z9 27 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAR PY 2009 VL 33 IS 3 BP 335 EP 341 DI 10.1038/ijo.2008.273 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 419TQ UT WOS:000264243000006 PM 19139752 ER PT J AU Nguyen, PL Chen, MH Catalona, WJ Moul, JW Sun, L D'Amico, AV AF Nguyen, Paul L. Chen, Ming-Hui Catalona, William J. Moul, Judd W. Sun, Leon D'Amico, Anthony V. TI PREDICTING PROSTATE CANCER MORTALITY AMONG MEN WITH INTERMEDIATE TO HIGH-RISK DISEASE AND MULTIPLE UNFAVORABLE RISK FACTORS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Prostate cancer; Prostate cancer mortality; Risk stratification; High-risk disease ID CONFORMAL RADIATION-THERAPY; RANDOMIZED CONTROLLED-TRIAL; LOCALLY ADVANCED-CARCINOMA; RADICAL PROSTATECTOMY; ANDROGEN DEPRIVATION; DEFINITIVE RADIOTHERAPY; DOSE-ESCALATION; ADJUVANT; RECURRENCE; VELOCITY AB Purpose: To determine whether the number of unfavorable risk factors could be used to predict the risk of prostate cancer-specific mortality (PCSM) among men with intermediate- to high-risk prostate cancer. Methods and Materials: We studied 1,063 men who underwent radical prostatectomy (n = 559), external beam radiotherapy (it = 288), or radiotherapy plus androgen suppression therapy (n = 116) for prostate cancer between 1965 and 2002. Fine and Gray's regression analysis was used to determine whether an increasing number of unfavorable risk factors (prostate-specific antigen level >10 ng/mL, Gleason score of >= 7, clinical Stage T2b or greater, or pretreatment prostate-specific antigen velocity >2.0 ng/mL/y) was associated with the interval to PCSM and all-cause mortality. Results: Median follow-up was 5.6 years. Compared with those with one risk factor, the adjusted hazard ratio for PCSM was 2.3 (95% confidence interval 1.1-4.8; p = 0.03) for two risk factors, 5.4 (95 % confidence interval 2.7-10.7; p < 0.0001) for three risk factors, and 13.6 (95% confidence interval 6.3-29.2; p < 0.0001) for all four risk factors. The 5-year cumulative incidence of PCSM was 2.4% for one factor, 2.4% for two factors, 7.0% for three factors, and 14.7% for all four factors. Prostate cancer deaths as a proportion of all deaths was 19% for one factor, 33% for two factors, 53% for three factors, and 80% for four factors. Conclusion: The number of unfavorable risk factors was significantly associated with PCSM. Prostate cancer was the major cause of death in men with at least three risk factors. Therefore, these men should be considered for clinical trials designed to assess whether survival is prolonged with the addition of novel agents to current standards of practice. (c) 2009 Elsevier Inc. C1 [Nguyen, Paul L.] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Catalona, William J.] NW Feinberg Sch Med, Dept Urol, Chicago, IL USA. [Moul, Judd W.; Sun, Leon] Duke Univ, Med Ctr, Div Urol, Dept Surg, Durham, NC USA. [Moul, Judd W.; Sun, Leon] Duke Univ, Med Ctr, Duke Prostate Ctr, Durham, NC USA. [D'Amico, Anthony V.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu NR 20 TC 39 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2009 VL 73 IS 3 BP 659 EP 664 DI 10.1016/j.ijrobp.2008.05.009 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 408NE UT WOS:000263440900005 PM 18692327 ER PT J AU Winkfield, KM Linsenmeier, C Yock, TI Grant, PE Yeap, BY Butler, WE Tarbell, NJ AF Winkfield, Karen M. Linsenmeier, Claudia Yock, Torunn I. Grant, P. Ellen Yeap, Beow Y. Butler, William E. Tarbell, Nancy J. TI SURVEILLANCE OF CRANIOPHARYNGIOMA CYST GROWTH IN CHILDREN TREATED WITH PROTON RADIOTHERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Craniopharyngioma; Proton radiotherapy; Cyst; Surveillance imaging; Pediatrics ID STEREOTACTIC CONFORMAL RADIOTHERAPY; CENTRAL-NERVOUS-SYSTEM; PHASE-II TRIAL; RADIATION-THERAPY; PEDIATRIC CRANIOPHARYNGIOMAS; CHILDHOOD CRANIOPHARYNGIOMA; BRAIN-TUMORS; MANAGEMENT; IRRADIATION; EXPERIENCE AB Purpose: Craniopharyngiomas are benign, slow-growing tumors that frequently contain a cystic component. Even with gross total resection, the cyst can reform and cause symptoms. Fluctuations in cyst volume during radiotherapy (RT) can affect treatment planning and delivery. The aim of this study was to report our experience with cyst enlargement during conformal proton RT for children with craniopharyngioma and to make recommendations regarding mid-treatment surveillance. Methods and Materials: Between January 2001 and August 2007, 24 children (aged :518 years) underwent proton RT at the Massachusetts General Hospital for craniopharyngioma. For all 24 patients, tumor size on magnetic resonance imaging and/or computed tomography was measured before and after RT. Surveillance imaging was available for review on 17 patients. During RT, cyst growth was assessed to determine whether the treatment fields needed to be altered. Results: Of the 17 children who underwent repeat imaging during RT, 6 required intervention because of changes in cyst dimensions. Four patients (24%) had cyst growth beyond the original treatment fields, requiring enlargement of the treatment plan. One patient's treatment field was reduced after a decreased in cyst size. Cyst drainage was performed in another patient to avoid enlargement of the treatment fields. Conclusion: In patients undergoing highly conformal RT for craniopharyngiomas with cysts, routine imaging during treatment is recommended. Surveillance imaging should be performed at least every 2 weeks during proton RT in an attempt to avoid marginal failure. Craniopharyngiomas with large cystic components or enlargement during treatment might require weekly imaging. (c) 2009 Elsevier Inc. C1 [Winkfield, Karen M.] Harvard Univ, Dept Radiat Oncol, Harvard Radiat Oncol Program, Sch Med, Boston, MA 02114 USA. [Linsenmeier, Claudia; Yock, Torunn I.; Tarbell, Nancy J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Butler, William E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Winkfield, KM (reprint author), Harvard Univ, Dept Radiat Oncol, Harvard Radiat Oncol Program, Sch Med, 100 Blossom St,Cox LL, Boston, MA 02114 USA. EM kwinkfield@partners.org NR 38 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2009 VL 73 IS 3 BP 716 EP 721 DI 10.1016/j.ijrobp.2008.05.010 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 408NE UT WOS:000263440900013 PM 18676089 ER PT J AU Li, XA Tai, A Arthur, DW Buchholz, TA Macdonald, S Marks, LB Moran, JM Pierce, LJ Rabinovitch, R Taghian, A Vicini, F Woodward, W White, JR AF Li, X. Allen Tai, An Arthur, Douglas W. Buchholz, Thomas A. Macdonald, Shannon Marks, Lawrence B. Moran, Jean M. Pierce, Lori J. Rabinovitch, Rachel Taghian, Alphonse Vicini, Frank Woodward, Wendy White, Julia R. TI VARIABILITY OF TARGET AND NORMAL STRUCTURE DELINEATION FOR BREAST CANCER RADIOTHERAPY: AN RTOG MULTI-INSTITUTIONAL AND MULTIOBSERVER STUDY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Breast radiotherapy; Breast treatment planning; Breast delineation; Breast cancer ID INTENSITY-MODULATED RADIOTHERAPY; VOLUME DELINEATION; CONFORMAL RADIOTHERAPY; RADIATION-THERAPY; INTACT BREAST; INTEROBSERVER VARIABILITY; LUMPECTOMY CAVITY; BRAIN-TUMORS; CT SCANS; IRRADIATION AB Purpose: To quantify the multi-institutional and multiobserver variability of target and organ-at-risk (OAR) delineation for breast-cancer radiotherapy (RT) and its dosimetric impact as the first step of a Radiation Therapy Oncology Group effort to establish a breast cancer atlas. Methods and Materials: Nine radiation oncologists specializing in breast RT from eight institutions independently delineated targets (e.g., lumpectomy cavity, boost planning target volume, breast, supraclavicular, axillary and internal mammary nodes, chest wall) and OARs (e.g., heart, lung) on the same CT images of three representative breast cancer patients. Interobserver differences in structure delineation were quantified regarding volume, distance between centers of mass, percent overlap, and average surface distance. Mean, median, and standard deviation for these quantities were calculated for all possible combinations. To assess the impact of these variations on treatment planning, representative dosimetric plans based on observer-specific contours were generated. Results: Variability in contouring the targets and OARs between the institutions and observers was substantial. Structure overlaps were as low as 10%, and volume variations had standard deviations up to 60%. The large variability was related both to differences in opinion regarding target and OAR boundaries and approach to incorporation of setup uncertainty and dosimetric limitations in target delineation. These interobserver differences result in substantial variations in dosimetric planning for breast RT. Conclusions: Differences in target and OAR delineation for breast irradiation between institutions/observers appear to be clinically and dosimetrically significant. A systematic consensus is highly desirable, particularly in the era of intensity-modulated and image-guided RT. (C) 2009 Elsevier Inc. C1 [Li, X. Allen; Tai, An; White, Julia R.] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Arthur, Douglas W.] Virginia Commonwealth Univ, Richmond, VA USA. [Buchholz, Thomas A.; Woodward, Wendy] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Macdonald, Shannon; Taghian, Alphonse] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marks, Lawrence B.] Duke Univ, Durham, NC USA. [Moran, Jean M.; Pierce, Lori J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Rabinovitch, Rachel] Univ Colorado, Aurora, CO USA. [Vicini, Frank] William Beaumont Hosp, Royal Oak, MI 48072 USA. RP Li, XA (reprint author), Med Coll Wisconsin, Dept Radiat Oncol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM ali@mcw.edu FU Susan Komen Breast Cancer Foundation FX XAL and JW were partially supported by a grant from the Susan Komen Breast Cancer Foundation. NR 37 TC 106 Z9 111 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2009 VL 73 IS 3 BP 944 EP 951 DI 10.1016/j.ijrobp.2008.10.034 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 408NE UT WOS:000263440900043 PM 19215827 ER PT J AU Jurkunas, UV Bitar, M Rawe, I AF Jurkunas, Ula V. Bitar, Maya Rawe, Ian TI Colocalization of Increased Transforming Growth Factor-beta-Induced Protein (TGFBIp) and Clusterin in Fuchs Endothelial Corneal Dystrophy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID KERATO-EPITHELIN MUTATIONS; IN-VITRO; BETA-IG-H3; EXPRESSION; ADHESION; GENE; FIBRONECTIN; PROMOTES; COLLAGEN; CLONING AB PURPOSE. To investigate the differential expression of TGFBIp in normal human and Fuchs endothelial corneal dystrophy (FECD) endothelial cell-Descemet's membrane (HCEC-DM) complex, and to asses the structural role of TGFBIp and clusterin (CLU) in guttae formation. METHODS. HCEC-DM complex was dissected from stroma in normal and FECD samples. Proteins were separated by 2-D gel electrophoresis and subjected to proteomic analysis. N-terminal processing of TGFBIp was detected by Western blot analysis with two separate antibodies against the N- and C-terminal regions of TGFBIp. Expression of TGFBI mRNA was compared by using real-time PCR. Subcellular localization of TGFBIp and CLU in corneal guttae was assessed by fluorescence confocal microscopy. RESULTS. A major 68-kDa fragment and a minor 39-kDa fragment of TGFBIp were identified on 2-D gels. Western blot analysis revealed an age-dependent proteolytic processing of the TGFBIp N terminus resulting in the increased formation of 57-kDa (P = 0.04) and 39-kDa (P = 0.03) fragments in older donors. FECD HCEC-DM showed a significant increase in the 68-kDa (P = 0.04), 57-kDa (P = 0.01), and 39-kDa (P = 0.03) fragments of TGFBIp. Real-time PCR analysis revealed that TGFBI mRNA was significantly increased (P = 0.04) in FECD samples. TGFBIp formed aggregates at the lower portions of guttae, next to Descemet's membrane, whereas CLU localized mostly on top of the TGFBIp-stained areas at the level of the endothelial cell nuclear plane. CONCLUSIONS. The overexpression of proaggregative protein CLU, and proadhesive protein TGFBIp, have been colocalized in the guttae. Such findings provide us with a better understanding of the major contributors involved in the aberrant cell-extracellular matrix interactions seen in the guttae of patients with FECD. (Invest Ophthalmol Vis Sci. 2009; 50: 1129-1136) DOI: 10.1167/iovs.08-2525 C1 [Jurkunas, Ula V.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Jurkunas, Ula V.; Bitar, Maya; Rawe, Ian] Schepens Eye Res Inst, Boston, MA USA. [Jurkunas, Ula V.; Bitar, Maya] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Jurkunas, UV (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM ula_jurkunas@meei.harvard.edu FU National Eye Institute [K12 EY016335]; Massachusetts Eye and Ear Lions Fund FX Supported by National Eye Institute Grant K12 EY016335 (UVJ) and by Massachusetts Eye and Ear Lions Fund (UVJ). NR 26 TC 22 Z9 22 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 MAR PY 2009 VL 50 IS 3 BP 1129 EP 1136 DI 10.1167/iovs.08-2525 PG 8 WC Ophthalmology SC Ophthalmology GA 411QO UT WOS:000263665000021 PM 19011008 ER PT J AU Hynes, BG Yan, BP Ruggiero, NJ Kiernan, GD Kiernan, TJ AF Hynes, B. G. Yan, B. P. Ruggiero, N. J., II Kiernan, G. D. Kiernan, T. J. TI The role of embolic protection in renal artery stenting SO ITALIAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Review DE Renal artery obstruction; Embolism, prevention and control; Stents ID ISCHEMIC NEPHROPATHY; BALLOON ANGIOPLASTY; DISTAL PROTECTION; RENOVASCULAR DISEASE; AORTIC-WALL; STENOSIS; PLACEMENT; REVASCULARIZATION; INTERVENTION; EMBOLIZATION AB Atherosclerotic renal artery stenosis (RAS) is increasingly recognized as a cause of severe secondary hypertension, renal dysfunction and end-stage renal failure. Percutaneous transluminal angioplasty with or without stenting of the renal artery has become the preferred mode of revascularization for RAS and has demonstrated beneficial effects with regards to improving control of hypertension and renal function in selected patients. Distal embolization of atherosclerotic debris during renal angioplasty and stenting is among the most feared complication of renal artery intervention. This paper aims to review the role of embolic protection devices in renal artery stenting for atherosclerotic renal artery stenosis. C1 [Ruggiero, N. J., II; Kiernan, T. J.] Massachusetts Gen Hosp, Dept Intervent Cardiol & Vasc Med, Boston, MA 02114 USA. [Hynes, B. G.] Cork Univ Hosp, Dept Cardiol, Cork, Ireland. [Yan, B. P.] Chinese Univ Hong Kong, Div Cardiol, Dept Med & Therapeut, Prince Wales Hosp, Hong Kong, Peoples R China. [Kiernan, G. D.] Univ Coll Dublin, Sch Med, Dublin 2, Ireland. RP Kiernan, TJ (reprint author), Massachusetts Gen Hosp, Dept Intervent Cardiol & Vasc Med, 55 Fruit St, Boston, MA 02114 USA. EM tjkiernan@partners.org RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015 NR 52 TC 0 Z9 0 U1 0 U2 5 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 1824-4777 J9 ITAL J VASC ENDOVASC JI Ital. J. Vasc. Endovasc. Surg. PD MAR PY 2009 VL 16 IS 1 BP 57 EP 64 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 421UX UT WOS:000264384900008 ER PT J AU Dirice, E Sanlioglu, AD Kahraman, S Balci, MK Omer, A Sanlioglu, S AF Dirice, Ercument Sanlioglu, Ahter D. Kahraman, Sevim Balci, Mustafa K. Omer, Abdulkadir Sanlioglu, Salih TI CELL AND GENE THERAPY APPROACHES TO PROLONG ISLET-GRAFT SURVIVAL IN PATIENTS WITH TYPE 1 DIABETES SO IUBMB LIFE LA English DT Meeting Abstract C1 [Dirice, Ercument; Sanlioglu, Ahter D.; Kahraman, Sevim; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Human Gene Therapy Unit, Antalya, Turkey. [Dirice, Ercument; Sanlioglu, Ahter D.; Kahraman, Sevim; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Dept Med Biol & Genet, Antalya, Turkey. [Balci, Mustafa K.] Akdeniz Univ, Fac Med, Div Endocrinol & Metab, TR-07058 Antalya, Turkey. [Omer, Abdulkadir] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. RI BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Salih/F-9305-2016 OI BALCI, Mustafa Kemal/0000-0002-6494-3249; NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD MAR PY 2009 VL 61 IS 3 BP 314 EP 314 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 417PV UT WOS:000264089500136 ER PT J AU Kahraman, S Dirice, E Balci, MK Omer, A Sanlioglu, S Sanlioglu, AD AF Kahraman, Sevim Dirice, Ercument Balci, Mustafa K. Omer, Abdulkadir Sanlioglu, Salih Sanlioglu, Ahter D. TI HIGHLIGHTS IN THE MOLECULAR PATHOGENESIS OF TYPE 1 DIABETES SO IUBMB LIFE LA English DT Meeting Abstract C1 [Kahraman, Sevim; Dirice, Ercument; Sanlioglu, Salih; Sanlioglu, Ahter D.] Akdeniz Univ, Fac Med, Human Gene Therapy Unit, TR-07070 Antalya, Turkey. [Kahraman, Sevim; Dirice, Ercument; Sanlioglu, Salih; Sanlioglu, Ahter D.] Akdeniz Univ, Fac Med, Dept Med Biol & Genet, TR-07070 Antalya, Turkey. [Balci, Mustafa K.] Akdeniz Univ, Fac Med, Div Endocrinol & Metab, TR-07070 Antalya, Turkey. [Omer, Abdulkadir] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. RI BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Salih/F-9305-2016 OI BALCI, Mustafa Kemal/0000-0002-6494-3249; NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD MAR PY 2009 VL 61 IS 3 BP 324 EP 325 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 417PV UT WOS:000264089500171 ER PT J AU Kahraman, S Drice, E Balci, MK Omer, A Sanlioglu, S Sanlioglu, AD AF Kahraman, Sevim Drice, Ercument Balci, Mustafa K. Omer, Abdulkadir Sanlioglu, Salih Sanlioglu, Ahter D. TI MOLECULAR PROFILE OF TRAIL AND ITS RECEPTOR EXPRESSION ON PANCREAS OF STREPTOZOTOCIN-INDUCED DIABETES IN NOD MICE SO IUBMB LIFE LA English DT Meeting Abstract C1 [Kahraman, Sevim; Drice, Ercument; Sanlioglu, Salih; Sanlioglu, Ahter D.] Akdeniz Univ, Fac Med, Gene Therapy Unit, TR-07058 Antalya, Turkey. [Balci, Mustafa K.] Akdeniz Univ, Fac Med, Div Endocrinol & Metab, TR-07058 Antalya, Turkey. [Omer, Abdulkadir] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Cambridge, MA 02138 USA. RI BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Salih/F-9305-2016 OI BALCI, Mustafa Kemal/0000-0002-6494-3249; NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD MAR PY 2009 VL 61 IS 3 BP 324 EP 324 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 417PV UT WOS:000264089500170 ER PT J AU Dirice, E Kahraman, S Balci, MK Omer, A Sanlioglu, S Sanlioglu, AD AF Dirice, Ercument Kahraman, Sevim Balci, Mustafa K. Omer, Abdulkadir Sanlioglu, Salih Sanlioglu, Ahter D. TI MOLECULAR CHARACTERIZATION OF TRAIL LIGAND AND RECEPTOR EXPRESSIONS IN CYCLOPHOSPHAMIDE-INDUCED TYPE 1 DIABETES IN NOD MICE SO IUBMB LIFE LA English DT Meeting Abstract C1 [Dirice, Ercument; Kahraman, Sevim; Sanlioglu, Salih; Sanlioglu, Ahter D.] Akdeniz Univ, Fac Med, Med Biol & Genet & Gene Therapy Unit, TR-07058 Antalya, Turkey. [Balci, Mustafa K.] Akdeniz Univ, Fac Med, Div Endocrinol & Metab, TR-07058 Antalya, Turkey. [Omer, Abdulkadir] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Cambridge, MA 02138 USA. RI Sanlioglu, Salih/F-9305-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD MAR PY 2009 VL 61 IS 3 BP 325 EP 325 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 417PV UT WOS:000264089500172 ER PT J AU Dirice, E Sanlioglu, AD Kahraman, S Omer, A Balci, MK Sanlioglu, S AF Dirice, Ercument Sanlioglu, Ahler D. Kahraman, Sevim Omer, Abdulkadir Balci, Mustafa K. Sanlioglu, Salih TI GENETICALLY ENGINEERED PANCREATIC ISLETS EXPRESSING TRAIL EXTENDS SURVIVAL OF TRANSPLANTED PANCREATIC ISLETS IN STZ-INDUCED DIABETIC RATS SO IUBMB LIFE LA English DT Meeting Abstract C1 [Dirice, Ercument; Sanlioglu, Ahler D.; Kahraman, Sevim; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Human Gene Therapy Unit, TR-07058 Antalya, Turkey. [Dirice, Ercument; Sanlioglu, Ahler D.; Kahraman, Sevim; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Dept Mol Biol & Genet, TR-07058 Antalya, Turkey. [Omer, Abdulkadir] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Cambridge, MA 02138 USA. [Balci, Mustafa K.] Akdeniz Univ, Fac Med, Div Endocrinol & Metab Dis, TR-07058 Antalya, Turkey. RI BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Salih/F-9305-2016 OI BALCI, Mustafa Kemal/0000-0002-6494-3249; NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD MAR PY 2009 VL 61 IS 3 BP 341 EP 341 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 417PV UT WOS:000264089500227 ER PT J AU Kahraman, S Dirice, E Sanlioglu, AD Balci, MK Omer, A Sanlioglu, S AF Kahraman, Sevim Dirice, Ercument Sanlioglu, Ahter D. Balci, Mustafa K. Omer, Abdulkadir Sanlioglu, Salih TI IN VIVO FLUORESCENT IMAGING OF ALLOGENEIC AND XENOGENEIC ISLET GRAFTS FOLLOWING TRANSPLANTATION SO IUBMB LIFE LA English DT Meeting Abstract C1 [Kahraman, Sevim; Dirice, Ercument; Sanlioglu, Ahter D.; Sanlioglu, Salih] Akdeniz Univ, Human Gene Therapy Unit, Antalya, Turkey. [Kahraman, Sevim; Dirice, Ercument; Sanlioglu, Ahter D.; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Dept Med Biol & Genet, Antalya, Turkey. [Balci, Mustafa K.] Akdeniz Univ, Fac Med, Div Endocrinol & Metab, Antalya, Turkey. [Omer, Abdulkadir] Harvard Univ, Sect Islet Transplantat & Cell Biol, Joslin Diabet Ctr, Cambridge, MA 02138 USA. RI BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Salih/F-9305-2016 OI BALCI, Mustafa Kemal/0000-0002-6494-3249; NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD MAR PY 2009 VL 61 IS 3 BP 378 EP 379 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 417PV UT WOS:000264089500363 ER PT J AU Skowron, G Spritzler, JG Weidler, J Robbins, GK Johnson, VA Chan, ES Asmuth, DM Gandhi, RT Lie, Y Bates, M Pollard, RB AF Skowron, Gail Spritzler, John G. Weidler, Jodi Robbins, Gregog K. Johnson, Victoria A. Chan, Ellen S. Asmuth, David M. Gandhi, Rajesh T. Lie, Yolanda Bates, Michael Pollard, Richard B. CA NIH NIAID ACTG Protocol Team & Mo TI Replication Capacity in Relation to Immunologic and Virologic Outcomes in HIV-1-Infected Treatment-Naive Subjects SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 4th International-AIDS-Society Conference on HIV Pathogenesis, Treatment and Prevention CY JUL 22-25, 2007 CL Sydney, AUSTRALIA SP Int AIDS Soc DE HIV; replication capacity; viral fitness; pathogenesis; immune reconstitution; activation; memory ID T-CELL-ACTIVATION; IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; PREDICTS DISEASE PROGRESSION; SUSTAINED VIRAL SUPPRESSION; SEQUENTIAL 3-DRUG REGIMENS; HIV-1 INFECTION; IMMUNE ACTIVATION; GASTROINTESTINAL-TRACT; INITIAL THERAPY AB Objectives: To evaluate the association between baseline (BL) replication capacity (RC) (RC(BL)) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. Methods: RC(BL) was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RC(BL) with BL and on-therapy virologic and immunologic outcomes. Results: Higher RC(BL), was associated with lower baseline CD4 (CD4(BL)) (r=-0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4(BL) activation percent (r=0.23, P < 0.0001), and lower CD4(BL) memory count (r=-0.21, P=0.0002). In a multivariable model, week 48 CD4 increase (Delta CD4(48)) was associated with lower CD4(BL) memory count and higher CD4(BL)-naive percent (P=0.004, P=0.015, respectively). The interaction between CD4(BL) and RC(BL) was significant (P=0.018), with a positive association between RC(BL) and Delta CD4(48) in subjects with higher CD4(BL) and a negative association at lower absCD4(BL). Conclusions: At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4(BL) counts. C1 [Skowron, Gail] Roger Williams Med Ctr, Div Infect Dis, Providence, RI 02908 USA. [Skowron, Gail] Miriam Hosp AIDS Clin Trials Unit, Providence, RI USA. [Spritzler, John G.; Chan, Ellen S.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Weidler, Jodi; Lie, Yolanda; Bates, Michael] Monogram Biosci Inc, Div Clin Res, San Francisco, CA USA. [Robbins, Gregog K.; Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Johnson, Victoria A.] Birmingham Vet Affairs Med Ctr, Dept Med & Microbiol, Birmingham, AL USA. [Johnson, Victoria A.] Univ Alabama, Sch Med, Birmingham, AL USA. [Asmuth, David M.; Pollard, Richard B.] Univ Calif Davis, Sch Med, Dept Internal Med Microbiol & Immunol, Sacramento, CA 95817 USA. RP Skowron, G (reprint author), Roger Williams Med Ctr, Div Infect Dis, 825 Chalkstone Ave, Providence, RI 02908 USA. EM gail_skowron@brown.edu RI Robbins, Gregory/F-7988-2011; Vella, Stefano/D-4912-2015 OI Vella, Stefano/0000-0003-2347-5984 FU NCRR NIH HHS [M01 RR000044, M01 RR000046, M01 RR000047, M01 RR000051, M01 RR000052, M01 RR000096, M01 RR005096]; NIAID NIH HHS [U01 AI039156-08, 1P30AI060354, AI46381, K01 AI062435, K01 AI062435-02, K01AI062435, P30 AI050410, P30 AI050410-04, P30 AI060354, P30 AI060354-01, R01 AI066992, R01 AI066992-01A1, R01AI066992, R44 AI050321, R44 AI050321-04, R44AI050321, U01 AI025859, U01 AI025859-13, U01 AI025868, U01 AI025868-16, U01 AI025879, U01 AI025879-13, U01 AI025897, U01 AI025897-12, U01 AI025903, U01 AI025903-13, U01 AI025915, U01 AI025915-13, U01 AI025924, U01 AI025924-13, U01 AI027658, U01 AI027659, U01 AI027659-13, U01 AI027660, U01 AI027661, U01 AI027661-14, U01 AI027664, U01 AI027665-13, U01 AI027666, U01 AI027666-13, U01 AI027668, U01 AI027670, U01 AI027670-13, U01 AI027673, U01 AI027673-13, U01 AI027675, U01 AI027675-13, U01 AI032770, U01 AI032770-13, U01 AI032775, U01 AI032775-08, U01 AI032782, U01 AI032782-12, U01 AI032783, U01 AI032783-12, U01 AI034832, U01 AI034832-11, U01 AI038858, U01 AI038858-029001, U01 AI038858-04, U01 AI039156, U01 AI046381, U01 AI046381-01, U01 AI046386, U01 AI068634, U01 AI068634-01, U01 AI068636, U01 AI068636-01, U01 AI38858, U01 AI68634, U01 AI68636, UM1 AI068634, UM1 AI068636, UM1 AI069477]; NIDDK NIH HHS [R01 DK056593] NR 42 TC 6 Z9 6 U1 0 U2 3 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 MAR 1 PY 2009 VL 50 IS 3 BP 250 EP 258 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 415FX UT WOS:000263920800002 PM 19194319 ER PT J AU Goetz, MB Leduc, R Kostman, JR Labriola, AM Lie, Y Weidler, J Coakley, E Bates, M Luskin-Hawk, R AF Goetz, Matthew Bidwell Leduc, Robert Kostman, Jay R. Labriola, Ann M. Lie, Yolanda Weidler, Jodi Coakley, Eoin Bates, Michael Luskin-Hawk, Roberta CA Long-Term Monitoring Study CPCRA TI Relationship Between HIV Coreceptor Tropism and Disease Progression in Persons With Untreated Chronic HIV Infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 47th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 17-20, 2007 CL Chicago, IL DE tropism; HIV receptors; natural history; progression; prognosis ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNCYTIUM-INDUCING PHENOTYPE; ANTIRETROVIRAL THERAPY; CLINICAL PROGRESSION; HOMOSEXUAL-MEN; CELL DEPLETION; T-CELLS; TYPE-1; AIDS; USAGE AB Objective: To assess the effect of HIV coreceptor tropism (CRT) on the relative risk of progression to a composite outcome of CD4(+) Count <= 350 cells per microliter, treatment initiation, or death. Methods: CRT assays were performed after Study Closure in baseline samples obtained from enrollees in a prospectively monitored cohort of treatment-naive adults with >= 450 CD4(+) cells per microliter and >= 1000 HIV-1 RNA copies per milliliter. Results: Dual/mixed (D/M) and R5 CRT were detected in 32 and 282 patients, respectively. The baseline CD4(+) count (617 versus 694 cells/mu L(-1) P = 0.05) differed in patients with D/M versus R5 CRT. Otherwise, baseline laboratory characteristics were similar. The relative risk of progression to the composite end point was 2.15 (P = 0.002) for D/M versus R5 CRT, 2.07 per 1.0 log(10) higher viral load (P < 0.001) and 0.87 per 50 cells per microliter higher CD4(+) cell count (P < 0.001). The effect of DIM CRT was also significant in separate analyses of time to initiation of antiretroviral therapy or CD4(+) cell count <= 350 cells per microliter. Conclusions: Untreated patients with D/M rather than R5 CRT had a faster rate of disease progression, whether assessed by a composite outcome of time to CD4(+) count <= 350 cells per microliter, treatment initiation, or death or by separate analyses of time to CD4(+) count <= 350 cells per microliter or treatment initiation. C1 [Goetz, Matthew Bidwell] Vet Affairs Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, Dept Med, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Leduc, Robert] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Kostman, Jay R.] Univ Penn Hlth Syst, Presbyterian Med Ctr, Dept Med, Philadelphia, PA USA. [Labriola, Ann M.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Lie, Yolanda; Weidler, Jodi; Coakley, Eoin; Bates, Michael] Monogram Biosci, San Francisco, CA USA. [Luskin-Hawk, Roberta] St Joseph Hosp, Dept Med, Chicago, IL USA. RP Goetz, MB (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM matthew.gowtz@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU NIAID NIH HHS [R44 AI050321, R44 AI050321-03A1, R44 AI050321-04, R44AI050321, U01 AI042170, U01 AI046362, U01 AI068641, U01 AI46362, U01AI042170] NR 56 TC 36 Z9 39 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2009 VL 50 IS 3 BP 259 EP 266 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 415FX UT WOS:000263920800003 PM 19194318 ER PT J AU Martinson, N Mohapi, L Bakos, D Gray, GE McIntyre, JA Holmes, CB AF Martinson, Neil Mohapi, Lerato Bakos, Darryl Gray, Glenda E. McIntyre, James A. Holmes, Charles B. TI Costs of Providing Care for HIV-Infected Adults in an Urban HIV Clinic in Soweto, South Africa SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral therapy; costs; HIV; PEPFAR; South Africa ID ANTIRETROVIRAL THERAPY; TRIAL AB Background: As access to antiretroviral therapy (ART) in sub-Saharan Africa expands, estimates of the costs of initiating and maintaining patients on ART are important to program planning, budgeting, and cost-effectiveness analyses. Methods: Total costs of providing HIV care, including ART, in an urban, nongovernmental, adult clinic in Soweto, South Africa, were estimated from October 2004 through March 2005. Personnel costs were estimated using individuals' work time and salary, and for across-organization services (eg, information technology), a proportion of entire annual costs was applied. Utilization of medications, laboratories, and radiographic tests were estimated by a random sample of patient charts (10%) and applied to the entire cohort. Results: Nine hundred sixty-six adult patients received care during the study period (75% female, median age 34 years, median CD4 count at ART initiation: 109 cells/mm(3)). Seventeen percent were stable on ART at entry, 61% initiated ART, and 22% did not receive ART over the course of the study Mean cost of the entire program (in US S) was $92,388 per month, and mean per patient cost of care-regardless of ART treatment status-was $98.1 per month. Among adults on ART, costs were lowest for those already on ART ($119.0/month) and highest for those initiating ART ($209.7/month) in the first month and $130.0 the following month. Human resources and antiretrovirals each accounted for one third of overall costs. Conclusions: The monthly cost of treating HIV-infected patients in an urban South African clinic was highest in the month of initiation and lower for stable patients, with costs driven predominantly by antiretrovirals and personnel. C1 [Martinson, Neil; Mohapi, Lerato; Bakos, Darryl; Gray, Glenda E.; McIntyre, James A.] Univ Witwatersrand, Perinatal HIV Res Unit, ZA-1864 Johannesburg, South Africa. [Martinson, Neil] Johns Hopkins Univ, Ctr TB Res, Baltimore, MD USA. [Holmes, Charles B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Martinson, N (reprint author), Univ Witwatersrand, Perinatal HIV Res Unit, POB 114, ZA-1864 Johannesburg, South Africa. EM neil1.martinson@gmail.com FU The President's Emergency Plan for AIDS Relief through the United States Agency for International Development [674-A-00-05-00003-00]; National Institutes of Health [RO1 A1058736-01A] FX Patient care is funded by The President's Emergency Plan for AIDS Relief through the United States Agency for International Development under the terms of award no. 674-A-00-05-00003-00. Data abstraction and managernent supported by National Institutes of Health grant RO1 A1058736-01A. NR 12 TC 25 Z9 25 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 MAR 1 PY 2009 VL 50 IS 3 BP 327 EP 330 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 415FX UT WOS:000263920800013 PM 19194308 ER PT J AU Nakajima, HH Dong, W Olson, ES Merchant, SN Ravicz, ME Rosowski, JJ AF Nakajima, Hideko Heidi Dong, Wei Olson, Elizabeth S. Merchant, Saumil N. Ravicz, Michael E. Rosowski, John J. TI Differential Intracochlear Sound Pressure Measurements in Normal Human Temporal Bones SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE middle ear; cochlea; cochlear impedance; scala vestibuli; scala tympani; stapes velocity ID HUMAN MIDDLE-EAR; INPUT IMPEDANCE; ROUND WINDOW; INNER-EAR; CONDUCTION STIMULATION; CADAVER EARS; COCHLEA; STAPES; HEARING; MOTION AB We present the first simultaneous sound pressure measurements in scala vestibuli and scala tympani of the cochlea in human cadaveric temporal bones. The technique we employ, which exploits microscale fiberoptic pressure sensors, enables the study of differential sound pressure at the cochlear base. This differential pressure is the input to the cochlear partition, driving cochlear waves and auditory transduction. In our results, the sound pressure in scala vestibuli (PSV) was much greater than scala tympani pressure (PST), except for very low and high frequencies where PST significantly affected the input to the cochlea. The differential pressure (PSV-PST) is a superior measure of ossicular transduction of sound compared to PSV alone: (PSV-PST) was reduced by 30 to 50 dB when the ossicular chain was disarticulated, whereas PSV was not reduced as much. The middle ear gain PSV/PEC and the differential pressure normalized to ear canal pressure ( PSV-PST)/PEC were generally bandpass in frequency dependence. At frequencies above 1 kHz, the group delay in the middle ear gain is about 83 mu s, over twice that of the gerbil. Concurrent measurements of stapes velocity produced estimates of cochlear input impedance, the differential impedance across the partition, and round window impedance. The differential impedance was generally resistive, while the round window impedance was consistent with compliance in conjunction with distributed inertia and damping. Our technique of measuring differential pressure can be used to study inner ear conductive pathologies (e. g., semicircular dehiscence), as well as non-ossicular cochlear stimulation (e. g., round window stimulation and bone conduction)-situations that cannot be completely quantified by measurements of stapes velocity or scala vestibuli pressure by themselves. C1 [Nakajima, Hideko Heidi; Merchant, Saumil N.; Ravicz, Michael E.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Nakajima, Hideko Heidi; Merchant, Saumil N.; Ravicz, Michael E.; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Ravicz, Michael E.; Rosowski, John J.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Merchant, Saumil N.; Rosowski, John J.] Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Dong, Wei; Olson, Elizabeth S.] Columbia Univ, Dept Otolaryngol Head & Neck Surg, New York, NY 10032 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM John_Rosowski@meei.harvard.edu FU NIH [R01 DC04798, T32 DC00020]; Wei Dong and Elizabeth Olson's time [R01 DC003130] FX This work was carried out in part through the use of MIT's Microsystems Technology Laboratories and the help of Kurt Broderick. We thank William Peake for valuable discussions and Diane Jones, Michael Slama, and Brian MacDonald for their generous efforts. This study was supported by grants R01 DC04798 and T32 DC00020 from the NIH. Wei Dong and Elizabeth Olson's time was supported by R01 DC003130. We also thank Mr. Axel Eliasen and Mr. Lakshmi Mittal for their support. NR 36 TC 54 Z9 59 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD MAR PY 2009 VL 10 IS 1 BP 23 EP 36 DI 10.1007/s10162-008-0150-y PG 14 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 438PO UT WOS:000265567900003 PM 19067078 ER PT J AU Maison, SF Casanova, E Holstein, GR Bettler, B Liberman, MC AF Maison, Stephane F. Casanova, Emilio Holstein, Gay R. Bettler, Bernhard Liberman, M. Charles TI Loss of GABA(B) Receptors in Cochlear Neurons: Threshold Elevation Suggests Modulation of Outer Hair Cell Function by Type II Afferent Fibers SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE inner ear; feedback; efferent ID GUINEA-PIG COCHLEA; SPIRAL GANGLION NEURONS; EFFERENT FIBERS; ACOUSTIC INJURY; MAMMALIAN COCHLEA; CAT COCHLEA; INNERVATION; RESPONSES; SYNAPSES; ALPHA-9 AB Despite pharmacological and immunohistochemical evidence for GABA as a neurotransmitter in the olivocochlear efferent bundle, a clear functional role of GABA in the inner ear has not emerged. To explore the role of metabotropic GABA(B) receptors, we characterized the cochlear phenotype of mice with targeted deletion of the GABA(B1) subunit and determined its tissue localization using a mouse line expressing a GFP-tagged GABAB1 subunit under the endogenous promoter. Immunostaining revealed GABAB1 expression in both type I and type II ganglion cells and in their synaptic terminals under inner and outer hair cells, respectively. No GABAB1 expression was observed in hair cells. Mean cochlear thresholds, measured via both auditory brainstem responses and distortion product otoacoustic emissions (DPOAEs), were elevated by similar to 10 dB in GABA(B1)-deficient mice, consistent with outer hair cell dysfunction. Olivocochlear efferent function, assessed via DPOAE suppression during efferent electrical stimulation, was unaffected by GABAB1 deletion. GABA(B1)-deficient mice showed increased resistance to permanent acoustic injury, with mean threshold shifts similar to 25 dB smaller than wild-types after exposure to 8-16-kHz noise at 100 dB for 2 h. In contrast, there was no vulnerability difference to temporary acoustic injury following exposure to the same noise at 94 dB for 15 min. Our results suggest that GABAergic signaling in type II afferent neurons may be required for normal outer hair cell amplifier function at low sound levels and may also modulate outer hair cell responses to high-level sound. C1 [Maison, Stephane F.; Liberman, M. Charles] Harvard Univ, Dept Otol & Laryngol, Sch Med, Boston, MA 02114 USA. [Maison, Stephane F.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Casanova, Emilio; Bettler, Bernhard] Univ Basel, Dept Biomed, Inst Physiol, Pharmazentrum, Basel, Switzerland. [Holstein, Gay R.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Holstein, Gay R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. RP Maison, SF (reprint author), Harvard Univ, Dept Otol & Laryngol, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM stephane_maison@meei.harvard.edu OI Casanova, Emilio/0000-0001-7992-5361 FU NIH-NIDCD [RO1 DC0188, R01 DC006677, P30 DC05029]; Swiss Science Foundation FX The skillful assistance of Leslie Dodds and Martin Gassmann is gratefully acknowledged. This work was supported by NIH-NIDCD grants RO1 DC0188, R01 DC006677, P30 DC05029, and the Swiss Science Foundation. NR 59 TC 17 Z9 17 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD MAR PY 2009 VL 10 IS 1 BP 50 EP 63 DI 10.1007/s10162-008-0138-7 PG 14 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 438PO UT WOS:000265567900005 PM 18925381 ER PT J AU Brown, MC Vetter, DE AF Brown, M. Christian Vetter, Douglas E. TI Olivocochlear Neuron Central Anatomy Is Normal in alpha 9 Knockout Mice SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article; Proceedings Paper CT 29th Midwinter Meeting of the Association-for-Research-in-Otolaryngology CY FEB 05-08, 2006 CL Baltimore, MD SP Assoc Res Otolaryngol DE superior olive; cochlear nucleus; acetylcholinesterase; auditory reflex; noise masking; cholinergic receptor ID RAT COCHLEAR NUCLEUS; BRAIN-STEM; HAIR-CELLS; ACETYLCHOLINE-RECEPTOR; NICOTINIC RECEPTOR; EFFERENT NEURONS; MOUSE; CAT; COLLATERALS; BRANCHES AB Olivocochlear (OC) neurons were studied in a transgenic mouse with deletion of the alpha 9 nicotinic acetylcholine receptor subunit. In this alpha 9 knockout mouse, the peripheral effects of OC stimulation are lacking and the peripheral terminals of OC neurons under outer hair cells have abnormal morphology. To account for this mouse's apparently normal hearing, it has been proposed to have central compensation via collateral branches to the cochlear nucleus. We tested this idea by staining OC neurons for acetylcholinesterase and examining their morphology in knockout mice, wild-type mice of the same background strain, and CBA/CaJ mice. Knockout mice had normal OC systems in terms of numbers of OC neurons, dendritic patterns, and numbers of branches to the cochlear nucleus. The branch terminations were mainly to edge regions and to a lesser extent the core of the cochlear nucleus, and were similar among the strains in terms of the distribution and staining density. These data demonstrate that there are no obvious changes in the central morphology of the OC neurons in alpha 9 knockout mice and make less attractive the idea that there is central compensation for deletion of the peripheral receptor in these mice. C1 [Brown, M. Christian] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Brown, M. Christian] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Brown, M. Christian] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. [Vetter, Douglas E.] Tufts Univ, Dept Neurosci, Sch Med, Boston, MA 02111 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Chris_Brown@meei.harvard.edu OI Vetter, Douglas/0000-0003-4580-3491 FU NIDCD NIH HHS [R01 DC006258, P30 DC005209]; NINDS NIH HHS [P30 NS047243]; PHS HHS [DCD 01089, DCD 006258] NR 46 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD MAR PY 2009 VL 10 IS 1 BP 64 EP 75 DI 10.1007/s10162-008-0144-9 PG 12 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 438PO UT WOS:000265567900006 PM 18941837 ER PT J AU Fava, M Wiltse, C Walker, D Brecht, S Chen, A Perahia, D AF Fava, Maurizio Wiltse, Curtis Walker, Daniel Brecht, Stephan Chen, Andrew Perahia, David TI Predictors of relapse in a study of duloxetine treatment in patients with major depressive disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Duloxetine; Placebo; Major depressive disorder; Relapse; Somatic symptoms ID PAINFUL PHYSICAL SYMPTOMS; PRIMARY-CARE; RECURRENT DEPRESSION; TREATMENT RESPONSE; REMISSION; IMPACT; VARIABILITY; SCALE AB Background: Using data from a relapse prevention study of duloxetine treatment for adults with major depressive disorder (MDD), we examined demographic- and illness-related variables to identify factors that may predict relapse of MDD. Methods: Post-hoc analyses, using the Cox proportional hazards model, were performed on data from a study designed to compare the time to relapse of MDD in duloxetine- and placebo-treated patients. Patients received open-label duloxetine 60 mg/day during a 12-week acute phase, and those who met response criteria were randomly assigned to duloxetine 60 mg/day (N= 136) or placebo (N= 142) during a 26-week double-blind continuation phase. Results: Significant predictors of relapse were VAS back pain score at entry >30, HAMD(17) total score at randomization >7, and geography (Europe vs. US). Four significant treatment-by-predictor interactions were identified: the SQ-SS pain subscale score at entry>median of 4, VAS overall pain score at entry >30, VAS overall pain score at entry>median of 26, and VAS overall pain score at randomization> median of 7. In the "greater severity" category, the risk of relapse was significantly lower for duloxetine-treated patients compared with placebo-treated patients. Limitations: These were post-hoc analyses. Conclusions: Higher levels of pain severity and depressive symptoms and a US geographical location were significant predictors of relapse in patients with MDD. (C) 2008 Published by Elsevier B.V. C1 [Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fava, Maurizio] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Wiltse, Curtis; Walker, Daniel; Chen, Andrew] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Brecht, Stephan] Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany. [Perahia, David] Eli Lilly & Co, Erl Wood, Windlesham, Surrey, England. [Perahia, David] Gordon Hosp, London, England. RP Fava, M (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bullfinch 351, Boston, MA 02114 USA. EM MFava@Partners.org NR 27 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR PY 2009 VL 113 IS 3 BP 263 EP 271 DI 10.1016/j.jad.2008.05.023 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 407UZ UT WOS:000263391100007 PM 18625521 ER PT J AU Pitteloud, N AF Pitteloud, Nelly TI GENETICS OF IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 9th International Congress of Andrology CY MAR 07-10, 2009 CL Barcelona, SPAIN SP Int Soc Androl C1 [Pitteloud, Nelly] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI PITTELOUD, Nelly/K-2709-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2009 VL 30 BP 12 EP 12 PG 1 WC Andrology SC Endocrinology & Metabolism GA 414FO UT WOS:000263849500025 ER PT J AU Tull, MT Stipelman, BA Salters-Pedneault, K Gratz, KL AF Tull, Matthew T. Stipelman, Brooke A. Salters-Pedneault, Kristalyn Gratz, Kim L. TI An examination of recent non-clinical panic attacks, panic disorder, anxiety sensitivity, and emotion regulation difficulties in the prediction of generalized anxiety disorder in an analogue sample SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Anxiety sensitivity; Emotion regulation; Generalized anxiety disorder; Panic attacks; Panic disorder ID BORDERLINE PERSONALITY-DISORDER; NATIONAL-COMORBIDITY-SURVEY; DELIBERATE SELF-HARM; STRESS SCALES DASS; DSM-IV; PSYCHOMETRIC PROPERTIES; HIERARCHICAL STRUCTURE; COLLEGE-STUDENTS; BODY VIGILANCE; CO-MORBIDITY AB Both non-clinical panic attacks and panic disorder (PD) have been found to be associated with generalized anxiety disorder (GAD). This study examined a proxy risk factor model of the relationship between non-clinical panic attacks, PD, and GAD. Specifically, it was proposed that non-clinical panic attacks and PD predict GAD only due to their shared association with anxiety sensitivity (AS) and difficulties in emotion regulation. Results demonstrated that emotion regulation difficulties reliably predicted GAD above and beyond the experience of non-clinical panic attacks and PD. However, although PD lost strength as a predictor, it remained significantly associated with GAD in the full model, providing only partial support for the proposed proxy risk factor model. Findings speak to the underlying role of emotion regulation difficulties in GAD, and suggest that it may be the shared relationship of these difficulties with both PD and GAD that partially explain the association of these disorders. (C) 2008 Elsevier Ltd All rights reserved. C1 [Tull, Matthew T.; Gratz, Kim L.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. [Stipelman, Brooke A.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Salters-Pedneault, Kristalyn] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. RP Tull, MT (reprint author), Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. EM MTull@psychiatry.umsmed.edu NR 79 TC 31 Z9 33 U1 8 U2 21 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 MAR PY 2009 VL 23 IS 2 BP 275 EP 282 DI 10.1016/j.janxdis.2008.08.002 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 407CH UT WOS:000263340700017 PM 18804947 ER PT J AU Gros, DF Antony, MM McCabe, RE Swinson, RP AF Gros, Daniel F. Antony, Martin M. McCabe, Randi E. Swinson, Richard P. TI Frequency and severity of the symptoms of irritable bowel syndrome across the anxiety disorders and depression SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Irritable bowel syndrome; Anxiety disorders; Depression; Comorbidity ID FUNCTIONAL GASTROINTESTINAL DISORDERS; PANIC DISORDER; PSYCHOMETRIC PROPERTIES; STRESS SCALES; COMORBIDITY; PREVALENCE; COMMUNITY; RELIABILITY; DISEASE; SAMPLE AB High rates of irritable bowel syndrome (IBS) symptoms have been reported in individuals diagnosed with anxiety and depressive disorders. However, most studies have investigated these relations in a single disorder, rather than a heterogeneous group of patients, thereby not allowing for comparisons across anxiety disorders and depression, or for considering the effects of comorbidity. Thus, the present study investigated the symptoms of IBS in a diverse group of patients (N = 357) by administering questionnaires and a diagnostic interview. A high frequency of IBS symptoms was found in patients with panic disorder, generalized anxiety disorder, and major depressive disorder. However, the frequency of IBS symptoms in patients with social anxiety disorder, specific phobia, and obsessive-compulsive disorder was comparable to rates found in community samples. In addition, anxiety sensitivity and illness attitudes and intrusiveness were predictive of elevated IBS symptomatology. Together, these findings emphasize the role physiological symptoms of anxiety and worry in the co-occurrence of the anxiety disorders and IBS. Published by Elsevier Ltd. C1 [Gros, Daniel F.] Ralph H Johnson VAMC, Mental Hlth Serv, Charleston, SC 29410 USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Gros, Daniel F.; Antony, Martin M.; McCabe, Randi E.; Swinson, Richard P.] St Josephs Healthcare, Anxiety Treatment & Res Ctr, Hamilton, ON, Canada. [Antony, Martin M.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [Antony, Martin M.; McCabe, Randi E.; Swinson, Richard P.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv, 109 Bee St, Charleston, SC 29410 USA. EM grosd@musc.edu RI Antony, Martin/K-1991-2012 OI Antony, Martin/0000-0002-3508-377X NR 49 TC 67 Z9 70 U1 8 U2 16 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 MAR PY 2009 VL 23 IS 2 BP 290 EP 296 DI 10.1016/j.janxdis.2008.08.004 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 407CH UT WOS:000263340700019 PM 18819774 ER PT J AU Xie, AL Skatrud, JB Barczi, SR Reichmuth, K Morgan, BJ Mont, S Dempsey, JA AF Xie, Ailiang Skatrud, James B. Barczi, Steven R. Reichmuth, Kevin Morgan, Barbara J. Mont, Sara Dempsey, Jerome A. TI Influence of cerebral blood flow on breathing stability SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE Pa(CO2); apnea ID CONGESTIVE-HEART-FAILURE; RABBIT CAROTID-BODY; SLEEP-APNEA; VENTILATORY RESPONSE; CARDIAC-FAILURE; CARBON-DIOXIDE; CYCLOOXYGENASE INHIBITORS; GRADED REDUCTION; INDOMETHACIN; HUMANS AB Xie A, Skatrud JB, Barczi SR, Reichmuth K, Morgan BJ, Mont S, Dempsey JA. Influence of cerebral blood flow on breathing stability. J Appl Physiol 106: 850-856, 2009. First published December 31, 2008; doi:10.1152/japplphysiol. 90914.2008.-Our previous work showed a diminished cerebral blood flow (CBF) response to changes in Pa(CO2) in congestive heart failure patients with central sleep apnea compared with those without apnea. Since the regulation of CBF serves to minimize oscillations in H(+) and PCO(2) at the site of the central chemoreceptors, it may play an important role in maintaining breathing stability. We hypothesized that an attenuated cerebrovascular reactivity to changes in Pa(CO2) would narrow the difference between the eupneic Pa(CO2) and the apneic threshold Pa(CO2) (Delta Pa(CO2)), known as the CO(2) reserve, thereby making the subjects more susceptible to apnea. Accordingly, in seven normal subjects, we used indomethacin (Indo; 100 mg by mouth) sufficient to reduce the CBF response to CO(2) by similar to 25% below control. The CO(2) reserve was estimated during non-rapid eye movement (NREM) sleep. The apnea threshold was determined, both with and without Indo, in NREM sleep, in a random order using a ventilator in pressure support mode to gradually reduce Pa(CO2) until apnea occurred. RESULTS: Indo significantly reduced the CO(2) reserve required to produce apnea from 6.3 +/- 0.5 to 4.4 +/- 0.7 mmHg (P = 0.01) and increased the slope of the ventilation decrease in response to hypocapnic inhibition below eupnea ( control vs. Indo: 1.06 +/- 0.10 vs. 1.61 +/- 0.27 l (.) min(-1) (.) mmHg(-1), P < 0.05). We conclude that reductions in the normal cerebral vascular response to hypocapnia will increase the susceptibility to apneas and breathing instability during sleep. C1 [Skatrud, James B.; Barczi, Steven R.] William S Middleton Mem Vet Adm Med Ctr, Genet Res Educ & Clin Ctr, Madison, WI USA. [Xie, Ailiang; Skatrud, James B.; Barczi, Steven R.; Reichmuth, Kevin; Mont, Sara] Univ Wisconsin, Dept Med, Madison, WI USA. [Dempsey, Jerome A.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. [Morgan, Barbara J.] Univ Wisconsin, Dept Orthoped & Rehabil, Madison, WI USA. RP Xie, AL (reprint author), William S Middleton Vet Hosp, Pulm Physiol Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. EM axie@facstaff.wisc.edu FU Veterans Affairs Research Service, National Heart, Lung, and Blood Institute, and American Lung Association of Wisconsin FX This work was supported by the Veterans Affairs Research Service, National Heart, Lung, and Blood Institute, and American Lung Association of Wisconsin. NR 54 TC 35 Z9 37 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2009 VL 106 IS 3 BP 850 EP 856 DI 10.1152/japplphysiol.90914.2008 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 412IY UT WOS:000263719700015 PM 19118158 ER PT J AU Adler, LA Spencer, T McGough, JJ Jiang, H Muniz, R AF Adler, Lenard A. Spencer, Thomas McGough, James J. Jiang, Hai Muniz, Rafael TI Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE adult ADHD; d-MPH-ER; long-term effectiveness; long-term safety ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DL-THREO-METHYLPHENIDATE; DOUBLE-BLIND; D,L-THREO-METHYLPHENIDATE HYDROCHLORIDE; ENANTIOSELECTIVE PHARMACOKINETICS; LABORATORY SCHOOL; BABOON BRAIN; CHILDREN; PHARMACODYNAMICS AB Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness outcomes included change from Week 5 on ADHD Rating Scale (ADHD-RS) and proportion of responders on Clinical Global Impressions-Improvement (CGI-I) scale. Results: 103 patients completed OLE, and effectiveness was evaluable in 102 patients. d-MPH-ER was well tolerated; the most common adverse events (>15%) were headache, insomnia, and decreased appetite. Mean improvements in ADHD-RS score were -10.2 for patients switched from placebo to d-MPH-ER (n = 20) and -8.4 for those maintained on d-MPH-ER (n = 82). Respective CGI-I responder rates were 95.0% and 95.1%. Conclusion: Once-daily d-MPH-ER 20 to 40 mg is safe and effective for long-term treatment of adult ADHD. (J. of Att. Dis. 2009; 12(5) 449-459) C1 [Adler, Lenard A.] New York VA Harbor Healthcare System, New York, NY USA. [Spencer, Thomas] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Spencer, Thomas] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [McGough, James J.] Univ Calif Los Angeles, Div Child & Adolescent Psychiat, Los Angeles, CA 90024 USA. [McGough, James J.] Univ Calif Los Angeles, Program Attent Deficit Hyperact Disorders, Los Angeles, CA 90024 USA. [Muniz, Rafael] Novartis Pharmaceut, USCD & MA, E Hanover, NJ USA. RP Adler, LA (reprint author), NYU, Schwartz Hlth Care Ctr, Sch Med, 5 A,530 1st Ave, New York, NY 10016 USA. EM lenard.adler@med.nyu.edu OI Adler, Len/0000-0002-9812-8234 FU Novartis Pharmaceuticals Corporation, East Hanover, NJ FX Funding for this study was provided by Novartis Pharmaceuticals Corporation, East Hanover, NJ. The Adult ADHD Research Group includes Charles E. Bailey, MD, Clinical Neuroscience Solutions, Inc., Orlando, FL; Joseph Biederman, MD, Massachusetts General Hospital, Boston; Jeffrey L. Blumer, MD, University Hospitals of Cleveland, OH; Daniel Connor, MD, University of Massachusetts Medical School, Worcester; Jeffrey N. Epstein, PhD; Duke University Medical Center, Durham, NC; Beal G. Essink, MD, Oregon Center for Clinical Investigations, Inc., Portland; Laurence L. Greenhill, MD, New York State Psychiatric Institute, New York; Howard A. Hassman, DO, CNS Research Institute, PC, Clementon, NJ; Debra J. Kelsh, MD, Vince & Associates Clinical Research, Overland Park, KS; Alan J. Levine, MD, Alpine Clinical Research Center, Boulder, CO; Peter Londborg, MD, Seattle Research Network (Seattle) LLC, WA; Moira A. Rynn, MD, University of Pennsylvania, Philadelphia; R. Bart Sangal, MD, Clinical Neurophysiology Service, PC, Troy, MI; Scott D. Segal, MD, Segal Institute for Clinical Research, North Miami, FL; Kathleen Toups, MD, Bay Area Research Institute, Lafayette, CA; and Paul K. Winner, DO, Premier Research Institute, West Palm Beach, FL. Address correspondence to Lenard A. Adler, MD, Associate Professor/Director, Adult ADHD Program, Schwartz Health Care Center, 5, A, New York University School of Medicine, 530 First Avenue, New York, NY 10016; phone: (212) 263-3580; fax: (212) 263-3581; e-mail: lenard.adler@med.nyu.edu. NR 23 TC 31 Z9 31 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 J9 J ATTEN DISORD JI J. Atten. Disord. PD MAR PY 2009 VL 12 IS 5 BP 449 EP 459 DI 10.1177/1087054708320397 PG 11 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA 583PG UT WOS:000276690200008 PM 19218542 ER PT J AU Abramowitz, JS Moore, EL Braddock, AE Harrington, DL AF Abramowitz, Jonathan S. Moore, Elizabeth L. Braddock, Autumn E. Harrington, Diana L. TI Self-help cognitive-behavioral therapy with minimal therapist contact for social phobia: A controlled trial SO JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY LA English DT Article DE Social phobia; Bibliotherapy; Self-help; Cognitive-behavioral therapy; Anxiety ID VALIDATION; DISORDER; SCALE AB Due to treatment accessibility and cost issues, interest in self-help programs (e.g., bibliotherapy, telehealth) for common psychological disorders is growing. Research supporting the efficacy of such a program for social anxiety, however, is limited. The present study examined the efficacy of an 8-week self-directed cognitive behavioral treatment with minimal therapist involvement for social phobia based on a widely available self-help book. Twenty-one adults with social phobia initially received either treatment (i.e. assigned readings in the workbook with limited therapist contact) OF were wait-listed. Wait-listed patients eventually received the same self-directed treatment. Results revealed that the self-help/minimal therapist contact treatment was superior to wait-list on most Outcome measures. Across the entire sample, reductions in social anxiety, global severity, general anxiety, and depression were observed at posttest and 3-month follow-up. These findings provide preliminary support for using this self-help workbook for individuals with mild to moderate social anxiety in conjunction with infrequent therapist visits to reinforce the treatment principles. Study limitations and future directions are discussed. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Abramowitz, Jonathan S.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Abramowitz, Jonathan S.; Moore, Elizabeth L.; Braddock, Autumn E.] Mayo Clin, Rochester, MN USA. [Moore, Elizabeth L.] Inst Living, Hartford, CT USA. [Braddock, Autumn E.] VA Greater Los Angels, Los Angeles, CA USA. RP Abramowitz, JS (reprint author), Univ N Carolina, Dept Psychol, CB 2370 Davie Hall, Chapel Hill, NC 27599 USA. EM jabramowitz@unc.edu NR 19 TC 17 Z9 18 U1 4 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7916 J9 J BEHAV THER EXP PSY JI J. Behav. Ther. Exp. Psychiatry PD MAR PY 2009 VL 40 IS 1 BP 98 EP 105 DI 10.1016/j.jbtep.2008.04.004 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 398TC UT WOS:000262753400009 PM 18514614 ER PT J AU Glaister, BC Schoen, JA Orendurff, MS Klute, GK AF Glaister, Brian C. Schoen, Jason A. Orendurff, Michael S. Klute, Glenn K. TI A Mechanical Model of the Human Ankle in the Transverse Plane During Straight Walking: Implications for Prosthetic Design SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE gait analysis; legged locomotion; physiological models; prosthetics; torsion; viscosity ID TIME AB In order to protect sensitive residual limb soft tissues, lower limb prostheses need to control torsional loads during gait. To assist with the design of a torsional prosthesis, this paper used simple mechanical elements to model the behavior of the human ankle in the transverse plane during straight walking. Motion capture data were collected from ten able-bodied subjects walking straight ahead at self-selected walking speeds. Gait cycle data were separated into four distinct states, and passive torsional springs and dampers were chosen to model the behavior in each state. Since prosthetic design is facilitated by simplicity, it was desirable to investigate if elastic behavior could account for the physiological ankle moment and include viscous behavior only if necessary to account for the inadequacies of the spring model. In all four states, a springlike behavior was able to account for most of the physiological ankle moments, rendering the use of a damper unnecessary. In State 1, a quadratic torsional spring was chosen to model the behavior, while linear torsional springs were chosen for States 2-4. A prosthetic system that actively changes stiffness could be able to replicate the physiological behavior of the human ankle in the transverse plane. The results of this study will contribute to the mechanical design and control of a biomimetic torsional prosthesis for lower limb amputees. C1 [Glaister, Brian C.; Klute, Glenn K.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Glaister, Brian C.; Schoen, Jason A.; Klute, Glenn K.] VA Puget Sound Hlth Care Syst, VA Ctr Excellence Limb Loss Prevent & Prosthet En, Seattle, WA 98108 USA. [Orendurff, Michael S.] Texas Scottish Rite Hosp Children, Movement Sci Lab, Dallas, TX 75219 USA. [Klute, Glenn K.] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. RP Glaister, BC (reprint author), Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. EM bglaiste@u.washington.edu FU Department of Veterans Affairs [A2661C, A3611I] FX This work was funded in part by the Department of Veterans Affairs Grant Nos. A2661C and A3611I. The authors wish to thank Greta Bernatz and Elizabeth Huff for assistance with data collection. NR 13 TC 3 Z9 3 U1 3 U2 12 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD MAR PY 2009 VL 131 IS 3 AR 034501 DI 10.1115/1.3005153 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 432MG UT WOS:000265137800013 PM 19154072 ER PT J AU Chen, YL Burnes, DL de Bruin, M Mujat, M de Boer, JF AF Chen, Yueli Burnes, Daina L. de Bruin, Martijn Mujat, Mircea de Boer, Johannes F. TI Three-dimensional pointwise comparison of human retinal optical property at 845 and 1060 nm using optical frequency domain imaging SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical frequency domain imaging; optical coherence tomography; image segmentation and registration; optical scattering and absorption; retina ID OCULAR FUNDUS TISSUES; COHERENCE TOMOGRAPHY; IN-VIVO; HIGH-SPEED; ULTRAHIGH-RESOLUTION; SWEPT-SOURCE; SPECTRAL INTERFEROMETRY; INTRAOCULAR DISTANCES; MODE-LOCKING; LASER AB To compare the optical properties of the human retina, 3-D volumetric images of the same eye are acquired with two nearly identical optical coherence tomography (OCT) systems at center wavelengths of 845 and 1060 nm using optical frequency domain imaging (OFDI). To characterize the contrast of individual tissue layers in the retina at these two wavelengths, the 3-D volumetric data sets are carefully spatially matched. The relative scattering intensities from different layers such as the nerve fiber, photoreceptor, pigment epithelium, and choroid are measured and a quantitative comparison is presented. OCT retinal imaging at 1060 nm is found to have a significantly better depth penetration but a reduced contrast between the retinal nerve fiber, the ganglion cell, and the inner plexiform layers compared to the OCT retinal imaging at 845 nm. (C) 2009 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3119103] C1 [Chen, Yueli; Burnes, Daina L.; de Bruin, Martijn; Mujat, Mircea; de Boer, Johannes F.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Chen, YL (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. EM jfdeboer@few.vu.nl RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU National Institutes of Health [R01-RR019768, R01-EY014975]; Department of Defense [F4 9620-01-10014] FX This research was supported in part by research grants from the National Institutes of Health (R01-RR019768 and R01-EY014975) and the Department of Defense (F4 9620-01-10014) NR 38 TC 19 Z9 19 U1 1 U2 3 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2009 VL 14 IS 2 AR 024016 DI 10.1117/1.3119103 PG 5 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 456SM UT WOS:000266868500040 PM 19405746 ER PT J AU Matsui, A Lomnes, SJ Frangioni, JV AF Matsui, Aya Lomnes, Stephen J. Frangioni, John V. TI Optical clearing of the skin for near-infrared fluorescence image-guided surgery SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical clearing; hyperosmotic agents; near-infrared fluorescence; image-guided surgery ID COHERENCE TOMOGRAPHY; HYPEROSMOTIC AGENTS; TISSUES; LIGHT; LASER; ENHANCEMENT; CONTRAST; NM AB Near-infrared (NIR) light penetrates relatively deep into skin, but its usefulness for biomedical imaging is constrained by high scattering of living tissue. Previous studies have suggested that treatment with hyperosmotic "clearing" agents might change the optical properties of tissue, resulting in improved photon transport and reduced scatter. Since this would have a profound impact on image-guided surgery, we seek to quantify the magnitude of the optical clearing effect in living subjects. A custom NIR imaging system is used to perform sentinel lymph node mapping and superficial perforator angiography in vivo on 35-kg pigs in the presence or absence of glycerol or polypropylene glycol: polyethylene glycol (PPG:PEG) pretreatment of skin. Ex-vivo, NIR fluorescent standards are placed at a fixed distance beneath sections of excised porcine skin, either preserved in saline or stored dry, then treated or not treated with glycerol. Fluorescence intensity through the skin is quantified and analyzed statistically. Surprisingly, the expected increase in intensity is not measurable either in vivo or ex vivo, unless the skin is previously dried. Histological evaluation shows a morphological difference only in stratum corneum, with this difference being negligible in living tissue. In conclusion, topically applied hyperosmotic agents are ineffective for imageguided surgery of living subjects. (C) 2009 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3103317] C1 [Matsui, Aya; Frangioni, John V.] BIDMC, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Lomnes, Stephen J.] GE Healthcare, Princeton, NJ 08540 USA. [Frangioni, John V.] BIDMC, Dept Radiol, Boston, MA 02215 USA. RP Frangioni, JV (reprint author), BIDMC, Dept Med, Div Hematol Oncol, Room SL-B05,330 Brookline Ave, Boston, MA 02215 USA. EM jfrangio@bidmc.harvard.edu FU NIH [R01-EB-005805, R01-CA-115296]; GE Healthcare FX We thank Alice Gugelmann and Barbara L. Clough for editing and Eugenia Trabucchi for administrative assistance. We would also like to thank Dr. Fumiya Iida, Massachusetts Institute of Technology, for advice on thermodynamics. This work was funded in part by NIH grants R01-EB-005805, R01-CA-115296, and research support from GE Healthcare. NR 30 TC 11 Z9 13 U1 2 U2 9 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2009 VL 14 IS 2 AR 024019 DI 10.1117/1.3103317 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 456SM UT WOS:000266868500043 PM 19405749 ER PT J AU Hwang, RW de Witte, PB Ring, D AF Hwang, Raymond W. de Witte, Pieter Bas Ring, David TI Compartment Syndrome Associated with Distal Radial Fracture and Ipsilateral Elbow Injury SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ORTHOPEDIC-TRAUMA; FOREARM FRACTURES; FLOATING ELBOW; ACUTE VOLAR; SUPRACONDYLAR; CHILDREN AB Background: Forearm compartment syndrome is an uncommon sequela of distal radial fractures. This investigation tested the hypothesis that the risk of forearm compartment syndrome associated with an unstable, operatively treated fracture of the distal end of the radius is higher with a concomitant injury of the ipsilateral elbow. Methods: All patients who sustained an unstable fracture of the distal end of the radius and/or injury to the elbow (a fracture of the proximal end of the radius and/or ulna, simple elbow dislocation, elbow fracture-dislocation, or distal humeral fracture) and were operatively treated at two level-I trauma centers over a five-year period were identified from a comprehensive database. The prevalence of compartment syndrome in a cohort with an isolated distal radial fracture and a cohort with a simultaneous distal radial fracture and elbow injury were compared. Results: Nine (15%) of fifty-nine patients who sustained a simultaneous ipsilateral distal radial fracture and elbow injury had forearm compartment syndrome develop compared with three (0.3%) of 869 patients with an isolated unstable distal radial fracture (p < 0.001, relative risk = 50). The average time from presentation to the development of compartment syndrome and subsequent fasciotomy was twenty-seven hours. Three of the nine patients with injuries to both the elbow and the wrist had a compartment syndrome develop after initial operative treatment of the injuries, requiring a return to the operating room for fasciotomy. Conclusions: Forearm compartment syndrome is a frequent complication of simultaneous unstable injuries to the elbow and the distal end of the radius. Heightened vigilance for compartment syndrome is paramount in patients with this combination of injuries. C1 [Hwang, Raymond W.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Hwang, RW (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, White 535,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 15 TC 4 Z9 5 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 2009 VL 91A IS 3 BP 642 EP 645 DI 10.2106/JBJS.H.00377 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 416CA UT WOS:000263981600017 PM 19255225 ER PT J AU Merchant, A Smielewska, M Patel, N Akunowicz, JD Saria, EA Delaney, JD Leach, RJ Seton, M Hansen, MF AF Merchant, Anand Smielewska, Magda Patel, Nimit Akunowicz, Jennifer D. Saria, Elizabeth A. Delaney, John D. Leach, Robin J. Seton, Margaret Hansen, Marc F. TI Somatic Mutations in SQSTM1 Detected in Affected Tissues From Patients With Sporadic Paget's Disease of Bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE Paget's disease of bone; pagetic osteosarcoma; Sequestosome 1; somatic mutations; laser capture microdissection ID RIBONUCLEIC-ACID; DOMAIN MUTATIONS; UBA DOMAIN; GENE; SARCOMA; LINKAGE; IDENTIFICATION; EXPRESSION; PHENOTYPE; PROTEIN AB Paget's disease of bone (PDB) is a focal disorder of bone remodeling that leads to overgrowth of affected bone, with rare progression to osteosarcoma. Extensive studies of familial PDB showed that a majority of cases harbor germline mutations in the Sequestosome1 gene (SQSTM1.). In contrast, little is known about the mutational status of SQSTM1 in sporadic PDB. We hypothesized that somatic SQSTM1 mutations might occur in the affected tissues of sporadic PDB and pagetic osteosarcoma. We used laser capture microdissection to capture homogeneous populations of cells from the affected bone or tumor of patients with sporadic PDB or pagetic osteosarcoma, respectively. DNA from these samples and appropriate controls was used for sequence analysis and allelic discrimination analysis. Two of five patients with sporadic PDB had SQSTM1(C1215T) mutations detected in their affected bone but not in their blood samples, indicating a somatic origin of the mutations. Samples from three of five sporadic pagetic osteosarcoma patients had the SQSTM1(C1215T) mutation, whereas the normal adjacent tissue from two of these tumors clearly lacked the mutation, again indicating an occurrence of somatic events. No SQSTM1 mutations were found in primary adolescent osteosarcomas. The discovery of somatic SQSTM1 mutations in sporadic PDB and pagetic osteosarcoma shows a role for SQSTM1 in both sporadic and inherited PDB. The discovery of somatically acquired mutations in both the diseased bone and tumor samples suggests a paradigm shift in our understanding of this disease. C1 [Merchant, Anand; Patel, Nimit; Akunowicz, Jennifer D.; Saria, Elizabeth A.; Hansen, Marc F.] Univ Connecticut, Ctr Hlth, Ctr Mol Med, Farmington, CT 06030 USA. [Smielewska, Magda; Delaney, John D.] Univ Connecticut, Ctr Hlth, Dept Genet, Farmington, CT 06030 USA. [Leach, Robin J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Seton, Margaret] Massachusetts Gen Hosp, New England Registry Pagets Dis Bone, Boston, MA 02114 USA. RP Hansen, MF (reprint author), Univ Connecticut, Ctr Hlth, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. EM mhansen@nso2.uchc.edu RI Merchant, Anand/B-3467-2010 FU NIAMS [AR054161, AR044904, AR047684] FX We thank the New England Registry for Paget's Disease, the Paget's Foundation for Paget's Disease of Bone and Related Disorders, and the Cooperative Human Tissue Network for support. We thank Drs G David Roodman and Deborah L Galson for the NIH3T3 cells containing MVNP; Drs Joseph Lorenzo, Yu-Feng Huang, Carmen Sapienza, and Andrew Arnold for helpful discussions and insights; and Pamela Vachon, Anita Marren, Vicki DuPaul-McGloin, and Theresa George for administrative work. This work was supported by grants from the NIAMS (AR054161, AR044904., and AR047684) and support from the Murray-Heilig Endowment. NR 46 TC 22 Z9 22 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2009 VL 24 IS 3 BP 484 EP 494 DI 10.1359/JBMR.081105 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 410JA UT WOS:000263572100012 PM 19016598 ER PT J AU Ix, JH Wassel, CL Bauer, DC Toroian, D Tylavsky, FA Cauley, JA Harris, TB Price, PA Cummings, SR Shlipak, MG AF Ix, Joachim H. Wassel, Christina L. Bauer, Douglas C. Toroian, Damon Tylavsky, Frances A. Cauley, Jane A. Harris, Tamara B. Price, Paul A. Cummings, Steven R. Shlipak, Michael G. CA Hlth ABC Study TI Fetuin-A and BMD in Older Persons: The Health Aging and Body Composition (Health ABC) Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE fetuin-A; BMD; elderly ID ALPHA-2 HS-GLYCOPROTEIN; VASCULAR CALCIFICATION; HUMAN-BONE; SERUM; DISEASE; PROTEIN; MINERALIZATION; ASSOCIATION; INHIBITION; MATRIX AB Fetuin-A is a hepatic secretory protein that promotes bone mineralization in vitro. Whether fetuin-A levels are associated with BMD in humans is unknown. The Health Aging and Body Composition study enrolled 3075 well-functioning black and white persons 70-79 yr of age and measured BMD. This cross-sectional study measured serum fetuin-A using ELISA among a random sample of 508 participants within sex and race strata. Multivariate linear regression analysis evaluated the associations of fetuin-A with BMD. Among women (n = 257), higher fetuin-A levels were significantly associated with higher total hip (p = 0.02), lumbar spine (p = 0.03), and whole body BMD (p = 0.01) in models adjusted for age, race, diabetes, alcohol and tobacco use, physical activity, body mass index, C-reactive protein levels, calcium supplement, and estrogen use. For example, each SD (0.38 g/liter) higher level of fetuin-A was associated with 0.0.16 g/cm(2) higher total hip area] BMD. The association was of similar magnitude and direction for femoral neck BMD but did not reach statistical significance (p = 0.11). In contrast, among men (n = 251), fetuin-A had no significant associations with total hip (p = 0.79), lumbar spine (p = 0.35), whole body (p = 0.46), or femoral neck BMD (p = 0.54) in multivariable models. We conclude that higher fetuin-A levels are independently associated with higher BMD among well-functioning community-dwelling older women but not older men. Future studies should evaluate whether fetuin-A may refine fracture risk assessment in older women. C1 [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92161 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92161 USA. [Wassel, Christina L.] Univ Minnesota, Dept Epidemiol & Community Hlth, Minneapolis, MN USA. [Wassel, Christina L.; Bauer, Douglas C.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med & Epidemiol & Biostat, San Francisco, CA 94143 USA. [Toroian, Damon; Price, Paul A.] Univ Calif San Diego, Div Biol Sci, San Diego, CA 92161 USA. [Tylavsky, Frances A.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Cummings, Steven R.] Calif Pacific Med Ctr, Dept Med, San Francisco, CA USA. [Cummings, Steven R.] San Francisco Coordinating Ctr, San Francisco, CA USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Med Sect, San Francisco, CA USA. RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU American Diabetes Association (ADA); Atlantic Philanthropies; John A. Hartford Foundation; ASP; American Heart Association Fellow to Faculty Transition Award (JHI) [N01-AG-6-2101, N01-AG-6-2103, N01-AG6-2106]; Intramural Research Program from the National Institutes on Aging (NIA) FX The authors thank the other investigators, the staff, and the participants of the Health ABC stud), for valuable contributions and Dr Elsa Strotmeyer for her critical review of the manuscript. This Study was supported by an American Diabetes Association (ADA)-ASP Young Investigator Innovation Award in Geriatric Endocrinology sponsored by the Atlantic Philanthropies, ADA, the John A. Hartford Foundation, and ASP, an American Heart Association Fellow to Faculty Transition Award (JHI), and Contracts N01-AG-6-2101. N01-AG-6-2103, and N01-AG6-2106 and an Intramural Research Program from the National Institutes on Aging (NIA). The funding sources NR 41 TC 21 Z9 21 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2009 VL 24 IS 3 BP 514 EP 521 DI 10.1359/JBMR.081017 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 410JA UT WOS:000263572100015 PM 19016589 ER PT J AU Schneider, JC Bassi, S Ryan, CM AF Schneider, Jeffrey C. Bassi, Sharon Ryan, Colleen M. TI Barriers Impacting Employment After Burn Injury SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID QUALITY-OF-LIFE; WORK STATUS; RETURN; PAIN; HEALTH; BACK; FENTANYL; EFFICACY; OUTCOMES; THERAPY AB This study investigates the barriers to return to work after burn injury. The electronic records of burn survivors treated at a Regional Burn Center outpatient clinic from 2001 to 2007 were retrospectively reviewed. Inclusion criteria included employment at the time of burn injury and age 18 years or older. Documentation of barriers to return to work were reviewed and classified into eight categories. Logistic regression analysis was used to determine predictors of return to work at more than 1 year. Ordered logistic regression analysis was performed to determine barrier predictors of employment. The authors identified 197 patients for inclusion in the study. The age was 37 +/- 0.8 (mean +/- SEM) and total body surface area burned was 16 +/- 1.3%. Two thirds (n = 132) of subjects returned to work by 1 year. The most common barriers included pain (n = 79), neurologic problems (n = 69), impaired mobility (n = 58), and psychiatric issues (n = 51). Pain was the most frequent barrier to return to work at all time intervals. Significant predictors of return to work at more than 12 months included length of hospital stay, inpatient rehabilitation, electric etiology, and burn at work (P < .05). Impaired mobility was a statistically significant (P < .05) barrier and other medical issues showed a trend toward statistical significance (P =.054) in predicting return to work at more than 12 months. There are many barriers that impede return to work in the burn population, including pain, neurologic problems, impaired mobility, and psychiatric issues. Early identification of those at risk for prolonged unemployment should prompt expeditious referral to comprehensive rehabilitation services that include work hardening and vocational training programs. (J Burn Care Res 2009;30:294-300) C1 [Schneider, Jeffrey C.; Bassi, Sharon] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Spaulding Rehabil Hosp,Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Ryan, Colleen M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Sumner Redstone Burn Ctr,Surg Serv, Boston, MA 02114 USA. [Ryan, Colleen M.] Shriners Burns Hosp, Boston, MA USA. RP Schneider, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Spaulding Rehabil Hosp,Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. OI Schneider, Jeffrey/0000-0002-7861-2854 NR 32 TC 22 Z9 22 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAR-APR PY 2009 VL 30 IS 2 BP 294 EP 300 DI 10.1097/BCR.0b013e318198a2c2 PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 412QI UT WOS:000263738900015 PM 19165112 ER PT J AU Shapiro, CL McCabe, MS Syrjala, KL Friedman, D Jacobs, LA Ganz, PA Diller, L Campell, M Orcena, K Marcus, AC AF Shapiro, Charles L. McCabe, Mary S. Syrjala, Karen L. Friedman, Debra Jacobs, Linda A. Ganz, Patricia A. Diller, Lisa Campell, Marci Orcena, Kathryn Marcus, Alfred C. TI The LIVESTRONG Survivorship Center of Excellence Network SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE LA English DT Article DE Lance armstrong foundation AB Introduction The LIVESTRONG (TM) Survivorship Center of Excellence Network consists of eight National Cancer Institute-designated Comprehensive Cancer Centers funded by the LAF between 2004 and 2008. The Network was created to accelerate the pace of progress in addressing the needs of the growing survivor community. Methods This paper will briefly describe some of the salient issues surrounding the care of cancer survivors, and examine models of survivorship care that are being developed in individual Centers of Excellence (COE) as well as in the overall Network. Results and Conclusions As the recommendations and policies for optimal survivorship care have to be feasible and relevant in the community setting, each COE is partnered with up to three community affiliates. Through these partnerships, the community affiliates develop survivorship initiatives at their institutions with support and guidance from their primary COE. C1 [Shapiro, Charles L.; Orcena, Kathryn] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [McCabe, Mary S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Syrjala, Karen L.; Friedman, Debra] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Jacobs, Linda A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Diller, Lisa] Dana Farber Canc Inst, Boston, MA 02115 USA. [Campell, Marci] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Marcus, Alfred C.] Univ Colorado, Ctr Canc, AMC Canc Res Ctr, Denver, CO 80262 USA. RP Shapiro, CL (reprint author), Ohio State Univ, Ctr Comprehens Canc, Starling Loving Hall,Rm B405,320 W 10th St, Columbus, OH 43210 USA. EM charles.shapiro@osumc.edu FU NCI NIH HHS [R01 CA112631] NR 40 TC 19 Z9 19 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD MAR PY 2009 VL 3 IS 1 BP 4 EP 11 DI 10.1007/s11764-008-0076-8 PG 8 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA V17XP UT WOS:000207970200002 PM 19169829 ER PT J AU Guy, TS Brzezinski, M Stechert, MM Tseng, E AF Guy, T. Sloane Brzezinski, Marek Stechert, Martin M. Tseng, Elaine TI Robotic Mammary Artery Harvest and Anastomotic Device Allows Minimally Invasive Mitral Valve Repair and Coronary Bypass SO JOURNAL OF CARDIAC SURGERY LA English DT Article ID SURGERY AB We report the case of a 60-year-old man requiring combined mitral valve repair and coronary artery bypass grafting. A unique minimally invasive approach was used combining robotic internal mammary artery harvesting, partial lower sternotomy, and single vessel coronary artery bypass grafting using an automated distal coronary artery anastomotic device. Issues in approaching the commonly encountered patient with mitral valve disease and coronary artery disease using minimally invasive techniques are discussed. (J Card Surg 2009;24:170-172). C1 [Guy, T. Sloane; Tseng, Elaine] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Surg, San Francisco, CA 94121 USA. [Brzezinski, Marek; Stechert, Martin M.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. RP Guy, TS (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Surg, 4150 Clement St, San Francisco, CA 94121 USA. EM sloane.guy@va.gov NR 7 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 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD MAR PY 2009 VL 24 IS 2 BP 170 EP 172 DI 10.1111/j.1540-8191.2008.00709.x PG 3 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 412AC UT WOS:000263694600016 PM 18778296 ER PT J AU Noygorodov, SA Gudz, TI AF Noygorodov, Sergei A. Gudz, Tatyana I. TI Ceramide and Mitochondria in Ischemia/Reperfusion SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Review DE apoptosis; mitochondria; ceramide synthase; LASS (Cer-S); sphingomyelinase; cytochrome c; Bax; PP2A; cathepsin D; Bcl-2 ID CYTOCHROME-C RELEASE; FOCAL CEREBRAL-ISCHEMIA; PERMEABILITY TRANSITION PORE; ISCHEMIC/REPERFUSED RAT-HEART; LONGEVITY ASSURANCE GENES; ACTIVATED PROTEIN-KINASES; PROGRAMMED CELL-DEATH; ACUTE-RENAL-FAILURE; JURKAT T-CELLS; INDUCED APOPTOSIS AB A hallmark of tissue injury in various models of ischemia/reperfusion (IR) is mitochondrial dysfunction and the release of mitochondrial proapoptotic proteins leading to cell death. Although IR-induced mitochondrial injury has been extensively Studied and key mitochondrial functions affected by IR are chiefly characterized, the nature of the molecule that causes loss of mitochondrial integrity and function remains obscure. It has become increasingly clear that ceramide, a membrane sphingolipid and a key mediator of cell stress responses, could play a critical role in IR-induced mitochondrial damage. Emerging data point to excessive ceramide accumulation in tissue and, specifically, ill mitochondria after IR. Exogenously added to isolated mitochondria, ceramide could mimic sonic of the mitochondrial dysfunctions Occurring ill IR. The recent identification and characterization of major enzymes in ceramide synthesis is expected to contribute to the understanding of molecular mechanisms of ceramide involvement in mitochondrial damage in IR. This review will examine the experimental evidence supporting the important role of ceramide in mitochondrial dysfunction in IR to highlight potential targets for pharmacological manipulation of ceramide levels. C1 [Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Noygorodov, Sergei A.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Noygorodov, Sergei A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Gudz, Tatyana I.] Ralph H Johnson Vet Aftairs Med Ctr, Charleston, SC 29425 USA. RP Gudz, TI (reprint author), Med Univ S Carolina, Dept Neurosci, 114 Doughty St, Charleston, SC 29425 USA. EM gudz@musc.edu FU NIH/NCCR [P20 RR 17677-04]; VA Merit award; NIH [AG16583] FX Supported by the NIH/NCCR COBRE in Lipidomics and Pathobiology P20 RR 17677-04 (T. I. Gudz), VA Merit award (T. I. Gudz). and S. A. Novgorodov was supported by NIH grant AG16583. NR 179 TC 0 Z9 0 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 EI 1533-4023 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD MAR PY 2009 VL 53 IS 3 BP 198 EP 208 PG 11 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 430TI UT WOS:000265011100003 ER PT J AU Sheng, SJ Qiao, M Pardee, AB AF Sheng, Shijie Qiao, Meng Pardee, Arthur B. TI Metastasis and AKT Activation SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Editorial Material ID GENE-EXPRESSION; PROSTATE-CANCER; BETA-CATENIN; CELL-DEATH; PATHWAY; PROLIFERATION; APOPTOSIS C1 [Sheng, Shijie] Wayne State Univ, Sch Med, Dept Pathol, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. [Qiao, Meng; Pardee, Arthur B.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sheng, SJ (reprint author), Wayne State Univ, Sch Med, Dept Pathol, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. EM ssheng@med.wayne.edu NR 20 TC 63 Z9 66 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAR PY 2009 VL 218 IS 3 BP 451 EP 454 DI 10.1002/jcp.21616 PG 4 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 404ZB UT WOS:000263190500001 PM 18988188 ER PT J AU Gascon, GG AF Gascon, Generoso G. TI Autobiography: A Clinician's Odyssey SO JOURNAL OF CHILD NEUROLOGY LA English DT Biographical-Item C1 [Gascon, Generoso G.] Brown Univ, Alpert Sch Med, Providence, RI 02912 USA. [Gascon, Generoso G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gascon, GG (reprint author), RHCI Children, 280-D Route 130,Suite 7, Forestdale, MA 02644 USA. EM ggascon@partners.org NR 0 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 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD MAR PY 2009 VL 24 IS 3 BP 379 EP 392 DI 10.1177/0883073808331356 PG 14 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 419KT UT WOS:000264219000019 ER PT J AU Buitelaar, JK Wilens, TE Zhang, SY Ning, Y Feldman, PD AF Buitelaar, Jan K. Wilens, Timothy E. Zhang, Shuyu Ning, Yu Feldman, Peter D. TI Comparison of symptomatic versus functional changes in children and adolescents with ADHD during randomized, double-blind treatment with psychostimulants, atomoxetine, or placebo SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Atomoxetine; attention deficit disorder with hyperactivity; Life Participation Scale; quality of life ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; QUALITY-OF-LIFE AB This meta-analysis was designed to determine the relationship between reduction of attention-deficit/hyperactivity disorder (ADHD) symptoms and improvement in functioning by examining short-term changes in functional and symptomatic scores in children and adolescents with ADHD. Search of atomoxetine's clinical trial database identified four studies involving a symptomatic measure, the ADHD Rating Scale-IV-Parent Version:Investigator-administered and -scored (ADHDRS-IV-Parent:Inv), and a functional measure, the Life Participation Scale for ADHD (LPS). Correlation analysis revealed a moderate-to-strong association between changes in the LPS total versus ADHDRS-IV-Parent:Inv total (r: -.68). The LPS Self-control subscale showed higher correlations than the Happy/Social subscale with the symptomatic measures. Regression analysis also showed high sensitivity for functional measures to changes in symptom severity. Stratified analysis of mean changes in ADHDRS-IV-Parent:Inv scores corresponding to standardized changes in LPS functional scores indicated that a threshold reduction of 16-18 points on the ADHDRS-IV-Parent:Inv total score was needed for functional improvements to become evident. Subjects' symptomatic improvements appear to be reflected in improvements in their social and behavioral function as measured by the LPS. These initial findings warrant verification by replication with other outcome measures. C1 [Buitelaar, Jan K.] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, NL-6500 HB Nijmegen, Netherlands. [Wilens, Timothy E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Zhang, Shuyu; Ning, Yu; Feldman, Peter D.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Buitelaar, Jan K.] Karakter Univ, Ctr Child & Adolescent Psychiat, NL-6500 HB Nijmegen, Netherlands. RP Buitelaar, JK (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM j.buitelaar@psy.umcn.nl RI Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 NR 17 TC 26 Z9 27 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD MAR PY 2009 VL 50 IS 3 BP 335 EP 342 DI 10.1111/j.1469-7610.2008.01960.x PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 417JY UT WOS:000264073500017 PM 19309330 ER PT J AU Biederman, J Petty, CR Monuteaux, MC Mick, E Clarke, A Ten Haagen, K Faraone, SV AF Biederman, Joseph Petty, Carter R. Monuteaux, Michael C. Mick, Eric Clarke, Allison Ten Haagen, Kristina Faraone, Stephen V. TI Familial risk analysis of the association between attention-deficit/hyperactivity disorder and psychoactive substance use disorder in female adolescents: a controlled study SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE ADHD; substance use; female; family risk ID DEFICIT HYPERACTIVITY DISORDER; SUBTHRESHOLD DIAGNOSES; LATE-ONSET; COMORBIDITY; ADULTS; ADHD; REPLICATION; RELATIVES; PATTERNS; PROBANDS AB A robust and bi-directional comorbidity between attention-deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD, alcohol or drug abuse, or dependence) has been consistently reported in the literature. However, this literature has been based almost exclusively on male only samples and, therefore, the findings may not generalize to females. First-degree relatives from a large sample of pediatrically and psychiatrically referred girls with (123 probands, 403 relatives) and without ADHD (112 probands, 359 relatives) were comprehensively assessed by blind raters with structured diagnostic interviews. Familial risk analysis examined the risks in first-degree relatives for ADHD and PSUD (alcohol or drug abuse or dependence) after stratifying probands by the presence and absence of these disorders. ADHD in the proband significantly increased the risk for ADHD in relatives independently of the comorbidity with PSUD. PSUD in the proband was associated with a significantly increased risk for PSUD in relatives regardless of ADHD status. There was no evidence of co-segregation or non-random mating in the families of probands with ADHD and PSUD. Patterns of familial risk analysis suggest that the association between ADHD and PSUD in adolescent females is most consistent with the hypothesis that these disorders are independently transmitted, although the hypothesis of variable expressivity could not be ruled out. These findings are consistent with previously reported patterns of familial associations between ADHD and PSUD found in adolescent males. Longer follow-up periods are needed to more fully clarify the relationship between ADHD and PSUD, as well as provide adequate power for separate analyses of alcohol and drug use. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Programs Pediat Psychopharmacol & Adul, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 55 Fruit St,YAW 6A-6900, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU Lilly Foundation; NIMH [1 R03 MH079954-01] FX This work was supported, in part, by a grant from the Lilly Foundation and NIMH grant 1 R03 MH079954-01 (Dr. Biederman). NR 29 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD MAR PY 2009 VL 50 IS 3 BP 352 EP 358 DI 10.1111/j.1469-7610.2008.02040.x PG 7 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 417JY UT WOS:000264073500018 PM 19309331 ER PT J AU Cryer, PE Axelrod, L Grossman, AB Heller, SR Montori, VM Seaquist, ER Service, FJ AF Cryer, Philip E. Axelrod, Lloyd Grossman, Ashley B. Heller, Simon R. Montori, Victor M. Seaquist, Elizabeth R. Service, F. John TI Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID INTENSIVE INSULIN THERAPY; DEPENDENT DIABETES-MELLITUS; NONINSULINOMA PANCREATOGENOUS HYPOGLYCEMIA; ISLET-CELL TUMORS; GASTRIC-BYPASS-SURGERY; BLOOD-GLUCOSE CONTROL; SURGICALLY TREATED PATIENTS; GROWTH-FACTOR-II; HYPERINSULINEMIC HYPOGLYCEMIA; GLYCEMIC CONTROL AB Objective: The aim is to provide guidelines for the evaluation and management of adults with hypoglycemic disorders, including those with diabetes mellitus. Evidence: Using the recommendations of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, the quality of evidence is graded very low (circle plus OOO), low (circle plus circle plus OO), moderate (circle plus circle plus circle plus O), or high (circle plus circle plus circle plus circle plus). `Conclusions: We recommend evaluation and management of hypoglycemia only in patients in whom Whipple's triad-symptoms, signs, or both consistent with hypoglycemia, a low plasma glucose concentration, and resolution of those symptoms or signs after the plasma glucose concentration is raised-is documented. In patients with hypoglycemia without diabetes mellitus, we recommend the following strategy. First, pursue clinical clues to potential hypoglycemic etiologies-drugs, critical illnesses, hormone deficiencies, nonislet cell tumors. In the absence of these causes, the differential diagnosis narrows to accidental, surreptitious, or even malicious hypoglycemia or endogenous hyperinsulinism. In patients suspected of having endogenous hyperinsulinism, measure plasma glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, and circulating oral hypoglycemic agents during an episode of hypoglycemia and measure insulin antibodies. Insulin or insulin secretagogue treatment of diabetes mellitus is the most common cause of hypoglycemia. We recommend the practice of hypoglycemia risk factor reduction-addressing the issue of hypoglycemia, applying the principles of intensive glycemic therapy, and considering both the conventional risk factors and those indicative of compromised defenses against falling plasma glucose concentrations-in persons with diabetes. (J Clin Endocrinol Metab 94: 709-728, 2009) C1 [Cryer, Philip E.] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Axelrod, Lloyd] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Axelrod, Lloyd] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Grossman, Ashley B.] Queen Mary Univ London, Barts & London Sch Med, London E1 2AD, England. [Heller, Simon R.] Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. [Seaquist, Elizabeth R.] Univ Minnesota, Minneapolis, MN 55455 USA. [Montori, Victor M.; Service, F. John] Mayo Clin, Rochester, MN 55905 USA. RP Cryer, PE (reprint author), Washington Univ, Sch Med, St Louis, MO 63110 USA. OI Heller, Simon/0000-0002-2425-9565; Montori, Victor/0000-0003-0595-2898 NR 190 TC 264 Z9 280 U1 0 U2 18 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 MAR PY 2009 VL 94 IS 3 BP 709 EP 728 DI 10.1210/jc.2008-1410 PG 20 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 416QN UT WOS:000264020700003 PM 19088155 ER PT J AU Travison, TG Araujo, AB Beck, TJ Williams, RE Clark, RV Leder, BZ McKinlay, JB AF Travison, Thomas G. Araujo, Andre B. Beck, Thomas J. Williams, Rachel E. Clark, Richard V. Leder, Benjamin Z. McKinlay, John B. TI Relation between Serum Testosterone, Serum Estradiol, Sex Hormone-Binding Globulin, and Geometrical Measures of Adult Male Proximal Femur Strength SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; PHYSICAL-ACTIVITY SCALE; X-RAY ABSORPTIOMETRY; ELDERLY-MEN; OSTEOPOROTIC FRACTURES; VERTEBRAL FRACTURES; STEROID-LEVELS; HIP FRACTURE; OLDER MEN; BIOCHEMICAL PARAMETERS AB Context: Although previous studies have indicated associations between circulating testosterone (T) or estradiol (E2) concentrations and bone mineral density, the relationship between gonadal steroids and skeletal geometry is not well defined. Objective: Our objective was to uncover the relation between circulating T or E2 and proximal femur geometry in a diverse sample of men. Design: We used data on 808 men enrolled in the Boston Area Community Health/Bone Study. Serum concentrations of total and calculated free T and E2 were obtained via early-morning blood sampling. The geometry of the proximal femur at three sites (the narrow neck, intertrochanter, and shaft) was obtained using the Hip Structural Analysis technology. Analyses adjusted for subjects' age, height, total body lean mass and fat mass, and level of physical activity were performed. Setting: In-home interviews accompanied by subject visits to the General Clinical Research Center at Boston University School of Medicine were performed. Study Participants: A randomly selected cohort of men living in Boston, MA (ages 30-79 yr) was included in the study. Interventions: These were not applicable. Main Outcome Measures: Bone mineral density and bone outer diameter, cross-sectional area (measuring bone material), and section modulus (an index of bending strength) were calculated. Results: In age-adjusted models, E2 was positively associated with hip strength parameters, whereas T was not. Adjustment for age and other parameters resulted in substantial reductions in, but not complete elimination of, associations between E2 and hip strength parameters. Conclusion: Circulating E2 is strongly associated with proximal femur strength, an association that is partially mediated by body composition. (J Clin Endocrinol Metab 94: 853-860, 2009) C1 [Travison, Thomas G.; Araujo, Andre B.; McKinlay, John B.] New England Res Inst, Watertown, MA 02472 USA. [Beck, Thomas J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Williams, Rachel E.; Clark, Richard V.] GlaxoSmithKline Res & Dev Ltd, Res Triangle Pk, NC 27709 USA. [Leder, Benjamin Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Travison, TG (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM ttravison@neriscience.com RI Travison, Thomas/C-7098-2011 FU National Institute on Aging [AG 20727]; National Institute of Diabetes and Digestive and Kidney Diseases [DK 56842]; GlaxoSmithKline Research and Development FX The Boston Area Community Health/Bone Survey was supported by Grant AG 20727 from the National Institute on Aging. The parent study (Boston Area Community Health) was supported by Grant DK 56842 from the National Institute of Diabetes and Digestive and Kidney Diseases. Analyses described in this manuscript were supported through an unrestricted educational grant to New England Research Institutes, Inc., from GlaxoSmithKline Research and Development. NR 47 TC 16 Z9 17 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2009 VL 94 IS 3 BP 853 EP 860 DI 10.1210/jc.2008-0668 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 416QN UT WOS:000264020700023 PM 19106273 ER PT J AU Brambilla, DJ Matsumoto, AM Araujo, AB McKinlay, JB AF Brambilla, Donald J. Matsumoto, Alvin M. Araujo, Andre B. McKinlay, John B. TI The Effect of Diurnal Variation on Clinical Measurement of Serum Testosterone and Other Sex Hormone Levels in Men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CIRCADIAN-RHYTHMS; DEHYDROEPIANDROSTERONE-SULFATE; PLASMA TESTOSTERONE; LUTEINIZING-HORMONE; BOUND TESTOSTERONE; HEALTHY-YOUNG; CORTISOL; MALES; SHBG; FSH AB Context: Although diurnal variation of testosterone and other hormones in men has been well documented, the effect of this variation on sampling during typical clinic hours has not been examined. Objective: Our objective was to examine temporal variation in serum testosterone and five other hormones in men over normal clinic hours. Design: Blood samples were collected at six separate visits, three morning visits 1-3 d apart and three afternoon visits 1-3 d apart. Setting and Participants: In Boston, MA, 66 men participated, 30-80 yr of age, randomly selected from the Boston Area Community Health Survey who completed at least five visits. Main Outcome Measures: The age-specific ratio of hormone level at times ranging from 0801-1600 h to hormone level at 0800 h was calculated. Ratios were calculated from parameter estimates obtained from cosinor models. Results: In men 30-40 yr old, testosterone levels were 20-25% lower at 1600 h than at 0800 h. The difference declined with age, with a 10% difference at 70 yr. 17 men with at least one of three measurements less than 300 ng/dl (10.4 nmol/liter) after 1200 h had normal testosterone levels at all three visits before 1200 h (five of eight men 30-47 yr old, four of nine men 66-80 yr old). Much lower levels of diurnal variation were found for dihydrotestosterone, SHBG, LH, FSH, and estradiol at all ages. Conclusions: Our results support the recommendation of restricting testosterone measurements to morning hours in both young and older men. Limited diurnal variation in other hormones indicates that sampling through the day is appropriate. (J Clin Endocrinol Metab 94: 907-913, 2009) C1 [Araujo, Andre B.; McKinlay, John B.] New England Res Inst, Watertown, MA 02472 USA. [Brambilla, Donald J.] Res Triangle Inst, Rockville, MD 20852 USA. [Matsumoto, Alvin M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98108 USA. [Matsumoto, Alvin M.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Araujo, AB (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM aaraujo@neriscience.com RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU National Institute on Aging of the National Institutes of Health [AG23027] FX This study was supported by Grant AG23027 from the National Institute on Aging of the National Institutes of Health. NR 21 TC 118 Z9 120 U1 0 U2 6 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 MAR PY 2009 VL 94 IS 3 BP 907 EP 913 DI 10.1210/jc.2008-1902 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 416QN UT WOS:000264020700030 PM 19088162 ER PT J AU Wide, L Eriksson, K Sluss, PM Hall, JE AF Wide, Leif Eriksson, Karin Sluss, Patrick M. Hall, Janet E. TI Serum Half-Life of Pituitary Gonadotropins Is Decreased by Sulfonation and Increased by Sialylation in Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; COMMON GENETIC VARIANT; LUTEINIZING-HORMONE; MOLECULAR-BASIS; HUMAN FSH; LUTROPIN; RECEPTOR; RECOGNITION; OLIGOSACCHARIDES; DISAPPEARANCE AB Context: The gonadotropins are secreted from the human pituitary as spectra of isoforms with different degrees of sulfonation and sialylation of the oligosaccharides, modifications suspected to determine their half-lives in the circulation. Objectives: Our objectives were to determine the isoform composition of the serum gonadotropins during GnRH receptor blockade, and to estimate the half-lives in circulation of isoforms with 0-1-2-3 sulfonated N-acetylgalactosamine (SO3-GalNAc) residues. Design/Participants: Serum samples were collected in seven healthy women before and up to 20 h after administration of the NAL-GLU GnRH antagonist. Main Outcome Measures: The number of sialic acid and SO3-GalNAc residues per LH and FSH molecule and the distribution of molecules with 0-1-2-3 sulfonated residues were measured. The half-lives were estimated by monoexponential decay. Results: More sialylated and less sulfonated gonadotropin isoforms remain longer in circulation during GnRH receptor blockade. LH isoforms with two and three sulfonated residues per molecule had shorter half- lives compared with those with zero and one (109 and 80 vs. 196 and 188 min; P < 0.01). FSH isoforms with one and two sulfonated residues had shorter half- lives than those with zero (485 and 358 vs. 988 min; P < 0.01). Conclusions: The decline in LH and FSH during GnRH receptor blockade is associated with a decrease in sulfonated and increase in sialylated residues. The rapid disappearance of LH isoforms with two and three SO3-GalNAc residues suggests their removal by hepatic SO3-GalNAc-receptors similar to those in rodents. Episodical secretion of spectra of isoforms with different half-lives is expected to lead to continuous changes in gonadotropin isoform compositions in blood. (J Clin Endocrinol Metab 94: 958-964, 2009) C1 [Wide, Leif; Eriksson, Karin] Univ Hosp, Dept Med Sci, SE-75185 Uppsala, Sweden. [Sluss, Patrick M.; Hall, Janet E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Wide, L (reprint author), Univ Hosp, Dept Clin Chem, SE-75185 Uppsala, Sweden. EM leif.wide@medsci.uu.se FU Academic Laboratory, University Hospital, Uppsala, Sweden; National Institutes of Health [NIH R01 AG13241] FX This work was supported by grants from the Academic Laboratory, University Hospital, Uppsala, Sweden (to L. W.), and from the National Institutes of Health (to J. E. H.) (NIH R01 AG13241). NR 21 TC 25 Z9 28 U1 2 U2 5 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 MAR PY 2009 VL 94 IS 3 BP 958 EP 964 DI 10.1210/jc.2008-2070 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 416QN UT WOS:000264020700038 PM 19116233 ER PT J AU Yoo, BK Emdad, L Su, Z Villanueva, A Chiang, DY Mukhopadhyay, ND Mills, AS Waxman, S Fisher, RA Llovet, JM Fisher, PB Sarkar, D AF Yoo, Byoung Kwon Emdad, Luni Su, Zao-zhong Villanueva, Augusto Chiang, Derek Y. Mukhopadhyay, Nitai D. Mills, Alan Scott Waxman, Samuel Fisher, Robert A. Llovet, Josep M. Fisher, Paul B. Sarkar, Devanand TI Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BETA-CATENIN GENE; PHASE-II; COMBINATION CHEMOTHERAPY; THYMIDYLATE SYNTHASE; TUMOR PROGRESSION; CANCER-CELLS; EXPRESSION; PROTEIN; VIRUS; 5-FLUOROURACIL AB Hepatocellular carcinoma (HCC) is a highly aggressive vascular cancer characterized by diverse etiology, activation of multiple signal transduction pathways, and various gene mutations. Here, we have determined a specific role for astrocyte elevated gene-1 (AEG1) in HCC pathogenesis. Expression of AEG1 was extremely low in human hepatocytes, but its levels were significantly increased in human HCC. Stable overexpression of AEG1 converted nontumorigenic human HCC cells into highly aggressive vascular tumors, and inhibition of AEG1 abrogated tumorigenesis by aggressive HCC cells in a xenograft model of nude mice. In human HCC, AEG1 overexpression was associated with elevated copy numbers. Microarray analysis revealed that AEG1 modulated the expression of genes associated with invasion, metastasis, chemoresistance, angiogenesis,and senescence. AEG1 also was found to activate Wnt/beta-catenin signaling via ERK42/44 activation and upregulated lymphoid-enhancing factor 1/T cell factor 1 (LEF1/TCF1), the ultimate executor of the Writ pathway, important for HCC progression. Inhibition studies further demonstrated that activation of Writ signaling played a key role in mediating AEG1 function. AEG1 also activated the NF-kappa B pathway, which may play a role in the chronic inflammatory changes preceding HCC development. These data indicate that AEG1 plays a central role in regulating diverse aspects of HCC pathogenesis. Targeted inhibition of AEG1 might lead to the shutdown of key elemental characteristics of HCC and could lead to an effective therapeutic strategy for HCC. C1 [Yoo, Byoung Kwon; Emdad, Luni; Su, Zao-zhong; Fisher, Paul B.; Sarkar, Devanand] Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA 23298 USA. [Villanueva, Augusto; Llovet, Josep M.] Hosp Clin Barcelona, Liver Unit, HCC Translat Res Lab, Barcelona Clin Liver Canc Grp,IDIBAPS,CIBERehd, Barcelona, Spain. [Chiang, Derek Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chiang, Derek Y.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Chiang, Derek Y.] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA USA. [Mukhopadhyay, Nitai D.] Virginia Commonwealth Univ, Sch Med, Dept Biostat, Richmond, VA USA. [Mills, Alan Scott] Virginia Commonwealth Univ, Sch Med, Dept Pathol, Richmond, VA USA. [Waxman, Samuel; Llovet, Josep M.] Mt Sinai Sch Med, Mt Sinai Liver Canc Program, New York, NY USA. [Fisher, Robert A.] Virginia Commonwealth Univ, Sch Med, Dept Surg, Div Transplant Surg, Richmond, VA USA. [Llovet, Josep M.] Inst Catalana Rec & Estudis Avancats, Barcelona, Spain. [Fisher, Paul B.; Sarkar, Devanand] Virginia Commonwealth Univ, Sch Med, Inst Mol Med, Richmond, VA USA. [Fisher, Paul B.; Sarkar, Devanand] Virginia Commonwealth Univ, Sch Med, Massey Canc Ctr, Richmond, VA USA. RP Sarkar, D (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, 401 Coll St,POB 980035, Richmond, VA 23298 USA. EM dsarkar@vcu.edu RI Augusto, Villanueva/F-9378-2012; Llovet, Josep M /D-4340-2014; OI Augusto, Villanueva/0000-0003-3585-3727; Llovet, Josep M /0000-0003-0547-2667; Chiang, Derek/0000-0002-1131-6065 FU Goldhirsh Foundation grant; NIH [P01 NS31492, R01 CA035675, R01 DK076986]; Spanish National Health Institute [SAF-2007-61898]; Samuel Waxman Cancer Research Foundation; Liver Tissue Cell Distribution System [N01DK92310] FX The authors would like to thank Nicollaq Vozhilla and Eun Sook Park for excellent technical assistance. The present study was supported in part by a Goldhirsh Foundation grant (to D. Sarkar), NIH grants (P01 NS31492 and R01 CA035675 to P.B. Fisher; R01 DK076986 to J.M. Llovet), a Spanish National Health Institute grant (SAF-2007-61898 to J.M. Llovet), the Samuel Waxman Cancer Research Foundation (to J.M. Llovet), and a grant from the Liver Tissue Cell Distribution System (LTCDS) (N01DK92310 to R-A. Fisher). D. Sarkar is the Harrison Endowed Scholar in Cancer Research. P.B. Fisher holds the Thelma Newmeyer Corman Chair in Cancer Research and is a Samuel Waxman Cancer Research Foundation investigator. NR 79 TC 201 Z9 225 U1 4 U2 16 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 MAR PY 2009 VL 119 IS 3 BP 465 EP 477 DI 10.1172/JCI36460 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 415NP UT WOS:000263941000010 PM 19221438 ER PT J AU Sugimoto, M Wu, JY Abudayyeh, S Hoffman, J Brahem, H Al-Khatib, K Yamaoka, Y Graham, DY AF Sugimoto, Mitsushige Wu, Jeng-Yih Abudayyeh, Suhaib Hoffman, Jill Brahem, Hajer Al-Khatib, Khaldun Yamaoka, Yoshio Graham, David Y. TI Unreliability of Results of PCR Detection of Helicobacter pylori in Clinical or Environmental Samples SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; IN-SITU HYBRIDIZATION; DENTAL PLAQUE; ORAL-CAVITY; CLARITHROMYCIN RESISTANCE; ERADICATION THERAPY; BIOPSY SPECIMENS; RAPID DETECTION; HIGH PREVALENCE; NESTED PCR AB The aim of this study was to compare published Helicobacter pylori primer pairs for their ability to reliably detect H. pylori in gastric biopsy specimens and salivary samples. Detection limits of the 26 PCR primer pairs previously described for detection of H. pylori DNA in clinical samples were determined. Sensitivity and specificity were determined using primers with detection limits of < 100 CFU/ml using 50 H. pylori-positive and -negative (by concordance by culture and histology) coded gastric biopsy specimens. These results were then confirmed with gastric biopsy specimens and saliva from patients with confirmed H. pylori status. Five of the twenty-six previously reported primer pairs (HP64-f/HP64-r, HP1/HP2, EHC-U/EHC-L, VAG-F/VAG-R, and ICT37/ICT38) had detection limits of < 100 CFU/ml in the presence of gastric tissue. None had 100% specificity or sensitivity; all produced false-positive results. The HP64-f/HP64-r for ureA and HP1/HP2 for 16S rRNA individually had sensitivities and specificities of > 90% with gastric biopsy specimens. No combinations of primer pairs improved the results. Using these five primer pairs, 54% of the positive saliva samples were determined to be false positive; both the HP64-f/HP64-r and the HP1/HP2 sets produced false positives with saliva. We conclude that clinicians should not rely on results using current PCR primers alone to decide the H. pylori status of an individual patient or as a basis for treatment decisions. The results of studies based on PCR identification of H. pylori in environmental samples should be viewed with caution. Possibly, specific primers sets can be identified based on the presence of multiple putative virulence factor genes. C1 [Graham, David Y.] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, RM 3A-320,111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu FU Office of Research and Development Medical Research Service Department of Veterans Affairs; Public Health Service [DK56338]; NIH [DK62813] FX This material is based upon work supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs and by Public Health Service grant DK56338, which funds the Texas Medical Center Digestive Diseases Center. In the last 3 years, D.Y.G. has received small amounts of grant support and/or free drugs or urea breath tests from Meretek, Jannsen/Eisai, and TAP, and BioHit for investigator- initiated and completely investigator-controlled research. D. Y. G. is a consultant for Novartis in relation to vaccine development for treatment or prevention of H. pylori infection. D. Y. G. is also a paid consultant for Otsuka Pharmaceuticals and until July 2007 was member of the Board of Directors of Meretek Diagnostics, the manufacturer of the 13C- urea breath test. D. Y. G. also receives royalties on the Baylor College of Medicine patent covering materials related to 13C-urea breath test. Y. Y. is supported in part by a grant from the NIH (DK62813). NR 57 TC 27 Z9 29 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2009 VL 47 IS 3 BP 738 EP 742 DI 10.1128/JCM.01563-08 PG 5 WC Microbiology SC Microbiology GA 413UU UT WOS:000263818800033 PM 19129407 ER PT J AU Mahlen, SD Clarridge, JE AF Mahlen, Steven D. Clarridge, Jill E., III TI Oral Abscess Caused by Campylobacter rectus: Case Report and Literature Review SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID WOLINELLA-RECTA; PERIODONTITIS LESIONS; GEN-NOV; GINGIVITIS; MICROBIOTA; INFECTIONS; GRACILIS; HEALTH; BONE AB Campylobacter rectus was isolated under routine anaerobic conditions (no additional hydrogen gas in the atmosphere) from an oral, nonperiodontal abscess from a patient with gastroesophageal adenocarcinoma. We report the first case of a palate abscess caused by C. rectus and review the literature and atmospheric requirements of this organism. C1 [Clarridge, Jill E., III] Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Serv, Seattle, WA 98108 USA. [Mahlen, Steven D.; Clarridge, Jill E., III] Univ Washington, Dept Lab Med, USA, Seattle, WA 98195 USA. RP Clarridge, JE (reprint author), VA PSHCS, Pathol & Lab Serv 113, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Jill.clarridge@va.gov NR 21 TC 10 Z9 10 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2009 VL 47 IS 3 BP 848 EP 851 DI 10.1128/JCM.01590-08 PG 4 WC Microbiology SC Microbiology GA 413UU UT WOS:000263818800060 PM 19109480 ER PT J AU Matthay, KK Quach, A Huberty, J Franc, BL Hawkins, RA Jackson, H Groshen, S Shusterman, S Yanik, G Veatch, J Brophy, P Villablanca, JG Maris, JM AF Matthay, Katherine K. Quach, Alekist Huberty, John Franc, Benjamin L. Hawkins, Randall A. Jackson, Hollie Groshen, Susan Shusterman, Suzanne Yanik, Gregory Veatch, Janet Brophy, Patricia Villablanca, Judith G. Maris, John M. TI Iodine-131-Metaiodobenzylguanidine Double Infusion With Autologous Stem-Cell Rescue for Neuroblastoma: A New Approaches to Neuroblastoma Therapy Phase I Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; HIGH-RISK NEUROBLASTOMA; REFRACTORY NEUROBLASTOMA; I-131 METAIODOBENZYLGUANIDINE; TARGETED RADIOTHERAPY; DOSE-ESCALATION; TUMOR RESPONSE; I-131-METAIODOBENZYLGUANIDINE; DOSIMETRY; TOXICITY AB Purpose Iodine-131-metaiodobenzylguanidine (I-131-MIBG) provides targeted radiotherapy with more than 30% response rate in refractory neuroblastoma, but activity infused is limited by radiation safety and hematologic toxicity. The goal was to determine the maximum-tolerated dose of I-131-MIBG in two consecutive infusions at a 2-week interval, supported by autologous stem-cell rescue (ASCR) 2 weeks after the second dose. Patients and Methods The I-131-MIBG dose was escalated using a 3 + 3 phase I trial design, with levels calculated by cumulative red marrow radiation index (RMI) from both infusions. Using dosimetry, the second infusion was adjusted to achieve the target RMI, except at level 4, where the second infusion was capped at 21 mCi/kg. Results Twenty-one patients were enrolled onto the study at levels 1 to 4, with 18 patients assessable for toxicity and 20 patients assessable for response. Cumulative I-131-MIBG given to achieve the target RMI ranged from 22 to 50 mCi/kg, with cumulative RMI of 3.2 to 8.92 Gy. No patient had a dose-limiting toxicity. Reversible grade 3 nonhematologic toxicity occurred in six patients at level 4, establishing the recommended cumulative dose as 36 mCi/kg. The median time to absolute neutrophil count more than 500/mu L after ASCR was 13 days (4 to 27 days) and to platelet independence was 17 days (6 to 47 days). Responses included two partial responses, eight mixed responses, three stable disease, and seven progressive disease. Responses by semiquantitative MIBG score occurred in eight patients, soft tissue responses occurred in five of 11 patients, but bone marrow responses occurred in only two of 13 patients. Conclusion The lack of toxicity with this approach allowed dramatic dose intensification of I-131-MIBG, with minimal toxicity and promising activity. J Clin Oncol 27: 1020-1025. (C) 2009 by American Society of Clinical Oncology C1 [Matthay, Katherine K.] Univ Calif San Francisco, Dept Pediat, Nucl Med Program, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, Nucl Med Program, San Francisco, CA 94143 USA. Univ Calif San Francisco, Childrens Hosp, San Francisco, CA 94143 USA. Univ So Calif, Keck Sch Med, Dept Radiol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Biostat, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. Childrens Hosp, Los Angeles, CA 90027 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. Univ Michigan, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Matthay, KK (reprint author), Univ Calif San Francisco, Dept Pediat, Nucl Med Program, 505 Parnassus,M647, San Francisco, CA 94143 USA. EM matthayk@peds.ucsf.edu FU National Institutes of Health [PO1 CA81403, R21 CA097758, CCSG CA82103, 2MO1 RR0127, M01- RR00240]; Campini Foundation; Conner Research Fund; Katie Dougherty Foundation; Kasle and Tkalcevik Neuroblastoma Research Fund; Thrasher Research Fund; Alex's Lemonade Stand Foundation; Evan T. J. Dunbar Neuroblastoma Foundation; Children's Neuroblastoma Cancer Foundation; Milken Family Foundation; Pediatric Cancer Research Foundation FX Supported in part by the National Institutes of Health Grants No. PO1 CA81403, R21 CA097758, CCSG CA82103, 2MO1 RR0127, M01- RR00240, as well by donations from the Campini Foundation, the Conner Research Fund, the Katie Dougherty Foundation, Kasle and Tkalcevik Neuroblastoma Research Fund, the Thrasher Research Fund, Alex's Lemonade Stand Foundation, the Evan T. J. Dunbar Neuroblastoma Foundation, Children's Neuroblastoma Cancer Foundation, Milken Family Foundation, and Pediatric Cancer Research Foundation. NR 30 TC 60 Z9 61 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2009 VL 27 IS 7 BP 1020 EP 1025 DI 10.1200/JCO.2007.15.7628 PG 6 WC Oncology SC Oncology GA 447LV UT WOS:000266193500005 PM 19171714 ER PT J AU Ajani, JA Winter, KA Gunderson, LL Pedersen, J Benson, AB Thomas, CR Mayer, RJ Haddock, MG Rich, TA Willett, CG AF Ajani, Jaffer A. Winter, Kathryn A. Gunderson, Leonard L. Pedersen, John Benson, Al B., III Thomas, Charles R., Jr. Mayer, Robert J. Haddock, Michael G. Rich, Tyvin A. Willett, Christopher G. TI US Intergroup Anal Carcinoma Trial: Tumor Diameter Predicts for Colostomy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADIATION; CANCER; CHEMOTHERAPY; RADIOTHERAPY AB Purpose The US Gastrointestinal Intergroup Radiation Therapy Oncology Group 98-11 anal carcinoma trial showed that cisplatin-based concurrent chemoradiotherapy resulted in a significantly higher rate of colostomy compared with mitomycin-based therapy. Established prognostic variables for patients with anal carcinoma include tumor diameter, clinical nodal status, and sex, but pretreatment variables that would predict the likelihood of colostomy are unknown. Methods A secondary analysis was performed by combining patients in the two treatment arms to evaluate whether new predictive and prognostic variables would emerge. Univariate and multivariate analyses were carried out to correlate overall survival (OS), disease-free survival, and time to colostomy (TTC) with pretreatment and treatment variables. Results Of 682 patients enrolled, 644 patients were assessable and analyzed. In the multivariate analysis, tumor-related prognosticators for poorer OS included node-positive cancer (P <= .0001), large (> 5 cm) tumor diameter (P = .01), and male sex (P = .016). In the treatment-related categories, cisplatin-based therapy was statistically significantly associated with a higher rate of colostomy (P = .03) than was mitomycin-based therapy. In the pretreatment variables category, only large tumor diameter independently predicted for TTC (P = .008). Similarly, the cumulative 5-year colostomy rate was statistically significantly higher for large tumor diameter than for small tumor diameter (Gray's test; P = .0074). Clinical nodal status and sex were not predictive of TTC. Conclusion The combined analysis of the two arms of RTOG 98-11, representing the largest prospective database, reveals that tumor diameter (irrespective of the nodal status) is the only independent pretreatment variable that predicts TTC and 5-year colostomy rate in patients with anal carcinoma. J Clin Oncol 27: 1116-1121. (C) 2009 by American Society of Clinical Oncology C1 [Ajani, Jaffer A.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. Mayo Clin, Scottsdale, AZ USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Oregon, Portland, OR USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Virginia, Charlottesville, VA USA. Duke Univ, Durham, NC USA. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. RP Ajani, JA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, 1515 Holcombe Blvd,Mail Stop 426, Houston, TX 77030 USA. EM jajani@mdanderson.org FU Radiation Therapy Oncology Group [U10 CA21661]; Community Clinical Oncology Program [U10 CA37422]; National Cancer Institute, Bethesda, MD [U10 CA32115] FX Supported by Grants No. Radiation Therapy Oncology Group U10 CA21661, Community Clinical Oncology Program U10 CA37422, and Stat U10 CA32115 from the National Cancer Institute, Bethesda, MD. NR 15 TC 39 Z9 40 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2009 VL 27 IS 7 BP 1116 EP 1121 DI 10.1200/JCO.2008.19.6857 PG 6 WC Oncology SC Oncology GA 447LV UT WOS:000266193500019 PM 19139424 ER PT J AU Szegedi, A Jansen, WT van Willigenburg, APP van der Meulen, E Stassen, HH Thase, ME AF Szegedi, Armin Jansen, Wim T. van Willigenburg, Arjen P. P. van der Meulen, Egbert Stassen, Hans H. Thase, Michael E. TI Early Improvement in the First 2 Weeks as a Predictor of Treatment Outcome in Patients With Major Depressive Disorder: A Meta-Analysis Including 6562 Patients SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID STAR-ASTERISK-D; ANTIDEPRESSANT ACTION; TREATMENT RESPONSE; DRUG RESPONSE; DELAYED-ONSET; FLUOXETINE; GUIDELINES; PAROXETINE; SERTRALINE; TITRATION AB Objective: New evidence indicates that treatment response can be predicted with high sensitivity after 2 weeks of treatment. Here, we assess whether early improvement with antidepressant treatment predicts treatment outcome in patients with major depressive disorder (MDD). Data Sources: Forty-one clinical trials comparing mirtazapine with active comparators or placebo in inpatients and outpatients (all-treated population, N = 6907; intent-to-treat population, N = 6562) with MDD (DSM-III-R or DSM-IV Criteria) were examined for early improvement (>= 20% score reduction from baseline on the 17-item Hamilton Rating Scale for Depression [HAM-D-17] within 2 weeks of treatment) and its relationship to treatment outcome. Study Selection: Data were obtained from a systematic search of single- or double-blind clinical trials (clinical trials database, Organon, a part of Schering-Plough Corporation, Oss, The Netherlands). All included trials (a total of 41) employed antidepressant treatment for more than 4 weeks and a maximum of 8 weeks. The studies ranged from March 1982 to December 2003. Trials were excluded if there were no HAM-D-17 ratings available, no diagnosis of MDD, or if the study was not blinded. Trials were also excluded if HAM-D-17 assessments were not available at week 2, week 4. and at least once beyond week 4. Data Synthesis: Early improvement predicted stable response and stable remission with high sensitivity (>= 81% and >= 87%, respectively). Studies utilizing rapid titration vs. slow titration of mirtazapine demonstrated improved sensitivity for stable responders (98%, [95% CI = 93% to 100%] vs. 91% [95% CI = 89% to 93%]) and stable remitters (100%, [95% CI = 92% to 100%] vs. 93% [95% CI = 91% to 95%]). Negative predictive values for stable responders and stable remitters were much higher (range = 82%-100%) than positive predictive values (range = 19%-60%). Conclusions: These results indicate that early improvement with antidepressant medication can predict subsequent treatment outcome with high sensitivity in patients with major depressive disorder. The high negative predictive values indicate little chance of stable response or stable remission in the absence of improvement within 2 weeks. A lack of improvement during the first 2 weeks of therapy may indicate that changes in depression management should be considered earlier than conventionally thought. C1 [Szegedi, Armin; van Willigenburg, Arjen P. P.] Organon, Roseland, NJ USA. [Stassen, Hans H.] Psychiat Univ Hosp, Zurich, Switzerland. [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. RP Szegedi, A (reprint author), Schering Plough Res Inst, Global Clin Res CNS, 56 Livingston Ave, Roseland, NJ 07068 USA. EM armin.szegedi@spcorp.com RI Szegedi, Armin/M-9184-2016 OI Szegedi, Armin/0000-0001-6487-4071 FU Organon FX Financial support for this report was provided by an unrestricted educational grant from Organon, a part of Schering-Plough Corporation. NR 34 TC 135 Z9 147 U1 0 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 MAR PY 2009 VL 70 IS 3 BP 344 EP 353 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 426VC UT WOS:000264735200006 PM 19254516 ER PT J AU Shapiro, MD Dodd, JD Kalva, S Wittram, C Hsu, J Nasir, K Liu, B Nagurney, JT Kalra, MK Nichols, JH Cury, RC Abbara, S Tawakol, A Brady, TJ Hoffman, U AF Shapiro, Michael D. Dodd, Jonathan D. Kalva, Sanjeeva Wittram, Conrad Hsu, Joe Nasir, Khurram Liu, Bob Nagurney, John T. Kalra, Mannudeep K. Nichols, John H. Cury, Ricardo C. Abbara, Suhny Tawakol, Ahmed Brady, Thomas J. Hoffman, Udo TI A Comprehensive Electrocardiogram-Gated 64-Slice Multidetector Computed Tomography Imaging Protocol to Visualize the Coronary Arteries, Thoracic Aorta, and Pulmonary Vasculature in a Single Breath Hold SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE multidetector computed tomography; computed tomography angiography; coronary artery disease; pulmonary embolism; aortic dissection ID ACUTE CHEST-PAIN; MYOCARDIAL-INFARCTION; EMERGENCY-DEPARTMENT; DIAGNOSTIC-ACCURACY; HEART-RATE; ANGIOGRAPHY; QUALITY; CT; EXPERIENCE; PATIENT AB Objectives: Advances in computed tomography technology may permit the evaluation of coronary disease, aortic dissection, and pulmonary embolism with a single contrast bolus and breath hold. We sought to determine whether 64-slice computed tomography angiography (CTA) allows for simultaneous visualization of the coronary. arteries, thoracic aorta, and pulmonary arteries (coronary, aorta, pulmonary [CAP]) with image quality comparable to routine CTA protocols. Materials and Methods: We prospectively enrolled 20 patients who underwent CAP CTA. Image quality of CAP CTA was assessed qualitatively and quantitatively and compared with dedicated coronary (n = 20) and pulmonary (n = 10) CTA data sets using matched controls. Results: The mean amount of contrast and radiation dose was 132 10 mL and 17.8 +/- 1.8 mSv, 78 +/- 9 mL and 13.7 +/- 3.4 mSv, and 135 mL and 11.9 +/- 1.5 mSv for CAP CTA, coronary CTA, and pulmonary CTA, respectively (P = 0.001). There was no difference in overall image quality (P = 0.88), presence of motion artifacts (P = 0.40), or enhancement of the proximal coronary arteries (median [interquartile range for contrast-noise ratio was 12.5 {9.9-15.2} vs 13.1 {10.3-16.9}; P = 0.17]) or thoracic aorta (264 [113-326] vs 245 [107-295]; P = 0.34) between CAP CTA and the dedicated coronary CTA, respectively. However, contrast attenuation was higher in the pulmonary arteries with CAP CTA (363 [253-424]) versus the standard pulmonary CTA protocol (235 [182-269]; P = 0.0001). Conclusions: Using an individually tailored single contrast injection, CAP CTA permits simultaneous visualization of the coronary arteries, thoracic aorta, and pulmonary arteries with excellent image quality. Further research is necessary to determine whether this protocol may enhance triage of patients with undifferentiated acute chest pain. C1 [Shapiro, Michael D.; Dodd, Jonathan D.; Hsu, Joe; Nasir, Khurram; Kalra, Mannudeep K.; Nichols, John H.; Cury, Ricardo C.; Abbara, Suhny; Tawakol, Ahmed; Brady, Thomas J.; Hoffman, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Shapiro, Michael D.; Dodd, Jonathan D.; Kalva, Sanjeeva; Wittram, Conrad; Hsu, Joe; Nasir, Khurram; Liu, Bob; Kalra, Mannudeep K.; Nichols, John H.; Cury, Ricardo C.; Abbara, Suhny; Brady, Thomas J.; Hoffman, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hoffman, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org FU NHLBI NIH HHS [1T32 HL076136-02] NR 31 TC 17 Z9 17 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2009 VL 33 IS 2 BP 225 EP 232 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 427KB UT WOS:000264777100012 PM 19346850 ER PT J AU Izikson, L Anderson, RR AF Izikson, Leonid Anderson, R. Rox TI Treatment endpoints for resistant port wine stains with a 755 nm laser SO JOURNAL OF COSMETIC AND LASER THERAPY LA English DT Article DE Alexandrite; endpoint; laser; port wine stain; resistant; treatment AB Laser therapy of port wine stains (PWS) resistant to pulsed dye laser is challenging and controversial. Based on the theory of selective photo thermolysis, vessels in such lesions may be specifically targeted with the laser wavelength of 755 nm. There is much deeper penetration of the near-infrared light and it is difficult to visualize laser-induced changes within the deeper dermis. The recognition of an appropriate immediate endpoint response with this wavelength would be helpful. This is a clinical observations report. We present examples of an appropriate PWS tissue response endpoint based on our clinical observations in resistant PWS treated with a 755 nm laser at high fluences (40-100 J/cm(2)), 1.5-ms pulse duration, with dynamic cooling device (DCD) cooling. Mild-to-moderate PWS lightening was associated with the immediate endpoint of a transient gray color that gradually evolved into persistent deep purpura within several minutes. We also discuss the clinical endpoints that represent undertreatment and overtreatment of PWS. It is important to attain, and maintain, the correct endpoint when treating PWS with this deeply penetrating near-infrared laser at high fluences in order to (a) induce lesional lightening, and (b) avoid deep dermal burns that may produce scarring. judicious use of the 755 nm laser can be beneficial for resistant PWS. C1 [Izikson, Leonid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Laser & Cosmet Dermatol Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Izikson, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Laser & Cosmet Dermatol Ctr, BHX 630,Bartlett Hall, Boston, MA 02114 USA. EM lizikson@partners.org NR 7 TC 21 Z9 24 U1 0 U2 1 PU INFORMA HEALTHCARE-SWEDEN PI STOCKHOLM PA PO BOX 3255, STOCKHOLM, SE-10365, SWEDEN SN 1476-4172 J9 J COSMET LASER THER JI J. Cosmet. Laser Ther. PD MAR PY 2009 VL 11 IS 1 BP 52 EP 55 DI 10.1080/14764170802524452 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 453EH UT WOS:000266592500010 PM 19012069 ER PT J AU Kaban, LB Cohen, MM AF Kaban, Leonard B. Cohen, M. Michael, Jr. TI Guest Editors' Introduction SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Editorial Material C1 [Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Cohen, M. Michael, Jr.] Dalhousie Univ, Fac Med, Halifax, NS, Canada. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. EM LKaban@Partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD MAR PY 2009 VL 20 BP 585 EP 586 PG 2 WC Surgery SC Surgery GA 424MM UT WOS:000264570800003 PM 19293673 ER PT J AU Lin, AE Yuzuriha, S McLean, S Mulliken, JB AF Lin, Angela E. Yuzuriha, Shunsuke McLean, Scott Mulliken, John B. TI Lesser Forms of Cleft Lip Associated With the Branchio-Oculo-Facial Syndrome SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Branchio-oculo-facial syndrome; cleft lip; cleft lip and palate; microform cleft lip; pseudocleft lip ID BILATERAL DERMAL THYMUS; MINI-MICROFORM; MUTATIONS; TISSUE; NECK AB Lesser forms of incomplete cleft lip (CL) have been called microfom, occult, forme fruste, and congenitally healed. The association of a minimal bilateral CL in branchio-oculo-facial syndrome (BOFS) is well described and commonly referred to as a "pseudocleft." We conducted a systematic analysis of CL types in BOFS, including a retrospective cross-sectional chart and photographic review with variable longitudinal follow-up of our patients and those described in the literature. We compared data on the type of CL and palate (CL/P) and craniofacial and extracranial anomalies in patients with BOFS and classified the lesser forms CL as either minor-form, microform, or mini-microform as defined by the extent of disruption at the vermilion-cutaneous junction. The study comprised 62 patients with BOFS (1 new and 61 in literature, 4 treated by J.B.M). Forty-four patients (71%) had CL only; 16 (26%) had CL/P; and 2 patients had neither CL nor isolated CP Thirty-five patients with CL had adequate information for analysis (defined as either seen by J.B.M., having a published photograph, or having a detailed description). The most common type was bilateral symmetrical, lesser form CL (n = 20): minor-form (n = 2), microform (n = 6), or mini-microform (n = 12). Among 17 asymmetrical forms, the left side was more severely affected side than the right (12 vs 5). Of 9 patients with CUP and adequate clinical description, 4 were bilaterally symmetrically complete. Other anomalies, in addition to the familiar cardinal features of BOFS, included facial nerve weakness (n = 6), chin dimple or cleft of the lower lip (n = 4), upper labial pits (n = 6), minor digital anomalies (n = 12), renal anomalies (n = 14), and ectopic thymus (n = 18). This analysis reaffirms the high frequency of CL or CL/P in BOFS and the rarity of isolated cleft palate and underscores that the term "pseudocleft" lip is incorrect. The more precise lesser form designations used in this study may prove useful for future clinical studies because the causative gene, TFAP2A, is known. Lesser forms of CL may be the most subtle expression of BOFS and assist in identifying patients. Unlike major forms of CL/P, either, syndromic or non syndromic, lesser forms suggest that the developmental insult occurs later in labial formation when fusion of the medial nasal process and maxillary process is nearly complete. The deficient vermilion-mucosa and hypoplastic orbicularis oris may be the result of incomplete or deficient mesodermal penetration of the ectodermal envelope. Another possible pathogenic explanation is that failure of labial closure occurs earlier than in a major cleft when the primitive cells of ectoderm and mesoderm retain the capacity to "heal" the defect. C1 [Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA USA. [Yuzuriha, Shunsuke; Mulliken, John B.] Childrens Hosp, Dept Plast Surg, Boston, MA 02115 USA. [McLean, Scott] Brooke Army Med Ctr, Dept Pediat, Houston, TX USA. RP Lin, AE (reprint author), 185 Cambridge St,Suite 2222, Boston, MA 02114 USA. EM lin.angela@mgh.harvard.edu NR 32 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD MAR PY 2009 VL 20 BP 608 EP 611 DI 10.1097/SCS.0b013e3181927fb6 PG 4 WC Surgery SC Surgery GA 424MM UT WOS:000264570800010 PM 19795528 ER PT J AU Kaban, LB AF Kaban, Leonard B. TI Mandibular Asymmetry and the Fourth Dimension SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Facial asymmetry; mandibular asymmetry; hemifacial microsomia; condylar hyperplasia; fourth dimension; mandibular growth ID COSTOCHONDRAL GRAFT CONSTRUCTION; HEMIFACIAL MICROSOMIA; SURGICAL-CORRECTION; FACIAL ASYMMETRY; OCCLUSAL CANT; FRONTAL PLANE; GROWTH; RAMUS; HYPOPLASIA AB This paper represents more than 30 years of discussion and collaboration with Drs Joseph Murray and John Mulliken in an attempt to understand growth patterns over time (ie, fourth dimension) in patients with hemifacial microsomia (HFM). This is essential for the development of rational treatment protocols for children and adults with jaw asymmetry. Traditionally. HFM was thought of as a unilateral deformity, but it was recognized that 20% to 30% of patients had bilateral abnormalities. However, early descriptions of skeletal correction addressed almost exclusively lengthening of the short (affected) side of the face. Based on longitudinal clinical observations of unoperated HFM patients, we hypothesized that abnormal mandibular growth is the earliest skeletal manifestation and that restricted growth of the mandible plays a pivotal role in progressive distortion of both the ipsilateral and contralateral facial skeleton. This hypothesis explains the progressive nature of the asymmetry in patients with HFM and provides the rationale for surgical lengthening of the inaudible in children to prevent end-stage deformity. During the past 30 years, we have learned that this phenomenon of progressive distortion of the adjacent and contralateral facial skeleton occurs with other asymmetric mandibular undergrowth (tumor resection, radiation therapy, or posttraumatic defects) and overgrowth (mandibular condylar hyperplasia) conditions. In this paper, I describe the progression of deformity with time in patients with mandibular asymmetry as a result of undergrowth and overgrowth. Understanding these concepts is critical for the development of rational treatment protocols for adults with end-stage asymmetry and for children to minimize secondary deformity. C1 Harvard Univ, Dept Oral & Maxillofacial Surg, Sch Dent Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Harvard Univ, Dept Oral & Maxillofacial Surg, Sch Dent Med, Massachusetts Gen Hosp, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM LKaban@Partners.org FU NIGH Department of Oral and Maxillofacial Surgery Education and Research Fund FX This work was supported in part by the NIGH Department of Oral and Maxillofacial Surgery Education and Research Fund. NR 26 TC 24 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD MAR PY 2009 VL 20 BP 622 EP 631 DI 10.1097/SCS.0b013e318195249c PG 10 WC Surgery SC Surgery GA 424MM UT WOS:000264570800013 PM 19182686 ER PT J AU Abramson, Z Susarla, S Troulis, M Kaban, L AF Abramson, Zachary Susarla, Srinivas Troulis, Maria Kaban, Leonard TI Age-Related Changes of the Upper Airway Assessed by 3-Dimensional Computed Tomography SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Three-dimensional; computed tomography; upper airway; normal ID OBSTRUCTIVE SLEEP-APNEA; NORMAL MEN; MAXILLOMANDIBULAR ADVANCEMENT; SURGERY; SIZE AB The purposes of this study were to establish normative data for airway size and shape and to evaluate differences associated with age and sex using 3-dimensional (3-D) imaging. Patients being evaluated by computed tomography (CT) for pathologic conditions not related to the airway were included. Using 3-D Slicer (Harvard Surgical Planning Laboratory, Brigham and Women's Hospital, Boston. MA), a software program, digital 3-D CT reconstructions were made and parameters of airway size analyzed: volume (VOL), surface area (SA), length (L), mean cross-sectional area (mean CSA). minimum retropalatal (RP), minimum retroglossal (RG), minimum cross-sectional area (min CSA), and lateral (LAT) and anteroposterior (AP) retroglossal airway dimensions. Evaluation of airway shape included LAT/AP and RP/RG ratios, uniformity (0, and sphericity. a measure of compactness (Psi). Children were stratified by stage of dentition: primary, 0 to 5 years; mixed, 6 to 11 years: permanent. 12 to 16 years: and adults, older than 16 years. Differences in airway parameters by age and sex were analyzed. Forty-six CT scans (31 males) were evaluated. Adults had larger (VOL, SA. L. mean CSA, and LAT), more elliptical (increased LAT/AP P = 0.01). less uniform (U, P = 0.02), and less compact (decreased Psi, P = 0.001) airways than children. Among children, those in the permanent dentition demonstrated greater VOL (P < 0.01), SA (P < 0.01), L (P < 0.01), and mean CSA (P < 0.01) than those in the primary dentition. There were no gender differences in airway parameters. Understanding differences in 3-D airway size and morphology by age may serve as a basis for evaluation of patients with obstructive sleep apnea and may help to predict and to evaluate outcomes of treatment. C1 [Abramson, Zachary; Susarla, Srinivas; Troulis, Maria; Kaban, Leonard] Harvard Univ, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Sch Dent Med, Boston, MA 02114 USA. RP Kaban, L (reprint author), Harvard Univ, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Sch Dent Med, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM LKaban@Partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU Hanson Foundation (Boston, MA); MGH Department of OMFS Education and Research Fund; Synthes CMF (West Chester, PA) FX This study was funded in part by the Hanson Foundation (Boston, MA), the MGH Department of OMFS Education and Research Fund, and Synthes CMF (West Chester, PA). NR 27 TC 52 Z9 55 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD MAR PY 2009 VL 20 BP 657 EP 663 DI 10.1097/SCS.0b013e318193d521 PG 7 WC Surgery SC Surgery GA 424MM UT WOS:000264570800019 PM 19182684 ER PT J AU Holmes, LB AF Holmes, Lewis B. TI Chorionic Villus Sampling and Hemangiomas SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE CVS; placenta; hemangioma ID VASCULAR DISRUPTIVE SYNDROMES; NEWBORN-INFANTS; LIMB DEFECTS; MALFORMATIONS; CHILDREN; MISOPROSTOL; ABNORMALITIES; DEFICIENCY; PREGNANCY; ANOMALIES AB Chorionic villus sampling (CVS) is a widely used and safe method of prenatal diagnosis. In the 1990s, concerns were raised at several medical centers that there was an increased risk to the exposed fetus for the occurrence of limb deficiencies, hemangiomas, and other vascular disruption defects. The risk was greater when the procedure was performed earlier in pregnancy, such as 8 or 9 weeks of gestation. The postulated mechanisms for the fetal injury included blood loss, hypoperfusion, hypoxia, endothelial cell damage, hemorrhage, and tissue loss. The effect was most common in tissues with end arteries, such as digits, tongue, brain stem, and intestine. The associated hemangiomas were infantile hemangiomas. They were more common on the head, neck, and thorax and more often multiple in infants exposed to CVS. One postulated mechanism for the occurrence of these hemangiomas is embolization of angioblasts or endothelial cells from the placenta to the fetal skin. A question to be answered is whether the infantile hemangiomas in children exposed to CVS differ in immunohistologic characteristics from similar hemangiomas in children not exposed to CVS during pregnancy. C1 MassGen Hosp Children, Genet Unit, Boston, MA 02114 USA. RP Holmes, LB (reprint author), MassGen Hosp Children, Genet Unit, 5th Floor,175 Cambridge St, Boston, MA 02114 USA. EM holmes.lewis@mgh.harvard.edu FU NIH [HD33222] FX This study was supported in part by NIH grant No. HD33222. NR 23 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD MAR PY 2009 VL 20 BP 675 EP 677 DI 10.1097/SCS.0b013e318193d61a PG 3 WC Surgery SC Surgery GA 424MM UT WOS:000264570800022 PM 19218861 ER PT J AU Trachtenberg, F Maserejian, NN Soncini, JA Hayes, C Tavares, M AF Trachtenberg, F. Maserejian, N. N. Soncini, J. A. Hayes, C. Tavares, M. TI Does Fluoride in Compomers Prevent Future Caries in Children? SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE compomers; dental amalgam; dental caries; dentition; primary; clinical trial ID ARTIFICIAL SECONDARY CARIES; GLASS-IONOMER CEMENT; RESTORATIVE MATERIALS; DEMINERALIZATION INHIBITION; AMALGAM TRIAL; RELEASE; RESIN; DYRACT AB Compomer restorations release fluoride to help prevent future caries. We tested the hypothesis that compomer is associated with fewer future caries compared with amalgam. The five-year New England Children's Amalgam Trial recruited 534 children aged 6-10 yrs with >= 2 carious posterior teeth. Children were randomized to receive compomer or amalgam restorations in primary posterior teeth, placed with a fluoride-releasing bonding agent. The association between restorative material and future caries was assessed by survival analysis. Average follow-up of restorations (N = 1085 compomer, 954 amalgams) was 2.8 +/- 1.4 yrs in 441 children. No significant difference between materials was found in the rate of new caries on different surfaces of the same tooth. Incident caries on other teeth appeared slightly more quickly after placement of compomer restorations (p = 0.007), but the difference was negligible after 5 yrs. Under the conditions of this trial, we found no preventive benefit to fluoride-releasing compomer compared with amalgam. C1 [Trachtenberg, F.; Maserejian, N. N.] New England Res Inst, Watertown, MA 02472 USA. [Soncini, J. A.; Tavares, M.] Forsyth Inst, Boston, MA USA. [Soncini, J. A.] Boston Univ, Sch Dent Med, Dept Pediat Dent, Boston, MA 02215 USA. [Hayes, C.] Tufts Univ, Sch Dent Med, Dept Publ Hlth & Community Serv, Boston, MA 02111 USA. RP Trachtenberg, F (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM ftrachtenberg@neriscience.com FU National Institute of Dental and Craniofacial Research, Bethesda, MD, USA [U01 DE11886]; Health Effects of Dental Amalgams in Children [NCT00065988] FX The study was supported by the National Institute of Dental and Craniofacial Research, Bethesda, MD, USA (U01 DE11886), which also participated in the design and conduct of the study. Trial Registration: Health Effects of Dental Amalgams in Children, NCT00065988, http://www.clinicaltrials.gov/ct/show/NCT00065988?order=1 NR 24 TC 4 Z9 4 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAR PY 2009 VL 88 IS 3 BP 276 EP 279 DI 10.1177/0022034508330884 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 424KP UT WOS:000264565900016 PM 19329464 ER PT J AU Nwasuruba, C Osuagwu, C Bae, S Singh, KP Egede, LE AF Nwasuruba, Chiagozie Osuagwu, Christie Bae, Sejong Singh, Karan P. Egede, Leonard E. TI Racial differences in diabetes self-management and quality of care in Texas SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Diabetes; Race; Ethnicity; Self-management; Survey research ID HEALTH-INSURANCE COVERAGE; RISK-FACTOR SURVEY; UNITED-STATES; RACIAL/ETHNIC DIFFERENCES; BLOOD-GLUCOSE; EXCESS MORTALITY; ADULTS; POPULATION; INDIVIDUALS; RELIABILITY AB Aim: To assess racial/ethnic differences in diabetes self-management behaviors and quality of care in Texas. Methods: This cross-sectional study assessed self-management behaviors and quality of care in 1720 adults with diabetes in the 2002-2004 Texas Behavioral Risk Factor Surveillance Survey. Multiple logistic regression models were used for assessing the independent association between race/ethnicity, self-management behaviors, and quality of care variables controlling for covariates. SAS (SAS Institute Inc, 2002-2003) was used for statistical analysis. Results: Eighteen percent of Hispanics, 14% of Blacks, and 10% of Whites reported never performing home glucose testing. Seventeen percent of Hispanics, 11% of Blacks, and 10% of Whites reported never doing home foot exam. Thirty-two percent of Hispanics, 21% of Blacks, and 16% of Whites did not have an A1C test in the prior 12 months. Twelve percent of Hispanics, 10% of Blacks, and 6% of Whites did not have a dilated eye exam in the prior 12 months. Fifty-four percent of Whites, 42% of Blacks, and 40% of Hispanics received a flu shot. Forty-nine percent of Whites, 30% of Blacks, and 26% of Hispanics received a pneumonia shot. In adjusted models, Hispanics were more likely to be sedentary (OR, 1.64; 95% CI, 1.08-2.49) compared to Whites. Blacks did not differ significantly from Whites (OR, 1.46; 95% CI, 0.92-2.34). Hispanics (OR, 1.61; 95% CI, 1.01-2.57) and Blacks (OR, 1.83; 95% CI, 1.10-3.03) were more likely to get an annual foot exam by a provider compared to Whites. Hispanics (OR, 0.54; 95% CI, 0.34-0.85) and Blacks (OR, 0.58; 95% CI, 0.35-0.98) were less likely to get a pneumonia shot compared to Whites. Conclusions: Hispanics have poorer access to care and poorer health status compared to Whites or Blacks. Controlling for socioeconomic and access to care variables eliminated disparities in self-management but did not eliminate disparities in quality of diabetes care. (C) 2009 Elsevier Inc. All rights reserved. C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Charleston VA TREP, Charleston, SC USA. [Bae, Sejong; Singh, Karan P.] Univ N Texas, Hlth Sci Ctr, Dept Biostat, Ft Worth, TX USA. [Osuagwu, Christie] Univ Texas Hlth Ctr Tyler, Dept Emergency Med, Tyler, TX USA. [Nwasuruba, Chiagozie] Univ Texas Hlth Ctr Tyler, Dept Med, Tyler, TX USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institutes of Health: National Center for Minority Health and Health Disparities [1R24 MD 535-1] FX We would like to acknowledge the East Texas Project EXPORT center. The East Texas Project EXPORT Center is funded by the National Institutes of Health: National Center for Minority Health and Health Disparities (Grant #1R24 MD 535-1). NR 31 TC 25 Z9 25 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAR-APR PY 2009 VL 23 IS 2 BP 112 EP 118 DI 10.1016/j.jdiacomp.2007.11.005 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 414TE UT WOS:000263887300006 PM 18413179 ER PT J AU Caballero, AE AF Caballero, A. Enrique TI Long-term benefits of insulin therapy and glycemic control in overweight and obese adults with type 2 diabetes SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Review DE Insulin; Obesity; Type 2 diabetes ID PEPTIDASE-4 INHIBITOR SITAGLIPTIN; IMPAIRED GLUCOSE-TOLERANCE; BETA-CELL FUNCTION; GLARGINE HOE 901; NPH INSULIN; METABOLIC SYNDROME; CARDIORESPIRATORY FITNESS; CARDIOVASCULAR-DISEASE; WEIGHT-GAIN; LIFE-STYLE AB Problem: Obesity and type 2 diabetes have reached epidemic proportions in the United States. Obese patients are at especially high risk for the development of metabolic syndrome, a clustering or metabolic abnormalities associated with insulin resistance that usually precede the development of cardiovascular disease. Overweight or obesity, along with insulin resistance, is frequently present in people with type 2 diabetes. Methods: A literature search of the PubMed and MEDLINE databases, using the terms diabetes, obesity, metabolic syndrome, glycemic control, antidiabetic therapy, and insulin, was performed. Articles published between 1985 and 2006 that examined diabetes management in the obese population were selected and reviewed. Results: There is new evidence suggesting that tight glycemic control and earlier initiation of insulin therapy can improve outcomes in obese patients with type 2 diabetes, thereby reducing the risk for the development of both macrovascular and microvascular complications of the disease. Insulin also appears to exhibit anti-inflammatory effects, which may provide additional protection against the development of atherosclerosis. Despite the benefits of insulin therapy, many patients and physicians remain reluctant to start insulin due to concerns about weight gain. Conclusion: Newer insulin formulations can effectively improve glycemic control without significant effects on patient weight and, therefore, may be particularly useful in patients who are overweight or obese. Implementation of comprehensive treatment regimens that emphasize dietary modification, physical activity, and exercise, and aggressive use or pharmacological agents to achieve tight glycemic control through physiological regimens offer the most promise for reducing long-term complications in obese patients with type 2 diabetes. (C) 2009 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Caballero, AE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM enrique.caballero@joslin.harvard.edu NR 89 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAR-APR PY 2009 VL 23 IS 2 BP 143 EP 152 DI 10.1016/j.jdiacomp.2007.06.002 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 414TE UT WOS:000263887300013 PM 18413192 ER PT J AU Reiter, MJ Harsch, M Lung, TH Munneke, D Kim, MH Shalaby, A AF Reiter, Michael J. Harsch, Manya Lung, Te-Hsin Munneke, Dave Kim, Michael H. Shalaby, Alaa CA Vitatron AFm Registry Investigator TI Influence of structural heart disease on characteristics of atrial fibrillation recurrence in patients with dual-chamber pacemakers SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Atrial fibrillation; Structural heart disease; Epidemiology; Cardiac pacing ID PREVENTION; STROKE; IMPLANTATION; RISK; DDDR; TACHYARRHYTHMIAS; DEVICE AB Aims: The aim of the study was to prospectively examine the influence of structural heart disease (SHD) and sinus node dysfunction (SND) on the frequency and duration of atrial fibrillation (AF) episodes in patients with implanted pacemakers. Methods: We examined episodes of AF in 207 patients (93 with SHD; 165 with SND) with known or suspected paroxysmal AF who underwent dual-chamber pacing. Results: Seventy-one percent of all patients experienced at least one episode of AF during follow-up, with a mean burden of 3.3 +/- 6.4 h/d (median, 0.2 hours) and a mean frequency of 11.7 +/- 26.0 episodes per day (median, 1.4). The proportion of episodes longer than 6 hours was greater in patients with SHD when compared to patients without SHD. In a logistic regression model adjusted for SND, gender, and the 2-way interactions of SND, sex, and SHD, SHD was a significant factor (P = .0188) with the odds ratio of having an episode longer than 6 hours 3.4 times higher for patients with SHD than for patients without SHD. Older patients with SHD had less frequent but longer episodes compared to younger patients. In patients without SHD, there was no comparable age difference. Burden, frequency, and average episode length were not influenced by the presence or absence of SND. Conclusions: Patients with SHD have longer episodes of AF supporting the concept that SHD influences the underlying substrate to favor perpetuation. (C) 2009 Elsevier Inc. All rights reserved. C1 [Reiter, Michael J.] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. [Harsch, Manya; Lung, Te-Hsin; Munneke, Dave] Vitatron Clin Res, Minneapolis, MN USA. [Kim, Michael H.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Shalaby, Alaa] VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. RP Reiter, MJ (reprint author), 5083 Oak Hollow Dr, Morrison, CO 80465 USA. EM michael.reiter@uchse.edu NR 28 TC 3 Z9 3 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD MAR-APR PY 2009 VL 42 IS 2 BP 128 EP 135 DI 10.1016/j.jelectrocard.2008.09.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 419LC UT WOS:000264220000005 PM 18976775 ER PT J AU DiGregorio, BV Fung, HB Muller, AA AF DiGregorio, Bobert V. Fung, Horatio B. Muller, Allison A. TI RAPID DOSING OF CRITICAL CARE INFUSIONS: THE DOPAMINE AND NOREPINEPHRINE "CLOCKS" SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material ID IN-HOSPITAL SETTINGS; ASHP NATIONAL-SURVEY; SAFETY C1 [DiGregorio, Bobert V.] Long Isl Univ, Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Brooklyn, NY USA. [DiGregorio, Bobert V.] Long Isl Univ, Pharmacotherapy Serv, Brooklyn, NY USA. [Fung, Horatio B.] James J Peters Vet Affairs Med Ctr, Med Surg Patient Care Ctr, Bronx, NY USA. RP DiGregorio, BV (reprint author), 73 Cty Courthouse Rd, Garden City Pk, NY 11040 USA. EM Robert.DiGregorio@liu.edu; mullera@email.chop.edu NR 13 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-1767 J9 J EMERG NURS JI J. Emerg. Nurs. PD MAR PY 2009 VL 35 IS 2 BP 165 EP 168 DI 10.1016/j.jen.2008.07.019 PG 4 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA 426TU UT WOS:000264731600030 ER PT J AU Chuckpaiwong, B Berkson, EM Theodore, GH AF Chuckpaiwong, Bavornrit Berkson, Eric M. Theodore, George H. TI Extracorporeal Shock Wave for Chronic Proximal Plantar Fasciitis: 225 Patients with Results and Outcome Predictors SO JOURNAL OF FOOT & ANKLE SURGERY LA English DT Article DE Extracorporeal shockwave; heel spur syndrome; patient outcome assessment; plantar fasciitis ID CONTROLLED MULTICENTER TRIAL; PAINFUL HEEL; BIOMECHANICAL CONSEQUENCES; OPERATIVE TREATMENT; LOCAL-ANESTHESIA; FASCIAL RELEASE; THERAPY ESWT; FOLLOW-UP; FASCIOTOMY; FASCIOPATHY AB Plantar fasciitis can be a chronic and disabling cause of foot pain in the adult population. For refractory cases, extracorporeal shock wave therapy (ESWT) has been proposed as therapeutic option to avoid the morbidity of surgery. We hypothesized that the success of extracorporeal shock wave therapy in patients with chronic plantar fasciitis is affected by patient-related factors. A retrospective review of 225 patients (246 feet) who underwent consecutive ESWT treatment by a single physician at our institution between July 2002 and July 2004 was performed. Subjects were included only if they had plantar fasciitis for more than 6 months and failure to response to at least 5 conservative modalities. Patients were evaluated prospectively with health questionnaires, Roles and Maudsley scores, and American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot scores at regular intervals. Follow-up was 30.2 +/- 8.7 months post procedure. Multivariable analysis was performed to assess factors leading to successful outcomes. Success rates of 70.7% at 3 months and 77.2% at 12 months were noted in this population. Previous cortisone injections, body mass index, duration of symptoms, presence of bilateral symptoms, and plantar fascia thickness did not influence the outcome of ESWT. The presence of diabetes mellitus, psychological issues, and older age were found to negatively influence ESWT outcome. Whereas many factors have been implicated in the development of plantar fasciitis, only diabetes mellitus, psychological issues, and age were found to negatively influence ESWT outcome. Level of Clinical Evidence: 2 (The Journal of Foot & Ankle Surgery 48(2):148-155, 2009) C1 [Chuckpaiwong, Bavornrit] Mahidol Univ, Dept Orthopaed, Siriraj Hosp, Bangkok 10700, Thailand. [Theodore, George H.] Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA USA. RP Chuckpaiwong, B (reprint author), Mahidol Univ, Dept Orthopaed, Siriraj Hosp, 2 Prannok St, Bangkok 10700, Thailand. EM chuck003@gmail.com NR 86 TC 20 Z9 24 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-2516 J9 J FOOT ANKLE SURG JI J. Foot Ankle Surg. PD MAR-APR PY 2009 VL 48 IS 2 BP 148 EP 155 DI 10.1053/j.jfas.2008.11.001 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 412YO UT WOS:000263760300010 PM 19232966 ER PT J AU Ohno, T Sugimoto, M Nagashima, A Ogiwara, H Vilaichone, RK Mahachai, V Graham, DY Yamaoka, Y AF Ohno, Tomoyuki Sugimoto, Mitsushige Nagashima, Aiko Ogiwara, Hiroaki Vilaichone, Ratha-Korn Mahachai, Varocha Graham, David Y. Yamaoka, Yoshio TI Relationship between Helicobacter pylori hopQ genotype and clinical outcome in Asian and Western populations SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE gastric cancer; Helicobacter pylori; hopQ; virulence factor ID VACA; CAGA; GASTRITIS; INFECTION; ALLELES; JAPAN; GENE; VARIANTS; STRAINS; ADHESIN AB Outer membrane proteins of Helicobacter pylori mediate important pathogen-host interactions such as colonization, adhesion and the inflammatory response. hopQ genotypes have been suggested to be associated with increased risk of peptic ulcer. The aim of this study was to test the relation of hopQ genotype to H. pylori-related disease and histological changes in Asian and Western countries. hopQ genotype, cagA status and vacA genotype of H. pylori isolated from patients from Asian and Western countries were determined and the results were compared with the clinical presentation and gastric histology. Most Asian strains possessed virulent genotypes (hopQ type I, vacA s1-m1 and cagA-positive). In Western countries, hopQ type I genotype was significantly linked with vacA s1 and m1 genotypes and cagA-positive status. Inflammatory cell infiltration and atrophy scores were significantly higher in patients with hopQ type I strains than those with type II in Western patients. However, the hopQ type I genotype was not associated with an increased risk for peptic ulcer or gastric cancer, and had no additive effects to vacA genotypes or cagA-positive status. The expression of multiple putative virulence factors in Asian strains likely explains the relatively high incidence of clinical outcomes including gastric cancer compared with other parts of the world. Although hopQ genotype did not improve the predictive value above other genotyping for development of H. pylori-related gastroduodenal diseases, the hopQ genotype might be able to add a useful virulence marker for gastroduodenal diseases. C1 [Ohno, Tomoyuki; Sugimoto, Mitsushige; Nagashima, Aiko; Ogiwara, Hiroaki; Graham, David Y.; Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. [Ohno, Tomoyuki; Sugimoto, Mitsushige; Nagashima, Aiko; Ogiwara, Hiroaki; Graham, David Y.; Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA. [Vilaichone, Ratha-Korn] Thammasat Univ Hosp, Dept Med, Gastroenterol Unit, Pathum Thani, Thailand. [Mahachai, Varocha] Chulalongkorn Univ Hosp, Dept Med, Gastroenterol Unit, Bangkok, Thailand. RP Yamaoka, Y (reprint author), Michael E Debakey Vet Affairs Med Ctr 111D, Dept Med Gastroenterol, Mol Pathogenesis Lab, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU Office of Research and Development Medical Research Service Department of Veterans Affairs; Public Health Service [DK56338]; Texas Gulf Coast Digestive Diseases Center; National Institutes of Health (NIH) [DK 62813] FX This material is based upon work supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs, by Public Health Service grant DK56338 which funds the Texas Gulf Coast Digestive Diseases Center. The project described was also supported by grant no. DK 62813 from the National Institutes of Health (NIH). These contents are solely the responsibility of the authors and do not necessarily represent the official views of the Veterans Affairs (VA) and NIH. The authors thank Professor Tatsuo Yamamoto (Niigata University School of Medicine) for suitable advice. NR 24 TC 12 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 2009 VL 24 IS 3 BP 462 EP 468 DI 10.1111/j.1440-1746.2008.05762.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 424FX UT WOS:000264552000020 PM 19226380 ER PT J AU Weisbord, SD Mor, MK Kim, S Hartwig, KC Sonel, AF Palevsky, PM Fine, MJ AF Weisbord, Steven D. Mor, Maria K. Kim, Sunghee Hartwig, Kathryn C. Sonel, Ali F. Palevsky, Paul M. Fine, Michael J. TI Factors Associated with the Use of Preventive Care for Contrast-Induced Acute Kidney Injury SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE predictors; contrast-induced acute kidney injury; patients; providers; preventive care ID HIGH-RISK PATIENTS; ACUTE-RENAL-FAILURE; INDUCED NEPHROPATHY; RADIOCONTRAST NEPHROPATHY; ACETYLCYSTEINE; MEDIA; METAANALYSIS; ANGIOGRAPHY; IODIXANOL; HYDRATION AB The factors that affect the implementation of preventive care for contrast-induced acute kidney injury (CIAKI) are unknown. To assess patient and provider factors associated with the use of preventive care for CIAKI. Prospective cohort study. Patients with kidney disease undergoing procedures with intravascular iodinated radiocontrast. We recorded the use of preventive care defined as the administration of: (1) pre- and post-procedure isotonic intravenous (IV) fluid, (2) N-acetylcysteine, and (3) iso-osmolal radiocontrast. We surveyed patients' providers to assess their knowledge, experience, and training on CIAKI and used multiple logistic regression to assess the independent associations of patient and provider factors with the use of these preventive interventions. We enrolled 660 patients and 87 providers. Patient factors associated with use of IV fluid and N-acetylcysteine were higher baseline serum creatinine (OR 1.5 and 5.0, p < 0.05) and inpatient status (OR 3.0 and 6.3, p < 0.05), while higher baseline serum creatinine was associated with the use of iso-osmolal contrast (OR = 13.4, p < 0.01). The primary provider characteristics associated with the use of IV fluid and N-acetylcysteine were a greater degree of prior training on CIAKI (OR 1.9 and 2.8, p < 0.05) and higher number of prior patients with CIAKI (OR 2.7 and 2.6, p < 0.05). Patient baseline kidney function and provider training and experience with CIAKI are independently associated with the use of preventive care. Efforts to increase and intensify the training providers receive on CIAKI may help decrease the incidence of this costly iatrogenic condition. C1 [Weisbord, Steven D.; Mor, Maria K.; Kim, Sunghee; Hartwig, Kathryn C.; Sonel, Ali F.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Hartwig, Kathryn C.; Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Mor, Maria K.; Kim, Sunghee] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15261 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Mailstop 111F-U,7E Room 120, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU VA Health Services Research and Development Career Development [RCD 03-176]; VA Stars and Stripes Competitive Pilot Project; National Institute of Allergy and Infectious Diseases [K24 AI001769] FX This study and Dr. Weisbord were supported by a VA Health Services Research and Development Career Development Award (RCD 03-176) and a VA Stars and Stripes Competitive Pilot Project Fund award. Dr. Fine was supported in part by a mid-career development award (K24 AI001769) from the National Institute of Allergy and Infectious Diseases. All of the listed authors contributed to this work. NR 29 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 MAR PY 2009 VL 24 IS 3 BP 289 EP 298 DI 10.1007/s11606-008-0894-4 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 407QL UT WOS:000263379300001 PM 19156472 ER PT J AU Liu, CF Bolkan, C Chan, D Yano, EM Rubenstein, LV Chaney, EF AF Liu, Chuan-Fen Bolkan, Cory Chan, Domin Yano, Elizabeth M. Rubenstein, Lisa V. Chaney, Edmund F. TI Dual Use of VA and Non-VA Services Among Primary Care Patients with Depression SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE dual use; depression; primary care; veterans ID OF-VETERANS-AFFAIRS; CLINICAL-PRACTICE GUIDELINES; ACUTE MYOCARDIAL-INFARCTION; MENTAL-HEALTH-SERVICES; FEMALE VETERANS; SCREENING QUESTIONNAIRES; MEDICARE SERVICES; AUDIT-C; DISORDERS; POPULATION AB Depression treatment requires close monitoring to achieve optimal, long-term control. Use of multiple sources of health care can affect coordination and continuity of treatment for depression. To assess levels of non-Veterans Health Administration (VA) use among depressed primary care patients by service type and examine patient factors associated with non-VA use. Cross-sectional comparison of dual and VA-only users among depressed primary care patients. Depression was defined as PHQ-9 a parts per thousand yen10. Five hundred fifty depressed patients from the baseline sample of a group-randomized trial of collaborative care for depression in ten VA primary care practices. VA and non-VA outpatient utilization for physical and emotional health problems in the prior 6 months, patient demographics, and co-morbid conditions. All measures were self-reported and obtained at the baseline interview. Overall, 46.8% of VA depressed primary care patients utilized non-VA care. Dual users were more likely to use acute care services (emergency room or inpatient), especially for physical health problems. Dual users of physical health services had more total visits, but fewer VA visits than VA-only users, while dual users of emotional health services had fewer total and VA visits. Factors associated with dual use were urban clinic location, having other insurance coverage, and dissatisfaction with physical health care in general. Almost half of depressed primary care patients used non-VA care, with most of their non-VA use for physical rather than emotional health problems. Care management strategies for depressed patients should include communication and coordination with non-VA providers. C1 [Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, Seattle, WA 98101 USA. [Liu, Chuan-Fen; Bolkan, Cory; Chaney, Edmund F.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98101 USA. [Liu, Chuan-Fen; Bolkan, Cory] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Yano, Elizabeth M.; Rubenstein, Lisa V.] VA Greater Angeles Healthcare Syst, Dept Vet Affairs, Hlth Serv Res & Dev Ctr Excellence, Sepulveda, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Dept Med, Los Angeles Sch Med, Los Angeles, CA 90024 USA. [Rubenstein, Lisa V.] RAND Hlth Program, Santa Monica, CA USA. [Chan, Domin; Chaney, Edmund F.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Liu, CF (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM fliu@u.washington.edu NR 46 TC 20 Z9 20 U1 3 U2 6 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 MAR PY 2009 VL 24 IS 3 BP 305 EP 311 DI 10.1007/s11606-008-0867-7 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 407QL UT WOS:000263379300003 PM 19101777 ER PT J AU Borrero, S Nikolajski, C Rodriguez, KL Creinin, MD Arnold, RM Ibrahim, SA AF Borrero, Sonya Nikolajski, Cara Rodriguez, Keri L. Creinin, Mitchell D. Arnold, Robert M. Ibrahim, Said A. TI "Everything I Know I Learned from My Mother...or Not": Perspectives of African-American and White Women on Decisions About Tubal Sterilization SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE tubal sterilization; race; qualitative research; focus groups; decision making AB African-American women have had higher rates of female sterilization compared to white women since its emergence as a contraceptive method. The reasons underlying this observed racial difference are unknown. The goals of this study were to (1) explore what factors shape black and white women's decisions about tubal sterilization as a contraceptive method and (2) generate hypotheses about the relationship of race to the decision-making process. We conducted six focus groups stratified by tubal sterilization status and race. During each of the audio-recorded sessions, participants were asked to discuss reasons that women choose sterilization as a contraceptive method. The participants of the study were 24 African-American women and 14 white women. Transcripts of the sessions were qualitatively analyzed with particular attention to factors that might be unique to each of the two racial groups. Personal factors shaped black and white women's decisions regarding tubal sterilization. Preference for a convenient, highly effective contraceptive method was the main reason to get a tubal sterilization for women of both racial groups. We also identified socio-cultural differences that might explain why black women are more likely than white women to choose tubal sterilization over other contraceptive methods. An unanticipated, but clinically important, finding was that women often reported feeling that their doctors and the health-care system served as barriers to obtaining the desired procedure. Socio-cultural differences may help explain why black and white women choose different contraceptive methods. C1 [Borrero, Sonya; Nikolajski, Cara; Rodriguez, Keri L.; Arnold, Robert M.; Ibrahim, Said A.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Borrero, Sonya; Nikolajski, Cara; Rodriguez, Keri L.; Ibrahim, Said A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Rodriguez, Keri L.; Arnold, Robert M.] Univ Pittsburgh, Inst Doctor Patient Commun, Pittsburgh, PA USA. [Creinin, Mitchell D.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Creinin, Mitchell D.] Magee Womens Res Inst, Pittsburgh, PA USA. [Creinin, Mitchell D.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Borrero, Sonya; Nikolajski, Cara; Rodriguez, Keri L.; Arnold, Robert M.; Ibrahim, Said A.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. RP Borrero, S (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 230 McKee Pl,Suite 600, Pittsburgh, PA 15260 USA. EM borrerosp@upmc.edu FU National Center for Research Resources (NCRR) [1 KL2 RR02415403]; National Institutes of Health (NIH); NIH Roadmap for Medical Research; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24AR055259]; VA HSR& D Merit Review Entry Program Award [MRP 04-410]; National Cancer Institute [3R01 CA-100387-03S1] FX This publication was made possible by Dr. Borrero's grant (no. 1 KL2 RR02415403) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The sponsors 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. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official view of the NCRR or NIH. Dr. Ibrahim is supported by grant no. K24AR055259 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Rodriguez is supported by a VA HSR& D Merit Review Entry Program Award (MRP 04-410) and a Minority Supplement Award from the National Cancer Institute (3R01 CA-100387-03S1). NR 31 TC 24 Z9 24 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 MAR PY 2009 VL 24 IS 3 BP 312 EP 319 DI 10.1007/s11606-008-0887-3 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 407QL UT WOS:000263379300004 PM 19107540 ER PT J AU Freiberg, MS Leaf, DA Goulet, JL Goetz, MB Oursler, KK Gibert, CL Rodriguez-Barradas, MC Butt, AA Justice, AC AF Freiberg, Matthew S. Leaf, David A. Goulet, Joseph L. Goetz, Matthew B. Oursler, Krisann K. Gibert, Cynthia L. Rodriguez-Barradas, Maria C. Butt, Adeel A. Justice, Amy C. TI The Association Between the Receipt of Lipid Lowering Therapy and HIV Status Among Veterans Who Met NCEP/ATP III Criteria for the Receipt of Lipid Lowering Medication SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE HIV; cholesterol; hepatitis C; men; veterans; cardiovascular diseases ID CORONARY-HEART-DISEASE; HEPATITIS-C VIRUS; ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; INFECTED INDIVIDUALS; RISK-FACTORS; PROTEASE INHIBITORS; ALCOHOL-USE; ADULTS AB To examine the association between HIV infection status and the receipt of lipid lowering therapy based on National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) guidelines and to assess whether HIV viral load and hepatitis C (HCV) status alters that association. A cross-sectional analysis of survey, laboratory, and pharmacy data from 1,577 male participants (59% HIV infected) of the Veterans Aging Cohort Five-Site Study, a prospective observational cohort of U.S. veterans with and without HIV infection. Receipt of lipid lowering therapy obtained from the VA pharmacy benefits management system was the main outcome. The prevalence of lipid lowering therapy among HIV-infected and HIV-uninfected veterans was 15.4% vs. 37.9%, respectively, p < 0.01. Among veterans who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans had a significantly lower prevalence for the receipt of lipid lowering therapy (adjusted odds ratio (OR) = 0.43, 95% confidence interval (C.I.) 0.28-0.67) as compared with HIV-uninfected veterans. Among HIV-infected veterans, log HIV viral load (adjusted OR = 0.57, 95% CI, 0.41-0.81) and HIV-HCV co-infection (adjusted OR = 0.31, 95% CI = 0.13-0.75) were negatively associated with receipt of lipid lowering therapy. Exposure to HAART was not associated with receipt of lipid lowering therapy. Among those who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans, particularly those with high HIV viral loads and HCV co-infection, were significantly less likely to receive lipid lowering therapy. This may be a modifiable mediator of cardiovascular disease among HIV-infected individuals. C1 [Freiberg, Matthew S.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. [Leaf, David A.; Goetz, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Goulet, Joseph L.; Justice, Amy C.] Yale Univ, Sch Med, VA Connecticut Healthcare Syst, New Haven, CT USA. [Oursler, Krisann K.] Univ Maryland, Sch Med, Baltimore VA Med Ctr, Baltimore, MD 21201 USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, VA Med Ctr, Washington, DC 20037 USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Freiberg, MS (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 230 McKee Pl, Pittsburgh, PA 15260 USA. EM freibergms@upmc.edu OI Goetz, Matthew/0000-0003-4542-992X; Goulet, Joseph/0000-0002-0842-804X FU NIH; NIAAA; NHLBI; [2U10 AA 13566]; [K23 AA015914]; [1R01HL095136-01] FX Funding: NIH, NIAAA, NHLBI: 2U10 AA 13566, K23 AA015914, and 1R01HL095136-01. NR 36 TC 13 Z9 13 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 MAR PY 2009 VL 24 IS 3 BP 334 EP 340 DI 10.1007/s11606-008-0891-7 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 407QL UT WOS:000263379300007 PM 19127386 ER PT J AU Hildebrand, C Trowbridge, E Roach, MA Sullivan, AG Broman, AT Vogelman, B AF Hildebrand, Christopher Trowbridge, Elizabeth Roach, Mary A. Sullivan, Anne Gravel Broman, Aimee Teo Vogelman, Bennett TI Resident Self-Assessment and Self-Reflection: University of Wisconsin-Madison's Five-Year Study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE practice-based learning and improvement; graduate medical education; chart review; ambulatory care settings ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-CARE; INTERNAL-MEDICINE; ACHIEVABLE BENCHMARKS; PRACTICE PERFORMANCE; PREVENTIVE HEALTH; IMPROVEMENT; EDUCATION; FEEDBACK; AUDIT AB Chart review represents a critical cornerstone for practice-based learning and improvement in our internal medicine residency program. To document residents' performance monitoring and improvement skills in their continuity clinics, their satisfaction with practice-based learning and improvement, and their ability to self-reflect on their performance. Retrospective longitudinal design with repeated measures. Eighty Internal Medicine residents abstracted data for 3 consecutive years from the medical records of their 4,390 patients in the University of Wisconsin-Madison (UW) Hospital and Clinics and William S. Middleton Veterans Administration (VA) outpatient clinics. Logistic modeling was used to determine the effect of postgraduate year, resident sex, graduation cohort, and clinic setting on residents' "compliance rate" on 17 nationally recognized health screening and chronic disease management parameters from 2003 to 2007. Residents' adherence to national preventive and chronic disease standards increased significantly from intern to subsequent years for administering immunizations, screening for diabetes, cholesterol, cancer, and behavioral risks, and for management of diabetes. Of the residents, 92% found the chart review exercise beneficial, with 63% reporting gains in understanding about their medical practices, 26% reflecting on specific gaps in their practices, and 8% taking critical action to improve their patient outcomes. This paper provides support for the feasibility and practicality of this limited-cost method of chart review. It also directs our residency program's attention in the continuity clinic to a key area important to internal medicine training programs by highlighting the potential benefit of enhancing residents' self-reflection skills. C1 [Hildebrand, Christopher] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Trowbridge, Elizabeth; Roach, Mary A.; Sullivan, Anne Gravel; Broman, Aimee Teo; Vogelman, Bennett] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. RP Vogelman, B (reprint author), 600 Highland Ave J5-237 Clin Sci Ctr, Madison, WI 53792 USA. EM bsv@medicine.wisc.edu FU University of Wisconsin-Madison School of Medicine and Public Health; Residency Review Committee for Internal Medicine; University of Wisconsin Institute for Clinical and Translational Research; NIH Clinical and Translational Science Award [1 UL1 RR025011] FX Completion of this paper was made possible by a grant from the Medical Education and Research Committee (MERC) of the University of Wisconsin-Madison School of Medicine and Public Health as well as by the support of the Education Innovation Project of the Residency Review Committee for Internal Medicine, of which we are a participating residency. This research was also supported by the University of Wisconsin Institute for Clinical and Translational Research, funded through an NIH Clinical and Translational Science Award (CTSA), grant no. 1 UL1 RR025011. Earlier results of this paper were presented at the Association of Program Directors in Internal Medicine meeting (2004). We wish to acknowledge the programmatic efforts of Suzy Griffiths, Toni Prisk, Vonnie Schoenleber, Jessalyn Richter, and Erik Stava at various stages in the process of this work. NR 34 TC 11 Z9 11 U1 4 U2 6 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 MAR PY 2009 VL 24 IS 3 BP 361 EP 365 DI 10.1007/s11606-009-0904-1 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 407QL UT WOS:000263379300011 PM 19156469 ER PT J AU Roy, CL Kachalia, A Woolf, S Burdick, E Karson, A Gandhi, TK AF Roy, Christopher L. Kachalia, Allen Woolf, Seth Burdick, Elisabeth Karson, Andrew Gandhi, Tejal K. TI Hospital Readmissions: Physician Awareness and Communication Practices SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hospital readmission; physician awareness; communication practice; quality of care AB Patients requiring early hospital readmission may be readmitted to different physicians, potentially without the knowledge of the prior caregivers. This lost opportunity to share information about readmitted patients may be detrimental to quality of care and resident education. To measure physician awareness of and communication about readmissions. Cross-sectional study. Two academic medical centers. A total of 432 patients discharged from the general medicine services and readmitted within 14 days. We identified patients discharged from the general medicine services and readmitted within 14 days, excluding patients readmitted to the same physician(s) and planned readmissions. We surveyed discharging and readmitting physicians 48 h after the time of readmission. Discharging physician teams were aware of 48.5% (95% CI 41.5%-55.5%) of patient readmissions. Communication between teams occurred on 43.7% (95% CI 37.1%-50.3%). Higher medical complexity was associated with an increased likelihood of physician communication (adjusted OR 1.12, 95% CI 1.06-1.19). When communication occurred, readmitting physicians received information about the discharging team's overall assessment (61.9%, 95% CI 51.9%-71.9%), psychosocial issues (52.6%, 95% CI 42.4%-62.8%), pending tests (34.0%, 95% CI 24.2%-43.8%), and discharge medications (30.9%, 95% CI 21.5%-40.3%). When communication did not occur, most physicians (60.8%, 95% CI 56.7%-64.9%) responded it would have been desirable to communicate. Physicians are frequently unaware of patient readmissions and often do not communicate when readmissions occur. This communication is often desired and frequently results in the exchange of important patient information. Further work is needed to design systems to address this potential discontinuity of care. C1 [Roy, Christopher L.; Kachalia, Allen; Woolf, Seth; Burdick, Elisabeth; Gandhi, Tejal K.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Karson, Andrew] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. RP Roy, CL (reprint author), Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. EM croy@partners.org NR 18 TC 11 Z9 11 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 MAR PY 2009 VL 24 IS 3 BP 374 EP 380 DI 10.1007/s11606-008-0848-x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 407QL UT WOS:000263379300014 PM 18982395 ER PT J AU Willett, LL Paranjape, A Estrada, C AF Willett, Lisa L. Paranjape, Anuradha Estrada, Carlos TI Identifying Key Components for an Effective Case Report Poster: An Observational Study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE case report; poster; evaluation tool; academic meetings ID PUBLICATION RATES; TRAINING-PROGRAMS; RESIDENT RESEARCH; ABSTRACTS; MEDICINE; MEETINGS AB Residents demonstrate scholarly activity by presenting posters at academic meetings. Although recommendations from national organizations are available, evidence identifying which components are most important is not. To develop and test an evaluation tool to measure the quality of case report posters and identify the specific components most in need of improvement. Faculty evaluators reviewed case report posters and provided on-site feedback to presenters at poster sessions of four annual academic general internal medicine meetings. A newly developed ten-item evaluation form measured poster quality for specific components of content, discussion, and format (5-point Likert scale, 1 = lowest, 5 = highest). Main outcome measure(s): Evaluation tool performance, including Cronbach alpha and inter-rater reliability, overall poster scores, differences across meetings and evaluators and specific components of the posters most in need of improvement. Forty-five evaluators from 20 medical institutions reviewed 347 posters. Cronbach's alpha of the evaluation form was 0.84 and inter-rater reliability, Spearman's rho 0.49 (p < 0.001). The median score was 4.1 (Q1 -Q3, 3.7-4.6)(Q1 = 25th, Q3 = 75th percentile). The national meeting median score was higher than the regional meetings (4.4 vs, 4.0, P < 0.001). We found no difference in faculty scores. The following areas were identified as most needing improvement: clearly state learning objectives, tie conclusions to learning objectives, and use appropriate amount of words. Our evaluation tool provides empirical data to guide trainees as they prepare posters for presentation which may improve poster quality and enhance their scholarly productivity. C1 [Willett, Lisa L.; Estrada, Carlos] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Paranjape, Anuradha] Temple Univ, Sch Med, Gen Internal Med Sect, Birmingham, AL USA. [Estrada, Carlos] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Willett, LL (reprint author), Univ Alabama, Dept Med, BDB 339,1530 3rd Ave S, Birmingham, AL 35294 USA. EM lwillett@uab.edu NR 26 TC 4 Z9 4 U1 1 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 MAR PY 2009 VL 24 IS 3 BP 393 EP 397 DI 10.1007/s11606-008-0860-1 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 407QL UT WOS:000263379300017 PM 19089510 ER PT J AU Sridhar, ARM Willett, LL Castiglioni, A Heudebert, G Landry, M Centor, RM Estrada, CA AF Sridhar, Arun R. Mahankali Willett, Lisa L. Castiglioni, Analia Heudebert, Gustavo Landry, Michael Centor, Robert M. Estrada, Carlos A. TI Scholarship Opportunities for Trainees and Clinician Educators: Learning Outcomes from a Case Report Writing Workshop SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE case reports; education; medical; educational measurement/methods; faculty; medical; internship and residency; internal medicine/education; mentors; program development; publishing; research/education; staff development; writing; writing/standards ID CASE SERIES; PROMOTION; DIAGNOSIS AB Publishing a case report demonstrates scholarly productivity for trainees and clinician-educators. To assess the learning outcomes from a case report writing workshop. Medical students, residents, fellows and clinician-educators attending a workshop. Case report writing workshop conducted nine times at different venues. Before and after each workshop, participants self-rated their perceived competence to write a case report, likelihood of submitting a case report to a meeting or for publication in the next 6-12 months, and perceived career benefit of writing a case report (on a five-point Likert scale). The 214 participants were from 3 countries and 27 states or provinces; most participants were trainees (64.5 %). Self-rated competence for writing a case report improved from a mean of 2.5 to 3.5 (a 0.99 increase; 95% CI, 0.88-1.12, p < 0.001). The perceived likelihood of submitting a case report, and the perceived career benefit of writing one, also showed statistically significant improvements (p = 0.002, p = 0.001; respectively). Nine of 98 participants published a case report 16-41 months after workshop completion. The workshop increased participants' perception that they could present or publish a case report. C1 [Castiglioni, Analia; Heudebert, Gustavo; Centor, Robert M.; Estrada, Carlos A.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Castiglioni, Analia; Heudebert, Gustavo; Centor, Robert M.; Estrada, Carlos A.] Univ Alabama, Div Gen Internal Med, Birmingham, AL USA. [Sridhar, Arun R. Mahankali] Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. [Willett, Lisa L.; Castiglioni, Analia; Heudebert, Gustavo; Centor, Robert M.; Estrada, Carlos A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Landry, Michael] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. RP Estrada, CA (reprint author), Birmingham VA Med Ctr, 732 Fac Off Tower,510 20th St S, Birmingham, AL 35294 USA. EM cestrada@uab.edu NR 31 TC 6 Z9 6 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 MAR PY 2009 VL 24 IS 3 BP 398 EP 401 DI 10.1007/s11606-008-0873-9 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 407QL UT WOS:000263379300018 PM 19104902 ER PT J AU Razani, J Wong, JT Dafaeeboini, N Edwards-Lee, T Lu, P Alessi, C Josephson, K AF Razani, Jill Wong, Jennifer T. Dafaeeboini, Natalia Edwards-Lee, Terri Lu, Po Alessi, Cathy Josephson, Karen TI Predicting Everyday Functional Abilities of Dementia Patients With the Mini-Mental State Examination SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE activities of daily living; functional ability; dementia; Mini-Mental State Examination; Direct Assessment of Functional Status ID ALZHEIMERS-DISEASE; NEUROPSYCHOLOGICAL PERFORMANCE; RATING-SCALE; IMPAIRMENT; DIAGNOSIS; UTILITY; HEALTH AB The Mini-Mental State Examination is a widely used cognitive screening measure. The purpose of the present study was to assess how 5 specific clusters of Mini-Mental State Examination items (ie, subscores) correlate with and predict specific areas of daily functioning in dementia patients, 61 patients with varied forms of dementia were administered the Mini-Mental State Examination and an observation-based daily functional test (the Direct Assessment of Functional Status). The results revealed that the orientation and attention subscores of the Mini-Mental State Examination correlated most significantly with most functional domains. The Mini-Mental State Examination language items correlated with all but the shopping and time orientation tasks, while the Mini-Mental State Examination recall items correlated with the Direct Assessment of Functional Status time orientation and shopping tasks. Stepwise regression analyses found that among the Mini-Mental State Examination subscores, orientation was the single, best independent predictor of daily functioning. C1 [Razani, Jill] Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. [Wong, Jennifer T.] Univ Detroit Mercy, Detroit, MI 48221 USA. [Edwards-Lee, Terri] Univ Calif Los Angeles, Dept Neurol, Harbor UCLA Med Ctr, David Geffen Sch Med,Los Angeles Med Res Inst, Los Angeles, CA 90024 USA. [Alessi, Cathy; Josephson, Karen] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Alessi, Cathy; Josephson, Karen] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Razani, J (reprint author), Calif State Univ Northridge, Dept Psychol, 18111 Nordhoff St, Northridge, CA 91330 USA. EM jill.razani@csun.edu FU National Institute of General Medical Sciences (NIGMS) [GM048680, GM063787, GM008395] FX This study was conducted at California State University, Northridge, and was supported by National Institute of General Medical Sciences (NIGMS) grant GM048680 to JR. Additional support for the project was provided by NIGMS grants GM063787 (Minority Biomedical Research Support Program-Research Initiative for Scientific Enhancement) and GM008395 (Minority Access to Research Career). NR 20 TC 5 Z9 8 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD MAR PY 2009 VL 22 IS 1 BP 62 EP 70 DI 10.1177/0891988708328217 PG 9 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 408ZL UT WOS:000263475400007 PM 19196632 ER PT J AU Helmerhorst, GTT Ring, D AF Helmerhorst, Gijs T. T. Ring, David TI Subtle Essex-Lopresti Lesions: Report of 2 Cases SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Essex-Lopresti injury; forearm; longitudinal instability; radial head fracture AB Two patients with high-energy elbow injuries were diagnosed with minimally displaced partial fractures of the radial head that subsequently displaced and were noted to be Essex-Lopresti injuries. The true complexity and instability of the fractures were not immediately obvious. High-energy partial radial head fractures may merit closer observation and evaluation for associated forearm ligament injury. (J Hand Surg 2009;34A:436-438. (C) 2009 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Small Bone Innovations; Wright Medical; Acumed; Tomier; Smith and Nephew FX Support was received from Small Bone Innovations, Wright Medical, Acumed, Tomier, and Smith and Nephew. NR 6 TC 8 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 MAR PY 2009 VL 34A IS 3 BP 436 EP 438 DI 10.1016/j.jhsa.2008.10.031 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 416BY UT WOS:000263981400009 PM 19258139 ER PT J AU Brouwer, KM Guitton, TV Doornberg, JN Kloen, P Jupiter, JB Ring, D AF Brouwer, Kim M. Guitton, Thierry V. Doornberg, Job N. Kloen, Peter Jupiter, Jesse B. Ring, David TI Fractures of the Medial Column of the Distal Humerus in Adults SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Distal humerus; medial column; trauma AB Purpose Medial column fractures of the distal humerus are uncommon in adults. Among 26 patients identified in the English language literature, only 2 had articular fragmentation. We reviewed the experience of 2 trauma centers with isolated medial column fractures to evaluate our impression that these fractures often involve complex articular fragmentation. Methods There were 10 men and 4 women with am average age of 61 years (range, 44-86 years). The incidence was 3% of all distal humerus fractures at one institution with a prospective fracture database. The mechanism of injury was a fall from standing height in most patients. There was one B2.1 fracture, 3 B2.2 fractures, 9 B2.3 (multifragmentary), and 1 C3.2 fracture. All patients were treated surgically; 7 were treated with an olecranon osteotomy. Eight patients had 1 or more postoperative complications and 5 patients underwent subsequent surgeries. Results We observed 11 patients for an average of 8 years (range, 14 months to 21 years). The are of ulnohumeral motion averaged 92 degrees, average flexion was 118 degrees, and average flexion contracture was 25 degrees. According to the Broberg and Morrey Functional Rating Index, the result was excellent in 4 patients, good in 6, and fair in 1. Six patients had arthrosis (3 grade 1 and 3 grade 2) according to the radiographic criteria of Broberg and Morrey. Conclusions Surgeons should be aware that the relatively uncommon medial column adult distal humerus fracture usually features complex articular fragmentation, but that satisfactory results can be obtained after open reduction and internal fixation. (J Hand Surg 2009;34A: 439-445. (C) 2009 Published by Elsevier Inc. on behalf of the American Society fur Surgery of the Hand.) C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. Univ Amsterdam, Orthotrauma Res Ctr Amsterdam, Amsterdam, Netherlands. Acad Med Ctr, Dept Orthopaed Surg, Amsterdam, Netherlands. RP Ring, D (reprint author), Massachusetts Gen Hosp, 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 FU AO Foundation; Wright Medical; Joint Active Systems; Smith and Nephew; Small Bone Innovations; Biomet; Acumed; Tomier; Doris Duke Fellowship FX Support was received in the form of unrestricted research grants from AO Foundation, Wright Medical, Joint Active Systems, Smith and Nephew, Small Bone Innovations, Biomet, Acumed, Tomier, and the Doris Duke Fellowship. NR 23 TC 4 Z9 4 U1 1 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2009 VL 34A IS 3 BP 439 EP 445 DI 10.1016/j.jhsa.2008.11.022 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 416BY UT WOS:000263981400010 PM 19258140 ER PT J AU Loggi, E Bihl, F Chisholm, JV Biselli, M Bontadini, A Vitale, G Ercolani, G Grazi, GL Pinna, AD Bernardi, M Brander, C Andreone, P AF Loggi, Elisabetta Bihl, Florian Chisholm, John V., III Biselli, Maurizio Bontadini, Andrea Vitale, Giovanni Ercolani, Giorgio Grazi, Gian Luca Pinna, Antonio D. Bernardi, Mauro Brander, Christian Andreone, Pietro TI Anti-HBs re-seroconversion after liver transplantation in a patient with past HBV infection receiving a HBsAg positive graft SO JOURNAL OF HEPATOLOGY LA English DT Article DE Orthotopic liver transplantation; HBsAg positive marginal graft; Humoral immunity; T cell immunity; Organ shortage ID HEPATITIS-B-VIRUS; CORE-ANTIBODY; DONOR LIVER; RECIPIENTS; ALLOGRAFTS; LAMIVUDINE; CIRRHOSIS; IMPACT AB Background/Aims:Orthotopic liver transplantation (OLT) is an important therapeutic option for HBV-related end-stage-liver disease, yet it is often hampered by a scarcity of organ availability. One option to increase organ availability is the use of virologically compromised organs from HBV-infected donors. Transplantation of anti-HBcore positive grafts has been associated with a low risk of HBV recurrence if adequately treated with nucleoside analogs, irrespective of concomitant HBV-specific immunoglobulin therapy. Experience using HBsAg positive grafts is, however, very limited. Methods: Here, the analysis of the cellular and Immoral HBV-specific immunity of a subject with past HBV infection (anti-HBs and anti-HBc positive) receiving an HBsAg positive liver graft is reported. Results: Nine months post-OLT, the patient experienced a spontaneous anti-HBs re-seroconversion allowing the discontinuation of HBIG. The data show a concurrent increase in the cellular and Immoral immunity at times of reduced viral antigenemia, demonstrating effective immune control of HBV post-OLT. Conclusions: These data support the use of marginal organs in this setting, providing a potential strategy to further alleviate organ shortage. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Loggi, Elisabetta; Biselli, Maurizio; Vitale, Giovanni; Bernardi, Mauro; Andreone, Pietro] Univ Bologna, Dept Clin Med, I-40138 Bologna, Italy. [Bihl, Florian] Univ Hosp Geneva, Div Gastroenterol & Hepatol, Geneva, Switzerland. [Bontadini, Andrea] St Orsola Marcello Malpighi Hosp, Transfus Serv, Bologna, Italy. [Ercolani, Giorgio; Grazi, Gian Luca; Pinna, Antonio D.] St Orsola Marcello Malpighi Hosp, Multiorgan Transplant Unit, Bologna, Italy. [Brander, Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. RP Andreone, P (reprint author), Univ Bologna, Dept Clin Med, Via Massarenti 9, I-40138 Bologna, Italy. EM pietro.andreone@unibo.it RI Loggi, Elisabetta/K-7848-2016; Vitale, Giovanni/K-6322-2016; OI Loggi, Elisabetta/0000-0003-4985-9783; Brander, Christian/0000-0002-0548-5778; Vitale, Giovanni/0000-0003-2603-8245; Ercolani, Giorgio/0000-0003-4334-5167; ANDREONE, PIETRO/0000-0002-4794-9809 FU Associazione per la Ricerca sulle Malattic Epatiche (ARME), Bologna, Italy; Swiss National Science Foundation [SNF-PBSKB102686] FX This study was supported by a grant to EL from Associazione per la Ricerca sulle Malattic Epatiche (ARME), Bologna, Italy and by a grant to FB from the Swiss National Science Foundation (SNF-PBSKB102686). NR 24 TC 19 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2009 VL 50 IS 3 BP 625 EP 630 DI 10.1016/j.jhep.2008.08.026 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 419MS UT WOS:000264224300024 PM 19157623 ER PT J AU Perone, MJ Bertera, S Shufesky, WJ Divito, SJ Montecalvo, A Mathers, AR Larregina, AT Pang, M Seth, N Wucherpfennig, KW Trucco, M Baum, LG Morelli, AE AF Perone, Marcelo J. Bertera, Suzanne Shufesky, William J. Divito, Sherrie J. Montecalvo, Angela Mathers, Alicia R. Larregina, Adriana T. Pang, Mabel Seth, Nilufer Wucherpfennig, Kai W. Trucco, Massimo Baum, Linda G. Morelli, Adrian E. TI Suppression of Autoimmune Diabetes by Soluble Galectin-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GALACTOSIDE-BINDING LECTIN; T-CELL DEATH; DENDRITIC CELLS; NOD MICE; RECOMBINANT GALECTIN-1; EXTRACELLULAR-MATRIX; TH2 CELLS; IN-VITRO; INHIBITION; EXPRESSION AB Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that targets the beta-cells of the pancreas. We investigated the ability (if soluble galectin-1 (gal-1), an endogenous lectin that promotes T cell apoptosis, to down-regulate the T cell response that destroys the pancreatic beta-cells. We demonstrated that in nonobese diabetic (NOD) mice, gal-1 therapy reduces significantly the amount of Th1 cells, augments the number of T cells secreting IL-A or IL-10 specific for islet cell Ag, and causes peripheral deletion of P-cell-reactive T cells. Administration or gal-1 prevented the onset of hyperglycemia in NOD mice at early and subclinical stages or 1, 11). Preventive gal-1 therapy shifted the composition of the insulitis into an infiltrate that did not invade the islets and that contained a significantly reduced number of Th1 cells and a higher percentage of CD4(+) T cells with content of IL-4, IL-5, or IL-10. The beneficial effects of gal-1 correlated with the ability of the lectin to trigger apoptosis of the T cell subsets that cause beta-cell damage while sparing naive T cells, Th2 lymphocytes, and regulatory T cells in NOD mice. Importantly, gal-1 reversed P-cell autoimmunity and hyperglycemia in NOD mice with ongoing T1D. Because gal-1 therapy did not cause major side effects or beta-cell toxicity in NOD mice, the use of gal-1 to control beta-cell autoimmunity represents a novel alternative for treatment of subclinical or ongoing T1D. The Journal of Immunology, 2009, 182: 2641-2653. C1 [Perone, Marcelo J.; Shufesky, William J.; Divito, Sherrie J.; Montecalvo, Angela; Morelli, Adrian E.] Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15213 USA. [Perone, Marcelo J.; Shufesky, William J.; Divito, Sherrie J.; Montecalvo, Angela; Morelli, Adrian E.] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA 15213 USA. [Mathers, Alicia R.; Larregina, Adriana T.] Univ Pittsburgh, Med Ctr, Dept Dermatol, Pittsburgh, PA 15213 USA. [Mathers, Alicia R.; Larregina, Adriana T.; Morelli, Adrian E.] Univ Pittsburgh, Med Ctr, Dept Immunol, Pittsburgh, PA 15213 USA. [Bertera, Suzanne; Trucco, Massimo] Univ Pittsburgh, Dept Pediat, Div Immunogenet, Pittsburgh, PA 15213 USA. [Bertera, Suzanne; Trucco, Massimo] Univ Pittsburgh, Rangos Res Ctr, Pittsburgh, PA 15213 USA. [Pang, Mabel; Baum, Linda G.] Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Pang, Mabel; Baum, Linda G.] Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Seth, Nilufer; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Canc Immunol & Aids, Dana Farber Canc Inst, Boston, MA 02115 USA. [Seth, Nilufer; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Seth, Nilufer; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Morelli, AE (reprint author), W1556 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. EM morelli@imap.pitt.edu OI Bertera, Suzanne/0000-0002-9228-4279 FU NHLBI NIH HHS [R01 HL077545-04, R01 HL075512-04, R01 HL077545, R01 HL075512]; NIDDK NIH HHS [R33 DK63499, R33 DK063499, R33 DK063499-04] NR 60 TC 52 Z9 56 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 MAR 1 PY 2009 VL 182 IS 5 BP 2641 EP 2653 DI 10.4049/jimmunol.0800839 PG 13 WC Immunology SC Immunology GA 411MG UT WOS:000263653100013 PM 19234158 ER PT J AU Mailloux, AW Young, MRI AF Mailloux, Adam W. Young, M. Rita I. TI NK-Dependent Increases in CCL22 Secretion Selectively Recruits Regulatory T Cells to the Tumor Microenvironment SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FOSTERS IMMUNE PRIVILEGE; DEFICIENT BEIGE MICE; GROWTH-FACTOR-BETA; BONE-MARROW; DOWN-REGULATION; MHC EXPRESSION; DENDRITIC-CELL; CD4(+) CD25(+); LYMPHOCYTES; AUTOIMMUNITY AB Tumor-induced immune suppression involves the accumulation of immune-suppressive infiltrates in the microenvironment. This study demonstrates increased numbers of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) in the lungs of C57BL/6 mice hearing it metastatic Lewis lung carcinoma (LLC) variant. These Tregs suppressed the proliferation of endogenous CD4(+)CD25(-) cells and expressed higher levels of the chemokine receptor CCR4 than other types of T cells. LLC-bearing lungs secreted elevated levels of the CCR4-associated chemokine CCL22 compared with normal lungs. However, CCL22 was not secreted by LLC or normal epithelial controls, suggesting that CCL22 is secreted fly a nonepithelial component of the microenvironment. Migration assays revealed that medium conditioned by LLC-bearing lungs selectively recruited Tregs at higher frequencies than did medium conditioned by normal lungs. Neutralization or CCL22 significantly reduced this selective recruitment toward both conditioned media. A series of immunomagnetic isolations, FACS, and flow cytometric analyses were used to isolate different cellular fractions from both normal and LLC-bearing lungs. When isolated, only the NK-containing fractions secreted CCL22, and the same fraction isolated from LLC-bearing lungs secreted higher levels. Depletion of INK cells from both normal and LLC-bearing lung tissue significantly reduced CCL22 secretion, suggesting that a large portion of secreted CCL22 is NK cell dependent. Flow cytometric analysis of the lung NK compartments revealed no significant increase in NK cell numbers across LLC-bearing lung tissue as a whole as compared with normal tissue. However, immunofluorescent staining revealed an increased frequency of NK cells at the tumor periphery that were closely associated with the elevated FoxP3(+) infiltrate. The Journal of Immunology, 2009, 182: 2753-2765. C1 [Mailloux, Adam W.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29403 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29403 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA. [Young, M. Rita I.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv 151, Charleston, SC USA. RP Young, MRI (reprint author), Ralph H Johnson Vet Affairs Hosp, Res Serv 151, 109 Bee st, Charleston, SC 29401 USA. EM rita.young@med.va.gov FU NCI NIH HHS [R01 CA097813, CA8566, R01 CA085266-06, CA97813, R01 CA085266, R01 CA128837, R01 CA128837-05] NR 56 TC 40 Z9 45 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 MAR 1 PY 2009 VL 182 IS 5 BP 2753 EP 2765 DI 10.4049/jimmunol.0801124 PG 13 WC Immunology SC Immunology GA 411MG UT WOS:000263653100025 PM 19234170 ER PT J AU Kim, AY Timm, J Nolan, BE Reyor, LL Kane, K Berical, AC Zachary, KC Lauer, GM Kuntzen, T Allen, TM AF Kim, Arthur Y. Timm, Joerg Nolan, Brian E. Reyor, Laura L. Kane, Katherine Berical, Andrew C. Zachary, Kimon C. Lauer, Georg M. Kuntzen, Thomas Allen, Todd M. TI Temporal Dynamics of a Predominant Protease Inhibitor-Resistance Mutation in a Treatment-Naive, Hepatitis C Virus-Infected Individual SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 15th International Symposium on Hepatitis C Virus and Related Viruses CY OCT 05-09, 2008 CL San Antonio, TX ID NS3 PROTEASE; POLYMERASE INHIBITORS; VARIANTS; REPLICATION; SENSITIVITY; TELAPREVIR; DOMINANT; HIV-1 AB The dramatic antiviral activities of drugs that specifically inhibit hepatitis C virus replication can be tempered by baseline mutations that confer resistance. We describe the kinetics of an R155K mutation in hepatitis C virus (HCV) NS3 protease known to confer resistance to specific protease inhibitors in an individual coinfected with human immunodeficiency virus-1 and HCV. Longitudinal sequences revealed changes in the relative frequency with which this variant was observed independent of HCV replication levels, illustrating that this mutation coexists with wild-type strains in vivo in the absence of drugs. The persistence of drug-resistance mutations argues for baseline resistance genotyping at the time therapy is initiated to accurately predict the efficacy of treatment. C1 [Kim, Arthur Y.; Timm, Joerg; Nolan, Brian E.; Reyor, Laura L.; Kane, Katherine; Berical, Andrew C.; Lauer, Georg M.; Kuntzen, Thomas; Allen, Todd M.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Kim, Arthur Y.; Zachary, Kimon C.; Allen, Todd M.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Lauer, Georg M.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. RP Kim, AY (reprint author), Harvard Univ, Sch Med, Partners AIDS Res Ctr, Cox 5,55 Fruit St, Boston, MA 02114 USA. EM akim1@partners.org; tallen2@partners.org RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [R01 AI067926, K23 AI054379, K23 AI054379-05, R01 AI067926-03, R01-AI67926, U19 AI066345, U19 AI066345-020004, U19 AI066345-030004, U19 AI066345-04] NR 15 TC 22 Z9 22 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2009 VL 199 IS 5 BP 737 EP 741 DI 10.1086/596657 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 406ND UT WOS:000263301300019 PM 19199553 ER PT J AU Tai, ES Sim, XL Ong, TH Wong, TY Saw, SM Aung, T Kathiresan, S Orho-Melander, M Ordovas, JM Tan, JT Seielstad, M AF Tai, E. Shyong Sim, Xue Ling Ong, Twee Hee Wong, Tien Yin Saw, Seang Mei Aung, Tin Kathiresan, Sekar Orho-Melander, Marju Ordovas, Jose M. Tan, Jonathan T. Seielstad, Mark TI Polymorphisms at newly identified lipid-associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population SO JOURNAL OF LIPID RESEARCH LA English DT Article DE genetics; ethnic group; coronary heart disease ID DENSITY-LIPOPROTEIN CHOLESTEROL; GLOBAL BURDEN; LDL; TRIGLYCERIDES; PREVENTION; RISK AB We conducted a cross-sectional study of Malay articipants aged 40-80 years (n = 2,932) to examine the associations between polymorphisms at newly identified, lipid-associated loci with blood lipid levels and prevalent cardiovascular disease (CVD) in a Malay population in Asia. A polymorphism adjacent to the TRIB1 locus (rs17321515) was associated with elevated total cholesterol and LDL-cholesterol (LDL-C) after adjustment for age and sex (both P values <0.007) and with increased risk of coronary heart disease and CVD [odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.03-1.46; and OR 1.2, 95% CI 1.02-1.42, respectively] under an additive model of inheritance. In addition, using recessive models of inheritance, polymorphisms on chromosome 19 adjacent to the CILP2 and PBX4 loci (rs16996148) and on chromosome 1 at the GALNT2 locus (rs4846914) were associated with elevated HDL-C (P = 0.005) and lower LDL-C (P = 0.048), respectively. Although novel, the former is consistent with the association between this polymorphism and lower blood triglycerides observed in the initial studies conducted in populations of European ancestry. Neither showed statistically significant association with CVD. These observations should form the basis of further investigation to identify the causative polymorphisms at this locus, and also to understand the mechanistic roles that this protein may play in lipoprotein metabolism in Asians and other populations.-Tai, E. S., X. L. Sim, T. H. Ong, T. Y. Wong, S. M. Saw, T. Aung, S. Kathiresan, M. Orho-Melander, J. M. Ordovas, J. T. Tan, and M. Seielstad. Polymorphisms at newly identified lipid-associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population. J. Lipid Res. 2009. 50: 514-520. C1 [Tai, E. Shyong] Singapore Gen Hosp, Dept Endocrinol, Singapore 169608, Singapore. [Sim, Xue Ling; Tan, Jonathan T.] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore. [Wong, Tien Yin; Saw, Seang Mei; Aung, Tin] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117595, Singapore. [Saw, Seang Mei] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Community Occupat & Family Med, Singapore 117595, Singapore. [Ong, Twee Hee; Seielstad, Mark] Genome Inst Singapore, Singapore, Singapore. [Wong, Tien Yin] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Orho-Melander, Marju] Lund Univ, Dept Clin Sci Diabet & Endocrinol, S-22100 Lund, Sweden. [Ordovas, Jose M.] Tufts Univ, Nutr & Genom Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Tai, ES (reprint author), Singapore Gen Hosp, Dept Endocrinol, Singapore 169608, Singapore. EM eshyong@pacific.net.sg OI Seielstad, Mark/0000-0001-5783-1401; Ordovas, Jose/0000-0002-7581-5680; Tai, E Shyong/0000-0003-2929-8966 FU National Medical Research Council [0796/2003, 0863/2004, CSI/0002/2005]; Biomedical Research Council [501/1/25-5]; Genome Institute of Singapore; Singapore Tissue Network; Ministry of Health, Singapore FX This study was supported by the National Medical Research Council, Grants 0796/2003, 0863/2004, and CSI/0002/2005, and Biomedical Research Council Grant 501/1/25-5. Additional support was provided by the Genome Institute of Singapore, the Singapore Tissue Network, and the Ministry of Health, Singapore. NR 27 TC 35 Z9 37 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 2009 VL 50 IS 3 BP 514 EP 520 DI 10.1194/jlr.M800456-JLR200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 406TK UT WOS:000263317600016 PM 18987386 ER PT J AU Reese, TG Benner, T Wang, R Feinberg, DA Wedeen, VJ AF Reese, Timothy G. Benner, Thomas Wang, Ruopeng Feinberg, David A. Wedeen, Van J. TI Halving Imaging Time of Whole Brain Diffusion Spectrum Imaging and Diffusion Tractography Using Simultaneous Image Refocusing in EPI SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MRI; diffusion imaging; fast imaging; tractography; pulse sequences ID SPIN-ECHO; MRI; ANISOTROPY; TENSOR AB Purpose: To increase the efficiency of densely encoded diffusion imaging of the brain, such as diffusion spectrum imaging (DSI), we time-multiplex multiple slices within the same readout using simultaneous image refocusing echo-planar imaging (SIR-EPI). Materials and Methods: Inefficiency in total scan time results from the long time of diffusion encoding gradient pulses which must be repeated for each and every image. We present a highly efficient multiplexing method, simultaneous image refocusing (SIR), for reducing the total scan time of diffusion imaging by nearly one-half. SIR DSI is performed in 10 minutes rather than 21 minutes, acceptable for routine clinical application. Results: Two identical studies Were completed, comparing conventional single-slice EPI DSI and SIR-EPI DSI, showing equal signal-to-noise ratio (SNR) and contrast and small differences in registration, likely due to typical subject motion. Comparison of DSI and DTI tractographs showed matching quality and detection of white matter tracts. Conclusion: The net reduction to nearly half the number of diffusion encoding gradient pulses in SIR-EPI significantly reduces acquisition times of DSI and DTI. C1 [Reese, Timothy G.; Benner, Thomas; Wang, Ruopeng; Wedeen, Van J.] Massachusetts Gen Hosp, Dept Radiol, A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Feinberg, David A.] Adv MRI Technol, Sebastapol, CA USA. RP Reese, TG (reprint author), Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Bldg 149,MS 2301,13th St, Charlestown, MA USA. EM reese@nmr.mgh.harvard.edu FU National Institutes of Health (NIH) [64044] FX Contract grant sponsor: National Institutes of Health (NIH); Contract grant number: 1RO1 MH 64044. NR 19 TC 31 Z9 33 U1 1 U2 3 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 MAR PY 2009 VL 29 IS 3 BP 517 EP 522 DI 10.1002/jmri.21497 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 415GT UT WOS:000263923000002 PM 19243032 ER PT J AU Magill, JC Byl, MF Goldwaser, B Papadaki, M Kromann, R Yates, B Morency, JR Kaban, LB Troulis, MJ AF Magill, John C. Byl, Marten F. Goldwaser, Batya Papadaki, Maria Kromann, Roger Yates, Brent Morency, Joseph R. Kaban, Leonard B. Troulis, Maria J. TI Automating Skeletal Expansion: An Implant for Distraction Osteogenesis of the Mandible SO JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME LA English DT Article DE automated medical device; implant distraction; ostco genesis ID BONE DISTRACTION; DEVICE; FREQUENCY; MINIPIGS; TISSUES; LATENCY; GENESIS; GROWTH AB Distraction osteogenesis is a technique of bone lengthening that makes use of the body's natural healing capacity An esteotomy is created and a rigid distraction device attached to the bone After a latency period the device is activated two to four tunes per day for a total of 1 mm/day of bone lengthening This technique is used to correct a variety of congenital and acquired deformities of the mandible midface and long bones to shorten the treatment period and to eliminate ths implications of patant activation of the device an automated continuous distraction device would be desirable It has been reported that continuous distraction generates adequate bone with lengthening at a rate of 2 mm/day thereby reducing the treatment time The device we describe here uses immature high pressure hydraulics position feedback, and a digital controller to achieve closed loop control of the distraction process The implanted actuator can produce up to 40 N of distraction force on linear trajectones as well as curved distraction paths In this paper we detail the spring-powered hydraulic reservoir controller and user interlace Experiments to test the new device design were performed in a poicine cadaver head and in live pigs In the cadaver head the device performed an 11 day/11 mm distraction with a root-mean squared position error of 0 09 mm The device functioned for period of several days in each of five live animals though some component failures occurred, leading to design revisions The test series showed that the novel design of this system provides the capabilities necessary to automate distraction of the mandible Further developments will focus on making the implanted position sensor more robust and then on carrying out clinical trials [DOI 10.1115/1.3071969] C1 [Magill, John C.; Byl, Marten F.; Morency, Joseph R.] Phys Sci Inc, Andover, MA 01810 USA. [Goldwaser, Batya; Papadaki, Maria; Kaban, Leonard B.; Troulis, Maria J.] Harvard Univ, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Sch Dent Med, Boston, MA 02114 USA. [Kromann, Roger; Yates, Brent] Embedded Syst Design Inc, Atlanta, GA 30308 USA. RP Magill, JC (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. FU NIH/NIDCR [5B44DE014803-03]; MGH Department of Oral and Maxillo-facial Education and Research Fund FX This work was funded by a Phase II SBIR grant (Grant No 5B44DE014803-03) from the NIH/NIDCR This work was also supported in part by the MGH Department of Oral and Maxillo-facial Education and Research Fund The authors wish to thank Dr Edward Seldin (MGH Department of OMFS), who was the first to conceptualize the importance of curvilinear distraction and to thank Synthes Maxillofacial for helpful discussions regarding distractor design and for assistance in machining necessary to use Synthes locking screws with our prototype distractors NR 19 TC 4 Z9 4 U1 1 U2 2 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 1932-6181 J9 J MED DEVICES JI J. Med. Devices PD MAR PY 2009 VL 3 IS 1 AR 014502 DI 10.1115/1.3071969 PG 7 WC Engineering, Biomedical SC Engineering GA 674QY UT WOS:000283763600009 PM 20740071 ER PT J AU Sofaer, N Thiessen, C Goold, SD Ballou, J Getz, KA Koski, G Krueger, RA Weissman, JS AF Sofaer, N. Thiessen, C. Goold, S. D. Ballou, J. Getz, K. A. Koski, G. Krueger, R. A. Weissman, J. S. TI Subjects' views of obligations to ensure post-trial access to drugs, care and information: qualitative results from the Experiences of Participants in Clinical Trials (EPIC) study SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID DEVELOPING-COUNTRIES; RESEARCHERS; HIV/AIDS; JUSTICE AB Objectives: To report the attitudes and opinions of subjects in US clinical trials about whether or not, and why, they should receive post-trial access (PTA) to the trial drug, care and information. Design: Focus groups, short self-administered questionnaires. Setting: Boston, Dallas, Detroit, Oklahoma City. Participants: Current and recent subjects in clinical trials, primarily for chronic diseases. Results: 93 individuals participated in 10 focus groups. Many thought researchers, sponsors, health insurers and others share obligations to facilitate PTA to the trial drug, if it benefited the subject, or to a therapeutic equivalent. Some thought PTA obligations include providing transition care (referrals to non-trial physicians or other trials, limited follow-up, short-term drug supply) or care for long-term adverse events. Others held, in contrast, that there are no PTA obligations regarding drugs or care. However, there was agreement that former subjects should receive information (drug name, dosage received, market approval date, long-term adverse effects, trial results). Participants frequently appealed to health need, cost, relationships, reciprocity, free choice and sponsor self-interest to support their views. Many of their reasons overlapped with those commonly discussed by bioethicists. Conclusion: Many participants in US trials for chronic conditions thought there are obligations to facilitate PTA to the trial drug at a "fair'' price; these views were less demanding than those of non-US subjects in other studies. However, our participants' views about informational obligations were broader than those of other subjects and many bioethicists. Our results suggest that the PTA debate should expand beyond the trial drug and aggregate results. C1 [Koski, G.; Weissman, J. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. [Sofaer, N.] Harvard Univ, Formery Program Eth & Hlth, Boston, MA 02114 USA. [Thiessen, C.] Harvard Univ, Massachusetts Gen Hosp, PhD Program Hlth Policy, Inst Hlth Policy, Boston, MA 02114 USA. [Goold, S. D.] Univ Michigan, Sch Med, Dept Internal Med, Bioeth Program, Ann Arbor, MI USA. [Ballou, J.] Math Policy Res Inc, Princeton, NJ USA. [Getz, K. A.] Tufts Univ, Tufts Ctr Study Drug Dev, Boston, MA 02111 USA. [Koski, G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Krueger, R. A.] Univ Minnesota, Educ Policy & Adm, Minneapolis, MN USA. RP Weissman, JS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jweissman@partners.org OI Goold, Susan Dorr/0000-0002-0258-9774; Thiessen, Carrie/0000-0002-1410-0112 FU National Institute of Nursing Research FX This study was funded by the National Institute of Nursing Research. The funders did not have any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 41 TC 13 Z9 13 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD MAR PY 2009 VL 35 IS 3 BP 183 EP 188 DI 10.1136/jme.2008.024711 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 412KA UT WOS:000263722500010 PM 19251971 ER PT J AU Adams, K Beal, MW AF Adams, Kate Beal, Margaret W. TI Implanon: A Review of the Literature With Recommendations for Clinical Management SO JOURNAL OF MIDWIFERY & WOMENS HEALTH LA English DT Article DE Implanon; progestin; contraception; contraceptive devices ID SINGLE CONTRACEPTIVE IMPLANT; ANTIRETROVIRAL THERAPY; ETONOGESTREL IMPLANT; INTRAUTERINE-DEVICE; WOMEN; NORPLANT; EFFICACY; SAFETY; USERS; ACCEPTABILITY AB Implanon is a new implantable, progestin-only contraceptive which was approved in the United States in July 2006. Implanon is comprised of a single ethylene vinylacetate copolymer rod that is 4 cm long and 2 min in diameter. It is inserted subdermally in the groove between the biceps and triceps of the nondominant arm. A literature review was conducted and side effects are discussed. Implanon offers promise as a high-efficacy, long-term contraceptive and can enhance the contraceptive options offered by the women's health care providers. Clinical trial data indicate that the device is both safe and effective. J Midwifery Womens Health 2009;54:142-149 (C) 2009 by the American College of Nurse-Midwives. C1 [Adams, Kate] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Beal, Margaret W.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Adams, K (reprint author), Yale Univ, Sch Nursing, New Haven, CT 06536 USA. EM kate.adams@aya.yale.edu NR 41 TC 8 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1526-9523 J9 J MIDWIFERY WOM HEAL JI J. Midwifery Women Health PD MAR-APR PY 2009 VL 54 IS 2 BP 142 EP 149 DI 10.1016/j.jmwh.2008.09.004 PG 8 WC Nursing SC Nursing GA 422US UT WOS:000264453800008 PM 19249660 ER PT J AU Tang, QZ Cai, J Shen, DF Bian, ZY Yan, L Wang, YX Lan, J Zhuang, GQ Ma, WZ Wang, W AF Tang, Qizhu Cai, Jun Shen, Difei Bian, Zhouyan Yan, Ling Wang, You-Xin Lan, Jie Zhuang, Guo-Qing Ma, Wen-Zhan Wang, Wei TI Lysosomal cysteine peptidase cathepsin L protects against cardiac hypertrophy through blocking AKT/GSK3 beta signaling SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE Cathepsin L; cardiac remodeling; AKT; Fibrosis; GSK3 beta ID MICE DEFICIENT; KNOCKOUT MICE; DISEASE; HEART; PROTEASES; PATHWAYS; CARDIOMYOPATHY; APOPTOSIS; TARGETS; CANCER AB The lysosomal cysteine peptidase cathepsin L (CTSL) is an important lysosomal proteinase involved in a variety of cellular functions including intracellular protein turnover, epidermal homeostasis, and hair development. Deficiency of CTSL in mice results in a progressive dilated cardiomyopathy. In the present study, we tested the hypothesis that cardiac overexpression of human CTSL in the murine heart would protect against cardiac hypertrophy in vivo. The effects of constitutive human CTSL expression on cardiac hypertrophy were investigated using in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding (AB) in CTSL transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by two-dimensional and M-mode echocardiography as well as by molecular and pathological analyses of heart samples. Constitutive overexpression of human CTSL in the murine heart attenuated the hypertrophic response, markedly reduced apoptosis, and fibrosis. Cardiac function was also preserved in hearts with increased CTSL levels in response to hypertrophic stimuli. These beneficial effects were associated with attenuation of the Akt/GSK3 beta signaling cascade. Our in vitro studies further confirmed that CTSL expression in cardiomyocytes blunts cardiac hypertrophy through blocking of Akt/GSK3 beta signaling. The study indicates that CTSL improves cardiac function and inhibits cardiac hypertrophy, inflammation, and fibrosis through blocking Akt/GSK3 beta signaling. C1 [Tang, Qizhu; Shen, Difei; Bian, Zhouyan; Yan, Ling] Wuhan Univ, Cardiovasc Res Inst, Wuhan 430060, Peoples R China. [Tang, Qizhu; Shen, Difei; Bian, Zhouyan; Yan, Ling] Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Peoples R China. [Cai, Jun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. [Cai, Jun] Capital Med Univ, Beijing Chaoyang Hosp, Dept Cardiol, Beijing 100020, Peoples R China. [Wang, You-Xin; Lan, Jie; Zhuang, Guo-Qing; Ma, Wen-Zhan; Wang, Wei] Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China. [Wang, You-Xin; Lan, Jie; Zhuang, Guo-Qing; Ma, Wen-Zhan; Wang, Wei] Capital Med Univ, Sch Publ Hlth & Family Med, Beijing 100069, Peoples R China. RP Tang, QZ (reprint author), Wuhan Univ, Cardiovasc Res Inst, Wuhan 430060, Peoples R China. EM qizhu.tang@ymail.com OI wang, wei/0000-0002-1430-1360; Wang, Youxin/0000-0002-6574-6706 FU National Natural Science Foundation of China [30771193]; Research Fund for the Doctoral Program of Higher Education of China [20050025002, 2007042086103]; Beijing Natural Science Foundation [5072007]; National Natural Science Foundation [30670216] FX National Natural Science Foundation of China ( 30771193), Research Fund for the Doctoral Program of Higher Education of China ( no. 20050025002) and Beijing Natural Science Foundation ( 5072007) to Wei Wang. National Natural Science Foundation of China ( 30670216), Research Fund for the Doctoral Program of Higher Education of China ( no. 2007042086103) to Qizhu Tang. NR 25 TC 37 Z9 41 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD MAR PY 2009 VL 87 IS 3 BP 249 EP 260 DI 10.1007/s00109-008-0423-2 PG 12 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 409JN UT WOS:000263502100004 PM 19096818 ER PT J AU Eddy, KT AF Eddy, Kamryn T. TI Integrated Treatment of Eating Disorders: Beyond the Body Betrayed SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 [Eddy, Kamryn T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Eddy, Kamryn T.] Harvard Univ, Sch Med, Boston, MA USA. RP Eddy, KT (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAR PY 2009 VL 197 IS 3 BP 213 EP 213 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 420BL UT WOS:000264263300016 ER PT J AU Shen, CC Silver, AL O'Donnell, TJ Fleming, JC Karcioglu, ZA AF Shen, Christopher C. Silver, Amanda L. O'Donnell, Thomas J. Fleming, James C. Karcioglu, Zeynel A. TI Optic Neuropathy Caused by Naso-Orbital Mass in Chronic Intranasal Cocaine Abuse SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID MIDLINE DESTRUCTIVE LESIONS; OSTEOCARTILAGINOUS NECROSIS; SINONASAL TRACT; GRANULOMA; SINUSITIS; CELLULITIS AB A 48-year-old woman with a history of chronic intranasal cocaine abuse presented with unilateral proptosis associated with severe visual loss from optic neuropathy in the right eye. Imaging showed extensive bone and soft tissue destruction in the paranasal region and ail orbital mass. Initial biopsies suggested a low-grade neoplasm. The correct diagnosis was established only on repeat biopsy, which revealed marked pleomorphism and nonspecific chronic inflammation with irregular collagen bundles containing thick-walled blood vessels. This case emphasizes that intranasal cocaine abuse may clinically, radiographically, and histopathologically mimic a neoplasm or a necrotizing vasculitis. C1 [Shen, Christopher C.; O'Donnell, Thomas J.; Fleming, James C.; Karcioglu, Zeynel A.] Univ Tennessee, Hlth Sci Ctr, Hamilton Eye Inst, Memphis, TN 38163 USA. [Silver, Amanda L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. RP O'Donnell, TJ (reprint author), Univ Tennessee, Hlth Sci Ctr, Hamilton Eye Inst, 930 Madison Ave,Suite 470,Room 485, Memphis, TN 38163 USA. EM todonnel@utmem.edu FU Research to Prevent Blindness; St. Giles Foundation of New York FX This work was supported in part by Research to Prevent Blindness (ZAK, TJO, JCF) and St. Giles Foundation of New York (ZAK). NR 25 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 MAR PY 2009 VL 29 IS 1 BP 50 EP 53 PG 4 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 418CZ UT WOS:000264126100012 PM 19458577 ER PT J AU Valencia, A Reeves, PB Sapp, E Li, X Alexander, J Kegel, KB Chase, K Aronin, N DiFiglia, M AF Valencia, A. Reeves, P. B. Sapp, E. Li, X. Alexander, J. Kegel, K. B. Chase, K. Aronin, N. DiFiglia, M. TI LIPID RAFTS ACCUMULATE MUTANT HUNTINGTIN AND REVEAL CHANGES IN AKT PATHWAY IN HUNTINGTON's DISEASE MICE: ROLE IN NEURODEGENERATION SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Valencia, A.; Reeves, P. B.; Sapp, E.; Li, X.; Alexander, J.; Kegel, K. B.; DiFiglia, M.] Massachusetts Gen Hosp, Charlestown, MA USA. [Valencia, A.; Reeves, P. B.; Sapp, E.; Li, X.; Alexander, J.; Kegel, K. B.; DiFiglia, M.] Harvard Univ, Sch Med, Charlestown, MA USA. [Chase, K.; Aronin, N.] Univ Massachusetts, Sch Med, Worcester, MA 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 MAR PY 2009 VL 108 BP 43 EP 43 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800092 ER PT J AU Dzhala, VI Staley, KJ AF Dzhala, V. I. Staley, K. J. TI NEONATAL SEIZURES REDUCE PHENOBARBITAL EFFICACY VIA INCREASED NKCC1 ACTIVITY SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Dzhala, V. I.; Staley, K. J.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 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 MAR PY 2009 VL 108 BP 45 EP 45 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800095 ER PT J AU Kindy, MS Yu, J Zhu, H Hook, V Hook, G AF Kindy, M. S. Yu, J. Zhu, H. Hook, V. Hook, G. TI NOVEL PROTEOLYTIC MECHANISMS FOR BETA-AMYLOID PRODUCTION. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Kindy, M. S.; Yu, J.; Zhu, H.] Med Univ S Carolina, Charleston, SC 29425 USA. [Hook, V.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Hook, G.] Amer Life Sci Pharmaceut Inc, San Diego, CA USA. [Kindy, M. S.] Ralph H Johnson Vet Affairs, Charleston, SC 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 MAR PY 2009 VL 108 BP 70 EP 71 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800149 ER PT J AU Eichler, FS McCampbell, A Hornemann, T Kuljis, D Garofalo, K Frosch, M Gable, K Harmon, J Dunn, TM Brown, RH AF Eichler, F. S. McCampbell, A. Hornemann, T. Kuljis, D. Garofalo, K. Frosch, M. Gable, K. Harmon, J. Dunn, T. M. Brown, R. H. TI OVEREXPRESSION OF SERINE PALMITOYLTRANSFERASE RESCUES THE PHENOTYPE OF HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Eichler, F. S.; Kuljis, D.; Garofalo, K.] Harvard Univ, Sch Med, Dept Neurol, MGH Neurosci Ctr, Boston, MA 02115 USA. [Hornemann, T.] Univ Zurich Hosp, Inst Clin Chem, CH-8091 Zurich, Switzerland. [McCampbell, A.] Merck & Co Inc, Philadelphia, PA USA. Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA USA. [Brown, R. H.] Day Lab Neuromuscular Res, Boston, MA USA. [Gable, K.; Harmon, J.; Dunn, T. M.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kub Lab Neuropathol,Dept Pathol, Boston, MA 02115 USA. [Frosch, M.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 87 EP 87 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800191 ER PT J AU Kuljis, D Garofalo, K Ransohoff, R Frosch, M Eichler, F AF Kuljis, D. Garofalo, K. Ransohoff, R. Frosch, M. Eichler, F. TI CHRONIC INSTALLATION OF LYSOPHOSPHATIDYL-CHOLINE (C24:0) INDUCES MIROGLIAL ACTIVATION AND DEMYELINATION SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Kuljis, D.; Garofalo, K.; Eichler, F.] Harvard Univ, Sch Med, Dept Neurol, MGH Neurosci Ctr, Boston, MA 02115 USA. [Ransohoff, R.] Cleveland Clin, Neuroinflammatory Res Ctr, Cleveland, OH 44106 USA. [Frosch, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kub Lab Neuropathol,Dept Pathol, 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2009 VL 108 BP 88 EP 88 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800192 ER PT J AU El-Amouri, SS Yu, J Zhu, H Kindy, MS AF El-Amouri, S. S. Yu, J. Zhu, H. Kindy, M. S. TI NEPRILYSIN: AN ENZYME CANDIDATE TO SLOW THE PROGRESSION OF ALZHEIMER'S DISEASE SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [El-Amouri, S. S.; Yu, J.; Zhu, H.; Kindy, M. S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Kindy, M. S.] Ralph H Johnson VA Med Ctr, Charleston, SC 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 MAR PY 2009 VL 108 BP 149 EP 149 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800346 ER PT J AU Arthur, JR Leroy, SG Baek, RC Seyfried, TN Sena-Esteves, M AF Arthur, J. R. Leroy, S. G. Baek, R. C. Seyfried, T. N. Sena-Esteves, M. TI VENTRICULAR INFUSION OF AAV2/8 VECTOR CORRECTS GM1 GANGLIOSIDE STORAGE IN CNS OF ADULT CULAR INFUSION OF AAV2/8 VECTOR CORRECTS GM1 GANGLIOSIDE STORAGE IN CNS OF ADULT beta GAL -/- MICE SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 40th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 07-11, 2009 CL Charleston, SC SP Amer Soc Neurochem C1 [Arthur, J. R.; Baek, R. C.; Seyfried, T. N.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. [Leroy, S. G.; Sena-Esteves, M.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Leroy, S. G.; Sena-Esteves, M.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 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 MAR PY 2009 VL 108 BP 152 EP 152 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407AU UT WOS:000263336800353 ER PT J AU Lilaonitkul, W Guinan, JJ AF Lilaonitkul, Watjana Guinan, John J., Jr. TI Reflex Control of the Human Inner Ear: A Half-Octave Offset in Medial Efferent Feedback That Is Consistent With an Efferent Role in the Control of Masking SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CROSSED OLIVOCOCHLEAR BUNDLE; EVOKED OTOACOUSTIC EMISSIONS; IN-NOISE INTELLIGIBILITY; AUDITORY-NERVE RESPONSES; OUTER HAIR-CELLS; CONTRALATERAL SUPPRESSION; NORMAL-HEARING; INTENSITY DISCRIMINATION; ELECTRICAL-STIMULATION; STIMULUS VARIABLES AB Lilaonitkul W, Guinan JJ. Reflex control of the human inner ear: A half-octave offset in medial efferent feedback that is consistent with an efferent role in the control of masking. J Neurophysiol 101: 1394-1406, 2009. First published December 31, 2008; doi:10.1152/jn.90925.2008. The high sensitivity and frequency selectivity of the mammalian cochlea is due to amplification produced by outer hair cells (OHCs) and controlled by medial olivocochlear (MOC) efferents. Data from animals led to the view that MOC fibers provide frequency-specific inhibitory feedback; however, these studies did not measure intact MOC reflexes. To test whether MOC inhibition is primarily at the frequency that elicits the MOC activity, acoustically elicited MOC effects were quantified in humans by the change in otoacoustic emissions produced by 60-dB SPL tone and half-octave-band noise elicitors at different frequencies relative to a 40-dB SPL, 1-kHz probe tone. On average, all elicitors produced MOC effects that were skewed (elicitor frequencies 1/2-1 octave below the probe produced larger effects than those 1/2-1 octave above). The largest MOC effects were from elicitors below the probe frequency for contra- and bilateral elicitors but were from elicitors centered at the probe frequency for ipsilateral elicitors. Typically, ipsilateral elicitors produced larger effects than contralateral elicitors and bilateral elicitors produced effects near the ipsi + contra sum. Elicitors at levels down to 30-dB SPL produced similar patterns. Tuning curves (TCs) interpolated from these data were V-shaped with Q10s similar to 2. These are sharper than MOC-fiber TCs found near 1 kHz in cats and guinea pigs. Because cochlear amplification is skewed (more below the best frequency of a cochlear region), these data are consistent with an anti-masking role of MOC efferents that reduces masking by reducing the cochlear amplification seen at 1 kHz. C1 [Lilaonitkul, Watjana; Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Lilaonitkul, Watjana] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Guinan, John J., Jr.] MIT, Harvard Mit Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM John_Guinan@meei.harvard.edu FU National Institute of Deafness and Other Communication Disorders Grants [RO1 DC-005977, P30 DC-05029] FX This work was supported by National Institute of Deafness and Other Communication Disorders Grants RO1 DC-005977 and P30 DC-05029. NR 67 TC 44 Z9 45 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 2009 VL 101 IS 3 BP 1394 EP 1406 DI 10.1152/jn.90925.2008 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 412SW UT WOS:000263745500024 PM 19118109 ER PT J AU Tang, XN Liu, LP Yenari, MA AF Tang, Xian N. Liu, Liping Yenari, Midori A. TI Combination Therapy with Hypothermia for Treatment of Cerebral Ischemia SO JOURNAL OF NEUROTRAUMA LA English DT Article; Proceedings Paper CT 2nd International Brain Hypothermia Symposium CY OCT, 2007 CL Miami Beach, FL DE hypothermia; neuroprotection; stroke; tissue plasminogen activator ID TISSUE-PLASMINOGEN ACTIVATOR; TRANSIENT GLOBAL-ISCHEMIA; COMBINED POSTISCHEMIC HYPOTHERMIA; PERMANENT FOCAL ISCHEMIA; MILD HYPOTHERMIA; ARTERY OCCLUSION; ACUTE STROKE; INFARCT SIZE; MODERATE HYPOTHERMIA; FOREBRAIN ISCHEMIA AB Mild hypothermia is an established neuroprotectant in the laboratory, showing remarkable and consistent effects across multiple laboratories and models of brain injury. At the clinical level, mild hypothermia has shown benefits in patients who have suffered cardiac arrest and in some pediatric populations suffering hypoxic brain insults. However, a review of the literature has demonstrated that in order to appreciate the maximum benefits of hypothermia, brain cooling needs to begin soon after the insult, maintained for relatively long period periods of time, and, in the case of ischemic stroke, should be applied in conjunction with the re-establishment of cerebral perfusion. Translating this to the clinical arena can be challenging, especially rapid cooling and the re-establishment of perfusion. The addition of a second neuroprotectant could potentially (1) enhance overall protection, (2) prolong the temporal therapeutic window for hypothermia, or (3) provide protection where hypothermic treatment is only transient. Combination therapies resulting in recanalization following ischemic stroke would improve the likelihood of a good outcome, as the experimental literature suggests more consistent neuroprotection against ischemia with reperfusion, than ischemia without. Since recombinant tissue plasiminogen activator (rt-PA) is the only FDA approved treatment for acute ischemic stroke, and acts to recanalize occluded vessels, it is an obvious initial strategy to combine with hypothermia. However, the effects of thrombolytics are also temperature dependent, and the risk of hemorrhage is significant. The experimental data nevertheless seem to favor a combinatorial approach. Thus, in order to apply hypothermia to a broader range of patients, combination strategies should be further investigated. C1 [Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, Neurol VAMC 127, San Francisco, CA 94121 USA. [Tang, Xian N.; Yenari, Midori A.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Tang, Xian N.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. [Liu, Liping] Capital Univ Med Sci, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, Neurol VAMC 127, 4150 Clement St, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu FU NINDS NIH HHS [P01 NS014543-300002, P01 NS037520, P01 NS37520, R01 NS040516, P50 NS014543, R01 NS40516, P01 NS014543, R01 NS040516-02, P01 NS037520-060004, R01 NS040516-01A1] NR 61 TC 23 Z9 26 U1 0 U2 3 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 MAR PY 2009 VL 26 IS 3 BP 325 EP 331 DI 10.1089/neu.2008.0594 PG 7 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 420ZO UT WOS:000264327900005 PM 19216635 ER PT J AU Fagan, SP Fischman, AJ AF Fagan, Shawn P. Fischman, Alan J. TI Pancreatic Imaging with C-11-Dihydrotetrabenazine PET: A Perspective SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; BETA-CELL MASS; CONGENITAL HYPERINSULINISM; DOPAMINE TRANSPORTER; PARKINSONS-DISEASE; DIAGNOSIS; INFANCY; F-18-FLUORO-L-DOPA; TERMINALS C1 [Fagan, Shawn P.; Fischman, Alan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children, Boston, MA USA. RP Fischman, AJ (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM fischman@pet.mgh.harvard.edu NR 22 TC 3 Z9 3 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAR PY 2009 VL 50 IS 3 BP 335 EP 337 DI 10.2967/jnumed.108.059568 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 417OB UT WOS:000264084500008 PM 19223411 ER PT J AU Zhu, CW Leibman, C Townsend, R Mclaughlin, T Scarmeas, N Albert, M Brandt, J Blacker, D Sano, M Stern, Y AF Zhu, C. W. Leibman, C. Townsend, R. Mclaughlin, T. Scarmeas, N. Albert, M. Brandt, J. Blacker, D. Sano, M. Stern, Y. TI BRIDGING FROM CLINICAL ENDPOINTS TO ESTIMATES OF TREATMENT VALUE FOR EXTERNAL DECISION MAKERS SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article CT 1st Conference Clinical Trials on Alzheimers Disease (CTAD) CY SEP 17-19, 2008 CL Montpellier, FRANCE ID PATIENT DEPENDENCE; ALZHEIMERS-DISEASE AB Aim: While clinical endpoints provide important information on the efficacy of treatment in controlled conditions, they often are not relevant to decision makers trying to gauge the potential economic impact or value of new treatments. Therefore, it is often necessary to translate changes in cognition, function or behavior into changes in cost or other measures, which can be problematic if not conducted in a transparent manner. The Dependence Scale (DS), which measures the level of assistance a patient requires due to AD-related deficits, may provide a useful measure of the impact of AD progression in a way that is relevant to patients, providers and payers, by linking clinical endpoints to estimates of cost effectiveness or value. The aim of this analysis was to test the association of the DS to clinical endpoints and AD-related costs. Method: The relationship between DS score and other endpoints was explored using the Predictors Study, a large, multi-center cohort of patients with probable AD followed annually for four years. Enrollment required a modified Mini-Mental State Examination (mMMS) score >= 30, equivalent to a score of approximately >= 16 on the MMSE. DS summated scores (range: 0-15) were compared to measures of cognition (MMSE), function (Blessed Dementia Rating Scale, BDRS, 0-17), behavior, extrapyramidal symptoms (EPS), and psychotic symptoms (illusions, delusions or hallucinations). Also, estimates for total cost (sum of direct medical cost, direct non-medical cost, and cost of informal caregivers' time) were compared to DS scores. Results: For the 172 patients in the analysis, mean baseline scores were: DS: 5.2 (SD: 2.0), MMSE: 23.0 (SD: 3.5), BDRS: 2.9 (SD: 1.3), EPS: 10.8%, behavior: 28.9% psychotic symptoms: 21.1%. After 4 years, mean scores were: DS: 8.9 (SD: 2.9), MMSE: 17.2 (SD: 4.7), BDRS: 5.2 (SD: 1.4), EPS: 37.5%, behavior: 60.0%, psychotic symptoms: 46.7%. At baseline, DS scores were significantly correlated with MMSE (r=-0.299, p<0.01), BDRS (r=0.610, p<0.01), behavior (r=.2633, p=0.0005), EPS (r=0.1910, p=0.0137) and psychotic symptoms (r=0.253, p<0.01); and at 4-year follow-up, DS scores were significantly correlated with MMSE (r=-0.3705, p=0.017), BDRS (r=0.6982, p<0.001). Correlations between DS and behavior (-0.0085, p=0.96), EPS (r=0.3824, p=0.0794), psychotic symptoms (r=0.130, ns) were not statistically significant at follow-up. DS scores were also significantly correlated with total costs at baseline (r=0.2615, p=0.0003) and follow-up (r=0.3359, p=0.0318). Discussion: AD is associated with deficits in cognition, function and behavior, thus it is imperative that these constructs are assessed in trials of AD treatment. However, assessing multiple endpoints can lead to confusion for decision makers if treatments do not impact all endpoints similarly, especially if the measures are not used typically in practice. One potential method for translating these deficits into a more meaningful outcome would be to identify a separate construct, one that takes a broader view of the overall impact of the disease. Patient dependence, as measured by the DS, would appear to be a reasonable choice - it is associated with the three clinical endpoints, as well as measures of cost (medical and informal), thereby providing a bridge between measures of clinical efficacy and value in a single, transparent measure. C1 [Zhu, C. W.; Sano, M.] James J Peters VA Med Ctr, Bronx, NY USA. [Zhu, C. W.] Mt Sinai Sch Med, Brookdale Dept Geriatr, New York, NY USA. [Leibman, C.; Townsend, R.; Mclaughlin, T.] Elan Pharmaceut Inc, San Francisco, CA USA. [Scarmeas, N.; Stern, Y.] Columbia Univ, Gertrude H Sergievsky Ctr, Med Ctr, New York, NY 10027 USA. [Scarmeas, N.; Stern, Y.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY 10027 USA. [Albert, M.; Brandt, J.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Blacker, D.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sano, M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Zhu, CW (reprint author), James J Peters VA Med Ctr, Bronx, NY USA. OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [M01 RR000645, M01 RR000645-260594, RR00645]; NIA NIH HHS [R01 AG007370, U01 AG010483, U01AG010483, Z01 AG007370] NR 5 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER FRANCE PI PARIS PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE SN 1279-7707 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD MAR PY 2009 VL 13 IS 3 BP 256 EP 259 PG 4 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA 443WJ UT WOS:000265941200017 PM 19262963 ER PT J AU Jones, DW Robertson, LD Figoni, SF AF Jones, D. W. Robertson, L. D. Figoni, S. F. TI A Strength-Endurance Index for Power Grip SO JOURNAL OF OCCUPATIONAL REHABILITATION LA English DT Article DE Exercise; Isometric; Hand strength; Muscle strength; Muscle fatigue ID PINCH STRENGTH AB Introduction The purpose of this study was to quantify muscle strength and endurance in power grip. Method Workers (74 M and 74 F, 18-72 years) squeezed a dynamometer for a 60 s, 18-cycle test. Initial strength (IS) and final strength (FS) were calculated as the mean peak force for cycles 1-3 and 16-18, respectively. Endurance was defined by the strength decrement index (SDI) where SDI = (IS - FS)/IS x 100. A grip strength-endurance analyzer was constructed from IS and SDI data which were depicted on two parallel, linearly scaled axes. Discrete IS and SDI scores were connected on each axis with a vector. The vector (Vmag) was measured directly from the analyzer and its direction identified from its slope. Integer scales transformed discrete IS and SDI scores into individual strength-endurance performance scores (SEPS). Results Better than 95% of the sample (n a parts per thousand yen 141) scored within acceptable test ranges defined as the combined sample mean +/- A 2SD, for SDI, Vmag and SEPS. Vmag was the best predictor for SEPS. Linear regression for SEPS was SEPS (combined) = 0.09 (Vmag) - 0.29: (SEE = 0.829). The analyzer revealed individual scores outside acceptable ranges for injured and uninjured efforts. Conclusion The development of a power grip strength-endurance analyzer provided a simple method to graph individual power grip performances. Converting strength and endurance scores to integers and summing them (SEPS) provided a simple means to represent individual estimates of power grip strength-endurance performance. C1 [Jones, D. W.] Calif State Univ Long Beach, Dept Kinesiol, Long Beach, CA 90840 USA. [Robertson, L. D.] Human Kinet Publisher, Champaign, IL 61825 USA. [Figoni, S. F.] VA Greater Angles Healthcare Syst, Dept Phys Med Kinesiotherapy, Los Angeles, CA 90073 USA. RP Jones, DW (reprint author), Calif State Univ Long Beach, Dept Kinesiol, 1250 Bellflower Blvd, Long Beach, CA 90840 USA. EM djones9@csulb.edu; loarnr@HKUSA.com; sfigoni@gmail.com NR 14 TC 2 Z9 3 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1053-0487 J9 J OCCUP REHABIL JI J. Occup. Rehabil. PD MAR PY 2009 VL 19 IS 1 BP 56 EP 63 DI 10.1007/s10926-009-9163-6 PG 8 WC Rehabilitation; Social Issues SC Rehabilitation; Social Issues GA 409RY UT WOS:000263524700006 PM 19214717 ER PT J AU Mawardi, H Treister, N Richardson, P Anderson, K Munshi, N Faiella, RA Woo, SB AF Mawardi, Hani Treister, Nathaniel Richardson, Paul Anderson, Kenneth Munshi, Nikhil Faiella, Robert A. Woo, Sook-Bin TI Sinus Tracts-An Early Sign of Bisphosphonate-Associated Osteonecrosis of the Jaws? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MULTIPLE-MYELOMA; RISK-FACTORS; PAMIDRONATE; NECROSIS; METASTASES; PREVENTION; CANCER; BREAST AB Purpose: Bisphosphonate associated osteonecrosis of die jaw (BONJ) is defined as the presence of exposed bone for at least 8 weeks in patients with exposure to bisphosphonates and no history of radiotherapy to the jaw. We report 5 patients with a history of bisphosphonate use, sinus tracts or deep periodontal pockets and radiographic findings typical for BONJ but with no evidence of exposed necrotic bone at the first evaluation visit. Patients and Methods: The mean age was 70 years (range 66-77) and all were males. Patients had multiple myeloma (2), multiple myeloma and prostate cancer (4), monoclonal gammopathy of unknown significance (1) and osteoporosis (1). Three cases involved the mandible and 2 the maxilla. Four patients were on intravenous pamidronate and/or zoledonic acid and 1, alendronate. All cases except 1 (with deep periodontal pockets) presented with intraoral draining sinus tracts. Results: Radiographic findings included persistence of extraction socket (2), mottled radio-opacity and radiolucency (1), presence of sequestrum (1) and no significant findings (1). Subsequently, 4 patients developed exposed bone and I patient had necrotic bone removed from the jaws. Conclusion: We report 5 patients with a history of bisphosphonate therapy where 4 patients had persistent sinus tracts and,I fifth, severe bone loss. Four patients had radiographic findings typical for BONJ, and all subsequently developed necrotic bone. We propose modifying the definition of BONJ to include a category of "suspected BONJ" Stage 0(sa) where patients have persistent sinus tracts or localized deep periodontal pockets and typical radiographic findings for BONJ but are asymptomatic, and Stage 0(ss) for those who are symptomatic. (C) 2009 American Association of Oral and Maxillofacial Surgeons C1 [Mawardi, Hani; Treister, Nathaniel; Woo, Sook-Bin] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Woo, Sook-Bin] Harvard Univ, Sch Dent Med, Dept Oral Med & Oral Pathol, Boston, MA 02115 USA. [Mawardi, Hani; Treister, Nathaniel] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Richardson, Paul; Anderson, Kenneth; Munshi, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Richardson, Paul; Anderson, Kenneth; Munshi, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Myeloma Ctr, 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 30 TC 63 Z9 63 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 MAR PY 2009 VL 67 IS 3 BP 593 EP 601 DI 10.1016/j.joms.2008.09.031 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 415UN UT WOS:000263961200020 PM 19231786 ER PT J AU Chakraverty, JK Weaver, MJ Smith, RM Vrahas, MS AF Chakraverty, Julian K. Weaver, Michael J. Smith, R. Malcolm Vrahas, Mark S. TI Surgical Management of Tibial Tubercle Fractures in Association With Tibial Plateau Fractures Fixed by Direct Wiring to a Locking Plate SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE tibial tubercle; tibial plateau; fracture; surgical technique; less invasive stabilization system ID INTERNAL-FIXATION; COMBINATION AB Tibial tubercle fractures disrupting the extensor mechanism of the knee can occur in association with complex tibial plateau fractures (AO type 41A, 13, C). The management of these fractures can be difficult; a stable repair of the tibial tubercle fragment is essential if the extensor mechanism is to be reconstituted. There are few reported techniques described to manage tibial tubercle fractures in conjunction with complex proximal tibial injuries. Traditionally, tibial tubercle fractures have been repaired by lagging the tubercle fragment to the posterior cortex of the tibia using I or more screws. However, the cortex of the posterior tibia does not always offer good purchase for screw fixation, particularly in osteopenic bone. Additionally, in complex proximal tibial fractures, comminution often extends posteriorly, further complicating stable lag screw fixation. Placement of an anteroposterior lag screw can also be complicated by "screw traffic" if there are a large number of screws fixing the primary fracture. In this article, we report a novel surgical approach for the management of tibial tubercle fracture fragments occurring in association with complex proximal tibial fractures. Using this technique, the tibial tubercle fragment is stabilized by wiring it directly to the screws of a locking plate. It allows for reduction and fixation of the tibial tubercle fragment that is stable enough to allow immediate full active range of motion. Over the past 5 years, we have applied this technique in 16 patients. Our preliminary results using this new technique have demonstrated a high rate of clinical and radiographic union with near normal return of extensor mechanism function. C1 [Vrahas, Mark S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Chakraverty, Julian K.] N Bristol NHS Trust, Frenchay Hosp, Bristol, Avon, England. [Weaver, Michael J.] Massachusetts Gen Hosp, Harvard Combined Orthopaed Program, Boston, MA 02114 USA. [Smith, R. Malcolm] Massachusetts Gen Hosp Orthopaed, Boston, MA USA. RP Vrahas, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,YAW 3600-3C, Boston, MA 02114 USA. FU Synthes FX The authors did not receive grants or outside funding in support of their research or preparation of this article. One author (M.S.V) has received all unrestricted educational grant from Synthes in support of his fellowship program. NR 13 TC 4 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD MAR PY 2009 VL 23 IS 3 BP 221 EP 225 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 414IV UT WOS:000263858000012 PM 19516098 ER PT J AU Pousman, RM Pepper, C Pandharipande, P Ayers, GD Mills, B Diaz, J Collier, B Miller, R Jensen, G AF Pousman, Robert M. Pepper, Colleen Pandharipande, Pratik Ayers, Gregory D. Mills, Beth Diaz, Jose Collier, Brian Miller, Rick Jensen, Gordon TI Feasibility of Implementing a Reduced Fasting Protocol for Critically Ill Trauma Patients Undergoing Operative and Nonoperative Procedures SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article DE enteral nutrition; critically ill trauma patients; mechanical ventilation; complications; reduced fasting; procedures ID PARENTERAL-NUTRITION; PRACTICE GUIDELINES; ABDOMINAL-TRAUMA; SEPTIC MORBIDITY; CARE-UNIT; DELIVERY AB Background: This prospective, observational cohort study was designed to determine the feasibility of implementing a reduced enteral fasting protocol in mechanically ventilated trauma patients undergoing selected operative and nonoperative procedures. Methods: Critically ill, mechanically ventilated trauma patients undergoing selected operative and nonoperative procedures received enteral nutrition up until the time of the procedure, if receiving small bowel feeds, or received enteral nutrition that was discontinued 45 minutes before the procedure, if receiving gastric feeds. Results: Measures of delivery of nutrition Such as total enteral nutrition delivered and days required to reach nutrition goal were collected. Complications measured were death, incidence of ventilator-associated pneumonia, urinary tract infection, catheter-related bloodstream infection, wound infection, hypoglycemia, and emesis during procedures. No significant demographic differences were observed between the 2 groups. Patients in the intervention group showed trends toward greater total enteral nutrition delivered and faster attainment of target nutrition goals, although these measures were not statistically significant. Patients in the intervention group had rates of infective complications similar to those in the standard group. The median (interquartile range) for intensive care unit length of stay in the intervention group vs standard group was 7 (5, 15) vs 7 (5, 12) (P = 0.94), and the ventilator days were 8 (4.2, 14) vs 7 (3, 11) (P = 0.37). Conclusions: A reduced fasting protocol was feasible for selected operative procedures, with trends toward improving nutrition delivery and no increase in adverse outcomes. A larger randomized study of this approach is warranted before adoption of this practice can be advocated. (JPEN J Parenter Enteral Nutr. 2009;33:176-180) C1 [Pousman, Robert M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, W Los Angeles VA, Los Angeles, CA 90095 USA. [Pepper, Colleen; Pandharipande, Pratik] Vanderbilt Univ, Med Ctr, Dept Anesthesia Crit Care, Nashville, TN USA. [Diaz, Jose; Collier, Brian; Miller, Rick] Vanderbilt Univ, Med Ctr, Dept Surg, Div Trauma, Nashville, TN USA. [Ayers, Gregory D.; Miller, Rick] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA. [Mills, Beth] Vanderbilt Univ, Med Ctr, Ctr Human Nutr, Nashville, TN USA. [Jensen, Gordon] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. RP Pousman, RM (reprint author), 757 Iestwood Plaza,Suite 3325, Los Angeles, CA 90095 USA. EM frostitude@yahoo.com NR 18 TC 17 Z9 17 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD MAR-APR PY 2009 VL 33 IS 2 BP 176 EP 180 DI 10.1177/0148607108327527 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 410RL UT WOS:000263595700002 PM 19251911 ER PT J AU Teles, RP Sakellari, D Konstantinidis, A Socransky, SS Haffajee, AD AF Teles, Ricardo P. Sakellari, Dimitra Konstantinidis, Antonis Socransky, Sigmund S. Haffajee, Anne D. TI Application of the Checkerboard Immunoblotting Technique to the Quantification of Host Biomarkers in Gingival Crevicular Fluid SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Chemokines; cytokines; gingival crevicular fluid; matrix metalloproteinases; periodontal diseases ID MATRIX METALLOPROTEINASE-8 LEVELS; PERIODONTITIS PATIENTS; ANTIBODY-LEVELS; THERAPY; INTERLEUKIN-1-BETA; DISEASE; HEALTHY; PATHOGENESIS; MAINTENANCE; SMOKING AB Background: The aim of this study was to describe the development and validation of the checkerboard immunoblotting (CBIB) technique for the high-throughput quantification of multiple inflammatory mediators in gingival crevicular fluid (GCF) samples. Methods: Monoclonal antibodies were used to bind GCF interleukin (IL)-1 beta and -8 and matrix metalloproteinase(MMP)-8 to the surface of membranes. Biotinylated antibodies were used to detect bound antigens in a checkerboard format. Signals were developed using chemiluminescence, captured on film, and quantified using software for array analysis. The assay was tested for potential cross-reactions among the three pairs of antibodies. Eleven CBIBs were processed to determine the analytical sensitivity of the assay. Forty GCF samples were analyzed using CBIB and enzyme-linked immunosorbent assay (ELISA) in parallel, and the significance of the correlations among the results was tested using the Pearson correlation coefficient. Nine hundred thirty-one GCF samples were collected from 20 periodontally healthy subjects and 20 periodontitis subjects and analyzed using CBIB to test the assay's sensitivity and dynamic ranges using clinical samples. Results: The CBIB was capable of distinguishing among the three analytes. The sensitivity and dynamic ranges of the assay were suitable for the detection of the three targets in the majority of GCF samples. There were highly statistically significant (P<0.0001) positive correlations between CBIB and ELISA data for all three biomarkers. The periodontitis subjects had statistically significantly higher mean levels of IL-1 beta and -8 compared to healthy subjects. Conclusion: The CBIB technique is a sensitive and specific assay for the high-throughput quantification of MMP-8 and IL-8 and -1 beta in GCF. J Periodontol 2009;80.447456. C1 [Teles, Ricardo P.; Socransky, Sigmund S.; Haffajee, Anne D.] Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. [Sakellari, Dimitra; Konstantinidis, Antonis] Aristotle Univ Thessaloniki, Sch Dent, Dept Periodontol, GR-54006 Thessaloniki, Greece. RP Teles, RP (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM rteles@forsyth.org RI SAKELLARI, DIMITRA/F-3299-2011 FU National Institute of Dental and Craniofacial Research, Bethesda, Maryland [DE-016700, DE-012861, DE-014242] FX This work was supported, in part, by research grants DE-016700, DE-012861, and DE-014242 from the National Institute of Dental and Craniofacial Research, Bethesda, Maryland. The authors report no conflicts of interest related to this study. NR 31 TC 11 Z9 12 U1 0 U2 1 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAR PY 2009 VL 80 IS 3 BP 447 EP 456 DI 10.1902/jop.2009.080440 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 419YX UT WOS:000264256700012 PM 19254129 ER PT J AU Yew, JY Wang, Y Barteneva, N Dikler, S Kutz-Naber, KK Li, LJ Kravitz, EA AF Yew, Joanne Y. Wang, Yun Barteneva, Natasha Dikler, Sergel Kutz-Naber, Kimberly K. Li, Lingjun Kravitz, Edward A. TI Analysis of Neuropeptide Expression and Localization in Adult Drosophila melanogaster Central Nervous System by Affinity Cell-Capture Mass Spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Review DE neuropeptide; Drosophila; mass spectrometry; MALDI-TOF; biogenic amine; dopamine; serotonin ID FMRFAMIDE-RELATED PEPTIDES; HAWKMOTH MANDUCA-SEXTA; PERIOD CLOCK GENE; GENOMIC ORGANIZATION; MOLECULAR-CLONING; ALLATOSTATIN PREPROHORMONE; TOBACCO HAWKMOTH; MALPIGHIAN TUBULES; LOCUSTA-MIGRATORIA; SIGNALING PATHWAY AB A combined approach using mass spectrometry, a novel neuron affinity capture technique, and Drosophila melanogaster genetic manipulation has been developed to characterize the expression and localization of neuropeptides in the adult D. melanogaster brain. In extract from the whole adult brain, 42 neuropeptides from 18 peptide families were sequenced. Neuropeptide profiling also was performed on targeted populations of cells which were enriched with immunoaffinity purification using a genetically expressed marker. C1 [Yew, Joanne Y.; Kravitz, Edward A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Wang, Yun; Kutz-Naber, Kimberly K.; Li, Lingjun] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. [Barteneva, Natasha] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Dikler, Sergel] Bruker Daltonics Inc, Billerica, MA 01821 USA. RP Yew, JY (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. EM joanne_yew@hms.harvard.edu RI Yew, Joanne/D-6562-2014 FU National Institute of Mental Health National Research Service Award; National Institute of Diabetes and Digestive and Kidney Diseases [DK071801]; National Institute of General Medical Sciences [GM074675, GM067645] FX This work was supported by a National Institute of Mental Health National Research Service Award grant (J.Y.Y.) and research grants from the National Institute of Diabetes and Digestive and Kidney Diseases DK071801 (L.L.), and the National Institute of General Medical Sciences GM074675 and GM067645 (E.A.K.). We wish to acknowledge members of the Kravitz laboratory (Olga Alekseyenko, Sarah Certel, Yick-Bun Chan, Jill Penn, Maria de la Paz Fernandez) for helpful discussions and, in particular, Adelaine Leung for acquiring some of the confocal microscopy images. We would also like to thank Rochelle Witt and Jessica Saulinier for excellent technical advice. Finally, we are grateful to Dr. Klaus Dreisewerd for critical reading of the manuscript, Dr. David Corey for use of the confocal microscope, and Drs. Alois Haufbauer, Randy Hewes, Jay Hirsh, Paul Taghert, and Ping Shen for generous gifts of reagents. NR 105 TC 34 Z9 34 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAR PY 2009 VL 8 IS 3 BP 1271 EP 1284 DI 10.1021/pr800601x PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 416WA UT WOS:000264035000017 PM 19199706 ER PT J AU Cho, JY Lee, M Ahn, JM Park, ES Cho, JH Lee, SJ Kim, BG Heo, SH Park, HJ Zerbini, LF Hwang, D Libermann, TA AF Cho, Je-Yoel Lee, Minjung Ahn, Jung-Mo Park, Eun-Sung Cho, Ji-Hoon Lee, Seung-Jin Kim, Byung-Gyu Heo, Sun-Hee Park, Hye-Jeong Zerbini, Luiz F. Hwang, Daehee Libermann, Towia A. TI Proteomic Analysis of a PDEF Ets Transcription Factor-interacting Protein Complex SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE Breast cancer; Prostate derived ETS transcription factor; LC-MS/MS ID PROSTATE-CANCER; BREAST-CANCER; GENE-EXPRESSION; CELLS; RECEPTOR; ANTIGEN; KINASE; TUMORS; OVEREXPRESSION; IDENTIFICATION AB Ets proteins are a family of transcription factors that share an 85 amino acid conserved DNA binding domain, the ETS domain. The 27 known human Ets transcription factors control multiple biological processes, including cellular proliferation, differentiation, apoptosis, angiogenesis, transformation, and invasion. Overexpression of some Ets genes has been linked to numerous malignancies, including breast cancers. The prostate derived Ets transcription factor (PDEF) is reported to be a breast and prostate tumor-associated Ets factor. To understand the roles of PDEF in breast cancers, we transiently overexpressed PDEF in MDA-MB-231 human breast cancer cells by adenoviral-mediated gene delivery. PDEF binding protein complexes were isolated by immunoprecipitation and PDEF-interacting proteins were analyzed by LC-MS/MS. After subtracting the proteins binding nonspecifically to antibody-bead complexes, we identified 286 proteins in the PDEF-associated protein complex. By comparison to published protein-protein interactions, we selected 121 proteins for further analysis. PDEF interactors distribute not only in the nucleus, but also in the cytoplasm, as well as other subcellular compartments. Our data reveals that PDEF interacts with a variety of proteins involved in cell cycle, DNA repair, cytoskeleton organization, mRNA processing, tRNA biosynthesis, protein folding, and cell signaling. Furthermore, the EGFR1- (Erbb1) and Erbb2- (HER2) related proteins erbin, an ERBB2 interacting protein, catenin delta-1 (which interacts with Erbin), and EGFR (a HER2-homology receptor) were associated with PDEF. These findings indicate that PDEF may be regulated by Erbb2 or EGFR-activated signaling pathways in breast cancer cells. Further analysis of these proteins will identify the roles of PDEF-interacting proteins in breast tumorigenesis. C1 [Cho, Je-Yoel; Lee, Minjung; Ahn, Jung-Mo; Park, Eun-Sung; Cho, Ji-Hoon; Lee, Seung-Jin; Kim, Byung-Gyu; Heo, Sun-Hee; Park, Hye-Jeong; Hwang, Daehee] Kyungpook Natl Univ, Sch Dent, Dept Biochem, Taegu 700422, South Korea. [Cho, Je-Yoel; Lee, Minjung; Ahn, Jung-Mo; Park, Eun-Sung; Cho, Ji-Hoon; Lee, Seung-Jin; Kim, Byung-Gyu; Heo, Sun-Hee; Park, Hye-Jeong; Hwang, Daehee] Pohang Univ Sci & Technol, Sch Interdisciplinary Biosci & Bioengn, Pohang 790784, Kyungpook, South Korea. [Zerbini, Luiz F.; Libermann, Towia A.] Harvard Univ, Sch Med, BIDMC Genom Ctr, Boston, MA 02115 USA. ProtAn, Taegu 700422, South Korea. RP Cho, JY (reprint author), Kyungpook Natl Univ, Sch Dent, Dept Biochem, 101 Dong In Dong, Taegu 700422, South Korea. EM jeycho@knu.ac.kr RI Libermann, Towia/F-9866-2010; Zerbini, Luiz /B-7720-2015; OI Libermann, Towia/0000-0002-4006-8179 FU Korea Science and Engineering Foundation (KOSEF) [M10649000184-08N4900-18410]; 21C Frontier Functional Proteomics Project [FPR08A2-120]; Korean government (MEST) [M1AN 29-2007-03990] FX This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant (M10649000184-08N4900-18410), a grant from the 21C Frontier Functional Proteomics Project (FPR08A2-120), and, partially, by a KOSEF Grant (M1AN 29-2007-03990) from the Korean government (MEST). NR 36 TC 12 Z9 12 U1 2 U2 4 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 MAR PY 2009 VL 8 IS 3 BP 1327 EP 1337 DI 10.1021/pr800683b PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 416WA UT WOS:000264035000022 PM 19203193 ER PT J AU Paukert, AL Phillips, L Cully, JA LoboPrabhu, SM Lomax, JW Stanley, MA AF Paukert, Amber L. Phillips, Laura Cully, Jeffrey A. LoboPrabhu, Sheila M. Lomax, James W. Stanley, Melinda A. TI Integration of Religion into Cognitive-Behavioral Therapy for Geriatric Anxiety and Depression SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE depression; anxiety; older patients; elderly; religion; spirituality; evidence-based treatment ID ILL OLDER PATIENTS; MENTAL-HEALTH; ELDERLY PERSONS; LATE-LIFE; PSYCHOTHERAPY; ADULTS; SPIRITUALITY; DISORDERS; INTERVENTIONS; OUTCOMES AB Religion is important to most older adults, and research generally finds a positive relationship between religion and mental health. Among psychotherapies used in the treatment of anxiety and depression in older adults, cognitive-behavioral therapy (CBT) has the strongest evidence base. Incorporation of religion into CBT may increase its acceptability and effectiveness in this population. This article reviews studies that have examined the effects of integrating religion into CBT for depression and anxiety. These studies indicate that improvement in depressive and anxiety symptoms occurs earlier in treatment when CBT incorporates religion, although effects are equivalent at follow-up. The authors present recommendations for integrating religious beliefs and behaviors into CBT based on empirical literature concerning which aspects of religion affect mental health. A case example is also included that describes the integration of religion into CBT for an older man with cognitive impairment experiencing comorbid generalized anxiety disorder and major depressive disorder. It is recommended that clinicians consider the integration of religion into psychotherapy for older adults with depression or anxiety and that studies be conducted to examine the added benefit of incorporating religion into CBT for the treatment of depression and anxiety in older adults. (Journal of Psychiatric Practice 2009;15:103-112) C1 [Paukert, Amber L.] Vet Affairs Med Ctr, Seattle, WA 98108 USA. [Cully, Jeffrey A.; LoboPrabhu, Sheila M.; Stanley, Melinda A.] Vet Affairs S Cent Mental Illness Res Educ & Clin, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Phillips, Laura; Cully, Jeffrey A.; LoboPrabhu, Sheila M.; Lomax, James W.; Stanley, Melinda A.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Paukert, AL (reprint author), Puget Sound Vet Affairs Med Ctr, 1660 S Columbian Way,Mail Stop,S-111-HBPC, Seattle, WA 98108 USA. EM Amber.Paukert@va.gov FU Houston VA HSR&D Center of Excellence [HFP90-020]; South Central Mental Illness Research Education and Clinical Center (MIRECC) FX This work was supported in part by the Houston VA HSR&D Center of Excellence (Houston Center for Quality of Care & Utilization Studies), HFP90-020, and a pilot grant to the last author from the South Central Mental Illness Research Education and Clinical Center (MIRECC). NR 80 TC 20 Z9 21 U1 2 U2 34 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-4160 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD MAR PY 2009 VL 15 IS 2 BP 103 EP 112 PG 10 WC Psychiatry SC Psychiatry GA 426PZ UT WOS:000264721500004 PM 19339844 ER PT J AU Bankier, B Barajas, J Martinez-Rumayor, A Januzzi, JL AF Bankier, Bettina Barajas, Justine Martinez-Rumayor, Abelardo Januzzi, James L. TI Association between major depressive disorder and C-reactive protein levels in stable coronary heart disease patients SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Cardiac biomarkers; Major depressive disorder; Stable coronary heart disease ID MYOCARDIAL-INFARCTION; STATIN THERAPY; INFLAMMATION; SYMPTOMS; RISK; MORTALITY; EVENTS; WOMEN AB Objective: This study aimed for a comprehensive evaluation of major depressive disorder (MDD) in stable coronary heart disease (CHD) patients, excluding all other potential psychiatric comorbidities, and including associations with cardiac biomarkers such as C-reactive protein (CRP), troponin T (TnT), and amino-terminal pro-B-type brain natriuretic peptide (NT-proBNP). Methods: Cross-sectional study of a consecutive series of 72 stable CHD outpatients (n=30 with MDD, n=42 with no psychiatric disorder). Psychiatric diagnoses were established by using the Structured Clinical Interview for DSM-IV (SCID), and psychiatric assessment was performed on Axis I, Axis III, Axis TV, and Axis V. Regression analyses were performed including CRP, TnT, and NT-proBNP as dependent variables, and MDD, demographics, and comorbid medical conditions as independent variables. Results: Stepwise multiple regression analyses showed a significant association between MDD and CRP (beta=0.262, P=.02), excluding all other demographic and medical variables from the models, except age (beta-0.266, P=.02). In addition, the results described a significant relationship between type 11 diabetes mellitus and TnT (beta=0.267, P=.02), and age and NT-proBNP levels (beta=0.374, P=.001). Conclusion: Major depressive disorder was associated with elevated CRP levels in a consecutive series of stable CHD patients. (c) 2009 Elsevier Inc. All rights, reserved. C1 [Bankier, Bettina] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bankier, Bettina; Barajas, Justine; Martinez-Rumayor, Abelardo; Januzzi, James L.] Harvard Univ, Sch Med, Boston, MA USA. [Barajas, Justine; Martinez-Rumayor, Abelardo; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Bankier, B (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM bettina.bankier@meduniwien.ac.at FU NARSAD Young Investigator Award 2005; Mental Health Research Association, Great Neck, New York [760-2339-5, 218960] FX This work was fully supported by a NARSAD Young Investigator Award 2005, Mental Health Research Association, Great Neck, New York (NARSAD Fund No. 760-2339-5. Grant 218960 to BB). NR 22 TC 17 Z9 17 U1 0 U2 1 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 MAR PY 2009 VL 66 IS 3 BP 189 EP 194 DI 10.1016/j.jpsychores.2008.09.010 PG 6 WC Psychiatry SC Psychiatry GA 413PT UT WOS:000263805700001 PM 19232230 ER PT J AU Meisenhelder, JB Marcum, JP AF Meisenhelder, Janice Bell Marcum, John P. TI Terrorism, Post-traumatic Stress, Coping Strategies, and Spiritual Outcomes SO JOURNAL OF RELIGION & HEALTH LA English DT Article DE Post-traumatic Stress; Terrorism; Coping; Spirituality; Outcomes ID LIFE EVENTS; SURVIVORS; DISORDER; SEPTEMBER-11; SYMPTOMS; GROWTH; PTSD; INTRUSION; VETERANS; VALIDITY AB This mail survey measured post-traumatic stress symptoms, spiritual and non-spiritual coping strategies, and positive spiritual outcomes following the tragedies of 9/11/01 in a national, random sample of 1,056 Presbyterians. Respondents reported mild to moderate degrees of re-experiencing and hyper-arousal symptoms of post-traumatic stress, unrelated to location or knowing someone involved. People experiencing high stress used greater frequency and variety of both spiritual and non-spiritual types of coping strategies. Positive spiritual outcomes were remarkably related to positive spiritual coping strategies, in contrast to no association with negative coping. This study illustrates the significant degree of post-traumatic stress experienced with vicarious exposure and a wide spectrum of coping strategies used following the major terrorist attacks. C1 [Meisenhelder, Janice Bell] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02129 USA. [Marcum, John P.] Presbyterian Church USA, Louisville, KY 40202 USA. RP Meisenhelder, JB (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, 36 1st Ave, Boston, MA 02129 USA. EM jmeisenhelder@mghihp.edu NR 43 TC 2 Z9 3 U1 1 U2 2 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 MAR PY 2009 VL 48 IS 1 BP 46 EP 57 DI 10.1007/s10943-008-9192-z PG 12 WC Public, Environmental & Occupational Health; Religion SC Public, Environmental & Occupational Health; Religion GA 409ZE UT WOS:000263543500007 PM 19229625 ER PT J AU Lee, L Garrett, L Lee, H Oliva, E Horowitz, N Duska, LR AF Lee, Lisa Garrett, Leslie Lee, Hang Oliva, Esther Horowitz, Neil Duska, Linda R. TI Association of Clear Cell Carcinoma of the Endometrium with a High Rate of Venous Thromboembolism SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE clear cell carcinoma; endometrial cancer; venous thromboembolism ID MOLECULAR-WEIGHT HEPARIN; BLEEDING COMPLICATIONS; ADVANCED MALIGNANCY; CANCER; SURVIVAL; THERAPY; DISEASE; OVARIAN; CHEMOTHERAPY; PREVENTION AB OBJECTIVE: To document the rate clinically significant venous thromboembolism (VTE) in patients with clear cell carcinoma tithe endometrium (CCC-E). STUDY DESIGN: Institutional review board permission was obtained to identify all cases of CCC-E between 1994 and 2004. Controls with high grade endometrial cancers were matched for stage, age and date if diagnosis. RESULTS: Complete data were available for 29. Age ranged from 38 to 85 (mean, 64.6) years. Thirty-five percent of the patients had stage 1 tumors, 10% stage II, 27.5% stage III and 27.5% stage IV tumors. Fifty-eight matched controls were selected. Overall there were 18 VTE events: 10 (34.5%) in patients with CCC-E and 8 (13.8%) in the controls (OR = 3.68, p = 0.032). More VTE occurred in patients With stage III/IV disease (n = 16) than those with early stage (n = 2). VTE in patients with CCC-E occurred at presentation or with disease recurrence rather than in the postoperative period (8 vs. 1). Among patients with CCC-E, VTE had an adverse effect on survival, with a hazard ratio of 3.65 (95% CI, 3.14-4.16; p = 0.011). CONCLUSION: Patients with CCC-E have greater risk of VTE than patients with other high-risk endometrial cancers. Consideration should be given to extended pro-STUDY DESIGN: Institutional review board permission was obtained to identify phylaxis in patients with CCC-E to prevent VTE. (J Reprod Med 2009;54:133-138) C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Duska, LR (reprint author), Univ Virginia, Div Gynecol Oncol, POB 800712, Charlottesville, VA 22908 USA. EM lduska@virginia.edu NR 22 TC 13 Z9 13 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 EI 1943-3565 J9 J REPROD MED JI J. Reprod. Med. PD MAR PY 2009 VL 54 IS 3 BP 133 EP 138 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 420LC UT WOS:000264290300004 PM 19370896 ER PT J AU Yang, CC Jiang, XG AF Yang, Claire C. Jiang, Xiaogang TI Clinical Autonomic Neurophysiology and the Male Sexual Response: An Overview SO JOURNAL OF SEXUAL MEDICINE LA English DT Article CT 16th Annual Meeting of the American-Urological-Association-Foundation/Summer Research Conference on Sexual Medicine CY AUG 07-09, 2008 CL Baltimore, MD SP Amer Urol Assoc Fdn, Natl Inst Diabetes & Digestive & Kidney Dis DE Autonomic Nervous System; Clinical Neurophysiology; Male Sexual Response; Electrodiagnostic Testing; Evoked Cavernous Activity; Corpus Cavernosum Electromyography ID CORPUS CAVERNOSUM ELECTROMYOGRAPHY; SYMPATHETIC SKIN-RESPONSE; SINGLE POTENTIAL ANALYSIS; ERECTILE DYSFUNCTION; ELECTRICAL-ACTIVITY; HEALTHY-VOLUNTEERS; INNERVATION; PENIS; METHODOLOGY; DISORDERS AB Introduction. Clinical neurophysiology is the study of the human nervous system through the recording of bioelectrical activity. In the realm of male sexual functioning, this includes using electrophysiologic techniques to study the nerves subserving erection, emission, ejaculation, and orgasm. Aim. To introduce the reader to the principles of clinical neurophysiology as they relate to the male sexual response, particularly erection. Methods. We review the pertinent autonomic neuroanatomy and neurophysiology of reflexes relevant to the male sexual response, as well as summarize the genital electrodiagnostic tests that are being used to interrogate the autonomic innervation pertinent to male sexual functioning. Conclusions. The male sexual response is a coordinated series of interactions between the somatic and the autonomic nervous systems. Measurement of the autonomically mediated portions of the sexual reflexes is of great clinical interest, particularly in relation to erection. Advances in clinical electrodiagnostics now allow for consistent recording of evoked and spontaneous intrapenile electrical activity. However, before broad and widespread use of these techniques is possible, more investigations are needed. Yang CC, and Jiang X. Clinical autonomic neurophysiology and the male sexual response: An overview. J Sex Med 2009;6(suppl 3):221-228. C1 [Yang, Claire C.] VA Puget Sound Hlth Care Syst, Dept Urol, Seattle, WA 98109 USA. [Jiang, Xiaogang] Univ Washington, Dept Urol, Seattle, WA 98195 USA. RP Yang, CC (reprint author), VA Puget Sound Hlth Care Syst, Dept Urol, Seattle, WA 98109 USA. EM cyang@u.washington.edu FU NIDDK NIH HHS [R21 DK069315, R21 DK069315-02] NR 31 TC 10 Z9 10 U1 2 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD MAR PY 2009 VL 6 BP 221 EP 228 DI 10.1111/j.1743-6109.2008.01180.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 452OZ UT WOS:000266552200004 PM 19267845 ER PT J AU LoCastro, JS Youngblood, M Cisler, RA Mattson, ME Zweben, A Anton, RF Donovan, DM AF LoCastro, Joseph S. Youngblood, Marston Cisler, Ron A. Mattson, Margaret E. Zweben, Allen Anton, Raymond F. Donovan, Dennis M. TI Alcohol Treatment Effects on Secondary Nondrinking Outcomes and Quality of Life: The COMBINE Study SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; COMPULSIVE DRINKING SCALE; DEPENDENT SUBJECTS; COMBINED PHARMACOTHERAPIES; BEHAVIORAL INTERVENTIONS; HEAVY DRINKING; HEALTH; INDIVIDUALS; CONSUMPTION; IMPROVEMENT AB Objective: To evaluate the full range of alcohol treatment effectiveness, it is important to assess secondary nondrinking outcome dimensions in addition to primary alcohol consumption outcomes. Method: We used a large sample (n = 1,226) of alcohol-dependent participants entering the National Institute on Alcohol Abuse and Alcohol ism-sponsored COMBINE (Combining Medications and Behavioral Interventions) Study, a multisite clinical trial of pharmacological (naltrexone [ReVia] and acamprosate [Campral]) and behavioral interventions, to examine the effects of specific treatment combinations on nondrinking functional outcomes. We assessed the outcomes at baseline and at the end of 16 weeks of alcohol treatment and again at the 26-week and/or 52-week postrandomization follow-ups. Results: (1) Drinking and secondary outcomes were significantly related, especially at the follow-up periods. A higher percentage of heavy drinking days, more drinks per drinking day, and lower percentage of days abstinent were associated with lower quality-of-life measures. (2) All nondrinking outcomes showed improvement at the end of 16 weeks of treatment and most maintained improvement over the 26-week and 52-week follow-ups. Only two measures returned to pretreatment levels at 52 weeks: percentage of days paid for work and physical health. Improvements of nondrinking outcomes remained even after adjusting for post-treatment heavy drinking status. (3) Although nondrinking outcomes showed overall improvement, specific pharmacological and behavioral treatment combinations were not differentially effective on specific secondary outcomes. Conclusions: In the current study, changes that resulted from treatment were multidimensional, and improvements in nondrinking outcomes reflected the overall significant improvement in drinking but they were not differentiated between treatment combination groups. Findings from this study support the importance of including secondary nondrinking outcomes in clinical alcohol-treatment trials. (J. Stud. Alcohol Drugs 70: 186-196, 2009) C1 [LoCastro, Joseph S.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP LoCastro, JS (reprint author), VA Boston Healthcare Syst, Psychol Serv, 116B,150 S Huntington Ave, Boston, MA 02130 USA. EM joseph.locastro@va.gov FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [UIOAA 11715, 11716, 11721, 11727, 11756, 11768, 11773, 11776, 11777, 11783, 11787, 11799, K05AA014715, K05AA00133, K02DA00326, K23AA00329]; NIAAA FX This research was supported by National Institute on Alcohol Abuse and Alcoholism (NIAAA) cooperative agreements UIOAA 11715, 11716, 11721, 11727, 11756, 11768, 11773, 11776, 11777, 11783, 11787, 11799, and 11773 and by career scientist awards K05AA014715, K05AA00133, K02DA00326, and K23AA00329. The reported data were collected as part of the multisite COMBINE Study sponsored by NIAAA. Further information about study site and other publications from the COMBINE Study can be found at: www.cscc.unc.edu/COMBINE. NR 49 TC 23 Z9 23 U1 3 U2 9 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAR PY 2009 VL 70 IS 2 BP 186 EP 196 PG 11 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 416SS UT WOS:000264026400004 PM 19261230 ER PT J AU Kinder, LS Bryson, CL Sun, H Williams, EC Bradley, KA AF Kinder, Leslie S. Bryson, Chris L. Sun, Haili Williams, Emily C. Bradley, Katharine A. TI Alcohol Screening Scores and All-Cause Mortality in Male Veterans Affairs Patients SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID PRIMARY-CARE PATIENTS; MENTAL-HEALTH; CONSUMPTION QUESTIONS; FOLLOW-UP; AUDIT-C; POPULATION; INTERVENTION; ASSOCIATION; VALIDATION; DISORDERS AB Objective: Extensive research demonstrates a J- or U-shaped association between in-depth interview measures of alcohol consumption and mortality. Little is known about the relationship between alcohol screening questionnaires and mortality. This study examined the association between scores (ranging from 0 to 12) on the three-item Alcohol Use Disorder Identification Test-Consumption Questionnaire (AUDIT-C) and mortality. Method: This cohort study included male outpatients from seven Veterans Affairs (VA) medical centers who completed the AUDIT-C on mailed surveys (1997-2000; n = 34,292) and who were followed for a mean of 2.5 years. Death was ascertained from VA databases. Results: In analyses adjusted for demographics, a U-shaped relationship was observed between AUDIT-C scores and all-cause mortality. Nondrinkers (AUDIT-C 0) and heavy drinkers (AUDIT-C 8-9 and 10-12) had increased risk of death compared with drinkers who screened negative for alcohol misuse (AUDIT-C 1-3): hazard ratios (HR) = 1.41 (95% confidence interval [Cl]: 1.29-1.54), 1.32 (1.03-1.69), and 1.47 (1.14-1.91), respectively. This association differed across age groups (p = .003). For men younger than 50 years, AUDIT-C scores 10-12 were associated with increased mortality (HR = 2.21, 95% Cl: 1.29-3.77), whereas for men age 50 or older, self-reported abstinence (AUDIT-C 0) was associated with increased mortality; compared with drinkers with AUDIT-C scores 1-3: HR for men 50-64 = 1.45 (1.19-1.77); HR for men 65 or older = 1.42 (1.28-1.58). Conclusions: A U-shaped association between the AUDIT-C and mortality was observed, with important differences by age group. This is the first study to demonstrate that a clinical scaled screening measure of alcohol use has a similar association with mortality to that observed in epidemiological research with lengthier measures. (J. Stud. Alcohol Drugs 70: 253-260, 2009) C1 [Kinder, Leslie S.; Bryson, Chris L.; Sun, Haili; Williams, Emily C.; Bradley, Katharine A.] NW Ctr Excellence Hlth Serv Res & Dev, Dept Vet Affairs, Seattle, WA 98101 USA. [Bryson, Chris L.] Primary & Specialty Med Care Serv, Dept Vet Affairs, VA Puget Sound, Seattle, WA USA. [Bryson, Chris L.; Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. [Williams, Emily C.] Ctr Excellence Substance Abuse Treatment & Educ, Dept Vet Affairs, VA Puget Sound, Seattle, WA USA. [Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Bryson, CL (reprint author), NW Ctr Excellence Hlth Serv Res & Dev, Dept Vet Affairs, 1100 Ol Way,Suite 1400, Seattle, WA 98101 USA. EM christopher.bryson@va.gov FU VA Health Services Research and Development (HSRD) [SDR96-002, HR99-376]; VA Investigator Initiated Research grant [IAC 05-206-1]; VA HSRD Fellowship; VA Career Development Award [RCD03-177] FX This research was supported by the Department of Veterans Affairs (VA) Ambulatory (Care Quality Improvement Project (ACQUIP), funded by VA Health Services Research and Development (HSR&D) grants SDR96-002 and HR99-376; VA Investigator Initiated Research grant IAC 05-206-1 awarded to Katharine A. Bradley, principal investigator; VA HSR&D Fellowship awarded to Leslie S. Kinder; and VA Career Development Award RCD03-177 awarded to Chris L. Bryson. The views expressed here are those of the authors and do not necessarily reflect the position or policy of the VA or the University of Washington. NR 39 TC 28 Z9 29 U1 1 U2 1 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAR PY 2009 VL 70 IS 2 BP 253 EP 260 PG 8 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 416SS UT WOS:000264026400011 PM 19261237 ER PT J AU Jayaraman, A Maguire, T Vemula, M Kwon, DW Vannucci, M Berthiaume, F Yarmush, ML AF Jayaraman, Arul Maguire, Tim Vemula, Murali Kwon, Deukwoo W. Vannucci, Marina Berthiaume, Francois Yarmush, Martin L. TI Gene Expression Profiling of Long-Term Changes in Rat Liver Following Burn Injury SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE liver gene expression; 20% burn injury; microarrays; energy expenditure ID LOW-MOLECULAR-WEIGHT; NF-KAPPA-B; SKELETAL-MUSCLE; THERMAL-INJURY; INFLAMMATORY CHANGES; LIPID-PEROXIDATION; PROTEIN; TISSUE; CELLS; INTERLEUKIN-6 AB The inflammatory response initiated upon burn injury is also associated with extensive metabolic adjustments. While there is a significant body of literature on the characterization of these changes at the metabolite level, little is known on the mechanisms of induction, especially with respect to the role of gene expression. We have comprehensively analyzed changes in gene expression in rat livers during the first 7 d after 20% total body surface area burn injury using Affymetrix microarrays. A total of 740 genes were significantly altered in expression at 1, 2, 4, and 7 d after burn injury compared to sham-burn controls. Functional classification based on gene ontology terms indicated that metabolism, transport, signaling, and defense/inflammation response accounted for more than 70% of the significantly altered genes. Fisher least-significant difference post-hoc testing of the 740 differentially expressed genes indicated that over 60% of the genes demonstrated significant changes in expression either on d I or on d 7 postburn. The gene expression trends were corroborated by biochemical measurements of triglycerides and fatty acids 24 h postburn but not at later time points. This suggests that fatty acids are used, at least in part, in the liver as energy substrates for the first 4 d after injury. Our data also suggest that long-term regulation of energy substrate utilization in the liver following burn injury is primarily at the posttranscriptional level. Last, relevance networks of significantly expressed genes indicate the involvement of key small molecules in the hepatic response to 20% total body surface area burn injury. (c) 2009 Elsevier Inc. All rights reserved. C1 [Kwon, Deukwoo W.; Vannucci, Marina] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Maguire, Tim] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. [Jayaraman, Arul; Vemula, Murali; Berthiaume, Francois; Yarmush, Martin L.] Shriners Hosp Children, Dept Surg, Boston, MA USA. [Jayaraman, Arul; Vemula, Murali; Berthiaume, Francois; Yarmush, Martin L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jayaraman, A (reprint author), Texas A&M Univ, Artie McFerrin Dept Chem Engn, College Stn, TX 77843 USA. EM arulj@tamu.edu FU Shriners Hospitals for Children [SHC 8560] FX This work was supported by a grant from the Shriners Hospitals for Children (SHC 8560). The use of facilities at the Special Shared Facility for Functional Genomics and Proteomics is acknowledged. NR 50 TC 4 Z9 4 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAR PY 2009 VL 152 IS 1 BP 3 EP 17 DI 10.1016/j.jss.2007.05.025 PG 15 WC Surgery SC Surgery GA 405SY UT WOS:000263245700002 PM 18755477 ER PT J AU Berthiaume, F Barbe, L Mokuno, Y MacDonald, AD Jindal, R Yarmush, ML AF Berthiaume, Francois Barbe, Laurent Mokuno, Yasuji MacDonald, Annette D. Jindal, Rohit Yarmush, Martin L. TI Steatosis Reversibly Increases Hepatocyte Sensitivity to Hypoxia-Reoxygenation Injury SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE steatosis; liver transplantation; choline and methionine-deficient diet; intracellular triglyceride; defatting ID ISCHEMIA-REPERFUSION INJURY; RAT FATTY LIVER; HEPATIC ISCHEMIA/REPERFUSION INJURY; ENDOTHELIAL-CELLS; COLD PRESERVATION; WARM ISCHEMIA; NITRIC-OXIDE; ZUCKER RAT; TRANSPLANTATION; MODEL AB Background. Steatosis decreases survival of liver grafts after transplantation due to poorly understood mechanisms. We examined the effect of steatosis on the survival of liver grafts in a rat liver transplantation model and the viability of cultured rat hepatocytes after hypoxia and reoxygenation. Materials and methods. Rats were fed a choline and methionine-deficient diet to induce hepatic steatosis, and the livers were transplanted into recipient rats after 6 h of cold storage. Cultured hepatocytes were made steatotic by incubation for 3 d in fatty acid-supplemented medium. Hypoxia and reoxygenation were induced by placing the cultures in a 90% N2/10% CO(2) atmosphere for 4 h, followed by return to normoxic conditions for 6 h. Hepatocyte viability was assessed by lactate dehydrogenase release and mitochondrial potential staining. Results. Transplanted steatotic livers exhibited 0% viability compared with 90% for lean liver controls. When donor choline and methionine-deficient diet rats were returned to a normal diet, hepatic fat content decreased while viability of the grafts after transplantation increased. Cultured steatotic hepatocytes generated more mitochondrial superoxide, exhibited a lowered mitochondrial membrane potential, and released significantly more lactate dehydrogenase after hypoxia and reoxygenation than lean hepatocyte controls. When steatotic hepatocytes were defatted by incubating in fatty acid-free medium, they became less sensitive to hypoxia and reoxygenation as the remaining intracellular triglyceride content decreased. Conclusions. Hepatic steatosis reversibly decreases viability of hepatocytes after hypoxia and reoxygenation in vitro. The decreased viability of steatotic livers after transplantation may be due to a direct effect of hypoxia and reoxygenation on hepatocytes, and can be reversed by defatting. (c) 2009 Elsevier Inc. All rights reserved. C1 [Berthiaume, Francois] Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA USA. RP Berthiaume, F (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM fberthiaume@hms.harvard.edu OI Barbe, Laurent/0000-0003-4475-6478 FU National Institutes of Health [R01DK059766, R01DK043371, P41EB002503]; Shriners Hospitals for Children FX The authors acknowledge partial supported for this work by the National Institutes of Health grants R01DK059766, R01DK043371, P41EB002503, and the Shriners Hospitals for Children. NR 35 TC 21 Z9 21 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAR PY 2009 VL 152 IS 1 BP 54 EP 60 DI 10.1016/j.jss.2007.12.784 PG 7 WC Surgery SC Surgery GA 405SY UT WOS:000263245700007 PM 18599084 ER PT J AU Barclay, RP AF Barclay, Rebecca P. TI Your Defiant Teen: 10 Steps to Resolve Conflict and Rebuild Your Relationship SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Barclay, Rebecca P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Barclay, RP (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rbarclay@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2009 VL 48 IS 3 BP 342 EP 343 DI 10.1097/CHI.0b013e318196b932 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 412RO UT WOS:000263742100015 ER PT J AU Pridgen, B AF Pridgen, Bryan TI Cyberbullying: Bullying in the Digital Age SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Pridgen, Bryan] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pridgen, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM bpridgen@partners.org NR 4 TC 0 Z9 0 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2009 VL 48 IS 3 BP 344 EP 346 DI 10.1097/01.CHI.0000314059.89413.f7 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 412RO UT WOS:000263742100017 ER PT J AU Albrecht, J Werth, VP Bigby, M AF Albrecht, Joerg Werth, Victoria P. Bigby, Michael TI The role of case reports in evidence-based practice, with suggestions for improving their reporting SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CUTANEOUS LUPUS-ERYTHEMATOSUS; MYCOPHENOLATE-MOFETIL; POTASSIUM-IODIDE; PEMPHIGUS-VULGARIS; CASE SERIES; VASCULITIS; PSORIASIS; NEPHROPATHY; TERBINAFINE; DISEASE AB Background: Case reports are part of the evidence hierarchy in evidence-based practice and guide an important part of dermatologic practice. Objective: This article discusses the role of case reports and series in evidence-based practice and suggests how to improve reporting. Methods: This article was inspired by a forum on the role of case reporting in dermatologic practice presented at a meeting of the American Academy of Dermatology. It is based on an informal literature review and the authors' experience in systematically reviewing case reports in medicine and dermatology. Results: Case reports significantly influence medicine. Often they are the first line of evidence for new therapies but rarely are sufficient to establish treatment efficacy. Frequently they are the first and sometimes major source for detecting rare adverse events. Guidelines for improving the reporting of case reports and series are discussed. Limitations: This paper represents the views of the authors and is neither a systematic review of the literature nor a formal consensus document. Conclusion: Case reports are an important part of medical literature and need to be taken seriously. (J Am Acad Dermatol 2009;60:412-8.) C1 [Albrecht, Joerg] John H Stroger Jr Hosp Cook Cty, Dept Med, Chicago, IL 60612 USA. [Albrecht, Joerg] John H Stroger Jr Hosp Cook Cty, Div Dermatol, Chicago, IL 60612 USA. [Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Bigby, Michael] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Bigby, Michael] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Albrecht, J (reprint author), John H Stroger Jr Hosp Cook Cty, Dept Med, Adm Bldg,5th Floor,1900 W Polk St, Chicago, IL 60612 USA. EM joerg.albrecht@gmail.com FU NIAMS NIH HHS [K24 AR002207] NR 50 TC 21 Z9 22 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2009 VL 60 IS 3 BP 412 EP 418 DI 10.1016/j.jaad.2008.10.023 PG 7 WC Dermatology SC Dermatology GA 415KZ UT WOS:000263934000006 PM 19231639 ER PT J AU Alora-Palli, MB Kimball, AB Van Cott, A AF Alora-Palli, Maria Beatrice Kimball, Alexa B. Van Cott, Alicia TI A new topically applied liquor carbonis distillate (coal tar) solution helps reduce regression of plaque psoriasis after 12 weeks of treatment: A 6-week comparison to calcipotriol cream SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Academy-of-Dermatology CY MAR 06-10, 2009 CL San Francisco, CA SP Amer Acad Dermatol C1 [Alora-Palli, Maria Beatrice; Kimball, Alexa B.; Van Cott, Alicia] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2009 VL 60 IS 3 BP AB174 EP AB174 PG 1 WC Dermatology SC Dermatology GA 415LA UT WOS:000263934100689 ER PT J AU Armstrong, A Kimball, A Watson, A Kvedar, J Kazanis, M AF Armstrong, April Kimball, Alexandra Watson, Alice Kvedar, Joseph Kazanis, Maryanne TI A randomized, controlled trial evaluating adherence to sunscreen using electronic monitoring and text message reminders SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Academy-of-Dermatology CY MAR 06-10, 2009 CL San Francisco, CA SP Amer Acad Dermatol C1 [Watson, Alice] Massachusetts Gen Hosp, Ctr Connected Hlth, Boston, MA 02114 USA. [Kazanis, Maryanne] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2009 VL 60 IS 3 BP AB88 EP AB88 PG 1 WC Dermatology SC Dermatology GA 415LA UT WOS:000263934100352 ER PT J AU Asrani, F Shah, A Anderson, RR Liu, V Farinelli, W AF Asrani, Falguni Shah, Ajay Anderson, R. Rox Liu, Vincent Farinelli, William TI Patterned blister micrografting to repigment stable vitiligo: A novel technique SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Academy-of-Dermatology CY MAR 06-10, 2009 CL San Francisco, CA SP Amer Acad Dermatol C1 [Asrani, Falguni] Massachusetts Gen Hosp, Malden, MA 02114 USA. [Asrani, Falguni] Harvard Univ, Sch Med, Malden, MA USA. [Shah, Ajay] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Anderson, R. Rox; Farinelli, William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Anderson, R. Rox] Harvard Univ, Sch Med, Boston, MA USA. [Liu, Vincent] MIT Harvard, Cambridge, MA USA. [Farinelli, William] Harvard Med Coll, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2009 VL 60 IS 3 BP AB157 EP AB157 PG 1 WC Dermatology SC Dermatology GA 415LA UT WOS:000263934100621 ER PT J AU Asrani, F Wadhwa, S Khopkar, U AF Asrani, Falguni Wadhwa, Satish Khopkar, Uday TI Epiluminescence microscopy: Study of hypopigmentary disorders in Fitzpatrick skin types IV and V SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Academy-of-Dermatology CY MAR 06-10, 2009 CL San Francisco, CA SP Amer Acad Dermatol C1 [Asrani, Falguni] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Asrani, Falguni] Harvard Univ, Sch Med, Topiwala Natl Med Coll, Malden, MA USA. [Asrani, Falguni] Harvard Univ, Sch Med, BYL Nair Hosp, Malden, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2009 VL 60 IS 3 BP AB7 EP AB7 PG 1 WC Dermatology SC Dermatology GA 415LA UT WOS:000263934100028 ER PT J AU Kazanis, M Kimball, AB Armstrong, AW Frangos, J Drake, L AF Kazanis, Maryanne Kimball, Alexandra B. Armstrong, April W. Frangos, Jason Drake, Lynn TI A case-control study of rosacea subjects compared to control subjects SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Academy-of-Dermatology CY MAR 06-10, 2009 CL San Francisco, CA SP Amer Acad Dermatol C1 [Kazanis, Maryanne; Armstrong, April W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kimball, Alexandra B.; Frangos, Jason; Drake, Lynn] 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2009 VL 60 IS 3 BP AB39 EP AB39 PG 1 WC Dermatology SC Dermatology GA 415LA UT WOS:000263934100156 ER PT J AU Watson, A Williams, C Bergman, H Kvedar, J AF Watson, Alice Williams, Christy Bergman, Hagit Kvedar, Joseph TI Evaluating electronic visits for remote management of acne: Clinical outcomes are equivalent to conventional care SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Academy-of-Dermatology CY MAR 06-10, 2009 CL San Francisco, CA SP Amer Acad Dermatol C1 [Watson, Alice; Bergman, Hagit; Kvedar, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Williams, Christy] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2009 VL 60 IS 3 BP AB88 EP AB88 PG 1 WC Dermatology SC Dermatology GA 415LA UT WOS:000263934100351 ER PT J AU Niederman, R AF Niederman, Richard TI Evidence-based dentistry finds a new forum Exelauno SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material C1 Forsyth Inst, Ctr Evidence Based Dent, Boston, MA 02115 USA. RP Niederman, R (reprint author), Forsyth Inst, Ctr Evidence Based Dent, 140 Fenway, Boston, MA 02115 USA. EM rniederman@forsyth.org NR 3 TC 3 Z9 3 U1 0 U2 0 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAR PY 2009 VL 140 IS 3 BP 272 EP + PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 418BI UT WOS:000264121800001 PM 19255164 ER PT J AU Tavares, M Chomitz, V AF Tavares, Mary Chomitz, Virginia TI A healthy weight intervention for children in a dental setting A pilot study SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE Dental care for children; dental offices; obesity; nutrition; weight loss; behavioral sciences ID PREVENTING CHILDHOOD OBESITY; PEDIATRIC OVERWEIGHT; OFFICE; CONSUMPTION; EPIDEMIC; TRIAL AB Background. There are twice as many U.S. children who are overweight or at risk of being overweight as there were 20 years ago. Dental care professionals have an opportunity to provide obesity prevention interventions to their patients. The authors present a dental office-based healthy weight intervention (HWI) protocol designed for all children. Conclusions. Preventive dental office visits are an opportunity for dental care professionals to provide HWIs to children. The authors found that the HWI they described is feasible and can be well-accepted in a pediatric dental care setting. Caregivers and dental care providers said they considered the HWI to be useful, and it was well-accepted by children. Clinical Implications. Healthy eating and lifestyle behaviors can have a positive effect on systemic health and oral health. Better food choices can reduce dental caries, and the prevention of obesity-related systemic diseases, particularly diabetes, can help patients maintain good oral health. C1 [Tavares, Mary] Forsyth Inst, Boston, MA 02115 USA. [Chomitz, Virginia] Inst Community Hlth, Cambridge, MA USA. RP Tavares, M (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM mtavares@forsyth.org FU National Institutes of Health [1 R21 DE017446-01] FX This study was supported by National Institutes of Health grant 1 R21 DE017446-01. NR 34 TC 14 Z9 15 U1 1 U2 3 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAR PY 2009 VL 140 IS 3 BP 313 EP 316 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 418BI UT WOS:000264121800016 PM 19255175 ER PT J AU Taylor, C Lamparello, B Kruczek, K Anderson, EJ Hubbard, J Misra, M AF Taylor, Catherine Lamparello, Brooke Kruczek, Kimberly Anderson, Ellen J. Hubbard, Jane Misra, Madhusmita TI Validation of a Food Frequency Questionnaire for Determining Calcium and Vitamin D Intake by Adolescent Girls with Anorexia Nervosa SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID BONE-DENSITY; HEALTHY ADOLESCENTS; WOMEN; REPRODUCIBILITY; POPULATION AB Assessing calcium and vitamin D intake becomes important in conditions associated with low bone density such as anorexia nervosa. Food records that assess intake over a representative time period are used in research and sometimes clinical settings. However, compliance in adolescents can be suboptimal. This study was undertaken to determine the validity of a food frequency questionnaire (FFQ) for assessing calcium and vitamin D intake in adolescent girls with anorexia nervosa and healthy girls compared to validated food records assessing intake during a 4-day period, the hypothesis being that intake Would be adequately predicted by the FFQ, Thirty-six girls with anorexia nervosa and 39 healthy girls aged 12 to 18 years completed both the food record and the FFQ. An additional 31 subjects (20 with anorexin nervosa, 11 controls) completed the FFQ, but not the food record, and one girl with anorexia nervosa completed the food record, but not the FFQ. Subjects demonstrated greater compliance with the FFQ (99%) than the food record (71%). Daily calcium and vitamin D intake calculated using the food record and FFQ did not differ, although the FFQ tended to under-report vitamin D intake corrected for energy intake. Using quartile analysis, no gross misclassification was noted of calcium or vitamin D intake calculated using the food record or FFQ in girls with anorexia nervosa. Strong correlations were observed for daily vitamin D intake derived from the FFQ vs the food record, particularly in girls with anorexia nervosa (r=0.78, P<0.0001). Less robust correlations were observed for calcium intake (r=0.65, P<0.0001). The FFQ used in this study can be effectively used to assess daily calcium and vitamin D intake in adolescent girls with anorexia nervosa. C1 [Taylor, Catherine; Lamparello, Brooke; Kruczek, Kimberly; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Taylor, Catherine; Lamparello, Brooke; Kruczek, Kimberly; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Anderson, Ellen J.; Hubbard, Jane] Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org RI Taylor, Catherine/B-9152-2014 FU National Institutes of Health [R01 DK 062249, K23 RR018851, M01-RR-01066] FX The authors thank the Bionutrition Core of the General Clinical Research Center of Massachusetts General Hospital for their contribution to this study. Catherine Taylor, Kimberly Kruczek, and Brooke Lamparello, MSc, worked on data collection and entry, data analysis, and the writing of the manuscript. Ellen Anderson, MS, RD, LDN, and Jane Hubbard, MS, RD, LDN, worked on the food frequency questionnaire and food records, analyzed the output, and helped with manuscript preparation. Madhusmita Misra, MD, MPH, worked with study design, recruitment, data analysis, and manuscript preparation. NR 21 TC 20 Z9 20 U1 1 U2 6 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 2009 VL 109 IS 3 BP 479 EP 485 DI 10.1016/j.jada.2008.11.025 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 420LZ UT WOS:000264292600022 PM 19248866 ER PT J AU Wenger, NS Roth, CP Shekelle, PG Young, RT Solomon, DH Kamberg, CJ Chang, JT Louie, R Higashi, T MacLean, CH Adams, J Min, LC Ransohoff, K Hoffing, M Reuben, DB AF Wenger, Neil S. Roth, Carol P. Shekelle, Paul G. Young, Roy T. Solomon, David H. Kamberg, Caren J. Chang, John T. Louie, Rachel Higashi, Takahiro MacLean, Catherine H. Adams, John Min, Lillian C. Ransohoff, Kurt Hoffing, Marc Reuben, David B. TI A Practice-Based Intervention to Improve Primary Care for Falls, Urinary Incontinence, and Dementia SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE practice-based intervention; geriatric quality of care; clinical care improvement ID RANDOMIZED CONTROLLED-TRIAL; QUALITY INDICATORS; OLDER-PEOPLE; CLINICAL-TRIAL; PRACTICE GUIDELINES; PREVENTING FALLS; GENERAL-PRACTICE; ELDERLY-PEOPLE; COMMUNITY; MANAGEMENT AB To determine whether a practice-based intervention can improve care for falls, urinary incontinence, and cognitive impairment. Controlled trial. Two community medical groups. Community-dwelling patients (357 at intervention sites and 287 at control sites) aged 75 and older identified as having difficulty with falls, incontinence, or cognitive impairment. Intervention and control practices received condition case-finding, but only intervention practices received a multicomponent practice-change intervention. Percentage of quality indicators satisfied measured using a 13-month medical record abstraction. Before the intervention, the quality of care was the same in intervention and control groups. Screening tripled the number of patients identified as needing care for falls, incontinence, or cognitive impairment. During the intervention, overall care for the three conditions was better in the intervention than the control group (41%, 95% confidence interval (CI)=35-46% vs 25%, 95% CI=20-30%, P <.001). Intervention group patients received better care for falls (44% vs 23%, P <.001) and incontinence (37% vs 22%, P <.001) but not for cognitive impairment (44% vs 41%, P=.67) than control group patients. The intervention was more effective for conditions identified by screening than for conditions identified through usual care. A practice-based intervention integrated into usual clinical care can improve primary care for falls and urinary incontinence, although even with the intervention, less than half of the recommended care for these conditions was provided. More-intensive interventions, such as embedding intervention components into an electronic medical record, will be needed to adequately improve care for falls and incontinence. C1 [Wenger, Neil S.; Young, Roy T.; Louie, Rachel; Min, Lillian C.; Reuben, David B.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Wenger, Neil S.; Roth, Carol P.; Shekelle, Paul G.; Solomon, David H.; Adams, John] RAND Corp, Santa Monica, CA USA. [Shekelle, Paul G.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Kamberg, Caren J.] RAND, Washington, DC USA. [Chang, John T.] Zynx Hlth, Los Angeles, CA USA. [Higashi, Takahiro] Natl Canc Ctr, Tokyo 104, Japan. [MacLean, Catherine H.] WellPoint Inc, Programs Clin Excellence, Woodland Hills, CA USA. [Ransohoff, Kurt] Sansum Santa Barbara Med Fdn Clin, Santa Barbara, CA USA. [Hoffing, Marc] Desert Med Grp, Palm Springs, CA USA. RP Wenger, NS (reprint author), Univ Calif Los Angeles, Dept Med, 911 Broxton Plaza, Los Angeles, CA 90095 USA. EM nwenger@mednet.ucla.edu NR 36 TC 50 Z9 51 U1 4 U2 15 PU WILEY-BLACKWELL PUBLISHING, INC 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 MAR PY 2009 VL 57 IS 3 BP 547 EP 555 DI 10.1111/j.1532-5415.2008.02128.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 414JL UT WOS:000263859600023 PM 19175441 ER PT J AU Azar, AR Rudolph, JL Cho, LJ Grande, LG Barber, C McGlinchey, R Lipsitz, LA Milberg, WP AF Azar, A. R. Rudolph, J. L. Cho, L. J. Grande, L. G. Barber, C. McGlinchey, R. Lipsitz, L. A. Milberg, W. P. TI Vascular risk and depressive symptoms in African-American older adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Azar, A. R.; Rudolph, J. L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Rudolph, J. L.; Cho, L. J.; Grande, L. G.; Barber, C.; McGlinchey, R.; Milberg, W. P.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [McGlinchey, R.; Milberg, W. P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Lipsitz, L. A.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. RI McGlinchey, Regina/R-1971-2016 NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC 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 MAR PY 2009 VL 57 BP S40 EP S41 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900114 ER PT J AU Braddy, K Imam, SN Palla, KR Lee, TA AF Braddy, K. Imam, S. N. Palla, K. R. Lee, T. A. TI Practice Patterns for Vitamin D Deficiency/Insufficiency in Longterm Care: Are We Doing Enough? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Braddy, K.; Imam, S. N.; Palla, K. R.; Lee, T. A.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S174 EP S175 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900501 ER PT J AU Chi, R Haight, S Neuzil, K AF Chi, R. Haight, S. Neuzil, K. TI Suboptimal Immune Response to Influenza Vaccine in Community-Dwelling Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Chi, R.; Neuzil, K.] Univ Washington, Seattle, WA 98195 USA. [Chi, R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Haight, S.] St Louis Univ, Sch Med, St Louis, MO USA. [Neuzil, K.] PATH, Seattle, WA USA. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S60 EP S60 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900171 ER PT J AU Cohen, JA Hwang, U Morrison, RS AF Cohen, J. A. Hwang, U. Morrison, R. S. TI A descriptive study of palliative care patients admitted via the emergency department SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Cohen, J. A.; Hwang, U.; Morrison, R. S.] Mt Sinai Sch Med, New York, NY USA. [Morrison, R. S.] James J Peters VAMC, GRECC, Bronx, NY 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S27 EP S27 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900074 ER PT J AU Diller, A Sanchez-Reilly, S Wittenberg-Lyles, E AF Diller, A. Sanchez-Reilly, S. Wittenberg-Lyles, E. TI Caregivers of Elderly with Cancer: Can Intervention before Hospice affect Quality of Life? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Diller, A.; Sanchez-Reilly, S.; Wittenberg-Lyles, E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sanchez-Reilly, S.] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. [Wittenberg-Lyles, E.] Univ N Texas, Denton, TX 76203 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC 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 MAR PY 2009 VL 57 BP S130 EP S130 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900370 ER PT J AU Gordon, W Polansky, J Boscardin, J Fung, K Patil, S Steinman, M AF Gordon, W. Polansky, J. Boscardin, J. Fung, K. Patil, S. Steinman, M. TI Point-based vs. equation-based Framingham risk models: Minor simplification with major consequences SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Gordon, W.] Weill Cornell Med Coll, New York, NY USA. [Gordon, W.] Med Student Training Aging Res Program, San Francisco, CA USA. [Polansky, J.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Fung, K.; Patil, S.; Steinman, M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Boscardin, J.; Fung, K.; Patil, S.; Steinman, M.] UCSF, Div Geriatr, San Francisco, CA USA. [Boscardin, J.] UCSF, Div Biostat, San Francisco, CA 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S5 EP S6 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900014 ER PT J AU Gray, S Boudreau, R Newman, A Studenski, S Shorr, R Bauer, D Simonsick, E Hanlon, J AF Gray, S. Boudreau, R. Newman, A. Studenski, S. Shorr, R. Bauer, D. Simonsick, E. Hanlon, J. TI Angiotensin-converting Enzyme Inhibitor (ACEI) Medication Use and Persistent Lower Extremity Limitation (PLL) in Community Elderly: The Health, Aging and Body Composition Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Gray, S.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Boudreau, R.; Newman, A.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Newman, A.; Studenski, S.; Hanlon, J.] Univ Pittsburgh, Sch Med, Dept Geriatr Med, Pittsburgh, PA USA. [Studenski, S.; Hanlon, J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. [Studenski, S.; Hanlon, J.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Shorr, R.] N Florida S Georgia Vet Hlth Syst, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA. [Bauer, D.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Simonsick, E.] NIA, Intramural Res Program, Baltimore, MD 21224 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S176 EP S176 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900505 ER PT J AU Hung, WW Liu, S Du, Q Boockvar, K AF Hung, W. W. Liu, S. Du, Q. Boockvar, K. TI Changes in functional status during acute illness episodes in nursing home residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Hung, W. W.; Du, Q.; Boockvar, K.] Mt Sinai Sch Med, New York, NY USA. [Hung, W. W.; Boockvar, K.] James J Peters VA Med Ctr, Bronx, NY USA. [Liu, S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S148 EP S148 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900424 ER PT J AU Husu, EN Roccaro, AM Mohler, MJ Ghobrial, IM Sacco, A Melhem, MR Azab, A Jia, X Ngo, HT Azab, F Rennels, J Quang, P Leleu, X Mohler, MJ Ghobrial, IM AF Husu, E. N. Roccaro, A. M. Mohler, M. J. Ghobrial, I. M. Sacco, A. Melhem, M. R. Azab, A. Jia, X. Ngo, H. T. Azab, F. Rennels, J. Quang, P. Leleu, X. Mohler, M. J. Ghobrial, I. M. TI Treatment of Waldenstrom Macroglobulinemia with a Dual PI3K and mTOR Inhibitior SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Husu, E. N.; Roccaro, A. M.; Ghobrial, I. M.; Sacco, A.; Melhem, M. R.; Azab, A.; Jia, X.; Ngo, H. T.; Azab, F.; Rennels, J.; Quang, P.; Leleu, X.; Ghobrial, I. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Husu, E. N.] Univ Arizona, Coll Med, Tucson, AZ USA. [Mohler, M. J.; Mohler, M. J.] Univ Arizona, Arizona Ctr Aging, Tucson, AZ 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S154 EP S154 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900442 ER PT J AU Kenfield, MC Arciniegas, DB Anderson, C Howard, KL Filley, CM AF Kenfield, M. C. Arciniegas, D. B. Anderson, C. Howard, K. L. Filley, C. M. TI When Cognitive Evaluation Does Not Disclose a Neurologic Disorder: Experience of a University Behavioral Neurology Clinic SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Kenfield, M. C.; Arciniegas, D. B.; Anderson, C.; Howard, K. L.; Filley, C. M.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Arciniegas, D. B.; Anderson, C.; Filley, C. M.] Denver Vet Affairs Med Ctr, Denver, CO 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S196 EP S197 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900563 ER PT J AU Linnebur, SA Fish, DD Ruscin, J Radcliff, T Oman, K Liebrecht, D Fish, R McNulty, MC Hutt, E AF Linnebur, S. A. Fish, D. D. Ruscin, J. Radcliff, T. Oman, K. Liebrecht, D. Fish, R. McNulty, M. C. Hutt, E. TI Impact of Educational Interventions Targeting Antibiotic Use for Nursing Home-Acquired Pneumonia (NHAP) SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Linnebur, S. A.; Fish, D. D.; Radcliff, T.; Oman, K.; Liebrecht, D.; Fish, R.; McNulty, M. C.; Hutt, E.] Univ Colorado Denver, Aurora, CO USA. [Ruscin, J.] So Illinois Univ, Edwardsville, IL 62026 USA. [Radcliff, T.; Hutt, E.] Denver VA Med Ctr, Denver, CO 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S6 EP S6 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900016 ER PT J AU Markland, AD Walsh-Covarrubias, JB DuBeau, C Urist, MM Bland, KI Kilgore, LC Amling, CL Richter, HE AF Markland, A. D. Walsh-Covarrubias, J. B. DuBeau, C. Urist, M. M. Bland, K. I. Kilgore, L. C. Amling, C. L. Richter, H. E. TI Utilization of a Learners Needs Assessment for Geriatric Training among Three Surgical Training Programs SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Markland, A. D.] Birmingham VAMC, Birmingham, AL USA. [Markland, A. D.; Walsh-Covarrubias, J. B.; Urist, M. M.; Bland, K. I.; Kilgore, L. C.; Amling, C. L.; Richter, H. E.] Univ Alabama, Birmingham, AL USA. [Richter, H. E.] Univ Chicago, Chicago, IL 60637 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S35 EP S35 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900099 ER PT J AU Meo, N Hwang, U Morrison, R AF Meo, N. Hwang, U. Morrison, R. TI Resident Perceptions of Palliative Care Training in the Emergency Department. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Hwang, U.; Morrison, R.] Brookdale Dept Geriatr & Adult Dev, New York, NY USA. [Hwang, U.] James J Peters VAMC, GRECC, Bronx, NY USA. [Morrison, R.] Lillian & Benjamin Hertzberg Palliat Care Ctr, New York, NY 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S39 EP S39 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900110 ER PT J AU Parr, JD Zhang, B Nilsson, M Wright, A Balboni, T Block, S Duthie, E Prigerson, H AF Parr, J. D. Zhang, B. Nilsson, M. Wright, A. Balboni, T. Block, S. Duthie, E. Prigerson, H. TI Age Differences in Advanced Cancer Patient Treatment Preferences, Care Received, Goal Attainment, and Quality of Life at End-of-Life SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Parr, J. D.; Zhang, B.; Nilsson, M.; Wright, A.; Balboni, T.; Block, S.; Prigerson, H.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Block, S.; Prigerson, H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Parr, J. D.; Duthie, E.] Med Coll Wisconsin, Div Geriatr Gerontol, Milwaukee, WI 53226 USA. [Balboni, T.] Radiat Oncol Program, Boston, MA USA. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S107 EP S108 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900304 ER PT J AU Patel, D Martin, J Josephson, K Alessi, C AF Patel, D. Martin, J. Josephson, K. Alessi, C. TI Earlier morning rise time predicts better functional outcomes of post-acute rehabilitation for orthopedic patients. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Patel, D.] Western Univ, Pomona, CA USA. [Martin, J.; Alessi, C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Martin, J.; Josephson, K.; Alessi, C.] VA Greater Los Angeles, North Hills, CA 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S110 EP S110 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900312 ER PT J AU Rudolph, JL Marcantonio, ER Jones, RN Shi, P Inouye, SK AF Rudolph, J. L. Marcantonio, E. R. Jones, R. N. Shi, P. Inouye, S. K. TI Delirium and Functional Decline after Cardiac Surgery SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Rudolph, J. L.] Boston VA Med Ctr, GRECC, Boston, MA USA. [Marcantonio, E. R.] BIDMC, Div Gen Med & Primary Care & Gerontol, Boston, MA USA. [Marcantonio, E. R.; Jones, R. N.; Shi, P.; Inouye, S. K.] Hebrew SeniorLife, Aging Brain Ctr, Boston, MA USA. [Jones, R. N.; Inouye, S. K.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S111 EP S111 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900314 ER PT J AU Schreiber, K Rudolph, JL AF Schreiber, K. Rudolph, J. L. TI Postoperative cognitive dysfunction after cardiac surgery: A Systematic Review SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Schreiber, K.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Rudolph, J. L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Rudolph, J. L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S159 EP S159 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900455 ER PT J AU Steinman, MA Patil, S Kamat, P Knight, S AF Steinman, M. A. Patil, S. Kamat, P. Knight, S. TI A Taxonomy of Reasons for Not Prescribing Guideline-Recommended Medications: Results from Physician Focus Groups. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Steinman, M. A.; Patil, S.; Kamat, P.; Knight, S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Steinman, M. A.; Knight, S.] Univ Calif San Francisco, San Francisco, CA 94143 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S49 EP S49 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900138 ER PT J AU Volandes, AE Paasche-Orlow, MK Barry, MJ Gillick, MR Minaker, KL Chang, Y Cook, EF Abbo, ED El-Jawahri, A Mitchell, SL AF Volandes, A. E. Paasche-Orlow, M. K. Barry, M. J. Gillick, M. R. Minaker, K. L. Chang, Y. Cook, E. F. Abbo, E. D. El-Jawahri, A. Mitchell, S. L. TI A Video Decision Support Tool for Advance Care Planning in Dementia: A Randomized Controlled Trial SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Volandes, A. E.; Barry, M. J.; Minaker, K. L.; Chang, Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Paasche-Orlow, M. K.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gillick, M. R.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Cook, E. F.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Abbo, E. D.] Univ Chicago, Chicago, IL 60637 USA. [Mitchell, S. L.] Aging Hebrew SeniorLife, Boston, MA USA. [Mitchell, S. L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S3 EP S4 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900009 ER PT J AU Wilton, N Hammond, D Tio-Matos, I AF Wilton, N. Hammond, D. Tio-Matos, I. TI Rapidly Progressive Dementia- a Diagnostic Conundrum. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Wilton, N.; Hammond, D.; Tio-Matos, I.] VA Puget Sound, Tacoma, WA USA. [Wilton, N.; Tio-Matos, I.] Madigan Army Med Ctr, Tacoma, WA 98431 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S23 EP S24 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900064 ER PT J AU Yung, VY Walling, AM Min, LC Wenger, NS Ganz, DA AF Yung, V. Y. Walling, A. M. Min, L. C. Wenger, N. S. Ganz, D. A. TI Advance Care Planning and End-of-life Care Preferences in Community-dwelling Elders SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 29-MAY 02, 2009 CL Chicago, IL SP Amer Geriatr Soc C1 [Yung, V. Y.; Walling, A. M.; Min, L. C.; Wenger, N. S.; Ganz, D. A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Walling, A. M.; Wenger, N. S.] Univ Calif Los Angeles, Hlth Syst Eth Ctr, Los Angeles, CA 90095 USA. [Ganz, D. A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2009 VL 57 BP S97 EP S97 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 425BL UT WOS:000264611900275 ER PT J AU Lester, WT Ashburner, JM Grant, RW Chueh, HC Barry, MJ Atlas, SJ AF Lester, William T. Ashburner, Jeffrey M. Grant, Richard W. Chueh, Henry C. Barry, Michael J. Atlas, Steven J. TI Mammography FastTrack: An Intervention to Facilitate Reminders for Breast Cancer Screening across a Heterogeneous Multi-clinic Primary Care Network SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID OLDER WOMEN; HEALTH-CARE; PREVENTIVE SERVICES; CONTROLLED TRIAL; CHRONIC DISEASE; QUALITY; PATIENT; METAANALYSIS; PHYSICIANS; BEHAVIOR AB Health care information technology can be a means to improve quality and efficiency in the primary care setting. However, merely applying technology without addressing how it fits into provider workflow and existing systems is unlikely to achieve improvement goals. Improving quality of primary care, such as cancer screening rates, requires addressing barriers at system, provider, and patient levels. The authors report the development, implementation, and preliminary use of a new breast cancer screening outreach program in a large multicenter primary care network. This installation paired population-based surveillance with customized information delivery based on a validated model linking patients to providers and practices. In the first six months, 86% of physicians and all case managers voluntarily participated in the program. Providers intervened in 83% of the mammogram-overdue population by initiating mailed reminders or deferring contact. Overall, 63%, of patients were successfully contacted. Systematic population-based efforts are promising tools to improve preventative care. C1 [Lester, William T.; Chueh, Henry C.] Harvard Univ, Sch Med, Comp Sci Lab, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grant, Richard W.; Chueh, Henry C.] Massachusetts Gen Hosp, Clin Res Program, Boston, MA 02114 USA. [Ashburner, Jeffrey M.; Grant, Richard W.; Barry, Michael J.; Atlas, Steven J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Lester, WT (reprint author), Harvard Univ, Sch Med, Comp Sci Lab, Massachusetts Gen Hosp, 50 Staniford St,7th Floor, Boston, MA 02114 USA. EM wlester@partners.org OI Lester, William/0000-0003-4086-9280; Grant, Richard/0000-0002-6164-8025 NR 53 TC 9 Z9 9 U1 4 U2 9 PU HANLEY & BELFUS-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR-APR PY 2009 VL 16 IS 2 BP 187 EP 195 DI 10.1197/jamia.M2813 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 423MD UT WOS:000264499500007 PM 19074304 ER PT J AU Russo, LM Sandoval, RM Campos, SB Molitoris, BA Comper, WD Brown, D AF Russo, Leileata M. Sandoval, Ruben M. Campos, Silvia B. Molitoris, Bruce A. Comper, Wayne D. Brown, Dennis TI Impaired Tubular Uptake Explains Albuminuria in Early Diabetic Nephropathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR CAPILLARY WALL; NEPHROTIC LEVELS; KIDNEY; PROTEINURIA; INSULIN; DISEASE; RAT AB Understanding the pathogenesis of albuminuria in diabetic nephropathy is important to improve methods for early diagnosis and treatment. In this study, we addressed whether albuminuria in diabetes results from altered glomerular filtration and/or altered processing of filtered albumin by the proximal tubule. Type 1 diabetic Munich Wistar rats developed albuminuria after 12 wk of diabetes, Intravital two-photon microscopy revealed similar glomerular permeability in the diabetic and control animals, assessed using both albumin-Alexa568 and 69-kD FITC-dextran; however, diabetic animals demonstrated significantly less filtered fluorescent albumin in renal proximal tubule (PT) cells compared with control animals. We also observed increased albumin-derived urinary pepticle excretion in diabetic animals, and hyperglycemia modulated this peptideuria. In conclusion, in the early stages of diabetic nephropathy, the PT plays a major role in the development of albuminuria, which may be preceded by peptideuria. C1 [Russo, Leileata M.; Brown, Dennis] Massachusetts Gen Hosp, Dept Med, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Sandoval, Ruben M.; Campos, Silvia B.; Molitoris, Bruce A.] Indiana Univ, Med Ctr, Dept Med, Div Nephrol,Indiana Ctr Biol Microscopy, Indianapolis, IN USA. [Molitoris, Bruce A.] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. [Comper, Wayne D.] Exosome Diagnost Inc, New York, NY USA. [Comper, Wayne D.] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia. RP Russo, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Program Membrane Biol, Simches Res Ctr,Div Nephrol, 185 Cambridge St,Room 8100, Boston, MA 02114 USA. EM leileata.russo@receptor.mgh.harvard.edu FU Juvenile Diabetes Research Foundation International; National Institutes of Health [DK 061594, DK38452]; NIGH Program in Membrane Biology; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Center for the Study of Inflammatory Bowel Disease [DK43341] FX This work was Supported by grants from the Juvenile Diabetes Research Foundation International (L.M.R. and W.D.C.). National Institutes of Health grant DK 061594 was awarded to B.A.M. to establish a George M. O'Brien Center for advanced renal microscopy analysis at the Indiana Centre for Biologic Microscopy. The Microscopy Core Facility of the NIGH Program in Membrane Biology receives support from National institutes of Health grant DK38452 (D.B.), the Boston Area Diabetes and Endocrinology Research Center (DK57521), and the Center for the Study of Inflammatory Bowel Disease (DK43341). We thank Dr. Tanya Osicka and Steve Sastra for performing the fractional clearance studies. NR 19 TC 117 Z9 122 U1 0 U2 7 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 MAR PY 2009 VL 20 IS 3 BP 489 EP 494 DI 10.1681/ASN.2008050503 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 417NZ UT WOS:000264084300011 PM 19118149 ER PT J AU Ueno, T Tanaka, K Jurewicz, M Murayama, T Guleria, I Fiorina, P Paez, JC Augello, A Vergani, A Wong, M Smith, RN Abdi, R AF Ueno, Takuya Tanaka, Katsunori Jurewicz, Mollie Murayama, Takaya Guleria, Indira Fiorina, Paolo Paez, Jesus C. Augello, Andrea Vergani, Andrea Wong, Masie Smith, R. Neal Abdi, Reza TI Divergent Role of Donor Dendritic Cells in Rejection versus Tolerance of Allografts SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID IN-VIVO DEPLETION; CD8(+) T-CELLS; BONE-MARROW; TRANSPLANTATION TOLERANCE; INDIRECT ALLORECOGNITION; BLOOD-TRANSFUSION; LYMPH-NODES; PATHWAYS; SURVIVAL; MONOCYTES AB Little is known about heart tissue/donor dendritic cells, which play a key role in mounting alloimmune responses. In this report, we focus on three primary features of donor dendritic cells: their generation, their trafficking after transplantation, and their role in regulating tolerance versus rejection. Using transgenic mice as donors of heart allografts enabled us to monitor trafficking of donor dendritic cells after transplantation. Donor dendritic cells rapidly migrated into secondary lymphoid tissues within 3 h of transplantation. We found that the chemokine receptor CX3CR1 regulates the generation of heart tissue dendritic cells constitutively. Compared with wild-type hearts, CX3CR1(-/-) hearts contained fewer dendritic cells, and heart allografts from CX3CR1(-/-) donors survived significantly longer without immunosuppression. Unexpectedly, though, co-stimulatory blockade with anti-CD154 or CTLA4-lg induced long-term survival for wild-type heart allografts but not for CX3CR1(-/-) heart allografts. Increasing the dendritic cell frequency in CX3CR1(-/-) hearts by treatment with FIt3L restored the anti-CD154-induced prolongation of CX3CR1(-/-) heart allograft survival. Compared with wild-type donors, depleting transgenic donors of dendritic cells before heart transplantation also markedly worsened chronic rejection under anti-CD154 treatment. These data indicate the importance of the CX3CR1 pathway in the generation of heart tissue dendritic cells and the divergent role of tissue/dendritic cells in rejection versus tolerance. C1 [Abdi, Reza] Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplantat Res Ctr,Renal Div, Boston, MA 02115 USA. [Ueno, Takuya; Tanaka, Katsunori; Jurewicz, Mollie; Murayama, Takaya; Guleria, Indira; Fiorina, Paolo; Paez, Jesus C.; Augello, Andrea; Vergani, Andrea; Wong, Masie; Abdi, Reza] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [Smith, R. Neal] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Abdi, R (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplantat Res Ctr,Renal Div, 221 Longwood Ave, Boston, MA 02115 USA. EM rabdi@rics.bwh.harvard.edu RI Augello, Andrea/C-7321-2013 OI Augello, Andrea/0000-0001-5959-7989 FU National Kidney Foundation; Roche Organ Transplantation Research Foundation; Juvenile Diabetes Research Foundation; John Merrill Transplant Scholar grant FX This work was supported by a National Kidney Foundation clinical scientist award, a Roche Organ Transplantation Research Foundation grant, the Juvenile Diabetes Research Foundation regular grant, and a John Merrill Transplant Scholar grant (to R.A.). NR 51 TC 12 Z9 12 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAR PY 2009 VL 20 IS 3 BP 535 EP 544 DI 10.1681/ASN.2008040377 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 417NZ UT WOS:000264084300016 PM 19129312 ER PT J AU Coit, DG Andtbacka, R Bichakjian, CK Dilawari, RA DiMaio, D Guild, V Halpern, AC Hodi, FS Kashani-Sabet, M Lange, JR Lind, A Martin, L Martini, MC Pruitt, SK Ross, MI Sener, SF Swetter, SM Tanabe, KK Thompson, JA Trisal, V Urist, MM Weber, J Wong, MK AF Coit, Daniel G. Andtbacka, Robert Bichakjian, Christopher K. Dilawari, Raza A. DiMaio, Dominick Guild, Valerie Halpern, Allan C. Hodi, F. Stephen Kashani-Sabet, Mohammed Lange, Julie R. Lind, Anne Martin, Lainie Martini, Mary C. Pruitt, Scott K. Ross, Merrick I. Sener, Stephen F. Swetter, Susan M. Tanabe, Kenneth K. Thompson, John A. Trisal, Vijay Urist, Marshall M. Weber, Jeffrey Wong, Michael K. TI Melanoma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID LYMPH-NODE BIOPSY; PRIMARY CUTANEOUS MELANOMA; POSITRON-EMISSION-TOMOGRAPHY; HIGH-RISK MELANOMA; COOPERATIVE-ONCOLOGY-GROUP; EARLY-STAGE MELANOMA; METASTATIC MALIGNANT-MELANOMA; HIGH-DOSE INTERFERON-ALPHA-2B; RANDOMIZED CONTROLLED-TRIALS; AMERICAN JOINT COMMITTEE C1 [Coit, Daniel G.; Halpern, Allan C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Andtbacka, Robert] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Bichakjian, Christopher K.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Dilawari, Raza A.] Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. [DiMaio, Dominick] Univ Nebraska Med Ctr, Eppley Canc Ctr, Omaha, NE USA. [Lind, Anne] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Martin, Lainie] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Martini, Mary C.; Sener, Stephen F.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Ross, Merrick I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Swetter, Susan M.] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Thompson, John A.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Urist, Marshall M.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL USA. [Wong, Michael K.] Roswell Pk Canc Inst, Buffalo, NY USA. RP Coit, DG (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 128 TC 78 Z9 81 U1 0 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2009 VL 7 IS 3 BP 250 EP 275 PG 26 WC Oncology SC Oncology GA 499ZC UT WOS:000270264600004 PM 19401060 ER PT J AU Liberman, M Mathisen, DJ AF Liberman, Moishe Mathisen, Douglas J. TI Tailored cricoplasty: An improved modification for reconstruction in subglottic tracheal stenosis SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID IDIOPATHIC LARYNGOTRACHEAL STENOSIS; WEGENERS-GRANULOMATOSIS; RESECTION; MANAGEMENT; LARYNGEAL; ANASTOMOSIS; DIAGNOSIS AB Objective: Subglottic laryngotracheal stenosis with side-to-side narrowing poses a challenge for successful reconstruction. The standard technique of anterior cricoid resection was modified to address a small ventricle with lateral narrowing. Methods: This study was a retrospective chart review and telephone questionnaire follow-up of consecutive patients with subglottic stenosis at a single institution. Follow-up questionnaires used Likert scales (ratings 1-10) to describe preoperative and postoperative symptoms, satisfaction, and perceived effectiveness. Once the anterior cricoid is removed, resection of thickened submucosal tissue is performed. The inner third to half of the lateral wall of the remaining cricoid cartilage is carefully excised. Advancing the preserved mucosa over the cricoid resurfaces the exposed cartilage. This results in additional horizontal enlargement of the luminal diameter of the airway of 3 to 5 mm. Results: Eighteen patients with subglottic stenosis, small laryngeal ventricle, and lateral narrowing underwent tailored cricoplasty during a 15-month period. Mean age was 51 years (range 20-75 years), and mean follow-up was 9.1 +/- 1.2 months (range 2-17 months). There were 2 self-limited airway complications. All patients reported that they were satisfied and would undergo surgery again. Overall satisfaction was rated at 9.5 +/- 1.0, and satisfactions with resting and exertional dyspnea were 9.7 +/- 0.5 and 9.5 +/- 1.0, respectively. Symptoms of recurrence at follow-up were rated as 0.6 +/- 1.4. Conclusion: Tailored cricoplasty is an effective technique to improve the outcome of reconstructive subglottic stenosis. It offers reconstructive possibilities for patients with diminished side-to-side dimensions in the subglottic airway. C1 [Liberman, Moishe; Mathisen, Douglas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg, Boston, MA USA. RP Mathisen, DJ (reprint author), 55 Fruit St,Blake 1570, Hopkinton, MA 01748 USA. EM dmathisen@partners.org NR 16 TC 8 Z9 8 U1 0 U2 0 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 MAR PY 2009 VL 137 IS 3 BP 573 EP 579 DI 10.1016/j.jtcvs.2008.11.020 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 413KH UT WOS:000263791500011 PM 19258068 ER PT J AU Wright, CD Kucharczuk, JC O'Brien, SM Grab, JD Allen, MS AF Wright, Cameron D. Kucharczuk, John C. O'Brien, Sean M. Grab, Joshua D. Allen, Mark S. TI Predictors of major morbidity and mortality after esophagectomy for esophageal cancer: A Society of Thoracic Surgeons General Thoracic Surgery Database risk adjustment model SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 10-14, 2008 CL San Diego, CA SP Amer Assoc Thorac Surg ID LEWIS,IVOR ESOPHAGOGASTRECTOMY; TRANSTHORACIC ESOPHAGECTOMY; PULMONARY COMPLICATIONS; ELDERLY-PATIENTS; UNITED-STATES; VOLUME; SURVIVAL; INCREASE; OUTCOMES AB Objective: To create a model for perioperative risk of esophagectomy for cancer using the Society of Thoracic Surgeons General Thoracic Database. Methods: The Society of Thoracic Surgeons General Thoracic Database was queried for all patients treated with esophagectomy for esophageal cancer between January 2002 and December 2007. A multivariable risk model for mortality and major morbidity was constructed. Results: There were 2315 esophagectomies performed by 73 participating centers. Hospital mortality was 63/2315 (2.7%). Major morbidity (defined as reoperation for bleeding [n = 12], anastomotic leak [n = 261], pneumonia [n = 188], reintubation [n = 227], ventilation beyond 48 hours [n = 71], or death [n = 63]) occurred in 553 patients (24%). Preoperative spirometry was obtained in 923/2315 (40%) of patients. A forced expiratory volume in 1 second < 60% of predicted was associated with major morbidity (P = .0044). Important predictors of major morbidity are: age 75 versus 55 (P = .005), black race (P = .08), congestive heart failure (P = .015), coronary artery disease (P = .017), peripheral vascular disease (P = .009), hypertension (P = .029), insulin-dependent diabetes (P = .009), American Society of Anesthesiology rating (P = .001), smoking status (P = .022), and steroid use (P = .026). A strong volume performance relationship was not observed for the composite measure of morbidity and mortality in this patient cohort. Conclusions: Thoracic surgeons participating in the Society of Thoracic Surgeons General Thoracic Database perform esophagectomy with a low mortality. We identified important predictors of major morbidity and mortality after esophagectomy for esophageal cancer. Volume alone is an inadequate proxy for quality assessment after esophagectomy. C1 [Wright, Cameron D.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Kucharczuk, John C.] Univ Penn, Div Thorac Surg, Philadelphia, PA 19104 USA. [O'Brien, Sean M.; Grab, Joshua D.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Allen, Mark S.] Mayo Clin, Sch Med, Div Gen Thorac Surg, Rochester, MN USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu RI O'Brien, Sean/H-6268-2013 NR 19 TC 141 Z9 148 U1 0 U2 5 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 MAR PY 2009 VL 137 IS 3 BP 587 EP 596 DI 10.1016/j.jtcvs.2008.11.042 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 413KH UT WOS:000263791500013 PM 19258071 ER PT J AU Sequist, LV Nagrath, S Toner, M Haber, DA Lynch, TJ AF Sequist, Lecia V. Nagrath, Sunitha Toner, Mehmet Haber, Daniel A. Lynch, Thomas J. TI The CTC-Chip An Exciting New Tool to Detect Circulating Tumor Cells in Lung Cancer Patients SO JOURNAL OF THORACIC ONCOLOGY LA English DT Editorial Material DE Circulating tumor cells; Non-small cell lung cancer; EGFR mutation; CTC-chip ID METASTATIC BREAST-CANCER; ACQUIRED-RESISTANCE; EGFR MUTATIONS; PHASE-II; GEFITINIB; ERLOTINIB; THERAPY AB Circulating tumor cells (CTCs) are rare cells that originate from a malignancy and circulate freely in the peripheral blood. The ability to capture and study CTCs is an emerging field with implications for early detection, diagnosis, determining prognosis and monitoring of cancer, as well as for understanding the fundamental biology of the process of metastasis, Here, we review the development and initial clinical studies with a novel microfluidic platform for isolating these cells, the CTC-chip, and discuss its potential uses in the study of lung cancer. C1 [Sequist, Lecia V.; Haber, Daniel A.; Lynch, Thomas J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Nagrath, Sunitha; Toner, Mehmet] Harvard Univ, Sch Med, BioMEMS Resource Ctr, Boston, MA USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM Ivsequist@partners.org FU NIBIB NIH HHS [U01 EB012493, P41 EB002503, R01 EB008047] NR 23 TC 67 Z9 76 U1 3 U2 45 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 MAR PY 2009 VL 4 IS 3 BP 281 EP 283 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 415UP UT WOS:000263961500005 PM 19247082 ER PT J AU Phelan, HA Velmahos, GC Jurkovich, GJ Friese, RS Minei, JP Menaker, JA Philp, A Evans, HL Gunn, ML Eastman, AL Rowell, SE Allison, CE Barbosa, RL Norwood, SH Tabbara, M Dente, CJ Carrick, MM Wall, MJ Feeney, J O'Neill, PJ Srinivas, G Brown, CVR Reifsnyder, AC Hassan, MO Albert, S Pascual, JL Strong, M Moore, FO Spain, DA Purtill, MA Edwards, B Strauss, J Durham, RM Duchesne, JC Greiffenstein, P Cothren, CC AF Phelan, Herb A. Velmahos, George C. Jurkovich, Gregory J. Friese, Randall S. Minei, Joseph P. Menaker, Jay A. Philp, Allan Evans, Heather L. Gunn, Martin L. Eastman, Alexander L. Rowell, Susan E. Allison, Carrie E. Barbosa, Ronald L. Norwood, Scott H. Tabbara, Malek Dente, Christopher J. Carrick, Matthew M. Wall, Matthew J. Feeney, Jim O'Neill, Patrick J. Srinivas, Gujjarappa Brown, Carlos V. R. Reifsnyder, Andrew C. Hassan, Moustafa O. Albert, Scott Pascual, Jose L. Strong, Michelle Moore, Forrest O. Spain, David A. Purtill, Mary-Anne Edwards, Byard Strauss, Jason Durham, Rodney M. Duchesne, Juan C. Greiffenstein, Patrick Cothren, C. Clay TI An Evaluation of Multidetector Computed Tomography in Detecting Pancreatic Injury: Results of a Multicenter AAST Study SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Pancreas; Multidetector computed tomography; Trauma ID BLUNT TRAUMA; DIAGNOSIS; MANAGEMENT; CT AB Background: Efforts to determine the suitability of low-grade pancreatic injuries for nonoperative management have been hindered by the inaccuracy of older computed tomography (CT) technology for detecting pancreatic injury (PI). This retrospective, multicenter American Association for the Surgery of Trauma-sponsored trial examined the sensitivity of newer 16- and 64-multidetector CT (MDCT) for detecting PI, and sensitivity/specificity for the identification of pancreatic ductal injury (PDI). Methods: Patients who received a preoperative 16- or 64-MDCT followed by laparotomy with a documented PI were enrolled. Preoperative MDCT scans were classified as indicating the presence (+) or absence (-) of PI and PDI. Operative notes were reviewed and all patients were confirmed as PI (+), and then classified as PDI (+) or (-). As all patients had PI, an analysis of PI specificity was not possible. PI patients formed the pool for further PDI analysis. As sensitivity and specificity data were available for PDI, multivariate logistic regression was performed for PDI patients using the presence or absence of agreement between CT and operative note findings as an independent variable. Covariates were age, gender, Injury Severity Score, mechanism of injury, presence of oral contrast, presence of other abdominal injuries, performance of the scan as part of a dedicated pancreas protocol, and image thickness >= 3 mm or >= 5 mm. Results: Twenty centers enrolled 206 PI patients, including 71 PDI (+) patients. Intravenous contrast was used in 203 studies; 69 studies used presence of oral contrast. Eight-nine percent were blunt mechanisms, and 96% were able to have their duct status operatively classified as PDI (+) or (-). The sensitivity of 16-MDCT for all PI was 60.1%, whereas 64-MDCT was 47.2%. For PDI, the sensitivities of 16- and 64-MDCT were 54.0% and 52.4%, respectively, with specificities of 94.8% for 16-MDCT scanners and 90.3% for 64-MDCT scanners. Logistic regression showed that no covariates were associated with an increased likelihood of detecting PDI for either 16- or 64-MDCT scanners. The area under the curve was 0.66 for the 16-MDCT PDI analysis and 0.77 for the 64-MDCT PDI analysis. Conclusion: Sixteen and 64-MDCT have low sensitivity for detecting PI and PDI, while exhibiting a high specificity for PDI. Their use as decision-making tools for the nonoperative management of PI are, therefore, limited. C1 [Phelan, Herb A.; Minei, Joseph P.; Eastman, Alexander L.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Velmahos, George C.; Tabbara, Malek] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jurkovich, Gregory J.; Evans, Heather L.; Gunn, Martin L.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Friese, Randall S.] Arizona Hlth Sci Ctr, Tucson, AZ 85724 USA. [Menaker, Jay A.; Philp, Allan] R Adams Cowley Shock Trauma Ctr, Baltimore, MD USA. [Rowell, Susan E.; Allison, Carrie E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Barbosa, Ronald L.] Legacy Emanuel Hosp, Portland, OR USA. [Norwood, Scott H.] E Texas Med Ctr, Tyler, TX USA. [Dente, Christopher J.] Emory Univ, Atlanta, GA 30322 USA. [Carrick, Matthew M.; Wall, Matthew J.] Baylor Coll Med, Houston, TX 77030 USA. [Feeney, Jim] Hartford Hosp, Hartford, CT 06115 USA. [O'Neill, Patrick J.; Srinivas, Gujjarappa] Maricopa Cty Gen Hosp, Phoenix, AZ USA. [Brown, Carlos V. R.; Reifsnyder, Andrew C.] Univ Med Ctr Brackenridge, Austin, TX USA. [Hassan, Moustafa O.; Albert, Scott] SUNY Upstate Med Univ, Syracuse, NY USA. [Pascual, Jose L.; Strong, Michelle] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Moore, Forrest O.] St Josephs Med Ctr, Phoenix, AZ USA. [Spain, David A.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Purtill, Mary-Anne] St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. [Edwards, Byard] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Strauss, Jason] Orlando Reg Med Ctr Inc, Orlando, FL USA. [Durham, Rodney M.] Tampa Gen Hosp, Tampa, FL 33606 USA. [Duchesne, Juan C.] Tulane Univ, Med Ctr, New Orleans, LA USA. [Greiffenstein, Patrick] LSU New Orleans Hlth Sci Ctr, New Orleans, LA USA. [Cothren, C. Clay] Denver Hlth Med Ctr, Denver, CO USA. RP Phelan, HA (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd,E5-508A, Dallas, TX 75390 USA. EM herb.phelan@utsouthwestern.edu RI Evans, Heather/B-7620-2008; OI Tabbara, Malek/0000-0003-1046-7803; Gunn, Martin/0000-0001-9879-8660 NR 20 TC 29 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAR PY 2009 VL 66 IS 3 BP 641 EP 646 DI 10.1097/TA.0b013e3181991a0e PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 419ZU UT WOS:000264259000009 PM 19276732 ER PT J AU Reisner, SL Mimiaga, MJ Case, P Johnson, CV Safren, SA Mayer, KH AF Reisner, Sari L. Mimiaga, Matthew J. Case, Patricia Johnson, Carey V. Safren, Steven A. Mayer, Kenneth H. TI Predictors of Identifying as a Barebacker among High-Risk New England HIV Seronegative Men Who Have Sex with Men SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE HIV/AIDS; STIs; MSM; Bareback; Prevention ID NEW-YORK-CITY; UNPROTECTED ANAL INTERCOURSE; BISEXUAL MEN; CAGE QUESTIONNAIRE; POSITIVE GAY; UNSAFE SEX; PREVENTION; REDUCTION; KNOWLEDGE; INTERNET AB Studies have found that between 14% and 46% of US men who have sex with men (MSM) consistently report "barebacking" behavior (i.e., intentional unprotected anal intercourse) with other men. This is of public health significance because MSM continue to constitute more than 50% of new HIV infections in the USA. Men who self-identify as barebackers may represent a different and unique subset of MSM with distinct HIV prevention needs. In 2007, 227 HIV seronegative MSM recruited through modified respondent-driven sampling completed an interviewer-administered survey which assessed barebacker identity (i.e., personally identifying with the barebacker scene), demographics, sexual risk behaviors, psychosocial variables, and drug/alcohol use. Bivariate and multivariable logistic regression procedures were used to examine predictors of barebacker identity in relation to HIV risk behavior. Overall, 31% of participants identified as a barebacker. In bivariate analyses, lower education (OR = 1.76; 95% CI = 0.99-3.13; p < 0.05), a current drinking problem (OR = 2.34, 95% CI = 1.29-4.23; p < 0.01), higher levels of HIV treatment optimism (OR = 1.06; 95% CI = 1.01-1.12; p < 0.05), meeting sexual partners at private sex parties (OR = 2.47; 95% CI = 1.28-4.74; p < 0.01) or at bars/cubs (OR = 1.97; 95% CI = 1.10-3.52; p < 0.05), and engaging in serodiscordant unprotected insertive anal sex (OR = 3.42; 95% CI = 1.27-9.21; p < 0.01) significantly predicted barebacker identification compared to those with no barebacker identification. In a multivariable model, barebackers were more likely to screen in for alcohol abuse (adjusted OR = 2.16; 95% CI = 1.09-4.27; p < 0.05) and engage in serodiscordant unprotected insertive anal sex (adjusted OR = 3.17; 95% CI = 1.09-9.20; p < 0.05) compared to their non-barebacker counterparts. No significant differences were found in serodiscordant unprotected receptive anal sex between barebackers and non-barebackers. These findings suggest that barebacker identity is related to intentional HIV sexual risk taking and alcohol abuse. Furthermore, strategic positioning (i.e., engaging in insertive rather than receptive sex) might be associated with barebacker identification and may indicate a harm-reduction strategy being used among some HIV-uninfected MSM to reduce their risk of becoming infected. Additional research is warranted to understand the social identity of barebacking among MSM in order to develop more nuanced prevention strategies. C1 [Reisner, Sari L.; Mimiaga, Matthew J.; Case, Patricia; Johnson, Carey V.; Safren, Steven A.; Mayer, Kenneth H.] Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Case, Patricia] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Brown Med Sch, Providence, RI USA. RP Mimiaga, MJ (reprint author), Fenway Inst, Boston, MA USA. EM mmimiaga@fenwayhealth.org FU NIAID NIH HHS [P30 AI042853, P30 AI42853]; NIMH NIH HHS [R01 MH068746, R01MH068746] NR 42 TC 12 Z9 13 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD MAR PY 2009 VL 86 IS 2 BP 250 EP 262 DI 10.1007/s11524-008-9333-4 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 413MU UT WOS:000263798000009 PM 19051039 ER PT J AU Prasad, SM Ferreria, M Berry, AM Lipsitz, SR Richie, JP Gawande, AA Hu, JC AF Prasad, Sandip M. Ferreria, Marcos Berry, Alexander M. Lipsitz, Stuart R. Richie, Jerome P. Gawande, Atul A. Hu, Jim C. TI Surgical Apgar Outcome Score: Perioperative Risk Assessment for Radical Cystectomy SO JOURNAL OF UROLOGY LA English DT Article DE bladder; cystectomy; prognosis; perioperative complications; outcome and process assessment (health care) ID NONCARDIAC SURGERY; HEART-RATE; MORTALITY; CARE; COMPLICATIONS; QUALITY AB Purpose: Currently objective perioperative risk assessment metrics are lacking for radical cystectomy. Using a simple 10-point scale similar to neonatal Apgar assessment we evaluated whether a surgical outcome score calculated immediately after radical cystectomy would predict major complications and mortality. Materials and Methods: We identified 155 consecutive radical cystectomies performed between 2005 and 2007 at our institution. Data were collected on 45 preoperative and intraoperative variables. We used a framework established by the National Surgical Quality Improvement Program to evaluate major complications within 30 days of surgery. We used a 10-point scoring system that had been previously validated in general and vascular surgery populations, comprising estimated blood loss, lowest heart rate and lowest mean arterial pressure. Results: A total of 40 (26%) patients undergoing radical cystectomy experienced a major complication within 30 days of the operation. There was a progressive decrease in complications with increasing surgical Apgar score, in that patients with a low vs a high Apgar score were more likely to experience complications (OR 6.9, 95% CI 1.9-24.2). Coronary artery disease, American Society of Anesthesiologists class, intraoperative blood transfusion, volume of intravenous fluid administered and female gender were also associated with major complications (p < 0.05). Conclusions: In patients undergoing radical cystectomy the surgical Apgar score predicts major postoperative complications and death. This simple and objective postoperative metric may be used to dictate the intensity of care. Prospective studies are needed to determine whether treatment decisions based on this scoring system improve radical cystectomy outcomes. C1 [Prasad, Sandip M.; Ferreria, Marcos; Berry, Alexander M.; Richie, Jerome P.] Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. [Richie, Jerome P.; Hu, Jim C.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Lipsitz, Stuart R.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Richie, Jerome P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Hu, JC (reprint author), Brigham & Womens Hosp, Div Urol Surg, 75 Francis St, Boston, MA 02115 USA. EM jhu2@partners.org OI Gawande, Atul/0000-0002-1824-9176 NR 14 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 MAR PY 2009 VL 181 IS 3 BP 1046 EP 1052 DI 10.1016/j.juro.2008.10.165 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 406VA UT WOS:000263321800027 PM 19150094 ER PT J AU Cosmopoulos, K Pegtel, M Hawkins, J Moffett, H Novina, C Middeldorp, J Thorley-Lawson, DA AF Cosmopoulos, Katherine Pegtel, Michiel Hawkins, Jared Moffett, Howell Novina, Carl Middeldorp, Jaap Thorley-Lawson, David A. TI Comprehensive Profiling of Epstein-Barr Virus MicroRNAs in Nasopharyngeal Carcinoma SO JOURNAL OF VIROLOGY LA English DT Article ID BAMHI-A REGION; IMMUNE-SYSTEM; IN-VIVO; EBV; EXPRESSION; TRANSCRIPTION; CELLS; RNAS; IDENTIFICATION; INFECTION AB Epstein-Barr Virus (EBV) establishes a long-term latent infection and is associated with a number of human malignancies that are thought to arise from deregulation of different stages of the viral life cycle. Recently, a large number of microRNAs (miRNAs) have been described for EBV, and it has been suggested that their expression may vary between the different latency states found in normal and malignant tissue. To date, however, no technique has been utilized to comprehensively and quantitatively test this idea by profiling expression of the EBV miRNAs in primary infected tissues. We describe here a multiplex reverse transcription-PCR assay that allows the profiling of 39 of the 40 known mature EBV miRNAs from as little as 250 ng of RNA. With this approach, we present a comprehensive profile of EBV miRNAs in primary nasopharyngeal carcinoma (NPC) tumors including estimates of miRNA copy number per tumor cell. This is the first comprehensive profiling of EBV miRNAs in any EBV-associated tumor. In contrast to previous suggestions, we show that the BART-derived miRNAs are present in a wide range of copy numbers from <= 10(3) per cell in both primary tumors and the widely used NPC-derived C666-1 cell line. However, we confirm the hypothesis that the BHRF1 miRNAs are not expressed in NPC. Lastly, we demonstrate that EBV miRNA expression in the widely used NPC line C666-1 is, with some caveats, broadly representative of primary NPC tumors. C1 [Cosmopoulos, Katherine; Hawkins, Jared; Thorley-Lawson, David A.] Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. [Pegtel, Michiel; Middeldorp, Jaap] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands. [Moffett, Howell; Novina, Carl] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moffett, Howell; Novina, Carl] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Thorley-Lawson, DA (reprint author), Tufts Univ, Sch Med, Dept Pathol, Jaharis Bldg,150 Harrison Ave, Boston, MA 02111 USA. EM david.thorley-lawson@tufts.edu RI Pegtel, Dirk/M-8393-2015; OI Pegtel, Dirk/0000-0002-7357-4406; Hawkins, Jared/0000-0002-6352-1618; Middeldorp, Jaap/0000-0002-0765-4125 FU Public Health Service [R01 CA65883, R01 AI18757, RO1 AI062989] FX This study was supported by Public Health Service grants R01 CA65883, R01 AI18757, and RO1 AI062989 to D. A. T.- L. NR 40 TC 95 Z9 100 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR 1 PY 2009 VL 83 IS 5 BP 2357 EP 2367 DI 10.1128/JVI.02104-08 PG 11 WC Virology SC Virology GA 405GB UT WOS:000263209900029 PM 19091858 ER PT J AU Pery, E Rajendran, KS Brazier, AJ Gabuzda, D AF Pery, Erez Rajendran, Kottampatty S. Brazier, Andrew Jay Gabuzda, Dana TI Regulation of APOBEC3 Proteins by a Novel YXXL Motif in Human Immunodeficiency Virus Type 1 Vif and Simian Immunodeficiency Virus SIVagm Vif SO JOURNAL OF VIROLOGY LA English DT Article ID VIRION INFECTIVITY FACTOR; E3 UBIQUITIN LIGASE; EDITING ENZYME APOBEC3G; AMINO-ACID-RESIDUES; HIV-1 VIF; ANTIVIRAL ACTIVITY; SOCS-BOX; ENDOGENOUS RETROVIRUSES; CYTIDINE DEAMINATION; STRESS GRANULES AB The APOBEC3 cytidine deaminases are potent antiviral factors that restrict the replication of human immunodeficiency virus type 1 (HIV-1). In HIV-1-infected CD4(+) T cells, the viral accessory protein Vif binds to APOBEC3G (A3G), APOBEC3F (A3F), and APOBEC3C (A3C) and targets these proteins for polyubiquitination by forming an E3 ubiquitin ligase with cullin 5. Previous studies identified regions of HIV-1 Vif, (40)YRHHY(44) and (12)QVDRMR(17), which are important for interaction with A3G and A3F, respectively, and showed that Vif residues 54 to 71 are sufficient for A3G binding. Here, we identify (69)YXXL(72) as a novel conserved motif in HIV-1 Vif that mediates binding to human A3G and its subsequent degradation. Studies on other APOBEC3 proteins revealed that Tyr69 and Leu72 are important for the degradation of A3F and A3C as well. Similar to A3F, A3C regulation is also mediated by Vif residues (12)QVDRMR(17). Simian immunodeficiency virus (SIV) Vif was shown to bind and degrade African green monkey A3G (agmA3G) and, unexpectedly, human A3C. The YXXL motif of SIVagm Vif was important for the inactivation of agmA3G and human A3C. Unlike HIV- 1 Vif, however, SIVagm Vif does not require Tyr40 and His43 for agmA3G degradation. Tyr69 in the YXXL motif was critical for binding of recombinant glutathione S- transferase-Vif(1-94) to A3G in vitro. These results suggest that the YXXL motif in Vif is a potential target for small- molecule inhibitors to block Vif interaction with A3G, A3F, and A3C, and thereby protect cells against HIV- 1 infection. C1 [Pery, Erez; Rajendran, Kottampatty S.; Brazier, Andrew Jay; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Pery, Erez; Rajendran, Kottampatty S.; Brazier, Andrew Jay] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,CLS1010, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIH [AI67032, AI62555]; Harvard Center for AIDS Research (CFAR); DF/HCC Cancer Center FX This work was supported by NIH grants AI67032 and AI62555. Core facilities were supported by Harvard Center for AIDS Research (CFAR) and DF/HCC Cancer Center grants. NR 59 TC 63 Z9 65 U1 0 U2 1 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 MAR 1 PY 2009 VL 83 IS 5 BP 2374 EP 2381 DI 10.1128/JVI.01898-08 PG 8 WC Virology SC Virology GA 405GB UT WOS:000263209900031 PM 19109396 ER PT J AU Franco, RA Andrus, JG AF Franco, Ramon A. Andrus, Jennifer Gail TI Aerodynamic and Acoustic Characteristics of Voice Before and After Adduction Arytenopexy and Medialization Laryngoplasty with GORE-TEX in Patients with Unilateral Vocal Fold Immobility SO JOURNAL OF VOICE LA English DT Article CT 36th Annual Symposium of the Voice-Foundation CY MAY 29-JUN 03, 2007 CL Philadelphia, PA SP Voice Fdn DE Vocal fold immobility; Adduction arytenopexy; Medialization laryngoplasty; GORE-TEX; Voice; Maximum phonation time; Vocal paralysis; Unilateral vocal immobility ID THYROPLASTY TYPE-I; CORD PARALYSIS; CRICOTHYROID SUBLUXATION; PHONOSURGERY; DYSPHONIA; PITCH AB Multiple surgical techniques have been developed to restore function in patients with vocal fold paralysis (VFP), ranging from open laryngeal framework procedures to endoscopic injection techniques. In our experience, adduction arytenopexy (AA) and medialization laryngoplasty with GORE-TEX (MLG), with Or Without cricothyroid subluxation (CTS), together offer patients optimal improvement ill Voice, based on the Subjective change ill voice quality and patient feedback obtained. In this Study, we analyze objective voice parameters in these patients before and after surgery. The objective of this retrospective chart review is to demonstrate the change in aerodynamic and acoustic properties of voice in patients with VFP who undergo combined AA and MLG, with or without CTS. Seventy-five patients underwent combined AA and MLG between May 2001 and September 2006; 28 completed both preoperative and postoperative voice evaluation including aerodynamic and acoustic testing. Retrospective chart review is used to compare pre- and postoperative voice parameters in these patients. Statistically significant increases in mean maximum phonation time (MPT) and mean intensity of "/pae/" during aerodynamic testing, with a statistically significant decrease in mean glottal airflow were observed. A notable increase ill mean glottal resistance was not statistically significant. No significant change was observed in the other parameters tested. Mean MPT increased and mean glottal airflow decreased. These objective results correlate with patients' Subjective improvement. However, while "objective," acoustic and aerodynamic testing are effort dependent, and thus may not be as reliable as other tools in measuring postsurgical voice outcomes. Patient surveys may be the best means of gauging surgical success. C1 [Franco, Ramon A.; Andrus, Jennifer Gail] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. RP Franco, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. EM ramon_franco@meei.harvard.edu NR 37 TC 18 Z9 19 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0892-1997 J9 J VOICE JI J. Voice PD MAR PY 2009 VL 23 IS 2 BP 261 EP 267 DI 10.1016/j.jvoice.2007.09.009 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 420QB UT WOS:000264303200018 PM 18456455 ER PT J AU Odden, MC Shlipak, MG Tager, IB AF Odden, Michelle C. Shlipak, Michael G. Tager, Ira B. TI Serum Creatinine and Functional Limitation in Elderly Persons SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Aging; Creatinine; Kidney disease; Mobility limiation ID CHRONIC KIDNEY-DISEASE; BODY-COMPOSITION; CYSTATIN-C; EXERCISE CAPACITY; RENAL-FUNCTION; OLDER-PEOPLE; ADULTS; HEALTH; RISK; ASSOCIATION AB Creatinine is a commonly used measure of kidney function, but serum levels are also influenced by muscle mass. We hypothesized that higher serum creatinine would be associated with self-reported functional limitation in community-dwelling elderly. Subjects (n = 1,553) were participants in the Study of Physical Performance and Age-Related Changes in Sonomans, a cohort to study aging and physical function. We explored three strategies to account for the effects of muscle mass on serum creatinine. We observed a J-shaped association of creatinine with functional limitation. Above the study-specific mean creatinine (0.97 mg/dL in women and 1.15 mg/dL in men), the unadjusted odds ratio of functional limitation per standard deviation (0.20 mg/dL in women and 0.23 mg/dL in men) higher creatinine was 2.27 (95% confidence interval [CI] 1.75-2.94, p < .001) in women and 1.42 (95% CI 1.12-1.80, p = .003) in men. This association was inverted in persons with creatinine levels below the mean. Adjustment for muscle mass did not have an important effect on the association between creatinine and functional limitation. These associations remained after multivariable adjustment for demographics and health conditions but were statistically significant only in women. In elderly adults, higher creatinine levels are associated with functional limitation, consistent with prior literature that has demonstrated reduced physical performance in persons with kidney disease. However, the association of low creatinine levels with functional limitation suggests that creatinine levels are influenced by factors other than kidney function and muscle mass in the elderly. C1 [Odden, Michelle C.; Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA 94121 USA. [Odden, Michelle C.; Tager, Ira B.] Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. RP Odden, MC (reprint author), San Francisco VA Med Ctr, Dept Gen Internal Med, 4150 Clement St 111Al, San Francisco, CA 94121 USA. EM michelleodden@berkeley.edu FU National Institute on Aging [R01-AG09389, R01-AG027002] FX This study was supported by grant R01-AG09389 from the National Institute on Aging. Dr M. G. S. is supported by grant R01-AG027002 from the National Institute on Aging. NR 29 TC 24 Z9 24 U1 0 U2 1 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2009 VL 64 IS 3 BP 370 EP 376 DI 10.1093/gerona/gln037 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 419AC UT WOS:000264190500006 PM 19181716 ER PT J AU Neuwelt, EA Hamilton, BE Varallyay, CG Rooney, WR Edelman, RD Jacobs, PM Watnick, SG AF Neuwelt, Edward A. Hamilton, Bronwyn E. Varallyay, Csanad G. Rooney, William R. Edelman, Robert D. Jacobs, Paula M. Watnick, Suzanne G. TI Ultrasmall superparamagnetic iron oxides (USPIOs): a future alternative magnetic resonance (MR) contrast agent for patients at risk for nephrogenic systemic fibrosis (NSF)? SO KIDNEY INTERNATIONAL LA English DT Article DE nephrogenic systemic fibrosis; magnetic resonance imaging; ferumoxytol; i.v. iron ID CENTRAL-NERVOUS-SYSTEM; BRAIN-TUMORS; IN-VITRO; GADOLINIUM; FERUMOXTRAN-10; FERUMOXYTOL; ANGIOGRAPHY; NANOPARTICLES; FERUMOXIDES; PARTICLES AB Gadolinium (Gd) based contrast agents (GBCAs) in magnetic resonance imaging (MRI) are used in daily clinical practice and appear safe in most patients; however, nephrogenic systemic fibrosis (NSF) is a recently recognized severe complication associated with GBCAs. It affects primarily patients with renal disease, such as stage 4 or 5 chronic kidney disease (CKD; glomerular filtration rate < 30 ml/min per 1.73 m(2)), acute kidney injury, or kidney and liver transplant recipients with kidney dysfunction. Contrast-enhanced MRI and computed tomography (CT) scans provide important clinical information and influence patient management. An alternative contrast agent is needed to obtain adequate imaging results while avoiding the risk of NSF in this vulnerable patient group. One potential alternative is ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, which provide enhancement characteristics similar to GBCAs. We review our experience in approximately 150 patients on the potential benefits of the USPIOs ferumoxtran-10 and ferumoxytol. We focus on central nervous system (CNS) MRI but also review imaging of other vascular beds. Safety studies, including USPIO administration (ferumoxytol) as iron supplement therapy in CKD patients on and not on dialysis, suggest that decreased kidney function does not alter the safety profile. We conclude that for both CNS MR imaging and MR angiography, USPIO agents like ferumoxytol are a viable option for patients at risk for NSF. C1 [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol & Neurosurg, Portland, OR 97239 USA. [Neuwelt, Edward A.; Watnick, Suzanne G.] Portland VA Med Ctr, Portland, OR USA. [Hamilton, Bronwyn E.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. [Varallyay, Csanad G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Rooney, William R.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97239 USA. [Edelman, Robert D.] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. [Jacobs, Paula M.] NCI Frederick, SAIC Frederick Inc, Natl Canc Inst, Canc Imaging Program, Frederick, MD USA. [Watnick, Suzanne G.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol & Neurosurg, 3181 SW Sam Jackson Pk Rd,Mailcode L603, Portland, OR 97239 USA. EM neuwelte@ohsu.edu FU NIH [NS33618, NS34608, NS44687]; National Institute of Neurological Disorders and Stroke [NIB1B EB007258] FX This research was supported by a Veteran's Administration Merit Review Grant and NIH grants NS33618, NS34608, and NS44687 from the National Institute of Neurological Disorders and Stroke to EAN and NIB1B EB007258 to WDR. AMAG Pharmaceuticals Inc. donated ferumoxtran-10 and ferumoxytol. NR 28 TC 109 Z9 113 U1 2 U2 15 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 MAR PY 2009 VL 75 IS 5 BP 465 EP 474 DI 10.1038/ki.2008.496 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 406UJ UT WOS:000263320100010 PM 18843256 ER PT J AU Fried, LF AF Fried, Linda F. TI Creatinine and cystatin C: what are the values? SO KIDNEY INTERNATIONAL LA English DT Editorial Material AB Recent studies indicate that serum cystatin C is a better marker of glomerular filtration rate (GFR) and is a stronger predictor of cardiovascular disease and mortality than serum creatinine. Before cystatin C can gain wide acceptance, information about factors that affect generation, elimination, and analysis is needed. Stevens et al. analyze non-GFR-related factors associated with cystatin C and creatinine levels. The results will be useful in interpreting cystatin C levels in research and clinical practice. C1 [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Fried, Linda F.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Fried, Linda F.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. RP Fried, LF (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr,Mailstop 111F-U, Pittsburgh, PA 15240 USA. EM Linda.Fried@va.gov NR 9 TC 8 Z9 8 U1 0 U2 1 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 MAR PY 2009 VL 75 IS 6 BP 578 EP 580 DI 10.1038/ki.2008.688 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 412KH UT WOS:000263723200003 PM 19247381 ER PT J AU Kalra, MK Dang, P Singh, S Saini, S Shepard, JAO AF Kalra, Mannudeep K. Dang, Pragya Singh, Sarabjeet Saini, Sanjay Shepard, Jo-Anne O. TI In-Plane Shielding for CT: Effect of Off-Centering, Automatic Exposure Control and Shield-to-Surface Distance SO KOREAN JOURNAL OF RADIOLOGY LA English DT Article DE Tomography scanners; Computed tomography (CT); Radiation protection; Radiation dosage ID DOSE ASSESSMENT; IMAGE QUALITY; DOSIMETRY; TISSUES; EYE AB Objective: To assess effects of off-centering, automatic exposure control, and padding on attenuation values, noise, and radiation dose when using in-plane bismuth-based shields for CT scanning. Materials and Methods: A 30 cm anthropomorphic chest phantom was scanned on a 64-multidetector CT, with the center of the phantom aligned to the gantry isocenter. Scanning was repeated after placing a bismuth breast shield on the anterior surface with no gap and with 1, 2, and 6 cm of padding between the shield and the phantom surface. The "shielded" phantom was also scanned with combined modulation and off-centering of the phantom at 2 cm, 4 cm and 6 cm below the gantry isocenter. CT numbers, noise, and surface radiation dose were measured. The data were analyzed using an analysis of variance. Results: The in-plane shield was not associated with any significant increment for the surface dose or CT dose index volume, which was achieved by comparing the radiation dose measured by combined modulation technique to the fixed mAs (p > 0.05). Irrespective of the gap or the surface CT numbers, surface noise increased to a larger extent compared to Hounsfield unit (HU) (0-6 cm, 26-55%) and noise (0-6 cm, 30-40%) in the center. With off-centering, in-plane shielding devices are associated with less dose savings, although dose reduction was still higher than in the absence of shielding (0 cm off-center, 90% dose reduction; 2 cm, 61%) (p < 0.0001). Streak artifacts were noted at 0 cm and 1 cm gaps but not at 2 cm and 6 cm gaps of shielding to the surface distances. Conclusion: In-plane shields are associated with greater image noise, artifactually increased attenuation values, and streak artifacts. However, shields reduce radiation dose regardless of the extent of off-centering. Automatic exposure control did not increase radiation dose when using a shield. C1 [Kalra, Mannudeep K.; Dang, Pragya; Singh, Sarabjeet; Saini, Sanjay; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400, Boston, MA 02114 USA. EM mkalra@partners.org NR 13 TC 33 Z9 37 U1 1 U2 3 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 J9 KOREAN J RADIOL JI Korean J. Radiol. PD MAR-APR PY 2009 VL 10 IS 2 BP 156 EP 163 DI 10.3348/kjr.2009.10.2.156 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 422JA UT WOS:000264422500009 PM 19270862 ER PT J AU DeMatteo, RP Ballman, KV Antonescu, CR Maki, RG Pisters, PWT Demetri, GD Blackstein, ME Blanke, CD von Mehren, M Brennan, MF Patel, S McCarter, MD Polikoff, JA Tan, BR Owzar, K AF DeMatteo, Ronald P. Ballman, Karla V. Antonescu, Cristina R. Maki, Robert G. Pisters, Peter W. T. Demetri, George D. Blackstein, Martin E. Blanke, Charles D. von Mehren, Margaret Brennan, Murray F. Patel, Shreyaskumar McCarter, Martin D. Polikoff, Jonathan A. Tan, Benjamin R. Owzar, Kouros CA ACOSOG Intergrp Adjuvant GIST Stud TI Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial SO LANCET LA English DT Article ID TYROSINE KINASE; PROGNOSTIC-FACTORS; DOSE IMATINIB; PHASE-III; KIT; MUTATIONS; RESISTANCE; INHIBITOR; SURVIVAL; PROGRESSION AB Background Gastrointestinal stromal tumour is the most common sarcoma of the intestinal tract. Imatinib mesylate is a small molecule that inhibits activation of the KIT and platelet-derived growth factor receptor a proteins, and is effective in first-fine treatment of metastatic gastrointestinal stromal tumour. We postulated that adjuvant treatment with imatinib would improve recurrence-free survival compared with placebo after, resection of localised, primary gastrointestinal stromal tumour. Methods We undertook a randomised phase III, double-blind, placebo-controlled, multicentre trial. Eligible patients had complete gross resection of a primary gastrointestinal stromal tumour-at least 3 cm in size and positive for the KIT protein by immunohistochemistry. Patients were randomly assigned, by A stratified biased coin design, to imatinib 400 mg (n=359) or to placebo (n=354) daily for 1 year after surgical resection. Patients and investigators were blinded to the treatment group. Patients assigned to placebo were eligible to crossover to imatinib treatment in the event of tumour recurrence. The primary endpoint was recurrence-free survival, and analysis was by intention to treat. Accrual was stopped early because the trial results crossed the interim analysis efficacy boundary for recurrence-free survival. This study is registered with ClinicalTrials.gov, number NCT00041197. Findings All randomised patients were included in the analysis. At median follow-up of 19.7 months (minimum-maximum 0-56-4), 30 (8%) patients in the imatinib group and 70 (20%) in the placebo group had had tumour recurrence or had died. Imatinib significantly improved recurrence-free survival compared with placebo (98% [95% CI 96-100] vs 83% [78-88] at 1 year; hazard ratio [HR] 0.35 [0.22-0.53]; one-sided p<0.0001). Adjuvant imatinib was well tolerated, with the most common serious events being dermatitis (11 [3%] vs 0), abdominal pain (12 [3%] vs six [1%]), and diarrhoea (ten [2%] vs five [1%]) in the imatinib group and hyperglycaemia (two [<1%] vs seven [2%]) in the placebo group. Interpretation Adjuvant imatinib therapy is safe and seems to improve recurrence-free survival compared with placebo after the resection of primary gastrointestinal stromal tumour. Funding US National Institutes of Health and Novartis Pharmaceuticals. C1 [DeMatteo, Ronald P.; Antonescu, Cristina R.; Maki, Robert G.; Brennan, Murray F.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Ballman, Karla V.] Mayo Clin, Rochester, MN USA. [Pisters, Peter W. T.; Patel, Shreyaskumar] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Blackstein, Martin E.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Blanke, Charles D.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Blanke, Charles D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [von Mehren, Margaret] Fox Chase Canc Ctr, Philadelphia, PA USA. [McCarter, Martin D.] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Polikoff, Jonathan A.] Kaiser Permanente So Calif, San Diego, CA USA. [Tan, Benjamin R.] Washington Univ, Sch Med, St Louis, MO USA. [Owzar, Kouros] Duke Univ, Durham, NC USA. RP DeMatteo, RP (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM dematter@mskcc.org OI Ballman, Karla/0000-0002-4492-0357; Brennan, Murray/0000-0003-2358-4371 FU American College of Surgeons Oncology Group (ACOSOG) and the National Cancer Institute (NCI) [ACOSOG Z9001]; Novartis and NCI under CRADA [1111.1]; Public Health Service Grants [U10 CA076001]; National Cancer Institute [CA94503, CA102613]; National Institutes of Health; Novartis FX The ACOSOG Z9001 trial was undertaken through a collaboration between the American College of Surgeons Oncology Group (ACOSOG) and the National Cancer Institute (NCI) and through a contract between Novartis and NCI under CRADA 1111.1. This work was supported by Public Health Service Grants U10 CA076001 (ACOSOG) and CA94503 and CA102613 (RPD) from the National Cancer Institute, National Institutes of Health, and by Novartis, who provided imatinib and the placebo. The views expressed are those of the authors and do not necessarily represent the official views of the National Cancer Institute. We are indebted to members of CTEP who made this trial possible. The trial was endorsed by the Southwest Oncology Group (SWC)G), Cancer and Leukemia Group B (CALGB), Eastern Cooperative Oncology Group (ECOG), and the National Cancer Institute of Canada (NCI-C), all of which participated through the Cancer Trials Support Unit (CTSU). We thank Samuel A Wells Jr and Vijaya Chadararn who were instrumental in the development and early conduct of this trial, and Sue Budinger who coordinated the study; Chris Corless for providing assistance with pathological review; and Linda McCall for doing the analyses and creating the tables and graphs. NR 30 TC 536 Z9 595 U1 2 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAR-APR PY 2009 VL 373 IS 9669 BP 1097 EP 1104 DI 10.1016/S0140-6736(09)60500-6 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 427IS UT WOS:000264773600030 PM 19303137 ER PT J AU Avram, MM Tope, WD Yu, T Szachowicz, E Nelson, JS AF Avram, Mathew M. Tope, Whitney D. Yu, Thomas Szachowicz, Edward Nelson, J. Stuart TI Hypertrophic Scarring of the Neck Following Ablative Fractional Carbon Dioxide Laser Resurfacing SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE fractional resurfacing; fractional photothermolysis; ablative fractional resurfacing; CO(2) laser resurfacing; fractional CO(2) resurfacing; laser complications; hypertrophic scar; Fraxel; neck rejuvenation ID FACIAL SKIN; PHOTOTHERMOLYSIS; DEVICE AB Background: Ablative fractional carbon dioxide (CO(2)) laser treatments have gained popularity due to their efficacy, shortened downtime, and decreased potential for scarring in comparison to traditional ablative CO(2) resurfacing. To date, scarring with fractional CO(2) lasers has not been reported. Objective: Five patients treated with the same fractional CO(2) laser technology for photodamage of the neck were referred to our practices 1-3 months after treatment. Each patient developed scarring. Of the five cases, two are discussed in detail. The first was treated under general anesthesia on the face and anterior neck at a pulse energy of 30 mJ (859 mu m depth) with 2517( coverage. Eleven days after treatment, three non-healing areas along the horizontal skin folds of the anterior neck were noted. At 2 weeks after CO., ablative fractional resurfacing, these areas had become thickened. These raised areas were treated with a non-ablative fractionated 1,550 nm laser to modify the wound healing milieu. One week later, distinct firm pale papules in linear arrays with mild hypopigmentation had developed along involved neck skin folds. Skin biopsy was performed. For the second patient, the neck was treated at a pulse energy of 20 mJ (630 mu m depth) with 30% coverage of the exposed skin, with a total treatment energy of 5.0 kJ. Minimal crusting was noted on the neck throughout the initial healing phase of 2 weeks. She then experienced tightness on her neck. Approximately 3 weeks after treatment, she developed multiple vertical and horizontal hypertrophic scars (HS). Results: Histopathology for the first case confirmed the presence of a hypertrophic sear. The papules in this case completely resolved with mild residual hypopigmentation after treatment with topical corticosteroids. HS failed to resolve in the second case to date after 1 month. Conclusion: As with traditional ablative CO(2) laser resurfacing, HS is a potential complication of ablative fractional CO(2) laser resurfacing, particularly on the neck. With early diagnosis and appropriate treatment HS of neck skin may be reversible. We urge caution when treating the neck with this device and close attention to Wound care in the post-operative period. Lasers Surg. Med. 41:185-1.88, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Avram, Mathew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Tope, Whitney D.] Advancements Dermatol, Edina, MN USA. [Yu, Thomas] Dermatol & Clin Skin Care Ctr, Bethesda, MD USA. [Szachowicz, Edward] Facial Plast Surg, Edina, MN USA. [Nelson, J. Stuart] Univ Calif Irvine, Beckman Laser Inst, Irvine, CA USA. RP Avram, MM (reprint author), 50 Staniford St,Suite 250, Boston, MA 02114 USA. EM mavram@partners.org FU NCRR NIH HHS [P41 RR001192, P41 RR001192-30] NR 8 TC 86 Z9 86 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2009 VL 41 IS 3 BP 185 EP 188 DI 10.1002/lsm.20755 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 430SC UT WOS:000265007800002 PM 19291746 ER PT J AU Roodman, GD AF Roodman, G. D. TI Pathogenesis of myeloma bone disease SO LEUKEMIA LA English DT Review DE multiple myeloma; osteoclast; osteoblast; bone disease ID KAPPA-B LIGAND; OSTEOCLAST DIFFERENTIATION FACTOR; ADVANCED MULTIPLE-MYELOMA; TUMOR-NECROSIS-FACTOR; RECEPTOR ACTIVATOR; IN-VIVO; INHIBITS OSTEOCLASTOGENESIS; OSTEOBLAST DIFFERENTIATION; MARROW MICROENVIRONMENT; OSTEOPROTEGERIN LIGAND AB Bone disease in multiple myeloma (MM) is characterized by lytic bone lesions, which can cause severe bone pain, pathologic fractures and hypercalcemia. However, the lytic bone disease in MM differs from that in other cancer patients who have lytic bone metastases. Although increased osteoclastic bone destruction is involved in MM and other tumors involving bone, in contrast to other tumors, once the MM tumor burden exceeds 50% in a local area, osteoblast activity is either suppressed or absent. 1 The basis for this severe imbalance between increased osteoclastic bone resorption and decreased bone formation has been a topic of intensive investigation over the last several years and will be reviewed in this article. C1 Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Dept Med Hematol Oncol, Sch Med, Pittsburgh, PA 15240 USA. RP Roodman, GD (reprint author), Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Dept Med Hematol Oncol, Sch Med, Res & Dev 151-U,Univ Dr C,Room 2E113, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu FU Multiple Myeloma Research Foundation; Department of Veteran's Affairs FX Preparation of this article was made possible by research funds from the Multiple Myeloma Research Foundation and from the Department of Veteran's Affairs (VA Merit Review Award). The materials are the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System, Research and Development. NR 75 TC 137 Z9 146 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2009 VL 23 IS 3 BP 435 EP 441 DI 10.1038/leu.2008.336 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 416VC UT WOS:000264032600002 PM 19039321 ER PT J AU Gray, RJ AF Gray, Robert J. TI Weighted analyses for cohort sampling designs SO LIFETIME DATA ANALYSIS LA English DT Article DE Subsampling; Horvitz-Thompson estimators; Cumulative hazard estimator; Cross-validation; Case-control study; Case-cohort design ID MODELS AB Weighted analysis methods are considered for cohort sampling designs that allow subsampling of both cases and non-cases, but with cases generally sampled more intensively. The methods fit into the general framework for the analysis of survey sampling designs considered by Lin (Biometrika 87:37-47, 2000). Details are given for applying the general methodology in this setting. In addition to considering proportional hazards regression, methods for evaluating the representativeness of the sample and for estimating event-free probabilities are given. In a small simulation study, the one-sample cumulative hazard estimator and its variance estimator were found to be nearly unbiased, but the true coverage probabilities of confidence intervals computed from these sometimes deviated significantly from the nominal levels. Methods for cross-validation and for bootstrap resampling, which take into account the dependencies in the sample, are also considered. C1 Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Gray, RJ (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM gray@jimmy.harvard.edu NR 19 TC 26 Z9 26 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD MAR PY 2009 VL 15 IS 1 BP 24 EP 40 DI 10.1007/s10985-008-9095-z PG 17 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 394WG UT WOS:000262483200002 PM 18712477 ER PT J AU Ghebremichael, M AF Ghebremichael, Musie TI Nonparametric estimation of mean residual functions SO LIFETIME DATA ANALYSIS LA English DT Article DE Mean residual life function; Strong uniform consistency; Survival function ID LIFE PROCESSES; THERAPY AB Situations frequently arise in practice in which mean residual life (mrl) functions must be ordered. For example, in a clinical trial of three experiments, let e (1), e (2) and e (3) be the mrl functions, respectively, for the disease groups under the standard and experimental treatments, and for the disease-free group. The well-documented mrl functions e (1) and e (3) can be used to generate a better estimate for e (2) under the mrl restriction e (1) a parts per thousand currency sign e (2) a parts per thousand currency sign e (3). In this paper we propose nonparametric estimators of the mean residual life function where both upper and lower bounds are given. Small and large sample properties of the estimators are explored. Simulation study shows that the proposed estimators have uniformly smaller mean squared error compared to the unrestricted empirical mrl functions. The proposed estimators are illustrated using a real data set from a cancer clinical trial study. C1 [Ghebremichael, Musie] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Ghebremichael, Musie] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ghebremichael, M (reprint author), Harvard Univ, Dept Biostat, 3 Blackfan Circle,CLS 11045, Boston, MA 02115 USA. EM musie@jimmy.harvard.edu NR 17 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD MAR PY 2009 VL 15 IS 1 BP 107 EP 119 DI 10.1007/s10985-008-9089-x PG 13 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 394WG UT WOS:000262483200006 PM 18543101 ER PT J AU Posse, S Otazo, R Tsai, SY Yoshimoto, AE Lin, FH AF Posse, Stefan Otazo, Ricardo Tsai, Shang-Yueh Yoshimoto, Akio Ernesto Lin, Fa-Hsuan TI Single-Shot Magnetic Resonance Spectroscopic Imaging with Partial Parallel Imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the International-Society-of-Magnetic-Resonance-in-Medicine/European-Society -of-Magnetic-Resonance-in-Medicine-and-Biology CY MAY 12-18, 2007 CL Berlin, GERMANY SP Int Soc Magnet Resonance Med, European Soc Magnet Resonance Med & Biol DE magnetic resonance spectroscopic imaging; single-shot encoding; proton-echo-planar-spectroscopic-imaging; parallel imaging; SENSE; spectral quantification ID TO-NOISE RATIO; HUMAN BRAIN; HYPERPOLARIZED C-13; IN-VIVO; SPIN-ECHOES; ARRAY COIL; 4 TESLA; DIFFUSION; NMR; RECONSTRUCTION AB A magnetic resonance spectroscopic imaging (MRSI) pulse sequence based on proton-echo-planar-spectroscopic-imaging (PEPSI) is introduced that measures two-dimensional metabolite maps in a single excitation. Echo-planar spatial-spectral encoding was combined with interleaved phase encoding and parallel imaging using SENSE to reconstruct absorption mode spectra. The symmetrical k-space trajectory compensates phase errors due to convolution of spatial and spectral encoding. Single-shot MRSI at short TE was evaluated in phantoms and in vivo on a 3-T whole-body scanner equipped with a 12-channel array coil. Four-step interleaved phase encoding and fourfold SENSE acceleration were used to encode a 16 x 16 spatial matrix with a 390-Hz spectral width. Comparison with conventional PEPSI and PEPSI with fourfold SENSE acceleration demonstrated comparable sensitivity per unit time when taking into account g-factor-related noise increases and differences in sampling efficiency. LCModel fitting enabled quantification of inositol, choline, creatine, and N-acetyl-aspartate (NAA) in vivo with concentration values in the ranges measured with conventional PEPSI and SENSE-accelerated PEPSI. Cramer-Rao lower bounds were comparable to those obtained with conventional SENSE-accelerated PEPSI at the same voxel size and measurement time. This single-shot MRSI method is therefore suitable for applications that require high temporal resolution to monitor temporal dynamics or to reduce sensitivity to tissue movement. Magn Reson Med 61:541-547, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Posse, Stefan] Univ New Mexico, Sch Med, Dept Neurol, Albuquerque, NM 87131 USA. [Posse, Stefan; Otazo, Ricardo; Yoshimoto, Akio Ernesto] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Tsai, Shang-Yueh] Chang Gung Univ, Dept Elect Engn, Taipei, Taiwan. [Lin, Fa-Hsuan] Harvard Univ, Massachusetts Gen Hosp, MIT, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Lin, Fa-Hsuan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. RP Posse, S (reprint author), Univ New Mexico, Sch Med, Dept Neurol, MSC10 5620, Albuquerque, NM 87131 USA. EM sposse@unm.edu RI Lin, Fa-Hsuan/G-6988-2012; Tsai, Shang-Yueh/O-2226-2013; OI Lin, Fa-Hsuan/0000-0002-9539-1731; Tsai, Shang-Yueh/0000-0002-6310-4750; Otazo, Ricardo/0000-0002-3782-4930 FU NCRR NIH HHS [P41 RR014075, P41 RR14075]; NIBIB NIH HHS [R01 EB000790, R01 EB000790-04, R21 EB007298, R21 EB007298-02]; NICHD NIH HHS [R01 HD040712]; NIDA NIH HHS [R01 DA014178, R01 DA14178-01]; NINDS NIH HHS [R01 NS037462] NR 39 TC 17 Z9 17 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAR PY 2009 VL 61 IS 3 BP 541 EP 547 DI 10.1002/mrm.21855 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 410WF UT WOS:000263608300006 PM 19097245 ER PT J AU Fukuoka, Y Oostendorp, TF Armoundas, AA AF Fukuoka, Yutaka Oostendorp, Thom F. Armoundas, Antonis A. TI Method for guiding the ablation catheter to the ablation site: a simulation and experimental study SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE Ablation; Cardiac arrhythmias; Catheter guiding; Body surface potentials; Equivalent dipole ID MOVING DIPOLE MODEL; VENTRICULAR-TACHYCARDIA; CARDIAC ELECTROPHYSIOLOGY; ELECTRICAL ACTIVATION; MYOCARDIAL-INFARCTION; NONCONTACT CATHETER; MAPPING TECHNIQUE; SINUS RHYTHM; TORSO MODEL; HUMAN-HEART AB Radiofrequency catheter ablation (RCA) procedures for treating ventricular arrhythmias have evolved significantly over the past several years; however, the use of RCA has been limited due to the difficulty in identifying the appropriate site for ablation. In this study, we investigate the accuracy of a computer algorithm to guide the tip of an ablation catheter to the exit site of the scar tissue or the site of abnormal automaticity (the "target site"). This algorithm involves modeling the body surface potentials corresponding to the wavefront at the target site for ablation and current pulses generated from a pair of electrodes at the tip of the ablation catheter with a single equivalent moving dipole (SEMD) in an infinite homogeneous volume conductor. Despite the fact that the use of the homogeneous volume conductor introduces systematic error in the estimated compared to the true dipole location, we find that the systematic error had minor influence in the ability of the algorithm to accurately guide the tip of the ablation catheter to the ablation site and the overall error (1.9 +/- A 1.1 mm) in the left ventricle is adequate for RCA procedures. These results were verified, in saline tank studies in which the distance between the dipole due to the catheter tip and the dipole due to the target site was found to be 2.66 +/- A 0.52 mm. In conclusion, our algorithm to estimate the SEMD parameters from body surface potentials can potentially be a useful method to rapidly and accurately guide the catheter tip to the arrhythmic site during an RCA procedure. C1 [Fukuoka, Yutaka] Tokyo Med & Dent Univ, Sch Biomed Sci, Tokyo, Japan. [Oostendorp, Thom F.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM aarmoundas@partners.org RI Oostendorp, Thom/B-9648-2013 FU American Heart Association [0365304U, 0635127 N] FX The work was supported by a Beginning Grant-in-Aid (#0365304U) and a Scientist Development Grant (#0635127 N) American Heart Association awards. NR 28 TC 5 Z9 7 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD MAR PY 2009 VL 47 IS 3 BP 267 EP 278 DI 10.1007/s11517-009-0441-4 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA 413YB UT WOS:000263830000004 PM 19194733 ER PT J AU Iezzoni, LI AF Iezzoni, Lisa I. TI Reinvigorating the Quality Improvement Incentives of Hospital Prospective Payment SO MEDICAL CARE LA English DT Editorial Material ID PERFORMANCE; ADMISSION; MEDICARE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Iezzoni, LI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@partners.org NR 14 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 2009 VL 47 IS 3 BP 269 EP 271 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 412VT UT WOS:000263753000001 PM 19194335 ER PT J AU Hysong, SJ AF Hysong, Sylvia J. TI Meta-Analysis Audit and Feedback Features Impact Effectiveness on Care Quality SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Annual Research Meeting of the Academy-Health CT Academy Health Annual Research Meeting CY JUN 09-10, 2008 CY JUN 08-10, 2008 CL Washington, DC CL Washington, DC SP Acad Hlth SP Acad Hlth DE audit and feedback; feedback intervention theory; meta-analysis; quality of health care; health services research ID RANDOMIZED CONTROLLED-TRIAL; CLINICAL-PRACTICE; PERFORMANCE; INTERVENTIONS; IMPROVE AB Background: Audit and feedback (A&F) has long been used to improve quality of care, albeit with variable results. This meta-analytic study tested whether Feedback Intervention Theory, a framework from industrial/organizational psychology, explains the observed variability in health care A&F research. Method: Data source: studies cited by Jamtvedt's 2006 Cochrane systematic review of A&F, followed by database searches using the Cochrane review's search strategy to identify more recent studies. Inclusion criteria: Cochrane review criteria, plus: presence of a treatment group receiving only A & F; a control group receiving no intervention; a quantitatively measurable outcome; minimum n of 10 per arm; sufficient statistics for effect size calculations. Moderators: presence of discouragement and praise; correct solution, attainment level, velocity, frequency, and non-native information; feedback format (verbal, textual, graphic, public, computerized, group vs. individual); goal setting activity. Procedure: meta-analytic procedures using the Hedges-Olkin method. Results: Of 519 studies initially identified, 19 met all inclusion criteria. Studies were most often excluded due to the lack of a feedback-only ann. A&F has a modest, though significant positive effect on quality outcomes (d = 0.40, 95% confidence interval +/- 0.20); providing specific Suggestions for improvement, written, and more frequent feedback strengthened this effect, whereas graphical and verbal feedback attenuated this effect. Conclusions: A&F effectiveness is improved when feedback is delivered with specific suggestions for improvement, in writing, and frequently. Other feedback characteristics Could also potentially improve effectiveness; however, research with stricter experimental controls is needed to identify the specific feedback characteristics that maximize its effectiveness. C1 [Hysong, Sylvia J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Hysong, Sylvia J.] Dept Vet Affairs Med Ctr, Hlth Serv, Res & Dev Serv, Houston VA HSR&D Ctr Excellence, Houston, TX USA. RP Hysong, SJ (reprint author), Baylor Coll Med, Dept Med, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hysong@bcm.tmc.edu RI Hysong, Sylvia/B-8420-2008 OI Hysong, Sylvia/0000-0002-9063-5207 FU NHLBI NIH HHS [1R01HL079173, R01 HL079173] NR 29 TC 109 Z9 111 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD MAR PY 2009 VL 47 IS 3 BP 356 EP 363 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 412VT UT WOS:000263753000013 PM 19194332 ER PT J AU Wolf, MS Shekelle, P Choudhry, NK Agnew-Blais, J Parker, RM Shrank, WH AF Wolf, Michael S. Shekelle, Paul Choudhry, Niteesh K. Agnew-Blais, Jessica Parker, Ruth M. Shrank, William H. TI Variability in Pharmacy Interpretations of Physician Prescriptions SO MEDICAL CARE LA English DT Article DE pharmacy; physician; prescription; sig; instruction; medication; variability; health literacy ID DRUG WARNING LABELS; LOW-LITERACY; MEDICATIONS AB Background: The clarity of prescription drug instructions is a health literacy and medication safety concern. Objective: To assess the variability of pharmacy interpretations of physician prescriptions. Design: Identically written prescriptions for 4 common medications (atorvastatin, alendronate, trimethoprim/sulfamethoxazole, ibuprofen) were filled in 6 pharmacies (2 largest chains, 2 grocery stores, 2 independents) in 4 cities (Boston, Chicago, Los Angeles, Austin). Measurement: Components of the instruction were coded as dose, frequency, administration route, timing, indication, and auxiliary instructions. Results: In all, 85 labels were evaluated. Dose frequency was omitted on 6% of instructions ("take 1 tablet for cholesterol"). Timing was explicitly stated on 2% of instructions ("in the morning"). All prescriptions included indications; pharmacies transcribed these onto 38% of labels. The prescription for alendronate stated not to lie down for at least 30 minutes after taking; this was transcribed with 50% of instructions. Reading difficulty was above recommended levels for 46% of instructions; with 14% greater than a high school level. Conclusions: Efforts are needed to ensure patients receive clear, consistent information supporting safe medication use. C1 [Wolf, Michael S.] Northwestern Univ, Inst Healthcare Studies, Ctr Commun Healthcare, Hlth Literacy & Learning Program,Feinberg Sch Med, Chicago, IL 60611 USA. [Wolf, Michael S.] Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Chicago, IL 60611 USA. [Choudhry, Niteesh K.; Agnew-Blais, Jessica; Shrank, William H.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Choudhry, Niteesh K.; Agnew-Blais, Jessica; Shrank, William H.] Harvard Univ, Sch Med, Boston, MA USA. [Parker, Ruth M.] Emory Univ, Sch Med, Atlanta, GA USA. [Shekelle, Paul] Greater Los Angeles Vet Affairs Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. RP Wolf, MS (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA. EM mswolf@northwestern.edu RI Agnew-Blais, Jessica/L-9236-2015 OI Agnew-Blais, Jessica/0000-0002-0755-6867 FU American College of Physicians Foundation; Disease Control and Prevention Career Development Award [K01 EF1000067-01] FX Supported by grants from the Prescription Drug Labeling Project funded by the American College of Physicians Foundation, and by a Centers for Disease Control and Prevention Career Development Award K01 EF1000067-01 (to M.S.W.) NR 18 TC 31 Z9 32 U1 0 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 MAR PY 2009 VL 47 IS 3 BP 370 EP 373 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 412VT UT WOS:000263753000015 PM 19194338 ER PT J AU Matheny, ME Morrow, DA Ohno-Machado, L Cannon, CP Sabatine, MS Resnic, FS AF Matheny, Michael E. Morrow, David A. Ohno-Machado, Lucila Cannon, Christopher P. Sabatine, Marc S. Resnic, Frederic S. TI Validation of an Automated Safety Surveillance System with Prospective, Randomized Trial Data SO MEDICAL DECISION MAKING LA English DT Article DE risk adjustment; risk stratification; decision support techniques; cardiology ID INTERVENTIONAL CARDIOLOGY; MYOCARDIAL-INFARCTION; CARDIAC-SURGERY; MORTALITY; METHODOLOGY; SHIPMAN; THERAPY; ASPIRIN; BRISTOL; MODELS AB Objective. We sought to validate 3 methods for automated safety monitoring by evaluating clinical trials with elevated adverse events. Methods. An automated outcomes surveillance system was used to retrospectively analyze data from 2 randomized, TIMI multicenter trials. Trial A was stopped early due to elevated 30-day mortality rates in the intervention arm. Trial B was not stopped early, but there was transient concern regarding 30-day intracranial hemorrhage rates. We compared statistical process control (SPC), logistic regression risk adjusted SPC (LR-SPC), and Bayesian updating statistic (BUS) methods with a standard prospective 2-arm event rate analysis. Each method compares observed event rates to alerting boundaries established with previously collected data. In this evaluation, the control arms approximated prior data, and the intervention arms approximated the observed data. Results. Trial A experienced elevated 30-day mortality rates beginning 7 months after the start of the trial and continuing until termination at month 14. Trial B did not experience elevated major bleeding rates. Combining the alerting performance of each method across both trials resulted in sensitivities and specificities of 100% and 85% for SPC, 0% and 100% for BUS, and 100% and 93% for both LR-SPC models, respectively. Conclusion. Both SPC and LR-SPC methods correctly identified the majority of months during which the cumulative event rates were elevated in trial A but were susceptible to false positive alerts in trial B. The BUS method did not result in any alerts in either trial and requires revision. C1 [Matheny, Michael E.; Ohno-Machado, Lucila; Resnic, Frederic S.] Brigham & Womens Hosp, Dept Radiol, Decis Syst Grp, Boston, MA 02115 USA. [Matheny, Michael E.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Morrow, David A.; Cannon, Christopher P.; Sabatine, Marc S.; Resnic, Frederic S.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Morrow, David A.; Cannon, Christopher P.; Sabatine, Marc S.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Ohno-Machado, Lucila] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Matheny, ME (reprint author), 1310 24th Ave S,GRECC,Room 4-B110, Nashville, TN 37212 USA. EM michael.matheny@vanderbilt.edu OI Ohno-Machado, Lucila/0000-0002-8005-7327; Matheny, Michael/0000-0003-3217-4147 FU National Institutes of Health [T15-LM-007092, R01-LM-008142, R01-LM-009520] FX This study was funded in part by grants T15-LM-007092, R01-LM-008142, and R01-LM-009520 from the National Library of Medicine of the National Institutes of Health. NR 28 TC 9 Z9 9 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAR PY 2009 VL 29 IS 2 BP 247 EP 256 DI 10.1177/0272989X08327110 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 432CB UT WOS:000265110000011 PM 19015285 ER PT J AU Bianchi, MT Pathmanathan, J Cash, SS AF Bianchi, Matt T. Pathmanathan, Jay Cash, Sydney S. TI From ion channels to complex networks: Magic bullet versus magic shotgun approaches to anticonvulsant pharmacotherapy SO MEDICAL HYPOTHESES LA English DT Review ID TEMPORAL-LOBE EPILEPSY; P/Q-TYPE CA2+; ANTIEPILEPTIC DRUG LEVETIRACETAM; SENSITIVE POTASSIUM CHANNELS; CULTURED HIPPOCAMPAL-NEURONS; GLYCINE RECEPTOR CHANNELS; CEREBELLAR GRANULE CELLS; PRIMARY AFFERENT NEURONS; CA1 PYRAMIDAL CELLS; DORSAL-HORN NEURONS AB Medical management and drug development for epilepsy emphasizes increasing pharmacological specificity to improve efficacy while minimizing side effects. However, growing evidence supports potential benefits of "magic shotgun" over "magic bullet" approaches to treatment of complex disease processes. We discuss experimental and theoretical evidence suggesting that seizures may be more amenable to a multi-target rather than a high-specificity approach. including evidence that individual anticonvulsants directly modulate a variety ion channel targets, the most direct determinants of neuronal excitability. Although the relevance of this promiscuity remains untested, it may contribute to anticonvulsant efficacy and should therefore be considered in drug development strategies and in therapeutic decision making. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Bianchi, Matt T.] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Pathmanathan, Jay; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Bianchi, MT (reprint author), Beth Israel Deaconess Med Ctr, 300 Brooklin Ave,KS-4, Boston, MA 02115 USA. EM thebianchi@gmail.com NR 188 TC 22 Z9 23 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD MAR PY 2009 VL 72 IS 3 BP 297 EP 305 DI 10.1016/j.mehy.2008.09.049 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 416WK UT WOS:000264036000018 PM 19046822 ER PT J AU Chen, Y Liu, B O'Connor, JM Didier, CS Glick, SJ AF Chen, Yu Liu, Bob O'Connor, J. Michael Didier, Clay S. Glick, Stephen J. TI Characterization of scatter in cone-beam CT breast imaging: Comparison of experimental measurements and Monte Carlo simulation SO MEDICAL PHYSICS LA English DT Article DE Compton effect; computerised tomography; image reconstruction; Monte Carlo methods; phantoms; Rayleigh scattering; X-ray scattering ID FLAT-PANEL IMAGER; X-RAY SCATTER; COMPUTED-TOMOGRAPHY; VEILING GLARE; RADIATION; MAMMOGRAPHY; DETECTORS; QUALITY; TOOLKIT; PHYSICS AB It is commonly understood that scattered radiation in x-ray computed tomography (CT) degrades the reconstructed image. As a precursor to developing scatter compensation methods, it is important to characterize this scatter using both empirical measurements and Monte Carlo simulations. Previous studies characterizing scatter using both experimental measurements and Monte Carlo simulations have been reported in diagnostic radiology and conventional mammography. The emerging technology of cone-beam CT breast imaging (CTBI) differs significantly from conventional mammography in the breast shape and imaging geometry, aspects that are important factors impacting the measured scatter. This study used a bench-top cone-beam CTBI system with an indirect flat-panel detector. A cylindrical phantom with equivalent composition of 50% fibroglandular and 50% adipose tissues was used, and scatter distributions were measured by beam stop and aperture methods. The GEANT4-based simulation package GATE was used to model x-ray photon interactions in the phantom and detector. Scatter to primary ratio (SPR) measurements using both the beam stop and aperture methods were consistent within 5% after subtraction of nonbreast scatter contributions and agree with the low energy electromagnetic model simulation in GATE. The validated simulation model was used to characterize the SPR in different CTBI conditions. In addition, a realistic, digital breast phantom was simulated to determine the characteristics of various scatter components that cannot be separated in measurements. The simulation showed that the scatter distribution from multiple Compton and Rayleigh scatterings, as well as from the single Compton scattering, has predominantly low-frequency characteristics. The single Rayleigh scatter was observed to be the primary contribution to the spatially variant scatter component. C1 [Chen, Yu; O'Connor, J. Michael; Didier, Clay S.; Glick, Stephen J.] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. [Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [O'Connor, J. Michael; Didier, Clay S.] Univ Massachusetts, Biomed Engn Program, Lowell, MA 01854 USA. RP Chen, Y (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. EM Yu.Chen@amedd.army.mil RI Chen, Yu/E-3788-2012 FU NIBIB NIH HHS [R01 EB002133] NR 35 TC 41 Z9 41 U1 0 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 MAR PY 2009 VL 36 IS 3 BP 857 EP 869 DI 10.1118/1.3077122 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 412II UT WOS:000263718100019 PM 19378746 ER PT J AU Gibbs-Strauss, SL O'Hara, JA Srinivasan, S Hoopes, PJ Hasan, T Pogue, BW AF Gibbs-Strauss, Summer L. O'Hara, Julia A. Srinivasan, Subhadra Hoopes, P. Jack Hasan, Tayyaba Pogue, Brian W. TI Diagnostic detection of diffuse glioma tumors in vivo with molecular fluorescent probe-based transmission spectroscopy SO MEDICAL PHYSICS LA English DT Article DE biomedical MRI; fluorescence spectroscopy; tumours ID BRAIN-STEM GLIOMA; LIGHT; MODEL AB The diffuse spread of glioma tumors leads to the inability to image and properly treat this disease. The optical spectral signature of targeted fluorescent probes provides molecular signals from the diffuse morphologies of glioma tumors, which can be a more effective diagnostic probe than standard morphology-based magnetic resonance imaging (MRI) sequences. Three orthotopic xenograft glioma models were used to examine the potential for transmitted optical fluorescence signal detection in vivo, using endogenously produced protoporphyrin IX (PpIX) and exogenously administered fluorescently labeled epidermal growth factor (EGF). Accurate quantification of the fluorescent signals required spectral filtering and signal normalization, and when optimized, it was possible to improve detection of sparse diffuse glioma tumor morphologies. The signal of endogenously produced PpIX provided similar sensitivity and specificity to MRI, while detection with fluorescently labeled EGF provided maximal specificity for tumors with high EGF receptor activity. Optical transmitted fluorescent signal may add significant benefit for clinical cases of diffuse infiltrative growth pattern glioma tumors given sufficient optimization of the signal acquisition for each patient. C1 [Gibbs-Strauss, Summer L.; O'Hara, Julia A.; Srinivasan, Subhadra; Hoopes, P. Jack; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [O'Hara, Julia A.] Dartmouth Med Sch, Dept Diagnost Radiol, Lebanon, NH 03756 USA. [Hoopes, P. Jack; Pogue, Brian W.] Dartmouth Med Sch, Dept Surg, Lebanon, NH 03756 USA. [Hasan, Tayyaba] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Hasan, Tayyaba; Pogue, Brian W.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Gibbs-Strauss, SL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM sgibbs@bidmc.harvard.edu FU National Cancer Institute [RO1CA109558, PO1CA084203] FX This work has been supported by the National Cancer Institute through research Grant Nos. RO1CA109558 and PO1CA084203. The authors would like to acknowledge Dr. Keith D. Paulsen for important advice and access to imaging facilities, as well as Dr. Hamid Dehghani and Dr. Scott C. Davis for light transport modeling assistance. The authors are grateful to LiCOR Biosciences for supply of some of the EGF-IRDye supply. NR 23 TC 8 Z9 8 U1 0 U2 1 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 MAR PY 2009 VL 36 IS 3 BP 974 EP 983 DI 10.1118/1.3075770 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 412II UT WOS:000263718100031 PM 19378758 ER PT J AU Shifren, JL AF Shifren, Jan L. TI Androgens, estrogens, and metabolic syndrome at midlife SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID WOMENS HEALTH; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR-DISEASE; PLUS PROGESTIN; NATION; RISK; MENOPAUSE; PREMENOPAUSAL; OOPHORECTOMY; HYSTERECTOMY C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Shifren, JL (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 16 TC 3 Z9 5 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAR-APR PY 2009 VL 16 IS 2 BP 226 EP 228 DI 10.1097/gme.0b013e3181974ffc PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 417GI UT WOS:000264064100003 PM 19179927 ER PT J AU Flaumenhaft, R Nachtigall, M Lowenstein, J Nachtigall, L Nachtigall, R Nachtigall, L AF Flaumenhaft, Robert Nachtigall, Margaret Lowenstein, Joanna Nachtigall, Lisa Nachtigall, Richard Nachtigall, Lila TI Association of oral but not transdermal estrogen therapy with enhanced platelet reactivity in a subset of postmenopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Estrogen therapy; Menopause; Transdermal estrogen; Platelet function ID FUNCTION ANALYZER PFA-100(R); HORMONE REPLACEMENT THERAPY; CORONARY-HEART-DISEASE; VENOUS THROMBOEMBOLISM; PRIMARY HEMOSTASIS; PLUS PROGESTIN; AGGREGATION; RISK; 17-BETA-ESTRADIOL; DISORDERS AB Objective: We sought to determine the effects of oral versus transdermal estrogen therapy oil platelet function in postmenopausal women. Methods: Blood obtained from 84 postmenopausal women was tested for closure times using the Platelet Function Analyzer-100 before and after administration of oral or transdermal estrogen for 8 weeks. Results: Women with normal closure times at baseline (n = 71) demonstrated no significant change after receiving estrogen therapy with oral (n = 29) or transdermnal (n = 42) estrogen. Women with borderline closure times of 61 to 66 seconds (n = 13) showed a significant acceleration Of Closure times (P = 0.0008) after oral estrogen therapy (-6.8 +/- 0.7 seconds, n = 5) but no significant change from baseline after transdermal estrogen therapy (1.1 +/- 0.5 seconds, n = 8). Conclusions: An acceleration of closure times as measured by the Platelet Function Analyzer-100 in women with borderline baseline closure times is associated with the use of oral, but not transdermal, estrogen therapy. These results suggest that oral estrogen therapy increases platelet reactivity in a Subset of women. C1 [Flaumenhaft, Robert] Harvard Univ, Sch Med, Div Hemostasis & Thrombosis, Beth Israel Deaconess Med Ctr,Dept Med, Boston, MA 02115 USA. [Nachtigall, Margaret; Nachtigall, Lila] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. [Lowenstein, Joanna; Nachtigall, Richard] NYU, Sch Med, Dept Med, New York, NY USA. [Nachtigall, Lisa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RP Flaumenhaft, R (reprint author), Harvard Univ, Sch Med, Div Hemostasis & Thrombosis, Beth Israel Deaconess Med Ctr,Dept Med, 41 Ave Louis Pasteur,RE319, Boston, MA 02115 USA. EM rflaumen@bidmc.harvard.edu OI Nachtigall, Lila/0000-0002-1457-748X NR 37 TC 5 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAR-APR PY 2009 VL 16 IS 2 BP 407 EP 412 DI 10.1097/gme.0b013e3181833886 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 417GI UT WOS:000264064100028 PM 18989235 ER PT J AU Schauer, IE Reusch, JEB AF Schauer, Irene E. Reusch, Jane E. -B. TI Nonesterified fatty acid exposure activates protective and mitogenic pathways in vascular smooth muscle cells by alternate signaling pathways SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID ELEMENT-BINDING PROTEIN; GROWTH-FACTOR-I; KINASE-C-DELTA; MEDIATED DOWN-REGULATION; OLEIC-ACID; ANGIOTENSIN-II; CARDIOVASCULAR-DISEASE; DOCOSAHEXAENOIC ACID; INSULIN SENSITIVITY; ENDOTHELIAL-CELLS AB Vascular smooth muscle cells (VSMC) are dynamic cells exposed to fluctuating concentrations of nutrients on a daily basis. Nonesterified fatty acids (NEFA) have been indicted as potential mediators of atherosclerosis and exaggerated VSMC remodeling observed in diabetes, and in vitro data support a model of VSMC activation by NEFA. However, recent observations suggest that metabolic stressors such as oxidants and NEFA may also simultaneously induce cytoprotective events as pail of a homeostatic "off switch." Our group has established that the transcription factor cyclic adenosine monophosphate response element binding protein (CREB) is important for maintenance of VSMC quiescence, differentiation, and survival. We therefore examined whether acute physiologic NEFA exposure would regulate CREB in primary cultures of bovine aortic VSMC and explored the relationship between signaling to the cytoprotective CREB and the activating mitogen-activated protein kinase pathways. In vitro exposure of VSMC to 3 classes of unsaturated NEFA leads to significant acute, transient, dose-dependent, and repeatedly inducible CREB activation. As expected, extracellular signal regulated kinase, P38 mitogen-activated protein kinase, Akt, Jun N-terminal kinase, and protein kinase C (PKC) pathways are also activated by NEFA. Using a battery of pharmacologic inhibitors and antioxidants, we demonstrate that CREB activation is mediated by a novel PKC isoform and is reactive oxygen species independent, whereas extracellular signal-regulated kinase activation, in contrast, is mediated by reactive oxygen species and is PKC independent. These data suggest parallel and mechanistically distinct stimulation of separate stabilizing and activating pathways in VSMC response to acute NEFA-mediated stress. Furthermore, the down-regulation of CRFB in models of chronic metabolic stress reported in the literature would be expected to disrupt this homeostasis and shift the balance toward VSMC activation, consistent with emerging models of atherosclerosis. (C) 2009 Elsevier Inc. All rights reserved. C1 [Schauer, Irene E.] Denver VA Med Ctr, Denver Res Inst, Denver, CO 80220 USA. Univ Colorado, Dept Med, Div Endocrinol Diabet & Metab, Aurora, CO 80045 USA. RP Schauer, IE (reprint author), Denver VA Med Ctr, Denver Res Inst, Denver, CO 80220 USA. FU National Institutes of Health [R01-DK064741-01]; Department of Veterans Affairs (VA Merit); American Heart Association FX This research was supported by grants from the National Institutes of Health (NIH T32 and NIH R01-DK064741-01), the Department of Veterans Affairs (VA Merit), an NIH P01 vascular core grant, and the American Heart Association. We appreciate the technical assistance of Jody Gunter, Dr Peter Watson, and Matthew Hockin, as well as the careful reading and advice of Dr Boris Draznin. NR 50 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAR PY 2009 VL 58 IS 3 BP 319 EP 327 DI 10.1016/j.metabol.2008.10.003 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 414RH UT WOS:000263882400009 PM 19217446 ER PT J AU Li, DM Zhang, CL Song, F Lubenec, I Tian, Y Song, QH AF Li, Dongmei Zhang, Cuili Song, F. Lubenec, I. Tian, Ye Song, Q. H. TI VEGF regulates FGF-2 and TGF-beta 1 expression in injury endothelial cells and mediates smooth muscle cells proliferation and migration SO MICROVASCULAR RESEARCH LA English DT Article DE Injury/wound; VEGF; FGF-2; TGF-beta 1; Smooth muscle cell (SMC); Endothelial cell (EC); Migration; Proliferation ID FIBROBLAST-GROWTH-FACTOR; FACTOR INCREASES; ATHEROSCLEROSIS; PROGRESSION; ACTIVATION; APOPTOSIS; RELEASE; COMPLEX; FLT-1 AB Background: Vascular endothelial growth factor (VEGF) is implicated in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA) as well as atherosclerosis. The purpose of our study was: 1) to evaluate the expression of endothelial cell (EC) fibroblast growth factor 2 (FGF-2) and transforming growth factor beta 1 (TGF-beta 1) mRNA expression following vascular injury and VEGF modulation and 2) to assess whether VEGF indirectly stimulates smooth muscle cell (SMC) migration and proliferation via growth factors released by injured EC. Methods: Bovine aortic endothelial cells (BAEC) were cultured to near confluency and were serum starved. Linear wounds were made in medium with and without VEGF. FGF-2 and TGF-beta 1 mRNA expression were evaluated. Bovine aortic organ culture experiments were also carried out and growth factor expression was assessed. SMC proliferation and migration was assessed in response to EC injury medium with/without VEGF. Results: EC injury in the presence of VEGF increased FGF-2 mRNA. EC injury also induced TGF-beta 1 mRNA expression; however VEGF inhibited TGF-beta 1 mRNA expression in both injured and noninjured ECs. VEGF increased FGF-2 mRNA stability and did not alter TGF-beta 1 mRNA stability. SMC proliferation and migration was found to be induced by injured EC media and injury EC medium with VEGF, respectively Conclusions: The results demonstrate that 1) VEGF indirectly stimulates SMC proliferation and migration through stimulation of the expression of FGF-2 and 2) VEGF inhibits the expression of TGF-beta\1 released by EC. Theses data further suggest an integral role for FGF-2 and TGF-beta 1 in wound repair. (c) 2008 Published by Elsevier Inc. C1 [Li, Dongmei; Zhang, Cuili; Tian, Ye; Song, Q. H.] Harbin Med Coll, Harbin 150081, Peoples R China. [Li, Dongmei; Zhang, Cuili; Song, F.; Lubenec, I.; Song, Q. H.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, BIDMC, Boston, MA 02214 USA. RP Tian, Y (reprint author), Harbin Med Coll, 194 Xuefu Lu, Harbin 150081, Peoples R China. EM tianye@ems.hrbmu.edu.cn; qsong@bidmc.harvard.edu FU National Institutes of Health [HL07374-22] FX This study was supported by National Institutes of Health Training Grant HL07374-22 (Dr. Qinhui Song). NR 32 TC 19 Z9 25 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAR PY 2009 VL 77 IS 2 BP 134 EP 142 DI 10.1016/j.mvr.2008.09.007 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 423CV UT WOS:000264474900010 PM 18948122 ER PT J AU Jarboe, EA Pizer, ES Miron, A Monte, N Mutter, GL Crum, CP AF Jarboe, Elke A. Pizer, Ellen S. Miron, Alexander Monte, Nick Mutter, George L. Crum, Christopher P. TI Evidence for a latent precursor (p53 signature) that may precede serous endometrial intraepithelial carcinoma SO MODERN PATHOLOGY LA English DT Article DE endometrial neoplasia; serous carcinoma; intraepithelial carcinoma; p53 ID FALLOPIAN-TUBE; GLANDULAR DYSPLASIA; BRCA MUTATIONS; CANCER; WOMEN; RISK; ADENOCARCINOMA; LESION AB Both serous intraepithelial carcinoma and endometrial glandular dysplasia are associated with uterine serous carcinoma. Recently a candidate serous cancer precursor containing p53 mutations ( p53 signature) was described in the fallopian tube. We analyzed normal and neoplastic endometrium for a similar entity. In total 10 endometrial polyps involved by intraepithelial and/or invasive carcinoma and 137 benign polyps were studied. All were stained for p53 and MIB-1. A subset of p53 signatures and carcinomas were analyzed for gamma-H2AX and p53 mutations. p53 signatures were identified in 7 of 10 cases intraepithelial carcinoma and were multicentric in 2. In one case, the signature was in continuity with intraepithelial carcinoma. Of 137 benign polyps (4%), 6 contained p53 signatures. The MIB-1 fraction in most signatures was less than 5%, and ranged from 50 to 90% in carcinomas. DNA damage (gamma-H2AX) was demonstrated in both p53 signatures and adjacent carcinomas but not in benign polyps. Shared identical p53 mutations were found in paired signatures and carcinomas in two of three cases analyzed, including one case with multiple signatures. In one, a coexistent invasive serous cancer was not found to contain a p53 mutation. In a third, a p53 signature and an invasive cancer harbored two different p53 mutations. This is the first description of p53 signatures adjacent to carcinoma, suggesting a role for this entity in the genesis of serous malignancy. The significance of p53 signatures in benign conditions ( polyps) remains to be determined. The role of the p53 signature in early serous neoplasia is discussed. C1 [Jarboe, Elke A.; Monte, Nick; Mutter, George L.; Crum, Christopher P.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Pizer, Ellen S.] CellNetix Pathol, Seattle, WA USA. [Miron, Alexander] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Crum, CP (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. EM ccrum@partners.org RI Mutter, George/C-5819-2009 FU NCI [P50 CA105009, KO8 CA108748, 1R21CA124688-01A1]; Columbia Hospital For Women Research Foundation; Francis Ward Paine; Division of Women's and Perinatal Pathology, Brigham and Women's Hospital FX This work was supported by grants from the NCI (P50 CA105009 ( SPORE): D Cramer, PI), NCI KO8 CA108748 ( R Drapkin, PI), NCI 1R21CA124688-01A1 (CP Crum, PI), The Columbia Hospital For Women Research Foundation ( CP Crum, PI), and the Francis Ward Paine and TSA Pemberton Funds from the Division of Women's and Perinatal Pathology, Brigham and Women's Hospital. NR 21 TC 24 Z9 25 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 MAR PY 2009 VL 22 IS 3 BP 345 EP 350 DI 10.1038/modpathol.2008.197 PG 6 WC Pathology SC Pathology GA 412KB UT WOS:000263722600001 PM 19151662 ER PT J AU Karaoglu, A Aydin, S Dagli, AF Cummings, DE Ozercan, IH Canatan, H Ozkan, Y AF Karaoglu, Aziz Aydin, Suleyman Dagli, Adile F. Cummings, David E. Ozercan, Ibrahim H. Canatan, Halit Ozkan, Yusuf TI Expression of obestatin and ghrelin in papillary thyroid carcinoma SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Papillary thyroid carcinoma; Obestatin; Ghrelin ID HASHIMOTOS THYROIDITIS; FOOD-INTAKE; HORMONE; PEPTIDE; GROWTH; TUMORS; ADENOCARCINOMA; DISCOVERY AB Ghrelin and obestatin are two peptide hormones with opposing roles in the control of appetite: orexigenic and anorexigenic, respectively. Loss of appetite is a common, serious complication of many forms of malignancy. The goals of this study were to investigate: (i) whether there are differences in ghrelin and obestatin peptide expression in thyroid tissues from a series of papillary carcinoma cases and normal controls, and (ii) whether there are correlations between tissue ghrelin and obestatin levels in series of papillary carcinoma cases and normal controls. Immunohistochemical analysis showed that in sections of benign human thyroid tissue, anti-ghrelin antibody reacted with intense staining in colloid-filled follicles. In benign thyroid tissues, colloids displayed plentiful dispersion in comparison with papillary microcarcinomas, whereas colloids in malignant thyroid tissues were uncommon. We found markedly lower tissue ghrelin levels in thyroid tissue of patients with papillary carcinomas, compared with normal thyroid tissues (P = 0.001). Immunohistochemical analysis also showed that obestatin in papillary carcinoma stained positively to various degrees. Obestatin tissue levels in papillary carcinomas tended to be slightly higher than those in normal thyroid tissue, but this was not statistically significant (P = 0.29). We also report that thyroid tissue of patients with Hashimoto's thyroiditis produced ghrelin and obestatin at similar levels as in normal thyroid tissue, even though colloid in Hashimoto's disease is scarce. We conclude that depressed expression of ghrelin, but not obestatin, is specific to papillary carcinoma, and this difference might constitute a diagnostic tool to differentiate papillary carcinoma from normal thyroid tissue. We currently do not know how these peptides are regulated and what factors are involved in papillary carcinoma, which inhibit the expression of ghrelin but not obestatin. This issue warrants further studies. C1 [Aydin, Suleyman] Firat Univ, Firat Univ Hosp, Sch Med, Dept Med Biochem & Clin Biochem, TR-23119 Elazig, Turkey. [Karaoglu, Aziz] Firat Univ, Sch Med, Dept Med Oncol, TR-23119 Elazig, Turkey. [Dagli, Adile F.; Ozercan, Ibrahim H.] Firat Univ, Sch Med, Dept Pathol, TR-23119 Elazig, Turkey. [Cummings, David E.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Canatan, Halit] Kuwait Univ, Hlth Sci Ctr, Fac Med, Dept Pharmacol & Toxicol, Safat 13110, Kuwait. [Ozkan, Yusuf] Firat Univ, Sch Med, Dept Endocrinol & Metab, TR-23119 Elazig, Turkey. RP Aydin, S (reprint author), Firat Univ, Firat Univ Hosp, Sch Med, Dept Med Biochem & Clin Biochem, TR-23119 Elazig, Turkey. EM saydin1@hotmail.com NR 25 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAR PY 2009 VL 323 IS 1-2 BP 113 EP 118 DI 10.1007/s11010-008-9969-0 PG 6 WC Cell Biology SC Cell Biology GA 403XU UT WOS:000263116100012 PM 19039650 ER PT J AU Schittenhelm, MM Kollmannsberger, C Oechsle, K Harlow, A Morich, J Honecker, F Kurek, R Storkel, S Kanz, L Corless, CL Wong, KK Bokemeyer, C Heinrich, MC AF Schittenhelm, Marcus M. Kollmannsberger, Christian Oechsle, Karin Harlow, Amy Morich, Jason Honecker, Friedemann Kurek, Raffael Stoerkel, Stephan Kanz, Lothar Corless, Christopher L. Wong, Kwok-Kin Bokemeyer, Carsten Heinrich, Michael C. TI Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GROWTH-FACTOR-RECEPTOR; METASTATIC COLORECTAL-CANCER; GENE COPY NUMBER; K-RAS MUTATION; KRAS MUTATION; TRANSIENT ACTIVATION; MONOCLONAL-ANTIBODY; HUMAN GLIOBLASTOMAS; CIGARETTE-SMOKING; EGFR MUTATIONS AB Antibodies targeting epidermal growth factor receptor (EGFR) have proven to be effective in patients with non-small cell lung cancer (NSCLC) that express EGFR. We recently published a phase I study of weekly matuzumab plus paclitaxel. This therapy was well tolerated and showed clinical responses in the majority of patients. Although matuzumab displays potent antitumor activity in some patients, not all patients respond well to treatment. Whether dysregulation of EGFR-mediated pathways precludes or sensitizes cells to paclitaxel is unknown. We sought to determine molecular predictive factors for therapy response in a phase I/II study patient cohort treated with matuzumab paclitaxel. Twenty-three cases including one complete response (CR), three partial responses (PR), 10 stable diseases (SW were screened using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), PCR/sequencing and denaturing wave high performance liquid chromatography (D-HPLC) for expression, amplification, and mutation status of EGFR and downstream signaling pathways. All patients with PR or CR displayed an either high overall or single-cell EGFR expression in the majority of cells. In addition, all of the moderate responders, who achieved SD after at least two cycles of therapy, showed diffuse EGFR expression rates and/or strong single-cell EGFR expression. In contrast, 44% of the nonresponders showed low overall or single-cell EGFR expression levels. No low-expressing EGFR cases were present within the responder group. In addition, among patients with a gain-of-function mutation in KRAS primary therapy failure and/or short responses to therapy were observed. Our data suggest that EGFR expression and KRAS mutation status is predictive for clinical response to matuzumab +/- paclitaxel in patients with advanced NSCLC. [Mol Cancer Ther 2009;8(3):481 - 9] C1 [Schittenhelm, Marcus M.; Kollmannsberger, Christian; Oechsle, Karin; Honecker, Friedemann; Kanz, Lothar; Bokemeyer, Carsten] Univ Tubingen Hosp, Dept Hematol Oncol Rheumatol Immunol & Pulmonol, Tubingen, Germany. [Schittenhelm, Marcus M.; Harlow, Amy; Morich, Jason; Corless, Christopher L.; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97201 USA. [Schittenhelm, Marcus M.; Harlow, Amy; Morich, Jason; Corless, Christopher L.; Heinrich, Michael C.] VA Med Ctr, Portland, OR USA. [Kollmannsberger, Christian] British Columbia Canc Agcy, Vancouver Canc Ctr, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Oechsle, Karin; Honecker, Friedemann; Bokemeyer, Carsten] Univ Hosp Hamburg Eppendorf, Dept Oncol, Sect Pneumol, Hamburg, Germany. [Kurek, Raffael] Merck KgaA, Clin Dev Unit Oncol, Darmstadt, Germany. [Stoerkel, Stephan] Helios Klinikum Wuppertal, Inst Pathol, Wuppertal, Germany. [Wong, Kwok-Kin] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wong, Kwok-Kin] Brigham & Womens Hosp, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Wong, Kwok-Kin] Harvard Univ, Sch Med, Boston, MA USA. RP Schittenhelm, MM (reprint author), Med Univ Klinikum Tubingen, Dept Hematol Oncol, Otfried Muller Str 10, D-72074 Tubingen, Germany. EM marcus.schittenhelm@med.uni-tuebingen.de OI wong, kwok kin/0000-0001-6323-235X FU Department of Veterans Affairs; Doris Duke Charitable Foundation; Deutsche Krebshilfe Foundation FX Grant support in part by a Merit Review Grant from the Department of Veterans Affairs (MCH), the Doris Duke Charitable Foundation (MCH), and the Deutsche Krebshilfe Foundation (MMS). One of the authors (RK) is employed by a company (Merck KGaA) whose product was studied in the present work. NR 50 TC 14 Z9 15 U1 0 U2 0 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 MAR PY 2009 VL 8 IS 3 BP 481 EP 489 DI 10.1158/1535-7163.MCT-08-1068 PG 9 WC Oncology SC Oncology GA 423CZ UT WOS:000264475300001 PM 19276157 ER PT J AU Punathil, T Katiyar, SK AF Punathil, Thejass Katiyar, Santosh K. TI Inhibition of Non-small Cell Lung Cancer Cell Migration by Grape Seed Proanthocyanidins Is Mediated Through the Inhibition of Nitric Oxide, Guanylate Cyclase, and ERK1/2 SO MOLECULAR CARCINOGENESIS LA English DT Article DE nitric oxide; mitogen-activated protein kinase; grape seed proanthocyanidins; guanylate cyclase; tumor cell migration; lung cancer cells ID HUMAN HEPATOCELLULAR-CARCINOMA; ACTIVATED PROTEIN-KINASES; SKH-1 HAIRLESS MICE; TUMOR PROGRESSION; SYNTHASE ACTIVITY; OXIDATIVE STRESS; BREAST-CANCER; EXPRESSION; GROWTH; ADENOCARCINOMA AB Tumor cell migration is considered as a major event in the metastatic cascade. Here we examined the effect of grape seed proanthocyanidins (GSPs) on migration capacity and signaling mechanisms using nonsmall cell human lung cancer cells. Using in vitro migration assay, we found that treatment of A549 and H 1299 cells with GSPs resulted in concentration-dependent inhibition of migration of these cells. The migration capacity of cells was reduced in presence of N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. GSPs suppressed the elevated levels of endogenous NO/NOS in A549 and H1299 cells and blocked the migration promoting capacity of L-arginine. Treatment with guanylate cyclase (GC) inhibitor 1-H-[1,2,4]oxadiaxolo[4,3-a]quinoialin-1-one (ODQ) reduced the migration of A549 cells whereas additional presence of 8-bromoguanosine 3'5'-cyclic monophosphate (8-Br-cGMP, cGMP analogue) restored the migration of these cells, suggesting a role for GC in migration of A549 cells. GSPs reduced the elevated levels of cGMP in cancer cells and also blocked the migration restoring activity of 8-Br-cGMP. The mitogen-activated protein kinase kinase (MAPKK) inhibitor, UO126, inhibited the migration of A549 cells, indicating a role for MAPKK in the migration. Additionally, UO126 and ODQ inhibited the migration restoring effects Of L-arginine in L-NAME-treated cells, suggesting the involvement of cGMP and MAPK pathways in NO-mediated migration. GSPs inhibited L-arginine and 8-Br-cGMP-induced activation of ERK1/2 in A549 cells. Together, these results indicate sequential inhibition of NOMOS, GC, and MAPK pathways by GSPs in mediating the inhibitory signals for cell migration, an essential step in invasion and metastasis. (C) 2008 Wiley-Liss, Inc. C1 [Punathil, Thejass; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Res Ctr, Dept Clin Nutr, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Dept Comprehens Canc Ctr, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. NR 36 TC 24 Z9 25 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 2009 VL 48 IS 3 BP 232 EP 242 DI 10.1002/mc.20473 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 415OI UT WOS:000263943000007 PM 18680102 ER PT J AU Jones, B Walsh, D Werner, L Fiumera, A AF Jones, Beatrix Walsh, Daniel Werner, Lillian Fiumera, Anthony TI Using blocks of linked single nucleotide polymorphisms as highly polymorphic genetic markers for parentage analysis SO MOLECULAR ECOLOGY RESOURCES LA English DT Article DE haplotype inference; microsatellite; parentage analysis; paternity; single nucleotide polymorphism ID DIFFERENTIAL REPRODUCTIVE SUCCESS; SALMON SALMO-SALAR; HAPLOTYPE RECONSTRUCTION; MICROSATELLITE MARKERS; NATURAL-POPULATION; MULTIPLE PATERNITY; GENOTYPING ERRORS; GENERAL PEDIGREES; MOTTLED SCULPIN; COTTUS-BAIRDI AB Single nucleotide polymorphisms (SNPs) are plentiful in most genomes and amenable to high throughput genotyping, but they are not yet popular for parentage or paternity analysis. The markers are bi-allelic, so individually they contain little information about parentage, and in nonmodel organisms the process of identifying large numbers of unlinked SNPs can be daunting. We explore the possibility of using blocks of between three and 26 linked SNPs as highly polymorphic molecular markers for reconstructing male genotypes in polyandrous organisms with moderate (five offspring) to large (25 offspring) clutches of offspring. Haplotypes are inferred for each block of linked SNPs using the programs Haplore and Phase 2.1. Each multi-SNP haplotype is then treated as a separate allele, producing a highly polymorphic, 'microsatellite-like' marker. A simulation study is performed using haplotype frequencies derived from empirical data sets from Drosophila melanogaster and Mus musculus populations. We find that the markers produced are competitive with microsatellite loci in terms of single parent exclusion probabilities, particularly when using six or more linked SNPs to form a haplotype. These markers contain only modest rates of missing data and genotyping or phasing errors and thus should be seriously considered as molecular markers for parentage analysis, particularly when the study is interested in the functional significance of polymorphisms across the genome. C1 [Jones, Beatrix] Massey Univ, Ctr Math Biol, N Shore Mail Ctr, Auckland 0745, New Zealand. [Jones, Beatrix] Massey Univ, Inst Informat & Math Sci, N Shore Mail Ctr, Auckland 0745, New Zealand. [Werner, Lillian] Dana Farber Canc Res Ctr, Boston, MA 02115 USA. [Fiumera, Anthony] Binghamton Univ, Dept Biol Sci, Binghamton, NY 13902 USA. RP Jones, B (reprint author), Massey Univ, Ctr Math Biol, N Shore Mail Ctr, Private Bag 102-904, Auckland 0745, New Zealand. EM m.b.jones@massey.ac.nz FU Marsden Fast Start; NSF [0746915] FX B.J. and L.W. were supported by a Marsden Fast Start Grant to B. J. A.C.F is supported by NSF (0746915). We thank A. DeWoody and A. Clark for useful discussions. NR 54 TC 13 Z9 14 U1 2 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-098X J9 MOL ECOL RESOUR JI Mol. Ecol. Resour. PD MAR PY 2009 VL 9 IS 2 BP 487 EP 497 DI 10.1111/j.1755-0998.2008.02444.x PG 11 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 406ZJ UT WOS:000263333100006 PM 21564678 ER PT J AU Rani, CSS Elango, N Wang, SS Kobayashi, K Strong, R AF Rani, C. S. Sheela Elango, Narayanasamy Wang, Shou-shu Kobayashi, Kazuto Strong, Randy TI Identification of an Activator Protein-1-Like Sequence as the Glucocorticoid Response Element in the Rat Tyrosine Hydroxylase Gene SO MOLECULAR PHARMACOLOGY LA English DT Article ID CYCLIC-AMP; RECEPTOR-BINDING; PHORBOL ESTER; TRANSCRIPTION FACTORS; PROMOTER REGION; AP-1 COMPLEX; DNA-SEQUENCE; C-FOS; EXPRESSION; CELLS AB Glucocorticoids (GCs) generally stimulate gene transcription via consensus glucocorticoid response elements (GREs) located in the promoter region. To identify the GRE in the rat tyrosine hydroxylase (TH) gene promoter, we transiently transfected PC12 cells with a 9-kilobase (kb) TH promoter-luciferase (Luc) construct. Dexamethasone (Dex) stimulated Luc activity, which was abolished by mifepristone (RU486). Serial deletion mutations revealed a Dex-responsive 7-base pair (bp) sequence, TGACTAA, located at -5734 to -5728. Deletion of just these seven nucleotides from the 9-kb promoter completely abolished the Dex response and partially reduced the response to phorbol ester but not to forskolin. The Dex response was fully retained in a construct in which most of the 9-kb promoter was deleted, except for 100 bp around the -5.7-kb region, clearly identifying this 7-bp sequence as solely responsible for GC responsiveness. Conversely, deletion of the proximal cAMPresponse element (-45/-38) or activator protein-1 (AP-1) (-207/-201) sites in the 9-kb promoter did not affect Dex and phorbol ester responses. A radiolabeled 25-bp promoter fragment bearing the 7-bp TH-GRE/AP-1 showed specific binding to PC12 nuclear proteins. Using antibodies against the glucocorticoid receptors and AP-1 family of proteins and primers for the TH-GRE/AP-1 region, we detected a specific DNA amplicon in a chromatin immunoprecipitation assay. This 7-bp TH-GRE/AP-1 sequence (TGACTAA) does not bear similarity to any known GRE but closely resembles the consensus AP-1 binding site, TGACTCA. Our studies describe for the first time a novel GRE/AP-1 site present in the TH gene promoter that is critical for glucocorticoid regulation of the TH gene. C1 [Rani, C. S. Sheela; Wang, Shou-shu; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Rani, C. S. Sheela; Wang, Shou-shu; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Elango, Narayanasamy; Strong, Randy] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Kobayashi, Kazuto] Fukushima Med Univ, Sch Med, Dept Mol Genet, Fukushima, Japan. RP Rani, CSS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kadapakkam@uthscsa.edu FU NIA NIH HHS [U01 AG022307, AG022307] NR 41 TC 15 Z9 18 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2009 VL 75 IS 3 BP 589 EP 598 DI 10.1124/mol.108.051219 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 410EE UT WOS:000263559500016 PM 19060113 ER PT J AU Elder, GA Cristian, A AF Elder, Gregory A. Cristian, Adrian TI Blast-Related Mild Traumatic Brain Injury: Mechanisms of Injury and Impact on Clinical Care SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE animal models; blast overpressure wave; blast-related brain injury; improvised explosive device; mild traumatic brain injury; Operation Enduring Freedom; Operation Iraqi Freedom; pathophysiology; postconcussion syndrome; posttraumatic stress disorder; shell shock ID POSTTRAUMATIC-STRESS-DISORDER; INDUCED NEUROTRAUMA; SHELL SHOCK; RAT-BRAIN; EXPOSURE; IRAQ; WAVE AB Mild traumatic brain injury has been called the signature injury of the wars in Iraq and Afghanistan. In both theaters of operation, traumatic brain injury has been a significant cause of mortality and morbidity, with blast-related injury the most common cause. Improvised explosive devices have been the major cause of blast injuries. It is estimated that 10% to 20% of veterans returning from these operations have suffered a traumatic brain injury, and there is concern that blast-related injury may produce adverse long-term health affects and affect the resilience and in-theater performance of troops. Blast-related injury occurs through several mechanisms related to the nature of the blast overpressure wave itself as well as secondary and tertiary injuries. Animal studies clearly show that blast overpressure waves are transmitted to the brain and can cause changes that neuropathologically are most similar to diffuse axonal injury. One striking feature of the mild traumatic brain injury cases being seen in veterans of the wars in Iraq and Afghanistan is the high association of mild traumatic brain injury with posttraumatic stress disorder. The overlap in symptoms between the disorders has made distinguishing them clinically challenging. The high rates of mild trumatic brain injury and posttraumatic stress disorder in the current operations are of significant concern for the long-term health of Us veterans with associated economic implications. Mt Sinai J Med 76.111-118, 2009 (C) 2009 Mount Sinai School of Medicine C1 [Elder, Gregory A.; Cristian, Adrian] Vet Affairs Med Ctr, James J Peters Dept, Rehabil Med Serv, Bronx, NY USA. RP Elder, GA (reprint author), Vet Affairs Med Ctr, James J Peters Dept, Rehabil Med Serv, Bronx, NY USA. EM gregory.elder@va.gov NR 26 TC 112 Z9 116 U1 0 U2 25 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD MAR-APR PY 2009 VL 76 IS 2 BP 111 EP 118 DI 10.1002/msj.20098 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 427OE UT WOS:000264787800004 PM 19306373 ER PT J AU Julian, LJ Vella, L Frankel, D Minden, SL Oksenberg, JR Mohr, DC AF Julian, L. J. Vella, L. Frankel, D. Minden, S. L. Oksenberg, J. R. Mohr, D. C. TI ApoE alleles, depression and positive affect in multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Article DE genetics; multiple sclerosis; quality of life ID WHITE-MATTER HYPERINTENSITIES; APOLIPOPROTEIN-E POLYMORPHISM; DISABILITY STATUS SCALE; LATE-LIFE DEPRESSION; COGNITIVE IMPAIRMENT; EPSILON-4 ALLELE; DISEASE SEVERITY; NEGATIVE AFFECT; E GENOTYPE; ASSOCIATION AB Background The role of apolipoprotein E ( ApoE) alleles has received recent attention in depressive disorders, the ApoE epsilon 4 conferring greater risk for poorer outcomes, and the ApoE epsilon 2 allele providing some protective effects. Depression is common in multiple sclerosis (MS) and the role of ApoE alleles is unknown. Aims To evaluate ApoE alleles in relation to symptoms of depression in a cohort of patients with MS participating in the Sonya Slifka Longitudinal Multiple Sclerosis Study (Slifka Study). To examine risk and protection, depressed mood and positive affect were each investigated with respect to the ApoE epsilon 4 and ApoE epsilon 2 alleles, respectively. Results Of the total 101 participants, 22.8% were ApoE epsilon 2 carriers and 21.8% were ApoE epsilon 4 carriers. Hierarchical linear regression analyses suggested that after controlling for demographics, disease duration, and disability, ApoE epsilon 2 significantly predicted increased positive affect (R(2)Delta = 0.05, F(1,94) = 5.44, P = 0.02) and was associated with decreased severity of depressive symptoms, although this did not reach statistical significance (R(2)Delta = 0.03, F(1,94) = 3.44, P = 0.06). ApoE epsilon 4 did not significantly predict depression status. Conclusion The presence of the ApoE epsilon 2 allele in this study is suggested to be protective against depressive symptoms in our subsample of patients recruited from the Slifka Study. These findings are consistent with reports in psychiatric populations linking ApoE epsilon 2 with decreased incidence of depressive disorders. Further investigation would be warranted to understand the role of ApoE genotypes and risk for depressive symptoms. Multiple Sclerosis 2009; 15: 311-315. http://msj.sagepub.com C1 [Julian, L. J.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Vella, L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Frankel, D.; Minden, S. L.] Abt & Associates Inc, Cambridge, MA USA. [Minden, S. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Minden, S. L.] ABT Associates Inc, Cambridge, MA USA. [Oksenberg, J. R.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Mohr, D. C.] Northwestern Univ, Hines VA Med Ctr, Dept Prevent Med, Chicago, IL 60611 USA. RP Julian, LJ (reprint author), Univ Calif San Francisco, Dept Med, 3333 Calif St,Suite 270, San Francisco, CA 94143 USA. EM laura.julian@ucsf.edu FU NCRR NIH HHS [UL1 RR025741]; NICHD NIH HHS [R01 HD043323-03, R01 HD043323]; NIMH NIH HHS [K08 MH 07272401A2] NR 37 TC 12 Z9 13 U1 2 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD MAR PY 2009 VL 15 IS 3 BP 311 EP 315 DI 10.1177/1352458508099478 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 423AF UT WOS:000264468100006 PM 19244396 ER PT J AU Oh, SJ Morgan, MB Lu, L Hatanaka, Y Hemmi, S Young, A Claussen, GC AF Oh, Shin J. Morgan, Marla B. Lu, Liang Hatanaka, Yuki Hemmi, Shoji Young, Angela Claussen, Gwendolyn C. TI RACIAL DIFFERENCES IN MYASTHENIA GRAVIS IN ALABAMA SO MUSCLE & NERVE LA English DT Article DE MuSK antibody; myasthenia gravis; racial differences ID ACETYLCHOLINE-RECEPTOR ANTIBODY; ONSET AB Demographic, clinical, and laboratory features were compared in 235 white and African-American (AA) patients with myasthenia gravis (MG) at the University of Alabama at Birmingham Neuromuscular Disease Clinic from May 2003 to January 2008. Seventy nine percent of patients were white. Acetylcholine receptor antibody was positive in 71% of white patients and in 59% of AA. In patients with seronegative generalized MG, the rate of positive muscle-specific tyrosine kinase antibody (MuSK-Ab) was significantly higher in AA than it was in whites (50% in AA vs. 17% in whites). Ocular MG was seronegative in 75% of AA patients. In AA, MG occurred earlier and more frequently in females, whereas, in whites, disease onset was later and more common in males. Another significant difference was a higher percentage of abnormality on repetitive nerve stimulation in AA. There was also a tendency for more severe forms of MG in AA. There are racial differences in MG between whites and AA in Alabama. These racial differences highlight the need to study biological factors in the pathogenesis of MG and to assess different approaches in diagnosis and treatment. Muscle Nerve 39: 328-332, 2009 C1 [Oh, Shin J.; Morgan, Marla B.; Lu, Liang; Hatanaka, Yuki; Hemmi, Shoji; Young, Angela; Claussen, Gwendolyn C.] Univ Alabama, Birmingham Vet Affairs Med Ctr, Dept Neurol, Birmingham, AL 35294 USA. RP Oh, SJ (reprint author), Univ Alabama, Birmingham Vet Affairs Med Ctr, Dept Neurol, Univ Stn, Birmingham, AL 35294 USA. EM shinjoh@uab.edu FU NINDS NIH HHS [K08 NS057664-02, K08 NS057664, K08 NS057664-01A2] NR 21 TC 13 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD MAR PY 2009 VL 39 IS 3 BP 328 EP 332 DI 10.1002/mus.21191 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 411NR UT WOS:000263656800007 PM 19127534 ER PT J AU Keng, VW Villanueva, A Chiang, DY Dupuy, AJ Ryan, BJ Matise, I Silverstein, KAT Sarver, A Starr, TK Akagi, K Tessarollo, L Collier, LS Powers, S Lowe, SW Jenkins, NA Copeland, NG Llovet, JM Largaespada, DA AF Keng, Vincent W. Villanueva, Augusto Chiang, Derek Y. Dupuy, Adam J. Ryan, Barbara J. Matise, Ilze Silverstein, Kevin A. T. Sarver, Aaron Starr, Timothy K. Akagi, Keiko Tessarollo, Lino Collier, Lara S. Powers, Scott Lowe, Scott W. Jenkins, Nancy A. Copeland, Neal G. Llovet, Josep M. Largaespada, David A. TI A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma SO NATURE BIOTECHNOLOGY LA English DT Article ID GROWTH-FACTOR-RECEPTOR; NF-KAPPA-B; SLEEPING-BEAUTY; IN-VITRO; LIVER-CANCER; EXPRESSION; KINASE; TUMOR; ACTIVATION; PATHWAY AB We describe a system that permits conditional mobilization of a Sleeping Beauty (SB) transposase allele by Cre recombinase to induce cancer specifically in a tissue of interest. To demonstrate its potential for developing tissue-specific models of cancer in mice, we limit SB transposition to the liver by placing Cre expression under the control of an albumin enhancer/promoter sequence and screen for hepatocellular carcinoma (HCC)-associated genes. From 8,060 nonredundant insertions cloned from 68 tumor nodules and comparative analysis with data from human HCC samples, we identify 19 loci strongly implicated in causing HCC. These encode genes, such as EGFR and MET, previously associated with HCC and others, such as UBE2H, that are potential new targets for treating this neoplasm. Our system, which could be modified to drive transposon-based insertional mutagenesis wherever tissue-specific Cre expression is possible, promises to enhance understanding of cancer genomes and identify new targets for therapeutic development. C1 [Keng, Vincent W.; Ryan, Barbara J.; Matise, Ilze; Silverstein, Kevin A. T.; Sarver, Aaron; Starr, Timothy K.; Largaespada, David A.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA. [Keng, Vincent W.; Ryan, Barbara J.; Starr, Timothy K.; Largaespada, David A.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA. [Villanueva, Augusto; Llovet, Josep M.] Hosp Clin Barcelona, CIBERehd, IDIBAPS, HCC Translat Res Lab,BCLC Grp Liver Unit, E-08036 Barcelona, Spain. [Chiang, Derek Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chiang, Derek Y.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Chiang, Derek Y.] Broad Inst Harvard, Canc Program, Cambridge, MA 02142 USA. [Chiang, Derek Y.] MIT, Cambridge, MA 02142 USA. [Dupuy, Adam J.] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Akagi, Keiko; Tessarollo, Lino] NCI, Frederick, MD 21702 USA. [Collier, Lara S.] Univ Wisconsin, Sch Pharm, Div Pharmaceut Sci, Madison, WI 53705 USA. [Powers, Scott; Lowe, Scott W.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Jenkins, Nancy A.; Copeland, Neal G.] Inst Mol & Cellular Biol, Singapore 138673, Singapore. [Llovet, Josep M.] Mt Sinai Sch Med, Mt Sinai Liver Canc Program, New York, NY 10029 USA. [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona 08010, Spain. RP Largaespada, DA (reprint author), Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA. EM larga002@umn.edu RI Augusto, Villanueva/F-9378-2012; Largaespada, David/C-9832-2014; Llovet, Josep M /D-4340-2014; OI Augusto, Villanueva/0000-0003-3585-3727; Llovet, Josep M /0000-0003-0547-2667; Chiang, Derek/0000-0002-1131-6065; Keng, Vincent/0000-0003-3473-0653; Starr, Timothy/0000-0002-6308-3451 FU European Association for the Study of the Liver; National Cancer Institute [1K01CA122183-01, U01 CA84221, R01 CA113636]; Department of Health and Human Services; National Institutes of Health; US National Institute of Diabetes; Digestive and Kidney Diseases [1R01DK076986-01]; Spanish National Institute of Health [SAF-200761898]; Samuel Waxman Cancer Research Foundation FX The authors wish to thank Christine E. Nelson, Stefanie S. Breitbarth, Michelle K. Gleason and Geoff Hart for their excellent technical support; Jason B. Bell for performing the hydrodynamic injections; and Heidi Gruelich, Dana Farber Cancer Institute, for her kind gift pBabe-Puro-LTR-EGFR. We are also grateful to the Minnesota Supercomputing Institute for providing extensive computational resources (hardware and systems administration support) used to carry out the sequence analysis. A.V. is supported by a Sheila Sherlock fellowship from the European Association for the Study of the Liver. L.S.C. is supported by a 1K01CA122183-01 grant from the National Cancer Institute. N.G.C., N.A.J. and L.T. are supported by the Department of Health and Human Services, National Institutes of Health and the National Cancer Institute. J.M.L. is supported by the US National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK076986-01), Spanish National Institute of Health (SAF-200761898) and Samuel Waxman Cancer Research Foundation. D.A.L. is supported by U01 CA84221 and R01 CA113636 grants from the National Cancer Institute. NR 52 TC 118 Z9 125 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2009 VL 27 IS 3 BP 264 EP 274 DI 10.1038/nbt.1526 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 416UJ UT WOS:000264030700020 PM 19234449 ER PT J AU van der Voet, M Berends, CWH Perreault, A Nguyen-Ngoc, T Gonczy, P Vidal, M Boxem, M van den Heuvel, S AF van der Voet, Monique Berends, Christian W. H. Perreault, Audrey Nguyen-Ngoc, Tu Goenczy, Pierre Vidal, Marc Boxem, Mike van den Heuvel, Sander TI NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/G alpha SO NATURE CELL BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS; C-ELEGANS; GENETIC INTERFERENCE; INTERACTOME NETWORK; PLANAR DIVISIONS; CLEAVAGE PLANE; OOCYTE CORTEX; PROTEIN; EMBRYOS; ORGANIZATION AB The spindle apparatus dictates the plane of cell cleavage, which is critical in the choice between symmetric or asymmetric division. spindle positioning is controlled by an evolutionarily conserved pathway, which involves LIN-5/GPr-1/2/G alpha in Caenorhabditis elegans, Mud/Pins/Ga in Drosophila and NuMA/IGN/G alpha in humans(1). GPr-1/2 and G alpha localize LIN-5 to the cell cortex, which engages dynein and controls the cleavage plane during early mitotic divisions in C. elegans(2-6). Here we identify AsPM-1 (abnormal spindle-like, microcephaly-associated) as a novel LIN-5 binding partner. AsPM-1, together with calmodulin (CMD-1), promotes meiotic spindle organization and the accumulation of LIN-5 at meiotic and mitotic spindle poles. spindle rotation during maternal meiosis is independent of GPR-1/2 and G alpha, yet requires LIN-5, AsPM-1, CMD-1 and dynein. Our data support the existence of two distinct LIN-5 complexes that determine localized dynein function: LIN-5/GPR-1/2/G alpha at the cortex, and LIN-5/AsPM-1/CMD-1 at spindle poles. these functional interactions may be conserved in mammals, with implications for primary microcephaly. C1 [van der Voet, Monique; Berends, Christian W. H.; Boxem, Mike; van den Heuvel, Sander] Univ Utrecht, Dept Biol, NL-3584 CH Utrecht, Netherlands. [Perreault, Audrey] MGH Canc Ctr, Charlestown, MA 02129 USA. [Nguyen-Ngoc, Tu; Goenczy, Pierre] Swiss Fed Inst Technol EPFL, Swiss Inst Expt Canc Res ISREC, Sch Life Sci, CH-1066 Lausanne, Switzerland. [Vidal, Marc; Boxem, Mike] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Vidal, Marc; Boxem, Mike] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Vidal, Marc; Boxem, Mike] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP van den Heuvel, S (reprint author), Univ Utrecht, Dept Biol, Padualaan 8, NL-3584 CH Utrecht, Netherlands. EM s.j.l.vandenheuvel@uu.nl RI Boxem, Mike/B-8857-2011; van den Heuvel, Sander/B-8892-2011; van der Voet, Monique/F-5772-2012 OI Boxem, Mike/0000-0003-3966-4173; van der Voet, Monique/0000-0002-8829-1767 FU National Institutes of Health [GM57990]; Swiss National Science Foundation [3100A0-102087]; Marie Curie International Reintegration [MIRG-CT-2007-046458] FX We are grateful to Steve Gygi and Ross Tomaino ( Taplin Biological Mass Spectrometry, Harvard Medical School) for analysis of peptides by mass spectrometry ( HMS), to Sean O'Rourke and Bruce Bowerman for the GFP - DHC- 1 strain EU1561, to Inge The for assistance with ASPM- 1 antibody production, Kristiaan de Vries for scoring embryonic lethality, and the Caenorhabditis Genetics Center ( National Institutes of Health, National Center for Research Resources) for providing strains. We thank Adri Thomas and Marjolein Wildwater for critically reading the manuscript. This work was supported in part by National Institutes of Health grant GM57990 to S. v. d. H, Swiss National Science Foundation grant 3100A0-102087 to P. G., and Marie Curie International Reintegration grant MIRG-CT-2007-046458 to M. B. NR 41 TC 61 Z9 73 U1 4 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAR PY 2009 VL 11 IS 3 BP 269 EP U101 DI 10.1038/ncb1834 PG 16 WC Cell Biology SC Cell Biology GA 413FI UT WOS:000263777900010 PM 19219036 ER PT J AU Stanton, BZ Peng, LF Maloof, N Nakai, K Wang, X Duffner, JL Taveras, KM Hyman, JM Lee, SW Koehler, AN Chen, JK Fox, JL Mandinova, A Schreiber, SL AF Stanton, Benjamin Z. Peng, Lee F. Maloof, Nicole Nakai, Kazuo Wang, Xiang Duffner, Jay L. Taveras, Kennedy M. Hyman, Joel M. Lee, Sam W. Koehler, Angela N. Chen, James K. Fox, Julia L. Mandinova, Anna Schreiber, Stuart L. TI A small molecule that binds Hedgehog and blocks its signaling in human cells SO NATURE CHEMICAL BIOLOGY LA English DT Article ID PATHWAY; CYCLOPAMINE; MICROARRAYS; ACTIVATION; MUTATIONS; CANCER; MICE AB Small-molecule inhibition of extracellular proteins that activate membrane receptors has proven to be extremely challenging. Diversity-oriented synthesis and small-molecule microarrays enabled the discovery of robotnikinin, a small molecule that binds the extracellular Sonic hedgehog (Shh) protein and blocks Shh signaling in cell lines, human primary keratinocytes and a synthetic model of human skin. Shh pathway activity is rescued by small-molecule agonists of Smoothened, which functions immediately downstream of the Shh receptor Patched. C1 [Stanton, Benjamin Z.; Peng, Lee F.; Maloof, Nicole; Wang, Xiang; Duffner, Jay L.; Taveras, Kennedy M.; Koehler, Angela N.; Schreiber, Stuart L.] Harvard Univ, Howard Hughes Med Inst, Broad Inst, Cambridge, MA 02142 USA. [Stanton, Benjamin Z.; Peng, Lee F.; Maloof, Nicole; Wang, Xiang; Duffner, Jay L.; Taveras, Kennedy M.; Koehler, Angela N.; Schreiber, Stuart L.] MIT, Cambridge, MA 02142 USA. [Stanton, Benjamin Z.; Peng, Lee F.; Nakai, Kazuo; Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Peng, Lee F.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Hyman, Joel M.; Chen, James K.] Stanford Univ, Sch Med, Dept Chem & Syst Biol, CCSR, Stanford, CA 94305 USA. [Lee, Sam W.; Mandinova, Anna] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Fox, Julia L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Peng, LF (reprint author), Harvard Univ, Howard Hughes Med Inst, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM lpeng@partners.org; stuart_schreiber@harvard.edu RI Chen, James/G-9972-2011 OI Chen, James/0000-0002-9220-8436 FU Howard Hughes Medical Institute; NCI NIH HHS [R01 CA195534, N01 CO012400, N01-CO-12400, N01CO12400, P01 CA080058, R01 CA149477]; NIGMS NIH HHS [GM-38627, R01 GM038627, R01 GM038627-17, R37 GM038627] NR 24 TC 164 Z9 168 U1 1 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD MAR PY 2009 VL 5 IS 3 BP 154 EP 156 DI 10.1038/nchembio.142 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 410DG UT WOS:000263556100012 PM 19151731 ER PT J AU Saenz, JB Sun, WJ Chang, JW Li, JM Bursulaya, B Gray, NS Haslam, DB AF Saenz, Jose B. Sun, William J. Chang, Jae Won Li, Jinmei Bursulaya, Badry Gray, Nathanael S. Haslam, David B. TI Golgicide A reveals essential roles for GBF1 in Golgi assembly and function SO NATURE CHEMICAL BIOLOGY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; BREFELDIN-A; TRANS-GOLGI; ENDOPLASMIC-RETICULUM; MEMBRANE-TRANSPORT; TYROSYLPROTEIN SULFOTRANSFERASE; RETROGRADE TRANSPORT; PLASMA-MEMBRANE; PROTEIN COMPLEX; SEC7 DOMAINS AB ADP ribosylation factor 1 (Arf1) plays a critical role in regulating secretory traffic and membrane transport within the Golgi of eukaryotic cells. Arf1 is activated by guanine nucleotide exchange factors (ArfGEFs), which confer spatial and temporal specificity to vesicular transport. We describe here the discovery and characterization of golgicide A, a potent, highly specific, reversible inhibitor of the cis-Golgi ArfGEF GBF1. Inhibition of GBF1 function resulted in rapid dissociation of COPI vesicle coat from Golgi membranes and subsequent disassembly of the Golgi and trans-Golgi network. Secretion of soluble and membrane-associated proteins was arrested at the endoplasmic reticulum-Golgi intermediate compartment, whereas endocytosis and recycling of transferrin were unaffected by GBF1 inhibition. Internalized shiga toxin was arrested within the endocytic compartment and was unable to reach the dispersed trans-Golgi network. Collectively, these results highlight the central role for GBF1 in coordinating bidirectional transport and maintaining structural integrity of the Golgi. C1 [Saenz, Jose B.; Sun, William J.; Li, Jinmei; Haslam, David B.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Saenz, Jose B.; Sun, William J.; Li, Jinmei; Haslam, David B.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Chang, Jae Won; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Chang, Jae Won; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Bursulaya, Badry] Genom Inst Novartis Res Fdn, San Diego, CA 92121 USA. RP Haslam, DB (reprint author), Washington Univ, Sch Med, Dept Pediat, 660 S Euclid Ave, St Louis, MO 63110 USA. EM haslam@kids.wustl.edu RI Haslam, David/G-3825-2012 FU NIAID NIH HHS [U54 AI057160, U54 AI057160-05S10028] NR 50 TC 79 Z9 80 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD MAR PY 2009 VL 5 IS 3 BP 157 EP 165 DI 10.1038/nchembio.144 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 410DG UT WOS:000263556100013 PM 19182783 ER PT J AU Haider, N Arbustini, E Gupta, S Liu, H Narula, N Hajjar, R Moorjani, N Westaby, S Semigran, MJ Dec, GW Chandrashekhar, Y Narula, J AF Haider, Nezam Arbustini, Eloisa Gupta, Sudhir Liu, Han Narula, Navneet Hajjar, Roger Moorjani, Narain Westaby, Stephen Semigran, Marc J. Dec, G. William Chandrashekhar, Y. Narula, Jagat TI Concurrent upregulation of endogenous proapoptotic and antiapoptotic factors in failing human hearts SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Article DE cardiomyopathy; caspases; cytochrome c1; heart failure; programmed cell death ID CYTOCHROME-C; APOPTOSIS; FAILURE; CASPASE-3; ACTIVATION; MYOCYTES; CLEAVAGE; DEATH; CARDIOMYOPATHY; MITOCHONDRIA AB Background Despite widespread activation of proapoptotic stimuli and mediators, the degree of apoptosis in failing hearts is not very high. Endogenous antiapoptotic mechanisms are thought to be triggered by the heart-failure process. We investigated whether activation of endogenous apoptosis inhibitors plays a part when death receptor and mitochondrial apoptotic pathways have been triggered. Methods We evaluated various proapoptotic and antiapoptotic factors in myocardial tissue specimens obtained from normal and explanted end-stage ischemic and dilated cardiomyopathic hearts. Caspases (CASPs) 3, 8 and 9, total and activated Bcl-2 homology domain 3-interacting domain death agonist, the X-linked inhibitor of apoptosis (XIAP), and DNA fragmentation factor (DFF) proteins were analyzed by western blotting. Expression of messenger RNA was measured by reverse-transcription polymerase chain reaction for the XIAP, DIABLO, CFLAR and DFF genes. We also assessed CASP3, CASP8 and CASP9 and DFF activity. Cytochrome c1 localization in myocytes was analyzed by immunohistochemistry and immunoelectron microscopy. Results We collected myocardial tissue from eight cardiomyopathic hearts and five normal hearts. Cytochrome c1 was released from mitochondria into the cytosol in the cardiomyopathic hearts but CASP9 was not activated. CASP8 activity was increased compared with that in normal myocardium. Although CASP3 was cleaved, activity was not greatly increased because of an increase in XIAP and decrease in DIABLO expression. DFF proteins were conspicuously absent. Conclusions Concurrent upregulation of endogenous antiapoptotic mechanisms can interrupt the apoptotic cascade and prevents cell loss despite the presence of multiple proapoptotic factors. This period might offer a therapeutic window for restoration of myocardial function in heart failure. C1 [Haider, Nezam; Gupta, Sudhir; Liu, Han; Narula, Navneet; Narula, Jagat] Univ Calif Irvine, Sch Med, Orange, CA 92868 USA. [Arbustini, Eloisa] Policlin San Matteo, IRCCS, Ctr Genet Cardiovasc Dis, I-27100 Pavia, Italy. [Hajjar, Roger; Semigran, Marc J.; Dec, G. William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moorjani, Narain; Westaby, Stephen] John Radcliffe Hosp, Oxford OX3 9DU, England. [Chandrashekhar, Y.] Univ Minnesota, Minneapolis, MN USA. RP Narula, J (reprint author), Univ Calif Irvine, Sch Med, 101 City Dr,Bldg 53,Mail Route 81, Orange, CA 92868 USA. EM narula@uci.edu OI Arbustini, Eloisa/0000-0003-2948-7994 NR 19 TC 11 Z9 11 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1743-4297 J9 NAT CLIN PRACT CARD JI Nat. Clin. Pract. Cardiovasc. Med. PD MAR PY 2009 VL 6 IS 3 BP 250 EP 261 DI 10.1038/ncpcardio1452 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 410IH UT WOS:000263570200019 PM 19234503 ER PT J AU Fotuhi, M Mohassel, P Yaffe, K AF Fotuhi, Majid Mohassel, Payam Yaffe, Kristine TI Fish consumption, long-chain omega-3 fatty acids and risk of cognitive decline or Alzheimer disease: a complex association SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Review DE Alzheimer disease; cognitive decline; dementia; fish consumption; long-chain omega-3 fatty acids ID N-3 FATTY-ACIDS; TUMOR-NECROSIS-FACTOR; CEREBRAL-BLOOD-FLOW; DOCOSAHEXAENOIC ACID; CARDIOVASCULAR-DISEASE; DIETARY SUPPLEMENTATION; SECONDARY-PREVENTION; VASCULAR DEMENTIA; BRAIN-DEVELOPMENT; PROSTAGLANDIN-E AB Long-chain omega-3 fatty acids could have neuroprotective properties against dementia, which is becoming a major global public health issue. We conducted a systematic review of the literature to establish the association between eating fish (a source of long-chain omega-3 fatty acids) or taking long-chain omega-3 fatty acid supplements and the risk of cognitive decline or Alzheimer disease (AD). We identified eleven observational studies and four clinical trials. All three observational studies that used cognitive decline as an outcome reported significant benefits, whereas only four of eight observational studies that used incidence of AD or dementia as an outcome reported positive findings. None of four small clinical trials provided convincing evidence for the use of this approach in the prevention or treatment of any form of dementia. In summary, the existing data favor a role for long-chain omega-3 fatty acids in slowing cognitive decline in elderly individuals without dementia, but not for the prevention or treatment of dementia (including AD). This apparent dichotomy might reflect differences in study designs with regard to participants, dosages, the ratio of long-chain omega-3 to omega-6 fatty acids, or the choice of outcome measurements. Large clinical trials of extended duration should help to provide definitive answers. C1 [Fotuhi, Majid] Sinai Hosp Baltimore, LifeBridge Hlth Brain & Spine Inst, Ctr Memory & Brain Hlth, Baltimore, MD 21209 USA. [Fotuhi, Majid; Mohassel, Payam] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, Memory Disorders Clin, San Francisco, CA USA. RP Fotuhi, M (reprint author), Sinai Hosp Baltimore, LifeBridge Hlth Brain & Spine Inst, Ctr Memory & Brain Hlth, 5051 Greenspring Ave, Baltimore, MD 21209 USA. EM mfotuhi@lifebridgehealth.org OI Fotuhi, Majid/0000-0002-0980-1176 FU NIA NIH HHS [AG 031155] NR 77 TC 143 Z9 147 U1 5 U2 65 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD MAR PY 2009 VL 5 IS 3 BP 140 EP 152 DI 10.1038/ncpneuro1044 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 414VE UT WOS:000263892500009 PM 19262590 ER PT J AU Boshoff, C Posner, M AF Boshoff, Chris Posner, Marshall TI Targeting EGFR in head and neck cancer: a decade of progress SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material C1 [Boshoff, Chris] UCL Canc Inst, London, England. [Posner, Marshall] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Boshoff, C (reprint author), UCL Canc Inst, London, England. NR 0 TC 1 Z9 2 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD MAR PY 2009 VL 6 IS 3 BP 123 EP 123 DI 10.1038/ncponc1328 PG 1 WC Oncology SC Oncology GA 412KG UT WOS:000263723100001 PM 19247309 ER PT J AU Erdmann, J Grosshennig, A Braund, PS Konig, IR Hengstenberg, C Hall, AS Linsel-Nitschke, P Kathiresan, S Wright, B Tregouet, DA Cambien, F Bruse, P Aherrahrou, Z Wagner, AK Stark, K Schwartz, SM Salomaa, V Elosua, R Melander, O Voight, BF O'Donnell, CJ Peltonen, L Siscovick, DS Altshuler, D Merlini, PA Peyvandi, F Bernardinelli, L Ardissino, D Schillert, A Blankenberg, S Zeller, T Wild, P Schwarz, DF Tiret, L Perret, C Schreiber, S El Mokhtari, NE Schafer, A Marz, W Renner, W Bugert, P Kluter, H Schrezenmeir, J Rubin, D Ball, SG Balmforth, AJ Wichmann, HE Meitinger, T Fischer, M Meisinger, C Baumert, J Peters, A Ouwehand, WH Deloukas, P Thompson, JR Ziegler, A Samani, NJ Schunkert, H AF Erdmann, Jeanette Grosshennig, Anika Braund, Peter S. Koenig, Inke R. Hengstenberg, Christian Hall, Alistair S. Linsel-Nitschke, Patrick Kathiresan, Sekar Wright, Ben Tregouet, David-Alexandre Cambien, Francois Bruse, Petra Aherrahrou, Zouhair Wagner, Arnika K. Stark, Klaus Schwartz, Stephen M. Salomaa, Veikko Elosua, Roberto Melander, Olle Voight, Benjamin F. O'Donnell, Christopher J. Peltonen, Leena Siscovick, David S. Altshuler, David Merlini, Piera Angelica Peyvandi, Flora Bernardinelli, Luisa Ardissino, Diego Schillert, Arne Blankenberg, Stefan Zeller, Tanja Wild, Philipp Schwarz, Daniel F. Tiret, Laurence Perret, Claire Schreiber, Stefan El Mokhtari, Nour Eddine Schaefer, Arne Maerz, Winfried Renner, Wilfried Bugert, Peter Klueter, Harald Schrezenmeir, Juergen Rubin, Diana Ball, Stephen G. Balmforth, Anthony J. Wichmann, H-Erich Meitinger, Thomas Fischer, Marcus Meisinger, Christa Baumert, Jens Peters, Annette Ouwehand, Willem H. Deloukas, Panos Thompson, John R. Ziegler, Andreas Samani, Nilesh J. Schunkert, Heribert CA Italian Atherosclerosis Thrombosis Myocardial Infarction Genetics Con Wellcome Trust Case Control Consor Cardiogenics Consortium TI New susceptibility locus for coronary artery disease on chromosome 3q22.3 SO NATURE GENETICS LA English DT Article ID ASSOCIATION; GENOME AB We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in similar to 25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 x 10(-13); OR = 1.15, 95% CI = 1.11-1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 x 10(-7); OR = 1.08, 95% CI = 1.05-1.11). C1 [Erdmann, Jeanette; Grosshennig, Anika; Linsel-Nitschke, Patrick; Bruse, Petra; Aherrahrou, Zouhair; Wagner, Arnika K.; Schunkert, Heribert] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany. [Grosshennig, Anika; Koenig, Inke R.; Schillert, Arne; Schwarz, Daniel F.; Ziegler, Andreas] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Braund, Peter S.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Ctr, Glenfield Hosp, Leicester LE3 9QP, Leics, England. [Hengstenberg, Christian; Stark, Klaus; Fischer, Marcus] Univ Regensburg, Klin & Poliklin Innere Med 2, D-93053 Regensburg, Germany. [Hall, Alistair S.; Ball, Stephen G.; Balmforth, Anthony J.] Univ Leeds, LIGHT, Leeds LS1 3EX, W Yorkshire, England. [Kathiresan, Sekar] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wright, Ben; Thompson, John R.] Univ Leicester, Dept Hlth Sci & Genet, Leicester LE1 7RH, Leics, England. [Tregouet, David-Alexandre; Cambien, Francois; Tiret, Laurence; Perret, Claire] Univ Paris 06, INSERM, UMR S 525, Paris, France. [Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98109 USA. [Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Gen Med, Seattle, WA 98109 USA. [Salomaa, Veikko] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Chron Dis Epidemiol Unit, FI-00271 Helsinki, Finland. [Elosua, Roberto] Inst Municipal Invest Med, Cardiovasc Epidemiol & Genet Grp, Barcelona 08036, Spain. [Elosua, Roberto] Ciber Epidemiol & Salud Publ, CIBERESP, Barcelona, Spain. [Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Hypertens & Cardiovasc Dis, SE-20502 Malmo, Sweden. [Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [O'Donnell, Christopher J.] NHLBI, NIH, Bethesda, MD 20824 USA. [Peltonen, Leena; Deloukas, Panos] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Altshuler, David] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA 02115 USA. [Altshuler, David] Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Merlini, Piera Angelica] Azienda Osped Niguarda Ca Granda, Div Cardiol, I-20162 Milan, Italy. [Peyvandi, Flora] Univ Milan, Osped Maggiore Mangiagalli & Regina Elena, Fdn Ist Ricovera & Cura Carattere Sci, Dept Internal Med & Med Special, I-20162 Milan, Italy. [Bernardinelli, Luisa] Univ Pavia, Dept Appl Hlth Sci, I-27100 Pavia, Italy. [Bernardinelli, Luisa] MRC, Biostat Unit, Cambridge CB2 0SR, England. [Ardissino, Diego] Univ Parma, Azienda Osped, Div Cardiol, I-43100 Parma, Italy. [Blankenberg, Stefan; Zeller, Tanja; Wild, Philipp] Johannes Gutenberg Univ Mainz, Dept Med 2, D-55099 Mainz, Germany. [Schreiber, Stefan; El Mokhtari, Nour Eddine; Schaefer, Arne] Univ Kiel, Inst Klin Mol Biol, D-24118 Kiel, Germany. [Maerz, Winfried] Synlab Ctr Lab Diagnost Heidelberg, D-69037 Heidelberg, Germany. [Renner, Wilfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8036 Graz, Austria. [Maerz, Winfried] Univ Heidelberg, Dept Publ Hlth Social & Prevent Med, D-69117 Heidelberg, Germany. [Bugert, Peter; Klueter, Harald] Univ Heidelberg, Inst Transfus Med & Immunol, D-69117 Heidelberg, Germany. [Bugert, Peter; Klueter, Harald] Med Fac Mannheim, D-68131 Mannheim, Germany. [Schrezenmeir, Juergen; Rubin, Diana] Inst Physiol & Biochem Ernahrung, Bundesforsch Sanstalt Ernahrung & Lebensmittel, D-24118 Kiel, Germany. [Wichmann, H-Erich; Meisinger, Christa; Baumert, Jens; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Neuherberg, Germany. [Wichmann, H-Erich] LMU, Inst Med Informat Sci Biometry & Epidemiol, D-80539 Munich, Germany. [Meitinger, Thomas] Deutsch Forschungszentrum Umwelt & Gesundheit, Helmholtz Zentrum Munchen, Inst Humangenet, D-85764 Neuherberg, Germany. [Meitinger, Thomas] Tech Univ Munich, Inst Humangenet, D-80333 Munich, Germany. [Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge CB2 2PT, England. RP Erdmann, J (reprint author), Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany. EM j.erdmann@cardiogenics.eu RI Erdmann, Jeanette/P-7513-2014; Erdmann, Jeanette/A-4417-2009; Schreiber, Stefan/B-6748-2008; Altshuler, David/A-4476-2009; Voight, Benjamin/F-1775-2011; Stark, Klaus/D-3813-2009; Deloukas, Panos/B-2922-2013; Meisinger, Christine/B-5358-2014; Peters, Annette/A-6117-2011; Meitinger, Thomas/O-1318-2015; Ziegler, Andreas/G-4246-2012; Tregouet, David-Alexandre/E-3961-2016; Konig, Inke/A-4544-2009 OI Erdmann, Jeanette/0000-0002-4486-6231; Peyvandi, Flora/0000-0001-7423-9864; Wagner, Arnika/0000-0002-0339-8259; Meisinger, Christa/0000-0002-9026-6544; ELOSUA, ROBERTO/0000-0001-8235-0095; Schreiber, Stefan/0000-0003-2254-7771; Altshuler, David/0000-0002-7250-4107; Stark, Klaus/0000-0002-7832-1942; Deloukas, Panos/0000-0001-9251-070X; Ziegler, Andreas/0000-0002-8386-5397; FU British Heart Foundation; Medical Research Council; NCRR NIH HHS [U54 RR020278, U54RR020278]; NHLBI NIH HHS [R01 HL056931-02, R01 HL056931, R01 HL056931-03, R01 HL056931-04, R01 HL087676, R01HL087676]; Wellcome Trust [, 076113, 077011, 089061] NR 14 TC 274 Z9 280 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2009 VL 41 IS 3 BP 280 EP 282 DI 10.1038/ng.307 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 411HL UT WOS:000263640200006 PM 19198612 ER PT J AU Yeger-Lotem, E Riva, L Su, LJ Gitler, AD Cashikar, AG King, OD Auluck, PK Geddie, ML Valastyan, JS Karger, DR Lindquist, S Fraenkel, E AF Yeger-Lotem, Esti Riva, Laura Su, Linhui Julie Gitler, Aaron D. Cashikar, Anil G. King, Oliver D. Auluck, Pavan K. Geddie, Melissa L. Valastyan, Julie S. Karger, David R. Lindquist, Susan Fraenkel, Ernest TI Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity SO NATURE GENETICS LA English DT Article ID DNA-DAMAGING AGENTS; REGULATORY PATHWAY INFERENCE; PARKINSONS-DISEASE; SACCHAROMYCES-CEREVISIAE; EXPRESSION PROFILES; PROTEIN NETWORKS; YEAST-CELLS; GENOME; CHOLESTEROL; MECHANISMS AB Cells respond to stimuli by changes in various processes, including signaling pathways and gene expression. Efforts to identify components of these responses increasingly depend on mRNA profiling and genetic library screens. By comparing the results of these two assays across various stimuli, we found that genetic screens tend to identify response regulators, whereas mRNA profiling frequently detects metabolic responses. We developed an integrative approach that bridges the gap between these data using known molecular interactions, thus highlighting major response pathways. We used this approach to reveal cellular pathways responding to the toxicity of alpha-synuclein, a protein implicated in several neurodegenerative disorders including Parkinson's disease. For this we screened an established yeast model to identify genes that when overexpressed alter alpha-synuclein toxicity. Bridging these data and data from mRNA profiling provided functional explanations for many of these genes and identified previously unknown relations between alpha-synuclein toxicity and basic cellular pathways. C1 [Yeger-Lotem, Esti; Su, Linhui Julie; Gitler, Aaron D.; Cashikar, Anil G.; King, Oliver D.; Auluck, Pavan K.; Geddie, Melissa L.; Valastyan, Julie S.; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Yeger-Lotem, Esti; Riva, Laura; Fraenkel, Ernest] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Auluck, Pavan K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Auluck, Pavan K.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Auluck, Pavan K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Valastyan, Julie S.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Karger, David R.; Fraenkel, Ernest] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Lindquist, Susan] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. RP Lindquist, S (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM lindquist_admin@wi.mit.edu; fraenkel-admin@mit.edu RI Auluck, Pavan/A-1160-2010; Cashikar, Anil/F-5968-2011; YEGER LOTEM, ESTI/F-1540-2012; OI Riva, Laura/0000-0001-5688-4915; Fraenkel, Ernest/0000-0001-9249-8181; Yeger-Lotem, Esti/0000-0002-8279-7898 FU EMBO long-term postdoctoral fellowship; National Parkinson Foundation; Roberto Rocca doctoral fellowship; CSBi Merck-MIT postdoctoral fellowship; American Cancer Society; FoldRx Pharmaceuticals; Eugene Bell Career Development Chair; HHMI; MGH/MIT Morris Udall Center of Excellence in PD Research [NS38372] FX E.Y.-L. has been supported by an EMBO long-term postdoctoral fellowship and by a research grant from the National Parkinson Foundation. L. R. has been supported by Roberto Rocca doctoral fellowship and the CSBi Merck-MIT postdoctoral fellowship. L.J.S. was supported by an American Cancer Society postdoctoral fellowship. A. D. G. was a Lilly Fellow of the Life Sciences Research Foundation. M. L. G is supported by a research grant from the National Parkinson Foundation. S. L. is a founder of and has received consulting fees from FoldRx Pharmaceuticals, a company that investigates drugs to treat protein folding diseases. A. D. G., A. G. C. and S. L. are inventors on patents and patent applications that have been licensed to FoldRx. E. F. is the recipient of the Eugene Bell Career Development Chair. This work was supported in part by HHMI and by MGH/MIT Morris Udall Center of Excellence in PD Research NS38372. We thank M. Taipale, S. Treusch and G. Caraveo Piso for helpful discussions and comments and T. DiCesare for help with figures. L. R. thanks G. Casari and S. Cerutti for support and helpful discussions. NR 48 TC 152 Z9 155 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2009 VL 41 IS 3 BP 316 EP 323 DI 10.1038/ng.337 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 411HL UT WOS:000263640200012 PM 19234470 ER PT J AU Kathiresan, S Altschuler, D Anand, S Ardissino, D Asselta, R Ball, SG Balmforth, AJ Berger, K Berglund, G Bernardi, F Bernardinelli, L Berzuini, C Braund, PS Burnett, MS Burtt, N Cambien, F Casari, G Celli, P Chen, Z Corrocher, R Daly, MJ Deloukas, P Devaney, J Do, R Duga, S Elosua, R Engert, JC Epstein, SE Erdmann, J Ferrario, M Fetiveau, R Fischer, M Friedlander, Y Gabriel, SB Galli, M Gianniny, L Girelli, D Grosshennig, A Guiducci, C Hakonarson, HH Hall, AS Havulinna, AS Hengstenberg, C Hirschhorn, JN Holm, H Huge, A Kent, KM Konig, IR Korn, JM Li, M Lieb, W Lindsay, JM Linsel-Nitschke, P Lucas, G MacRae, CA Mannucci, PM Marrugat, J Martinelli, N Marziliano, N Matthai, W McCarroll, SA McKeown, PP Meigs, JB Melander, O Merlini, PA Mirel, D Morgan, T Musunuru, K Nathan, DM Nemesh, J O'Donnell, CJ Olivieri, O Ouwehand, W Parkin, M Patterson, CC Peltonen, L Peyvandi, F Piazza, A Pichard, AD Preuss, M Purcell, S Qasim, A Rader, DJ Ramos, R Reilly, MP Ribichini, F Rossi, M Sala, J Salomaa, V Samani, NJ Satler, L Scheffold, T Scholz, M Schreiber, S Schunkert, H Schwartz, SM Siscovick, DS Spertus, JA Spreafico, M Stark, K Stefansson, K Stoll, M Subirana, I Surti, A Thompson, JR Thorleifsson, G Thorsteinsdottir, U Tubaro, M Voight, BF Waksman, R Wichmann, HE Wilensky, R Williams, G Wright, BJ Xie, C Yee, J Ziegler, A Zonzin, P AF Kathiresan, Sekar Altschuler, David Anand, Sonia Ardissino, Diego Asselta, Rosanna Ball, Stephen G. Balmforth, Anthony J. Berger, Klaus Berglund, Goran Bernardi, Francesco Bernardinelli, Luisa Berzuini, Carlo Braund, Peter S. Burnett, Mary-Susan Burtt, Noel Cambien, Francois Casari, Giorgio Celli, Patrizia Chen, Zhen Corrocher, Roberto Daly, Mark J. Deloukas, Panos Devaney, Joe Do, Ron Duga, Stefano Elosua, Roberto Engert, James C. Epstein, Stephen E. Erdmann, Jeanette Ferrario, Maurizio Fetiveau, Raffaela Fischer, Marcus Friedlander, Yechiel Gabriel, Stacey B. Galli, Michele Gianniny, Lauren Girelli, Domenico Grosshennig, Anika Guiducci, Candace Hakonarson, Hakon H. Hall, Alistair S. Havulinna, Aki S. Hengstenberg, Christian Hirschhorn, Joel N. Holm, Hilma Huge, Andreas Kent, Kenneth M. Konig, Inke R. Korn, Joshua M. Li, Mingyao Lieb, Wolfgang Lindsay, Joseph M. Linsel-Nitschke, Patrick Lucas, Gavin MacRae, Calum A. Mannucci, Pier M. Marrugat, Jaume Martinelli, Nicola Marziliano, Nicola Matthai, William McCarroll, Steven A. McKeown, Pascal P. Meigs, James B. Melander, Olle Merlini, Pier Angelica Mirel, Daniel Morgan, Thomas Musunuru, Kiran Nathan, David M. Nemesh, James O'Donnell, Christopher J. Olivieri, Oliviero Ouwehand, Willem Parkin, Melissa Patterson, Chris C. Peltonen, Leena Peyvandi, Flora Piazza, Alberto Pichard, Augusto D. Preuss, Michael Purcell, Shaun Qasim, Atif Rader, Daniel J. Ramos, Rafael Reilly, Muredach P. Ribichini, Flavio Rossi, Marco Sala, Joan Salomaa, Veikko Samani, Nilesh J. Satler, Lowell Scheffold, Thomas Scholz, Michael Schreiber, Stefan Schunkert, Heribert Schwartz, Stephen M. Siscovick, David S. Spertus, John A. Spreafico, Marta Stark, Klaus Stefansson, Kari Stoll, Monika Subirana, Isaac Surti, Aarti Thompson, John R. Thorleifsson, Gudmar Thorsteinsdottir, Unnur Tubaro, Marco Voight, Benjamin F. Waksman, Ron Wichmann, H-Erich Wilensky, Robert Williams, Gordon Wright, Benjamin J. Xie, Changchun Yee, Jean Ziegler, Andreas Zonzin, Pietro CA Myocardial Infarction Genetics Consortium TI Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants SO NATURE GENETICS LA English DT Article ID CORONARY-ARTERY-DISEASE; LDL-RECEPTOR GENE; HEART-DISEASE; CARDIOVASCULAR-DISEASE; COMMON VARIANTS; RISK; CHOLESTEROL; LOCI; PCSK9; HYPERCHOLESTEROLEMIA AB We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases ad 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations(1-4) (9p21, 1p13 near CERSL2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (> 1% allele frequency) and none met the pre-specified threshold for replication (P < 10(-3)). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Hum Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Gen Med Div, Boston, MA 02114 USA. Broad Inst MIT & Harvard, Prgm Med Populat Genet, Cambridge, MA 02142 USA. Harvard Med Sch, Dept Med, Boston, MA 02115 USA. Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. Univ Parma, Azienda Osped, I-43100 Parma, Italy. Univ Milan, Dept Intern Med & Med Specialities, Fdn Ist Ricov & Cura Carattere Sci, Osped Maggiore Mangiagalle & Regina Elena, I-20122 Milan, Italy. Univ Milan, Dept Biol Genet Med Sci, I-20133 Milan, Italy. McMaster Univ, Populat Hlth Res Inst, Hamilton Hlth Sci, Hamilton, ON L8L 2X2, Canada. McMaster Univ, Hamilton Hlth Sci, Dept Med, Hamilton, ON L8L 2X2, Canada. McMaster Univ, Hamilton Hlth Sci, Dept Clin Epidemiol, Hamilton, ON L8L 2X2, Canada. McMaster Univ, Hamilton Hlth Sci, Dept Biostatist, Hamilton, ON L8L 2X2, Canada. McGill Univ, Dept Med, Quebec City, PQ H3A 1A1, Canada. McGill Univ, Dept Human Genet, Quebec City, PQ H3A 1A1, Canada. Azienda Osped Niguarda Ca Granda, Div Cardiol, I-20162 Milan, Italy. Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Cardiovasc Endocrinol Sect, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. Univ Kiel, Inst Klin Molekularbiol, D-24105 Kiel, Germany. CIBER Epidemiol & Salud Publ, Barcelona 08003, Spain. Ctr Mathemat Sci, Stat Lab, Cambridge CB3 0WA, England. deCODE Genet Inc, IS-101 Reykjavik, Iceland. Framingham Heart Study &, Natl Heart Lung Blood Inst, Framingham, MA 01702 USA. Hebrew Univ Hadassah Sch Publ Hlth, Epidemiol, IL-91120 Jerusalem, Israel. Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, D-85764 Neuherberg, Germany. Hosp Girona Josep Trueta, Cardiol, Coronar, Girona 17007, Spain. Inst Catala Salut, IDIAP Jordi Gol, Barcelona 08007, Spain. Inst Invest Biomed Girona, Girona 17007, Spain. Inst Municip Invest Med, Cardiovasc Epidemiol & Genet, Barcelona 08003, Spain. Ist Clin Humanitas, Fdn Ist Ricov & Cura Carrattere Sci, Div Cardiol, I-20089 Milan, Italy. Ludwig Maximilians Univ Munchen, Inst Med Inform Sci Biometr & Epidemiol, D-81377 Munich, Germany. Lund Univ, Univ Hosp Malmo, Dept Clin Sci Hypertens & Cardiovasc Dis, S-20502 Malmo, Sweden. Lund Univ, Univ Hosp Malmo, Dept Clin Sci, Int Med, S-20502 Malmo, Sweden. MRC, Biostat Unit, Cambridge, England. Mid America Heart Inst & Univ Missouri, Kansas City, MO 64111 USA. Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki 00300, Finland. Osped Livorno, Div Cardiol, I-57100 Livorno, Italy. Osped San Camillo, Div Cardiol, I-00151 Rome, Italy. Osped San Filippo Neri, Div Cardiol, I-00135 Rome, Italy. Policlin San Matteo, Fdn Ist Ricov & Cura Carrattere Sci, I-27100 Pavia, Italy. Queens Univ Belfast, Ctr Publ Hlth, Inst Clin Sci, Belfast BT12 6BJ, North Ireland. Ist Sci San Raffaele, Milan, Italy. San Raffaele Univ, Vita Salute, I-20132 Milan, Italy. Trium Anal Online GmbH, D-81677 Munich, Germany. Univ Cambridge, Dept Hematol, Cambridge CB2 2PT, England. Univ Ferrara, Dept Biochem & Mol Biol, I-44100 Ferrara, Italy. Univ Helsinki, Inst Mol Med, Helsinki 00029, Finland. Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. Univ Leeds, LIGHT Res Inst, Fac Med & Hlth, Leeds LS1 3EX, England. Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, England. Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, England. Univ Lubeck, Med Klinik 2, D-23538 Lubeck, Germany. Univ Lubeck, Inst Med Biometr & Stat, D-23538 Lubeck, Germany. Univ Munster, Liebniz Inst Arterioscler Res, D-48149 Munster, Germany. Univ Munster, Inst Epidemiol & Social Med, D-48149 Munster, Germany. Univ Paris 06, INSERM UMR S 525, F-75634 Paris, France. Univ Pavia, Dept Appl Hlth Sci, I-27100 Pavia, Italy. Univ Pennsylvania, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. Univ Pennsylvania, Cardiovasc Inst, Philadelphia, PA 19104 USA. Univ Pennsylvania, Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Regensburg, Klin & Poliklin Innere Med 2, D-93042 Regensburg, Germany. Osped Rovigo, Div Cardiol, I-45100 Rovigo, Italy. Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy. Univ Verona, Dept Clin & Expt Med, I-37134 Verona, Italy. Univ Verona, Osped Borgo Trento, Div Cardiol, I-37126 Verona, Italy. Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA. Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Witten Herdecke, Inst Heart & Circulat Res, D-44227 Dortmund, Germany. Vanderbilt Univ Sch Med, Dept Pediat, Nashville, TN 37232 USA. Washington Hosp Ctr, MedStar Res Inst, Cardiovasc Res Inst, Washington, DC 20010 USA. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM skathiresan1@partners.org RI Erdmann, Jeanette/A-4417-2009; Erdmann, Jeanette/P-7513-2014; Altshuler, David/A-4476-2009; Schreiber, Stefan/B-6748-2008; Ramos , Rafel/D-9627-2016; Voight, Benjamin/F-1775-2011; Stark, Klaus/D-3813-2009; Martinelli, Nicola/J-5622-2016; Konig, Inke/A-4544-2009; Morgan, Tom/C-3478-2012; Lieb, Wolfgang/C-1990-2012; Lucas, Gavin/D-4346-2012; Deloukas, Panos/B-2922-2013; Mannucci, Pier/C-3102-2014; Duga, Stefano/F-8173-2014; Ziegler, Andreas/G-4246-2012; OI Piazza, Alberto/0000-0002-2355-4183; Asselta, Rosanna/0000-0001-5351-0619; Ramos , Rafel/0000-0001-7970-5537; ELOSUA, ROBERTO/0000-0001-8235-0095; CASARI, Giorgio/0000-0002-0115-8980; Erdmann, Jeanette/0000-0002-4486-6231; Peyvandi, Flora/0000-0001-7423-9864; Altshuler, David/0000-0002-7250-4107; Schreiber, Stefan/0000-0003-2254-7771; Ramos , Rafel/0000-0001-8146-5288; Stark, Klaus/0000-0002-7832-1942; Martinelli, Nicola/0000-0001-6465-5119; Deloukas, Panos/0000-0001-9251-070X; Ziegler, Andreas/0000-0002-8386-5397; Duga, Stefano/0000-0003-3457-1410; Marrugat, Jaume/0000-0003-3320-554X FU Canada Graduate Scholarship Doctoral Award from the Canadian Institutes for Health Research; May Cohen Eli Lilly Endowed Chair in Womens Health Research, McMaster University; Michael G. DeGroote and Heart and Stroke Foundation of Ontario Chair in Population Health; Cardiovascular Institute of the University of Pennsylvania; UK Medical Research Council; European Union [LSHM-CT- 2006-037593]; Canadian Institutes for Health Research; German Federal Ministry of Education and Research; Deutsche Forschungsgemeinschaft; Heart Trust Fund (Royal Victoria Hospital); Northern Ireland Chest, Heart and Stroke Association; Royal Victoria Hospital Research Fellowship; Northern Ireland Research and Development Office; Cariverona Foundation, Verona, Italy; Veneto Region; Italian Ministry of University and Research; MedStar Research Institute; GlaxoSmithKline; British Heart Foundation; Wellcome Trust; Finnish Foundation for Cardiovascular Research; Nordic Center of Excellence in Disease Genetics; Center of Excellence in Complex Disease Genetics of the Academy of Finland; Sigrid Juselius Foundation; National Center for Research Resources [U54 RR020278]; The Broad Institute Center for Genotyping and Analysis; Department of Medicine and Cardiovascular Research Center at Massachusetts General Hospital; Donovan Family Foundation; Fannie E. Rippel Foundation; Doris Duke Charitable Foundation Clinical Scientist Development Award; National Heart, Lung, and Blood Institute; AGAUR Generalitat de Catalunya; FIS de Catalunya; CIBER Epidemiologia y Salud Publica; Ministerio de Sanidad y Consumo Instituto de Salud Carlos III [Red HERACLES RD06/0009]; US National Institutes of Health [K24 DK080140, N01HD013107, P30ES007033, R01HL056931] FX The HARPS study was supported by the grants (R01HL056931, P30ES007033) and a contract (N01HD013107) from US National Institutes of Health.; The REGICOR study was partially funded by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (Red HERACLES RD06/0009), the CIBER Epidemiologia y Salud Publica, the FIS and AGAUR Generalitat de Catalunya.; Massachusetts General Hospital. The MIGen study was funded by the US National Institutes of Health (NIH) and National Heart, Lung, and Blood Institutes STAMPEED genomics research program through a grant to D.A. S.K. is supported by a Doris Duke Charitable Foundation Clinical Scientist Development Award, a charitable gift from the Fannie E. Rippel Foundation, the Donovan Family Foundation, a career development award from the NIH and the Department of Medicine and Cardiovascular Research Center at Massachusetts General Hospital. J.B.M. is supported by grant K24 DK080140 from the NIH.; Broad Institute. Genotyping was partially funded by The Broad Institute Center for Genotyping and Analysis, which is supported by grant U54 RR020278 from the National Center for Research Resources.; FINRISK. V.S. was supported by the Sigrid Juselius Foundation. L.P. was supported by the Center of Excellence in Complex Disease Genetics of the Academy of Finland, the Nordic Center of Excellence in Disease Genetics and the Finnish Foundation for Cardiovascular Research.; WTCCC Study. The study was funded by the Wellcome Trust. Recruitment of cases for the WTCCC Study was carried out by the British Heart Foundation (BHF) Family Heart Study Research Group and supported by the BHF and the UK Medical Research Council. N.J.S. and S.G.B. hold chairs funded by the BHF.; PennCATH/MedStar. Recruitment of the PennCATH cohort was supported by the Cardiovascular Institute of the University of Pennsylvania. Recruitment of the MedStar cohort was supported by a research grant from GlaxoSmithKline and from the MedStar Research Institute. Genotyping was done at the Center for Applied Genomics at the Childrens Hospital of Philadelphia and supported by GlaxoSmithKline through an Alternate Drug Discovery Initiative research alliance award (to M.P.R. and D.J.R.) with the University of Pennsylvania School of Medicine. D.J.R. was supported by a Doris Duke Charitable Foundation Distinguished Clinical Scientist Award.; Verona Heart Study. The study was supported by a grant from the Italian Ministry of University and Research and grants from the Veneto Region and the Cariverona Foundation, Verona, Italy; Mid-America Heart Institute. T.M. is supported by a career development grant from the NIH.; Irish Family Study. We thank the clinical staff members for their valuable contribution to the collection of families for this study. The research was supported by the Northern Ireland Research and Development Office, a Royal Victoria Hospital Research Fellowship, the Northern Ireland Chest, Heart and Stroke Association, and the Heart Trust Fund (Royal Victoria Hospital).; GerMIFS I and II. The German Study was supported by the Deutsche Forschungsgemeinschaft and the German Federal Ministry of Education and Research in the context of the German National Genome Research Network. Cardiogenics. Cardiogenics is an EU-funded integrated project (LSHM-CT- 2006-037593).; INTERHEART. S.A. holds the Michael G. DeGroote and Heart and Stroke Foundation of Ontario Chair in Population Health and the May Cohen Eli Lilly Endowed Chair in Womens Health Research, McMaster University. We acknowledge the contribution of S. Yusuf who initiated and, together with the Steering Committee, supervised the conduct of the INTERHEART study. We thank members of the Project Office, S. Rangarajan (study coordinator) and K. Hall (laboratory manager), for their assistance in coordinating the genetics component of the INTERHEART project. R.D. is a recipient of a Canada Graduate Scholarship Doctoral Award from the Canadian Institutes for Health Research. NR 30 TC 538 Z9 548 U1 5 U2 62 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2009 VL 41 IS 3 BP 334 EP 341 DI 10.1038/ng.327 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 411HL UT WOS:000263640200023 ER PT J AU Newton-Cheh, C Larson, MG Vasan, RS Levy, D Bloch, KD Surti, A Guiducci, C Kathiresan, S Benjamin, EJ Struck, J Morgenthaler, NG Bergmann, A Blankenberg, S Kee, F Nilsson, P Yin, XY Peltonen, L Vartiainen, E Salomaa, V Hirschhorn, JN Melander, O Wang, TJ AF Newton-Cheh, Christopher Larson, Martin G. Vasan, Ramachandran S. Levy, Daniel Bloch, Kenneth D. Surti, Aarti Guiducci, Candace Kathiresan, Sekar Benjamin, Emelia J. Struck, Joachim Morgenthaler, Nils G. Bergmann, Andreas Blankenberg, Stefan Kee, Frank Nilsson, Peter Yin, Xiaoyan Peltonen, Leena Vartiainen, Erkki Salomaa, Veikko Hirschhorn, Joel N. Melander, Olle Wang, Thomas J. TI Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; HYPERTENSION; PLASMA; RISK; PROJECT; IMPACT; CONTRIBUTE; MUTATIONS; MORTALITY AB We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 10(-68)). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were also found to be associated with lower systolic (P = 2 x 10(-6) and 6 x 10(-5), respectively) and diastolic blood pressure (P = 1 x 10(-6) and 5 x 10(-5)), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 x 10(-5); OR = 0.90, 95% CI = 0.85-0.95, P = 2 x 10(-4), respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension. C1 [Newton-Cheh, Christopher; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Bloch, Kenneth D.; Kathiresan, Sekar; Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Surti, Aarti; Guiducci, Candace; Kathiresan, Sekar; Hirschhorn, Joel N.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Newton-Cheh, Christopher; Larson, Martin G.; Vasan, Ramachandran S.; Levy, Daniel; Kathiresan, Sekar; Benjamin, Emelia J.; Yin, Xiaoyan; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Larson, Martin G.] Boston Univ, Sch Med, Dept Math, Boston, MA 02215 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Levy, Daniel] NHLBI, Bethesda, MD 20892 USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Struck, Joachim; Morgenthaler, Nils G.; Bergmann, Andreas] BRAHMS AG, Dept Res, D-16761 Hennigsdorf, Germany. [Blankenberg, Stefan] Johannes Gutenberg Univ Mainz, Dept Med 2, D-55131 Mainz, Germany. [Kee, Frank] Royal Victoria Hosp, Ctr Excellence Publ Hlth NI, A UKCRC, Belfast BT12 6BJ, Antrim, North Ireland. [Nilsson, Peter; Melander, Olle] Malmo Univ Hosp, CRC, SE-20502 Malmo, Sweden. [Peltonen, Leena; Vartiainen, Erkki; Salomaa, Veikko] KTL Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, FI-00300 Helsinki, Finland. [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Peltonen, Leena] Inst Mol Med Finland FIMM, Biomedicum Helsinki, FI-00290 Helsinki, Finland. [Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 55 Fruit St, Boston, MA 02114 USA. EM cnewtoncheh@chgr.mgh.harvard.edu; tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Medical Research Council [G0601463: 80983]; NHLBI NIH HHS [HL66582, K23 HL074077, K23 HL074077-05, K23 HL080025, K23 HL080025-04, K23-HL-074077, K23-HL-080025, K24 HL004334, K24-HL-04334, N01-HC-25195, N01HC25195, R01 HL070896, R01 HL083197, R01 HL086875, R01 HL093328, R01-HL-070896, R01-HL-083197, R01-HL-086875, U01 HL066582]; NIDDK NIH HHS [R01 DK081572, R01-DK-081572]; Wellcome Trust [089061] NR 30 TC 183 Z9 193 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2009 VL 41 IS 3 BP 348 EP 353 DI 10.1038/ng.328 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 411HL UT WOS:000263640200017 PM 19219041 ER PT J AU Kolasinska-Zwierz, P Down, T Latorre, I Liu, T Liu, XS Ahringer, J AF Kolasinska-Zwierz, Paulina Down, Thomas Latorre, Isabel Liu, Tao Liu, X. Shirley Ahringer, Julie TI Differential chromatin marking of introns and expressed exons by H3K36me3 SO NATURE GENETICS LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTION ELONGATION; SACCHAROMYCES-CEREVISIAE; MAMMALIAN CHROMATIN; METHYLATION STATES; X-CHROMOSOME; HISTONE H3; SET2; GENOME; METHYLTRANSFERASE AB Variation in patterns of methylations of histone tails reflects and modulates chromatin structure and function(1). To provide a framework for the analysis of chromatin function in Caenorhabditis elegans, we generated a genome-wide map of histone H3 tail methylations. We find that C. elegans genes show distributions of histone modifications that are similar to those of other organisms, with H3K4me3 near transcription start sites, H3K36me3 in the body of genes and H3K9me3 enriched on silent genes. We also observe a novel pattern: exons are preferentially marked with H3K36me3 relative to introns. H3K36me3 exon marking is dependent on transcription and is found at lower levels in alternatively spliced exons, supporting a splicing-related marking mechanism. We further show that the difference in H3K36me3 marking between exons and introns is evolutionarily conserved in human and mouse. We propose that H3K36me3 exon marking in chromatin provides a dynamic link between transcription and splicing. C1 [Kolasinska-Zwierz, Paulina; Down, Thomas; Latorre, Isabel; Ahringer, Julie] Univ Cambridge, Gurdon Inst, Cambridge CB2 1QN, England. [Kolasinska-Zwierz, Paulina; Down, Thomas; Latorre, Isabel; Ahringer, Julie] Univ Cambridge, Dept Genet, Cambridge CB2 1QN, England. [Liu, Tao; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Ahringer, J (reprint author), Univ Cambridge, Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England. EM ja219@cam.ac.uk RI Liu, Tao/G-3585-2010; OI Liu, Tao/0000-0002-8818-8313; Liu, Tao/0000-0003-0446-9001; Latorre, Isabel/0000-0003-0638-1783 FU National Human Genome Research Institute [1-U01HG004270-01]; Wellcome Trust Senior Research Fellowship [054523]; Cambridge Newton Trust; Gates Foundation; Wellcome Trust Research Career Development Fellowship [083563] FX We thank all the members of our modENCODE consortium for help and advice, and especially J. Lieb's laboratory for help with ChIP protocol development and S. Strome's laboratory for discussions about H3K36me3. We are very grateful to H. Holster for expert microarray processing at Roche. This work was supported by National Human Genome Research Institute modENCODE grant 1-U01HG004270-01, by a Wellcome Trust Senior Research Fellowship (054523) and Cambridge Newton Trust funding to J. A., by a Gates Foundation studentship to P. K.-Z. and by a Wellcome Trust Research Career Development Fellowship (083563) to T. D. NR 30 TC 323 Z9 331 U1 0 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAR PY 2009 VL 41 IS 3 BP 376 EP 381 DI 10.1038/ng.322 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 411HL UT WOS:000263640200022 PM 19182803 ER PT J AU Sui, JH Hwang, WC Perez, S Wei, G Aird, D Chen, LM Santelli, E Stec, B Cadwell, G Ali, M Wan, HQ Murakami, A Yammanuru, A Han, T Cox, NJ Bankston, LA Donis, RO Liddington, RC Marasco, WA AF Sui, Jianhua Hwang, William C. Perez, Sandra Wei, Ge Aird, Daniel Chen, Li-mei Santelli, Eugenio Stec, Boguslaw Cadwell, Greg Ali, Maryam Wan, Hongquan Murakami, Akikazu Yammanuru, Anuradha Han, Thomas Cox, Nancy J. Bankston, Laurie A. Donis, Ruben O. Liddington, Robert C. Marasco, Wayne A. TI Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID MEMBRANE-FUSION; HEMAGGLUTININ STRUCTURES; MONOCLONAL-ANTIBODY; RECEPTOR-BINDING; DIFFRACTION DATA; H5N1; PROTEIN; EPITOPE; SUBTYPES; RESIDUES AB Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses. (c) 2009 Nature America, Inc. All rights reserved. C1 [Sui, Jianhua; Aird, Daniel; Ali, Maryam; Murakami, Akikazu; Yammanuru, Anuradha; Han, Thomas; Marasco, Wayne A.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Sui, Jianhua; Aird, Daniel; Murakami, Akikazu; Yammanuru, Anuradha; Han, Thomas; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Hwang, William C.; Wei, Ge; Santelli, Eugenio; Stec, Boguslaw; Cadwell, Greg; Bankston, Laurie A.; Liddington, Robert C.] Burnham Inst Med Res, Infect & Inflammatory Dis Ctr, La Jolla, CA 92037 USA. [Perez, Sandra; Chen, Li-mei; Wan, Hongquan; Cox, Nancy J.; Donis, Ruben O.] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. RP Sui, JH (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM jianhua_sui@dfci.harvard.edu; rvd6@cdc.gov; wayne_marasco@dfci.harvard.edu RI Chiang, Vincent, Ming-Hsien/D-4312-2016; OI Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863; SUI, JIANHUA/0000-0002-1272-9662 FU NIH [P41 RR-01081, U01-AI074518-01, P01-AI055789] FX We thank J. Appleton (Cornell University) for the gift of mouse mAbs against H5N1, 17A2.1.2 and 22F; A. Klimov (CDC) and A. Balish (CDC) for providing ferret antiserum and virus sequences; R. Webster (St. Jude Children's Research Hospital) for H11N9, H13N6 and H16N3; L. Quynh Mai (National Institute of Hygiene and Epidemiology, Vietnam Ministry of Health) for H5N1; W. Lim (Hong Kong Department of Health) for H5N1 and H9N2, as well as E. Sedyaningsih, T. Soendoro (National Institute of Health Research and Development, Indonesian Ministry of Health) for H5N1 specimens; P. Palese (Mount Sinai School of Medicine) for pCAGGS-H1(SC) plasmid encoding the full-length hemagglutinin protein of H1-SC1918; M. Farzan (New England Primate Research Center, Harvard Medical School) for pCAGGS-H1 (PR) plasmid encoding the hemagglutinin protein of H1-PR34 and X. Yang (Beth Israel Deaconess Medical Center, Harvard Medical School) for pCAGGS-H7 (FPV) encoding H7-FP34 hemagglutinin; and R. Fuller (University of Michigan) for furin cDNA. We thank W. Yuan and W. Li for helpful discussions and Y. Lin for assistance in crystallization and critical discussion. We thank the US National Institutes of Health (NIH) and the Department of Energy (DOE) for access to the Stanford Synchrotron Radiation Facility and the facility staff for assistance in X-ray data collection. Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR-01081). This work was supported by NIH (U01-AI074518-01) to W. A. M. and in part by NIH (P01-AI055789) to R. C. L. NR 61 TC 613 Z9 630 U1 16 U2 148 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAR PY 2009 VL 16 IS 3 BP 265 EP 273 DI 10.1038/nsmb.1566 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 415AF UT WOS:000263906000008 PM 19234466 ER PT J AU Asselbergs, FW Mozaffarian, D Katz, R Kestenbaum, B Fried, LF Gottdiener, JS Shlipak, MG Siscovick, DS AF Asselbergs, Folkert W. Mozaffarian, Dariush Katz, Ronit Kestenbaum, Bryan Fried, Linda F. Gottdiener, John S. Shlipak, Michael G. Siscovick, David S. TI Association of renal function with cardiac calcifications in older adults: the cardiovascular health study SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE chronic kidney disease; cohort; creatinine; cystatin C; elderly ID MITRAL ANNULAR CALCIFICATION; GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; PERITONEAL-DIALYSIS PATIENTS; SERUM CYSTATIN-C; VALVE CALCIFICATION; HEMODIALYSIS-PATIENTS; ELDERLY PERSONS; ALL-CAUSE; CREATININE AB Background. Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are highly prevalent in patients with end-stage renal disease. It is less well established whether milder kidney disease is associated with cardiac calcifications. We evaluated the relationships between renal function and MAC, aortic annular calcification (AAC) and AVS in the elderly. Methods. From the Cardiovascular Health Study, a community-based cohort of ambulatory adults >= age 65, a total of 3929 individuals (mean +/- SD age 74 +/- 5 years, 60% women) were evaluated with two-dimensional echocardiography. Renal function was assessed by means of creatinine-based estimated glomerular filtration rate (eGFR) and cystatin C. Results. The prevalences of MAC and AAC were significantly higher in individuals with an eGFR < 45 mL/ min/1.73 m(2) (P < 0.01 for each), and cystatin C levels were significantly higher in individuals with MAC or AAC compared to individuals without these cardiac calcifications (P < 0.001 for each). After multivariate-adjustment, an eGFR < 45 mL/min/1.73 m(2) was significantly associated with MAC [odds ratio 1.54 (95% CI 1.16-2.06), P = 0.003] and not associated with AAC [1.30 (0.97-1.74), P = 0.085] and AVS [1.15 (0.86-1.53), P = 0.355]. In addition, cystatin C levels were independently associated with MAC [odds ratio per SD 1.12 (1.05-1.21), P = 0.001] and not associated with AAC [1.07 (1.00-1.15), P = 0.054] and AVS [0.99 (0.93-1.06), P = 0.82]. Furthermore, the prevalence of multiple cardiac calcifications was higher in subjects with an eGFR < 45 mL/ min/1.73 m(2) and increased per quartile of cystatin C (P-values < 0.001). In addition, a significant trend was observed between an eGFR < 45 mL/min/1.73 m(2), increasing levels of cystatin C and the number of cardiac calcifications (P < 0.05). Conclusions. In a community-based cohort of the elderly, moderate kidney disease as defined by an eGFR < 45 mL/min/1.73m(2) and elevated levels of cystatin C was associated with prevalent MAC. In addition, a significant trend was observed between an eGFR < 45 mL/min/1.73m(2), increasing levels of cystatin C and the number of cardiac calcifications. No associations were found between renal function and AAC or AVS. C1 [Asselbergs, Folkert W.] Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, NL-9713 GZ Groningen, Netherlands. [Mozaffarian, Dariush] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mozaffarian, Dariush] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA. [Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Katz, Ronit] Univ Washington, Coordinating Ctr, Seattle, WA 98195 USA. [Kestenbaum, Bryan] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Med Serv, Renal Sect, Pittsburgh, PA USA. [Gottdiener, John S.] Univ Maryland Hosp, Div Cardiol, Baltimore, MD 21201 USA. [Shlipak, Michael G.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94143 USA. [Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Asselbergs, FW (reprint author), Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM fwasselbergs@hotmail.com RI Mozaffarian, Dariush/B-2276-2008 FU Netherlands Heart Foundation [2003T010]; Dutch Inter University Cardiology Institute Netherlands; American Federation for Aging Research and National Institute on Aging; Robert Wood Johnson Foundation [R01 DK066488]; National Heart, Lung and Blood Institute (NHLBI) [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103]; [R01 HL073208-01]; [R01 AG027002] FX Dr F. W. Asselbergs is a research fellow of the Netherlands Heart Foundation (2003T010) and the Dutch Inter University Cardiology Institute Netherlands. Drs Shlipak, Fried and Katz are funded by R01 HL073208-01. Dr Shlipak is also supported by the American Federation for Aging Research and National Institute on Aging (Paul Beeson Scholars Program), by the Robert Wood Johnson Foundation (Generalist Faculty Scholars Program) and by R01 DK066488. Drs Fried, Shlipak and Siscovick are also supported by R01 AG027002. The Cardiovascular Health Study (CHS) is supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129 and N01-HC-15103 from the National Heart, Lung and Blood Institute ( NHLBI). A full list of participating CHS investigators and institutions can be found at www.chs-nhlbi.org. NR 28 TC 15 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAR PY 2009 VL 24 IS 3 BP 834 EP 840 DI 10.1093/ndt/gfn544 PG 7 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 410UY UT WOS:000263605000024 PM 18840892 ER PT J AU Pompili, M Innamorati, M Giupponi, G Pycha, R Rihmer, Z Casale, AD Manfredi, G Celentano, A Fiori-Nastro, P Ferracuti, S Girardi, P Tatarelli, R Akiskal, HS AF Pompili, M. Innamorati, M. Giupponi, G. Pycha, R. Rihmer, Z. Casale, A. D. Manfredi, G. Celentano, A. Fiori-Nastro, Paolo Ferracuti, S. Girardi, P. Tatarelli, R. Akiskal, H. S. TI Predicting risk of suicide in bipolar and unipolar depression. Correlation between temperament and personality SO NERVENARZT LA German DT Article DE Suicide; Temperament; Personality traits; Mood disorders ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; CYCLOTHYMIC TEMPERAMENT; CLINICAL PREDICTORS; AFFECTIVE-DISORDER; MAJOR DEPRESSION; MOOD DISORDERS; SAN-DIEGO; DSM-IV; BEHAVIOR; HOPELESSNESS AB Objective. The aim of this study was to evaluate the roles of personality and affective temperament traits in the prediction of suicide risk in mood disorders. Methods. The participants were 147 psychiatric inpatients with bipolar disorders I and II and major depressive disorder. Patients undertook the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego self-rating questionnaire, the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), and the Beck Hopelessness Scale. Results. Sixty-four subjects were diagnosed with increased suicidal risk based on the Mini International Neuropsychiatric Interview (MINI). Logistic regression analysis resulted in two models predictive of MINI-based suicidal risk: irritable temperament and the MMPI-2 scale. Multiple regression analysis further indicated that higher hyperthymic values are protective against hopelessness, while MINI-based suicidal intent is a predictor of hopelessness. Conclusions. Personality and affective temperament traits may have a role in the prediction of suicide. C1 [Pompili, M.; Casale, A. D.; Manfredi, G.; Celentano, A.; Ferracuti, S.; Girardi, P.; Tatarelli, R.] Univ Roma La Sapienza, St Andrea Hosp, Dept Psychiat, I-1035 Rome, Italy. [Pompili, M.; Innamorati, M.] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. [Pompili, M.; Innamorati, M.] Div Massachusetts Gen Hosp, Int Consortium Bipolar Disorder Res, Belmont, MA USA. [Innamorati, M.] Univ Europea Roma, Rome, Italy. [Giupponi, G.] Osped S Maurizio Bolzano, Bolzano, Italy. [Rihmer, Z.] Semmelweis Univ, Dept Psychiat & Psychotherapy, H-1085 Budapest, Ungam, Hungary. [Rihmer, Z.] Natl Inst Psychiat & Neurol, Budapest, Hungary. [Akiskal, H. S.] Int Mood Ctr, La Jolla, CA USA. [Akiskal, H. S.] San Diego Vet Adm Med Ctr, San Diego, CA USA. RP Pompili, M (reprint author), Univ Roma La Sapienza, St Andrea Hosp, Dept Psychiat, Via Grottarossa 1035, I-1035 Rome, Italy. EM mpompili@mclean.harvard.edu RI Manfredi, Giovanni/C-2176-2011; Innamorati, Marco/H-8877-2013; Giupponi, Giancarlo/J-9824-2016; Fiori Nastro, Paolo/B-3135-2012; OI Innamorati, Marco/0000-0003-1389-2290; Giupponi, Giancarlo/0000-0001-6430-0000; Fiori Nastro, Paolo/0000-0002-6722-942X; Tatarelli, Roberto/0000-0003-4396-2632; Pompili, Maurizio/0000-0003-1886-4977 NR 60 TC 5 Z9 5 U1 3 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-2804 J9 NERVENARZT JI Nervenarzt PD MAR PY 2009 VL 80 IS 3 BP 315 EP 323 DI 10.1007/s00115-008-2611-2 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 428TH UT WOS:000264872400008 PM 19104766 ER PT J AU Feczko, E Augustinack, JC Fischl, B Dickerson, BC AF Feczko, Eric Augustinack, Jean C. Fischl, Bruce Dickerson, Bradford C. TI An MRI-based method for measuring volume, thickness and surface area of entorhinal, perirhinal, and posterior parahippocampal cortex SO NEUROBIOLOGY OF AGING LA English DT Article DE Entorhinal cortex; Perirhinal cortex; Parahippocampal cortex; Alzheimer's disease; Magnetic resonance imaging; Memory ID MEDIAL TEMPORAL-LOBE; MILD ALZHEIMERS-DISEASE; HUMAN CEREBRAL-CORTEX; CORTICAL SURFACE; COORDINATE SYSTEM; TEMPOROPOLAR; HIPPOCAMPUS; RELIABILITY; IMPAIRMENT; ATROPHY AB Several quantitative MRI-based protocols have been developed for measuring the volume of entorhinal (ERC), perirhinal (PRC), and posterior parahippocampal (PPHC) cortex. However, since the volume of a cortical region is a composite measure, relating directly to both thickness and surface area, it would be ideal to be able to quantify all of these morphometric measures, particularly since disease-related processes, such as Alzheimer's disease (AD), may preferentially affect thickness. This study describes a novel protocol for measuring the thickness, surface area, and volume of these three medial temporal lobe (MTL) subregions. Participants included 29 younger normal subjects (ages 18-30), 47 older normal subjects (ages 66-90), and 29 patients with mild AD (ages 56-90). Cortical surface models were reconstructed from the gray/white and gray/cerebrospinal fluid boundaries, and a hybrid visualization approach was implemented to trace the ERC, PRC, and PPHC using both orthogonal MRI slice- and cortical surface-based visualization of landmarks. Anatomic variants of the collateral sulcus (CS) were classified in all 105 participants, and the relationship between CS variants and corresponding morphometric measures was examined. One CS variant-deep, uninterrupted CS not connected with nearby sulci-was the most common configuration and was associated with thinner cortex within the ERC and PRC regions. This novel protocol enables the reliable measurement of both the thickness and surface area of ERC, PRC, and PPHC. (C) 2007 Elsevier Inc. All rights reserved, C1 [Feczko, Eric; Augustinack, Jean C.; Fischl, Bruce; Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Feczko, Eric] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Augustinack, Jean C.; Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Augustinack, Jean C.; Fischl, Bruce; Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU National Institute on Aging [K23-AG22509, P50-AG05681, P01-AG03991]; National Center for Research Resources [P41-RR14075, R01 RR16594-01A1]; NCRR BIRN Morphometric Project [BIRN002, U24 RR021382, U24-RR021382]; Mental Illness and Neuroscience Discovery (MIND) Institute; National Institute for Biomedical Imaging and Bioengineering [R01 EB001550]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; National Alliance for Medical Image Computing (NAMIC); National Institutes of Health through the NIH Roadmap for Medical Research [U54 EB005149] FX We thank Dr. Randy Buckner and Dr. John Morris for providing the data. We also express special appreciation to the participants in this study for their valuable contributions, without which this research would not have been possible. NR 36 TC 28 Z9 30 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2009 VL 30 IS 3 BP 420 EP 431 DI 10.1016/j.neurobiolaging.2007.07.023 PG 12 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 404LV UT WOS:000263154700008 PM 17850926 ER PT J AU Dickerson, BC Feczko, E Augustinack, JC Pacheco, J Morris, JC Fischl, B Buckner, RL AF Dickerson, Bradford C. Feczko, Eric Augustinack, Jean C. Pacheco, Jenni Morris, John C. Fischl, Bruce Buckner, Randy L. TI Differential effects of aging and Alzheimer's disease on medial temporal lobe cortical thickness and surface area SO NEUROBIOLOGY OF AGING LA English DT Article DE Entorhinal cortex; Perirhinal cortex; Parahippocampal cortex; Magnetic resonance imaging; Alzheimer's disease; Aging ID MILD COGNITIVE IMPAIRMENT; ENTORHINAL CORTEX NEURONS; RHESUS-MONKEY; MEMORY PERFORMANCE; COORDINATE SYSTEM; CEREBRAL-CORTEX; ATROPHY RATES; MRI MEASURES; HIPPOCAMPUS; DEMENTIA AB The volume of parcellated conical regions is a composite measure related to both thickness and surface area. It is not clear whether volumetric decreases in medial temporal lobe (MTL) cortical regions in aging and Alzheimer's disease (AD) are due to thinning, loss of surface area, or both, nor is it clear whether aging and AD differ in their effects on these properties. Participants included 28 Younger Normals, 47 Older Normals, and 29 patients with mild AD. T1-weighted MRI data were analyzed using a novel semi-automated protocol (presented in a companion article) to delineate the boundaries of entorhinal (ERC), perirhinal (PRC), and posterior parahippocampal (PPHC) cortical regions and calculate their mean thickness, surface area, and volume. Compared to Younger Normals, Older Normals demonstrated moderately reduced ERC and PPHC volumes, which were due primarily to reduced surface area. In contrast. the expected AD-related reduction in ERC volume was produced by a large reduction in thickness with minimal additional effect (beyond that of aging) on surface area. PRC and PPHC also showed large AD-related reductions in thickness. Of all these MTL morphometric measures, ERC and PRC thinning were the best predictors of poorer episodic memory performance in AD. Although the volumes of MTL cortical regions may decrease with both aging and AD, thickness is relatively preserved in normal aging, while even in its mild clinical stage, AD is associated with a large degree of thinning of MTL cortex. These differential morphometric effects of aging and AD may reflect distinct biologic processes and ultimately may provide insights into the anatomic substrates of change in memory-related functions of MTL cortex. (C) 2007 Elsevier Inc. All rights reserved. C1 [Dickerson, Bradford C.; Feczko, Eric; Augustinack, Jean C.; Pacheco, Jenni; Fischl, Bruce; Buckner, Randy L.] Harvard Univ, Sch Med, Boston, MA USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Feczko, Eric] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Augustinack, Jean C.; Pacheco, Jenni; Fischl, Bruce; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Dickerson, Bradford C.; Augustinack, Jean C.; Pacheco, Jenni; Fischl, Bruce; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Morris, John C.] Washington Univ, Sch Med, Alzheimers Dis Res Ctr, St Louis, MO 63110 USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu RI Morris, John/A-1686-2012 FU NIA [K23-AG22509, P50-AG15681, P01-AG03991]; NCRR [P41-RR14075 R01 RR16594-01A1, BIRN002, U24 RR021382]; Mental Illness and Neuroscience Discovery (MIND) Institute; National Institute for Biomedical Imaging and Bioengineering [R01 EB001550]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; National Alliance for Medical Image Computing (NAMIC); National Institutes of Health through the NIH Roadmap for Medical Research [U54 EB005149] FX We thank Drs. Leyla deToledo-Morrell and Gary Van Hoesen for helpful discussions, and the faculty and staff of the Washington University ADRC. We express special appreciation to the participants in this study for their valuable contributions, without which this research would not have been possible. NR 50 TC 102 Z9 103 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2009 VL 30 IS 3 BP 432 EP 440 DI 10.1016/j.neurobiolaging.2007.07.022 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 404LV UT WOS:000263154700009 PM 17869384 ER PT J AU Field, HA Kelley, KA Martell, L Goldstein, AM Serluca, FC AF Field, H. A. Kelley, K. A. Martell, L. Goldstein, A. M. Serluca, F. C. TI Analysis of gastrointestinal physiology using a novel intestinal transit assay in zebrafish SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE enteric nervous system; gastrointestinal; motility; transit; zebrafish ID ENTERIC NERVOUS-SYSTEM; DANIO-RERIO EMBRYOS; GUT MOTILITY; HIRSCHSPRUNGS-DISEASE; NITRIC-OXIDE; LARVAE; MICE; ONTOGENY; TRACT; CELLS AB Gastrointestinal function depends upon coordinated contractions to mix and propel food through the gut. Deregulation of these contractions leads to alterations in the speed of material transit through the gut, with potentially significant consequences. We have developed a method for visualizing intestinal transit, the physiological result of peristaltic contractions, in larval zebrafish. This method allows direct, non-invasive observation of luminal content as it traverses the gut. Using this method, we characterized gastrointestinal transit in zebrafish larvae at 7 days postfertilization. In addition, we used this transit assay to assess the physiological consequences of reduced or absent enteric neurones on intestinal transit in larval zebrafish. This may facilitate the use of the zebrafish for investigating the effect of compounds and candidate genes on gastrointestinal motility. C1 [Field, H. A.; Kelley, K. A.; Serluca, F. C.] NIBR, Dev & Mol Pathways, Cambridge, MA 02139 USA. [Martell, L.] Novartis Vaccines & Diagnost, Cambridge, MA USA. [Goldstein, A. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. RP Serluca, FC (reprint author), NIBR, Dev & Mol Pathways, 250 Massachusetts Ave, Cambridge, MA 02139 USA. EM fabrizio.serluca@novartis.com NR 27 TC 20 Z9 20 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD MAR PY 2009 VL 21 IS 3 BP 304 EP 312 DI 10.1111/j.1365-2982.2008.01234.x PG 9 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 409QZ UT WOS:000263522200010 PM 19140958 ER PT J AU McLaren, DG Kosmatka, KJ Oakes, TR Kroenke, CD Kohama, SG Matochik, JA Ingram, DK Johnson, SC AF McLaren, Donald G. Kosmatka, Kristopher J. Oakes, Terrance R. Kroenke, Christopher D. Kohama, Steven G. Matochik, John A. Ingram, Don K. Johnson, Sterling C. TI A population-average MRI-based atlas collection of the rhesus macaque SO NEUROIMAGE LA English DT Article DE Rhesus macaque; MRI; Atlas; Macaca mulatta; Priors; Brain mapping; Probabilistic ID AUTOMATED IMAGE REGISTRATION; HUMAN PARIETAL OPERCULUM; PRIMATE CEREBRAL-CORTEX; SURFACE-BASED ATLASES; NONHUMAN PRIMATE; TEMPLATE IMAGES; HUMAN BRAIN; PROBABILISTIC ATLAS; MONKEY BRAIN; BABOON AB Magnetic resonance imaging (MRI) studies of non-human primates are becoming increasingly common; however, the well-developed voxel-based methodologies used in human studies are not readily applied to non-human primates. In the present study, we create a population-average MRI-based atlas collection for the rhesus macaque (Macaca mulatta) that can be used with common brain mapping packages such as SPM or FSL. In addition to creating a publicly available T1-weighted atlas (http://www.brainmap.wisc.edu/monkey. html), probabilistic tissue classification maps and T2-weighted atlases were also created. Theses atlases are aligned to the MRI volume from the Saleem, K. S. and Logothetis, N. K. (2006) atlas providing an explicit link to histological sections. Additionally, we have created a transform to integrate these atlases with the F99 surface-based atlas in CARET. It is anticipated that these tools will help facilitate voxel-based imaging methodologies in non-human primate species, which in turn may increase our understanding of brain function, development, and evolution. Published by Elsevier Inc. C1 [McLaren, Donald G.; Kosmatka, Kristopher J.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. [McLaren, Donald G.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. [McLaren, Donald G.; Kosmatka, Kristopher J.; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [Kroenke, Christopher D.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97239 USA. [Kroenke, Christopher D.; Kohama, Steven G.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA. [Matochik, John A.] Natl Inst Drug Abuse, Intramural Res Program, Neuroimaging Res Branch, Baltimore, MD 21224 USA. [Ingram, Don K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA. [Oakes, Terrance R.] Univ Wisconsin, Waisman Ctr Brain Imaging Lab, Madison, WI 53705 USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, 2500 Overlook Terrace 11G, Madison, WI 53705 USA. EM scj@medicine.wisc.edu RI McLaren, Donald/G-9906-2011; OI Johnson, Sterling/0000-0002-8501-545X FU National Institutes of Health [RR000167, AG11915, AG20013, GM007507, RR00163, AG029612]; National Institute on Aging FX This study was supported in part by the National Institutes of Health RR000167 (UW), AG11915 (UW), AG20013 (UW), GM007507 (UW), RR00163 (ONPRC), AG029612 (OHSU) and the Intramural Research Program of the National Institute on Aging. This study was also supported with resources and use of facilities at the William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. John Matochik is now at the National Institute on Alcohol Abuse and Alcoholism. The assistance of Erik K. Kastman, Brent W. Thiel, Michele E. Fitzgerald, Ron Fisher, Scott T. Baum, Josh Smith, Ricki J. Colman, Ph. D., Andy. A. Alexander, Ph. D., Barbara B. Bendlin, Ph. D. and the Waisman Center for Brain Imaging was greatly appreciated. We would especially like to thank Drs. Kadharbatcha S. Saleem and Nikos K. Logothetis for providing a digital copy of the D99-SL atlas. GRECC Manuscript Number: 2008-31. NR 66 TC 103 Z9 104 U1 3 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2009 VL 45 IS 1 BP 52 EP 59 DI 10.1016/j.neuroimage.2008.10.058 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KR UT WOS:000263862900007 PM 19059346 ER PT J AU Yu, ZY Fan, X Lo, EH Wang, XY AF Yu, Zhanyang Fan, Xiang Lo, Eng H. Wang, Xiaoying TI Neuroprotective roles and mechanisms of neuroglobin SO NEUROLOGICAL RESEARCH LA English DT Article DE Neuroglobin; hypoxia; ischemia; neuroprotection; mechanism ID NUCLEOTIDE DISSOCIATION INHIBITOR; MITOCHONDRIAL-COMPLEX-III; CYTOCHROME BC(1) COMPLEX; NITRIC-OXIDE; OXIDATIVE STRESS; CEREBRAL-ISCHEMIA; OXYGEN-AFFINITY; MOUSE-BRAIN; IN-VIVO; EXPRESSION AB Objective: The objectives of this work were to update and summarize recent experimental works on neuroglobin, mainly focus on its neuroprotective effects and the mechanisms. Methods: The literature was reviewed using PubMed database, and some of the recent findings from our laboratory were included. Results: Neuroglobin is a recently discovered tissue globin with a high affinity for oxygen and is widely and specifically expressed in neurons of vertebrate's central and peripheral nervous systems. Investigations in the past several years have advanced our knowledge on the functions and mechanisms of neuroglobin, but many issues remain unclear. Emerging reports have shown that overexpression of neuroglobin confers neuroprotection against neuronal hypoxia or ischemia-induced damage in cultured neurons and in cerebral ischemic animal models. Accumulating findings suggest several possible neuroprotective roles and mechanisms including ligand binding and oxygen sensing, modulation of cell signaling pathways and maintenance of mitochondria function. Conclusion: Emerging experimental works suggest that neuroglobin is neuroprotective against hypoxic/ischemic insults, probably via ligand binding and oxygen sensing, modulation of cell signaling pathways and maintenance of mitochondria function. [Neurol Res 2009; 31:122-127] C1 [Yu, Zhanyang] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Yu, ZY (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. EM zyu@partners.org FU NIH [R01-NS049476, R01-NS48422, R01-NS53560, P01-NS55104]; American Heart Association [0435087N] FX This work was supported in part by an NIH grant (no. R01-NS049476) and a Scientist Development Grant (no. 0435087N) from American Heart Association to X. W. and NIH grants (no. R01-NS48422, R01-NS53560 and P01-NS55104) to E. H. L. NR 65 TC 33 Z9 37 U1 0 U2 5 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD MAR PY 2009 VL 31 IS 2 BP 122 EP 127 DI 10.1179/174313209X389866 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 424QO UT WOS:000264581800003 PM 19298751 ER PT J AU Kopelman, MD Bright, P Fulker, H Hinton, N Morrison, A Verfaellie, M AF Kopelman, Michael D. Bright, Peter Fulker, Helena Hinton, Nicola Morrison, Amy Verfaellie, Mieke TI Remote Semantic Memory in Patients With Korsakoff's Syndrome and Herpes Encephalitis SO NEUROPSYCHOLOGY LA English DT Article DE amnesia; retrograde; semantic; vocabulary; episodic ID MEDIAL TEMPORAL-LOBE; MRI VOLUMETRIC-ANALYSIS; RETROGRADE-AMNESIA; EPISODIC MEMORY; AUTOBIOGRAPHICAL MEMORY; ANTEROGRADE MEMORY; ORGANIC AMNESIA; ACQUISITION; CONSOLIDATION; HIPPOCAMPAL AB Performance of patients with Korsakoff's syndrome and herpes encephalitis was compared on a retrograde amnesia (RA) test, asking subjects to recall and recognize the definitions of words that had come into the language at different time periods. Performance was also compared on a related test in which participants were asked to produce the words to definitions they were given in free recall and cued recall versions. It was hypothesized that, if the temporal gradient in remote memory results from a shift of information from episodic to semantic memory, then there should be a temporal gradient on these tasks, possibly steeper (i.e., greater relative sparing of early memories) in the patients in the Korsakoff group than in the herpes encephalitis group, who have widespread temporal lobe damage. Furthermore, in comparing semantic and episodic remote memory tests, consolidation theory would predict uniform temporal gradients across such tasks, whereas multiple trace theory would predict a differential pattern. The results showed that patients with Korsakoff's syndrome and patients with herpes encephalitis were significantly impaired across all time periods on the vocabulary tests, with only minimal evidence of temporal gradients, relative to healthy participants, and there was no evidence of a differential pattern of impairment between the two patient groups. Comparison with performance on measures of episodic retrograde amnesia, in which there was a differential pattern of temporal gradient, suggests that the relative preservation of early episodic remote memories in patients with Korsakoff's syndrome does not result from an episodic-to-semantic shift in the quality with which memories are stored. These findings are discussed in relation to existing theories of RA and to the patients' underlying patterns of neuropathology. C1 [Kopelman, Michael D.; Bright, Peter; Fulker, Helena; Hinton, Nicola; Morrison, Amy] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Verfaellie, Mieke] Boston Univ, Memory Disorders Res Ctr, Boston VA Healthcare Syst, Boston, MA 02215 USA. RP Kopelman, MD (reprint author), St Thomas Hosp, Adamson Ctr, Univ Dept Neuropsychiat, 3rd Floor,Westminster Bridge Rd, London SE1 7EH, England. EM michacl.kopelman@kcl.ac.uk OI Verfaellie, Mieke/0000-0001-5535-4584 NR 47 TC 9 Z9 9 U1 2 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD MAR PY 2009 VL 23 IS 2 BP 144 EP 157 DI 10.1037/a0014447 PG 14 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 416VR UT WOS:000264034100002 PM 19254087 ER PT J AU Strangman, GE Goldstein, R O'Neil-Pirozzi, TM Kelkar, K Supelana, C Burke, D Katz, DI Rauch, SL Savage, CR Glenn, MB AF Strangman, Gary E. Goldstein, Richard O'Neil-Pirozzi, Therese M. Kelkar, Kalika Supelana, Christina Burke, David Katz, Douglas I. Rauch, Scott L. Savage, Cary R. Glenn, Mel B. TI Neurophysiological Alterations During Strategy-Based Verbal Learning in Traumatic Brain Injury SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE Cognitive rehabilitation; Functional neuroimaging; Behavioral neurology; Semantic clustering; Brain trauma ID POSITRON-EMISSION-TOMOGRAPHY; WORKING-MEMORY; COGNITIVE REHABILITATION; SIGNIFICANT ACTIVATION; CORTEX CONTRIBUTES; PREFRONTAL CORTEX; FUNCTIONAL MRI; FREE-RECALL; AGE; DAMAGE AB Background. Verbal learning and strategic processing deficits are common sequelae of traumatic brain injury (TBI); however, the neurophysiological mechanisms underlying such deficits remain poorly understood. Methods. We performed functional magnetic resonance imaging (fMRI) in 25 individuals with chronic TBI (> 1 year after injury) and 20 matched healthy controls. Subjects were scanned while encoding word lists, with free recall and recognition assessed after each scanning run. To vary the strategic processing load, participants learned semantically unrelated words (Unrelated condition), semantically related words under null instruction conditions (Spontaneous condition), and semantically related words following training on the use of a semantic clustering strategy (Directed condition). Results. Behavioral performance on recall, recognition, and semantic clustering improved significantly as follows: Unrelated < Spontaneous < Directed. Individuals with TBI exhibited impaired yet parallel behavioral performance relative to control participants. The fMRI measures of brain activity during verbal encoding revealed decreased activity in participants with TBI relative to controls in left dorsolateral prefrontal cortex (DLPFC; BA 9) and in a region spanning the left angular and supramarginal gyri (BA 39/40). Functional connectivity analysis revealed evidence of a functional-but not anatomical-breakdown in the connectivity between the DLPFC and other regions specifically when participants with TBI were directed to use the semantic encoding strategy. Conclusion. After TBI, the DLPFC appears to be decoupled from other active brain regions specifically when strategic control is required. We hypothesize that approaches designed to help re-couple DLPFC under such conditions may aid TBI cognitive rehabilitation. C1 [Strangman, Gary E.; Supelana, Christina] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Strangman, Gary E.; Goldstein, Richard; O'Neil-Pirozzi, Therese M.; Kelkar, Kalika; Glenn, Mel B.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Charlestown, MA USA. [O'Neil-Pirozzi, Therese M.] Northeastern Univ, Dept Speech Language Pathol & Audiol, Boston, MA 02115 USA. [Burke, David] Emory Univ, Dept Rehabil Med, Atlanta, GA 30322 USA. [Katz, Douglas I.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Katz, Douglas I.] Braintree Rehabil Hosp, Braintree, MA USA. [Rauch, Scott L.] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. [Savage, Cary R.] Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66103 USA. RP Strangman, GE (reprint author), Neural Syst Grp, 149 13th St Psychiat Room 2651, Charlestown, MA 02129 USA. EM strang@nmr.mgh.harvard.edu FU National Institute on Disability and Rehabilitation; US Department of Education [NIDRR: H133A020513]; NIH [NINDS: K25-NS046554] FX We thank Dana Christina, the Statewide Head Injury Program, and Community Rehabilitation Care for their help and support. Funding for this project came from the National Institute on Disability and Rehabilitation, US Department of Education (NIDRR: H133A020513), and the NIH (NINDS: K25-NS046554). NR 44 TC 26 Z9 26 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD MAR PY 2009 VL 23 IS 3 BP 226 EP 236 DI 10.1177/1545968308324225 PG 11 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 410NF UT WOS:000263583700005 PM 19047359 ER PT J AU Sani, S Shimamoto, S Turner, RS Levesque, N Starr, PA AF Sani, Sepehr Shimamoto, Shoichi Turner, Robert S. Levesque, Nadia Starr, Philip A. TI MICROELECTRODE RECORDING IN THE POSTERIOR HYPOTHALAMIC REGION IN HUMANS SO NEUROSURGERY LA English DT Article DE Cluster headache; Electrophysiology; Hypothalamus; Microelectrode; Periventricular gray; Single-unit recording microelectrode ID DEEP-BRAIN-STIMULATION; CHRONIC CLUSTER HEADACHE; TRIGEMINAL AUTONOMIC CEPHALALGIAS; OCCIPITAL NERVE-STIMULATION; NEURONAL-ACTIVITY; HYPOCRETIN-RECEPTOR-2 GENE; G1246A POLYMORPHISM; FOLLOW-UP; AREA; EXPERIENCE AB INTRODUCTION: Deep brain stimulation of the posterior hypothalamic region (PHR) is an emerging technique for the treatment of medically intractable Cluster headache. Few reports have analyzed single unit neuronal recordings in the human PHR. We report properties of spontaneous neuronal discharge in PHR for 6 patients who underwent DBS for cluster headaches. METHODS: Initial target coordinates, determined by magnetic resonance imaging stereotactic localization, were 2 mm lateral, 3 mm posterior, and 5 mm inferior to the midpoint of the anterior commissure-posterior commissure plane. A single microelectrode penetration was performed beginning 10 mm above the anatomic target, without systemic sedation. Single units were discriminated off-line by cluster Cutting in principal components space. Discharge rates, interspike intervals, and oscillatory activity were analyzed and compared between ventromedial thalamic and hypothalamic units. RESULTS: Six patients and 24 units were evaluated, Units in the PHR had a slow, regular spontaneous discharge with wide, low-amplitude action potentials. The mean discharge rate of hypothalamic neurons was significantly lower (mean +/- standard deviation, 13.2 +/- 12,2) than that of medial thalamic units (28.0 +/- 8.2). Oscillatory activity was not detected. Microelectrode recording in this region caused no morbidity. CONCLUSION: The single-unit discharge rate of neurons in the PHR of awake humans was 13.2 Hz and was significantly lower than medial thalamic neurons recorded dorsal to the tat-get. The findings will he of use for microelectrode localization of the cluster headache target and for comparison with animal studies. C1 [Sani, Sepehr; Shimamoto, Shoichi; Turner, Robert S.; Levesque, Nadia; Starr, Philip A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94112 USA. [Sani, Sepehr; Turner, Robert S.; Starr, Philip A.] San Francisco VA Med Ctr, Ctr Clin, San Francisco, CA USA. RP Sani, S (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,Room M-779, San Francisco, CA 94112 USA. EM sepehr.sani@ucsf.edu NR 47 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAR PY 2009 VL 64 IS 3 BP S161 EP S169 DI 10.1227/01.NEU.0000334051.91501.E3 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 411MN UT WOS:000263653800020 ER PT J AU Wu, YN Johnson, SW AF Wu, Yan-Na Johnson, Steven W. TI Rotenone reduces Mg2+-dependent block of NMDA currents in substantia nigra dopamine neurons SO NEUROTOXICOLOGY LA English DT Article DE Dopamine; Magnesium; Voltage-dependent; N-methyl-D-aspartate; Brain slice; Tyrosine kinase ID METHYL-D-ASPARTATE; RECEPTOR CHANNELS; PARKINSONS-DISEASE; CORTICAL-NEURONS; TYROSINE KINASE; MG2+ BLOCK; CELL-DEATH; COMPLEX-I; RAT; INHIBITION AB Rotenone is a pesticide that has been successfully used to produce a rodent model of Parkinson's disease. We reported previously that rotenone potently augmented N-methyl-D-aspartate (NMDA)-evoked currents in rat dopamine neurons via a tyrosine kinase-dependent mechanism. In this study, we investigated the effect of rotenone on the current-voltage relationship of NMIDA-induced currents in substantia nigra zona compacta neurons recorded with whole-cell patch pipettes in slices of rat brain. In a physiologic concentration of extracellular Mg2+ (1.2 mM), a 30 min perfusion with rotenone (100 nM) produced a marked increase in current evoked by bath application of NMIDA (30 mu M), especially when measured at relatively hyperpolarized currents. In the presence of rotenone, NMDA currents lost the characteristic region of negative-slope conductance that is normally produced by voltage-dependent block by Mg2+. The voltage-dependent effect of rotenone on NMDA currents was mimicked by a low extracellular concentration of Mg2+ (0.2 mM) and was antagonized by a high level of Mg2+ (6.0 mM). Moreover, we report that the tyrosine kinase inhibitor genistein blocked the ability of rotenone to augment NMDA receptor currents. These results suggest that rotenone potentiates NMDA currents by a tyrosine kinase-dependent process that attenuates voltage-dependent Mg2+ block of NMDA-gated channels. These results support the hypothesis that an excitotoxic mechanism might participate in rotenone-induced toxicity of midbrain dopamine neurons. Published by Elsevier Inc. C1 [Wu, Yan-Na; Johnson, Steven W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, Steven W.] Portland VA Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM johnsost@ohsu.edu FU Veterans Affairs Merit Review Grant; Portland VA Parkinson's Disease Research, Education, and Clinical Center; American Parkinson Disease Association FX This work was supported by a Veterans Affairs Merit Review Grant, the Portland VA Parkinson's Disease Research, Education, and Clinical Center, and a grant from the American Parkinson Disease Association. NR 40 TC 15 Z9 15 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAR PY 2009 VL 30 IS 2 BP 320 EP 325 DI 10.1016/j.neuro.2009.01.002 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 429HY UT WOS:000264912700020 PM 19428506 ER PT J AU Sogg, S Mori, DL AF Sogg, Stephanie Mori, DeAnna L. TI Psychosocial Evaluation for Bariatric Surgery: The Boston Interview and Opportunities for Intervention SO OBESITY SURGERY LA English DT Review DE Bariatric surgery/psychology; Behavior; Humans; Obesity; Morbid/psychology/surgery ID GASTRIC BYPASS-SURGERY; WEIGHT-LOSS EXPECTATIONS; QUALITY-OF-LIFE; TERM FOLLOW-UP; ANTI-FAT BIAS; MORBID-OBESITY; HEALTH-PROFESSIONALS; EATING DISTURBANCES; SEXUAL-ABUSE; PROGNOSTIC-SIGNIFICANCE AB The process of psychosocial evaluation for weight loss surgery (WLS) is one that goes beyond serving the function of information-gathering (Bauchowitz et al. in Surg Obes Relat Dis 3:554-558, 2007; Friedman et al. in Surg Obes Relat Dis 3:376-382, 2007; Lanyon and Maxwell in Obes Surg 17:321-328, 2007; Sogg and Mori in Obes Surg 14:370-380, 2004; Sogg and Mori in Surg Obes Relat Dis 4:455-463, 2008). This process offers myriad opportunities for delivering significant and powerful interventions that can enhance the patient's success in the WLS process. A discussion of the unique opportunities for psychosocial intervention afforded by the pre-surgical evaluation process is presented, using The Boston Interview for Bariatric Surgery (Sogg and Mori in Surg Obes Relat Dis 4:455-463, 2008) as the organizing framework. C1 [Sogg, Stephanie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Weight Ctr, Boston, MA 02163 USA. [Mori, DeAnna L.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Sogg, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Weight Ctr, Boston, MA 02163 USA. EM ssogg@partners.org NR 76 TC 20 Z9 20 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 J9 OBES SURG JI Obes. Surg. PD MAR PY 2009 VL 19 IS 3 BP 369 EP 377 DI 10.1007/s11695-008-9676-7 PG 9 WC Surgery SC Surgery GA 409ZR UT WOS:000263544800017 PM 18795379 ER PT J AU Levin, M Naseri, A Stewart, JM AF Levin, Marc Naseri, Aynan Stewart, Jay M. TI Resident-Performed Prophylactic Retinopexy and the Risk of Retinal Detachment SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID POSTERIOR VITREOUS DETACHMENT; ARGON-LASER PHOTOCOAGULATION; FELLOW EYES; BREAKS; DEGENERATIONS AB BACKGROUND AND OBJECTIVE: To examine the natural history of retinopexies performed by ophthalmology residents at universiry-affiliated clinics and to determine the rate of progression to rhegmatogenous retinal detachment. PATIENTS AND METHODS: Charts of patients receiving prophylactic thermal coagulation between 1997 and 2006 were reviewed retrospectively. Outcome measures included subsequent rhegmatogenous retinal detachment and additional prophylactic treatments. RESULTS: Review of the medical records identified 166 eyes with peripheral retinal lesions treated by residents, with an average follow-up of 2.4 +/- 0.2 years. At presentation, only 43.4% of patients were symptomatic. Two (1.2%) eyes developed rhegmatogenous retinal detachment during follow-up, with each arising in a previously healthy area of retina in a patient with a history of detachment of the fellow retina. Twenty-five eyes (15%) received at least one additional prophylactic procedure. CONCLUSION: The rate of rhegmatogenous retinal detachment following prophylactic retinopexy performed by residents at hospital-based clinics is low, supporting this standard practice. [Ophthalmic Surg Lasers Imaging 2009;40:120-126.] C1 [Levin, Marc; Naseri, Aynan; Stewart, Jay M.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Naseri, Aynan] San Francisco VA Med Ctr, San Francisco, CA USA. [Stewart, Jay M.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. RP Stewart, JM (reprint author), Univ Calif San Francisco, Dept Ophthalmol, 10 Koret Way,Room K301,Box 0730, San Francisco, CA 94143 USA. FU Thai Man May See, Inc., San Francisco, California; Research to Prevent Blindness, Inc., New York, New York FX Supported by Thai Man May See, Inc., San Francisco, California, and an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York. NR 18 TC 7 Z9 7 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1542-8877 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD MAR-APR PY 2009 VL 40 IS 2 BP 120 EP 126 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 418SU UT WOS:000264170000006 PM 19320300 ER PT J AU Rutar, T Porco, TC Naseri, A AF Rutar, Tina Porco, Travis C. Naseri, Ayman TI Risk Factors for Intraoperative Complications in Resident-Performed Phacoemulsification Surgery SO OPHTHALMOLOGY LA English DT Article ID VITREOUS LOSS; CATARACT-EXTRACTION; TOPICAL ANESTHESIA; VISUAL OUTCOMES; EXPERIENCE AB Purpose: To determine the risk factors for intraoperative complications in resident-performed phacoemulsification surgery and the effect of complications on postoperative visual acuity. Design: Retrospective case series. Participants: A total of 320 consecutive eyes of predominantly male (96.6%) and elderly patients (mean age 1 standard deviation = 73.1 +/- 10.0 years) undergoing phacoemulsification surgery by ophthalmology residents at a Veterans Administration Hospital between January 2006 and 2007. There were no exclusion criteria for type of cataract undergoing phacoemulsification surgery. Methods: Data were collected by review of patients' electronic medical records. Collected data included the patient demographics, ocular comorbidities, cataract features, resident, resident experience, attending, right or left eye, anesthesia type, wound type, phacoemulsification technique, preoperative and postoperative visual acuities, and presence of any intraoperative complication. Multivariate models were constructed to determine potential risk factors for intraoperative complications. Main Outcome Measures: Major intraoperative complication rate, risk factors for major intraoperative complications, and best-corrected postoperative visual acuity. Results: The major intraoperative complication rate was 4.7%, which included 3.1% of cases with vitreous loss. The strongest association with a major complication was the presence of a case identified as challenging preoperatively, which had an odds ratio of 6.0 (95% confidence interval [CI], 1.5-24.1, P = 0.01). The challenging features most strongly associated with major complications were mature 4+ nuclear sclerotic cataracts and zonular pathology (antecedent trauma and pseudoexfoliation), which had odds ratios of 18.9 (95% CI, 3.1-117, P = 0.002) and 26.2 (95% CI, 4.3-159, P = 0.003), respectively. A major complication decreased the likelihood of achieving 20/40 or better visual acuity within 90 days of surgery (95% of uncomplicated eyes vs. 71% of complicated eyes; P = 0.009). Conclusions: Residents performing phacoemulsification surgery achieved a low overall rate of major complications. However, specific features of cataracts, such as mature nuclei and zonular pathology, carried increased intraoperative risk. Anticipating risk may help to decrease surgical complications further and to counsel patients appropriately. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:431-436 (C) 2009 by the American Academy of Ophthalmology. C1 [Naseri, Ayman] San Francisco Vet Adm Med Ctr, Dept Ophthalmol, San Francisco, CA 94121 USA. [Rutar, Tina; Naseri, Ayman] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Porco, Travis C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Prevent Med & Publ Hlth, Francis I Proctor Fdn Res Ophthalmol, San Francisco, CA 94143 USA. [Naseri, Ayman] Univ Calif San Francisco, Dept Ophthalmol Proctor Fdn, San Francisco, CA 94143 USA. RP Naseri, A (reprint author), San Francisco Vet Adm Med Ctr, Dept Ophthalmol, 4150 Clement St, San Francisco, CA 94121 USA. EM ayman.naseri@va.gov FU Man May See, a nonprofit organization; University of California Institutional Core Grant For Vision Research [NIH P30] FX Supported in part by an unrestricted grant from That Man May See, a nonprofit organization, and by the University of California Institutional Core Grant For Vision Research (NIH P30). NR 16 TC 51 Z9 52 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 2009 VL 116 IS 3 BP 431 EP 436 DI 10.1016/j.ophtha.2008.10.028 PG 6 WC Ophthalmology SC Ophthalmology GA 416KQ UT WOS:000264005400011 PM 19167084 ER PT J AU Bundy, MJ Cavola, CF Dodson, TB AF Bundy, Michael James Cavola, Cameron Frank Dodson, Thomas B. TI Panoramic radiographic findings as predictors of mandibular nerve exposure following third molar extraction: Digital versus conventional radiographic techniques SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article ID 3RD-MOLAR EXTRACTION; ALVEOLAR; SURGERY; DYSESTHESIA; QUALITY; INJURY AB Objective. The aim was to compare digital and conventional panoramic imaging techniques for identifying high-risk radiographic markers associated with mandibular nerve (MN) injury after mandibular third molar (M3) removal. Study design. The study used a retrospective cohort model. The predictor variable was the presence or absence of radiographic signs associated with MN exposure during M3 removal. The outcome variable was MN exposure. Intraexaminer variability was estimated using a kappa statistic. Logistic regression modeling was used to measure the association between radiographic signs and MN exposure and determine if imaging technique modified that association. The level of statistical significance was set at P < .05. Results. The sample was composed of 571 patients having 1,017 mandibular M3s removed. The MN was visualized in 66 extraction sites (6.5%). In the adjusted logistic model, radiographic signs were statistically associated with MN exposure (P < .001) and imaging technique was a statistically insignificant effect modifying variable (P = .4). Conclusion. The results of this study suggest that imaging technique does not modify the relationship between high-risk panoramic radiographic signs and MN exposure. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:e36-e40) C1 [Dodson, Thomas B.] Massachusetts Gen Hosp, Ctr Appl Clin Investigat, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Bundy, Michael James] Univ Calif Los Angeles, Dept Oral & Maxillofacial Surg, Los Angeles, CA 90024 USA. [Cavola, Cameron Frank] Louisiana State Univ, Hlth Sci Ctr, Dept Oral & Maxillofacial Surg, New Orleans, LA USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Ctr Appl Clin Investigat, Dept Oral & Maxillofacial Surg, Warren Bldg Suite 1201,55 Fruit St, Boston, MA 02114 USA. EM tbdodson@partners.org FU Center for Applied Clinical Investigation and Education and Research Fund; Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital; Massachusetts General Physicians Organization FX Supported in part by the Center for Applied Clinical Investigation and Education and Research Fund, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, and the Massachusetts General Physicians Organization. NR 18 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD MAR PY 2009 VL 107 IS 3 BP E36 EP E40 DI 10.1016/j.tripleo.2008.12.004 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 406KT UT WOS:000263295000030 PM 19217011 ER PT J AU Baron, R AF Baron, R. TI THE FUTURE OF OSTEOPOROSIS TREATMENTS: A LOOK INTO NEW TARGETS AND COMPOUNDS SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT 9th European Congress on Clinical an dEconomic Aspects of Osteoporosis and Osteoarthritis CY MAR 19-21, 2009 CL Athens, GREECE C1 [Baron, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. [Baron, R.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2009 VL 20 SU 1 BP 1 EP 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 536AE UT WOS:000273012800002 ER PT J AU Grady, D Cauley, J Stock, J Cox, D Mitlak, B Song, J Cummings, S AF Grady, D. Cauley, J. Stock, J. Cox, D. Mitlak, B. Song, J. Cummings, S. TI EFFECT OF RALOXIFENE ON ALL-CAUSE MORTALITY ACROSS CLINICAL TRIALS SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT 9th European Congress on Clinical an dEconomic Aspects of Osteoporosis and Osteoarthritis CY MAR 19-21, 2009 CL Athens, GREECE C1 [Grady, D.; Cummings, S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Grady, D.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cauley, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Stock, J.; Cox, D.; Mitlak, B.; Song, J.] Lilly Res Labs, Indianapolis, IN USA. [Cummings, S.] Calif Pacific Med Res Inst, San Francisco Coordinating Ctr, San Francisco, CA USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2009 VL 20 SU 1 BP 13 EP 13 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 536AE UT WOS:000273012800027 ER PT J AU Morse, LR Battaglino, RA Stolzmann, KL Hallett, LD Waddimba, A Gagnon, D Lazzari, AA Garshick, E AF Morse, L. R. Battaglino, R. A. Stolzmann, K. L. Hallett, L. D. Waddimba, A. Gagnon, D. Lazzari, A. A. Garshick, E. TI Osteoporotic fractures and hospitalization risk in chronic spinal cord injury SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone fracture; Hospitalization; Osteoporosis; Rehabilitation; Spinal cord injury ID BONE-MINERAL DENSITY; ALCOHOL-CONSUMPTION; GROWING RATS; ALENDRONATE; METABOLISM; MORTALITY; VETERANS; HEALTH; LIFE; MASS AB Osteoporosis is a well acknowledged complication of spinal cord injury. We report that motor complete spinal cord injury and post-injury alcohol consumption are risk factors for hospitalization for fracture treatment. The clinical assessment did not include osteoporosis diagnosis and treatment considerations, indicating a need for improved clinical protocols. Treatment of osteoporotic long bone fractures often results in lengthy hospitalizations for individuals with spinal cord injury. Clinical features and factors that contribute to hospitalization risk have not previously been described. Three hundred and fifteen veterans a parts per thousand yen 1 year after spinal cord injury completed a health questionnaire and underwent clinical exam at study entry. Multivariate Cox regression accounting for repeated events was used to assess longitudinal predictors of fracture-related hospitalizations in Veterans Affairs Medical Centers 1996-2003. One thousand four hundred and eighty-seven hospital admissions occurred among 315 participants, and 39 hospitalizations (2.6%) were for fracture treatment. Median length of stay was 35 days. Fracture-related complications occurred in 53%. Independent risk factors for admission were motor complete versus motor incomplete spinal cord injury (hazard ratio = 3.73, 95% CI = 1.46-10.50). There was a significant linear trend in risk with greater alcohol consumption after injury. Record review indicated that evaluation for osteoporosis was not obtained during these admissions. Assessed prospectively, hospitalization in Veterans Affairs Medical Centers for low-impact fractures is more common in motor complete spinal cord injury and is associated with greater alcohol use after injury. Osteoporosis diagnosis and treatment considerations were not part of a clinical assessment, indicating the need for improved protocols that might prevent low-impact fractures and related admissions. C1 [Morse, L. R.] Harvard Univ, Sch Med, Dept PMR, Forsyth Inst, Boston, MA 02118 USA. [Morse, L. R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02215 USA. [Morse, L. R.] Spaulding Rehabil Hosp, Boston, MA USA. [Battaglino, R. A.] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. [Stolzmann, K. L.; Hallett, L. D.; Waddimba, A.; Gagnon, D.; Lazzari, A. A.; Garshick, E.] VA Boston Healthcare Syst, Dept Vet Affairs, Res & Dev Serv, Boston, MA USA. [Stolzmann, K. L.; Hallett, L. D.; Waddimba, A.; Garshick, E.] Harvard Univ, Sch Med, Programs Res VA Boston, Boston, MA 02118 USA. [Gagnon, D.] Boston Univ, Sch Publ Hlth, VA Cooperat Studies Program, VA Boston Healthcare Syst,Dept Biostat, Boston, MA USA. [Waddimba, A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Lazzari, A. A.] VA Boston Healthcare Syst, Div Primary Care, Rheumatol Sect, Osteoporosis Prevent Clin,Boston Div, Boston, MA USA. [Lazzari, A. A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Garshick, E.] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. [Waddimba, A.; Garshick, E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02118 USA. RP Morse, LR (reprint author), Harvard Univ, Sch Med, Dept PMR, Forsyth Inst, 140 Fenway, Boston, MA 02118 USA. EM lmorse4@partners.org RI battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015; OI Morse, Leslie/0000-0002-7426-6341; Gagnon, David/0000-0002-6367-3179 FU Office of Research and Development, Health Services RD Service [RRP-07-312]; NIH/NICHD [RO1 HD42141] FX The project reported/outlined here was supported by the Office of Research and Development, Health Services R&D Service, Quality Enhancement Research Initiative RRP-07-312 and NIH/NICHD RO1 HD42141 ( Dr. Garshick). Dr. Garshick is the Associate Chief of Pulmonary and Critical Care Medicine at VA Boston Healthcare System. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 36 TC 52 Z9 54 U1 0 U2 9 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2009 VL 20 IS 3 BP 385 EP 392 DI 10.1007/s00198-008-0671-6 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 405YR UT WOS:000263260600005 PM 18581033 ER PT J AU Abu Bakar, S Martinez-Alvernia, EA Mankarious, LA AF Abu Bakar, Saraiza Martinez-Alvernia, Efrain A. Mankarious, Leila A. TI Drainage post-thyroglossal duct remnant surgery: Possible source and analysis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID MOLECULAR-CLONING; SALIVARY-GLANDS; MUCIN; EXPRESSION; TRACT; CYSTS AB OBJECTIVE: To establish the distance between tongue base salivary tissue and hyoid. Also, to identify protein differences between thyroglossal duct (TGD) remnants and salivary tissue in order to distinguish drainage source post Sistrunk surgery. METHODS/SETTING: The anterior neck block was obtained from 10 adult cadavers with no known neck pathology. The distance between the normal salivary tissue and hyoid was measured histologically. Immunohistochemistry (IHC) was then performed oil 20 archived tissue blocks from pediatric patients post Sistrunk surgery to identify the presence of amylase, MUC5AC (tracheobronchial mucin), and MUC7 (salivary mucin) within the excised specimen. RESULTS: Average distance between salivary tissue and the hyoid within adult human cadavers was 3.3 mm (range, 1.0-4.2 mm). IHC revealed all excised TGD remnants contained amylase and MUC5AC but none contained MUC7 Both amylase and MUC7 were present within adjacent salivary tissues. CONCLUSIONS: Salivary tissue of the tongue base normally resides an average of 3.3 mm from the hyoid within the adult population. Biochemical analysis showed MUC5AC was specific for TGD remnants while MUC7 was specific for salivary tissue. Amylase does not distinguish between the two tissues. C1 [Abu Bakar, Saraiza; Martinez-Alvernia, Efrain A.; Mankarious, Leila A.] Harvard Univ, Med School, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. RP Mankarious, LA (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Leila_mankarious@meei.harvard.edu NR 16 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 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 2009 VL 140 IS 3 BP 343 EP 347 DI 10.1016/j.otohns.2008.12.010 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 413RQ UT WOS:000263810600012 ER PT J AU Bradfield, J Warner, A Bersohn, MM AF Bradfield, Jason Warner, Alberta Bersohn, Malcolm M. TI Low Referral Rate for Prophylactic Implantation of Cardioverter-Defibrillators in a Tertiary Care Medical Center SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE implantable cardioverter-defibrillator; sudden death; sudden death prevention; left ventricular dysfunction ID SUDDEN CARDIAC DEATH; PREVENTION AB Background: Implantable cardioverter-defibrillators (ICDs) for primary prevention became standard of care after the publication of the second Multicenter Automatic Defibrillator Implantation Trial (MADIT-II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Objective: To determine the percentage of patients in a Veterans Affairs medical center appropriately referred for primary prophylaxis ICD and to further categorize the reasons patients are not being referred. Methods: Echocardiograms obtained since the release of MADIT-II in 2002 were searched for a left ventricular ejection fraction (LVEF) <= 35% and <= 30%. We randomly selected 120 patients per year from 2002 to 2006, for a total of 600 patients in each group. Data were reviewed to determine the number of ICD recipients and the reasons patients were not referred. Results: In the LVEF <= 35% group an ICD was implanted in 28% of 392 eligible patients. Nonreferral (58%) was the most common reason that eligible patients did not receive an ICD. Patients were not referred for ICD because of appropriate contraindications in 26% of cases. Overall mortality was 29% (15% with and 31% without ICD). In the LVEF <= 30% group an ICD was implanted in 33% of 388 eligible patients. Nonreferral (51%) was the most common reason that eligible patients did not receive an ICD. Patients were not referred for ICD because of appropriate contraindications in 24% of cases. Overall mortality was 28% (18% with and 32% without ICD). Conclusions: After the publication of MADIT-II and SCD-HeFT, only 42% of eligible patients with LVEF <= 35% and 49% of patients with LVEF <= 30% were offered a potentially life-saving ICD between 2002 and 2006 in our medical center, sometimes with considerable delay. (PACE 2009; 32:S194-S197) C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Bersohn, MM (reprint author), Cardiol 111E,11201 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mbersohn@ucla.edu NR 8 TC 18 Z9 18 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAR PY 2009 VL 32 BP S194 EP S197 PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 452TA UT WOS:000266562900045 PM 19250092 ER PT J AU Amaya, F Samad, TA Barrett, L Broom, DC Woolf, CJ AF Amaya, Fumimasa Samad, Tarek A. Barrett, Lee Broom, Daniel C. Woolf, Clifford J. TI Periganglionic inflammation elicits a distally radiating pain hypersensitivity by promoting COX-2 induction in the dorsal root ganglion SO PAIN LA English DT Article DE Inflammation; Low back pain; Sciatica; Dorsal root ganglion; Cyclooxygenase 2 ID LOW-BACK-PAIN; LUMBAR DISC HERNIATION; SPARED NERVE INJURY; PROSTAGLANDIN E-2; RAT MODEL; CHRONIC COMPRESSION; NEUROPATHIC PAIN; NUCLEUS PULPOSUS; ANTIINFLAMMATORY DRUGS; CYCLOOXYGENASE-2 COX-2 AB We have developed a model in which inflammation contiguous to and within a dorsal root ganglion (DRG) was generated by local application of complete Freund's adjuvant (CFA) to the [A lumbar spinal nerve as it exits from the intervertebral foramen. The periganglionic inflammation (PGI) elicited a marked reduction in withdrawal threshold to mechanical stimuli and in increase in heat pain sensitivity in the ipsilateral hindpaw in the absence of any hindpaw inflammation. The pain sensitivity appeared within hours and lasted for a week. The PGI also induced a prominent increase in IL-1 beta and TNF-alpha levels in the DRG and of cyclooxygenase-2 (COX-2) expression in neurons and satellite cells. A selective COX-2 inhibitor reduced the PGI-induced hyperalgesia. We also show that IL-1 beta induces COX-2 expression and prostaglandin release in DRG neurons in vitro in a MAP kinase-dependent fashion. The COX-2 induction was prevented by ERK and p38 inhibitors. We conclude that periganglionic inflammation increases cytokine levels, including IL-1 beta, leading to the transcription of COX-2 and prostaglandin production in the affected DRG, and thereby to the development of a dermatomally distributed pain hypersensitivity. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Amaya, Fumimasa; Samad, Tarek A.; Barrett, Lee; Broom, Daniel C.; Woolf, Clifford J.] Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Amaya, Fumimasa; Samad, Tarek A.; Barrett, Lee; Broom, Daniel C.; Woolf, Clifford J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Amaya, Fumimasa] Kyoto Prefectural Univ Med, Dept Anesthesiol, Kyoto 602, Japan. RP Samad, TA (reprint author), Wyeth Ayerst Res, Pain Mol Neurobiol Grp, Neurosci Discovery, 865 Ridge Rd, Princeton, NJ 08852 USA. EM samadt@wyeth.com FU NIH [NS38253, NS039518]; JSPS [18791094] FX C.J.W. was supported by the NIH (NS38253 and NS039518). F.A. was supported by JSPS (18791094). The authors are grateful to Ms. Mika Sasaki for her technical assistance and Dr. Richard Mannion for discussion. NR 63 TC 28 Z9 29 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 2009 VL 142 IS 1-2 BP 59 EP 67 DI 10.1016/j.pain.2008.11.013 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 420GA UT WOS:000264275800013 PM 19135800 ER PT J AU Hanlon, JT Weiner, DK AF Hanlon, Joseph T. Weiner, Debra K. TI Methadone for Chronic Pain in Older Adults: Blast from the Past But Are We Ready for It to Return to Prime Time? SO PAIN MEDICINE LA English DT Editorial Material ID ANALGESICS C1 [Hanlon, Joseph T.] VA Pittsburgh Healthcare Syst, Dept Med Geriatr Med, Dept Pharm & Therapeut, Sch Pharm,CHERP, Pittsburgh, PA USA. [Hanlon, Joseph T.] VA Pittsburgh Healthcare Syst, Dept Med Geriatr Med, Dept Pharm & Therapeut, Sch Pharm,Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Med Geriatr Med, Dept Anesthesiol, Pittsburgh, PA 15260 USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Med Geriatr Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Hanlon, JT (reprint author), VA Pittsburgh Healthcare Syst, Dept Med Geriatr Med, Dept Pharm & Therapeut, Sch Pharm,CHERP, Pittsburgh, PA USA. FU NIA NIH HHS [R01 AG027017] NR 8 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD MAR PY 2009 VL 10 IS 2 BP 287 EP 288 DI 10.1111/j.1526-4637.2009.00560.x PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 415CC UT WOS:000263910900002 PM 19284485 ER PT J AU Kulich, R Maciewicz, R Scrivani, SJ AF Kulich, Ronald Maciewicz, Raymond Scrivani, Steven J. TI Functional Magnetic Resonance Imaging (fMRI) and Expert Testimony SO PAIN MEDICINE LA English DT Article DE Forensic Medicine; Magnetic Resonance Imaging (MRI); Pain Medicine; Sociocultural; Bioethics ID POSITRON-EMISSION-TOMOGRAPHY; MOTOR CORTEX STIMULATION; PHANTOM LIMB PAIN; LOW-BACK-PAIN; BLOOD OXYGENATION; NEUROPATHIC PAIN; HUMAN BRAIN; BOLD; ACTIVATION; DECEPTION AB Medical experts frequently use imaging studies to illustrate points in their court testimony. This article reviews how these studies impact the credibility of expert testimony with judges and juries. The apparent "objective" evidence provided by such imaging studies can lend strong credence to a judge's or jury's appraisal of medical expert's testimony. However, as the court usually has no specialized scientific expertise, the use of complex images as part of courtroom testimony also has the potential to mislead or at least inappropriately bias the weight given to expert evidence. Recent advances in brain imaging may profoundly impact forensic expert testimony. Functional magnetic resonance imaging and other physiologic imaging techniques currently allow visualization of the activation pattern of brain regions associated with a wide variety of cognitive and behavioral tasks, and more recently, pain. While functional imaging technology has a valuable role in brain research and clinical investigation, it is important to emphasize that the use of imaging studies in forensic matters requires a careful scientific foundation and a rigorous legal assessment. C1 [Kulich, Ronald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02111 USA. [Kulich, Ronald; Scrivani, Steven J.] Tufts Univ, Craniofacial Pain & Headache Ctr, Medford, MA 02155 USA. [Maciewicz, Raymond] PBS Med Consulting, Boston, MA USA. RP Kulich, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02111 USA. EM rkulich@partners.org NR 60 TC 4 Z9 4 U1 0 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD MAR PY 2009 VL 10 IS 2 BP 373 EP 380 DI 10.1111/j.1526-4637.2009.00567.x PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 415CC UT WOS:000263910900013 PM 19254335 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI Obama Health Care for All Americans: Practical Implications SO PAIN PHYSICIAN LA English DT Article DE Health care reform; universal health care; national health expenditures; gross domestic product; sustained growth rate formula; physician payments; American Recovery and Reinvestment Act of 2009; Children's Health Insurance Program; health information technology ID INTERVENTIONAL PAIN MANAGEMENT; EVIDENCE-BASED MEDICINE; CHRONIC LOW-BACK; SYSTEMATIC REVIEWS; EPIDURAL INJECTIONS; MEDICARE POPULATION; PRACTICE GUIDELINES; REFORM; TRIALS AB Rapidly rising health care costs over the decades have prompted the application of business practices to medicine with goals of improving the efficiency, restraining expenses, and increasing quality. Average health insurance premiums and individual contributions for family coverage have increased approximately 120% from 1999 to 2008. Health care spending in the United States is stated to exceed 4 times the national defense, despite the wars in Iraq and Afghanistan. The U.S. health care system has been blamed for inefficiencies, excessive administrative expenses, inflated prices, inappropriate waste, and fraud and abuse. While many people lack health insurance, others who do have health insurance allegedly receive care ranging from superb to inexcusable. In criticism of health care in the United States and the focus on savings, methodologists, policy makers, and the public in general seem to ignore the major disadvantages of other global health care systems and the previous experiences of the United States to reform health care. Health care reform is back with the Obama administration with great expectations. It is also believed that for the first time since 1993, momentum is building for policies that would move the United States towards universal health insurance. President Obama has made health care a central part of his domestic agenda, with spending and investments in Children's Health Insurance Program (CHIP), American Recovery and Reinvestment Act of 2009, and proposed 2010 budget. It is the consensus now that since we have a fiscal emergency, Washington is willing to deal with the health care crisis. Many of the groups long opposed to reform, appear to be coming together to accept a major health care reform. Reducing costs is always at the center of any health care debate in the United States. These have been focused on waste, fraud, and abuse; administrative costs; improving the quality with health technology information dissemination; and excessive regulations on the health care industry in the United States. Down payment on health care reform, American Recovery and Reinvestment Act, and CHIP include many provisions to reach towards universal health care. C1 [Manchikanti, Laxmaiah] Pain Management Ctr, Paducah, KY 42003 USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), Pain Management Ctr, 2531 Lone Oak Rd, Paducah, KY 42003 USA. EM drlin@thepainmd.com RI toro, edgardo/F-2748-2014 NR 82 TC 34 Z9 36 U1 0 U2 7 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAR-APR PY 2009 VL 12 IS 2 BP 289 EP 304 PG 16 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 431EX UT WOS:000265045200003 PM 19305481 ER PT J AU Boros, LG Deng, Q Pandol, SJ Tsukamoto, H Go, VLW Lee, WNP AF Boros, Laszlo G. Deng, Qinggao Pandol, Stephen J. Tsukamoto, Hidekazu Go, Vay Liang W. Lee, Wai-Nang Paul TI Ethanol Diversely Alters Palmitate, Stearate, and Oleate Metabolism in the Liver and Pancreas of Rats Using the Deuterium Oxide Single Tracer SO PANCREAS LA English DT Article DE palmitic acid; stearic acid; oleic acid; fatty acid ratios; deuterium ID INTRAGASTRIC INFUSION; METABOLOMICS; ALCOHOL; LIPOGENESIS; FIBROSIS; FAT AB Objective: To determine tissue-specific effects of alcohol on fatty acid synthesis and distribution as related to functional changes in triglyceride transport and membrane formation. Methods: Tissue fatty acid profile and de novo lipogenesis were determined in adult male Wistar rats after 5 weeks of ethanol feeding using deuterated water and gas chromatography/mass spectrometry. Liver and pancreas fatty acid profiles and new synthesis fractions were compared with those from control rats on an isocaloric diet. Results: Fatty acid ratios in the liver indicated that there was a more than 2-fold accumulation of stearate to that of palmitate, with an apparent decrease in oleate content. On the other hand, in the pancreas, there was a 17% decrease in the stearate-to-palmitate ratio, whereas the oleate-to-palmitate ratio was increased by 30%. The fractions of deuterium-labeled palmitate and stearate were substantially reduced in the liver and pancreas of the alcohol-treated animals. Deuterium labeling of oleate was reduced in the liver but not in the pancreas, consistent with the oleate/stearate ratios in these tissues. Conclusions: Long-term alcohol exposure results in opposite effects on the desaturase activity in the liver and pancreas, limiting fatty acid transport in the liver but promoting the exocrine function of the pancreas. C1 [Boros, Laszlo G.; Lee, Wai-Nang Paul] Harbor UCLA Med Ctr, Dept Pediat Endocrinol & Metab, Torrance, CA 90502 USA. [Deng, Qinggao; Pandol, Stephen J.; Tsukamoto, Hidekazu] Univ So Calif, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA 90089 USA. [Pandol, Stephen J.; Tsukamoto, Hidekazu] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Internal Med, Los Angeles, CA USA. [Go, Vay Liang W.; Lee, Wai-Nang Paul] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Ctr Excellence Pancreat Dis, Los Angeles, CA 90095 USA. RP Boros, LG (reprint author), Harbor UCLA Med Ctr, Dept Pediat Endocrinol & Metab, 1124 W Carson St,RB1, Torrance, CA 90502 USA. EM boros@labiomed.org FU NCCIH NIH HHS [P01 AT003960-01A1, P01 AT003960]; NCI NIH HHS [P01-CA42710, P01 CA042710, P30 CA042710]; NCRR NIH HHS [M01-RR00425, M01 RR000425]; NIAAA NIH HHS [P50 AA011999, P50AA11999] NR 30 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 2009 VL 38 IS 2 BP E47 EP E52 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 415AC UT WOS:000263905700031 PM 19248221 ER PT J AU Mamikonyan, E Moberg, PJ Siderowf, A Duda, JE Ten Have, T Hurtig, HI Stern, MB Weintraub, D AF Mamikonyan, Eugenia Moberg, Paul J. Siderowf, Andrew Duda, John E. Ten Have, Tom Hurtig, Howard I. Stern, Matthew B. Weintraub, Daniel TI Mild cognitive impairment is common in Parkinson's disease patients with normal Mini-Mental State Examination (MMSE) scores SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Mild cognitive impairment; Parkinson's disease; Mini-Mental State Examination; Neuropsychology ID DAYTIME SLEEPINESS; DEMENTIA; DYSFUNCTION; POPULATION; PROFILE; COHORT; SCALE; AGE AB Purpose: Cognitive impairment occurs in the majority of Parkinson's disease (PD) patients, but little is known about detection of mild cognitive impairment (MCI) in this population. We report on the frequency and characteristics of cognitive deficits in PD, patients with intact global cognition based on Mini-Mental State Examination (MMSE) performance. Methods: One hundred and six PD patients with normal age- and education-adjusted MMSE scores (mean [SD] score = 29.1 [1.1]) were administered standardized neuropsychological tests assessing memory, executive function, and attention. Impairment on a cognitive domain was a low score (i.e., >= 1.5 SD below the published normative mean) on at least two measures or tests (for memory and executive abilities) or a single measure (for attention). Results: Mild cognitive impairment was found in 29.2% of PD patients, with 17.9% demonstrating single domain and 11.3% multiple domain impairment. Memory and attention impairment were most common (15.1% and 17.0% , respectively), followed by executive impairment (8.5%). Depending on the measure of disease severity chosen, increasing age and disease severity, anti-anxiety medication use, and a suggestion for increasing severity of daytime sleepiness were independent predictors of cognitive impairment. Conclusions: Cognitive deficits are common in PD patients with "normal" cognition based on MMSE performance, suggesting that MCI is under-recognized in clinical practice due to routine use of insensitive screening instruments. In contrast with some previous reports, early memory impairment may be as common as either executive or attentional deficits in PD. In addition, psychiatric medication use and daytime sleepiness may be reversible or treatable contributors to cognitive impairment. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Mamikonyan, Eugenia; Moberg, Paul J.; Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Siderowf, Andrew; Duda, John E.; Hurtig, Howard I.; Stern, Matthew B.; Weintraub, Daniel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Duda, John E.; Stern, Matthew B.; Weintraub, Daniel] Philadelphia Vet Affairs Med Center, PADRECC, Philadelphia, PA USA. [Ten Have, Tom] Univ Penn, Ctr Clin & Epidemiol Biostat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Center, MIRECC, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3615 Chestnut St,Room 330, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH [067894] FX Funded in part by NIMH grant #067894. NR 43 TC 88 Z9 94 U1 3 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD MAR PY 2009 VL 15 IS 3 BP 226 EP 231 DI 10.1016/j.parkreldis.2008.05.006 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 424RJ UT WOS:000264584700009 PM 18595765 ER PT J AU Fuzaylov, G Fidkowski, CW AF Fuzaylov, Gennadiy Fidkowski, Christina W. TI Anesthetic considerations for major burn injury in pediatric patients SO PEDIATRIC ANESTHESIA LA English DT Review DE burn injury; anesthesia; pediatric ID ABDOMINAL COMPARTMENT SYNDROME; EXTENSIVE THERMAL-INJURY; SKIN-GRAFTING PROCEDURES; SMOKE-INHALATION INJURY; SPINAL-CORD-INJURY; ACUTE LUNG INJURY; PAIN MANAGEMENT; INTRAABDOMINAL HYPERTENSION; PARENTERAL-NUTRITION; BACKGROUND PAIN AB Major burn injury remains a significant cause of morbidity and mortality in pediatric patients. With advances in burn care and with the development of experienced multi-disciplinary teams at regionalized burn centers, many children are surviving severe burn injury. As members of the multi-disciplinary care team, anesthesia providers are called upon to care for these critically ill children. These children provide several anesthetic challenges, such as difficult airways, difficult vascular access, fluid and electrolyte imbalances, altered temperature regulation, sepsis, cardiovascular instability, and increased requirements of muscle relaxants and opioids. The anesthesia provider must understand the physiologic derangements that occur with severe burn injury as well as the subsequent anesthetic implications. C1 [Fuzaylov, Gennadiy; Fidkowski, Christina W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Fuzaylov, G (reprint author), Massachusetts Gen Hosp, Pediat Anesthesia Serv, 55 Fruit St,Gray Bigelow 444, Boston, MA 02114 USA. EM gfuzaylov@partners.org NR 95 TC 3 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD MAR PY 2009 VL 19 IS 3 BP 202 EP 211 DI 10.1111/j.1460-9592.2009.02924.x PG 10 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 406NP UT WOS:000263302500002 PM 19187044 ER PT J AU DuBois, SG Krailo, MD Lessnick, SL Smith, R Chen, ZJ Marina, N Grier, HE Stegmaier, K AF DuBois, Steven G. Krailo, Mark D. Lessnick, Stephen L. Smith, Richard Chen, Zhengjia Marina, Neyssa Grier, Holcombe E. Stegmaier, Kimberly TI Phase II Study of Intermediate-Dose Cytarabine in Patients With Relapsed or Refractory Ewing Sarcoma: A Report From the Children's Oncology Group SO PEDIATRIC BLOOD & CANCER LA English DT Article DE cytarabine; Ewing sarcoma; EWS/FLI1 ID CYTOSINE-ARABINOSIDE; SOLID TUMORS; RECURRENCE; SURVIVAL; LEUKEMIA; THERAPY; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; EXPERIENCE AB Background. Patients with relapsed or refractory Ewing sarcoma have a poor Outcome with conventional therapies. Cytarabine decreases EWS/FLI1 protein levels in Ewing sarcoma cells and has demonstrated preclinical activity against Ewing sarcoma in vitro and in vivo. The purpose of this phase II clinical trial was to estimate the response rate of intermediate-dose cytarabine in patients with relapsed or refractory Ewing sarcoma. Procedure. Patients with a histologic diagnosis of Ewing sarcoma were eligible if they were <30 years of age, had relapsed or refractory measurable disease, and met standard or an function requirements. Patients received cytarabine 500 mg/m(2)/dose intravenously over 2 hr every 12 hr for 10 doses with cycles repeated every 21 clays. Response was assessed according to RECIST criteria. Results. Ten patients (median age 20 years;. 7 males) were treated. Only five patients had documented EWS/FLI1 translocated tumors. No objective responses were seen. One patient had stable disease for 5 cycles before developing progressive disease. All patients evaluable for hematologic toxicity developed grade 4 neutropenia and thrombocytopenia during protocol therapy. Patients were not able to receive therapy according to the planned 21-day cycles, with a median interval of 26.5 days. Conclusions. Cytarabine at the dose and schedule utilized in this trial resulted in hematologic toxicity that limited delivery of this therapy. This regimen also had minimal activity in this patient Population. Pediatr Blood Cancer 2009;52:324-327. (C) 2008 Wiley-Liss, Inc. C1 [DuBois, Steven G.] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. [Krailo, Mark D.; Chen, Zhengjia] Childrens Oncol Grp, Arcadia, CA USA. [Krailo, Mark D.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Lessnick, Stephen L.; Smith, Richard] Univ Utah, Sch Med, Div Pediat Hematol Oncol, Ctr Children,Huntsman Canc Inst, Salt Lake City, UT USA. [Marina, Neyssa] Stanford Univ, Lucile Packard Childrens Hosp, Sch Med, Dept Pediat, Stanford, CA USA. [Grier, Holcombe E.; Stegmaier, Kimberly] Harvard Univ, Sch Med, Childrens Hosp Boston, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA USA. RP DuBois, SG (reprint author), Univ Calif San Francisco, Sch Med, Dept Pediat, 505 Parnassus Ave,M646, San Francisco, CA 94143 USA. EM duboiss@peds.ucsf.edu FU ASCO Young-Investigator Award/WWWW Foundation; Terri Anna Perine Sarcoma Fund; Huntsman Cancer Institute/Huntsman Cancer Foundation; Huntsman Cancer Institute [P30 CA 042014]; COG Chairs [U10-CA98543] FX ASCO Young-Investigator Award/WWWW Foundation, Grant sponsor: Terri Anna Perine Sarcoma Fund: Grant sponsor: Huntsman Cancer Institute/Huntsman Cancer Foundation; Grant sponsor: Huntsman Cancer Institute; Grant number: P30 CA 042014 Grant sponsor: COG Chairs; Grant number: U10-CA98543. NR 19 TC 35 Z9 37 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAR PY 2009 VL 52 IS 3 BP 324 EP 327 DI 10.1002/pbc.21822 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 396PP UT WOS:000262603900007 PM 18989890 ER PT J AU Morrissey, LK Shea, LO Kalish, LA Weiner, DL Branowicki, P Heeney, MM AF Morrissey, Lisa K. Shea, Loan O'Brien Kalish, Leslie A. Weiner, Debra L. Branowicki, Patricia Heeney, Matthew M. TI Clinical Practice Guideline Improves the Treatment of Sickle Cell Disease Vasoocclusive Pain SO PEDIATRIC BLOOD & CANCER LA English DT Article DE pain; practice guideline; sickle cell anemia AB Background. Pain is the most common complication of sickle cell disease requiring emergency department (FD) visits and hospitalization. A Clinical Practice Guideline (CPG) to manage acute sickle cell pain offers clinicians a standardized approach for the provision of evidence-based, cost-effective care. After CPG implementation, monitoring of pre-established indicators is a strategy to evaluate progress toward meeting the goal of providing rapid, effective pain relief for patients With acute sickle cell pain. Methods. A retrospective chart review of patients with sickle cell disease admitted through the ED at Children's Hospital Boston with the primary diagnosis of vaso-occlusive pain was performed for a period before and after implementation of the CPG. Endpoints measured were: use Of a validated pain scale, time from ED triage to first close of analgesic, use of adequate weight-based analgesic dosing, frequency and location of PCA initiation, and time from ED triage to patient controlled analgesia (PCA) initiation. Results. Two hundred sixty three sickle cell pain admissions in 93 unique subjects; were analyzed, 51 pre-CPG and 212 post-CPG. Statistically significant improvements in use of pain scale, appropriate weight-based analgesic closing, utilization of PCA, and time to initiation of PCA were observed. There was not a statistically significant improvement in the percentage of subjects who received their 1st dose of analgesic within 1 hr; however the median time to first analgesic was reduced from 80 to 65 min (P = 0.003). Conclusions. Implementation of a CPG to manage acute sickle cell pain in the ED improves the ability to deliver timely, effective analgesia to this patient population. Establishing and monitoring internal benchmarks provides a means for ongoing evaluation of the pre-established goals for patient care. Pediatr Blood Cancer 2009;52:369-372. (C) 2008 Wiley-Liss, Inc. C1 [Morrissey, Lisa K.; Shea, Loan O'Brien; Branowicki, Patricia] Childrens Hosp, Dept Nursing, Boston, MA 02115 USA. [Branowicki, Patricia] Dana Farber Canc Inst, Dept Nursing, Patient Care Serv, Boston, MA 02115 USA. [Kalish, Leslie A.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Weiner, Debra L.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Heeney, Matthew M.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Heeney, MM (reprint author), Childrens Hosp, Dept Nursing, Fegan 704,300 Longwood Ave, Boston, MA 02115 USA. EM matthew.heeney@childrens.harvard.edu RI Heeney, Matthew/J-6838-2015 OI Heeney, Matthew/0000-0002-1104-6843 FU [K12 HL087164]; [MO1 RR021782] FX The authors would like to acknowledge the following clinicians who contributed to the development and ongoing monitoring of the sickle cell pain CPG: Charles Berde MD, Mary Fallon Smith MSN, RN, Stephanie Harrison BSN, RN, Brooke Hoffman RN, PNP, CPON, Kathleen Houlahan MS, RN, Shannon Manzi Pharml), Elizabeth Mullen, MD, Ellis Neufeld MD, and Diana Volpe BSN, RN. We also acknowledge Kim Vingh-Vo, BS, for help with data abstraction. This work was supported by K12 HL087164 (M.M.H., L.A.K.) and MO1 RR021782 (J.O.S.). NR 8 TC 20 Z9 20 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAR PY 2009 VL 52 IS 3 BP 369 EP 372 DI 10.1002/pbc.21847 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 396PP UT WOS:000262603900015 PM 19023890 ER PT J AU Lewis, MJ DuBois, SG Fligor, B Li, XC Goorin, A Grier, HE AF Lewis, Matthew J. DuBois, Steven G. Fligor, Brian Li, Xiaochun Goorin, Allen Grier, Holcombe E. TI Ototoxicity in Children Treated for Osteosarcoma SO PEDIATRIC BLOOD & CANCER LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol DE cisplatin; hearing loss; osteosarcoma; ototoxicity ID HEARING-LOSS; RECEIVING CISPLATIN; DOSE CISPLATIN; CHEMOTHERAPY; SYSTEM; AGE AB Background Cisplatin is an effective agent against osteosarcoma, Ototoxicity from osteosarcoma treatment protocols has not been well defined. The aim of this study was to determine the incidence and risk factors for hearing loss in children treated for osteosarcoma. Procedure. Eligible patients had osteosarcoma diagnosed and treated at the Datia-Farber Cancer Institute/Children's Hospital Boston from January 1, 1995 to December 12, 2004, were 3-18 years of age at diagnosis, and had a normal audiogram prior to the start of chemotherapy. Patients received cisplatin according to the standard practice of current open protocol. Patients who developed hearing loss during treatment had cisplatin held oil ail individualized basis. Hearing function was, evaluated prior to the start of therapy, before each cycle, and off-therapy. Fisher's exact test and logistic regression models were used to identify univariate and independent predictors of hearing loss, respectively. Results. Seven Out of nine patients (78%) who received cisplatin 120 mg/m(2)/day on 1 day developed hearing loss compared to 8/27 (30%) who received 60 mg/m(2)/day for 2 days (P=0.019). Logistic regression showed that age, Cumulative cisplatin close, and administration of cisplatin 120 mg/m(2)/day were independent predictors of hearing loss. Cisplatin administered as 60 mg/m(2)/day for 2 days resulted in a low incidence. (30%) of any hearing loss and a very low incidence (4%) Of educationally significant hearing loss. Conclusions. Cisplatin administered as 60 mg/m(2)/day for 2 days resulted in a low incidence of significant hearing loss. These results suggest that cisplatin as 120 mg/m(2)/day be avoided due to an unacceptable incidence of hearing loss. Pediatr Blood Cancer 2009;52:387-391. (C) 2008 Wiley-Liss, Inc. C1 [Lewis, Matthew J.; DuBois, Steven G.; Goorin, Allen; Grier, Holcombe E.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Lewis, Matthew J.; DuBois, Steven G.; Fligor, Brian; Li, Xiaochun; Goorin, Allen; Grier, Holcombe E.] Harvard Univ, Sch Med, Boston, MA USA. [Fligor, Brian] Childrens Hosp, Dept Audiol, Boston, MA 02115 USA. [Li, Xiaochun] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Grier, HE (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Binney St, Boston, MA 02115 USA. EM holcombe_grier@dfci.harvard.edu NR 27 TC 32 Z9 35 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAR PY 2009 VL 52 IS 3 BP 387 EP 391 DI 10.1002/pbc.21875 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 396PP UT WOS:000262603900019 PM 19061216 ER PT J AU Singh, H Dumas, GJ Silvestri, AP Young, S Martin, CR Bistrian, BR Driscoll, DF AF Singh, Hardeep Dumas, Gregory J. Silvestri, Anthony P. Young, Susan Martin, Camilia R. Bistrian, Bruce R. Driscoll, David F. TI Physical compatibility of neonatal total parenteral nutrition admixtures containing organic calcium and inorganic phosphate salts in a simulated infusion at 37 degrees C SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article CT Annual Meeting of the American-Association-of-Pharmaceutical-Scientists CY NOV 11-15, 2007 CL San Diego, CA SP Amer Assoc Pharmaceut Scientists DE total parenteral nutrition; neonates; amino acids; dextrose; calcium; phosphate; precipitation; particulates; thermoregulation ID PRECIPITATION; PHOSPHORUS; HAZARDS AB Objective: Within an incubator environment at 37 degrees C, we evaluated the physical compatibility of calcium (Ca) and phosphate (P) in simulated neonatal total parenteral nutrition (TPN) infusions. Design: Representative neonatal TPN formulas containing four concentrations of amino acids [AA] (1-4 g/dL) and two levels of dextrose [D] (5 and 10 g/dL) were monitored for calcium-phosphate precipitate formation over 24 hours using a laser-based particle counting technique. Setting. Research Laboratory. Subjects: None. Measurements and Main Results: Of the eight AA-D combinations studied, two formulas containing 1 g/dL AA with either 5 g/dL or 10 g/dL of D and high amounts of Ca and P resulted in significant increases in particle counts and visibly evident precipitation during the 24-hour infusion. Precipitation was noted only after the Infusion passed through the incubator, but not in the TPN bags, demonstrating the heightened risk of calcium-phosphate incompatibility with increased temperatures. Conclusions. Low AA concentrations and high temperatures are significant risk factors for the precipitation of the insoluble dibasic calcium phosphate that may be fatal upon intravenous infusion. When thermoregulation is required, the AA concentration of the TPN formula should not be less than 1.5 g/dL (and ideally; >= 3 g/dL) when high intakes of calcium (60 mg/dL) and phosphate (46.5 mg/dL) are prescribed. (Pediatr Crit Care Med 2009; 10:213-216) C1 [Singh, Hardeep] Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. [Dumas, Gregory J.; Silvestri, Anthony P.] Beth Israel Deaconess Med Ctr, Dept Pharm, Boston, MA 02215 USA. [Young, Susan] BIDMC, Dept Nursing, Boston, MA USA. [Martin, Camilia R.] BIDMC, Dept Neonatol, Boston, MA USA. [Bistrian, Bruce R.; Driscoll, David F.] BIDMC, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Singh, H (reprint author), Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. EM ddriscol@bidmc.harvard.edu NR 15 TC 9 Z9 9 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD MAR PY 2009 VL 10 IS 2 BP 213 EP 216 DI 10.1097/PCC.0b013e31819a3bf4 PG 4 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 419VK UT WOS:000264247600011 PM 19188866 ER PT J AU Nansel, TR Anderson, BJ Laffel, LMB Simons-Morton, BG Weissberg-Benchell, J Wysocki, T Iannotti, RJ Holmbeck, GN Hood, KK Lochrie, AS AF Nansel, Tonja R. Anderson, Barbara J. Laffel, Lori M. B. Simons-Morton, Bruce G. Weissberg-Benchell, Jill Wysocki, Tim Iannotti, Ronald J. Holmbeck, Grayson N. Hood, Korey K. Lochrie, Amanda S. TI A multisite trial of a clinic-integrated intervention for promoting family management of pediatric type 1 diabetes: feasibility and design SO PEDIATRIC DIABETES LA English DT Article DE adolescent; child; clinical trial; family; type 1 diabetes mellitus ID PEER-GROUP INTERVENTION; QUALITY-OF-LIFE; GLYCEMIC CONTROL; METABOLIC-CONTROL; SELF-MANAGEMENT; BEHAVIOR-THERAPY; ADOLESCENTS; ADHERENCE; CHILDREN; MELLITUS AB Nansel TR, Anderson BJ, Laffel LMB, Simons-Morton BG, Weissberg-Benchell J, Wysocki T, Iannotti RJ, Holmbeck GN, Hood KK, Lochrie AS. A multisite trial of a clinic-integrated intervention for promoting family management of pediatric type 1 diabetes: feasibility and design.Pediatric Diabetes 2009: 10: 105-115. The feasibility of a family-based clinic-integrated behavioral intervention to improve family management of type 1 diabetes was evaluated. In each of four clinical sites, 30-32 families (a total of 122) were randomized to intervention or usual care comparison groups. The WE*CAN intervention, based on family problem-solving methods, was delivered during three routine clinic visits by trained 'Health Advisors'. Of eligible families across the four sites, 83% agreed to participate, of whom 96% completed the baseline, mid-term, and postintervention assessments. Families participated in an average of 2.85 intervention sessions over an 8-month period. The intervention was integrated into the clinic setting without impairing clinic flow and was implemented with fidelity and consistency across sites by trained non-professionals. The findings provide evidence of the feasibility of conducting a multisite trial to evaluate the effects of a clinic-integrated problem-solving intervention to improve family management. Many lessons were learned that provide guidance for recruitment, measurement, and intervention for the larger clinical trial. C1 [Nansel, Tonja R.; Simons-Morton, Bruce G.] NIH, Div Epidemiol Stat & Prevent Res, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, DHHS, Bethesda, MD 20892 USA. [Anderson, Barbara J.; Iannotti, Ronald J.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Laffel, Lori M. B.; Hood, Korey K.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Weissberg-Benchell, Jill] Childrens Mem Hosp, Dept Child & Adolescent Psychiat, Chicago, IL 60614 USA. [Holmbeck, Grayson N.] Loyola Univ Chicago, Dept Psychol, Chicago, IL USA. [Wysocki, Tim; Lochrie, Amanda S.] Nemours Childrens Clin, Dept Biomed Res, Jacksonville, FL USA. RP Nansel, TR (reprint author), 6100 Execut Blvd,Room 7B13R,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Simons-Morton, Bruce/0000-0003-1099-6617 FU National Institutes of Health; National Institute of Child Health and Human Development FX This research was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. The following institutions and investigators comprised the steering committee of the Family Management of Diabetes multisite trial. Eunice Kennedy Shriver National Institute of Child Health and Human Development: T. R. N., B. G. S.-M., R. J. I. Joslin Diabetes Center: L. M. B. L., K. K. H., Contract N01-HD-4-3364. Nemours Children's Clinic: T. W., A. S. L., Contract N01-HD-4-3361. Texas Children's Hospital, Houston, TX: B. J. A., Contract N01-HD-4-3362. Children's Memorial Hospital: J. W.-B., G. N. H., Contract N01-HD-4-3363. James Bell Associates, Arlington, VA: Cheryl McDonnell, PhD, MaryAnn D'Elio, Contract N01-HD-3-3360. NR 34 TC 25 Z9 27 U1 4 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD MAR PY 2009 VL 10 IS 2 BP 105 EP 115 DI 10.1111/j.1399-5448.2008.00448.x PG 11 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 412DQ UT WOS:000263704100004 PM 18721167 ER PT J AU Simson, GG Goldberg, JD Rolnitzky, LM Mull, J Leyne, M Voustianiouk, A Slaugenhaupt, SA Axelrod, FB AF Simson, Gabrielle Gold-von Goldberg, Judith D. Rolnitzky, Linda M. Mull, James Leyne, Maire Voustianiouk, Andre Slaugenhaupt, Susan A. Axelrod, Felicia B. TI Kinetin in Familial Dysautonomia Carriers: Implications for a New Therapeutic Strategy Targeting mRNA Splicing SO PEDIATRIC RESEARCH LA English DT Article ID GENE-EXPRESSION; IKBKAP; MUTATION; IDENTIFICATION; CELLS AB Familial dysautonomia (FD) is caused by an intronic splice mutation in the I kappa B kinase-associated protein gene (IKBKAP) that leads to partial skipping of exon 20 and tissue-specific reduction Of I kappa B kinase-associated protein/elongator protein 1 (IKAP/ELP-1 protein). Kinetin increases IKBKAP mRNA and protein expression in FD cell lines. To determine whether oral kinetin alters IKBKAP splicing in vivo, we administered kinetin to 29 healthy carriers of the major FD mutation for 8 d. Adverse effects, kinetin, and IKBKAP mRNA levels were monitored. In the highest dosing cohorts (23.5 mg/kg/d), the target plasma kinetin level was achieved in 91% of subjects at 2 h. After 8 d, IKBKAP mRNA expression in leukocytes increased as kinetin levels increased. There is a linear association between log plasma kinetin level and corresponding log change from baseline in IKBKAP mRNA expression that allows estimation of IKBKAP mRNA levels because of kinetin ingestion. Adverse effects were transient and mild. This is the first report of in vivo IKBKAP splicing modification and strongly suggests kinetin's therapeutic potential in FD and perhaps in other splicing disorders. Furthermore, our findings support our hypothesis that treatments, which target a particular splicing mutation, can be successfully developed. (Pediatr Res 65: 341-346, 2009) C1 [Simson, Gabrielle Gold-von; Voustianiouk, Andre; Axelrod, Felicia B.] NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. [Goldberg, Judith D.; Rolnitzky, Linda M.] NYU, Sch Med, Div Biostat, New York, NY 10016 USA. [Mull, James; Leyne, Maire; Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Dept Neurol Genet, Ctr Human Genet Res, Boston, MA 02114 USA. [Mull, James; Leyne, Maire; Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Dept Neurol Genet, Boston, MA 02115 USA. RP Simson, GG (reprint author), NYU Med Ctr, Dysautonomia Ctr, 530 1st Ave,Suite 9Q, New York, NY 10016 USA. EM gold01@med.nyu.edu NR 20 TC 16 Z9 16 U1 0 U2 5 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAR PY 2009 VL 65 IS 3 BP 341 EP 346 PG 6 WC Pediatrics SC Pediatrics GA 409YZ UT WOS:000263543000016 ER PT J AU Thornley, I Eapen, M Sung, L Lee, SJ Davies, SM Joffe, S AF Thornley, Ian Eapen, Mary Sung, Lillian Lee, Stephanie J. Davies, Stella M. Joffe, Steven TI Private Cord Blood Banking: Experiences and Views of Pediatric Hematopoietic Cell Transplantation Physicians SO PEDIATRICS LA English DT Article DE hematopoietic stem cell transplantation; cord blood stem cell transplantation; bioethics ID BONE-MARROW-TRANSPLANTATION; SEVERE APLASTIC-ANEMIA; POTENTIAL FUTURE TRANSPLANTATION; UNRELATED DONORS; ACUTE-LEUKEMIA; CHILDREN; NEUROBLASTOMA; ADULTS; CRYOPRESERVATION; COLLECTION AB OBJECTIVE. Private cord blood banks are for-profit companies that facilitate storage of umbilical cord blood for personal or family use. Pediatric hematopoietic cell transplantation physicians are currently best situated to use cord blood therapeutically. We sought to describe the experiences and views of these physicians regarding private cord blood banking. PARTICIPANTS AND METHODS. We e-mailed a cross-sectional survey to pediatric hematopoietic cell transplantation physicians in the United States and Canada; 93 of 152 potentially eligible physicians (93 of 130 confirmed survey recipients) from 57 centers responded. Questions addressed the number of transplants performed by using privately banked cord blood, willingness to use banked autologous cord blood in specific clinical settings, and recommendations to parents regarding private cord blood banking. RESULTS. Respondents reported having performed 9 autologous and 41 allogeneic transplants using privately banked cord blood. In 36 of 40 allogeneic cases for which data were available, the cord blood had been collected because of a known indication in the recipient. Few respondents would choose autologous cord blood over alternative stem cell sources for treatment of acute lymphoblastic leukemia in second remission. In contrast, 55% would choose autologous cord blood to treat high-risk neuroblastoma, or to treat severe aplastic anemia in the absence of an available sibling donor. No respondent would recommend private cord blood banking for a newborn with 1 healthy sibling when both parents were of northern European descent; 11% would recommend banking when parents were of different minority ethnicities. CONCLUSIONS. Few transplants have been performed by using cord blood stored in the absence of a known indication in the recipient. Willingness to use banked autologous cord blood varies depending on disease and availability of alternative stem cell sources. Few pediatric hematopoietic cell transplantation physicians endorse private cord blood banking in the absence of an identified recipient, even for mixed-ethnicity children for whom finding a suitably matched unrelated donor may be difficult. Pediatrics 2009;123:1011-1017 C1 [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Joffe, Steven] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Thornley, Ian] N Shore Med Ctr, Dept Pediat, Salem, MA USA. [Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Sung, Lillian] Hosp Sick Children, Div Pediat Hematol Oncol, Toronto, ON M5G 1X8, Canada. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Davies, Stella M.] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM steven_joffe@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [U24 CA076518, U24 CA076518-14] NR 54 TC 28 Z9 30 U1 1 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2009 VL 123 IS 3 BP 1011 EP 1017 DI 10.1542/peds.2008-0436 PG 7 WC Pediatrics SC Pediatrics GA 413XH UT WOS:000263825500038 PM 19255033 ER PT J AU Baldessarini, RJ Tondo, L AF Baldessarini, R. J. Tondo, L. TI Suicidal Risks during Treatment of Bipolar Disorder Patients with Lithium versus Anticonvulsants SO PHARMACOPSYCHIATRY LA English DT Article ID CONTROLLED 18-MONTH TRIAL; MAINTENANCE TREATMENT; I DISORDER; BEHAVIOR; PREVENTION; DIVALPROEX; CARBAMAZEPINE; LAMOTRIGINE AB The aim of this study was to compare suicidal risks during long-term treatment of bipolar disorder (BPD) patients with lithium versus anticonvulsants (ACs). Medline (R) searching identified 6 reports of direct comparisons of patients diagnosed with BPD by modern criteria, treated :6 months with lithium versus ACs (carbamazepine, divalproex, lamotrigine), with non-zero risk of suicide or attempts in at least one study-arm. We extracted rates (events/persons/exposure time) for each treatment arm, and applied random-effects meta-analysis to determine pooled risk ratio, risk difference, and their 95% confidence intervals (CI). Overall, rates of suicidal acts were 2.86-times (95% Cl: 2.29-3.57; p<0.0001) higher during treatment with ACs versus lithium, and no AC emerged as clearly superior to the others. Comparisons of suicidal risks during treatment with lithium versus ACs remain rare and methodologically limited, but favor lithium and encourage further study in this era of growing regulatory concern about possible adverse effects of ACs. C1 [Baldessarini, R. J.; Tondo, L.] Massachusetts Gen Hosp, Int Consortium Bipolar Disorder Res, Mailman Res Ctr, McLean Div, Belmont, MA USA. [Baldessarini, R. J.; Tondo, L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Tondo, L.] Univ Cagliari, Dept Psychol, Cagllari, Sardinia, Italy. [Tondo, L.] Lucio Bini Mood Disorders Ctr, Cagliari, Sardinia, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 312, 115 Mill St, Belmont, MA 02178 USA. EM rjb@mclean.org FU Bruce J. Anderson Foundation; McLean Private Donors Research Fund; Lucio Bini Center Private Donors Research Fund FX Supported in part by a grant from the Bruce J. Anderson Foundation and by the McLean Private Donors Research Fund (to RJB), and the Lucio Bini Center Private Donors Research Fund (to L.T.). NR 21 TC 15 Z9 15 U1 2 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD MAR PY 2009 VL 42 IS 2 BP 72 EP 75 DI 10.1055/s-0028-1103291 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 430YH UT WOS:000265028000006 PM 19308882 ER PT J AU Abedini, A Raleigh, DP AF Abedini, Andisheh Raleigh, Daniel P. TI A role for helical intermediates in amyloid formation by natively unfolded polypeptides? SO PHYSICAL BIOLOGY LA English DT Article ID SOLID-STATE NMR; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; PROTEIN AGGREGATION; FIBRIL FORMATION; EMERGING ROLE; 2D IR; MEMBRANE; NEURODEGENERATION; FIBRILLOGENESIS AB Amyloid formation and aberrant protein aggregation have been implicated in more than 15 different human diseases and an even wider range of proteins form amyloid in vitro. From a structural perspective the proteins which form amyloid can be divided into two classes: those which adopt a compact globular fold and must presumably at least partially unfold to form amyloid and those which are unstructured in their monomeric state. Important examples of the latter include the A beta peptide of Alzheimer's disease, atrial natriuretic factor, calcitonin, pro-calcitonin, islet amyloid polypeptide ( IAPP, amylin), alpha-synuclein and the medin polypeptide. The kinetics of amyloid assembly are complex and typically involve a lag phase during which little or no fibril material is formed, followed by a rapid growth stage leading to the beta-sheet-rich amyloid structure. Increasing evidence suggests that some natively unfolded polypeptides populate a helical intermediate during the lag phase. We propose a model in which early oligomerization is linked to helix formation and is promoted by helix-helix association. Recent work has highlighted the potential importance of polypeptide membrane interactions in amyloid formation and helical intermediates appear to play an important role here as well. Characterization of helical intermediates is experimentally challenging but new spectroscopic techniques are emerging which hold considerable promise and even have the potential to provide residue specific information. C1 [Abedini, Andisheh] Harvard Univ, Sch Med, Div Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02250 USA. [Raleigh, Daniel P.] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA. [Raleigh, Daniel P.] SUNY Stony Brook, Grad Program Biophys, Grad Program Biochem & Struct Biol, Stony Brook, NY 11794 USA. RP Abedini, A (reprint author), Harvard Univ, Sch Med, Div Cellular & Mol Physiol, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02250 USA. EM Andisheh.Abedini@joslin.harvard.edu; draleigh@notes.cc.sunysb.edu OI Abedini, Andisheh/0000-0002-1396-1420 FU NIH [GM078114] FX We thank members of the Raleigh group for helpful discussions. This work was supported by a grant from the NIH to DPR GM078114. NR 52 TC 98 Z9 98 U1 4 U2 16 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 J9 PHYS BIOL JI Phys. Biol. PD MAR PY 2009 VL 6 IS 1 AR 015005 DI 10.1088/1478-3975/6/1/015005 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 446VE UT WOS:000266148700007 PM 19208933 ER PT J AU Chandran, D Tai, YC Hather, G Dewdney, J Denoux, C Burgess, DG Ausubel, FM Speed, TP Wildermuth, MC AF Chandran, Divya Tai, Yu Chuan Hather, Gregory Dewdney, Julia Denoux, Carine Burgess, Diane G. Ausubel, Frederick M. Speed, Terence P. Wildermuth, Mary C. TI Temporal Global Expression Data Reveal Known and Novel Salicylate-Impacted Processes and Regulators Mediating Powdery Mildew Growth and Reproduction on Arabidopsis SO PLANT PHYSIOLOGY LA English DT Article ID SYSTEMIC ACQUIRED-RESISTANCE; PROTEIN FAMILIES DATABASE; INDUCED CELL-DEATH; PROBE LEVEL DATA; PLANT-DEFENSE; TRANSCRIPTION FACTORS; DISEASE-RESISTANCE; BROAD-SPECTRUM; PENETRATION RESISTANCE; ENDOPLASMIC-RETICULUM AB Salicylic acid (SA) is a critical mediator of plant innate immunity. It plays an important role in limiting the growth and reproduction of the virulent powdery mildew (PM) Golovinomyces orontii on Arabidopsis (Arabidopsis thaliana). To investigate this later phase of the PM interaction and the role played by SA, we performed replicated global expression profiling for wildtype and SA biosynthetic mutant isochorismate synthase1 (ics1) Arabidopsis from 0 to 7 d after infection. We found that ICS1-impacted genes constitute 3.8% of profiled genes, with known molecular markers of Arabidopsis defense ranked very highly by the multivariate empirical Bayes statistic (T-2 statistic). Functional analyses of T-2 -selected genes identified statistically significant PM-impacted processes, including photosynthesis, cell wall modification, and alkaloid metabolism, that are ICS1 independent. ICS1-impacted processes include redox, vacuolar transport/secretion, and signaling. Our data also support a role for ICS1 (SA) in iron and calcium homeostasis and identify components of SA cross talk with other phytohormones. Through our analysis, 39 novel PM-impacted transcriptional regulators were identified. Insertion mutants in one of these regulators, PUX2 (for plant ubiquitin regulatory X domain-containing protein 2), results in significantly reduced reproduction of the PM in a cell death-independent manner. Although little is known about PUX2, PUX1 acts as a negative regulator of Arabidopsis CDC48, an essential AAA-ATPase chaperone that mediates diverse cellular activities, including homotypic fusion of endoplasmic reticulum and Golgi membranes, endoplasmic reticulum-associated protein degradation, cell cycle progression, and apoptosis. Future work will elucidate the functional role of the novel regulator PUX2 in PM resistance. C1 [Chandran, Divya; Hather, Gregory; Burgess, Diane G.; Wildermuth, Mary C.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA. [Tai, Yu Chuan] Univ Calif Berkeley, Div Biostat, Berkeley, CA 94720 USA. [Hather, Gregory; Speed, Terence P.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. [Dewdney, Julia; Denoux, Carine; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Dewdney, Julia; Denoux, Carine; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Wildermuth, MC (reprint author), Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA. EM wildermuth@nature.berkeley.edu RI Speed, Terence /B-8085-2009; Chandran, Divya/A-4236-2012 OI Speed, Terence /0000-0002-5403-7998; FU National Science Foundation [MCB-0420267, DBI-0114783]; Winkler Family Foundation FX This work was supported by the National Science Foundation (Arabidopsis 2010 grant nos. MCB-0420267 to M. C. W. and T. P. S. and DBI-0114783 to X. Dong, S. Somerville, and F. M. A.) and the Winkler Family Foundation (grant to M. C. W.). NR 99 TC 28 Z9 30 U1 0 U2 9 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 EI 1532-2548 J9 PLANT PHYSIOL JI Plant Physiol. PD MAR PY 2009 VL 149 IS 3 BP 1435 EP 1451 DI 10.1104/pp.108.132985 PG 17 WC Plant Sciences SC Plant Sciences GA 414DI UT WOS:000263843700019 PM 19176722 ER PT J AU Blomquist, P Devor, A Indahl, UG Ulbert, I Einevoll, GT Dale, AM AF Blomquist, Patrick Devor, Anna Indahl, Ulf G. Ulbert, Istvan Einevoll, Gaute T. Dale, Anders M. TI Estimation of Thalamocortical and Intracortical Network Models from Joint Thalamic Single-Electrode and Cortical Laminar-Electrode Recordings in the Rat Barrel System SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID PRIMARY SOMATOSENSORY CORTEX; SPINY STELLATE CELLS; RESPONSE TRANSFORMATIONS; FEEDFORWARD INHIBITION; WHISKER/BARREL SYSTEM; SYNAPTIC CONNECTIONS; LATERAL-INHIBITION; NEURONAL NETWORKS; PYRAMIDAL NEURONS; PATTERN-FORMATION AB A new method is presented for extraction of population firing-rate models for both thalamocortical and intracortical signal transfer based on stimulus-evoked data from simultaneous thalamic single-electrode and cortical recordings using linear (laminar) multielectrodes in the rat barrel system. Time-dependent population firing rates for granular (layer 4), supragranular (layer 2/3), and infragranular (layer 5) populations in a barrel column and the thalamic population in the homologous barreloid are extracted from the high-frequency portion (multi-unit activity; MUA) of the recorded extracellular signals. These extracted firing rates are in turn used to identify population firing-rate models formulated as integral equations with exponentially decaying coupling kernels, allowing for straightforward transformation to the more common firing-rate formulation in terms of differential equations. Optimal model structures and model parameters are identified by minimizing the deviation between model firing rates and the experimentally extracted population firing rates. For the thalamocortical transfer, the experimental data favor a model with fast feedforward excitation from thalamus to the layer-4 laminar population combined with a slower inhibitory process due to feedforward and/or recurrent connections and mixed linear-parabolic activation functions. The extracted firing rates of the various cortical laminar populations are found to exhibit strong temporal correlations for the present experimental paradigm, and simple feedforward population firing-rate models combined with linear or mixed linear-parabolic activation function are found to provide excellent fits to the data. The identified thalamocortical and intracortical network models are thus found to be qualitatively very different. While the thalamocortical circuit is optimally stimulated by rapid changes in the thalamic firing rate, the intracortical circuits are low-pass and respond most strongly to slowly varying inputs from the cortical layer-4 population. C1 [Blomquist, Patrick; Indahl, Ulf G.; Einevoll, Gaute T.] Norwegian Univ Life Sci, Dept Math Sci & Technol, As, Norway. [Blomquist, Patrick; Indahl, Ulf G.; Einevoll, Gaute T.] Norwegian Univ Life Sci, Ctr Integrat Genet, As, Norway. [Devor, Anna] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. [Devor, Anna; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Devor, Anna; Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Ulbert, Istvan] Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. [Ulbert, Istvan] Peter Pazmany Catholic Univ, Dept Informat Technol, Budapest, Hungary. RP Blomquist, P (reprint author), Norwegian Univ Life Sci, Dept Math Sci & Technol, As, Norway. EM Gaute.Einevoll@umb.no RI Ulbert, Istvan/F-2213-2010; Dale, Anders/A-5180-2010 FU Research Council of Norway; National Institute of Health [R01 EB00790, NS051188] FX Work was financially supported by the Research Council of Norway under the BeMatA and eVITA programmes, and by the National Institute of Health [R01 EB00790, NS051188]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 76 TC 14 Z9 14 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAR PY 2009 VL 5 IS 3 AR e1000328 DI 10.1371/journal.pcbi.1000328 PG 24 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 447TF UT WOS:000266214000033 PM 19325875 ER PT J AU Bohland, JW Wu, CZ Barbas, H Bokil, H Bota, M Breiter, HC Cline, HT Doyle, JC Freed, PJ Greenspan, RJ Haber, SN Hawrylycz, M Herrera, DG Hilgetag, CC Huang, ZJ Jones, A Jones, EG Karten, HJ Kleinfeld, D Kotter, R Lester, HA Lin, JM Mensh, BD Mikula, S Panksepp, J Price, JL Safdieh, J Saper, CB Schiff, ND Schmahmann, JD Stillman, BW Svoboda, K Swanson, LW Toga, AW Van Essen, DC Watson, JD Mitra, PP AF Bohland, Jason W. Wu, Caizhi Barbas, Helen Bokil, Hemant Bota, Mihail Breiter, Hans C. Cline, Hollis T. Doyle, John C. Freed, Peter J. Greenspan, Ralph J. Haber, Suzanne N. Hawrylycz, Michael Herrera, Daniel G. Hilgetag, Claus C. Huang, Z. Josh Jones, Allan Jones, Edward G. Karten, Harvey J. Kleinfeld, David Kotter, Rolf Lester, Henry A. Lin, John M. Mensh, Brett D. Mikula, Shawn Panksepp, Jaak Price, Joseph L. Safdieh, Joseph Saper, Clifford B. Schiff, Nicholas D. Schmahmann, Jeremy D. Stillman, Bruce W. Svoboda, Karel Swanson, Larry W. Toga, Arthur W. Van Essen, David C. Watson, James D. Mitra, Partha P. TI A Proposal for a Coordinated Effort for the Determination of Brainwide Neuroanatomical Connectivity in Model Organisms at a Mesoscopic Scale SO PLOS COMPUTATIONAL BIOLOGY LA English DT Review ID BIOTINYLATED DEXTRAN-AMINE; CENTRAL-NERVOUS-SYSTEM; WHITE-MATTER; CAENORHABDITIS-ELEGANS; CORPUS-CALLOSUM; LABELED NEURONS; CHOLERA-TOXIN; MOTOR CORTEX; MOUSE-BRAIN; AUTISM AB In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is critical, however, for both basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brainwide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brainwide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open-access data repository; compatibility with existing resources; and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget. C1 [Bohland, Jason W.; Wu, Caizhi; Bokil, Hemant; Cline, Hollis T.; Huang, Z. Josh; Lin, John M.; Stillman, Bruce W.; Watson, James D.; Mitra, Partha P.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Barbas, Helen] Boston Univ, Dept Hlth Sci, Boston, MA 02215 USA. [Bota, Mihail; Swanson, Larry W.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. [Bokil, Hemant] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Doyle, John C.] CALTECH, Dept Elect Engn, Pasadena, CA 91125 USA. [Freed, Peter J.] Columbia Univ, New York State Psychiat Inst, Med Ctr, New York, NY USA. [Greenspan, Ralph J.] Inst Neurosci, San Diego, CA USA. [Haber, Suzanne N.] Univ Rochester, Med Ctr, Dept Physiol & Pharmacol, Rochester, NY 14642 USA. [Hawrylycz, Michael; Jones, Allan] Allen Inst Brain Sci, Seattle, WA USA. [Herrera, Daniel G.] Harvard Univ, Brigham & Womens Hosp, Dept Psychiat, Sch Med, Boston, MA 02115 USA. [Hilgetag, Claus C.] Jacobs Univ Bremen, Sch Sci & Engn, Bremen, Germany. [Jones, Edward G.; Mikula, Shawn] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. [Karten, Harvey J.] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. [Kleinfeld, David] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA. [Kotter, Rolf] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci,NeuroPI, NL-6525 ED Nijmegen, Netherlands. [Lester, Henry A.] CALTECH, Dept Biol, Pasadena, CA 91125 USA. [Mensh, Brett D.] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA. [Panksepp, Jaak] Washington State Univ, Coll Vet Med, Pullman, WA 99164 USA. [Price, Joseph L.; Van Essen, David C.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Safdieh, Joseph; Schiff, Nicholas D.] Weill Cornell Med Coll, Dept Neurol, New York, NY USA. [Saper, Clifford B.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Svoboda, Karel] Howard Hughes Med Inst, Ashburn, VA USA. [Toga, Arthur W.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab NeuroImaging, Los Angeles, CA 90024 USA. RP Bohland, JW (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA. EM bohland@cshl.edu RI Kotter, Rolf/A-2565-2010; Hilgetag, Claus/L-7282-2013; Bohland, Jason/L-4807-2016; OI Hilgetag, Claus/0000-0003-2129-8910; Bohland, Jason/0000-0002-6305-5848; Huang, Z. Josh/0000-0003-0592-028X; Stillman, Bruce/0000-0002-9453-4091 FU W. M. Keck Foundation FX This paper is a result of discussions at the 2007 and 2008 Brain Architecture Project Banbury Center Meetings, funded by the W. M. Keck Foundation. The sponsors had no role in the conception or preparation of this manuscript. NR 72 TC 121 Z9 123 U1 3 U2 26 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAR PY 2009 VL 5 IS 3 AR e1000334 DI 10.1371/journal.pcbi.1000334 PG 9 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 447TF UT WOS:000266214000038 PM 19325892 ER PT J AU Harris, JB Podolsky, MJ Bhuiyan, TR Chowdhury, F Khan, AI LaRocque, RC Logvinenko, T Kendall, J Faruque, ASG Nagler, CR Ryan, ET Qadri, F Calderwood, SB AF Harris, Jason B. Podolsky, Michael J. Bhuiyan, Taufiqur R. Chowdhury, Fahima Khan, Ashraful I. LaRocque, Regina C. Logvinenko, Tanya Kendall, Jennifer Faruque, Abu S. G. Nagler, Cathryn R. Ryan, Edward T. Qadri, Firdausi Calderwood, Stephen B. TI Immunologic Responses to Vibrio cholerae in Patients Co-Infected with Intestinal Parasites in Bangladesh SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID VACCINE CVD 103-HGR; ANTIBODY-RESPONSE; IMMUNE-RESPONSES; CHILDREN; TOXIN; SUSCEPTIBILITY; PROTECTION; CONTACTS; EFFICACY; ASCARIS AB Background: Infection with intestinal helminths is common and may contribute to the decreased efficacy of Vibrio cholerae vaccines in endemic compared to non-endemic areas. However, the immunomodulatory effects of concomitant intestinal parasitic infection in cholera patients have not been systematically evaluated. Methods: We evaluated V. cholerae-specific immune responses in a cohort of patients with severe cholera. 361 patients completed 21 days of observation and 53 (15%) had evidence of a concomitant intestinal parasitic infection based on direct microscopy. Although there were no significant differences in the vibriocidal or lipopolysaccharide (LPS)-specific immune responses to V. cholerae, helminth-infected cholera patients had decreased fecal and serum IgA immune responses to the B subunit of cholera toxin (CTB) as well as a more modest decrease in serum IgG response to CTB. These findings remained significant for all classes of helminth infection and when controlling for potential confounding variables such as age and nutritional status. Although we hypothesized the differential effect on CTB and LPS immune responses was due to T-celldependent immunomodulatory effects of helminth infection, we did not find additional evidence to support a classic Th1 or Th2 polarization of the immune response to V. cholerae infection related to parasite infection. Conclusions/Significance: The finding that helminth infection has a profound association with the mucosal humoral immune response to V. cholerae has implications for the development of protective immunity in cholera-endemic areas and provides an additional basis for deworming programs in cholera-endemic areas. Additional studies, including further characterization of the role of T cells in the immune response to human V. cholerae infection and the development of an animal model of co-infection, may provide additional insight into the mechanisms underlying these findings. C1 [Harris, Jason B.; Podolsky, Michael J.; LaRocque, Regina C.; Kendall, Jennifer; Faruque, Abu S. G.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Harris, Jason B.; Nagler, Cathryn R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Bhuiyan, Taufiqur R.; Chowdhury, Fahima; Khan, Ashraful I.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Logvinenko, Tanya] Tufts Med Ctr, ICRHPS, Biostat Res Ctr, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM jbharris@partners.org FU ICDDR, B: Centre for Health and Population Research; International Research Scientist Development Award [K01 TW07144]; Pediatric Scientist Development Program [K12 HD00850]; International Research Scientist Development [K01 TW07409]; Fogarty International Clinical Research Scholars Program [D43 TW05572]; [U01 AI058935]; [RO3 AI063079]; [R01 AI40725] FX This research was supported by ICDDR, B: Centre for Health and Population Research and by the following grants: U01 AI058935 (SBC); RO3 AI063079 (FQ); R01 AI40725 (ETR); International Research Scientist Development Award K01 TW07144 (RCL); Pediatric Scientist Development Program K12 HD00850 (JBH); International Research Scientist Development Award K01 TW07409 (JBH); and Fogarty International Clinical Research Scholars Program D43 TW05572 (AIK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 34 Z9 35 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAR PY 2009 VL 3 IS 3 AR e403 DI 10.1371/journal.pntd.0000403 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 438DT UT WOS:000265536800019 PM 19333369 ER PT J AU Yan, N Cherepanov, P Daigle, JE Engelman, A Lieberman, J AF Yan, Nan Cherepanov, Peter Daigle, Janet E. Engelman, Alan Lieberman, Judy TI The SET Complex Acts as a Barrier to Autointegration of HIV-1 SO PLOS PATHOGENS LA English DT Article ID TYPE-1 PREINTEGRATION COMPLEXES; RETROVIRAL DNA INTEGRATION; AICARDI-GOUTIERES-SYNDROME; INNATE IMMUNE-RESPONSE; ASSEMBLY PROTEIN SET; MEDIATED CELL-DEATH; GRANZYME-A; EXONUCLEASE TREX1; STRAND-TRANSFER; REPAIR PROTEIN AB Retroviruses and retrotransposons are vulnerable to a suicidal pathway known as autointegration, which occurs when the 3'-ends of the reverse transcript are activated by integrase and then attack sites within the viral DNA. Retroelements have diverse strategies for suppressing autointegration, but how HIV-1 protects itself from autointegration is not well-understood. Here we show that knocking down any of the components of the SET complex, an endoplasmic reticulum-associated complex that contains 3 DNases (the base excision repair endonuclease APE1, 5'-3' exonuclease TREX1, and endonuclease NM23-H1), inhibits HIV-1 and HIV-2/SIV, but not MLV or ASV, infection. Inhibition occurs at a step in the viral life cycle after reverse transcription but before chromosomal integration. Antibodies to SET complex proteins capture HIV-1 DNA in the cytoplasm, suggesting a direct interaction between the SET complex and the HIV preintegration complex. Cloning of HIV integration sites in cells with knocked down SET complex components revealed an increase in autointegration, which was verified using a novel semi-quantitative nested PCR assay to detect autointegrants. When SET complex proteins are knocked down, autointegration increases 2-3-fold and chromosomal integration correspondingly decreases,3-fold. Therefore, the SET complex facilitates HIV-1 infection by preventing suicidal autointegration. C1 [Yan, Nan; Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Cherepanov, Peter] Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. [Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Med, London, England. [Daigle, Janet E.; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Yan, N (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu; lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015; Cherepanov, Peter/F-6859-2010 OI Cherepanov, Peter/0000-0002-0634-538X FU NIH [AI45587, AI39394, AI52014]; UK Medical Research Council; Harvard CFAR scholar award FX This work was supported by NIH grants AI45587 (JL), AI39394 (AE), and AI52014 (AE), the UK Medical Research Council (PC), and a Harvard CFAR scholar award (NY). NR 70 TC 47 Z9 47 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD MAR PY 2009 VL 5 IS 3 AR e1000327 DI 10.1371/journal.ppat.1000327 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 447TZ UT WOS:000266216000008 PM 19266025 ER PT J AU Aragaki, DR Nasmyth, MC Schultz, SC Nguyen, GM Yentes, JM Kao, K Perell, K Fang, MA AF Aragaki, Dixie R. Nasmyth, Mary C. Schultz, Scott C. Nguyen, Gretchen M. Yentes, Jennifer M. Kao, Kaly Perell, Karen Fang, Meika A. TI Immediate Effects of Contralateral and Ipsilateral Cane Use On Normal Adult Gait SO PM&R LA English DT Article AB Objective: To determine the effects of ipsilateral and contralateral cane use on gait kinematics and peak vertical force in young healthy adults. Design: Prospective observational study. Setting: Veterans Affairs Healthcare Center. Participants: Fifteen healthy adults of aged 26 to 52 years (mean age 31 years) with no gait impairment and minimal experience using single-point canes. Methods: The Pedar-X Mobile System plantar pressure measurement system was used to collect kinematic data from subjects walking in 3 different conditions (relative to a randomly "assigned" limb): contralateral cane (C), ipsilateral cane (I), and no cane (N). Main Outcome Measures: Peak vertical force, cadence, percentage swing phase and double limb support, and regional plantar pressure ratios. Results: Peak vertical force (normalized for body weight) was reduced during both cane use conditions on the randomly assigned limb when compared to walking unaided (P<.001). The peak vertical force was 7% to 11% lower for the assigned limb than the opposite limb when a cane was used on either side (P<.016). Mean cadence was higher when participants ambulated without a cane (113 steps/min) than with a cane used on either the contralateral (98 steps/min) or ipsilateral (98 steps/min) side (P<.0001). Mean cadence did not significantly differ between the cane use conditions (P=.93). Regional plantar pressure ratios did not significantly change on either limb in any of the tested conditions. Double limb support slightly increased with cane use (P<.016). Conclusion: Both ipsilateral and contralateral cane use reduced cadence and mean peak vertical plantar force on the limb advanced with the cane in healthy young adults. Double limb support increased with cane use likely due to the reduced cadence and initial unfamiliarity with using an assistive device. A clinical implication of these findings is that prescription of canes for either ipsilateral or contralateral use effectively offloads a designated lower limb. C1 [Aragaki, Dixie R.; Nasmyth, Mary C.; Schultz, Scott C.; Nguyen, Gretchen M.] VA Greater Los Angeles Healthcare Syst, Dept Phys Med & Rehabil, Los Angeles, CA 90073 USA. [Aragaki, Dixie R.; Nasmyth, Mary C.; Schultz, Scott C.; Nguyen, Gretchen M.; Kao, Kaly; Fang, Meika A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Fang, Meika A.] VA Greater Los Angeles Healthcare Syst, Rheumatol Sect, Los Angeles, CA 90073 USA. [Perell, Karen] Calif State Univ Fullerton, Fullerton, CA 92634 USA. [Yentes, Jennifer M.] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. RP Aragaki, DR (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Phys Med & Rehabil, 11301 Wilshire Blvd,Mailcode 117, Los Angeles, CA 90073 USA. EM Dixie.Aragaki@va.gov OI Yentes, Jennifer/0000-0001-6550-7759 FU Office of Research and Development, Rehabilitation Research and Development Service, Department of Veterans Affairs [F3873R] FX This work was supported by the Office of Research and Development, Rehabilitation Research and Development Service, Department of Veterans Affairs (Grant F3873R). NR 27 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAR PY 2009 VL 1 IS 3 BP 208 EP 213 DI 10.1016/j.pmrj.2008.10.002 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LF UT WOS:000208411200002 PM 19627896 ER PT J AU Morse, LR Giangregorio, L Battaglino, RA Holland, R Craven, BC Stolzmann, KL Lazzari, AA Sabharwal, S Garshick, E AF Morse, Leslie R. Giangregorio, Lora Battaglino, Ricardo A. Holland, Robert Craven, B. Catharine Stolzmann, Kelly L. Lazzari, Antonio A. Sabharwal, Sunil Garshick, Eric TI VA-Based Survey of Osteoporosis Management in Spinal Cord Injury SO PM&R LA English DT Article AB Objective: Although osteoporosis is common following spinal cord injury (SCI), no guidelines exist for its treatment, diagnosis, or prevention. The authors hypothesized that wide variations in diagnosis and treatment practices result from the absence of guidelines. This study sought to characterize the diagnosis and management practices within the VA health care system for osteoporosis following SCI. Design: Online survey regarding osteoporosis management in SCI composed of 27 questions designed to gather information on responder demographics, osteoporosis diagnostics, and treatment options. Setting: VA health care system. Participants: VHA National SCI Staff Physicians and VHA National SCI Nurses (total n = 450) were sent an email with an invitation to participate. Intervention: Not applicable. Main Outcome Measures: Practice patterns were assessed, including factors associated with ordering a clinical workup and prescribing osteoporosis treatment. Results: The response rate was 28%. Ninety-two prescribing practitioners (physicians, nurse practitioners, and physician assistants) were included in the analysis. Of these respondents, 50 (54%) prescribe medications for SCI-induced bone loss; 39 (42%) prescribe bisphosphonates and 46 (50%) prescribe vitamin D. There were 54 (59%) respondents who routinely order diagnostic tests, including dual energy x-ray absorptiometry scans in 50 (54%). Variations in practice were not explained by age, gender, or years practicing SCI medicine. Many respondents (23%) reported barriers to osteoporosis testing including lack of scanning protocols, cost, wheelchair inaccessibility of scanning facilities, and lack of effective treatment guidelines once osteoporosis is diagnosed. Conclusions: Despite an absence of screening and treatment guidelines, more than half of all respondents are actively diagnosing and treating osteoporosis with bisphosphonates within the VA health care setting. These data suggest that evidence-based practice guidelines are necessary to reduce practice variations and improve clinical care for this population. C1 [Morse, Leslie R.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Giangregorio, Lora] Univ Waterloo, Dept Kinesiol, Waterloo, ON N2L 3G1, Canada. [Battaglino, Ricardo A.] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. [Holland, Robert] Staten Isl Univ Hosp, Staten Isl, NY USA. [Craven, B. Catharine] Univ Toronto, Dept Med, Toronto Rehabil Inst, Toronto, ON M5S 1A1, Canada. [Stolzmann, Kelly L.] VA Boston Healthcare Syst, Dept Vet Affairs, Res & Dev Serv, Boston, MA USA. [Stolzmann, Kelly L.] Harvard Univ, Sch Med, Programs Res VA Boston, Boston, MA USA. [Lazzari, Antonio A.] VA Boston Healthcare Syst, Dept Vet Affairs, Res & Dev Serv, Boston, MA USA. [Lazzari, Antonio A.] VA Boston Healthcare Syst, Div Primary Care, Boston, MA USA. [Lazzari, Antonio A.] VA Boston Healthcare Syst, Rheumatol Sect, Boston, MA USA. [Sabharwal, Sunil] VA Boston Healthcare Syst, Spinal Cord Injury Serv, Boston, MA USA. [Lazzari, Antonio A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Garshick, Eric] Boston Healthcare Syst, Dept Vet Affairs, Res & Dev Serv, Boston, MA USA. [Garshick, Eric] VA Boston, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. [Garshick, Eric] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Morse, LR (reprint author), Harvard Univ, Sch Med, Dept PMR, Forsyth Inst, 140 Fenway, Boston, MA 02118 USA. EM lmorse4@partners.org RI battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015; Craven, Beverley /D-5001-2015 OI Morse, Leslie/0000-0002-7426-6341; Craven, Beverley /0000-0001-8234-6803 FU Office of Research and Development, Health Services R&D Service, Quality Enhancement Research Initiative [RRP-07-312]; NIH/NICHD [R01 HD42141, R21HD057030, K12 HD001097-08]; Merck Frosst FX The project reported/outlined here was supported by the Office of Research and Development, Health Services R&D Service, Quality Enhancement Research Initiative RRP-07-312, NIH/NICHD R01 HD42141 (Dr. Garshick), R21HD057030 (Morse), and K12 HD001097-08 (Dr. Morse).; 7A, co-investigation on Merck Frosst-funded study NR 26 TC 16 Z9 17 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAR PY 2009 VL 1 IS 3 BP 240 EP 244 DI 10.1016/j.pmrj.2008.10.008 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LF UT WOS:000208411200007 PM 19627901 ER PT J AU Edgley, SR Lew, HL Moroz, A Chae, J Lombard, LA Reddy, CC AF Edgley, Steven R. Lew, Henry L. Moroz, Alex Chae, John Lombard, Lisa A. Reddy, Cara Camiolo TI Stroke and Neurodegenerative Disorders: 4. Community Integration SO PM&R LA English DT Article AB Objective: This self-directed learning module highlights common rehabilitation issues in stroke survivors with chronic impairments with emphasis on community integration. It is part of the study guide on stroke and neurodegenerative disorders in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. Using a case vignette format, this article specifically focuses on management of shoulder pain, management of hypertonia, secondary stroke prevention, vocational reintegration including strategies for return to driving, and treatment of sexual dysfunction following stroke. The goal of this article is to improve the learner's ability to implement community integration strategies after a stroke. C1 [Edgley, Steven R.] Univ Utah, Div Phys Med & Rehabil, Salt Lake City, UT 84132 USA. [Lew, Henry L.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Phys Med & Rehabil Serv, Boston, MA USA. [Moroz, Alex] NYU, Sch Med, Rusk Inst Rehabil Med, New York, NY USA. [Chae, John] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Phys Med & Rehabil, Cleveland, OH 44106 USA. [Lombard, Lisa A.] Santa Clara Valley Med Ctr, Dept Phys Med & Rehabil, San Jose, CA 95128 USA. [Reddy, Cara Camiolo] Univ Pittsburgh, Univ Hlth Ctr Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. RP Edgley, SR (reprint author), Univ Utah, Div Phys Med & Rehabil, 30 North,1900 East, Salt Lake City, UT 84132 USA. EM steven.edgley@hsc.utah.edu NR 51 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAR PY 2009 VL 1 IS 3 SU 1 BP S27 EP S34 DI 10.1016/j.pmrj.2009.01.022 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LG UT WOS:000208411300005 PM 19627970 ER PT J AU Lew, HL Lombard, LA Reddy, CC Moroz, A Edgley, SR Chae, J AF Lew, Henry L. Lombard, Lisa A. Reddy, Cara Camiolo Moroz, Alex Edgley, Steven R. Chae, John TI Stroke and Neurodegenerative Disorders: 3. Poststroke Rehabilitation SO PM&R LA English DT Article AB Objective: This self-directed learning module highlights rehabilitation strategies in poststroke rehabilitation. It is part of the study guide on stroke and neurodegenerative disorders in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. Using a case vignette format, this article specifically focuses on typical clinical presentations, recovery patterns, and traditional and innovative therapeutic interventions in poststroke rehabilitation such as constraint-induced movement therapy, treadmill training, functional electrical stimulation, robot-aided therapy, virtual reality treatment, cortical stimulation, speech therapy for aphasia, and orthotic management. The goal of this article is to influence the learner's knowledge on the delivery of poststroke rehabilitation treatment. C1 [Lew, Henry L.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Phys Med & Rehabil Serv, Boston, MA 02130 USA. [Lombard, Lisa A.] Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. [Reddy, Cara Camiolo] Univ Pittsburgh, Univ Hlth Ctr Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Moroz, Alex] NYU, Sch Med, Rusk Inst Rehabil Med, New York, NY USA. [Edgley, Steven R.] Univ Utah, Salt Lake City, UT USA. [Chae, John] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Phys Med & Rehabil, Cleveland, OH USA. RP Lew, HL (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Phys Med & Rehabil Serv, 150 S Huntington Ave, Boston, MA 02130 USA. EM henry.lew@va.gov NR 63 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAR PY 2009 VL 1 IS 3 SU 1 BP S19 EP S26 DI 10.1016/j.pmrj.2009.01.017 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LG UT WOS:000208411300004 PM 19627969 ER PT J AU Lombard, LA Reddy, CC Moroz, A Lew, HL Chae, J Edgley, SR AF Lombard, Lisa A. Reddy, Cara Camiolo Moroz, Alex Lew, Henry L. Chae, John Edgley, Steven R. TI Stroke and Neurodegenerative Disorders: 2. Poststroke Medical Complications SO PM&R LA English DT Article AB Objective: This self-directed learning module highlights common poststroke medical complaints encountered on an inpatient rehabilitation unit. It is part of the study guide on stroke and neurodegenerative disorders in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. Using a case vignette format, this article specifically focuses on the differential diagnosis, evaluation and management of chest pain, mental status changes, weight loss and poor motivation in stroke patients. The goal of this article is to expand the learner's knowledge of how to diagnose and manage common medical complications of stroke patients in rehabilitation. C1 [Lombard, Lisa A.] Santa Clara Valley Med Ctr, Dept Phys Med & Rehabil, San Jose, CA 95128 USA. [Reddy, Cara Camiolo] Univ Pittsburgh, Dept Phys Med & Rehabil, Med Ctr, Pittsburgh, PA USA. [Moroz, Alex] NYU, Sch Med, Rusk Inst Rehabil Med, New York, NY USA. [Moroz, Alex] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Phys Med & Rehabil Serv, Boston, MA USA. [Chae, John] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Phys Med & Rehabil, Cleveland, OH USA. [Edgley, Steven R.] Univ Utah, Salt Lake City, UT USA. RP Lombard, LA (reprint author), Santa Clara Valley Med Ctr, Dept Phys Med & Rehabil, 751 S Bascom Ave, San Jose, CA 95128 USA. EM Lisa.Lombard@hhs.sccgov.org NR 45 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAR PY 2009 VL 1 IS 3 SU 1 BP S13 EP S18 DI 10.1016/j.pmrj.2009.01.016 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LG UT WOS:000208411300003 PM 19627968 ER PT J AU Moroz, A Edgley, SR Lew, HL Chae, J Lombard, LA Reddy, CC Robinson, KM AF Moroz, Alex Edgley, Steven R. Lew, Henry L. Chae, John Lombard, Lisa A. Reddy, Cara Camiolo Robinson, Keith M. TI Rehabilitation Interventions in Parkinson Disease SO PM&R LA English DT Review AB Objective: This self-directed learning module provides an evidence-based update of exercise-based rehabilitation interventions to treat Parkinson disease (PD). It is part of the study guide on stroke and neurodegenerative disorders in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This focused review emphasizes treatment of locomotion deficits, upper limb motor control deficits, and hypokinetic dysarthria. New dopaminergic agents and deep brain stimulation are facilitating longer periods of functional stability for patients with PD. Adjunctive exercise-based treatments can therefore be applied over longer periods of time to optimize function before inevitable decline from this neurodegenerative disease. As function deteriorates in patients with PD, the role of caregivers becomes more critical, thus training caregivers is of paramount importance to help maintain a safe environment and limit caregiver anxiety and depression. The overall goal of this article is to enhance the learner's existing practice techniques used to treat PD through exercise-based intervention methods. C1 [Moroz, Alex] NYU, Sch Med, Rusk Inst Rehabil Med, New York, NY 10003 USA. [Edgley, Steven R.] Univ Utah, Salt Lake City, UT USA. [Lew, Henry L.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Phys Med & Rehabil Serv, Boston, MA USA. [Chae, John] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Phys Med & Rehabil, Cleveland, OH USA. [Lombard, Lisa A.] Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. [Reddy, Cara Camiolo] Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Robinson, Keith M.] Hosp Univ Penn, Dept Phys & Rehabil, Philadelphia, PA 19104 USA. RP Moroz, A (reprint author), NYU, Sch Med, Rusk Inst Rehabil Med, New York, NY 10003 USA. EM moroza@gmail.com NR 85 TC 1 Z9 1 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAR PY 2009 VL 1 IS 3 SU 1 BP S42 EP S48 DI 10.1016/j.pmrj.2009.01.018 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LG UT WOS:000208411300006 PM 19627972 ER PT J AU Reddy, CC Moroz, A Edgley, SR Lew, HL Chae, J Lombard, LA AF Reddy, Cara Camiolo Moroz, Alex Edgley, Steven R. Lew, Henry L. Chae, John Lombard, Lisa A. TI Stroke and Neurodegenerative Disorders: 1. Stroke Management in the Acute Care Setting SO PM&R LA English DT Article AB Objective: This self-directed learning module highlights management of stroke in the acute care setting. It is part of the study guide on stroke and neurodegenerative disorders in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. Using a case vignette format, this article specifically focuses on initial assessment and management of acute ischemic and hemorrhagic stroke, descriptions of posterior circulation and lacunar stroke, and criteria for admission to acute inpatient rehabilitation after stroke and secondary stroke prevention. The goal of this article is to improve the learner's ability to identify, treat and manage a patient with a stroke in the acute care setting. C1 [Reddy, Cara Camiolo] Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Moroz, Alex] NYU, Sch Med, Rusk Inst Rehabil Med, New York, NY USA. [Edgley, Steven R.] Univ Utah, Salt Lake City, UT USA. [Lew, Henry L.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Phys Med & Rehabil Serv, Boston, MA USA. [Chae, John] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Phys Med & Rehabil, Cleveland, OH USA. [Lombard, Lisa A.] Santo Clara Valley Med Ctr, Dept Phys Med & Rehabil, San Jose, CA USA. RP Reddy, CC (reprint author), Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, 3471 5th Ave,LKB Ste 201, Pittsburgh, PA 15213 USA. EM camioloce1@upmc.edu NR 44 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD MAR PY 2009 VL 1 IS 3 SU 1 BP S4 EP S12 DI 10.1016/j.pmrj.2009.01.015 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LG UT WOS:000208411300002 PM 19627971 ER PT J AU Koepsell, TD Forsberg, CW Littman, AJ AF Koepsell, Thomas D. Forsberg, Christopher W. Littman, Alyson J. TI Obesity, overweight, and weight control practices in US veterans SO PREVENTIVE MEDICINE LA English DT Article DE Obesity; Overweight; Veterans health; Weight control ID RISK-FACTORS; PREVALENCE; HEALTH; CONSEQUENCES; FACILITIES; BURDEN; ADULTS AB Objectives. We assessed the burden of obesity and overweight, as well as trends in weight control practices, among U.S. veterans and users of Department of Veterans Affairs (VA) health care in a large national survey. Methods. Data were combined from the 2003 and 2004 Behavioral Risk Factor Surveillance System surveys of U.S. adults (n = 558,426), a large telephone survey conducted in all states. Results. Some 24% of veterans were obese (Body Mass Index [BMI] >= 30 kg/m(2)), and 48% were overweight (BMI 25-29.9 kg/m(2)). After adjustment for age and gender, obesity prevalence was similar between veterans and non-veterans, but overweight was about 3.8 percentage points more frequent in veterans. Among veterans, obesity was more common among users of VA care, especially those who received all health care through the VA. Obese and overweight VA users were significantly more likely than non-users to report advice from a health care provider to lose weight, but no more likely to report that they were actually trying to lose weight. Conclusions. Obesity and overweight pose special burdens on veterans who use VA care. These results strengthen the case for system-wide interventions aimed at weight control. (C) 2009 Elsevier Inc. All rights reserved. C1 [Koepsell, Thomas D.; Littman, Alyson J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Koepsell, Thomas D.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Koepsell, Thomas D.; Forsberg, Christopher W.; Littman, Alyson J.] Seattle Epidemiol Res & Informat Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. RP Koepsell, TD (reprint author), Seattle Epidemiol Res & Informat Ctr, VA Puget Sound Hlth Care Syst 152E, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM koepsell@u.washington.edu FU Office of Research and Development; Cooperative Studies Program; Department of Veterans Affairs FX This material is based upon work supported by the Office of Research and Development, Cooperative Studies Program, Department of Veterans Affairs. NR 27 TC 29 Z9 29 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR PY 2009 VL 48 IS 3 BP 267 EP 271 DI 10.1016/j.ypmed.2009.01.008 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 426WL UT WOS:000264738900013 PM 19297689 ER PT J AU Wiklund, F Zheng, SL Sun, JL Adami, HO Lilja, H Hsu, FC Stattin, P Adolfsson, J Cramer, SD Duggan, D Carpten, JD Chang, BL Isaacs, WB Gronberg, H Xu, JF AF Wiklund, Fredrik Zheng, S. Lilly Sun, Jielin Adami, Hans-Olov Lilja, Hans Hsu, Fang-Chi Stattin, Par Adolfsson, Jan Cramer, Scott D. Duggan, David Carpten, John D. Chang, Bao-Li Isaacs, William B. Gronberg, Henrik Xu, Jianfeng TI Association of Reported Prostate Cancer Risk Alleles With PSA Levels Among Men Without a Diagnosis of Prostate Cancer SO PROSTATE LA English DT Article DE genetic; bias; KLK3 ID GENOME-WIDE ASSOCIATION; FACTOR BINDING PROTEIN-3; ANTIGEN GENE PROMOTER; ANDROGEN RECEPTOR; JAPANESE POPULATION; G/A POLYMORPHISM; VARIANTS; SUSCEPTIBILITY; LOCI; PROTEASE AB BACKGROUND. Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels. METHODS. We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer. RESULTS. Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P <= 0.05) were found for six SNPs. These six SNP's had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend = 3.4 x 10(-14). In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients. CONCLUSIONS. Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening. Prostate 69: 419-427, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Isaacs, William B.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Duggan, David; Carpten, John D.] Translat Genom Res Inst TGen, Phoenix, AZ USA. [Cramer, Scott D.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27109 USA. [Adolfsson, Jan] Karolinska Inst, CLINTEC, Ctr Oncol, Stockholm, Sweden. [Stattin, Par] Umea Univ Hosp, Dept Surg & Perioperat Sci, S-90185 Umea, Sweden. [Hsu, Fang-Chi] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Lilja, Hans] Lund Univ, Univ Hosp UMAS, Dept Lab Med, Malmo, Sweden. [Lilja, Hans] Mem Sloan Kettering Canc Ctr, Dept Med GU Oncol, New York, NY 10021 USA. [Lilja, Hans] Mem Sloan Kettering Canc Ctr, Dept Urol Surg, New York, NY 10021 USA. [Lilja, Hans] Mem Sloan Kettering Canc Ctr, Dept Clin Labs, New York, NY 10021 USA. [Adami, Hans-Olov] Dana Farber Canc Inst, Boston, MA 02115 USA. [Adami, Hans-Olov] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Zheng, S. Lilly; Sun, Jielin; Hsu, Fang-Chi; Chang, Bao-Li; Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC 27109 USA. [Zheng, S. Lilly; Sun, Jielin; Hsu, Fang-Chi; Chang, Bao-Li; Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC 27109 USA. [Wiklund, Fredrik; Adami, Hans-Olov; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Isaacs, WB (reprint author), Johns Hopkins Univ Hosp, Marburg 115,600 N Wolfe St, Baltimore, MD 21287 USA. EM wisaacs@jhmi.edu; henrik.gronberg@ki.se; jxu@wfubmc.edu OI Lilja, Hans/0000-0001-5871-7846; Adolfsson, Jan/0000-0003-2992-1869 FU NCI NIH HHS [R01 CA106523-02, CA105055, CA106523, CA129684, CA95052, P50 CA092629, P50 CA092629-01, P50-CA92629, R01 CA095052, R01 CA095052-02, R01 CA105055, R01 CA105055-01A1, R01 CA106523, R01 CA106523-01A1, R01 CA129684, R01 CA129684-02, R21 CA108625] NR 35 TC 27 Z9 27 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAR 1 PY 2009 VL 69 IS 4 BP 419 EP 427 DI 10.1002/pros.20908 PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 410AC UT WOS:000263546000010 PM 19116992 ER PT J AU Glynn, SM Randolph, ET Garrick, T Lui, A AF Glynn, Shirley M. Randolph, Eugenia T. Garrick, Thomas Lui, Anna TI A Proof of Concept Trial of an Online Psychoeducational Program for Relatives of Both Veterans and Civilians Living with Schizophrenia SO PSYCHIATRIC REHABILITATION JOURNAL LA English DT Article DE clinical trials; family services; schizophrenia; mental health education programs ID COGNITIVE-BEHAVIOR THERAPY; MULTIPLE-FAMILY GROUPS; RANDOMIZED CONTROLLED-TRIAL; ATTITUDE SCALE; INTERNET; INTERVENTION; METAANALYSIS; DISORDERS; SUPPORT; TELEHEALTH AB Objectives: Family psychoeducation has been found to reduce relapse in schizophrenia but penetration rates are low. In this study, we evaluate the feasibility of an online multifamily group program for relatives of persons with schizophrenia that can be accessed from participants' homes. Methods: We explored participation rates and evaluations of a 12-month multimodal website intervention. Using a quasi-experimental design, we compared illness outcomes (factors on the Brief Psychiatric Rating Scale, hospitalizations) of persons with diagnosed schizophrenia, and relative distress outcomes (somatic concerns and anxiety/depression subscales on the Brief Symptom Inventory) from relatives participating in the intervention (n = 26) to archival data we had from comparable dyads who received customary care (n =16). Results: The majority of participants in the program attended more than half the core online support sessions, expressed high levels of satisfaction, and found the technology easy to access. There appeared to be little impact of online participation on clinical status of persons with schizophrenia or relatives' distress, although there was a trend for fewer hospitalizations in the online group. Small sample size is a factor in interpreting results. Conclusions: Online interventions for relatives of persons with schizophrenia, while feasible, present unique challenges. These include 1) assuring access to the intervention in populations who do not own a computer; 2) addressing privacy concerns; 3) overcoming the special challenges of conducting groups in real time; 4) managing emergent situations adequately; and 5) questions about efficacy. C1 [Glynn, Shirley M.; Randolph, Eugenia T.; Garrick, Thomas] Univ Calif Los Angeles, Semel Inst Neurosci & Biobehav, VA Greater Los Angeles Healthcare Syst W Los Ange, Los Angeles, CA 90024 USA. RP Glynn, SM (reprint author), VA GLA W Los Angeles, B151J,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sglynn@ucla.edu FU NIMH NIH HHS [R21 MH62135] NR 34 TC 19 Z9 19 U1 1 U2 15 PU CENTER PSYCHIATRIC REHABILITATION PI BOSTON PA BOSTON UNIV, 930 COMMONWEALTH AVE, BOSTON, MA 02215 USA SN 1095-158X J9 PSYCHIATR REHABIL J JI Psychiatr. Rehabil. J. PD SPR PY 2009 VL 33 IS 4 SI SI BP 278 EP 287 DI 10.2975/33.4.2010.278.287 PG 10 WC Psychiatry; Rehabilitation SC Psychiatry; Rehabilitation GA 586RM UT WOS:000276929700006 PM 20374986 ER PT J AU Salzer, MS Katz, J Kidwell, B Federici, M Ward-Colasante, C AF Salzer, Mark S. Katz, Jason Kidwell, Betsy Federici, Matthew Ward-Colasante, Carol TI Pennsylvania Certified Peer Specialist Initiative: Training, Employment and Work Satisfaction Outcomes SO PSYCHIATRIC REHABILITATION JOURNAL LA English DT Article DE peer specialists; knowledge gain; employment outcomes; job satisfaction AB Objective: Certified Peer Specialist training initiatives leading to paid peer support positions are increasing nationally. This longitudinal study examines a comprehensive set of outcomes associated with such an initiative undertaken in Pennsylvania beginning in 2004. Methods: Certified Peer Specialist Training participants in three regions of Pennsylvania responded to a 60-item, multiple choice knowledge test based on the Certified Peer Specialist training curriculum. Additionally, these individuals were asked to provide permission to be contacted up to one year after completing the program to obtain employment information related to their experience as a certified peer specialist. Results: Ninety-seven percent of the trainees successfully completed the program with a 22% increase in knowledge. Eighty-two percent were working one year later. Peer specialists were very satisfied with their employment; felt accepted by co-workers and reported receiving good, but infrequent supervision. Conclusions: The results suggest that these initiatives can be successfully implemented, although greater attention is needed to ensure that new jobs are being created for trainees and that they are being property supervised like all other employees. C1 [Salzer, Mark S.] Univ Penn, Dept Psychiat, CMHPSR, Philadelphia, PA 19104 USA. [Salzer, Mark S.] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. [Katz, Jason] Univ S Carolina, Columbia, SC 29208 USA. [Kidwell, Betsy; Federici, Matthew] Mental Hlth Assoc SE PA, Inst Recovery & Community Integrat, Philadelphia, PA USA. [Ward-Colasante, Carol] PA Dept Publ Welf, Ofc Mental Hlth & Subst Abuse Serv, Harrisburg, PA USA. [Salzer, Mark S.] UPENN Collaborat Community Integrat, Philadelphia, PA USA. [Ward-Colasante, Carol] Penn Off Mental Hlth & Subst Abuse Serv, Philadelphia, PA USA. RP Salzer, MS (reprint author), Univ Penn, Dept Psychiat, CMHPSR, 3535 Market St,3rd Floor, Philadelphia, PA 19104 USA. EM Mark.Salzer@uphs.upenn.edu NR 4 TC 10 Z9 11 U1 1 U2 2 PU CENTER PSYCHIATRIC REHABILITATION PI BOSTON PA BOSTON UNIV, 930 COMMONWEALTH AVE, BOSTON, MA 02215 USA SN 1095-158X J9 PSYCHIATR REHABIL J JI Psychiatr. Rehabil. J. PD SPR PY 2009 VL 32 IS 4 BP 301 EP 305 DI 10.2975/32.4.2009.301.305 PG 5 WC Psychiatry; Rehabilitation SC Psychiatry; Rehabilitation GA 435LU UT WOS:000265346200009 PM 19346209 ER PT J AU Chua, EF Schacter, DL Sperling, RA AF Chua, Elizabeth F. Schacter, Daniel L. Sperling, Reisa A. TI Neural Basis for Recognition Confidence in Younger and Older Adults SO PSYCHOLOGY AND AGING LA English DT Article DE aging; memory; metamemory; monitoring; fMRI ID EVENT-RELATED FMRI; AGE-RELATED DIFFERENCES; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE; COGNITIVE CONTROL; DECISION-MAKING; BRAIN ACTIVITY; SUBJECTIVE EXPERIENCE; ALZHEIMERS-DISEASE; PARIETAL CORTICES AB Although several studies have examined the neural basis for age-related changes in objective memory performance, less is known about how the process of memory monitoring changes with aging. The authors used functional magnetic resonance imaging to examine retrospective confidence in memory performance in aging. During low confidence, both younger and older adults showed behavioral evidence that they were guessing during recognition and that they were aware they were guessing when making confidence judgments. Similarly, both younger and older adults showed increased neural activity during low- compared to high-confidence responses in the lateral prefrontal cortex, anterior cingulate cortex, and left intraparietal sulcus. In contrast, older adults showed more high-confidence errors than younger adults. Younger adults showed greater activity for high compared to low confidence in medial temporal lobe structures, but older adults did not show this pattern. Taken together, these findings may suggest that impairments in the confidence-accuracy relationship for memory in older adults, which are often driven by high-confidence errors, may be primarily related to altered neural signals associated with greater activity for high-confidence responses. C1 [Chua, Elizabeth F.; Schacter, Daniel L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Sperling, Reisa A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Psychol, Charlestown, MA USA. RP Chua, EF (reprint author), Harvard Univ, Dept Psychol, William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM echua@nmr.mgh.harvard.edu RI Chua, Elizabeth/B-3770-2010; OI Schacter, Daniel/0000-0002-2460-6061 FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIA NIH HHS [R37 AG008441-12, R01 AG027435, P01 AG004953, P01-AG-04953, R01 AG008441, R01 AG027435-01, R01 AG027435-03, R37 AG008441-11, R37 AG008441-13, R37 AG008441-15, R37 AG008441-17, R37 AG008441-19, AG08441, R01 AG027435-02, R01 AG027435-02S1, R01-AG027435, R37 AG008441, R37 AG008441-14, R37 AG008441-16, R37 AG008441-18]; NINDS NIH HHS [K23-NS02189, K23 NS002189] NR 92 TC 19 Z9 19 U1 1 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD MAR PY 2009 VL 24 IS 1 BP 139 EP 153 DI 10.1037/a0014029 PG 15 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 420UX UT WOS:000264315800013 PM 19290745 ER PT J AU Gold, SD Dickstein, BD Marx, BP Lexington, JM AF Gold, Sari D. Dickstein, Benjamin D. Marx, Brian P. Lexington, Jennifer M. TI PSYCHOLOGICAL OUTCOMES AMONG LESBIAN SEXUAL ASSAULT SURVIVORS: AN EXAMINATION OF THE ROLES OF INTERNALIZED HOMOPHOBIA AND EXPERIENTIAL AVOIDANCE SO PSYCHOLOGY OF WOMEN QUARTERLY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SELF-REPORTED CHILDHOOD; HETEROSEXUAL WOMEN; GENERAL-POPULATION; BISEXUAL ADULTS; UNITED-STATES; GAY MEN; ABUSE; PREVALENCE; THERAPY AB This study explored the relations among internalized homophobia (IH), experiential avoidance, and psychological symptom severity in a community sample of 72 lesbian sexual assault survivors. Results indicated that IH is associated with both experiential avoidance and posttraumatic stress disorder (PTSD) symptom severity. In addition, experiential avoidance is related to both PTSD and depression symptom severity. Finally, experiential avoidance completely mediated the relation between IH and PTSD symptom severity. The implications of these findings are discussed and suggestions for future research are provided. C1 [Marx, Brian P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Marx, Brian P.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Lexington, Jennifer M.] Univ Massachusetts, Univ Hlth Serv, Amherst, MA 01003 USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM brian.marx@va.gov NR 96 TC 12 Z9 12 U1 2 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-6843 J9 PSYCHOL WOMEN QUART JI Psychol. Women Q. PD MAR PY 2009 VL 33 IS 1 BP 54 EP 66 DI 10.1111/j.1471-6402.2008.01474.x PG 13 WC Psychology, Multidisciplinary; Women's Studies SC Psychology; Women's Studies GA 399WV UT WOS:000262830900008 ER PT J AU Silberbogen, AK Ulloa, EW Janke, EA Mori, DL AF Silberbogen, Amy K. Ulloa, Erin W. Janke, E. Amy Mori, Deanna L. TI Psychosocial Issues and Mental Health Treatment Recommendations for Patients With Hepatitis C SO PSYCHOSOMATICS LA English DT Review ID QUALITY-OF-LIFE; INTERFERON-ALPHA TREATMENT; INJECTION-DRUG USERS; LIVER-CIRRHOSIS; VIRUS-INFECTION; ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; CHRONIC ILLNESS; INDUCED DEPRESSION; INITIAL TREATMENT AB Background: Mental health needs of patients with HCV are increasingly being addressed in medical contexts. Objective: The authors review the psychosocial issues relevant to patients with hepatitis C and provide mental health treatment recommendations. Findings: Patients with HCV are faced with a number of challenges, including adjustment to a chronic medical illness, management of symptoms and treatment side effects, and making and maintaining lifestyle changes. Given these issues, mental health clinicians have the opportunity to make a significant contribution to patient care. Conclusion: After reviewing the relevant research on these psychosocial issues, the authors have identified areas in which clinicians can intervene; these include adjustment to having a chronic medical illness, coping with stigma and relationship changes, management of side effects, and implementing healthy lifestyle changes. C1 [Silberbogen, Amy K.] Boston Univ, Psychol Serv 116B, VA Boston Healthcare Syst, Sch Med, Boston, MA 02130 USA. RP Silberbogen, AK (reprint author), Boston Univ, Psychol Serv 116B, VA Boston Healthcare Syst, Sch Med, 150 S Huntington Ave, Boston, MA 02130 USA. EM amy.silberbogen@va.gov FU Veterans Health Administration Rehabilitation, Research, and Development Service [F3332P, F4120] FX Preparation of this manuscript was supported by two grants (F3332P and F4120) from the Veterans Health Administration Rehabilitation, Research, and Development Service. NR 99 TC 13 Z9 13 U1 3 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2009 VL 50 IS 2 BP 114 EP 122 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 434JG UT WOS:000265270400003 PM 19377019 ER PT J AU Tsai, CL Rowe, BH Camargo, CA AF Tsai, Chu-Lin Rowe, Brian H. Camargo, Carlos A., Jr. TI Factors associated with short-term recovery of health status among emergency department patients with acute exacerbations of chronic obstructive pulmonary disease SO QUALITY OF LIFE RESEARCH LA English DT Article DE Chronic obstructive pulmonary disease; Emergency department; Exacerbation; Health status; Recovery ID QUALITY-OF-LIFE; CLINICAL-SIGNIFICANCE; RHEUMATOID-ARTHRITIS; CHRONIC-BRONCHITIS; COPD EXACERBATION; OUTCOMES; TRIALS; MANAGEMENT; FREQUENCY; DIAGNOSIS AB To determine the factors associated with short-term recovery of health status following chronic obstructive pulmonary disease (COPD) exacerbation. In a prospective multicenter cohort study, consecutive emergency department (ED) patients with COPD exacerbation were enrolled. Patients were interviewed and instructed to complete the validated Short Form Chronic Respiratory disease Questionnaire. Follow-up data were collected 2 weeks later, and included the global transition question. The primary outcome was recovery of health status, which was assigned to patients who stated that their COPD was "a little better" or "much better" than at the time of their ED presentation. Of the 330 patients, 270 [82%; 95% confidence interval (CI), 77-86%] reported recovery of health status following acute exacerbations. Multivariable analysis showed that recovery of health status was associated with having a primary care provider (PCP) [odds ratio (OR), 3.1; 95% CI, 1.5-6.4] and a co-diagnosis of asthma (OR, 2.2; 95% CI, 1.2-3.8). By contrast, frequent exacerbations (two or more exacerbations in the past year) (OR, 0.4; 95% CI, 0.2-0.7) was inversely associated with recovery. Reducing exacerbation frequency and provision of adequate PCP follow-up after ED visit may help improve the recovery of health status following acute exacerbations of COPD. C1 [Tsai, Chu-Lin; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Tsai, Chu-Lin; Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. RP Tsai, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Boehringer Ingelheim (Ridgefield, CT, USA and Burlington, Ontario, Canada) FX Funding: The cohort studies were supported by an unrestricted grant from Boehringer Ingelheim (Ridgefield, CT, USA and Burlington, Ontario, Canada). NR 39 TC 3 Z9 3 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD MAR PY 2009 VL 18 IS 2 BP 191 EP 199 DI 10.1007/s11136-008-9437-z PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 404UO UT WOS:000263178700007 PM 19123070 ER PT J AU Cai, WL Kassarjian, A Bredella, MA Harris, GJ Yoshida, H Mautner, VF Wenzel, R Plotkin, SR AF Cai, Wenli Kassarjian, Ara Bredella, Miriam A. Harris, Gordon J. Yoshida, Hiroyuki Mautner, Victor F. Wenzel, Ralph Plotkin, Scott R. TI Tumor Burden in Patients with Neurofibromatosis Types 1 and 2 and Schwannomatosis: Determination on Whole-Body MR Images SO RADIOLOGY LA English DT Article ID PHASE-I TRIAL; PLEXIFORM NEUROFIBROMAS; INTRAOBSERVER VARIABILITY; VOLUME MEASUREMENT; SOLID TUMORS; LUNG LESIONS; INTEROBSERVER; CT; REPRODUCIBILITY; MANAGEMENT AB Purpose: To develop a three-dimensional (3D) segmentation and computerized volumetry technique for use in the assessment of neurofibromatosis and to assess the ability of this technique to aid in the calculation of tumor burden in patients with neurofibromatosis types 1 and 2 (NF1 and NF2, respectively) and schwannomatosis detected with whole-body magnetic resonance (MR) imaging. Materials and Methods: Institutional review board approval and written informed consent were obtained for this prospective HIPAA-compliant study. Fifty-two subjects (27 women, 25 men; mean age, 42 years +/- 15 [standard deviation]; age range, 24-86 years) underwent whole-body MR imaging performed with coronal short inversion time inversion-recovery (STIR) sequences. Whole-body tumor burden was estimated with a 3D segmentation method (the dynamic-threshold [DT] level set method) in 29 subjects (16 with NF1, six with NF2, and seven with schwannomatosis) in whom at least one nerve sheath tumor was reliably identified on MR images. Fifty tumors (25 plexiform and 25 discrete tumors) were randomly selected and subjected to manual and computerized volumetry to assess reliability. Ten plexiform tumors 5 cm or larger in diameter were retrospectively selected and segmented with three initialization methods for computerized volumetry and manually contoured by three radiologists to assess repeatability. Bland-Altman analysis was performed, and intraclass correlation coefficients (ICCs) were calculated. Results: A total of 398 nerve sheath tumors (185 plexiform and 213 discrete tumors) were identified in 29 subjects. Volumetric measurements obtained with the computerized method and manual contouring were highly correlated (r(ICC) = 0.99). Bland-Altman analysis showed that computerized volumetry had a mean difference of -2.6% compared with manual volumetry. The repeatability coefficient of the computerized scheme was +/- 5% compared with +/- 30% for manual contouring. Conclusion: This 3D segmentation and computerized volumetry technique is reliable relative to manual segmentation and has the advantage of being less labor intensive and more repeatable. This technique can be paired with whole-body MR imaging to determine tumor burden in patients with neurofibromatosis. (c) RSNA, 2009 C1 [Cai, Wenli; Kassarjian, Ara; Bredella, Miriam A.; Harris, Gordon J.; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mautner, Victor F.; Wenzel, Ralph] Univ Hamburg Hosp, Dept Neurol, D-2000 Hamburg, Germany. RP Cai, WL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,400C, Boston, MA 02114 USA. EM cai.wenli@mgh.harvard.edu NR 24 TC 48 Z9 51 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2009 VL 250 IS 3 BP 665 EP 673 DI 10.1148/radiol.2503080700 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 439QU UT WOS:000265642900008 PM 19244040 ER PT J AU Pedrosa, I Lafornara, M Pandharipande, PV Goldsmith, JD Rofsky, NM AF Pedrosa, Ivan Lafornara, Michelle Pandharipande, Pari V. Goldsmith, Jeffrey D. Rofsky, Neil M. TI Pregnant Patients Suspected of Having Acute Appendicitis: Effect of MR Imaging on Negative Laparotomy Rate and Appendiceal Perforation Rate SO RADIOLOGY LA English DT Article ID LOWER-QUADRANT PAIN; COMPUTED-TOMOGRAPHY; LABORATORY FINDINGS; RADIATION-EXPOSURE; APPENDECTOMY RATE; ABDOMINAL-PAIN; DIAGNOSIS; CT; WOMEN; ULTRASONOGRAPHY AB Purpose: To investigate the effect of magnetic resonance (MR) imaging on the negative laparotomy rate (NLR) and the perforation rate (PR) in pregnant patients suspected of having acute appendicitis (AA) and to assess the need for computed tomography (CT) in this setting. Materials and Methods: The data of 148 consecutive pregnant patients (mean age, 29 years; age range, 15-42 years; mean gestational age, 20 weeks; gestational age range, 4-37 weeks) who were clinically suspected of having AA and examined with MR imaging between March 2002 and August 2007 were retrospectively analyzed in an institutional review board-approved HIPAA-compliant protocol. One hundred forty patients underwent ultrasonography (US) before MR imaging. The clinical and laboratory data and the findings of the initial US and MR image interpretations were recorded and analyzed at Student t and Fisher exact testing. The NLR and PR were calculated. Results: Fourteen (10%) patients had AA, and perforation occurred in three (21%) of them. US results were positive for AA in five (36%) patients with proved AA. MR results were positive in all 14 patients with AA. MR results were negative in 125 of the 134 patients without AA; there were nine false-positive cases (two positive, seven inconclusive). Among the patients without AA, the normal appendix could be visualized on US images in less than 2% (two of 126) of cases and on MR images in 87% (116 of 134) of cases (P < .0001). Twenty-seven (18%) patients underwent surgical exploration, and eight of them had negative laparotomy results, yielding an NLR of 30% and a PR of 21% (three of 14 patients). Only four (3%) patients underwent CT. Conclusion: For pregnant patients clinically suspected of having AA, use of MR imaging yields favorable combinations of NLR and PR compared with previously reported values. The radiation exposure associated with CT examination can be avoided in most cases. (c) RSNA, 2009 C1 [Pedrosa, Ivan; Rofsky, Neil M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Lafornara, Michelle] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Goldsmith, Jeffrey D.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Pandharipande, Pari V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02215 USA. RP Pedrosa, I (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, 1 Deaconess Rd, Boston, MA 02215 USA. EM ipedrosa@bidmc.harvard.edu NR 49 TC 55 Z9 57 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2009 VL 250 IS 3 BP 749 EP 757 DI 10.1148/radiol.2503081078 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 439QU UT WOS:000265642900017 PM 19244044 ER PT J AU Copen, WA Gharai, LR Barak, ER Schwamm, LH Wu, O Kamalian, S Gonzalez, RG Schaefer, PW AF Copen, William A. Gharai, Leila Rezai Barak, Elizabeth R. Schwamm, Lee H. Wu, Ona Kamalian, Shahmir Gonzalez, R. Gilberto Schaefer, Pamela W. TI Existence of the Diffusion-Perfusion Mismatch within 24 Hours after Onset of Acute Stroke: Dependence on Proximal Arterial Occlusion SO RADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN-ACTIVATOR; POSITRON-EMISSION-TOMOGRAPHY; FOCAL CEREBRAL-ISCHEMIA; THROMBOLYTIC THERAPY; PERIINFARCT DEPOLARIZATIONS; INTRAARTERIAL THROMBOLYSIS; INTRAVENOUS THROMBOLYSIS; CONTROLLED-TRIAL; BLOOD-VOLUME AB Purpose: To assess the existence of a mismatch between lesions on diffusion-weighted (DW) and perfusion-weighted (PW) magnetic resonance (MR) images obtained within 24 hours after onset of acute stroke and to use mismatch data and angiographic evidence of proximal arterial occlusion (PAO) to investigate whether the existence of the mismatch depends on the existence of PAO. Materials and Methods: In this institutional review board-approved, HIPAA-compliant study, 109 retrospectively identified patients had undergone DW and PW imaging within 24 hours of stroke onset. Relative mismatch was computed as the difference between lesion volumes on mean transit time maps and DW images, divided by DW lesion volume. Computed tomographic (CT) angiography or MR angiography distinguished patients with PAO (n = 68) from those with no PAO (NPAO; n = 41). Eligibility for hypothetical thrombolysis was assessed with two different criteria: (a) one derived from the successful Desmoteplase in Acute Ischemic Stroke Trial (DIAS) and Dose Escalation of Desmoteplase for Acute Ischemic Stroke Trial (DEDAS), and (b) another requiring 160% mismatch. Results: Of the 109 patients, 77 (71%) satisfied the DIAS-DEDAS eligibility criteria, and 61 (56%) satisfied the 160% criterion. The NPAO patients demonstrated decreasing eligibility with increasing time after onset by using DIAS-DEDAS criteria (P = .015) and showed a similar trend with the 160% criterion (P = .078). The NPAO patients were less likely to be eligible after 9 hours than before 9 hours (17% for > 9 hours vs 72% for < 9 hours with DIAS-DEDAS criteria, P = .002; and 8% for > 9 hours vs 45% for < 9 hours with 160% criterion, P = .033). However, PAO patients demonstrated a trend toward increasing eligibility with the DIAS-DEDAS criteria (P = .099) and no significant difference for after 9 hours versus before 9 hours (84% for > 9 hours vs 78% for < 9 hours with DIAS-DEDAS criteria, P = .742; and 68% for > 9 hours vs 69% for < 9 hours with 160% criterion, P > .999). Conclusion: Persistence of mismatch after 9 hours is common and occurs most often in patients with PAO. (c) RSNA, 2009 C1 [Copen, William A.; Gharai, Leila Rezai; Barak, Elizabeth R.; Wu, Ona; Kamalian, Shahmir; Gonzalez, R. Gilberto; Schaefer, Pamela W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Copen, William A.; Schwamm, Lee H.; Wu, Ona; Gonzalez, R. Gilberto; Schaefer, Pamela W.] Harvard Univ, Sch Med, Boston, MA USA. RP Copen, WA (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB 273A,55 Fruit St, Boston, MA 02114 USA. EM wcopen@partners.org OI Kamalian, Shahmir/0000-0002-9640-8144; Schwamm, Lee/0000-0003-0592-9145 NR 43 TC 44 Z9 51 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2009 VL 250 IS 3 BP 878 EP 886 DI 10.1148/radiol.2503080811 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 439QU UT WOS:000265642900031 PM 19164120 ER PT J AU Stone, ME AF Stone, Martha E. TI Literary Research and the American Modernist Era: Strategies and Sources. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 [Stone, Martha E.] Massachusetts Gen Hosp, Treadwell Lib, Coordinator Reference Serv, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Coordinator Reference Serv, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD SPR PY 2009 VL 48 IS 3 BP 312 EP 312 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 425BA UT WOS:000264610800026 ER PT J AU Rueda, BR Sakamoto, H Blok, LJ Yu, J Taylor, RN AF Rueda, Bo R. Sakamoto, Hideo Blok, Leen J. Yu, Jie Taylor, Robert N. TI Cables 1 Is a Crucial Mediator of Progesterone-Induced Endometrial Cell Differentiation SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 56th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 17-21, 2009 CL Glasgow, SCOTLAND SP Soc Gynecol Invest C1 [Rueda, Bo R.; Sakamoto, Hideo] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. [Blok, Leen J.] Erasmus Univ, Dept Obstet & Gynaecol, Med Ctr, Rotterdam, Netherlands. [Yu, Jie; Taylor, Robert N.] Emory Univ, Atlanta, GA 30322 USA. 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 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2009 VL 16 IS 3 MA 75 BP 90A EP 90A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 410WU UT WOS:000263609800076 ER PT J AU Skaznik-Wikiel, ME Sharma, R Selesniemi, K Lee, HJ Tilly, J Falcone, T AF Skaznik-Wikiel, Malgorzata E. Sharma, Rakesh Selesniemi, Kaisa Lee, Ho-Joon Tilly, Jonathan Falcone, Tommaso TI Granulocyte Colony Stimulating Factor (G-CSF) in Conjunction with Vascular Endothelial Growth Factor(VEGF) Increases Primordial Follicle Numbers in Transplanted Mammalian Ovaries SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 56th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 17-21, 2009 CL Glasgow, SCOTLAND SP Soc Gynecol Invest C1 [Skaznik-Wikiel, Malgorzata E.; Sharma, Rakesh; Falcone, Tommaso] Cleveland Clin, Cleveland, OH 44106 USA. [Selesniemi, Kaisa; Lee, Ho-Joon; Tilly, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. 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 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2009 VL 16 IS 3 MA 95 BP 95A EP 96A PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 410WU UT WOS:000263609800096 ER PT J AU Kamat, A Cox, LA McDonald, TJ Nathanielsz, PW Li, C AF Kamat, Amrita Cox, Laura A. McDonald, Thomas J. Nathanielsz, Peter W. Li, Cun TI Maternal 30% Global Nutrient Restriction (MNR) Increases Fetal Baboon Liver beta 2-Adrenergic Receptor (beta 2-AR) Immunoreactivity (IR) at 0.5 Gestation (G) but Normalization Occurs by 0.9 (G) Despite Continuing MNR. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 56th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 17-21, 2009 CL Glasgow, SCOTLAND SP Soc Gynecol Invest C1 [Kamat, Amrita] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Kamat, Amrita] Audie Murphy Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Cox, Laura A.] SW Fdn Biomed Res, SW Natl Reg Primate Ctr, Dept Genet, San Antonio, TX 78284 USA. [McDonald, Thomas J.; Nathanielsz, Peter W.; Li, Cun] Univ Texas Hlth Sci Ctr San Antonio, Dept OB GYN, Ctr Pregnancy & Newborn Res, San Antonio, TX 78229 USA. 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 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2009 VL 16 IS 3 MA 239 BP 138A EP 138A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 410WU UT WOS:000263609800240 ER PT J AU Kiatpongsan, S Niikura, Y Selesniemi, K Lee, HJ Tilly, JL AF Kiatpongsan, Sorapop Niikura, Yuichi Selesniemi, Kaisa Lee, Ho-Joon Tilly, Jonathan L. TI Oocyte Formation within Embryonic Stem Cell (ESC)-Derived Teratomas SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 56th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 17-21, 2009 CL Glasgow, SCOTLAND SP Soc Gynecol Invest C1 [Kiatpongsan, Sorapop; Niikura, Yuichi; Selesniemi, Kaisa; Lee, Ho-Joon; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol,Med Sch, Boston, MA USA. 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 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2009 VL 16 IS 3 MA 736 BP 282A EP 282A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 410WU UT WOS:000263609801198 ER PT J AU Failure, O Selesniemi, KL Tilly, JL AF Failure, Ovarian Selesniemi, Kaisa L. Tilly, Jonathan L. TI Short-Term Fasting Does Not Protect Against Chemotherapy-induced Ovarian Failure SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 56th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 17-21, 2009 CL Glasgow, SCOTLAND SP Soc Gynecol Invest C1 [Failure, Ovarian; Selesniemi, Kaisa L.; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Obstet & Gynecol Serv, Boston, MA USA. 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 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD MAR PY 2009 VL 16 IS 3 MA 1046 BP 371A EP 371A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 410WU UT WOS:000263609801508 ER PT J AU Allan, JS Garrity, JM Donahue, DM AF Allan, James S. Garrity, Julie M. Donahue, Dean M. TI High-Frequency Chest-Wall Compression During the 48 Hours Following Thoracic Surgery SO RESPIRATORY CARE LA English DT Article DE postoperative pneumonia; thoracic surgery; high frequency chest wall compression; HFCWC ID CYSTIC-FIBROSIS; EXPIRATORY PRESSURE; AIRWAY CLEARANCE; CONTROLLED-TRIAL; OSCILLATION; PHYSIOTHERAPY AB BACKGROUND: Postoperative pneumonia continues to be a leading cause of mortality and morbidity after thoracic surgery. High-frequency chest-wall compression (HFCWC) is an established therapeutic adjunct for patients with chronic pulmonary disorders that impair bronchopulmonary secretion clearance. We studied the feasibility of applying HFCWC following thoracic surgery. METHODS: Twenty-five consecutive adult patients who underwent a variety of thoracic operations received at least one HFCWC treatment in the first 2 postoperative days, along with routine postoperative care. HFCWC was applied at 12 Hz, for 10 min. Routine hemodynamic and pulse oximetry data were collected before, during, and after HFCWC. We also collected qualitative data on patient tolerance and preference for HFCWC versus percussive chest physiotherapy. RESULTS: No major adverse events were encountered. Hemodynamic and pulse oximetry values remained stable before, during, and after HFCWC. Eighty-four percent of the subjects reported little or no discomfort during therapy, and the subjects who expressed a preference preferred HFCWC to conventional chest physiotherapy by more than two to one. CONCLUSIONS: HFCWC is a safe, well-tolerated adjunct after thoracic surgery. The observation of hemodynamic stability is especially important, considering that the patients were studied in the early postoperative period, during epidural analgesia. C1 [Allan, James S.; Garrity, Julie M.; Donahue, Dean M.] Massachusetts Gen Hosp, Div Thorac Surg, Dept Surg, Boston, MA 02114 USA. RP Allan, JS (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Dept Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. FU Hill-Rom FX This research was partly supported by Hill-Rom. NR 23 TC 8 Z9 14 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAR PY 2009 VL 54 IS 3 BP 340 EP 343 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 417XU UT WOS:000264112600007 PM 19245727 ER PT J AU Kacmarek, RM Durbin, CG Barnes, TA Kageler, WV Walton, JR O'Neil, EH AF Kacmarek, Robert M. Durbin, Charles G. Barnes, Thomas A. Kageler, Woody V. Walton, John R. O'Neil, Edward H. TI Creating a Vision for Respiratory Care in 2015 and Beyond SO RESPIRATORY CARE LA English DT Article DE respiratory care; respiratory therapist; iatrogenic injury; manpower; education; training; competency ID OBSTRUCTIVE SLEEP-APNEA; MECHANICALLY VENTILATED PATIENTS; ELECTRICAL-IMPEDANCE TOMOGRAPHY; CARDIOVASCULAR-DISEASE; PULMONARY DELIVERY; NASAL SPRAY; MANAGEMENT; PREVENTION; ASSIST; TRIAL AB The respiratory care profession is over 60 years old. Throughout its short history, change and innovation have been the terms that best describe the development of the profession. The respiratory therapist (RT) of today barely resembles the clinicians of 60 years ago, and the future role of the RT is clearly open to debate. Medicine is continually changing, with new approaches to disease management emerging almost daily. Third-party payers are challenging payment for iatrogenic injury, manpower issues are affecting all disciplines in medicine, and the nonphysician and physician work force is aging. These factors make us question what the respiratory care profession will look like in the year 2015. To address this issue the American Association for Respiratory Care established a task force to envision the RT of the future. The goal is to identify potential new roles and responsibilities of RTs in 2015 and beyond, and to suggest the elements of education, training, and competency-documentation needed to assure safe and effective execution of those roles and responsibilities. We present the initial findings of that task force. C1 [Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Serv, Dept Anesthesiol, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Boston, MA USA. [Durbin, Charles G.] Univ Virginia, Sch Med, Med Ctr, Dept Anesthesiol, Charlottesville, VA 22908 USA. [Durbin, Charles G.] Univ Virginia, Sch Med, Med Ctr, Dept Surg, Charlottesville, VA 22908 USA. [Barnes, Thomas A.] Northeastern Univ, Boston, MA 02115 USA. [Kageler, Woody V.] Tarrant Cty Coll, Dept Hlth Sci, Hurst, TX USA. [Walton, John R.] Resurrect Hlth Care, Chicago, IL USA. [O'Neil, Edward H.] Univ Calif San Francisco, Dept Family & Community Med & Social & Behav Sci, San Francisco, CA 94143 USA. [O'Neil, Edward H.] Univ Calif San Francisco, Ctr Hlth Profess, San Francisco, CA 94143 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Serv, Dept Anesthesiol, 55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org NR 97 TC 24 Z9 25 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAR PY 2009 VL 54 IS 3 BP 375 EP 389 PG 15 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 417XU UT WOS:000264112600012 PM 19245732 ER PT J AU Marder, SR Cohen, AN Hamilton, A Saks, E Glynn, S Hollan, D Brekke, J AF Marder, Stephen R. Cohen, A. N. Hamilton, A. Saks, E. Glynn, S. Hollan, D. Brekke, J. TI CHARACTERISTICS OF HIGH FUNCTIONING INDIVIDUALS WITH SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Marder, Stephen R.; Cohen, A. N.; Hamilton, A.; Glynn, S.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Marder, Stephen R.; Cohen, A. N.; Glynn, S.] Mental Illness Res Educ & Clin Ctr, VA Greater Los Angeles, Los Angeles, CA USA. [Hamilton, A.; Hollan, D.] Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90024 USA. [Brekke, J.] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 11 EP 11 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700036 ER PT J AU Jindal, RD Pillai, AK Mahadik, SR Keshavan, MS AF Jindal, Ripu D. Pillai, A. K. Mahadik, S. R. Keshavan, M. S. TI DECREASED BDNF IN PATIENTS WITH FIRST EPISODE TREATMENT NAIVE PSYCHOSIS SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Jindal, Ripu D.; Keshavan, M. S.] Univ Pittsburgh, Pittsburgh, PA USA. [Pillai, A. K.; Mahadik, S. R.] Med Coll Georgia, Augusta, GA 30912 USA. [Keshavan, M. S.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 24 EP 24 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700075 ER PT J AU Copeland, LA Zeber, JE Parchman, ML Lawrence, VA Hosek, BJ Miller, AL AF Copeland, Laurel A. Zeber, J. E. Parchman, M. L. Lawrence, V. A. Hosek, B. J. Miller, A. L. TI PRE-DIABETES AND DIABETES ASSESSMENT IN VETERANS WITH SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Copeland, Laurel A.; Zeber, J. E.; Parchman, M. L.; Lawrence, V. A.; Hosek, B. J.] S Texas Vet Hlth Care Syst, VERDICT HSRD, San Antonio, TX USA. [Copeland, Laurel A.; Zeber, J. E.; Miller, A. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Lawrence, V. A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Parchman, M. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 36 EP 36 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700109 ER PT J AU Wirshing, DA Rosen, J Pierre, JM Erickson, ZD Guzik, LH Mena, SJ AF Wirshing, Donna A. Rosen, J. Pierre, J. M. Erickson, Z. D. Guzik, L. H. Mena, S. J. TI SUBJECTIVE EXPERIENCE MEASUREMENT IN PATIENTS WITH SCHIZOPHRENIA/SCHIZOAFFECTIVE DISORDER USING THE NOVEL ANTIPSYCHOTIC MEDICATION EXPERIENCE SCALE (NAMES) SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Wirshing, Donna A.; Rosen, J.; Pierre, J. M.; Erickson, Z. D.; Guzik, L. H.; Mena, S. J.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 36 EP 36 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700108 ER PT J AU Horan, WP Wynn, JK Kring, AM Simons, RF Crosby, SM Nori, P Mancini, L Tripp, C Green, MF AF Horan, William Powers Wynn, J. K. Kring, A. M. Simons, R. F. Crosby, S. M. Nori, P. Mancini, L. Tripp, C. Green, M. F. TI ELECTROPHYSIOLOGICAL CORRELATES OF EMOTIONAL EXPERIENCE IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Horan, William Powers; Wynn, J. K.; Crosby, S. M.; Nori, P.; Mancini, L.; Tripp, C.; Green, M. F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Kring, A. M.] UC Berkeley, Berkeley, CA USA. [Simons, R. F.] Univ Delaware, Newark, DE USA. [Horan, William Powers; Wynn, J. K.; Crosby, S. M.; Nori, P.; Mancini, L.; Tripp, C.; Green, M. F.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 45 EP 45 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700135 ER PT J AU Wynn, JK Horan, WP Simons, R Kring, A Nori, P Mancini, L Crosby, S Tripp, C Green, MF AF Wynn, Jonathan K. Horan, W. P. Simons, R. Kring, A. Nori, P. Mancini, L. Crosby, S. Tripp, C. Green, M. F. TI ELECTROPHYSIOLOGICAL CORRELATES OF EMOTION ANTICIPATION IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Wynn, Jonathan K.; Horan, W. P.] VA Greater Angeles Healthcare Syst, MIRECC, Los Angeles, CA USA. [Wynn, Jonathan K.; Horan, W. P.; Nori, P.; Mancini, L.; Crosby, S.; Tripp, C.; Green, M. F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Kring, A.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Simons, R.] Univ Delaware, Newark, DE USA. RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 45 EP 45 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700136 ER PT J AU Mathalon, DH Roach, BJ Ford, JM AF Mathalon, Daniel H. Roach, B. J. Ford, J. M. TI ELECTROPHYSIOLOGICAL EVIDENCE OF ABNORMAL AUTOMATIC ACTIVATION OF SEMANTIC NETWORKS IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Mathalon, Daniel H.; Ford, J. M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mathalon, Daniel H.; Roach, B. J.; Ford, J. M.] San Francisco VA Med Ctr, Psychiat Serv 116d, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 50 EP 51 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700152 ER PT J AU Condray, R Steinhauer, SR Siegle, GJ Keshavan, MS Montrose, DM Chakraborty, B AF Condray, Ruth Steinhauer, S. R. Siegle, G. J. Keshavan, M. S. Montrose, D. M. Chakraborty, B. TI EFFECTS OF WORD FREQUENCY ON SEMANTIC MEMORY IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Condray, Ruth; Steinhauer, S. R.; Siegle, G. J.; Keshavan, M. S.; Montrose, D. M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Condray, Ruth; Steinhauer, S. R.; Siegle, G. J.; Chakraborty, B.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Keshavan, M. S.] Wayne State Univ, Dept Psychiat, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 57 EP 57 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700173 ER PT J AU Moore, M Austin, BP Dyckman, KA Li, Q Amlung, MT Meyer, F Clementz, BA McDowell, JE AF Moore, Madison Austin, B. P. Dyckman, K. A. Li, Q. Amlung, M. T. Meyer, F. Clementz, B. A. McDowell, J. E. TI BEHAVIORAL CHANGES FOLLOWING DAILY PRACTICE OF SACCADE TASKS IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Austin, B. P.; Li, Q.; Amlung, M. T.] Univ Georgia, Dept Psychol, Bioimaging Res Ctr, Athens, GA 30602 USA. [Clementz, B. A.; McDowell, J. E.] Univ Georgia, Dept Psychol & Neurosci, Bioimaging Res Ctr, Athens, GA USA. [Dyckman, K. A.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Meyer, F.] Univ Konstanz, Dept Psychol, Constance, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 62 EP 62 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700184 ER PT J AU Khandaker, G Barnett, JH White, IR Jones, PB AF Khandaker, Golam Barnett, J. H. White, I. R. Jones, P. B. TI SYSTEMATIC REVIEW AND META-ANALYSIS OF POPULATION-BASED STUDIES OF PREMORBID INTELLIGENCE AND SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Khandaker, Golam] Avon & Wiltshire Mental Hlth Partnership NHS Trus, Bristol, Avon, England. [Barnett, J. H.; Jones, P. B.] Univ Cambridge, Dept Psychiat, Cambridge, England. [Barnett, J. H.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [White, I. R.] Univ Cambridge, Biostat Unit, MRC, Cambridge, England. [Jones, P. B.] Cambridge & Peterborough NHS Fdn Trust, Cameo Cambridge Early Intervent Psychosis Serv, Cambridge, England. NR 1 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 66 EP 67 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700196 ER PT J AU Donatelli, JA Seidman, LJ Goldstein, JM Tsuang, MT Buka, SL AF Donatelli, Jo-Ann Seidman, L. J. Goldstein, J. M. Tsuang, M. T. Buka, S. L. TI CHILDREN OF PARENTS WITH AFFECTIVE AND NON-AFFECTIVE PSYCHOSES: A PROSPECTIVE STUDY OF CHILDHOOD INTERNALIZING AND EXTERNALIZING BEHAVIOR SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Donatelli, Jo-Ann; Buka, S. L.] Brown Univ, Providence, RI 02912 USA. [Seidman, L. J.; Goldstein, J. M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Boston, MA 02215 USA. [Seidman, L. J.] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Seidman, L. J.] MIT, Charlestown, MA USA. [Goldstein, J. M.] Harvard Univ, Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Sch Med, Boston, MA 02115 USA. [Tsuang, M. T.] Univ Calif San Diego, Ctr Behav Genet, San Diego, CA 92103 USA. [Buka, S. L.] Harvard Univ, Sch Publ Hlth, Soc Human Dev & Hlth, Boston, MA 02115 USA. RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 82 EP 82 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700242 ER PT J AU Cherkerzian, S Buka, SL Donatelli, JL Remington, A Tsuang, MT Goldstein, JM AF Cherkerzian, Sara Buka, S. L. Donatelli, J. L. Remington, A. Tsuang, M. T. Goldstein, J. M. TI IMPACT OF GENETIC VULNERABILITY FOR PSYCHOSIS, FETAL INFLAMMATION, AND GENDER ON AGE 7 COGNITIVE AND BEHAVIORAL FUNCTIONING SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Cherkerzian, Sara] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med,Div Womens Hosp,Connors Ctr Womens Hlth &, Boston, MA 02115 USA. [Buka, S. L.; Donatelli, J. L.; Goldstein, J. M.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Remington, A.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Tsuang, M. T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Goldstein, J. M.] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Goldstein, J. M.] MIT, Charlestown, MA USA. [Tsuang, M. T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, San Diego, CA 92103 USA. [Buka, S. L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth & Epidemiol, Boston, MA 02115 USA. RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 90 EP 90 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700266 ER PT J AU Sitnikova, T Roffman, JL Santangelo, SL Kuperberg, GR Goff, DC AF Sitnikova, Tatiana Roffman, J. L. Santangelo, S. L. Kuperberg, G. R. Goff, D. C. TI COMT AND MTHFR GENOTYPES ARE ASSOCIATED WITH NEUROCOGNITIVE ABNORMALITIES DURING REAL-WORLD COMPREHENSION IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Sitnikova, Tatiana; Roffman, J. L.; Santangelo, S. L.; Kuperberg, G. R.; Goff, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sitnikova, Tatiana; Roffman, J. L.; Santangelo, S. L.; Goff, D. C.] Harvard Univ, Sch Med, Boston, MA USA. [Kuperberg, G. R.] Tufts Univ, Medford, MA 02155 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 116 EP 117 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700339 ER PT J AU Goldstein, JM Buka, SL Cherkerzian, S Abbs, B Makris, N Donatelli, J Tsuang, MT Seidman, LJ AF Goldstein, Jill M. Buka, S. L. Cherkerzian, S. Abbs, B. Makris, N. Donatelli, J. Tsuang, M. T. Seidman, L. J. TI SEX-SPECIFIC TRANSMISSION OF PSYCHOSIS SUGGESTS X-LINKAGE: IMPLICATIONS FOR SEX DIFFERENCES IN MEMORY DYSFUNCTION IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Goldstein, Jill M.; Cherkerzian, S.; Abbs, B.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Goldstein, Jill M.; Cherkerzian, S.; Abbs, B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, Jill M.; Makris, N.; Seidman, L. J.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci, Boston, MA 02114 USA. [Buka, S. L.; Donatelli, J.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Buka, S. L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth & Epidemiol, Boston, MA 02115 USA. [Tsuang, M. T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Tsuang, M. T.] Univ Calif San Diego, Ctr Behav Gen, San Diego, CA 92103 USA. [Seidman, L. J.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA USA. RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 121 EP 121 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700352 ER PT J AU Greenwood, TA Light, GA Swerdlow, NR Geyer, MA Radant, AD Braff, DL AF Greenwood, Tiffany A. Light, G. A. Swerdlow, N. R. Geyer, M. A. Radant, A. D. Braff, D. L. TI LARGE-SCALE CANDIDATE GENE ANALYSIS OF ENDOPHENOTYPES FOR SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Greenwood, Tiffany A.; Light, G. A.; Swerdlow, N. R.; Geyer, M. A.; Braff, D. L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Greenwood, Tiffany A.; Geyer, M. A.] San Diego VA Healthcare Syst, San Diego, CA USA. [Radant, A. D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, A. D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 122 EP 122 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700356 ER PT J AU Pietersen, CY Lim, M McCarley, RM Woo, TU AF Pietersen, Charmaine Yvonne Lim, M. McCarley, R. M. Woo, T. -U. TI GENE PROFILING OF SINGLE-CELL POPULATIONS OF THE SUPERIOR TEMPORAL GYRUS IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Pietersen, Charmaine Yvonne; Lim, M.; Woo, T. -U.] McLean Hosp, Belmont, MA 02178 USA. [McCarley, R. M.] VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA USA. [McCarley, R. M.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Woo, T. -U.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 123 EP 123 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700359 ER PT J AU Miller, AL Velligan, DI Maples, N Li, X Copeland, L Dassori, A Moore, T Mintz, J Zeber, J Boone, C Evans, L Rodriguez, J AF Miller, Alexander L. Velligan, D. I. Maples, N. Li, X. Copeland, L. Dassori, A. Moore, T. Mintz, J. Zeber, J. Boone, C. Evans, L. Rodriguez, J. TI CONTINUITY OF CARE AFTER PSYCHIATRIC HOSPITALIZATION SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Miller, Alexander L.; Velligan, D. I.; Maples, N.; Li, X.; Copeland, L.; Dassori, A.; Moore, T.; Mintz, J.; Zeber, J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Copeland, L.; Dassori, A.; Zeber, J.] S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res, San Antonio, TX USA. [Boone, C.; Evans, L.] Ctr Hlth Care Serv, San Antonio, TX USA. RI Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 131 EP 132 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700381 ER PT J AU Yao, J Condray, R Reddy, RD Keshavan, MS Montrose, DM Matson, WR McEvoy, J Kaddurah-Daouk, R AF Yao, Jeffrey Condray, R. Reddy, R. D. Keshavan, M. S. Montrose, D. M. Matson, W. R. McEvoy, J. Kaddurah-Daouk, R. TI 3-HYDROXYKYNURENINE AND COGNITIVE IMPAIRMENT IN FIRST-EPISODE NEUROLEPTIC-NAIVE PATIENTS WITH SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Yao, Jeffrey; Condray, R.; Reddy, R. D.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Yao, Jeffrey; Condray, R.; Reddy, R. D.; Keshavan, M. S.; Montrose, D. M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Keshavan, M. S.] Wayne State Univ, Dept Psychiat, Detroit, MI USA. [Matson, W. R.] Bedford VA Med Ctr, Med Res Serv, Bedford, MA USA. [McEvoy, J.; Kaddurah-Daouk, R.] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 151 EP 151 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700437 ER PT J AU Pendergrass, JC Weiss, AP Heckers, SH AF Pendergrass, Jo Cara Weiss, A. P. Heckers, S. H. TI ABNORMAL CORTICAL-THALAMIC-CEREBELLAR RECRUITMENT DURING SUCCESSFUL MEMORY RETRIEVAL IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Pendergrass, Jo Cara; Heckers, S. H.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Weiss, A. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 175 EP 175 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700504 ER PT J AU Roffman, JL Goff, DC Schacter, DL Ellis, CB Stufflebeam, S Hamalainen, MS Duff, M Weiss, AP AF Roffman, Joshua L. Goff, D. C. Schacter, D. L. Ellis, C. B. Stufflebeam, S. Hamalainen, M. S. Duff, M. Weiss, A. P. TI ALTERED PREFRONTAL-PARIETAL PHYSIOLOGY DURING OLD-NEW ITEM RECOGNITION IN SCHIZOPHRENIA: A MULTIMODAL NEUROIMAGING INVESTIGATION SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Roffman, Joshua L.; Goff, D. C.; Ellis, C. B.; Duff, M.; Weiss, A. P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Schacter, D. L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Roffman, Joshua L.; Ellis, C. B.; Stufflebeam, S.; Hamalainen, M. S.; Duff, M.; Weiss, A. P.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RI Hamalainen, Matti/C-8507-2013 NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 177 EP 177 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700510 ER PT J AU Austin, BP Dyckman, KA Amlung, MT Li, Q Clementz, BA McDowell, JE AF Austin, Benjamin Piya Dyckman, K. A. Amlung, M. T. Li, Q. Clementz, B. A. McDowell, J. E. TI PRACTICE-INDUCED CHANGES IN NEURAL CIRCUITRIES SUPPORTING SACCADE PERFORMANCE IN SCHIZOPHRENIA: AN FMRI STUDY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Clementz, B. A.; McDowell, J. E.] Univ Georgia, Dept Psychol, Bioimaging Res Ctr, Dept Neurosci, Athens, GA 30602 USA. [Dyckman, K. A.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 178 EP 178 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700513 ER PT J AU Holt, DJ Cassidy, BS Lee, SM Gabrieli, JD Goff, DC Moran, JM AF Holt, Daphne Jane Cassidy, B. S. Lee, S. M. Gabrieli, J. D. Goff, D. C. Moran, J. M. TI ELEVATED ACTIVITY WITHIN THE POSTERIOR CINGULATE CORTEX IN SCHIZOPHRENIA DURING SELF-REFLECTION SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Holt, Daphne Jane; Cassidy, B. S.; Goff, D. C.] Massachusetts Gen Hosp, Charlestown, MA USA. [Gabrieli, J. D.; Moran, J. M.] MIT, Cambridge, MA 02139 USA. [Lee, S. M.] Yale Univ, New Haven, CT USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 178 EP 179 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700515 ER PT J AU Melonakos, ED Shenton, ME Rathi, Y Bouix, S Kubicki, M AF Melonakos, Eric D. Shenton, M. E. Rathi, Y. Bouix, S. Kubicki, M. TI CAN WHOLE BRAIN VOXEL-BASED MORPHOMETRY STUDIES APPLIED TO DTI DATA LOCALIZE WHITE MATTER CHANGES IN SCHIZOPHRENIA? SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Melonakos, Eric D.; Shenton, M. E.; Rathi, Y.; Bouix, S.; Kubicki, M.] Harvard Univ, Sch Med, Psychiat Neuroimaging Lab, Dept Psychiat,Brigham & Womens Hosp, Boston, MA USA. [Shenton, M. E.; Kubicki, M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 202 EP 203 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700584 ER PT J AU Whitford, T Kubicki, M King, R Khan, U Markant, D Alvarado, J McCarley, RW Shenton, ME AF Whitford, Thomas Kubicki, M. King, R. Khan, U. Markant, D. Alvarado, J. McCarley, R. W. Shenton, M. E. TI ABNORMALITIES IN TENSOR MORPHOLOGY IN PATIENTS WITH SCHIZOPHRENIA: A DTI STUDY OF THE CORPUS CALLOSUM SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Whitford, Thomas; Kubicki, M.; King, R.; Khan, U.; Markant, D.; Alvarado, J.; Shenton, M. E.] Harvard Univ, Sch Med, Psychiat Neuroimaging Lab, Dept Psychiat,Brigham & Womens Hosp, Boston, MA USA. [Whitford, Thomas] Univ Melbourne, Melbourne Neuropsychiat Ctr, Dept Psychiat, Melbourne, Vic, Australia. [McCarley, R. W.; Shenton, M. E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat,Clin Neurosci Lab, Brockton, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 203 EP 204 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700587 ER PT J AU White, T Magnotta, VA Bockholt, HJ Williams, S Gollub, RL Mueller, BA Ho, BC Jung, R Clark, VP Lauriello, J Bustillo, JR Schulz, SC Andreasen, NC Calhoun, VD Lim, KO AF White, Tonya Magnotta, V. A. Bockholt, H. J. Williams, S. Gollub, R. L. Mueller, B. A. Ho, B. C. Jung, R. Clark, V. P. Lauriello, J. Bustillo, J. R. Schulz, S. C. Andreasen, N. C. Calhoun, V. D. Lim, K. O. TI PROGRESSIVE WHITE MATTER ABNORMALITIES IN SCHIZOPHRENIA: A MULTI-SITE DIFFUSION TENSOR IMAGING STUDY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [White, Tonya; Lim, K. O.] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN USA. [Magnotta, V. A.; Ho, B. C.; Andreasen, N. C.] Univ Iowa, Iowa City, IA USA. [Bockholt, H. J.; Williams, S.; Jung, R.; Clark, V. P.; Calhoun, V. D.] Mind Res Network, Albuquerque, NM USA. [Gollub, R. L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Clark, V. P.; Calhoun, V. D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. RI bustillo, juan/J-7067-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 204 EP 205 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700590 ER PT J AU Voineskos, AN Lobaugh, NJ Bouix, S Kennedy, JL Mulsant, BH Pollock, BG Shenton, ME AF Voineskos, Aristotle Nicholas Lobaugh, N. J. Bouix, S. Kennedy, J. L. Mulsant, B. H. Pollock, B. G. Shenton, M. E. TI CHANGES IN THREE MAJOR FRONTOTEMPORAL WHITE MATTER TRACTS IN SCHIZOPHRENIA ACROSS THE ADULT LIFESPAN: A DIFFUSION TENSOR TRACTOGRAPHY STUDY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Voineskos, Aristotle Nicholas; Mulsant, B. H.; Pollock, B. G.] Univ Toronto, Ctr Addict & Mental Hlth, Geriatr Mental Hlth Program, Toronto, ON, Canada. [Voineskos, Aristotle Nicholas; Kennedy, J. L.] Univ Toronto, Ctr Addict & Mental Hlth, Neurosci Program, Toronto, ON, Canada. [Lobaugh, N. J.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Bouix, S.; Shenton, M. E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Shenton, M. E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RI Voineskos, Aristotle/J-5014-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 206 EP 207 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700595 ER PT J AU Rosso, IM Makris, N Hodge, SM Thermenos, HW Brown, A Faraone, SV Tsuang, MT Seidman, LJ AF Rosso, Isabelle M. Makris, N. Hodge, S. M. Thermenos, H. W. Brown, A. Faraone, S. V. Tsuang, M. T. Seidman, L. J. TI REGIONAL PREFRONTAL CORTICAL GRAY MATTER VOLUMES IN ADOLESCENTS AND YOUNG ADULTS AT FAMILIAL RISK FOR SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Rosso, Isabelle M.; Makris, N.; Hodge, S. M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Rosso, Isabelle M.] McLean Hosp, Neuroimaging Ctr, Belmont, MA 02178 USA. [Makris, N.; Hodge, S. M.] Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA USA. [Makris, N.; Hodge, S. M.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Makris, N.; Hodge, S. M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Thermenos, H. W.; Seidman, L. J.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Boston, MA 02215 USA. [Thermenos, H. W.] MGH MIT HMS, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Brown, A.] Boston Univ, Sch Med, Div Grad Med Sci, Boston, MA 02118 USA. [Brown, A.] Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY USA. [Faraone, S. V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY USA. [Tsuang, M. T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Seidman, L. J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 213 EP 213 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700613 ER PT J AU Olson, SC White, T Vuchetich, J Lim, KO Ho, BC Lauriello, J Andreasen, NC Magnotta, VA Bockholt, HJ Calhoun, V Gollub, RL Schulz, SC AF Olson, Stephen C. White, T. Vuchetich, J. Lim, K. O. Ho, B. C. Lauriello, J. Andreasen, N. C. Magnotta, V. A. Bockholt, H. J. Calhoun, V. Gollub, R. L. Schulz, S. C. TI FRACTIONAL ANISOTROPY AND MOVEMENT DISORDER IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Olson, Stephen C.; White, T.; Vuchetich, J.; Lim, K. O.; Schulz, S. C.] Univ Minnesota, Minneapolis, MN USA. [Ho, B. C.; Andreasen, N. C.; Magnotta, V. A.] Univ Iowa, Iowa City, IA USA. [Lauriello, J.; Calhoun, V.] Univ New Mexico, Albuquerque, NM 87131 USA. [Bockholt, H. J.; Calhoun, V.] Mind Res Network, Albuquerque, NM USA. [Gollub, R. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 222 EP 222 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700639 ER PT J AU Kern, RS Gold, J Dickinson, D Green, M Nuechterlein, K Baade, L Keefe, R Mesholam-Gately, R Seidman, L Marder, S AF Kern, Robert S. Gold, J. Dickinson, D. Green, M. Nuechterlein, K. Baade, L. Keefe, R. Mesholam-Gately, R. Seidman, L. Marder, S. TI PATTERNS OF COGNITIVE DYSFUNCTION IN SCHIZOPHRENIA: RESULTS FROM THE MATRICS PSYCHOMETRIC AND STANDARDIZATION STUDY (PASS) SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Kern, Robert S.; Green, M.; Nuechterlein, K.; Marder, S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Kern, Robert S.; Green, M.; Marder, S.] Dept Vet Affairs VISN 22 MIRECC, Los Angeles, CA USA. [Gold, J.] Univ Maryland, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA. [Nuechterlein, K.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Baade, L.] Univ Kansas, Sch Med, Wichita, KS 67214 USA. [Keefe, R.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Mesholam-Gately, R.; Seidman, L.] Harvard Univ, Sch Med, Dept Psychiat,Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Publ Psychiat Div, Boston, MA 02115 USA. [Seidman, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dickinson, D.] Dept Vet Affairs VISN 5 MIRECC, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 283 EP 283 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700820 ER PT J AU Schooler, NR Green, MF Kern, RS Deng, BH AF Schooler, Nina. R. Green, M. F. Kern, R. S. Deng, B. H. TI FUNCTIONAL CAPACITY AND INTERVIEW-BASED MEASURES: RAND PANEL JUDGMENTS SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Schooler, Nina. R.] Suny Downstate Med Ctr, Dept Psychiat & Behav Sci, Brooklyn, NY 11203 USA. [Schooler, Nina. R.] Washington DC VA Med Ctr, VISN MIRECC 5, Washington, DC USA. [Green, M. F.; Kern, R. S.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Green, M. F.; Kern, R. S.] VA Greater Los Angeles Healthcare Syst, VISN MIRECC 22, Los Angeles, CA USA. [Deng, B. H.] Claremont Grad Univ, Dept Psychol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 305 EP 306 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700888 ER PT J AU Muller, AM Wirshing, DA Guzik, LH Erickson, ZD Mena, SJ AF Muller, Anna Mia Wirshing, D. A. Guzik, L. H. Erickson, Z. D. Mena, S. J. TI IMPACT OF A SHORT-TERM SKILLS-BASED INTERVENTION PROGRAM ON LEVEL OF INSIGHT AND ENGAGEMENT IN FOLLOW-UP PSYCHIATRIC CARE SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Muller, Anna Mia; Wirshing, D. A.; Guzik, L. H.; Erickson, Z. D.; Mena, S. J.] W Los Angeles VA Med Ctr, Schizophrenia Res Clin, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 310 EP 310 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700901 ER PT J AU Rassovsky, Y Lee, J Sergi, M Nori, P Crosby, S Green, MF AF Rassovsky, Yuri Lee, J. Sergi, M. Nori, P. Crosby, S. Green, M. F. TI MEDIATORS AND MODERATORS BETWEEN NEUROCOGNITION AND FUNCTIONAL STATUS IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Rassovsky, Yuri; Lee, J.; Sergi, M.; Nori, P.; Crosby, S.; Green, M. F.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Lee, J.; Nori, P.; Crosby, S.; Green, M. F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Sergi, M.] Calif State Univ Northridge, Northridge, CA 91330 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 312 EP 313 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700908 ER PT J AU Caponigro, J Valenti, LM Molz, AR Luther, J Paldino, DM Haas, GL AF Caponigro, Janelle Valenti, L. M. Molz, A. R. Luther, J. Paldino, D. M. Haas, G. L. TI RELIABILITY AND VALIDITY OF A BEHAVIORAL MEASURE OF SOCIAL COGNITION IN AN INTERPERSONAL SETTING SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Caponigro, Janelle; Haas, G. L.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Valenti, L. M.; Molz, A. R.; Luther, J.; Paldino, D. M.; Haas, G. L.] Mental Illness Res Educ & Clin Ctr, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Caponigro, Janelle] Univ Calif Berkeley, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 317 EP 318 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700923 ER PT J AU Haas, GL Valenti, L Caponigro, J Molz, A Goldstein, G Luther, J AF Haas, Gretchen L. Valenti, L. Caponigro, J. Molz, A. Goldstein, G. Luther, J. TI DISSECTING SOCIAL INFORMATION PROCESSING DEFICITS IN SCHIZOPHRENIA: CONTRIBUTION OF AFFECTIVE AND NON-AFFECTIVE COGNITIVE COMPONENTS SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Haas, Gretchen L.; Luther, J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Haas, Gretchen L.; Valenti, L.; Caponigro, J.; Molz, A.; Goldstein, G.; Luther, J.] VA Pittsburgh Healthcare Syst, MIRECC, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 331 EP 332 PG 2 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964700965 ER PT J AU Wood, AE Kennedy, A Martin, LM Kilzieh, N Sellars, VS Tapp, A AF Wood, Amanda Ernst Kennedy, A. Martin, L. M. Kilzieh, N. Sellars, V. S. Tapp, A. TI PILOT PROGRAM FOR MEDICATION OPTIMIZATION: SOMETIMES LESS IS MORE SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Wood, Amanda Ernst; Kennedy, A.; Martin, L. M.; Kilzieh, N.; Sellars, V. S.; Tapp, A.] VA Puget Hlth Care Syst, Tacoma, WA USA. [Wood, Amanda Ernst; Martin, L. M.; Kilzieh, N.; Tapp, A.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 349 EP 349 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964701013 ER PT J AU Green, MF Horan, WP Shokat-Fadai, K Sergi, MJ Waldon, C Ofek, A Kern, RS AF Green, Michael F. Horan, W. P. Shokat-Fadai, K. Sergi, M. J. Waldon, C. Ofek, A. Kern, R. S. TI INITIAL EFFICACY DATA ON A SOCIAL COGNITIVE SKILLS TRAINING PROGRAM SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Green, Michael F.; Horan, W. P.; Sergi, M. J.; Waldon, C.; Ofek, A.; Kern, R. S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Green, Michael F.; Horan, W. P.; Waldon, C.; Ofek, A.; Kern, R. S.] VA Greater Angeles Healthcare Syst, MIRECC, Los Angeles, CA USA. [Shokat-Fadai, K.; Sergi, M. J.] Cal State Univ Northridge, Northridge, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 350 EP 350 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964701017 ER PT J AU Freudenreich, O Henderson, DC Macklin, EA Evins, AE Fan, X Cather, C Walsh, JP Goff, DC AF Freudenreich, Oliver Henderson, D. C. Macklin, E. A. Evins, A. E. Fan, X. Cather, C. Walsh, J. P. Goff, D. C. TI MODAFINIL FOR CLOZAPINE-TREATED SCHIZOPHRENIA PATIENTS. A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Freudenreich, Oliver; Henderson, D. C.; Macklin, E. A.; Evins, A. E.; Fan, X.; Cather, C.; Walsh, J. P.; Goff, D. C.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 358 EP 358 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964701040 ER PT J AU Amatniek, J Canuso, CM Rodriguez, S Mao, L Youssef, EA Navarro, V Henderson, DC AF Amatniek, Joan Canuso, C. M. Rodriguez, S. Mao, L. Youssef, E. A. Navarro, V. Henderson, D. C. TI SUBJECTS WITH SCHIZOPHRENIA OR SCHIZOAFFECTIVE DISORDER AND HEPATIC ILLNESS: BASELINE CHARACTERISTICS FROM ATRIAL OF PALIPERIDONE EXTENDED-RELEASE SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Amatniek, Joan; Canuso, C. M.; Rodriguez, S.; Mao, L.; Youssef, E. A.] Ortho McNeil Janssen Sci Affairs LLC, Titusville, NJ USA. [Navarro, V.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Henderson, D. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 362 EP 362 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964701050 ER PT J AU Nuechterlein, KH Green, MF Kern, RS AF Nuechterlein, Keith H. Green, M. F. Kern, R. S. TI TRANSLATION AND CULTURAL ADAPTATION OF THE MATRICS CONSENSUS COGNITIVE BATTERY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Nuechterlein, Keith H.; Green, M. F.; Kern, R. S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Green, M. F.; Kern, R. S.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 372 EP 372 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964701079 ER PT J AU Kasckow, J Gurklis, J Thompson, R Crofutt, R Murray, T Richmond, I Haas, G AF Kasckow, John Gurklis, J. Thompson, R. Crofutt, R. Murray, T. Richmond, I. Haas, G. TI TELEHEALTH MONITORING OF PATIENTS WITH SCHIZOPHRENIA AND SUICIDAL BEHAVIOR SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 12th International Congress on Schizophrenia Research CY MAR 28-APR 01, 2009 CL San Diego, CA C1 [Kasckow, John; Gurklis, J.; Thompson, R.; Crofutt, R.; Murray, T.; Richmond, I.; Haas, G.] VA Pittsburgh Hlth Care Syst, MIRECC & Behav Hlth, Pittsburgh, PA USA. [Kasckow, John; Haas, G.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Crofutt, R.; Murray, T.; Richmond, I.] VA Pittsburgh Hlth Care Syst, Nursing Serv, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2009 VL 35 BP 374 EP 374 PG 1 WC Psychiatry SC Psychiatry GA 415VP UT WOS:000263964701084 ER PT J AU Lee, K Yoshida, T Kubicki, M Bouix, S Westin, CF Kindlmann, G Niznikiewicz, M Cohen, A McCarley, RW Shenton, ME AF Lee, KangUk Yoshida, Takeshi Kubicki, Marek Bouix, Sylvain Westin, Carl-Fredrik Kindlmann, Gordon Niznikiewicz, Margaret Cohen, Adam McCarley, Robert W. Shenton, Martha E. TI Increased diffusivity in superior temporal gyrus in patients with schizophrenia: A Diffusion Tensor Imaging study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Superior temporal gyrus; Diffusion Tensor Imaging; Mean diffusivity; Fractional anisotropy; Auditory hallucination ID AUDITORY HALLUCINATIONS; WHITE-MATTER; 1ST-EPISODE SCHIZOPHRENIA; NEGATIVE SYMPTOMS; PLANUM TEMPORALE; HESCHLS GYRUS; HUMAN-BRAIN; ABNORMALITIES; VOLUME; INVOLVEMENT AB Background: Superior temporal gyrus (STG) volume reduction is one of the most consistent findings in schizophrenia. The goal of this study was to conduct the first Diffusion Tensor Imaging (DTI) study to investigate altered structural integrity in STG gray and white matter in patients with chronic schizophrenia compared with healthy controls. Methods: Magnetic resonance imaging (MRI) and DTI were acquired in 21 male patients with schizophrenia and 22 age-, handedness-, and parental social economic status-matched male comparison subjects. After manual segmentation of gray and white matter, mean diffusivity and fractional anisotropy were measured within STG. Correlational analyses were also conducted to test possible associations between DTI and clinical measures, including positive and negative symptoms of schizophrenia. Results: Compared with controls, patients demonstrated reduced volume, bilaterally, in STG gray matter but not in white matter. For DTI measures, patients showed increased mean diffusivity, bilaterally, in STG gray matter, and in left STG white matter. In addition, mean diffusivity in left STG white matter showed statistically significant correlations with auditory hallucinations and attentional impairments in patients. Conclusions: These findings suggest a disruption of tissue integrity in STG gray and white matter in schizophrenia. In addition, increased water diffusivity in left-side STG, which was associated with auditory hallucinations and attentional impairments, Suggests the possibility of a disconnection among auditory/language processing regions in schizophrenia. (C) 2008 Elsevier B.V. All rights reserved. C1 [Lee, KangUk; Kubicki, Marek; Bouix, Sylvain; Cohen, Adam; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02215 USA. [Lee, KangUk; Yoshida, Takeshi; Kubicki, Marek; Bouix, Sylvain; Niznikiewicz, Margaret; McCarley, Robert W.; Shenton, Martha E.] VA Boston Healthcare, Neurosci Lab, Clin Neurosci Div, Brockton, MA 02301 USA. [Lee, KangUk] Kangwon Natl Univ, Dept Psychiat, Coll Med, Chunchon, Kangwon Do, South Korea. [Westin, Carl-Fredrik; Kindlmann, Gordon] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Lab Math Imaging,Med Sch, Boston, MA 02115 USA. [Yoshida, Takeshi] Natl Def Med Coll, Dept Psychiat, Tokorozawa, Saitama 3598513, Japan. RP Lee, K (reprint author), Kangwon Natl Univ Hosp, Dept Psychiat, 17-1 Hyoja Dong, Chunchon 200947, Kangwon Do, South Korea. EM kuleemd@kangwon.ac.kr RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Bouix, Sylvain/0000-0003-1326-6054; Cohen, Adam/0000-0003-2719-3351 FU National Institute of Health [K05 MH070047, R01 MH 50740, R01 MH 40799, R01 MH 074794, P50 MH 080272]; Department of Veterans Affairs Merit Awards; VA Schizophrenia Center Grant; National Alliance for Medical Image Computing; National Institutes of Health through the NIH Roadmap for Medical Research, [U54 EB005149] FX Tile authors would like to thank Nancy Maxwell for administrative support; Takeshi Yoshida for his assistance in the segmentation and in the statistical analyses; Marek Kubicki and Martha Shenton for their assistance with the design of the study and for reviewing multiple versions of the manuscript; Sylvain Bouix, Carl-Fredrik Westin and Gordon KindIniann for their technical assistance; Adam Cohen for his support as research assistant; Margaret Niznikiewicz for her assistance in the characterization of the subject sample; and Robert McCarley for his support in providing subjects and for reviewing parts of the manuscript. Additionally, we gratefully acknowledge the support of the National Institute of Health (K05 MH070047 and R01 MH 50740 to MES, R01 MH 40799 to RWM and R01 MH 074794 to CFW, P50 MH 080272 to RWIVI, MES), the Department of Veterans Affairs Merit Awards (MES, RWM), and the VA Schizophrenia Center Grant (RWM, MES). This work is also part of the National Alliance for Medical Image Computing (NA-MIC), funded by the National Institutes of Health through the NIH Roadmap for Medical Research, U54 EB005149 (MK, MES). NR 45 TC 35 Z9 36 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 2009 VL 108 IS 1-3 BP 33 EP 40 DI 10.1016/j.schres.2008.11.024 PG 8 WC Psychiatry SC Psychiatry GA 423OV UT WOS:000264506500005 PM 19135872 ER PT J AU Antoun, TA Palevsky, PM AF Antoun, Tania Abi Palevsky, Paul M. TI Selection of Modality of Renal Replacement Therapy SO SEMINARS IN DIALYSIS LA English DT Article ID CRITICALLY-ILL PATIENTS; ACUTE KIDNEY INJURY; INTENSIVE-CARE-UNIT; CONTINUOUS ARTERIOVENOUS HEMOFILTRATION; CONTINUOUS VENOVENOUS HEMODIAFILTRATION; RANDOMIZED CLINICAL-TRIAL; INTERMITTENT HEMODIALYSIS; CYTOKINE REMOVAL; FAILURE; MULTICENTER AB The proliferation of new technologies has led to the availability of a broad range of options for the management of renal replacement therapy (RRT) in patients with acute kidney injury. We provide a review of the published literature comparing the continuous RRTs (CRRT) with other modalities of renal support, including intermittent hemodialysis and the more recently described "hybrid" therapies such as sustained, low efficiency dialysis as well as compare arteriovenous and venovenous and convective and diffusive modalities of CRRT. While there is clear evidence that venovenous therapies are superior to arteriovenous therapies, current evidence does not support superiority of convective when compared with diffusive therapies or greater survival or recovery of kidney function with any individual modality of RRT. Selection of modality of RRT should therefore rely on the resources and expertise available. C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. [Antoun, Tania Abi; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Room 7E123 111F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 53 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR-APR PY 2009 VL 22 IS 2 BP 108 EP 113 DI 10.1111/j.1525-139X.2008.00540.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 435XX UT WOS:000265377700002 ER PT J AU Palevsky, PM AF Palevsky, Paul M. TI Intensity of Continuous Renal Replacement Therapy in Acute Kidney Injury SO SEMINARS IN DIALYSIS LA English DT Article ID CONTINUOUS VENOVENOUS HEMOFILTRATION; ULTRAFILTRATION FLOW-RATES; SOLUTE CLEARANCES; RANDOMIZED-TRIAL; SEPTIC SHOCK; FAILURE; HEMODIALYSIS; SURVIVAL AB The intensity of continuous renal replacement therapy (CRRT) is generally assessed on the basis of small solute clearance with dosing usually expressed in terms of total effluent volume per unit time (e.g., ml/kg/hour). Although several clinical trials have suggested an improvement in survival with higher doses of CRRT, results have not been consistent across all studies. The results of recent trials of intensity of CRRT are reviewed. The largest and most recent trials suggest that there is no additional benefit to using effluent flow rates in excess of 20 ml/kg/hour, although earlier studies suggested improved survival with doses of 35 to 45 ml/kg/hour. C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Univ Drive Div, Renal Sect, Pittsburgh, PA 15240 USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Univ Drive Div, Renal Sect, Room 7E123 111F-U, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 16 TC 4 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR-APR PY 2009 VL 22 IS 2 BP 151 EP 154 DI 10.1111/j.1525-139X.2008.00543.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 435XX UT WOS:000265377700009 PM 19426419 ER PT J AU Williams, ME AF Williams, Mark E. TI Chronic Kidney Disease/Bone and Mineral Metabolism: The Imperfect Storm SO SEMINARS IN NEPHROLOGY LA English DT Review DE Kidney; mineral; hyperparathyroidism; vitamin D ID TREAT SECONDARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE SECRETION; VITAMIN-D; VASCULAR CALCIFICATION; DIETARY PHOSPHATE; HEMODIALYSIS-PATIENTS; SERUM PHOSPHORUS; RENAL-FUNCTION; CALCIUM; FIBROBLAST-GROWTH-FACTOR-23 C1 [Williams, Mark E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Williams, ME (reprint author), Harvard Univ, Sch Med, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 59 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 0270-9295 EI 1558-4488 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 2009 VL 29 IS 2 BP 97 EP 104 DI 10.1016/j.semnephrol.2009.01.002 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 437BA UT WOS:000265459400002 PM 19371800 ER PT J AU Tanrikut, C Goldstein, M AF Tanrikut, Cigdem Goldstein, Marc TI Obstructive Azoospermia: A Microsurgical Success Story SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE Obstructive azoospermia; sperm retrieval; intracytoplasmic sperm injection; male infertility; microsurgery ID INTRACYTOPLASMIC SPERM INJECTION; EJACULATORY DUCT OBSTRUCTION; IN-VITRO FERTILIZATION; CONGENITAL BILATERAL ABSENCE; FEMALE PARTNER AGE; VASECTOMY REVERSAL; TESTICULAR SPERMATOZOA; EPIDIDYMAL SPERM; VAS-DEFERENS; TRANSURETHRAL RESECTION AB Microsurgical techniques used in the treatment of male factor infertility have provided used in a revolutionary adjunct to the advent of intracytoplasmic sperm injection conjunction with in vitro fertilization. Previously infertile couples may now parent their own biological children and, in some cases, may even conceive naturally owing to technical advances within the past decade. This article outlines the modern methods currently employed to address vasal and epididymal obstruction with special emphasis on the importance of microsurgical techniques. The multiple reconstructive and sperm aspiration techniques at our disposal for treatment of vasal and epididymal obstruction as well as the management of ejaculatory duct obstruction are reviewed. The various procedures discussed allow reproductive urologists to maximize male fertility potential in the era of assisted reproductive technologies. C1 [Tanrikut, Cigdem] Massachusetts Gen Hosp, Fertil Ctr, Boston, MA 02114 USA. [Goldstein, Marc] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Urol, New York, NY USA. RP Tanrikut, C (reprint author), Massachusetts Gen Hosp, Fertil Ctr, 55 Fruit St,YAW-10A, Boston, MA 02114 USA. EM ctanrikut@partners.org NR 51 TC 3 Z9 11 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD MAR PY 2009 VL 27 IS 2 BP 159 EP 164 DI 10.1055/s-0029-1202304 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 413YY UT WOS:000263832300008 PM 19247917 ER PT J AU Hough, S AF Hough, Sigmund TI Untitled SO SEXUALITY AND DISABILITY LA English DT Editorial Material C1 VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, W Roxbury, MA 02132 USA. RP Hough, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Sigmund_Hough@hms.harvard.edu 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 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD MAR PY 2009 VL 27 IS 1 BP 1 EP 1 DI 10.1007/s11195-009-9110-7 PG 1 WC Rehabilitation SC Rehabilitation GA 409ZU UT WOS:000263545100001 ER PT J AU Hough, S AF Hough, Sigmund TI Ageing, Disability and Spirituality: Addressing the Challenge of Disability in Later Life SO SEXUALITY AND DISABILITY LA English DT Book Review C1 [Hough, Sigmund] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Hough, Sigmund] VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, Boston, MA 02132 USA. [Hough, Sigmund] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Hough, S (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM Sigmund_Hough@hms.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD MAR PY 2009 VL 27 IS 1 BP 65 EP 66 DI 10.1007/s11195-009-9109-0 PG 2 WC Rehabilitation SC Rehabilitation GA 409ZU UT WOS:000263545100009 ER PT J AU Calhoun, AW Rider, EA Meyer, EC Lamiani, G Truog, RD AF Calhoun, Aaron W. Rider, Elizabeth A. Meyer, Elaine C. Lamiani, Giulia Truog, Robert D. TI Assessment of Communication Skills and Self-Appraisal in the Simulated Environment: Feasibility of Multirater Feedback with Gap Analysis SO SIMULATION IN HEALTHCARE LA English DT Article DE Simulated parent interactions; Simulation of physician communication; Assessment of communication skills; Multirater feedback; Gap analysis; Evaluation; Medical education; Self-appraisal; Self-assessment; ACGME competencies ID MULTISOURCE FEEDBACK; PROFESSIONAL COMPETENCE; PSYCHOMETRIC PROPERTIES; CONSENSUS STATEMENT; PATIENT; 360-DEGREE; CARE; INFORMATION; INSTRUMENT; CHECKLIST AB Introduction: Multirater assessment is a powerful means of measuring communication skills. The use of gap analysis to assess self-appraisal is a strength of this technique. On the basis of Kalamazoo Consensus Statement framework and 360-degree assessment models, we developed a multirater instrument with gap analysis, with the goals of examining both communication skills and situational self-appraisal, and assessing the feasibility of the combined approach. Methods: The multirater communication skills instrument was used to assess Pediatric and Neonatal Intensive Care fellows after participation in seven simulated family meetings. Instrument reliability was determined using Cronbach's Alpha and Factorial Analysis. Correlations between rater groups were examined with Spearman's Rank Coefficient. Gap analyses and rater perceptions of the instruments were analyzed using descriptive statistics. Results: Seven pediatric intensive care unit and neonatal intensive care fellows were each assessed by 11 to 18 raters (108 total assessments). Correlations were identified between disciplinary groups within each encounter. Among the 7 fellows, 30 communication strengths or areas needing improvement and 24 significant gaps were identified, indicating self under-appraisals, 9 (38%) of which overlapped. The instrument was logistically feasible and well received. Conclusions: Our multirater communication skills instrument with gap analysis proved useful in identifying areas of strength and areas needing improvement, and in highlighting areas of self over-and under-appraisal that require focused feedback. The use of multirater assessment with gap analysis, in a simulated and "safe" environment, may assist in the delivery of feedback to trainees. (Sim Healthcare 4: 22-29, 2009) C1 [Calhoun, Aaron W.] Univ Louisville, Div Pediat Crit Care Med, Louisville, KY 40292 USA. [Calhoun, Aaron W.; Rider, Elizabeth A.; Meyer, Elaine C.; Lamiani, Giulia] Harvard Univ, Sch Med, Childrens Hosp Boston, Inst Professionalism & Eth Practice, Boston, MA USA. [Rider, Elizabeth A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Truog, Robert D.] Harvard Univ, Sch Med, Dept Med Eth, Boston, MA USA. [Rider, Elizabeth A.] Massachusetts Gen Hosp, Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. [Meyer, Elaine C.; Truog, Robert D.] Childrens Hosp, Dept Anaesthesia, Boston, MA 02115 USA. [Meyer, Elaine C.] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Lamiani, Giulia] Univ Milan, Inst Med Psychol, San Paolo Hosp, Milan, Italy. RP Calhoun, AW (reprint author), 571 S Floyd St,STE 332, Louisville, KY 40202 USA. EM aaron.calhoun@louisville.edu OI Giulia, Lamiani/0000-0002-1943-3282 NR 48 TC 19 Z9 20 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 J9 SIMUL HEALTHC JI Simul. Healthc. PD SPR PY 2009 VL 4 IS 1 BP 22 EP 29 DI 10.1097/SIH.0b013e318184377a PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 588EG UT WOS:000277049700005 PM 19212247 ER PT J AU Hadjikhani, N Joseph, RM Manoach, DS Naik, P Snyder, J Dominick, K Hoge, R Van den Stock, J Flusberg, HT de Gelder, B AF Hadjikhani, Nouchine Joseph, Robert M. Manoach, Dara S. Naik, Paulami Snyder, Josh Dominick, Kelli Hoge, Rick Van den Stock, Jan Flusberg, Helen Tager de Gelder, Beatrice TI Body expressions of emotion do not trigger fear contagion in autism spectrum disorder SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE autism; emotion; functional magnetic resonance imaging (fMRI); bodily expression; amygdala; pulvinar; subcortical processing; mirror neurons system ID PERVASIVE DEVELOPMENTAL DISORDERS; SURFACE-BASED ANALYSIS; FUSIFORM FACE AREA; ASPERGERS-SYNDROME; AMYGDALA THEORY; FACIAL EXPRESSIONS; SOCIAL COGNITION; FUNCTIONAL MRI; NORMAL ADULTS; WHOLE-BODY AB Although there is evidence of emotion perception deficits in autism spectrum disorder (ASD), research on this topic has been mostly confined to perception of emotions in faces. Using behavioral measures and 3T functional magnetic resonance imaging (fMRI), we examined whether such deficits extend to the perception of bodily expressed emotions. We found that individuals with ASD, in contrast to neurotypical (NT) individuals, did not exhibit a differential pattern of brain activation to bodies expressing fear as compared with emotionally neutral bodies. ASD and NT individuals showed similar patterns of activation in response to bodies engaged in emotionally neutral actions, with the exception of decreased activation in the inferior frontal cortex and the anterior insula in ASD. We discuss these findings in relation to possible abnormalities in a network of cortical and subcortical mechanisms involved in social orienting and emotion contagion. Our data suggest that emotion perception deficits in ASD may be due to compromised processing of the emotional component of observed actions. C1 [Hadjikhani, Nouchine; Manoach, Dara S.; Naik, Paulami; Snyder, Josh; de Gelder, Beatrice] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Hadjikhani, Nouchine; Manoach, Dara S.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA. [Hadjikhani, Nouchine] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lausanne, Switzerland. [Joseph, Robert M.; Dominick, Kelli; Flusberg, Helen Tager] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Manoach, Dara S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Hoge, Rick] Univ Montreal, UNF CRIUGM, Montreal, PQ, Canada. [Van den Stock, Jan; de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. RP Hadjikhani, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM nouchine@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008; Van den Stock, Jan/F-1906-2014 OI Hadjikhani, Nouchine/0000-0003-4075-3106; Van den Stock, Jan/0000-0001-5756-3195 FU National Institute of Health [RO1 NS44824-01, K01 MH073944-01, U19 DC 03610]; Swiss National Foundation [PPOOB-110741]; Canadian Institute of Health Research [200703MOP-172783-MPI-CFCL-155844] FX We wish to thank Mary Foley for contributing to data collection. National Institute of Health (RO1 NS44824-01 to N. H.; K01 MH073944-01 to R. M. J.; U19 DC 03610 to H. T. F.); Swiss National Foundation (PPOOB-110741 to N. H.); Canadian Institute of Health Research (200703MOP-172783-MPI-CFCL-155844 to R. H.). NR 65 TC 28 Z9 30 U1 12 U2 28 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD MAR PY 2009 VL 4 IS 1 BP 70 EP 78 DI 10.1093/scan/nsn038 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 421ZY UT WOS:000264398000007 PM 19151375 ER PT J AU Krogh, K Perkash, I Stiens, SA Biering-Sorensen, F AF Krogh, K. Perkash, I. Stiens, S. A. Biering-Sorensen, F. TI International bowel function basic spinal cord injury data set SO SPINAL CORD LA English DT Article DE spinal cord injury; spinal cord lesion; constipation; fecal incontinence; colon; rectum ID FECAL INCONTINENCE; COLONIC TRANSIT; DYSFUNCTION; LESIONS; POPULATION; MANAGEMENT AB Study design: International expert working group. Objective: To develop an International Bowel Function Basic Spinal Cord Injury (SCI) Data Set presenting a standardized format for the collection and reporting of a minimal amount of information on bowel function in daily practice or in research. Setting: Working group consisting of members appointed by the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS). Methods: A draft prepared by the working group was reviewed by Executive Committee of the International SCI Standards and Data Sets, and later by ISCoS Scientific Committee and the ASIA Board. Relevant and interested scientific and professional (international) organizations and societies (approximately 40) were also invited to review the data set and it was posted on the ISCoS and ASIA websites for 3 months to allow comments and suggestions. The ISCoS Scientific Committee, Council and ASIA Board received the data set for final review and approval. Results: The International Bowel Function Basic SCI Data Set includes the following 12 items: date of data collection, gastrointestinal or anal sphincter dysfunction unrelated to SCI, surgical procedures on the gastrointestinal tract, awareness of the need to defecate, defecation method and bowel care procedures, average time required for defecation, frequency of defecation, frequency of fecal incontinence, need to wear pad or plug, medication affecting bowel function/constipating agents, oral laxatives and perianal problems. Conclusion: An International Bowel Function Basic SCI Data Set has been developed. C1 [Krogh, K.] Aarhus Univ Hosp, Dept Hepatol & Gastroenterol 5, Neurogastroenterol Unit, DK-8000 Aarhus, Denmark. [Krogh, K.] Aarhus Univ Hosp, Dept Surg P, DK-8000 Aarhus, Denmark. [Perkash, I.] Stanford Univ, Palo Alto, CA 94304 USA. [Perkash, I.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Stiens, S. A.] VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. [Biering-Sorensen, F.] Copenhagen Univ Hosp, Rigshosp, Ctr Neurosci, Clin Spinal Cord Injuries, Copenhagen, Denmark. RP Krogh, K (reprint author), Aarhus Univ Hosp, Dept Hepatol & Gastroenterol 5, Neurogastroenterol Unit, Norrebrogade 44, DK-8000 Aarhus, Denmark. EM krogh@as.aaa.dk FU Coloplast A/S, Denmark FX Coloplast A/S, Denmark has supported this study with this data set with an unconditional grant. We are thankful for comments and suggestions received from Susan Charlifue, Lawrence Vogel, Dan Lammertse, William Donovan, Inge Eriks Hoogland, Karen Smith and Peter Christensen. NR 20 TC 35 Z9 36 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD MAR PY 2009 VL 47 IS 3 BP 230 EP 234 DI 10.1038/sc.2008.102 PG 5 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 415AG UT WOS:000263906100008 PM 18725887 ER PT J AU Krogh, K Perkash, I Stiens, SA Biering-Sorensen, F AF Krogh, K. Perkash, I. Stiens, S. A. Biering-Sorensen, F. TI International bowel function extended spinal cord injury data set SO SPINAL CORD LA English DT Article DE spinal cord injury; spinal cord lesion; constipation; fecal incontinence; colon; rectum ID FECAL INCONTINENCE; ANORECTAL FUNCTION; COLONIC TRANSIT; ABDOMINAL-PAIN; DYSFUNCTION; LESIONS; POPULATION; MANAGEMENT; PHYSIOLOGY; DISORDERS AB Study design: International expert working group. Objective: To develop an International Bowel Function Extended Spinal Cord Injury (SCI) Data Set presenting a standardized format for the collection and reporting of an extended amount of information on bowel function. Setting: Working group consisting of members appointed by the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS). Methods: A draft prepared by the working group was reviewed by Executive Committee of the International SCI Standards and Data Sets and later by the ISCoS Scientific Committee and the ASIA Board. Relevant and interested scientific and professional organizations and societies (around 40) were also invited to review the data set and it was posted on the ISCoS and ASIA websites for 3 months to allow comments and suggestions. The ISCoS Scientific Committee, ISCoS Council and ASIA Board received the data set for final review and approval. Results: The International Bowel Function Basic SCI Data Set includes 26 items providing a thorough description of bowel- related symptoms as well as clinical assessment of anal sphincter function and description of total gastrointestinal or segmental colorectal transit times. Conclusion: An International Bowel Function Extended SCI Data Set has been developed. This Data Set is mainly for research purposes and it should be used in combination with the information obtained from the International SCI Core Data Set and the International Bowel Function Basic SCI Data Set. C1 [Krogh, K.] Aarhus Univ Hosp, Dept Hepatol & Gastroenterol 5, Neurogastroenterol Unit, DK-8000 Aarhus, Denmark. [Krogh, K.] Aarhus Univ Hosp, Dept Surg P, DK-8000 Aarhus, Denmark. [Perkash, I.] Stanford Univ, Palo Alto, CA 94304 USA. [Perkash, I.] Va Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Stiens, S. A.] VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. [Biering-Sorensen, F.] Copenhagen Univ Hosp, Rigshosp, Ctr Neurosci, Clin Spinal Cord Injuries, Copenhagen, Denmark. RP Krogh, K (reprint author), Aarhus Univ Hosp, Dept Hepatol & Gastroenterol 5, Neurogastroenterol Unit, Norrebrogade 44, DK-8000 Aarhus, Denmark. EM krogh@as.aaa.dk FU Coloplast A/S (Denmark) FX Coloplast A/S (Denmark) has supported the work with this Data Set with an unconditional grant. We are thankful for all comments and suggestions received. We thank Susan Charlifue, Lawrence Vogel, Dan Lammertse, William Donovan, Inge Eriks Hoogland, Karen Smith and Peter Christensen. NR 31 TC 22 Z9 24 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD MAR PY 2009 VL 47 IS 3 BP 235 EP 241 DI 10.1038/sc.2008.103 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 415AG UT WOS:000263906100009 PM 18725886 ER PT J AU Sims, K Politei, J Banikazemi, M Lee, P AF Sims, Katherine Politei, Juan Banikazemi, Maryam Lee, Philip TI Stroke in Fabry Disease Frequently Occurs Before Diagnosis and in the Absence of Other Clinical Events Natural History Data From the Fabry Registry SO STROKE LA English DT Article DE Fabry disease; cerebrovascular accident; stroke; registries ID ENZYME REPLACEMENT THERAPY; AGALSIDASE-BETA THERAPY; ALPHA-GALACTOSIDASE; CEREBROVASCULAR COMPLICATIONS; CEREBRAL HYPERPERFUSION; CRYPTOGENIC STROKE; MANIFESTATIONS; SAFETY; TRIAL; PREVALENCE AB Background and Purpose-Stroke is a common and serious clinical manifestation of Fabry disease, an X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A activity. This study was undertaken to better understand the natural history of cerebrovascular manifestations of Fabry disease. Methods-Data from 2446 patients in the Fabry Registry were analyzed to identify clinical characteristics of patients experiencing stroke during the natural history period (ie, before enzyme replacement therapy). Results-A total of 138 patients (86 of 1243 males [ 6.9%] and 52 of 1203 females [ 4.3%]) experienced strokes. Median age at first stroke was 39.0 years in males and 45.7 years in females. Most patients (70.9% of males and 76.9% of females) had not experienced renal or cardiac events before their first stroke. Fifty percent of males and 38.3% of females experienced their first stroke before being diagnosed with Fabry disease. Thirty patients (21 males and 9 females) had strokes at age <30 years. Most patients (86.8%) had ischemic strokes, but 16.9% of males and 6.9% of females had hemorrhagic strokes, among those for whom stroke type was reported. At the most recently available follow-up examination after their first stroke, 60% of males and 25.5% of females exhibited stage 3 to 5 chronic kidney disease and 66.1% of males and 59.5% of females had left ventricular hypertrophy. Conclusions-All patients with Fabry disease, regardless of age or gender, should be monitored for possible cerebrovascular complications, as stroke can occur in the absence of other key signs of the disease. (Stroke. 2009; 40: 788-794.) C1 [Sims, Katherine] Massachusetts Gen Hosp, Ctr Human Genet Res, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Sims, Katherine] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Politei, Juan] Juan Fernandez Hosp, Neurol Serv, Buenos Aires, DF, Argentina. [Banikazemi, Maryam] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. [Banikazemi, Maryam] Columbia Univ, Coll Phys & Surg, Dept Pediat, New York, NY USA. [Lee, Philip] Natl Hosp Neurol & Neurosurg, Charles Dent Metab Unit, London WC1N 3BG, England. RP Sims, K (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Richard B Simches Res Ctr, CPZN 5300,185 Cambridge St, Boston, MA 02114 USA. EM ksims@partners.org FU Genzyme Corporation FX The Fabry Registry is sponsored by Genzyme Corporation. K. S., M. B., and P. L. serve on the Genzyme-sponsored North American Fabry Registry Board of Advisors. J. P. serves as a Latin American Fabry Registry Coordinator. NR 32 TC 131 Z9 143 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2009 VL 40 IS 3 BP 788 EP 794 DI 10.1161/STROKEAHA.108.526293 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 410PN UT WOS:000263590200035 PM 19150871 ER PT J AU Chang, YC Cortellini, L Greenberg, SM Rosand, J Singer, D Schwab, K Selim, M Meschia, J Eckman, MH Silliman, S Brown, D Worrall, WB Tirschwell, D Gage, BF AF Chang, Yuchiao Cortellini, Lynelle Greenberg, Steven M. Rosand, Jonathan Singer, Daniel Schwab, Kristen Selim, Magdy Meschia, James Eckman, Mark H. Silliman, Scott Brown, Devon Worrall, W. Bradford Tirschwell, David Gage, Brian F. CA Genes Cerebral Hemorrhage Anticoag TI Exploiting Common Genetic Variation to Make Anticoagulation Safer SO STROKE LA English DT Editorial Material DE anticoagulation ID ATRIAL-FIBRILLATION; CYTOCHROME P450CYP2C9-ASTERISK-2; CYP2C9-ASTERISK-3 ALLELES; HEMORRHAGIC COMPLICATIONS; INTRACEREBRAL HEMORRHAGE; BLEEDING COMPLICATIONS; WARFARIN THERAPY; RISK; CYP2C9; POLYMORPHISMS C1 [Chang, Yuchiao; Cortellini, Lynelle; Greenberg, Steven M.; Rosand, Jonathan; Singer, Daniel; Schwab, Kristen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Selim, Magdy] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Meschia, James] Mayo Clin, Jacksonville, FL 32224 USA. [Eckman, Mark H.] Univ Cincinnati, Cincinnati, OH 45221 USA. [Silliman, Scott] Univ Florida, Gainesville, FL 32611 USA. [Brown, Devon] Univ Michigan, Ann Arbor, MI 48109 USA. [Worrall, W. Bradford] Univ Virginia, Charlottesville, VA 22903 USA. [Tirschwell, David] Univ Washington, Seattle, WA 98195 USA. [Gage, Brian F.] Washington Univ, St Louis, MO 63130 USA. RP Chang, YC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2009 VL 40 IS 3 BP S64 EP S66 DI 10.1161/STROKEAHA.108.533190 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 410QW UT WOS:000263594200020 ER PT J AU Furie, K Gwinn, K AF Furie, Karen Gwinn, Katrina TI Introduction to Genetics SO STROKE LA English DT Editorial Material DE genetics C1 [Furie, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Furie, Karen] Harvard Univ, Sch Med, Boston, MA USA. [Gwinn, Katrina] Baylor Coll Med, Houston, TX 77030 USA. RP Furie, K (reprint author), J Philip Kistler MGH Stroke Res Ctr, MGH Stroke Serv, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM kfurie@partners.org RI Gwinn, Katrina/C-2508-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2009 VL 40 IS 3 BP S56 EP S56 DI 10.1161/STROKEAHA.108.534941 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 410QW UT WOS:000263594200017 ER PT J AU Guo, SZ Lo, EH AF Guo, Shuzhen Lo, Eng H. TI Dysfunctional Cell-Cell Signaling in the Neurovascular Unit as a Paradigm for Central Nervous System Disease SO STROKE LA English DT Article DE neuroprotection; cell-cell signaling ID BLOOD-BRAIN-BARRIER; AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURONS; MOUSE MODEL; NEURODEGENERATIVE DISEASE; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; MUTANT HUNTINGTIN; EXTEND SURVIVAL; GLIAL-CELLS AB The fundamental premise of neuroprotection has historically focused on the prevention of neuronal death. However, despite tremendous advances in the molecular biology of intraneuronal mechanisms and pathways, a clinically effective neuroprotectant does not yet exist. This problem is especially clear for stroke, for which a large number of neuroprotection trials have failed. The concept of the neurovascular unit emphasizes that cell-cell signaling among the various neuronal, glial, and vascular compartments underlies the homeostasis of normal brain function. Conversely, dysfunctional signaling within the neurovascular unit should contribute to disease. This minireview surveys recent data that support this basic idea, with examples drawn from experimental models broadly relevant to stroke and neurodegeneration. (Stroke. 2009;40[suppl 1]:S4-S7.) C1 [Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA USA. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, MGH E 149-2401,13th St, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU National Institute of Neurological Disorders and Stroke; American Heart Association FX This study was supported in part by grants from the National Institute of Neurological Disorders and Stroke and the American Heart Association. NR 39 TC 70 Z9 73 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2009 VL 40 IS 3 BP S4 EP S7 DI 10.1161/STROKEAHA.108.534388 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 410QW UT WOS:000263594200003 PM 19064781 ER PT J AU Lo, EH Rosenberg, GA AF Lo, Eng H. Rosenberg, Gary A. TI The Neurovascular Unit in Health and Disease Introduction SO STROKE LA English DT Editorial Material DE cerebrovascular disease; astrocytes; blood-brain barrier; vascular cognitive impairment; Huntingtin; pericytes ID BLOOD-BRAIN-BARRIER; VASCULAR DEMENTIA C1 [Rosenberg, Gary A.] Univ New Mexico, Hlth Sci Ctr, Dept Neurol, Albuquerque, NM 87131 USA. Harvard Univ, Sch Med, Boston, MA USA. [Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rosenberg, Gary A.] Univ New Mexico, Hlth Sci Ctr, Dept Neurosci & Cell Biol, Albuquerque, NM 87131 USA. [Rosenberg, Gary A.] Univ New Mexico, Hlth Sci Ctr, Dept Physiol, Albuquerque, NM 87131 USA. RP Rosenberg, GA (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Neurol, Albuquerque, NM 87131 USA. EM grosenberg@salud.unm.edu FU NINDS NIH HHS [R01 NS021169-12, R01 NS021169, R01 NS045847, R01 NS045847-01] NR 14 TC 41 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2009 VL 40 IS 3 BP S2 EP S3 DI 10.1161/STROKEAHA.108.534404 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 410QW UT WOS:000263594200002 PM 19064779 ER PT J AU Ramoni, RB Himes, BE Sale, MM Furie, KL Ramoni, MF AF Ramoni, Rachel Badovinac Himes, Blanca E. Sale, Michele M. Furie, Karen L. Ramoni, Marco F. TI Predictive Genomics of Cardioembolic Stroke SO STROKE LA English DT Article DE Bayesian networks; genetics; ischemic stroke; prediction; risk factors ID GENETIC POLYMORPHISMS; FAMILY-HISTORY; SUBTYPES AB Cardioembolic stroke is a complex disease resulting from the interaction of numerous factors. Using data from Genes Affecting Stroke Risk and Outcome Study (GASROS), we show that a multivariate predictive model built using Bayesian networks is able to achieve a predictive accuracy of 86% on the fitted values as computed by the area under the receiver operating characteristic curve relative to that of the individual single nucleotide polymorphism with the highest prognostic performance (area under the receiver operating characteristic curve = 60%). (Stroke. 2009;40[suppl 1]:S67-S70.) C1 [Ramoni, Marco F.] Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. [Ramoni, Rachel Badovinac] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Himes, Blanca E.; Ramoni, Marco F.] Harvard Mit Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA USA. [Sale, Michele M.] Univ Virginia, Dept Med, Charlottesville, VA USA. [Furie, Karen L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Ramoni, MF (reprint author), Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM marco_ramoni@harvard.edu FU NHGRI/National Institutes of Health [R01 HG003354]; National Institute of Dental and Craniofacial Research [K08 DE016956]; National Institute of Neurological Diseases and Stroke [K23 NS042720]; Mallinckrodt GCRC at Massachusetts General Hospital [M01RR-01066]; National Center for Research Resources; National Institutes of Health; Deane Institute of Integrative Research in Stroke and Atrial Fibrillation FX This research was supported, in part, by the NHGRI/National Institutes of Health (R01 HG003354), National Institute of Dental and Craniofacial Research (K08 DE016956), National Institute of Neurological Diseases and Stroke (K23 NS042720), the Mallinckrodt GCRC at Massachusetts General Hospital, grant number M01RR-01066, National Center for Research Resources, National Institutes of Health, and the Deane Institute of Integrative Research in Stroke and Atrial Fibrillation. DNA panels from the National Institute of Neurological Diseases and Stroke Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds) were used in this study. NR 15 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2009 VL 40 IS 3 BP S67 EP S70 DI 10.1161/STROKEAHA.108.533273 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 410QW UT WOS:000263594200021 PM 19064790 ER PT J AU Vosler, PS Chen, J AF Vosler, Peter S. Chen, Jun TI Potential Molecular Targets for Translational Stroke Research SO STROKE LA English DT Editorial Material DE molecular targets; neuroprotection; translational stroke research ID ISCHEMIC-STROKE C1 [Chen, Jun] Univ Pittsburgh, Sch Med, Dept Neurol, BST, Pittsburgh, PA 15213 USA. [Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, BST, S-507, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu FU NINDS NIH HHS [R01 NS045048, R01 NS043802, R01 NS045048-05, R01 NS043802-05, R01 NS044178-05, NS56118, NS44178, R01 NS056118, R01 NS056118-03, NS45048, NS43802, R01 NS036736-11, R01 NS044178, R01 NS036736, NS36736] NR 8 TC 17 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2009 VL 40 IS 3 BP S119 EP S120 DI 10.1161/STROKEAHA.108.533109 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 410QW UT WOS:000263594200039 PM 19064800 ER PT J AU Stearns, AT Balakrishnan, A Rhoads, DB Ashley, SW Tavakkolizadeh, A AF Stearns, Adam T. Balakrishnan, Anita Rhoads, David B. Ashley, Stanley W. Tavakkolizadeh, Ali TI Diurnal expression of the rat intestinal sodium-glucose cotransporter 1 (SGLT1) is independent of local luminal factors SO SURGERY LA English DT Article; Proceedings Paper CT 3rd Annual Academic Surgical Congress CY FEB 12-15, 2008 CL Huntington Beach, CA SP Assoc Acad Surg, Soc Univ Surg ID NA+/GLUCOSE COTRANSPORTER; MESSENGER-RNA; CIRCADIAN RHYTHMICITY; EPITHELIAL-CELLS; ABSORPTION; TRANSPORT; JEJUNUM; CLOCK; GLYCOSYLATION; ADAPTATION AB Background. The intestinal sodium-glucose cotransporter 1 (SGLT1) is responsible for (all secondary active transport of dietary glucose, and it presents a potential therapeutic target for obesity and diabetes. SGLT1 expression varies with a profound diurnal rhythm, matching expression to nutrient intake. The mechanisms entraining this rhythm remain unknown. We investigated the role of local nutrient signals in diurnal SGLT1 entrainment. Methods. Mole Sprague-Dawley rats, which were acclimatized to a 12:12 light:dark cycle, underwent laparotomy with formation of isolated proximal jejunal loops (Thiry-Vella loops). Animals Were recovered for 10 days before harvesting at 4 6-h intervals (Zeilgeber times ZT3, ZT9, ZT15, and ZT21, where ZTO is lights on; n = 6-8). SGLT1 expression was assessed in protein, and mRNA extracts Of mucosa were harvested from both isolated loops (LOOP) and remnant jejunum, (JEJ). Results. Isolated loops were healthy but atrophic with minimal changes to villus architecture. A normal anticipatory rhythm was observed in Sglt1 transcription in both LOOP and JEJ, with the peak signal at ZT9 (2.7 fold, P<.001). Normal diurnal rhythms were also observed in the protein signal, with peak expression in both LOOP and JEJ at ZT9 to 15 (2.1-fold, P<.05). However, an additional more mobile polypeptide hand was also observed in all LOOP samples but not in JEJ samples (61 kDa vs 69 kDa). Enzymatic deglycosylation suggested this to be deglycosylated SGLF1. Conclusion. The persistence of SGLT1 rhythmicity in isolated loops indicates that diurnal induction is independent of local luminal nutrient delivery, and it. suggests a reliance on systemic entrainment pathways. However, local luminal signals may regulate glycosylation and, therefore, the posttranslational handling of SGLT1 (Surgery 2009;145:294-302.) C1 [Stearns, Adam T.; Balakrishnan, Anita; Ashley, Stanley W.; Tavakkolizadeh, Ali] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Stearns, Adam T.; Balakrishnan, Anita; Rhoads, David B.; Ashley, Stanley W.; Tavakkolizadeh, Ali] Harvard Univ, Sch Med, Boston, MA USA. [Stearns, Adam T.] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England. [Balakrishnan, Anita] Univ Liverpool, Sch Clin Sci, Div Gastroenterol, Liverpool L69 3BX, Merseyside, England. [Rhoads, David B.] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. RP Tavakkolizadeh, A (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM atavakkoli@partners.org OI Stearns, Adam/0000-0003-4327-7360 FU NIDDK NIH HHS [P30 DK040561-13, 5 R01 DK047326, P30 DK040561, P30-DK040561, R01 DK047326, R01 DK047326-10S1] NR 39 TC 16 Z9 16 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2009 VL 145 IS 3 BP 294 EP 302 DI 10.1016/j.surg.2008.11.004 PG 9 WC Surgery SC Surgery GA 412PN UT WOS:000263736800007 PM 19231582 ER PT J AU Henry, FP Goyal, NA David, WS Wes, D Bujold, KE Randolph, MA Winograd, JM Kochevar, IE Redmond, RW AF Henry, Francis P. Goyal, Namita A. David, William S. Wes, David Bujold, Kenneth E. Randolph, Mark A. Winograd, Jonathan M. Kochevar, Irene E. Redmond, Robert W. TI Improving electrophysiologic and histologic outcomes by photochemically sealing amnion to the peripheral nerve repair site SO SURGERY LA English DT Article ID BENGAL I 131; ROSE-BENGAL; PENETRATING KERATOPLASTY; COMPRESSIVE NEUROPATHY; CORNEAL INCISIONS; EPITHELIAL-CELLS; MEMBRANE GRAFT; RAT MODEL; PHOTOSENSITIZATION; TRANSPLANTATION AB Background. The surgical approach used today in the repair of peripheral nerve injuries rarely achieves full functional recovery. This study determines whether isolation of the nerve repair site using photochemical tissue bonding (PTB) in combination with human amniotic membrane can improve both functional and histologic recovery. Methods. New Zealand white rabbits (n = 24) underwent transection of the right common Peroneal nerve. Epineural nerve repair was performed using 10-0 nylon sutures. The repair site was then wrapped in a cuff of human amniotic membrane, which either was secured with sutures or sealed using PTB. Standard neurorrhaphy alone was assessed as a control group. Functional recovery was recorded at 30-day intervals postoperatively by electrophysiologic assessment. At 120 days, animals were, killed humanely and nerves harvester for histomorphometry. Results. Nerves healed with amnion wraps and sealed with PTB demonstrated a statistically significant improvement across both functional and histologic parameters. Functional recovery, as measured by repeated electrophysiologic studies over time, revealed a 26.2% improvement over standard neurorrhaphy alone (P<.05). Nerves treated with PTB-sealed amnion wraps had significantly greater (P<.001) axon (5.08 +/- 1.00 mu m) and fiber diameters (7.46 +/- 137 mu m), as well as in myelin thickness (2.39 +/- 0.7 mu m) and the g ratio (axon diameter/fiber diameter ratio; 0.68 +/- 0.07) distal to the repair site compared to standard neurorrhaphy alone (4.98 +/- 1.81 mu m, 6.77 +/- 1.94 mu m, 1.79 +/- 0.42 mu m, and 0.71 +/- 0.09, respectively). Conclusion. Isolation of the repair site using a photochemically sealed amnion wrap improves electrophysiologic and histologic recovery compared to standard suture neurorrhaphy. (Surgery 2009;145:313-21.) C1 [Henry, Francis P.; Bujold, Kenneth E.; Kochevar, Irene E.; Redmond, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Henry, Francis P.; Wes, David; Randolph, Mark A.; Winograd, Jonathan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA 02114 USA. [Goyal, Namita A.; David, William S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuromuscular Diagnost Ctr, Boston, MA 02114 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Thier-224, Boston, MA 02114 USA. EM Redmond@helix.mgh.harvard.edu OI Henry, Francis P./0000-0003-4170-7806 FU Department of Defense, Medical Free Electron Laser Program [F4 9620-01-1-0014]; Bullock-Wellman Fellowship; Wellman Center for Photomedicine FX Supported in part by a grant from the Department of Defense, Medical Free Electron Laser Program (F4 9620-01-1-0014) and the Bullock-Wellman Fellowship, awarded to F.P.H. by the Wellman Center for Photomedicine. NR 44 TC 26 Z9 33 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2009 VL 145 IS 3 BP 313 EP 321 DI 10.1016/j.surg.2008.11.005 PG 9 WC Surgery SC Surgery GA 412PN UT WOS:000263736800009 PM 19231584 ER PT J AU Wasfy, JH AF Wasfy, Jason H. TI Inheriting the values of a profession SO SURGERY LA English DT Editorial Material C1 [Wasfy, Jason H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wasfy, Jason H.] Harvard Univ, Sch Med, Boston, MA USA. RP Wasfy, JH (reprint author), Massachusetts Gen Hosp, Dept Med, 44 Fruit St, Boston, MA 02114 USA. EM jwasfy@partners.org 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 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2009 VL 145 IS 3 BP 335 EP 336 DI 10.1016/j.surg.2008.11.006 PG 2 WC Surgery SC Surgery GA 412PN UT WOS:000263736800012 PM 19231587 ER PT J AU Chia, S Van Cott, EM Raffell, OC Jang, IK AF Chia, Stanley Van Cott, Elizabeth M. Raffell, O. Christopher Jang, Ik-Kyung TI Comparison of activated clotting times obtained using Hemochron and Medtronic analysers in patients receiving anti-thrombin therapy during cardiac catheterisation SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Activated clotting time; antithrombin; cardiac catheterisation; heparins ID PERCUTANEOUS CORONARY INTERVENTION; HEPARIN-INDUCED THROMBOCYTOPENIA; UNFRACTIONATED HEPARIN; ANTICOAGULATION; ARGATROBAN; ANGIOPLASTY; INHIBITORS; TRIALS AB Accurate monitoring of anti-thrombin therapy with activated clotting time (ACT) is important to prevent thrombotic and haemorrhagic complications during cardiac catheterisation. Significant variability in ACT tests exists when different analysers are used. Our objective was to compare ACT results obtained using Hemochron (R) and MedtronicACT PLUS (R) devices and anti-Xa activity in patients undergoing cardiac catheterisation. Thirty-two, patients who received unfractionated heparin or argatroban therapy during cardiac catheterisation were enrolled. Blood sampling was performed to determine ACT values using Hemochron and Medtronic (with high-range cartridges) devices in all patients (n=130 pairs), and anti-Xa activity following heparin administration. In the heparin group,ACT tests (n=95 pairs) showed very good correlation (r=0.84,y=1.3 1 x-0.8 1; p<0.001). However, Hemochron values were consistently higher and the difference more pronounced with increasing ACT (for ACT>150 sec, mean difference 65 +/- 48 sec; p<0.001). Both Hemochron and Medtronic ACT tests correlated well with plasma anti-Xa levels (r=0.85, r=0.81, respectively; p<0.001); Hemochron ACT>300 sec corresponded to anti-Xa>1.48 IU/ml. With concomitant eptifibatide therapy, the divergence in ACT was greater compared to heparin alone. In the argatroban group, ACT tests (n=35 pairs) demonstrated excellent correlation (r=0.94, Y=0.61x+79.9; p<0.001). In contrast to the heparin group,ACT values were higher with Medtronic compared to Hemochron. Therefore, despite good correlation between Hemochron and Medtronic ACT results, and strong association with anti-Xa activity, Medtronic ACT values were consistently lower compared to Hemochron following heparin anticoagulation. Paradoxically, Medtronic ACT results were higher after argatroban therapy. Understanding this discrepancy is crucial when using ACT to guide invasive cardiac procedures. C1 [Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Ctr Heart, Boston, MA 02114 USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Ctr Heart, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ijang@partners.org FU Cardiology Division, Massachusetts General Hospital; Health Manpower Development Program Fellowship; National Medical Research Council Medical Research Fellowship, Singapore FX Funding was provided by the Cardiology Division, Massachusetts General Hospital. S. Chia is the recipient of the Health Manpower Development Program Fellowship and National Medical Research Council Medical Research Fellowship, Singapore. NR 22 TC 9 Z9 10 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD MAR PY 2009 VL 101 IS 3 BP 535 EP 540 DI 10.1160/TH08-08-0528 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 421TY UT WOS:000264382400020 PM 19277416 ER PT J AU Keil, DE McGuinn, WD Dudley, AC EuDaly, JG Gilkeson, GS Peden-Adams, MM AF Keil, Deborah E. McGuinn, W. David Dudley, Andrew C. EuDaly, Jackie G. Gilkeson, Gary S. Peden-Adams, Margie M. TI N,N,-Diethyl-m-Toluamide (DEET) Suppresses Humoral Immunological Function in B6C3F1 Mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE DEET; immune function; Gulf War Illness; PFC response; T-cell subpopulations ID LISTERIA-MONOCYTOGENES INFECTION; REPELLENT N,N-DIETHYL-M-TOLUAMIDE DEET; NATURAL-KILLER-CELLS; GULF-WAR SYNDROME; PYRIDOSTIGMINE BROMIDE; INSECT REPELLENT; HOST-RESISTANCE; TOXIC ENCEPHALOPATHY; MOSQUITO REPELLENTS; RISK-ASSESSMENT AB N,N-diethyl-meta-toluamide (DEET) is a particularly effective broad-spectrum insect repellent used commonly in recreational, occupational and military environments. Due to its widespread use and suggested link to Gulf War Illness, this study examined the immunotoxicity of DEET. Adult female B6C3F1 mice were injected sc for 14 days with DEET at 0, 7.7, 15.5, 31, or 62 mg/kg/day. Due to differences in the dermal absorption of DEET between mice and humans, this study eliminated this confounding factor by utilizing sc injection and measured circulating blood levels of DEET to assess bioavailability from sc administration. Effects on lymphocyte proliferation, natural killer cell activity, thymus and spleen weight and cellularity, the antibody plaque-forming cell (PFC) response, and thymic and splenic CD4/CD8 lymphocyte subpopulations were assessed 24 h after the last dose. No effect was observed in lymphocyte proliferation, natural killer cell activity, thymic weight, splenic weight, thymic cellularity, or splenic cellularity. Significant decreases were observed in the percentage of splenic CD4-/CD8- and CD4+/CD8- lymphocytes but only at the 62 mg DEET/kg/day treatment level and not in absolute numbers of these cells types. Additionally, significant decreases in the antibody PFC response were observed following treatment with 15.5, 31, or 62 mg DEET/kg/day. Pharmacokinetic (PK) data from the current study indicate 95% bioavailability of the administered dose. Therefore, it is likely that DEET exposure ranges applied in this study are comparable to currently reported occupational usage. Together, the evidence for immunosuppression and available PK data suggest a potential human health risk associated with DEET in the occupational or military environments assuming similar sensitivity between human and rodent responses. C1 [Keil, Deborah E.] Univ Nevada, Clin Sci Lab, Las Vegas, NV 89154 USA. US FDA, Silver Spring, MD 20993 USA. [EuDaly, Jackie G.; Peden-Adams, Margie M.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29412 USA. [McGuinn, W. David; EuDaly, Jackie G.; Gilkeson, Gary S.; Peden-Adams, Margie M.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29412 USA. [Dudley, Andrew C.; EuDaly, Jackie G.; Peden-Adams, Margie M.] Med Univ S Carolina, Marine Biomed & Environm Sci Ctr, Charleston, SC 29412 USA. [Gilkeson, Gary S.] Ralph Johnson VAMC, Med Res Serv, Charleston, SC 29425 USA. RP Keil, DE (reprint author), Univ Nevada, Clin Sci Lab, 4505 Maryland Pkwy,Box 453021, Las Vegas, NV 89154 USA. EM deborah.keil@unlv.edu OI Keil, Deborah/0000-0002-5787-8514 FU U. S. Department of Defense [DAMD17-99-1-9013] FX U. S. Department of Defense (grant # DAMD17-99-1-9013) to D. E. K.; the Veterans Administration Medical Research Service to G. S. G.; and internal support from UNLV. NR 74 TC 7 Z9 8 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2009 VL 108 IS 1 BP 110 EP 123 DI 10.1093/toxsci/kfp001 PG 14 WC Toxicology SC Toxicology GA 410VO UT WOS:000263606600012 PM 19141786 ER PT J AU Brown, D Breton, S Ausiello, DA Marshansky, V AF Brown, Dennis Breton, Sylvie Ausiello, Dennis A. Marshansky, Vladimir TI Sensing, Signaling and Sorting Events in Kidney Epithelial Cell Physiology SO TRAFFIC LA English DT Review DE acidification; aquaporin 2; endocytosis; exocytosis; intercalated cell; phosphorylation; principal cell; proximal tubule; vasopressin receptor; V-ATPase ID VACUOLAR H+-ATPASE; NEPHROGENIC DIABETES-INSIPIDUS; AQUAPORIN-2 WATER CHANNEL; RENAL PROXIMAL TUBULE; VASOPRESSIN TYPE-2 RECEPTOR; PROTEIN-COUPLED RECEPTORS; V-ATPASE; COLLECTING DUCT; INTERCALATED CELLS; MEMBRANE TRAFFICKING AB The kidney regulates body fluid, ion and acid/base homeostasis through the interaction of a host of channels, transporters and pumps within specific tubule segments, specific cell types and specific plasma membrane domains. Furthermore, renal epithelial cells have adapted to function in an often unique and challenging environment that includes high medullary osmolality, acidic pHs, variable blood flow and constantly changing apical and basolateral 'bathing' solutions. In this review, we focus on selected protein trafficking events by which kidney epithelial cells regulate body fluid, ion and acid-base homeostasis in response to changes in physiological conditions. We discuss aquaporin 2 and G-protein-coupled receptors in fluid and ion balance, the vacuolar H(+)-adenosine triphosphatase (V-ATPase) and intercalated cells in acid/base regulation and acidification events in the proximal tubule degradation pathway. Finally, in view of its direct role in vesicle trafficking that we outline in this study, we propose that the V-ATPase itself should, under some circumstances, be considered a fourth category of vesicle 'coat' protein (COP), alongside clathrin, caveolin and COPs. C1 [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. EM brown.dennis@mgh.harvard.edu FU National Institutes of Health (NIH) [DK38452, DK42956, HD40793] FX We are grateful to the National Institutes of Health (NIH) for supporting the work from our own laboratory that is included in this review. Much of this work was carried out under the auspices of an NIH Program Project Grant, DK38452, as well as individual RO1 grants DK42956 (D. B.) and HD40793 (S. B.). We are grateful to our many excellent colleagues who have made such important contributions to our work on trafficking processes in the kidney over the years. We apologize that we could not cite many important original articles because of space constraints. NR 85 TC 41 Z9 43 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD MAR PY 2009 VL 10 IS 3 BP 275 EP 284 DI 10.1111/j.1600-0854.2008.00867.x PG 10 WC Cell Biology SC Cell Biology GA 404GJ UT WOS:000263138900003 PM 19170982 ER PT J AU Wu, JD Lin, DW Page, ST Lundgren, AD True, LD Plymate, SR AF Wu, Jennifer D. Lin, Daniel W. Page, Stephanie T. Lundgren, Ashley D. True, Lawrence D. Plymate, Stephen R. TI Oxidative DNA damage in the prostate may predispose men to a higher risk of prostate cancer SO TRANSLATIONAL ONCOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; ATM ACTIVATION; T-CELLS; ANTICANCER BARRIER; MEDICAL CASTRATION; NKG2D RECEPTOR; NK CELLS; EXPRESSION; LIGANDS; STRESS AB DNA damage has been associated with prostate cancer risk. Men who were referred for initial prostate biopsy for elevated prostate-specific antigen or abnormal digital rectal examination are often found with no cancer but have a higher risk of developing prostate cancer than the general population of men in their lifetime In this study, we investigated whether DNA damage is one of the factors that predispose these men referred for prostate biopsies to a higher risk of prostate cancer. We found significantly elevated levels of 8-oxo-2-deoxyguanosine immunoreactivity in the prostates of the referred men (n = 50) in comparison to the control prostates of men (n = 32) with no indication for referral for prostate biopsy. Twelve of these control men were healthy middle-aged men and 20 of them were older men whose conditions were diagnosed with bladder cancer but with normal serum prostate-specific antigen and digital rectal examination and no evidence of prostate disease. In all the 8-oxo-2-deoxyguanosine-positive prostates, we detected phosphorylation of the ataxia telangiectasia mutated kinase and expression of the immune-stimulatory molecule MIC in the prostate epithelium These data suggest that 1) oxidative DNA damage has occurred in the "referred" but pathologically normal prostates, indicating that these prostates may be subjected to genomic instability and eventually neoplastic transformation; 2) in response to DNA damage, two surveillance pathways, represented by ataxia telangiectasia mutated phosphorylation and induction of the NKG2D ligand MIC, were activated to prevent tumorigenesis. C1 [Wu, Jennifer D.; Page, Stephanie T.; Lundgren, Ashley D.; Plymate, Stephen R.] Univ Washington, Dept Med, Seattle, WA USA. [Lin, Daniel W.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [True, Lawrence D.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Plymate, Stephen R.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Wu, JD (reprint author), Box 359755,325 9th Ave, Seattle, WA 98104 USA. FU Department of Defense New Invastigator's [W81XWH-04-1-0577]; National Institutes of Health Temin [1 K01 CA 116002]; Pacific Northwest Prostate Cancer SPORE Pilot [P50-CA97186]; National Institutes of Health [K23DK65083, CA 085859]; Veterans Affairs Research Service FX Supported by Department of Defense New Invastigator's Award (W81XWH-04-1-0577), National Institutes of Health Temin Award (1 K01 CA 116002), the Pacific Northwest Prostate Cancer SPORE Pilot Award (P50-CA97186) to J Wu and S.R. Plymate; National Institutes of Health Award (K23DK65083) to D Lin, and Veterans Affairs Research Service and National Institutes of Health awards (CA 085859) to S.R. Plymate NR 37 TC 8 Z9 8 U1 0 U2 4 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD MAR PY 2009 VL 2 IS 1 BP 39 EP 45 DI 10.1593/tlo.08217 PG 7 WC Oncology SC Oncology GA 529WW UT WOS:000272550900005 PM 19252750 ER PT J AU Horner, BM Randolph, MA Duran-Struuck, R Hirsh, EL Ferguson, KK Teague, AGS Butler, PEM Huang, CA AF Horner, B. M. Randolph, M. A. Duran-Struuck, R. Hirsh, E. L. Ferguson, K. K. Teague, A. G. S. Butler, P. E. M. Huang, C. A. TI Induction of Tolerance to an Allogeneic Skin Flap Transplant in a Preclinical Large Animal Model SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st American Conference on Reconstructive Transplantation Surgery CY JUL 18-19, 2008 CL Philadelphia, PA ID ALLOGRAFT TOLERANCE AB Clinical composite tissue allotransplantation can adequately reconstruct defects that are not possible by other means. However, immunosuppressant toxicity limits the use of these techniques. Clinical attempts to reduce the amount of immunosuppression required by induction of an immunologically permissive state have so far been unsuccessful. The aim of this study was to induce tolerance in a preclinical large animal model. Donor hematopoietic stem cell (HSC) engraftment was induced by T-cell depletion, irradiation, and a short course of cyclosporine administered to the recipient, along with a hematopoietic cell infusion from a single haplotype major histocompatibility complex (MHC) mismatched donor. Skin was then allotransplanted from the donor. Both primarily vascularized skin flaps and secondarily vascularized conventional skin grafts were allotransplanted to investigate if the mode of transplantation affected outcome. Control animals received the skin allotransplants without conditioning. Tolerance was defined as no evidence of rejection at 90 days following transplantation. Conventional skin grafts only achieved prolonged survival (<65 days) in HSC-engrafted animals (P <.01). In contrast, there was indefinite skin flap survival with the achievement of tolerance in HSC-engrafted animals; this was confirmed on histology with donor-specific unresponsiveness on MLR and CML. Furthermore, a conventional skin donor graft subsequently applied to an animal tolerant to a skin flap was not rejected and did not trigger skin flap rejection. To our knowledge, this is the first time skin tolerance has been achieved across a MHC barrier in a large animal model. This is a significant step toward the goal of clinical skin tolerance induction. C1 [Horner, B. M.; Randolph, M. A.] Massachusetts Gen Hosp, Dept Surg, Plast Surg Res Lab, Boston, MA 02114 USA. [Horner, B. M.; Butler, P. E. M.] UCL, Royal Free Hosp, Dept Plast Surg, London, England. [Duran-Struuck, R.; Hirsh, E. L.; Ferguson, K. K.; Teague, A. G. S.; Huang, C. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RP Randolph, MA (reprint author), Massachusetts Gen Hosp, Dept Surg, Plast Surg Res Lab, WAC 453, Boston, MA 02114 USA. EM marandolph@partners.org OI Ferguson, Kelly/0000-0001-8467-3250; Butler, Peter/0000-0001-7419-1493 FU NCRR NIH HHS [K01 RR024466]; NIAID NIH HHS [R01 AI084657-02, F32 AI009589, F32 AI009589-03, R01 AI084657, R01 AI084657-01A2, R01 AI084657-02S1, R01 AI084657-02S2, R01 AI084657-03] NR 7 TC 25 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD MAR PY 2009 VL 41 IS 2 BP 539 EP 541 DI 10.1016/j.transproceed.2009.01.015 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 427OX UT WOS:000264789700019 PM 19328921 ER PT J AU Sitkovsky, MV AF Sitkovsky, Michail V. TI T regulatory cells: hypoxia-adenosinergic suppression and re-direction of the immune response SO TRENDS IN IMMUNOLOGY LA English DT Review ID INDUCIBLE FACTOR-1-ALPHA; RECEPTOR PROTECTS; GENE-EXPRESSION; DENDRITIC CELLS; FOXP3; CD73; MACROPHAGES; ACTIVATION; TOLERANCE; MONOPHOSPHATE AB T regulatory cells (Treg cells) suppress immune responses to maintain self tolerance, but they also protect cancerous tissues. I propose a model to potentially unify the diverse functions of Treg cells. This assumes that Treg cells provide a complementary immunological arm to a physiological tissue-protecting mechanism, driven by low oxygen tension (i.e. hypoxia) in inflamed or cancerous tissues. The cAMP-elevating A2A and A2B adenosine receptors, hypoxia inducible transcription factor 1 alpha (HIF), the cAMP response element (CRE)- and hypoxia response element (HRE)-mediated transcription in Treg and effector cells have key roles in this model. Both the T cell receptor (TCR) -triggered- and HRE- and CRE-driven activities of Treg cells are required to achieve a maximal level of immune suppression. C1 [Sitkovsky, Michail V.] Northeastern Univ, New England Inflammat & Tissue Protect Inst, Boston, MA 02115 USA. [Sitkovsky, Michail V.] Harvard Inst Med, Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sitkovsky, MV (reprint author), Northeastern Univ, New England Inflammat & Tissue Protect Inst, 360 Hungtington Ave, Boston, MA 02115 USA. EM m.sitkovsky@neu.edu FU National Institutes of Health [RO1 CA 111985, 1101 CA 112561, R21 AT 002788] FX This work was supported by National Institutes of Health grants RO1 CA 111985, 1101 CA 112561 and R21 AT 002788 to M.V.S. NR 55 TC 77 Z9 80 U1 4 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD MAR PY 2009 VL 30 IS 3 BP 102 EP 108 DI 10.1016/j.it.2008.12.002 PG 7 WC Immunology SC Immunology GA 423SL UT WOS:000264515900002 PM 19201652 ER PT J AU Spires-Jones, TL Stoothoff, WH de Calignon, A Jones, PB Hyman, BT AF Spires-Jones, Tara L. Stoothoff, William H. de Calignon, Alix Jones, Phiflip B. Hyman, Bradley T. TI Tau pathophysiology in neurodegeneration: a tangled issue SO TRENDS IN NEUROSCIENCES LA English DT Review ID PAIRED HELICAL FILAMENT; PROGRESSIVE SUPRANUCLEAR PALSY; TRANSGENIC MOUSE MODEL; PROTEIN KINASE-II; INHERITED DEMENTIA FTDP-17; SPLICE-SITE MUTATIONS; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; CASPASE CLEAVAGE; FRONTOTEMPORAL DEMENTIA AB Neurodegenerative tauopathies are marked by their common pathologic feature of aggregates formed of hyperphosphorylated tau protein, which are associated with synapse and neuronal loss. Changes in tau conformation result in both loss of normal function and gain of fibrillogenicity that leads to aggregation. Here, we discuss the pathophysiology of tau and emerging evidence of how changes in this protein might ultimately lead to neuronal death. In particular, based on recent evidence, we propose that a non-apoptotic caspase-associated form of death is occurring in tauopathy. C1 [Hyman, Bradley T.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Moss, Mark/0000-0001-7330-3836; Jones, Phillip/0000-0003-0525-6323; Spires-Jones, Tara/0000-0003-2530-0598 FU National Institutes of Health [AG08487, AG00277]; John D. French Foundation Fellowship; Alzheimer's Drug Discovery Foundation; Alzheimer's Association Pioneer Award [EB00768] FX We are supported by National Institutes of Health (www.nih.gov) grants AG08487 and AG00277, a John D. French Foundation Fellowship (www.jdfaf.org), the Alzheimer's Drug Discovery Foundation (www.alzdiscovery.org) and Alzheimer's Association Pioneer Award and grant EB00768 (www.alz.org). NR 114 TC 145 Z9 155 U1 1 U2 15 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 2009 VL 32 IS 3 BP 150 EP 159 DI 10.1016/j.tins.2008.11.007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 426BA UT WOS:000264681200004 PM 19162340 ER PT J AU Brown, JA Rodin, DM Harisinghani, M Dahl, DM AF Brown, James A. Rodin, David M. Harisinghani, Mukesh Dahl, Douglas M. TI Impact of preoperative endorectal MRI stage classification on neurovascular bundle sparing aggressiveness and the radical prostatectomy positive margin rate SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Magnetic resonance imaging (MRI); Endorectal MRI; Prostatectomy; Laparoscopic prostatectomy; Neurovascular bundle sparing; Nerve sparing; Surgical margins; Positive margins ID RETROPUBIC PROSTATECTOMY; SURGICAL MARGINS; TRANSRECTAL ULTRASONOGRAPHY; EXTRAPROSTATIC CANCER; EXTENSION; PREDICTION; EXCISION; BIOPSY; REGION; TUMOR AB Introduction: Inability to accurately determine extracapsular extension (ECE) and neurovascular bundle (NVB) tumor involvement prior to or during radical prostatectomy (RP) remains problematic. Laparoscopic prostatectomy has the additional challenge of lack of tactile tumor assessment. Our goal is to determine the impact of preoperative endorectal magnetic resonance imaging (eMRI) staging upon NVB sparing aggressiveness and the RP surgical margin rate. Methods: Sixty-two patients who underwent RP (46 laparoscopic and 16 open retropubic) from March 2002 to February 2005 and had preoperative eMRI staging were evaluated to determine the impact of apparent ECE upon NVB sparing aggressiveness and subsequent RP margin positivity. Results: Thirty-four (83%) of 41 pathologic stage T2 tumors and 8 (38%) of 21 pathologic stage T3 tumors were accurately classified by eMRI. Eighty-three percent of eMRI stage T2 classified tumors underwent bilateral NVB sparing, whereas only 55% of laparoscopic (P = 0.09) and 75% of open RP (P = 1.0) tumors classified as eMRI stage T3 underwent bilateral NVB sparing. The overall surgical margin positive rate was 30% for laparoscopic and 25% for open RPs. Pathologic T3 tumors erroneously classified as T2 demonstrated a trend towards greater positive margin rate (54% vs. 13% (P = 0.07], 63% vs. 14% laparoscopic RP [P = 0.12]). Eighty percent of clinical Tic, Gleason score 6, pathologic T3 tumors classified erroneously as T2 by eMRI had positive margins. Conclusions: The usefulness of endorectal MRI in detecting ECE is limited. Patients with eMRIs suggesting no ECE demonstrated a trend towards more aggressive NVB sparing and an increased positive surgical margin rate at laparoscopic prostatectomy. (C) 2009 Elsevier Inc. All rights reserved. C1 [Brown, James A.] Med Coll Georgia, Div Urol, Augusta, GA 30912 USA. [Rodin, David M.; Harisinghani, Mukesh; Dahl, Douglas M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brown, JA (reprint author), Med Coll Georgia, Div Urol, Augusta, GA 30912 USA. EM jbrown@smail.umaryland.edu NR 21 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD MAR-APR PY 2009 VL 27 IS 2 BP 174 EP 179 DI 10.1016/j.urolonc.2008.04.009 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 424OL UT WOS:000264575900022 PM 18640062 ER PT J AU Olumi, AF DeWolf, WC AF Olumi, Aria F. DeWolf, William C. TI The hybrid of basic science and clinical training for the urologic oncologist: Necessity or waste? SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Urologic oncology; Training; Basic science; Clinical medicine ID SCIENTIST AB Objective: To examine the necessity and adequacy of basic science training for Urologic oncology training programs. Methods: Evaluated whether urology physician scientist's are adequately trained in the basic sciences. Results: The current urologic oncology training system does not adequately train physician scientists. We propose a major reform to define, train, and maintain the urology physician scientists. Conclusions: Urology physician scientists have played a major role in advancement of urologic oncology. Major reform is necessary, if we wish to continue to successfully train urologic oncology physician scientists. (c) 2009 Elsevier Inc. All rights reserved. C1 [Olumi, Aria F.] Harvard Univ, Sch Med, Dept Urol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [DeWolf, William C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. RP Olumi, AF (reprint author), Harvard Univ, Sch Med, Dept Urol, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM aolumi@partners.org NR 6 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD MAR-APR PY 2009 VL 27 IS 2 BP 205 EP 207 DI 10.1016/j.urolonc.2008.07.027 PG 3 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 424OL UT WOS:000264575900029 PM 19285235 ER PT J AU Hay, JW Lawler, E Yucel, K Guo, A Balzer, T Gaziano, JM Scranton, RE AF Hay, Joel W. Lawler, Elizabeth Yucel, Kent Guo, Amy Balzer, Thomas Gaziano, John Michael Scranton, Richard E. TI Cost Impact of Diagnostic Imaging for Lower Extremity Peripheral Vascular Occlusive Disease SO VALUE IN HEALTH LA English DT Article DE contrast-enhanced magnetic resonance imaging; diagnostic imaging; digital subtraction imaging; peripheral vascular disease; VA treatment costs ID INTERMITTENT CLAUDICATION; WORK-UP; COMPLICATIONS; ANGIOGRAPHY AB The evaluation of peripheral vascular disease in the primary care setting is routinely performed by contrast-enhanced magnetic resonance angiography (CE-MRA) and digital subtraction angiography (DSA). However, limited data are available on the relative costs and clinical outcomes following these diagnostic procedures. The objective of this study is to assess and compare costs associated with diagnostic imaging in peripheral vascular occlusive disease (PAOD). US veterans (n = 19,209) with CE-MRA or DSA for the assessment of PAOD from fiscal year (FY) 1999 to FY 2004. Main outcome measure(s) using the Department of Veterans Affairs' (VA) costing algorithms, cost, and log-cost of interventions (e.g., revascularization, stent, angioplasty), amputations or mortality rates within 30/90 days and 1 year of DSA or CE-MRA were compared, and adjusted for patient characteristics and disease severity using multivariate regression. Imaging modality selection bias was evaluated with propensity score, instrumental variables, and Heckman methods using untransformed costs and log-costs with smearing retransformation. Initial CE-MRA imaging was significantly more likely among patients with prior renal disease or bypass surgery [odds ratio (OR) > 2; P < 0.001], and less likely among patients with prior amputation, peripheral vascular disease (PVD), claudication, or other cardiovascular disease (OR < 0.7; P < 0.001). After adjusting for endogenous choice of initial imaging modality, 30-day treatment costs were US$3500-$4300 lower (P < 0.001) for patients with initial CE-MRA. Eighty-two percent of DSA imaging patients had no additional procedures or events within 30 days, and 65% at 90 days. Less than 3.2% (3.6%) of patients had any repeat imaging within 30 (90) days of initial imaging. Relative to DSA, CE-MRA imaging was associated with substantial treatment episode savings, beyond the US$950 direct savings in imaging cost per procedure. Substituting CE-MRA for DSA among those not planning or requiring any follow-up procedures within 30 days, could have reduced outpatient imaging costs by up to 55%, and reduced VA system costs by US$13.2 million over the six-year period. C1 [Hay, Joel W.] Univ So Calif, Dept Pharmaceut Econ & Policy, Los Angeles, CA 90089 USA. [Lawler, Elizabeth; Gaziano, John Michael; Scranton, Richard E.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Lawler, Elizabeth; Gaziano, John Michael; Scranton, Richard E.] VA Boston Healthcare Syst, Boston, MA USA. [Yucel, Kent] Tufts Med Ctr, Dept Radiol, Boston, MA USA. [Guo, Amy; Balzer, Thomas] Bayer Healthcare Pharmaceuticals, Wayne, NJ USA. [Balzer, Thomas] Bayer Healthcare Pharmaceut, Wayne, NJ USA. RP Hay, JW (reprint author), Univ So Calif, Dept Pharmaceut Econ & Policy, CHP 140,1540 E Alcazar St, Los Angeles, CA 90089 USA. EM jhay@usc.edu NR 15 TC 4 Z9 4 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAR-APR PY 2009 VL 12 IS 2 BP 262 EP 266 DI 10.1111/j.1524-4733.2008.00438.x PG 5 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 408WY UT WOS:000263467500011 PM 18657093 ER PT J AU Kramer, BJ Jouldjian, S Washington, DL Harker, JO Saliba, D Yano, EM AF Kramer, B. Josea Jouldjian, Stella Washington, Donna L. Harker, Judith O. Saliba, Debra Yano, Elizabeth M. TI HEALTH CARE FOR AMERICAN INDIAN AND ALASKA NATIVE WOMEN The Roles of the Veterans Health Administration and The Indian Health Service SO WOMENS HEALTH ISSUES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; AMBULATORY-CARE; PREVALENCE; AFFAIRS; VA; AVAILABILITY; DISPARITIES; COMMUNITY; TRAUMA; ACCESS AB Background. Many American Indian and Alaska Native (AIAN) women serve in the military and are eligible for healthcare from both the Veterans Health Administration (VHA) and the Indian Health Service (IHS). Little was known about these women's patterns of health care utilization when VHA and IHS executed a resource-sharing agreement in 2003 to improve access and health outcomes. Objective. We sought to describe women's healthcare utilization in VHA and IHS. Methods. We conducted a descriptive secondary data analysis of linked IHS and VHA administrative records from fiscal years 2002 and 2003 for women among all IHS beneficiaries who were veterans or used VHA for health care (n = 64,746). Results. Among these IHS beneficiaries, 4,338 (6.7%) were female veterans and 1,518 (2.8%) were female nonveterans. Comparing IHS services to VHA, the VHA provided the majority of outpatient specialty care to veterans, providing 89.9% of diagnostic and imaging services, 84.4% of mental health care, and 78.1%, of physical medicine and rehabilitation. Conversely, the IHS provided the majority of ambulatory and inpatient care for obstetrics and gynecology to these veterans. Dual users received primary care from both organizations. Nonveterans generally accessed VHA under sharing agreements and their use of health care was generally limited to outpatient diagnostic and imaging. Conclusions. The VHA seems to supplement healthcare provided by the IHS for female AIAN veterans, as well as for a small proportion of nonveterans. The VHA and the IHS have developed specialized and complementary expertise, which might be aligned to serve the needs of female AIAN veterans. C1 [Kramer, B. Josea; Saliba, Debra] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, Sepulveda, CA 91343 USA. [Kramer, B. Josea; Saliba, Debra] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr Med, Los Angeles, CA 90095 USA. [Jouldjian, Stella; Washington, Donna L.; Harker, Judith O.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Saliba, Debra; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, Hlth Serv Res Ctr Excellence, Sepulveda, CA USA. [Saliba, Debra] RAND Corp, Santa Monica, CA USA. RP Kramer, BJ (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, 16111 Plummer St 11E, Sepulveda, CA 91343 USA. EM Josea.Kramer@va.gov NR 38 TC 3 Z9 3 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAR-APR PY 2009 VL 19 IS 2 BP 135 EP 143 DI 10.1016/j.whi.2008.11.002 PG 9 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 423CA UT WOS:000264472800007 PM 19272564 ER PT J AU Bates-Jensen, B Guihan, M Chin, A AF Bates-Jensen, Barbara Guihan, Marylou Chin, Amy TI ASSESSING A BIOPHYSICAL DEVICE TO PREDICT PRESSURE ULCERS IN SPINAL CORD INJURY SO WOUND REPAIR AND REGENERATION LA English DT Meeting Abstract C1 [Bates-Jensen, Barbara] Univ Calif Los Angeles, Sch Nursing & Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Guihan, Marylou; Chin, Amy] Northwestern Univ, Ctr Management Complex Chron Care, Edward Hines Jr VA Hosp, Inst Healthcare Studies, Chicago, IL 60611 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 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2009 VL 17 IS 2 BP A45 EP A45 PG 1 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 418ZJ UT WOS:000264188600158 ER PT J AU Raugi, G Reiber, G AF Raugi, Gregory Reiber, Gayle TI REDUCTION IN TIME TO HEALING AND AMPUTATIONS IN RURAL CARE SETTINGS SO WOUND REPAIR AND REGENERATION LA English DT Meeting Abstract C1 [Raugi, Gregory; Reiber, Gayle] VA Puget Sound, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2009 VL 17 IS 2 BP A20 EP A20 PG 1 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 418ZJ UT WOS:000264188600056 ER PT J AU Wu, GX Hu, WG Shahsafaei, A Song, WP Dobarro, M Sukhova, GK Bronson, RR Shi, GP Rother, RP Halperin, JA Qin, XB AF Wu, Gongxiong Hu, Weiguo Shahsafaei, Aliakbar Song, Wenping Dobarro, Martin Sukhova, Galina K. Bronson, Rod R. Shi, Guo-Ping Rother, Russell P. Halperin, Jose A. Qin, Xuebin TI Complement Regulator CD59 Protects Against Atherosclerosis by Restricting the Formation of Complement Membrane Attack Complex SO CIRCULATION RESEARCH LA English DT Article DE CD59; complement; endothelial dysfunction; atherosclerosis; occlusive coronary atherosclerosis and vulnerable plaque ID RECEPTOR-DEFICIENT MICE; SMOOTH-MUSCLE-CELLS; MYOCARDIAL-INFARCTION; KNOCKOUT MICE; REDUCES ATHEROSCLEROSIS; VASCULAR COMPLICATIONS; LESION DEVELOPMENT; C5B-9; ACTIVATION; MOUSE AB Complement is a central effector system within the immune system and is implicated in a range of inflammatory disorders. CD59 is a key regulator of complement membrane attack complex (MAC) assembly. The atherogenic role of terminal complement has long been suspected but is still unclear. Here, we demonstrate that among mice deficient in apolipoprotein (Apo)E, the additional loss of murine CD59 (mCd59ab(-/-)/ApoE(-/-)) accelerated advanced atherosclerosis featuring occlusive coronary atherosclerosis, vulnerable plaque, and premature death and that these effect could be attenuated by overexpression of human CD59 in the endothelium. Complement inhibition using a neutralizing anti-mouse C5 antibody attenuated atherosclerosis in mCd59ab(-/-)/ApoE(-/-) mice. Furthermore, MAC mediated endothelial damage and promoted foam cell formation. These combined results highlight the atherogenic role of MAC and the atheroprotective role of CD59 and suggest that inhibition of MAC formation may provide a therapeutic approach for the treatment of atherosclerosis. (Circ Res. 2009;104:550-558.) C1 [Wu, Gongxiong; Hu, Weiguo; Halperin, Jose A.; Qin, Xuebin] Harvard Univ, Sch Med, Lab Translat Res, Cambridge, MA 02139 USA. [Wu, Gongxiong; Hu, Weiguo; Shahsafaei, Aliakbar; Song, Wenping; Dobarro, Martin; Sukhova, Galina K.; Shi, Guo-Ping; Halperin, Jose A.; Qin, Xuebin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wu, Gongxiong] Sun Yat Sen Univ, Sch Med, Dept Med Neurobiol & Neuroanat, Guangzhou 510275, Guangdong, Peoples R China. [Bronson, Rod R.] Dana Farber Harvard Univ, Sch Med, Boston, MA USA. [Rother, Russell P.] Alex Pharmaceut Inc, Cheshire, CT USA. RP Qin, XB (reprint author), Harvard Univ, Sch Med, Lab Translat Res, 1 Kendall Sq,Bldg 600,3rd Floor, Cambridge, MA 02139 USA. EM xuebin_qin@hms.harvard.edu FU NIH [R01 DK060979, R01 AI061174]; Scientist Development Grant from the American Heart Association [0435483N] FX This work was supported by NIH grants R01 DK060979 (to J.A.H.) and R01 AI061174 (to X.Q.) and by a Scientist Development Grant from the American Heart Association 0435483N (to X.Q.). NR 48 TC 62 Z9 65 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD FEB 27 PY 2009 VL 104 IS 4 BP 550 EP U260 DI 10.1161/CIRCRESAHA.108.191361 PG 22 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 413CX UT WOS:000263771600018 PM 19131645 ER PT J AU Zhou, XH Li, F Kong, L Chodosh, J Cao, W AF Zhou, Xiaohong Li, Feng Kong, Li Chodosh, James Cao, Wei TI Anti-inflammatory effect of pigment epithelium-derived factor in DBA/2J mice SO MOLECULAR VISION LA English DT Article ID NECROSIS-FACTOR-ALPHA; OPTIC-NERVE HEAD; RETINAL GANGLION-CELLS; FIBRILLARY ACIDIC PROTEIN; CEREBELLAR GRANULE CELLS; MOUSE MODEL; MATRIX METALLOPROTEINASES; ISCHEMIC-INJURY; MOTOR-NEURONS; IRIS ATROPHY AB Purpose: Glaucoma is the second leading cause of blindness. The ultimate cause of vision loss in glaucoma is thought to be retinal ganglion cell (RGC) death. Neuroprotection of RGC is therefore an important goal of glaucoma therapy. Several lines of evidence suggest that pigment epithelium derived factor (PEDF) is a potent anti-angiogenic, neuroprotective, and anti-inflammatory factor for neurons. In this study, we examined the potential role of PEDF in protection of RGC in the DBA/2J mouse, an animal model of inherited glaucoma. Methods: DBA/2J mice at two months of age were transfected intravitreally with adeno-associated virus (AAV)-PEDF or AAV-green fluorescent protein (AAV-GFP). RGC and nerve fiber layer protection were evaluated in retinal cross sections. Biochemical alterations in the retinas of DBA/2J mice in response to intravitreal transfection of PEDF were also examined by reverse transcriptase PCR (RT-PCR) and western blot. Cellular localization of PEDF and glial fibrillary acidic protein (GFAP) was determined by immunohistochemistry. Visual acuity was determined by optomotor testing. Results: PEDF protein levels in the retina and optic nerves of DBA/2J mice declined with age. The expression of tumor necrosis factor (TNF), GFAP, and interleukin-18 (IL-18) increased with age in the retina and optic nerve of DBA/2J mice. Intravitreal PEDF transfection in DBS/2J mice reduced loss of RGC and nerve fiber layer, delayed vision loss, and reduced TNF, IL-18, and GFAP expression in the retina and optic nerve. Conclusions: Transduced PEDF potently and efficaciously reduces RGC loss and vision decline in DBA/2J mice, possibly via the reduction of TNF and IL-18, and downregulation of GFAP. The anti-inflammatory effect of PEDF represents a novel approach to the prevention of glaucomatous RGC death. C1 [Zhou, Xiaohong; Li, Feng; Kong, Li; Chodosh, James; Cao, Wei] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Dean McGee Eye Inst, Oklahoma City, OK USA. RP Chodosh, J (reprint author), Massachusetts Eye & Ear Infirm, Howe Lab, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu FU USA Public Health Service [P30 EY12190, P20RR017703-030007, EY014427]; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK FX Supported by USA Public Health Service grants P30 EY12190, P20RR017703-030007, and EY014427, and a an unrestricted grant from Research to Prevent Blindness, New York, NY to the Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK. NR 60 TC 21 Z9 22 U1 2 U2 7 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD FEB 27 PY 2009 VL 15 IS 43-46 BP 438 EP 450 PG 13 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 427NU UT WOS:000264786800002 PM 19247457 ER PT J AU Cheng, G Tse, J Jain, RK Munn, LL AF Cheng, Gang Tse, Janet Jain, Rakesh K. Munn, Lance L. TI Micro-Environmental Mechanical Stress Controls Tumor Spheroid Size and Morphology by Suppressing Proliferation and Inducing Apoptosis in Cancer Cells SO PLOS ONE LA English DT Article AB Background: Compressive mechanical stress produced during growth in a confining matrix limits the size of tumor spheroids, but little is known about the dynamics of stress accumulation, how the stress affects cancer cell phenotype, or the molecular pathways involved. Methodology/Principal Findings: We co-embedded single cancer cells with fluorescent micro-beads in agarose gels and, using confocal microscopy, recorded the 3D distribution of micro-beads surrounding growing spheroids. The change in micro-bead density was then converted to strain in the gel, from which we estimated the spatial distribution of compressive stress around the spheroids. We found a strong correlation between the peri-spheroid solid stress distribution and spheroid shape, a result of the suppression of cell proliferation and induction of apoptotic cell death in regions of high mechanical stress. By compressing spheroids consisting of cancer cells overexpressing anti-apoptotic genes, we demonstrate that mechanical stress-induced apoptosis occurs via the mitochondrial pathway. Conclusions/Significance: Our results provide detailed, quantitative insight into the role of micro-environmental mechanical stress in tumor spheroid growth dynamics, and suggest how tumors grow in confined locations where the level of solid stress becomes high. An important implication is that apoptosis via the mitochondrial pathway, induced by compressive stress, may be involved in tumor dormancy, in which tumor growth is held in check by a balance of apoptosis and proliferation. C1 [Cheng, Gang; Tse, Janet; Jain, Rakesh K.; Munn, Lance L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Cheng, Gang; Tse, Janet; Jain, Rakesh K.; Munn, Lance L.] Harvard Univ, Sch Med, Boston, MA USA. [Tse, Janet] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Cheng, G (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. EM lance@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NIH [P01CA80124, R01CA085140, R01CA126642] FX This work was supported by NIH grants P01CA80124, R01CA085140 and R01CA126642. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 108 Z9 108 U1 4 U2 32 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 27 PY 2009 VL 4 IS 2 AR e4632 DI 10.1371/journal.pone.0004632 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437LA UT WOS:000265487800014 PM 19247489 ER PT J AU Kwiatkowski, TJ Bosco, DA LeClerc, AL Tamrazian, E Vanderburg, CR Russ, C Davis, A Gilchrist, J Kasarskis, EJ Munsat, T Valdmanis, P Rouleau, GA Hosler, BA Cortelli, P de Jong, PJ Yoshinaga, Y Haines, JL Pericak-Vance, MA Yan, J Ticozzi, N Siddique, T McKenna-Yasek, D Sapp, PC Horvitz, HR Landers, JE Brown, RH AF Kwiatkowski, T. J., Jr. Bosco, D. A. LeClerc, A. L. Tamrazian, E. Vanderburg, C. R. Russ, C. Davis, A. Gilchrist, J. Kasarskis, E. J. Munsat, T. Valdmanis, P. Rouleau, G. A. Hosler, B. A. Cortelli, P. de Jong, P. J. Yoshinaga, Y. Haines, J. L. Pericak-Vance, M. A. Yan, J. Ticozzi, N. Siddique, T. McKenna-Yasek, D. Sapp, P. C. Horvitz, H. R. Landers, J. E. Brown, R. H., Jr. TI Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis SO SCIENCE LA English DT Article ID RNA-BINDING PROTEIN; PRO-ONCOPROTEIN TLS/FUS; TARDBP MUTATIONS; TLS; IDENTIFICATION; TRANSCRIPTION; LIPOSARCOMA; ACTIVATION; NUCLEAR; DISEASE AB Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders. C1 [Kwiatkowski, T. J., Jr.; Bosco, D. A.; LeClerc, A. L.; Tamrazian, E.; Russ, C.; Davis, A.; Hosler, B. A.; Yan, J.; Ticozzi, N.; McKenna-Yasek, D.; Sapp, P. C.; Landers, J. E.; Brown, R. H., Jr.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Bosco, D. A.; LeClerc, A. L.; Landers, J. E.; Brown, R. H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Vanderburg, C. R.] Massachusetts Gen Hosp, Massachusetts Gen Inst Neurodegenerat, Charlestown, MA 02129 USA. [Russ, C.] MIT, Broad Inst, Cambridge, MA 02141 USA. [Gilchrist, J.] Rhode Isl Hosp, Dept Neurol, Providence, RI 02912 USA. [Kasarskis, E. J.] Univ Kentucky, Vet Affairs Med Ctr, Dept Neurol, Lexington, KY 40511 USA. [Munsat, T.] Tufts Univ, Tufts New England Med Ctr, Dept Neurol, Boston, MA 02111 USA. [Valdmanis, P.; Rouleau, G. A.] Univ Montreal, Ctr Hosp, Ctr Rech, Dept Neurol, Montreal, PQ H2L 4M1, Canada. [Cortelli, P.] Univ Bologna, Dipartimento Sci Neurol, Neurol Clin, I-40123 Bologna, Italy. [de Jong, P. J.; Yoshinaga, Y.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. [Haines, J. L.] Vanderbilt Univ, Ctr Human Genet Res Mol Physiol & Biophys, Nashville, TN 37240 USA. [Pericak-Vance, M. A.] Miami Inst Human Genet, Miami, FL 33136 USA. [Yan, J.; Siddique, T.] NW Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Yan, J.; Siddique, T.] NW Feinberg Sch Med, Dept Mol & Cell Biol, Chicago, IL 60611 USA. [Ticozzi, N.] Univ Milan, Sch Med, Dept Neurol, Dino Ferrari Ctr,Ist Auxol Italiano, I-20149 Milan, Italy. [Sapp, P. C.; Horvitz, H. R.] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. RP Kwiatkowski, TJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM tkwiatkowski@partners.org; robert.brown@umassmed.edu RI Haines, Jonathan/C-3374-2012; Ticozzi, Nicola/K-8094-2016; OI Ticozzi, Nicola/0000-0001-5963-7426; Cortelli, Pietro/0000-0002-3633-8818 FU NIH [NS050557, NS050641]; Angel Fund; ALS Therapy Alliance; ALS Association Project ALS; Al-Athel ALS Research Foundation; Pierre L. de Bourgknecht ALS Research Foundation; The Les Turner ALS Foundation; Vena E. Schaff ALS Research Fund; Harold Post Research Professorship; Herbert and Florence C. Wenske Foundation; Ralph and Marian Falk Medical Research Trust; The David C. Asselin M.D. Memorial Fund; Les Turner ALS Foundation/Herbert C. Wenske Foundation Professorship; Help America Foundation; ALS Therapy Alliance, Inc.; Howard Hughes Medical Institute FX We gratefully acknowledge I. Carr (University of Leeds, UK) for support with AutoSNPa and IBDfinder software, A. Storey for assistance with sequencing, C. LeClerc for genealogical investigations, and D. Crowe for administrative assistance. This work was supported by NIH grants NS050557 (R.H.B. and T.K.) and NS050641 (T.S., R.H.B., J.L. H., and M.P.-V.). R.H.B. also receives support from the Angel Fund, the ALS Therapy Alliance, the ALS Association Project ALS, the Al-Athel ALS Research Foundation, and the Pierre L. de Bourgknecht ALS Research Foundation. T.S. also receives support from The Les Turner ALS Foundation, Vena E. Schaff ALS Research Fund, Harold Post Research Professorship, Herbert and Florence C. Wenske Foundation, Ralph and Marian Falk Medical Research Trust, The David C. Asselin M.D. Memorial Fund, Les Turner ALS Foundation/Herbert C. Wenske Foundation Professorship, Help America Foundation and the ALS Therapy Alliance, Inc. H.R.H. is an investigator of and was supported by the Howard Hughes Medical Institute. R.H.B. is a cofounder of AviTx Inc., which targets development of ALS therapies. R.H.B. and T.J.K. have applied for a patent covering FUS mutations in ALS. We dedicate this report to the memories of Jimmy and Christopher Kennedy, Sharon Timlin, and Ginny Delvecchio. NR 22 TC 987 Z9 1008 U1 5 U2 74 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 27 PY 2009 VL 323 IS 5918 BP 1205 EP 1208 DI 10.1126/science.1166066 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411XT UT WOS:000263687600036 ER PT J AU Kuchibhotla, KV Lattarulo, CR Hyman, BT Bacskai, BJ AF Kuchibhotla, Kishore V. Lattarulo, Carli R. Hyman, Bradley T. Bacskai, Brian J. TI Synchronous Hyperactivity and Intercellular Calcium Waves in Astrocytes in Alzheimer Mice SO SCIENCE LA English DT Article ID MOUSE MODEL; AMYLOID DEPOSITION; BETA-PLAQUES; IN-VIVO; DISEASE; PROPAGATION AB Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time-lapse imaging revealed that calcium transients in astrocytes were more frequent, synchronously coordinated across long distances, and uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-beta plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-beta deposits, there exists a more general astrocyte-based network response to focal pathology. C1 [Kuchibhotla, Kishore V.; Lattarulo, Carli R.; Hyman, Bradley T.; Bacskai, Brian J.] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. [Kuchibhotla, Kishore V.] Harvard Univ, Program Biophys, Cambridge, MA 02138 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, 114 16th St, Charlestown, MA 02129 USA. EM bbacskai@partners.org FU NIH [EB000768, AG08487, NS580752] FX We thank K. O. Ohki and R. C. Reid for assistance with the multicell bolus loading technique. This work was supported by NIH grants EB000768 (B.J.B.), AG08487 (B.T.H.), and NS580752 (K.V.K.). NR 24 TC 266 Z9 275 U1 6 U2 26 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 27 PY 2009 VL 323 IS 5918 BP 1211 EP 1215 DI 10.1126/science.1169096 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411XT UT WOS:000263687600038 PM 19251629 ER PT J AU Breimer, ME Rydberg, L Jackson, AM Lucas, DP Zachary, AA Melancon, JK Von Visger, J Pelletier, R Saidman, SL Williams, WW Holgersson, J Tyden, G Klintmalm, GK Coultrup, S Sumitran-Holgersson, S Grufman, P AF Breimer, Michael E. Rydberg, Lennart Jackson, Annette M. Lucas, Donna P. Zachary, Andrea A. Melancon, Joseph K. Von Visger, Jon Pelletier, Ronald Saidman, Susan L. Williams, Winfred W., Jr. Holgersson, Jan Tyden, Gunnar Klintmalm, Goeran K. Coultrup, Sonnya Sumitran-Holgersson, Suchitra Grufman, Per TI Multicenter Evaluation of a Novel Endothelial Cell Crossmatch Test in Kidney Transplantation SO TRANSPLANTATION LA English DT Article DE Histocompatibility; Crossmatch; Humoral allograft rejection; Endothelium; kidney transplantation; Alloantibodies ID RENAL-ALLOGRAFT REJECTION; NON-HLA ANTIBODIES; ORGAN-TRANSPLANTATION; FLOW-CYTOMETRY; CARDIAC TRANSPLANTATION; ACCELERATED REJECTION; GRAFT-SURVIVAL; ANTIGENS; ALLOANTIBODIES; CLASSIFICATION AB Background. Despite their clinical importance, clinical routine tests to detect anti-endothelial cell antibodies (AECA) in organ transplantation have not been readily available. This Multicenter prospective kidney transplantation trial evaluates the efficacy of a novel endothelial cell crossmatch (ECXM) test to detect donor-reactive AECA associated with kidney allograft rejection. Methods. Pretransplant serum samples from 147 patients were tested for AECA by a novel flow cytometric crossmatch technique (XM-ONE) using peripheral blood endothelial progenitor cells as targets. Patient enrolment was based on acceptance for transplantation determined by donor lymphocyte crossmatch results. Results. Donor-reactive AECA were found in 35 of 147 (24%) patients. A significantly higher proportion of patients with a positive ECXM had rejections (16 of 35, 46%) during the follow-up of at least 3 months compared with those without AECA (13 of 112, 12%; P<0.00005). Both IgG and IgM AECAs were associated with graft rejections. Mean serum creatinine levels were significantly higher in patients with a positive ECXM test at 3 and 6 months posttransplant. Conclusions. XM-ONE is quick, easy to perform on whole blood samples and identifies patients at risk for rejection and reduced graft function not identified by conventional lymphocyte crossmatches. C1 [Breimer, Michael E.] Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Surg, Sahlgrenska Acad, Gothenburg, Sweden. [Rydberg, Lennart] Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Transfus Med & Clin Chem, Sahlgrenska Acad, Gothenburg, Sweden. [Jackson, Annette M.; Lucas, Donna P.; Zachary, Andrea A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Melancon, Joseph K.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Von Visger, Jon] Ohio State Univ, Med Ctr, Dept Med, Columbus, OH 43210 USA. [Pelletier, Ronald] Ohio State Univ, Med Ctr, Dept Surg, Columbus, OH 43210 USA. [Saidman, Susan L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Williams, Winfred W., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Holgersson, Jan] Karolinska Univ Hosp, Div Clin Immunol & Transfus Med, Karolinska Inst, S-14186 Huddinge, Stockholm, Sweden. [Tyden, Gunnar; Sumitran-Holgersson, Suchitra] Karolinska Univ Hosp Huddinge, Karolinska Inst, Div Transplantat Surg, Stockholm, Sweden. [Klintmalm, Goeran K.; Coultrup, Sonnya] Baylor Univ, Med Ctr, Transplantat Serv, Dallas, TX 75246 USA. [Grufman, Per] AbSorber AB, Stockholm, Sweden. RP Holgersson, J (reprint author), Karolinska Univ Hosp, Div Clin Immunol & Transfus Med, Karolinska Inst, F79, S-14186 Huddinge, Stockholm, Sweden. EM jan.holgersson@ki.se NR 32 TC 65 Z9 67 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 27 PY 2009 VL 87 IS 4 BP 549 EP 556 DI 10.1097/TP.0b013e3181949d4e PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 411IQ UT WOS:000263643400014 PM 19307793 ER PT J AU Craig, TJ Petzel, R AF Craig, Thomas J. Petzel, Robert TI Management perspectives on research contributions to practice through collaboration in the U. S. Veterans Health Administration: QUERI Series SO IMPLEMENTATION SCIENCE LA English DT Article ID QUALITY-OF-CARE AB The Quality Enhancement Research Initiative (QUERI) is a unique quality improvement program designed to connect health services researchers to Veterans Health Administration (VHA) management and operations, as well as to provide the science and initiative for making change. Through this process, QUERI stakeholders have learned that success and impact in improving healthcare quality and outcomes largely depends on coordination and collaboration among numerous VHA programs and organizations working to develop and implement evidence-based clinical policies, practices, and quality improvement strategies. This Commentary discusses some of these collaborative efforts and perceived successes in achieving common goals from the viewpoints of two closely involved VHA Operations/Support stakeholders. The Commentary is part of a Series of articles documenting implementation science frameworks and tools developed by the U. S. Department of Veterans Affairs Quality Enhancement Research Initiative (QUERI). C1 [Petzel, Robert] US Dept Vet Affairs Midwest Hlth Care Network, Minneapolis, MN USA. [Craig, Thomas J.] US Dept Vet Affairs, Vet Hlth Adm, Off Qual & Performance, Washington, DC USA. RP Petzel, R (reprint author), US Dept Vet Affairs Midwest Hlth Care Network, Minneapolis, MN USA. EM tlc1963@earthlink.net; Robert.Petzel@va.gov NR 10 TC 5 Z9 5 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD FEB 26 PY 2009 VL 4 AR 8 DI 10.1186/1748-5908-4-8 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 433KK UT WOS:000265202500001 PM 19245708 ER PT J AU Hartnick, CJ Barth, WH Cote, CJ Albrecht, MA Grant, PE Geyer, JT Harris, NL AF Hartnick, Christopher J. Barth, William H., Jr. Cote, Charles J. Albrecht, Meredith A. Grant, P. Ellen Geyer, Julia T. Harris, Nancy Lee TI A Pregnant Woman with a Large Mass in the Fetal Oral Cavity Foregut-duplication cyst, arising from the ventral surface of the tongue SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INTRAPARTUM TREATMENT PROCEDURE; SURGERY; HYPOPHARYNX; TRACT C1 [Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Barth, William H., Jr.] Massachusetts Gen Hosp, Dept Maternal & Fetal Med, Boston, MA 02114 USA. [Cote, Charles J.; Albrecht, Meredith A.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Grant, P. Ellen] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Geyer, Julia T.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. [Barth, William H., Jr.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Cote, Charles J.; Albrecht, Meredith A.] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Grant, P. Ellen] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Geyer, Julia T.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 21 TC 3 Z9 3 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 26 PY 2009 VL 360 IS 9 BP 913 EP 921 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 411CD UT WOS:000263624700012 PM 19246364 ER PT J AU Smouse, JH Cibas, ES Janne, PA Joshi, VA Zou, KH Lindeman, NI AF Smouse, Jason H. Cibas, Edmund S. Jaenne, Pasi A. Joshi, Victoria A. Zou, Kelly H. Lindeman, Neal I. TI EGFR Mutations Are Detected Comparably in Cytologic and Surgical Pathology Specimens of Nonsmall Cell Lung Cancer SO CANCER CYTOPATHOLOGY LA English DT Article DE cytology; epidermal growth factor receptor; nonsmall cell lung cancer; surgical pathology ID GROWTH-FACTOR RECEPTOR; GEFITINIB; INHIBITOR; TRIAL; SENSITIVITY; THERAPY; IMPACT AB BACKGROUND: Somatic mutations in the epidermal growth factor receptor (EGFR) are present in similar to 10% of nonsmall cell lung cancers, and higher in never-smokers, women, and Asians. Small in-frame deletions in exon 19 (similar to 45%) and L858R mutation in exon 21 (similar to 40%) predict response to treatment with tyrosine kinase inhibitors, whereas some others herald resistance. Direct sequencing of tumor DNA detects all EGFR mutations, but is limited by interference from nonmalignant cells within the samples. Concern over such interference has discouraged testing cytologic samples, but the adequacy of cytologic specimens for EGFR sequencing has not been studied, METHODS: EGFR sequencing of surgical and cytologic specimens at Brigham and Women's Hospital over the past 2 years was reviewed. Of 239 specimens, 227 (95%) were surgical, and 12 (5%) were cytologic (fine needle aspirations, pleural fluids, bronchial washings, and bronchoalveolar lavages). RESULTS: Sixty-three (28%) surgical specimens showed EGFR mutations, whereas 143 (63%) were negative, 8 (3.5%) failed, and 14 (6.2%) were inconclusive (negative result in a heterogeneous sample). Seven (58%) cytologic specimens showed EGFR Mutations, whereas 4 (33%) were negative, and 1 (8.3%) was inconclusive. Cytologic specimens were more likely to have a mutation than surgical specimens (P .02). There was no significant difference in the frequency of inconclusive results. CONCLUSIONS., Cytologic specimens are suitable for EGFR sequencing and show comparable sensitivity for mutation detection as compared with surgical specimens. The suitability of a sample should be determined on a case-by-case basis, and cytologic samples should not be dismissed as inadequate without a thorough review. Cancer (Cancer Cytopathol) 2009;117:67-72. (C) 2009 American Cancer Society. C1 [Smouse, Jason H.; Cibas, Edmund S.; Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Smouse, Jason H.; Cibas, Edmund S.; Jaenne, Pasi A.; Joshi, Victoria A.; Zou, Kelly H.; Lindeman, Neal I.] Harvard Univ, Sch Med, Boston, MA USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Thorac Oncol, Boston, MA 02115 USA. [Joshi, Victoria A.] Harvard Partners Healthcare Ctr Genet & Genom, Boston, MA USA. RP Lindeman, NI (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 2-217 Days, Boston, MA 02115 USA. EM nlindeman@partners.org NR 20 TC 106 Z9 109 U1 1 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD FEB 25 PY 2009 VL 117 IS 1 BP 67 EP 72 DI 10.1002/cncy.20011 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA 407XW UT WOS:000263398600012 PM 19347832 ER PT J AU Capellini, I McNamara, P Preston, BT Nunn, CL Barton, RA AF Capellini, Isabella McNamara, Patrick Preston, Brian T. Nunn, Charles L. Barton, Robert A. TI Does Sleep Play a Role in Memory Consolidation? A Comparative Test SO PLOS ONE LA English DT Article ID PHYLOGENETIC ANALYSIS; EVOLUTION; MAMMALS; BRAIN; AMYGDALA; SPECIALIZATION; PRIMATES; SYSTEMS AB Sleep is a pervasive characteristic of mammalian species, yet its purpose remains obscure. It is often proposed that 'sleep is for the brain', a view that is supported by experimental studies showing that sleep improves cognitive processes such as memory consolidation. Some comparative studies have also reported that mammalian sleep durations are higher among more encephalized species. However, no study has assessed the relationship between sleep and the brain structures that are implicated in specific cognitive processes across species. The hippocampus, neocortex and amygdala are important for memory consolidation and learning and are also in a highly actived state during sleep. We therefore investigated the evolutionary relationship between mammalian sleep and the size of these brain structures using phylogenetic comparative methods. We found that evolutionary increases in the size of the amygdala are associated with corresponding increases in NREM sleep durations. These results are consistent with the hypothesis that NREM sleep is functionally linked with specializations of the amygdala, including perhaps memory processing. C1 [Capellini, Isabella; Barton, Robert A.] Univ Durham, Dept Anthropol, Durham, England. [McNamara, Patrick] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McNamara, Patrick] Boston VA Healthcare Syst, Boston, MA USA. [Preston, Brian T.; Nunn, Charles L.] Harvard Univ, Dept Anthropol, Cambridge, MA 02138 USA. [Nunn, Charles L.] Max Planck Inst Evolutionary Anthropol, Leipzig, Germany. [Nunn, Charles L.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. RP Capellini, I (reprint author), Univ Durham, Dept Anthropol, Durham, England. EM Isabella.Capellini@durham.ac.uk RI Capellini, Isabella/H-4813-2013 OI Capellini, Isabella/0000-0001-8065-2436 FU NIMH [1R01MH070415-01A1]; Max Planck Society FX This work was supported by NIMH grant number 1R01MH070415-01A1 to PM, RB and CN and the Max Planck Society (CN, BP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 12 Z9 13 U1 3 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 25 PY 2009 VL 4 IS 2 AR e4609 DI 10.1371/journal.pone.0004609 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 601TH UT WOS:000278086700019 PM 19240803 ER PT J AU Baldys, A Gooz, M Morinelli, TA Lee, MH Raymond, JR Luttrell, LM Raymond, JR AF Baldys, Aleksander Goeoz, Monika Morinelli, Thomas A. Lee, Mi-Hye Raymond, John R., Jr. Luttrell, Louis M. Raymond, John R., Sr. TI Essential Role of c-Cbl in Amphiregulin-Induced Recycling and Signaling of the Endogenous Epidermal Growth Factor Receptor SO BIOCHEMISTRY LA English DT Article ID CLATHRIN-COATED PITS; EGF RECEPTOR; TYROSINE PHOSPHORYLATION; DOWN-REGULATION; RING FINGER; MEDIATED UBIQUITINYLATION; ENDOCYTIC SYSTEM; EPITHELIAL-CELLS; EARLY ENDOSOMES; UBIQUITINATION AB The intracellular processing of the epidermal growth factor receptor (EGFR) induced by epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) has been studied meticulously, with the former resulting in EGFR degradation and the latter in EGFR recycling to the plasma membrane. However, little is known about how other EGF family growth factors affect the trafficking of the EGFR. Additionally, although both EGF and TGF-alpha have been shown to effectively induce initial c-Cbl (ubiquitin ligase)-mediated ubiquitination of the EGFR, limited information is available regarding the role of c-Cbl in the trafficking and signaling of recycling EGFR. Thus, in this study, we investigated the roles of c-Cbl in endogenous EGFR trafficking and signaling after stimulation with amphiregulin (AR). We demonstrated that a physiological concentration of AR induced recycling of the endogenous EGFR to the plasma membrane, which correlated closely with transient association of the EGFR with c-Cbl and transient EGFR ubiquitination. Most importantly, we used c-Cbl small interfering RNA (siRNA) duplexes and a c-Cbl dominant negative mutant to show that c-Cbl is critical for the efficient transition of the EGFR from early endosomes to a recycling pathway and that c-Cbl regulates the duration of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2 MAPK) phosphorylation. These data support novel functions of c-Cbl in mediating recycling of EGF receptors to the plasma membrane, as well as in mediating the duration of activation (transient vs sustained) of ERK1/2 MAPK phosphorylation. C1 [Baldys, Aleksander; Goeoz, Monika; Morinelli, Thomas A.; Raymond, John R., Jr.; Raymond, John R., Sr.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Lee, Mi-Hye; Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. [Baldys, Aleksander; Goeoz, Monika; Morinelli, Thomas A.; Lee, Mi-Hye; Luttrell, Louis M.; Raymond, John R., Sr.] Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, Charleston, SC 29425 USA. RP Raymond, JR (reprint author), Room 213,Colcock Hall,179 Ashley Ave, Charleston, SC 29425 USA. EM raymondj@musc.edu; raymondj@musc.edu FU Department of Veterans Affairs Merit; Research Enhancement Award Program; National Institutes of Health [DK052448, GM063909]; American Heart Association; Medical University of South Carolina, Division of Nephrology, and Dialysis Clinics, Inc FX This work was supported by Department of Veterans Affairs Merit and Research Enhancement Award Program grants (to J. R. Raymond, Sr.), by National Institutes of Health Grants DK052448 and GM063909, by an American Heart Association (Mid-Atlantic) fellowship (to A.B.), and by a laboratory endowment jointly supported by the Medical University of South Carolina, Division of Nephrology, and Dialysis Clinics, Inc. (to J. R. Raymond Sr.). NR 50 TC 30 Z9 31 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 24 PY 2009 VL 48 IS 7 BP 1462 EP 1473 DI 10.1021/bi801771g PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 408JK UT WOS:000263431100005 PM 19173594 ER PT J AU Collins, P Mosca, L Geiger, MJ Grady, D Kornitzer, M Amewou-Atisso, MG Effron, MB Dowsett, SA Barrett-Connor, E Wenger, NK AF Collins, Peter Mosca, Lori Geiger, Mary Jane Grady, Deborah Kornitzer, Marcel Amewou-Atisso, Messan G. Effron, Mark B. Dowsett, Sherie A. Barrett-Connor, Elizabeth Wenger, Nanette K. TI Effects of the Selective Estrogen Receptor Modulator Raloxifene on Coronary Outcomes in The Raloxifene Use for the Heart Trial Results of Subgroup Analyses by Age and Other Factors SO CIRCULATION LA English DT Article DE coronary disease; hormones; raloxifene; randomized controlled trial; risk factors; women ID HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CONTROLLED-TRIAL; HORMONE REPLACEMENT THERAPY; BREAST-CANCER; PLUS PROGESTIN; CARDIOVASCULAR-DISEASE; CLINICAL-TRIAL; RISK; INITIATION; MENOPAUSE AB Background-The Raloxifene Use for The Heart (RUTH) trial showed that raloxifene, a selective estrogen receptor modulator, had no overall effect on the incidence of coronary events in women with established coronary heart disease or coronary heart disease risk factors. We provide detailed results of the effect of raloxifene on coronary outcomes over time and for 24 subgroups (17 predefined, 7 post hoc). Methods and Results-Postmenopausal women (n = 10 101; mean age, 67 years) were randomized to raloxifene 60 mg/d or placebo for a median of 5.6 years. Coronary outcomes were assessed by treatment group in women with coronary heart disease risk factors and those with established coronary heart disease. Raloxifene had no effect on the incidence of coronary events in any subgroup except in the case of a post hoc age subgroup analysis using age categories defined in the Women's Health Initiative randomized trials. The effect of raloxifene on the incidence of coronary events differed significantly by age ( interaction P = 0.0118). The incidence of coronary events in women < 60 years of age was significantly lower in those assigned raloxifene ( 50 events) compared with placebo ( 84 events; hazard ratio, 0.59; 95% confidence interval, 0.41 to 0.83; P=0.003; absolute risk reduction, 36 per 1000 women treated for 1 year). No difference was found between treatment groups in the incidence of coronary events in women >= 60 and < 70 or >= 70 years of age. Conclusions-In postmenopausal women at increased risk of coronary events, the overall lack of benefit of raloxifene was similar across the prespecified subgroups. (Circulation. 2009; 119: 922-930.) C1 [Collins, Peter] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, London SW3 6NP, England. [Collins, Peter] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6NP, England. [Mosca, Lori] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Geiger, Mary Jane; Amewou-Atisso, Messan G.; Effron, Mark B.; Dowsett, Sherie A.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Grady, Deborah] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. [Kornitzer, Marcel] Free Univ Brussels, Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Brussels, Belgium. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Wenger, Nanette K.] Emory Univ, Sch Med, Atlanta, GA USA. RP Collins, P (reprint author), Univ London Imperial Coll Sci Technol & Med, Royal Brompton & Harefield NHS Trust, Dept Cardiol, Sydney St, London SW3 6NP, England. EM peter.collins@imperial.ac.uk RI Effron, Mark/P-9300-2015 FU Eli Lilly and Co, Indianapolis, Ind FX This study was sponsored by Eli Lilly and Co, Indianapolis, Ind. NR 31 TC 66 Z9 69 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 24 PY 2009 VL 119 IS 7 BP 922 EP 930 DI 10.1161/CIRCULATIONAHA.108.817577 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 410RT UT WOS:000263596500004 PM 19204301 ER PT J AU Brown, LCW Acker, MG Clardy, J Walsh, CT Fischbach, MA AF Brown, Laura C. Wieland Acker, Michael G. Clardy, Jon Walsh, Christopher T. Fischbach, Michael A. TI Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE biosynthesis; natural products; thiazolylpeptides ID BIOSYNTHETIC GENE-CLUSTER; THIOPEPTIDE ANTIBIOTICS; MICROCIN B17; NONRIBOSOMAL PEPTIDES; MICROCOCCIN; SYNTHETASE; BACILLUS; THIOSTREPTON; LACTICIN-481; EVOLUTION AB The thiazolylpeptides are a family of > 50 bactericidal antibiotics that block the initial steps of bacterial protein synthesis. Here, we report a biosynthetic gene cluster for thiocillin and establish that it, and by extension the whole class, is ribosomally synthesized. Remarkably, the C-terminal 14 residues of a 52-residue peptide precursor undergo 13 posttranslational modifications to give rise to thiocillin, making this antibiotic the most heavily posttranslationally-modified peptide known to date. C1 [Brown, Laura C. Wieland; Acker, Michael G.; Clardy, Jon; Walsh, Christopher T.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Brown, Laura C. Wieland; Fischbach, Michael A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Walsh, CT (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM christopher_walsh@hms.harvard.edu; mfischbach@partners.org FU National Institutes of Health Grants [CA24487, CA59021, GM20011, GM49338]; Department of Molecular Biology; Center for Computational and Integrative Biology at Massachusetts General Hospital; Broad Institute of Massachusetts Institute of Technology and Harvard FX This work was supported by National Institutes of Health Grants CA24487 and CA59021 (to J.C.) and GM20011 and GM49338 (to C. T. W.). M. A. F. is supported by the Department of Molecular Biology and the Center for Computational and Integrative Biology at Massachusetts General Hospital. L. C. W. B. is supported by a Scientific Planning and Allocation of Resounces Committee grant from the Broad Institute of Massachusetts Institute of Technology and Harvard. NR 32 TC 87 Z9 88 U1 2 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 24 PY 2009 VL 106 IS 8 BP 2549 EP 2553 DI 10.1073/pnas.0900008106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411ME UT WOS:000263652900017 ER PT J AU Zhu, H Acquaviva, J Ramachandran, P Boskovitz, A Woolfenden, S Pfannl, R Bronson, RT Chen, JW Weissleder, R Housman, DE Charesta, A AF Zhu, Haihao Acquaviva, Jaime Ramachandran, Pranatartiharan Boskovitz, Abraham Woolfenden, Steve Pfannl, Rolf Bronson, Roderick T. Chen, John W. Weissleder, Ralph Housman, David E. Charesta, Al TI Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glioblastoma; mouse model; receptor tyrosine kinase; mTORC1/2; STAT3 ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR; HUMAN GLIOMAS; EXPRESSION; CANCER; GLIOBLASTOMA; REVEALS; CELLS; MTOR AB Glioblastoma multiforme (GBM) is a highly lethal brain tumor for which little treatment is available. The epidermal growth factor receptor (EGFR) signaling pathway is thought to play a crucial role in GBM pathogenesis, initiating the early stages of tumor development, sustaining tumor growth, promoting infiltration, and mediating resistance to therapy. The importance of this pathway is highlighted in the fact that EGFR is mutationally activated in over 50% of GBM tumors. Consistent with this, we show here that concomitant activation of wild-type and/or mutant (vIII) EGFR and ablation of Ink4A/Arf and PTEN tumor suppressor gene function in the adult mouse central nervous system generates a fully penetrant, rapid-onset high-grade malignant glioma phenotype with prominent pathological and molecular resemblance to GBM in humans. Studies of the activation of signaling events in these GBM tumor cells revealed notable differences between wild-type and vIII EGFR-expressing cells. We show that wild-type EGF receptor signals through its canonical pathways, whereas tumors arising from expression of mutant EGFRvIII do not use these same pathways. Our findings provide critical insights into the role of mutant EGFR signaling function in GBM tumor biology and set the stage for testing of targeted therapeutic agents in the preclinical models described herein. C1 [Woolfenden, Steve; Housman, David E.; Charesta, Al] MIT, Dept Biol, Cambridge, MA 02139 USA. [Housman, David E.; Charesta, Al] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Zhu, Haihao; Acquaviva, Jaime; Woolfenden, Steve; Charesta, Al] Tufts Univ, Sch Med, Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Ramachandran, Pranatartiharan; Boskovitz, Abraham; Pfannl, Rolf; Charesta, Al] Tufts Univ, Sch Med, Tufts Med Ctr, Dept Neurosurg, Boston, MA 02111 USA. [Chen, John W.; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Bronson, Roderick T.] Tufts Univ, Sch Vet, Dept Biomed Sci, North Grafton, MA 01536 USA. RP Housman, DE (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dhousman@mit.edu; charest@tufts.edu FU CNS/MGI Pharma Fellowship in Tumor Research; National Institutes of Health [K08HL081170, U54 CA119349]; Cam Neely Foundation FX We thank Drs. Marius Werning and Rudolf Jaenisch (Whitehead Institute, Cambridge, MA) for the CAGGS-Col1 alpha 1 plasmid and E2 ES cells, and Drs. Philip Hinds and Julia Alberta for critical review of the manuscript. We also thank Jenny Chan, Anne Yu, and Greg Wojtkiewicz for experimental assistance. This work was supported in part by a CNS/MGI Pharma Fellowship in Tumor Research (to A. B.); National Institutes of Health Grants K08HL081170 (to J.W.C.) and U54 CA119349 (to D. H., R. W., and A. C.); and The Cam Neely Foundation (A. C.). NR 18 TC 99 Z9 103 U1 2 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 24 PY 2009 VL 106 IS 8 BP 2712 EP 2716 DI 10.1073/pnas.0813314106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411ME UT WOS:000263652900045 PM 19196966 ER PT J AU Cheng, HL Vuong, BQ Basu, U Franklin, A Schwer, B Astarita, J Phan, RT Datta, A Manis, J Alt, FW Chaudhuri, J AF Cheng, Hwei-Ling Vuong, Bao Q. Basu, Uttiya Franklin, Andrew Schwer, Bjoern Astarita, Jillian Phan, Ryan T. Datta, Abhishek Manis, Jjohn Alt, Frederick W. Chaudhuri, Jayanta TI Integrity of the AID serine-38 phosphorylation site is critical for class switch recombination and somatic hypermutation in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE activation-induced deaminase; protein kinase A; R-loop ID INDUCED CYTIDINE DEAMINASE; ANTIBODY DIVERSIFICATION ENZYME; ACTIVATION-INDUCED DEAMINASE; SINGLE-STRANDED-DNA; B-CELLS; REGIONS; TRANSLOCATIONS; MICRORNA-155; MECHANISM; GENOME AB Activation-induced cytidine deaminase (AID) is a single-stranded (ss) DNA-specific cytidine deaminase that initiates Ig heavy chain (IgH) class switch recombination (CSR) and Ig somatic hypermutation (SHM) by deaminating cytidines within, respectively, IgH switch (S) regions and Ig variable region (V) exons. AID that is phosphorylated on serine residue 38 interacts with replication protein A (RPA), a ssDNA binding protein, to promote deamination of transcribed double-stranded DNA in vitro, which, along with other evidence, suggests that AID may similarly gain access to transcribed S regions and V exons in vivo. However, the physiological role of AID phosphorylation at serine residue 38 (S38), and even the requirement for the S38 residue, with respect to CSR or SHM has been debated. To address this issue, we used gene targeting to generate an endogenous mouse AID locus that produces AID in which S38 is substituted with alanine (AID(S38A)), a mutant form of AID that retains similar catalytic activity on ssDNA as WT AID (AID(WT)). B cells homozygous for the AID(S38A) mutation show substantially impaired CSR and SHM, correlating with inability of AID(S38A) to interact with endogenous RPA. Moreover, mice haploinsufficient for AID(S38A) have even more severely impaired CSR when compared with mice haploinsufficient for AID(WT), with CSR levels reduced to nearly background levels. These results unequivocally demonstrate that integrity of the AID S38 phosphorylation site is required for normal CSR and SHM in mice and strongly support a role for AID phosphorylation at S38 and RPA interaction in regulating CSR and SHM. C1 [Cheng, Hwei-Ling; Basu, Uttiya; Franklin, Andrew; Schwer, Bjoern; Phan, Ryan T.; Datta, Abhishek; Manis, Jjohn; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Cheng, Hwei-Ling; Basu, Uttiya; Franklin, Andrew; Schwer, Bjoern; Phan, Ryan T.; Datta, Abhishek; Manis, Jjohn; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Cheng, Hwei-Ling; Basu, Uttiya; Franklin, Andrew; Schwer, Bjoern; Phan, Ryan T.; Datta, Abhishek; Manis, Jjohn; Alt, Frederick W.] Immune Dis Inst, Boston, MA 02115 USA. [Vuong, Bao Q.; Astarita, Jillian; Chaudhuri, Jayanta] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu; chaudhuj@mskcc.org FU National Institutes of Health [AI31541]; Bressler Foundation; Damon Runyon Cancer Research Institute; Leukemia and Lymphoma Society of America; Ellison Medical Foundation/American Federation for Aging Research senior FX We thank Tasuku Honjo for providing us with AID-deficient mice. We thank Aimee Williams, Lisa Aquaviva, and Yuko Fujiwara for technical assistance in generating and maintaining mice for experiments used in this work and Mark Curry of the Dana-Farber Cancer Research Institute for cell sorting. This work was supported by National Institutes of Health Grant AI31541 (to F. W. A.). F. W. A. is an Investigator of the Howard Hughes Medical Institute. J.C. is supported by a Scholars Grant from the Bressler Foundation and a Scholars Grant from the Damon Runyon Cancer Research Institute, U. B. is a Special Fellow of the Leukemia and Lymphoma Society of America, and B. S. is supported by an Ellison Medical Foundation/American Federation for Aging Research senior postdoctoral fellow research grant. NR 38 TC 58 Z9 61 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 24 PY 2009 VL 106 IS 8 BP 2717 EP 2722 DI 10.1073/pnas.0812304106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411ME UT WOS:000263652900046 PM 19196992 ER PT J AU Powell, JR Kim, DH Ausubel, FM AF Powell, Jennifer R. Kim, Dennis H. Ausubel, Frederick M. TI The G protein-coupled receptor FSHR-1 is required for the Caenorhabditis elegans innate immune response SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE host-pathogen interactions; leucine-rich repeat ID FOLLICLE-STIMULATING-HORMONE; TOLL-LIKE RECEPTOR; C-ELEGANS; BACTERIAL PATHOGENS; RECOGNITION; PATHWAY; ACTIVATION; RESISTANCE; INFECTION; DAF-16 AB Innate immunity is an ancient defense system used by both vertebrates and invertebrates. Previously characterized innate immune responses in plants and animals are triggered by detection of pathogens using specific receptors, which typically use a leucine-rich repeat (LRR) domain to bind molecular patterns associated with infection. The nematode Caenorhabditis elegans uses defense pathways conserved with vertebrates; however, the mechanism by which C. elegans detects pathogens is unknown. We screened all LRR-containing transmembrane receptors in C. elegans and identified the G protein-coupled receptor FSHR-1 as an important component of the C. elegans immune response to Gram-negative and Gram-positive bacterial pathogens. FSHR-1 acts in the C. elegans intestine, the primary site of exposure to ingested pathogens. FSHR-1 signals in parallel to the known p38 MAPK pathway but converges to regulate the transcriptional induction of an overlapping but nonidentical set of antimicrobial effectors. FSHR-1 may act generally to boost the nematode immune response, or it may function as a pathogen receptor. C1 [Powell, Jennifer R.; Kim, Dennis H.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Powell, Jennifer R.; Kim, Dennis H.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Powell, Jennifer R.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM ausubel@molbio.mgh.harvard.edu FU National Institutes of Health (NIH) National Center for Research Resources; NIH [P01 AI044220, R01 AI064332]; Burroughs Wellcome Fund; NIH National Institute of Allergy and Infectious Dieases K08 award; Kirschstein National Research Service Award [F32 AI068376] FX We thank Anna Ausubel for technical assistance; and E. Troemel, R. Feinbaum, and J. Irazoqui formanyhelpful discussions and for critical reading of the manuscript. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health (NIH) National Center for Research Resources. This work was supported by NIH grants P01 AI044220 and R01 AI064332 ( to F. M. A.), a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund and an NIH National Institute of Allergy and Infectious Dieases K08 award ( to D. H. K.), and a Ruth L. Kirschstein National Research Service Award postdoctoral fellowship (F32 AI068376 to J. R. P.). NR 36 TC 48 Z9 48 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 24 PY 2009 VL 106 IS 8 BP 2782 EP 2787 DI 10.1073/pnas.0813048106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411ME UT WOS:000263652900057 PM 19196974 ER PT J AU Awano, T Johnson, GS Wade, CM Katz, ML Johnson, GC Taylor, JF Perloski, M Biagi, T Baranowska, I Long, S March, PA Olby, NJ Shelton, GD Khan, S O'Brien, DP Lindblad-Toh, K Coates, JR AF Awano, Tomoyuki Johnson, Gary S. Wade, Claire M. Katz, Martin L. Johnson, Gayle C. Taylor, Jeremy F. Perloski, Michele Biagi, Tara Baranowska, Izabella Long, Sam March, Philip A. Olby, Natasha J. Shelton, G. Diane Khan, Shahnawaz O'Brien, Dennis P. Lindblad-Toh, Kerstin Coates, Joan R. TI Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CU,ZN SUPEROXIDE-DISMUTASE; POSTERIOR COLUMN INVOLVEMENT; GERMAN SHEPHERD DOG; HYALINE INCLUSIONS; MOTOR-NEURONS; ALS; GENE; DISEASE; MICE; RADICULOMYELOPATHY AB Canine degenerative myelopathy (DM) is a fatal neurodegenerative disease prevalent in several dog breeds. Typically, the initial progressive upper motor neuron spastic and general proprioceptive ataxia in the pelvic limbs occurs at 8 years of age or older. If euthanasia is delayed, the clinical signs will ascend, causing flaccid tetraparesis and other lower motor neuron signs. DNA samples from 38 DM-affected Pembroke Welsh corgi cases and 17 related clinically normal controls were used for genome-wide association mapping, which produced the strongest associations with markers on CFA31 in a region containing the canine SOD1 gene. SOD1 was considered a regional candidate gene because mutations in human SOD1 can cause amyotrophic lateral sclerosis (ALS), an adult-onset fatal paralytic neurodegenerative disease with both upper and lower motor neuron involvement. The resequencing of SOD1 in normal and affected dogs revealed a G to A transition, resulting in an E40K missense mutation. Homozygosity for the A allele was associated with DM in 5 dog breeds: Pembroke Welsh corgi, Boxer, Rhodesian ridgeback, German Shepherd dog, and Chesapeake Bay retriever. Microscopic examination of spinal cords from affected dogs revealed myelin and axon loss affecting the lateral white matter and neuronal cytoplasmic inclusions that bind anti-superoxide dismutase 1 antibodies. These inclusions are similar to those seen in spinal cord sections from ALS patients with SOD1 mutations. Our findings identify canine DM to be the first recognized spontaneously occurring animal model for ALS. C1 [Awano, Tomoyuki; Johnson, Gary S.; Katz, Martin L.; Johnson, Gayle C.; Khan, Shahnawaz] Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. [O'Brien, Dennis P.; Coates, Joan R.] Univ Missouri, Dept Vet Med & Surg, Columbia, MO 65211 USA. [Katz, Martin L.] Univ Missouri, Mason Eye Inst, Columbia, MO 65211 USA. [Taylor, Jeremy F.] Univ Missouri, Div Anim Sci, Columbia, MO 65211 USA. [Wade, Claire M.; Perloski, Michele; Biagi, Tara; Lindblad-Toh, Kerstin] 7 Cambridge Ctr, Broad Inst Harvard, Cambridge, MA 02141 USA. [Wade, Claire M.; Perloski, Michele; Biagi, Tara; Lindblad-Toh, Kerstin] 7 Cambridge Ctr, MIT, Cambridge, MA 02141 USA. [Wade, Claire M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Baranowska, Izabella] Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Biomed Ctr, SE-75124 Uppsala, Sweden. [Long, Sam] Univ Penn, Sect Neurol & Neurosurg, Philadelphia, PA 19104 USA. [March, Philip A.] Tufts Univ, Dept Clin Sci, North Grafton, MA 01536 USA. [Olby, Natasha J.] N Carolina State Univ, Dept Clin Sci, Raleigh, NC 27606 USA. [Shelton, G. Diane] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, SE-75124 Uppsala, Sweden. RP Johnson, GS (reprint author), Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. EM johnsongs@missouri.edu OI Wade, Claire/0000-0003-3413-4771 FU American Kennel Club Canine Health Foundation [821, 732]; Swedish Research Council; European Science Foundation FX We thank Dr. Alexander de Lahunta for helpful critique of the manuscript. This work was supported by American Kennel Club Canine Health Foundation Grants 821 and 732, a Research to Prevent Blindness, Inc. unrestricted grant, the Swedish Research Council, and the European Science Foundation. NR 39 TC 125 Z9 129 U1 5 U2 30 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 24 PY 2009 VL 106 IS 8 BP 2794 EP 2799 DI 10.1073/pnas.0812297106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411ME UT WOS:000263652900059 PM 19188595 ER PT J AU Cowen, LE Singh, SD Kohler, JR Collins, C Zaas, AK Schell, WA Aziz, H Mylonakis, E Perfect, JR Whitesell, L Lindquist, S AF Cowen, Leah E. Singh, Sheena D. Koehler, Julia R. Collins, Cathy Zaas, Aimee K. Schell, Wiley A. Aziz, Hamza Mylonakis, Eleftherios Perfect, John R. Whitesell, Luke Lindquist, Susan TI Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antifungal; Aspergillus fumigatus; azole; Candida albicans; drug resistance ID HEAT-SHOCK PROTEINS; DRUG-RESISTANCE; CANDIDA-ALBICANS; CHAPERONE MACHINERY; GALLERIA-MELLONELLA; TRANSPLANT RECIPIENTS; PLASMODIUM-FALCIPARUM; ASPERGILLUS-FUMIGATUS; INVASIVE CANDIDIASIS; AMPHOTERICIN-B AB Invasive fungal infections are a leading cause of mortality among immunocompromised individuals. Treatment is notoriously difficult with the limited armamentarium of antifungal drugs, whose efficacy is compromised by host toxicity, a limited activity spectrum, or the emergence of drug resistance. We previously established that the molecular chaperone Hsp90 enables the emergence and maintenance of fungal drug resistance. For the most prevalent fungal pathogen of humans, Candida albicans, Hsp90 mediates resistance to azoles, which inhibit ergosterol biosynthesis and are the most widely deployed antifungals in the clinic. For the emerging opportunistic pathogen Aspergillus terreus, Hsp90 is required for basal resistance to echinocandins, which inhibit beta(1, 3)-glucan synthesis and are the only new class of antifungals to reach the clinic in decades. Here, we explore the therapeutic potential of Hsp90 inhibitors in fungal disease using a tractable host-model system, larvae of the greater wax moth Galleria mellonella, and a murine model of disseminated disease. Combination therapy with Hsp90 inhibitors that are well tolerated in humans and an azole rescued larvae from lethal C. albicans infections. Combination therapy with an Hsp90 inhibitor and an echinocandin rescued larvae from infections with the most lethal mold, Aspergillus fumigatus. In a murine model of disseminated candidiasis, genetic compromise of C. albicans HSP90 expression enhanced the therapeutic efficacy of an azole. Thus, harnessing Hsp90 provides a much-needed strategy for improving the treatment of fungal disease because it enhances the efficacy of existing antifungals, blocks the emergence of drug resistance, and exerts broad-spectrum activity against diverse fungal pathogens. C1 [Cowen, Leah E.; Singh, Sheena D.; Collins, Cathy] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Koehler, Julia R.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Zaas, Aimee K.; Schell, Wiley A.; Aziz, Hamza; Perfect, John R.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Mylonakis, Eleftherios] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Perfect, John R.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Whitesell, Luke; Lindquist, Susan] MIT, Howard Hughes Med Inst, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Cowen, LE (reprint author), Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada. EM leah.cowen@utoronto.ca; lindquist_admin@wi.mit.edu FU Damon Runyon Cancer Research Foundation [DRG1765-03]; Genzyme Fellowship; Burroughs Wellcome Fund; Canada Research Chair in Microbial Genomics and Infectious Disease; Canadian Institutes of Health Research [MOP-86452]; University of Toronto Open Fellowship; National Institutes of Health/National Institute of Allergies and Infectious Diseases [K08AI065837-04]; Public Health Service [AI73896, AI28388]; G. Harold and Leila Y. Mather Charitable Foundation; Howard Hughes Medical Institute FX We thank Eileen Gorss for A. fumigatus isolates, Sara Vargas for histopathology, and Rochelle Bagatell for caspofungin. L. E. C. was supported by Damon Runyon Cancer Research Foundation Grant DRG1765-03 and a Genzyme Fellowship, and is now supported by a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund, by a Canada Research Chair in Microbial Genomics and Infectious Disease, and by Canadian Institutes of Health Research Grant MOP-86452. S. D. S. is supported by a University of Toronto Open Fellowship; A. K. Z. is supported by National Institutes of Health/National Institute of Allergies and Infectious Diseases Grant K08AI065837-04; and J. R. P. is supported by Public Health Service Grants AI73896 and AI28388. S. L. is supported by the G. Harold and Leila Y. Mather Charitable Foundation and by the Howard Hughes Medical Institute. NR 39 TC 173 Z9 183 U1 3 U2 24 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 24 PY 2009 VL 106 IS 8 BP 2818 EP 2823 DI 10.1073/pnas.0813394106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411ME UT WOS:000263652900063 PM 19196973 ER PT J AU Crittenden, JR Cantuti-Castelvetri, I Saka, E Keller-McGandy, CE Hernandez, LF Kett, LR Young, AB Standaert, DG Graybiel, AM AF Crittenden, Jill R. Cantuti-Castelvetri, Ippolita Saka, Esen Keller-McGandy, Christine E. Hernandez, Ledia F. Kett, Lauren R. Young, Anne B. Standaert, David G. Graybiel, Ann M. TI Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side-effects induced by anti-parkinsonian therapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dyskinesia; ERK; L-DOPA; Parkinson's disease; striatum ID DOPA-INDUCED DYSKINESIA; STRIATAL PROJECTION NEURONS; NUCLEOTIDE-RELEASING PROTEIN; SIGNAL-REGULATED KINASE; BASAL GANGLIA; HUNTINGTONS-DISEASE; DEPLETED STRIATUM; ACTIVATION; STRIOSOMES; EXPRESSION AB Voluntary movement difficulties in Parkinson's disease are initially relieved by L-DOPA therapy, but with disease progression, the repeated L-DOPA treatments can produce debilitating motor abnormalities known as L-DOPA-induced dyskinesias. We show here that 2 striatum-enriched regulators of the Ras/Rap/ERK MAP kinase signal transduction cascade, matrix-enriched CalDAG-GEFI and striosome-enriched CalDAG-GEFII (also known as RasGRP), are strongly and inversely dysregulated in proportion to the severity of abnormal movements induced by L-DOPA in a rat model of parkinsonism. In the dopamine-depleted striatum, the L-DOPA treatments produce down-regulation of CalDAG-GEFI and upregulation of CalDAG-GEFII mRNAs and proteins, and quantification of the mRNA levels shows that these changes are closely correlated with the severity of the dyskinesias. As these CalDAG-GEFs control ERK cascades, which are implicated in L-DOPA-induced dyskinesias, and have differential compartmental expression patterns in the striatum, we suggest that they may be key molecules involved in the expression of the dyskinesias. They thus represent promising new therapeutic targets for limiting the motor complications induced by L-DOPA therapy. C1 [Crittenden, Jill R.; Keller-McGandy, Christine E.; Hernandez, Ledia F.; Graybiel, Ann M.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Crittenden, Jill R.; Keller-McGandy, Christine E.; Hernandez, Ledia F.; Graybiel, Ann M.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Cantuti-Castelvetri, Ippolita; Kett, Lauren R.; Young, Anne B.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. [Saka, Esen] Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey. [Standaert, David G.] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA. RP Graybiel, AM (reprint author), MIT, Dept Brain & Cognit Sci, 43 Vassar St, Cambridge, MA 02139 USA. EM graybiel@mit.edu RI F. Hernandez, Ledia/J-3077-2012; OI F. Hernandez, Ledia/0000-0002-5293-3748; Standaert, David/0000-0003-2921-8348 FU National Institutes of Health [NS38372]; National Institute of Child Health and Human Development [R01-HD28341]; National Parkinson Foundation; Stanley H. and Sheila G. Sydney Fund FX We thank Dr. Robert E. Burke for his critical reading of the manuscript. This work was supported by the Massachusetts General Hospital/Massachusetts Institute of Technology Morris Udall Center of Excellence in Parkinson's Disease Research (National Institutes of Health Grant NS38372), National Institute of Child Health and Human Development Grant R01-HD28341, the National Parkinson Foundation, and the Stanley H. and Sheila G. Sydney Fund. NR 42 TC 35 Z9 35 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 24 PY 2009 VL 106 IS 8 BP 2892 EP 2896 DI 10.1073/pnas.0812822106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411ME UT WOS:000263652900076 PM 19171906 ER PT J AU Ginde, AA Mansbach, JM Camargo, CA AF Ginde, Adit A. Mansbach, Jonathan M. Camargo, Carlos A., Jr. TI Association Between Serum 25-Hydroxyvitamin D Level and Upper Respiratory Tract Infection in the Third National Health and Nutrition Examination Survey SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID VITAMIN-D DEFICIENCY; BRONCHIAL EPITHELIAL-CELLS; COMMON COLD; 1,25-DIHYDROXYVITAMIN D-3; UNITED-STATES; CUTTING EDGE; RICKETS; CHILDREN; CATHELICIDIN; FREQUENCY AB Background: Recent studies suggest a role for vitamin D in innate immunity, including the prevention of respiratory tract infections (RTIs). We hypothesize that serum 25-hydroxyvitamin D (25[ OH] D) levels are inversely associated with self-reported recent upper RTI (URTI). Methods: We performed a secondary analysis of the Third National Health and Nutrition Examination Survey, a probability survey of the US population conducted between 1988 and 1994. We examined the association between 25(OH) D level and recent URTI in 18 883 participants 12 years and older. The analysis adjusted for demographics and clinical factors (season, body mass index, smoking history, asthma, and chronic obstructive pulmonary disease). Results: The median serum 25(OH) D level was 29 ng/mL (to convert to nanomoles per liter, multiply by 2.496) (interquartile range, 21-37 ng/mL), and 19% (95% confidence interval [CI], 18%-20%) of participants reported a recent URTI. Recent URTI was reported by 24% of participants with 25(OH) D levels less than 10 ng/mL, by 20% with levels of 10 to less than 30 ng/mL, and by 17% with levels of 30 ng/mL or more (P <.001). Even after adjusting for demographic and clinical characteristics, lower 25(OH) D levels were independently associated with recent URTI (compared with 25[ OH] D levels of >= 30 ng/mL: odds ratio [OR], 1.36; 95% CI, 1.01-1.84 for < 10 ng/mL and 1.24; 1.07-1.43 for 10 to < 30 ng/mL). The association between 25(OH) D level and URTI seemed to be stronger in individuals with asthma and chronic obstructive pulmonary disease (OR, 5.67 and 2.26, respectively). Conclusions: Serum 25(OH) D levels are inversely associated with recent URTI. This association may be stronger in those with respiratory tract diseases. Randomized controlled trials are warranted to explore the effects of vitamin D supplementation on RTI. C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Med Network,Dep Emergency Med, Boston, MA 02114 USA. [Ginde, Adit A.] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Med Network,Dep Emergency Med, 326 Cambridge St,Ste 410, Boston, MA 02114 USA. EM ccamargo@partners.org RI Siry, Bonnie/D-7189-2017 FU Massachusetts General Hospital Center for D-receptor Activation Research; National Institutes of Health, National Heart, Lung, and Blood Institute [R01 HL84401] FX Dr Camargo was supported by the Massachusetts General Hospital Center for D-receptor Activation Research and grant R01 HL84401 from the National Institutes of Health, National Heart, Lung, and Blood Institute. NR 50 TC 374 Z9 397 U1 5 U2 23 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 23 PY 2009 VL 169 IS 4 BP 384 EP 390 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 410SW UT WOS:000263599600009 PM 19237723 ER PT J AU Gohil, VM Greenberg, ML AF Gohil, Vishal M. Greenberg, Miriam L. TI Mitochondrial membrane biogenesis: phospholipids and proteins go hand in hand SO JOURNAL OF CELL BIOLOGY LA English DT Editorial Material ID SYNTHETIC LETHAL INTERACTION; SACCHAROMYCES-CEREVISIAE; CARDIOLIPIN BIOSYNTHESIS; BARTH-SYNDROME; PHOSPHATIDYLETHANOLAMINE; SYNTHASE; TEMPERATURE; INOSITOL; COMPLEX; TAM41 AB Mitochondrial membrane biogenesis requires the import and synthesis of proteins as well as phospholipids. How the mitochondrion regulates phospholipid levels and maintains a tight protein-to-phospholipid ratio is not well understood. Two recent papers (Kutik, S., M. Rissler, X.L. Guan, B. Guiard, G. Shui, N. Gebert, P.N. Heacock, P. Rehling, W. Dowhan, M.R. Wenk, et al. 2008. J. Cell Biol. 183: 1213 1221; Osman, C., M. Haag, C. Potting, J. Rodenfels, P.V. Dip, F.T. Wieland, B. Brugger, B. Westermann, and T. Langer. 2009. J. Cell Biol. 184: 583-596) identify novel regulators of mitochondrial phospholipid biosynthesis. The biochemical approach of Kutik et al. (2008) uncovered an unexpected role of the mitochondrial translocator assembly and maintenance protein, Tam41, in the biosynthesis of cardiolipin (CL), the signature phospholipid of mitochondria. The genetic analyses of Osman et al. (2009) led to the discovery of a new class of mitochondrial proteins that coordinately regulate CL and phosphatidylethanolamine, another key mitochondrial phospholipid. These elegant studies highlight overlapping functions and interdependent roles of mitochondrial phospholipid biosynthesis and protein import and assembly. C1 [Greenberg, Miriam L.] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. [Gohil, Vishal M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Gohil, Vishal M.] Inst Technol & Harvard, Broad Inst Massachusetts, Cambridge, MA 02142 USA. [Gohil, Vishal M.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02446 USA. RP Greenberg, ML (reprint author), Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. EM mgreenberg@.wayne.edu NR 25 TC 41 Z9 41 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB 23 PY 2009 VL 184 IS 4 BP 468 EP 472 DI 10.1083/jcb.200901127 PG 4 WC Cell Biology SC Cell Biology GA 416OY UT WOS:000264016600002 PM 19237595 ER PT J AU Yoon, J Deisboeck, TS AF Yoon, Jeongah Deisboeck, Thomas S. TI Investigating Differential Dynamics of the MAPK Signaling Cascade Using a Multi-Parametric Global Sensitivity Analysis SO PLOS ONE LA English DT Article AB Cell growth critically depends on signalling pathways whose regulation is the focus of intense research. Without utilizing a priori knowledge of the relative importance of pathway components, we have applied in silico computational methods to the EGF-induced MAPK cascade. Specifically, we systematically perturbed the entire parameter space, including initial conditions, using a Monte Carlo approach, and investigate which protein components or kinetic reaction steps contribute to the differentiation of ERK responses. The model, based on previous work by Brightman and Fell (2000), is composed of 28 reactions, 27 protein molecules, and 48 parameters from both mass action and Michaelis-Menten kinetics. Our multiparametric systems analysis confirms that Raf inactivation is one of the key steps regulating ERK responses to be either transient or sustained. Furthermore, the results of amplitude-differential ERK phosphorylations within the transient case are mainly attributed to the balance between activation and inactivation of Ras while duration-differential ERK responses for the sustained case are, in addition to Ras, markedly affected by dephospho-/phosphorylation of both MEK and ERK. Our sub-module perturbations showed that MEK and ERK's contribution to this differential ERK activation originates from fluctuations in intermediate pathway module components such as Ras and Raf, implicating a cooperative regulatory mode among the key components. The initial protein concentrations of corresponding reactions such as Ras, GAP, and Raf also influence the distinct signalling outputs of ERK activation. We then compare these results with those obtained from a single-parametric perturbation approach using an overall state sensitivity (OSS) analysis. The OSS findings indicate a more pronounced role of ERK's inhibitory feedback effect on catalysing the dissociation of the SOS complex. Both approaches reveal the presence of multiple specific reactions involved in the distinct dynamics of ERK responses and the cell fate decisions they trigger. This work adds a mechanistic insight of the contribution of key pathway components, thus may support the identification of biomarkers for pharmaceutical drug discovery processes. C1 [Yoon, Jeongah; Deisboeck, Thomas S.] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Harvard MIT HST, Complex Biosyst Modeling Lab, Charlestown, MA USA. RP Yoon, J (reprint author), Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Harvard MIT HST, Complex Biosyst Modeling Lab, Charlestown, MA USA. EM deisboec@helix.mgh.harvard.edu FU NIH [CA 113004]; Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital FX This work has been supported in part by NIH grant CA 113004 and by the Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 17 Z9 17 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 23 PY 2009 VL 4 IS 2 AR e4560 DI 10.1371/journal.pone.0004560 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437KU UT WOS:000265487200014 PM 19234599 ER PT J AU Thomas, GH Zucker, J Macdonald, SJ Sorokin, A Goryanin, I Douglas, AE AF Thomas, Gavin H. Zucker, Jeremy Macdonald, Sandy J. Sorokin, Anatoly Goryanin, Igor Douglas, Angela E. TI A fragile metabolic network adapted for cooperation in the symbiotic bacterium Buchnera aphidicola SO BMC SYSTEMS BIOLOGY LA English DT Article ID ESCHERICHIA-COLI K-12; GENOME-SCALE; SP APS; RESOURCE; APHIDS AB Background: In silico analyses provide valuable insight into the biology of obligately intracellular pathogens and symbionts with small genomes. There is a particular opportunity to apply systems-level tools developed for the model bacterium Escherichia coli to study the evolution and function of symbiotic bacteria which are metabolically specialised to overproduce specific nutrients for their host and, remarkably, have a gene complement that is a subset of the E. coli genome. Results: We have reconstructed and analysed the metabolic network of the gamma-proteobacterium Buchnera aphidicola ( symbiont of the pea aphid) as a model for using systems-level approaches to discover key traits of symbionts with small genomes. The metabolic network is extremely fragile with > 90% of the reactions essential for viability in silico; and it is structured so that the bacterium cannot grow without producing the essential amino acid, histidine, which is released to the insect host. Further, the amount of essential amino acid produced by the bacterium in silico can be controlled by host supply of carbon and nitrogen substrates. Conclusion: This systems-level analysis predicts that the fragility of the bacterial metabolic network renders the symbiotic bacterium intolerant of drastic environmental fluctuations, whilst the coupling of histidine production to growth prevents the bacterium from exploiting host nutrients without reciprocating. These metabolic traits underpin the sustained nutritional contribution of B. aphidicola to the host and, together with the impact of host-derived substrates on the profile of nutrients released from the bacteria, point to a dominant role of the host in controlling the symbiosis. C1 [Thomas, Gavin H.; Macdonald, Sandy J.; Douglas, Angela E.] Univ York, Dept Biol, York YO10 5YW, N Yorkshire, England. [Zucker, Jeremy] Dana Farber Canc Inst, Boston, MA USA. [Sorokin, Anatoly; Goryanin, Igor] Univ Edinburgh, Sch Informat, Ctr Intelligent Syst & Their Applicat, Edinburgh EH8 9LE, Midlothian, Scotland. [Douglas, Angela E.] Cornell Univ, Dept Entomol, Ithaca, NY 14853 USA. RP Thomas, GH (reprint author), Univ York, Dept Biol, POB 373, York YO10 5YW, N Yorkshire, England. EM ght2@york.ac.uk; zucker@research.dfci.harvard.edu; ajm513@york.ac.uk; sorokin@inf.ed.ac.uk; goryanin@inf.ed.ac.uk; aes326@cornell.edu RI Thomas, Gavin/E-5753-2011; Sorokin, Anatoly/A-9090-2008; Zucker, Jeremy/M-3643-2016; OI Thomas, Gavin/0000-0002-9763-1313; Sorokin, Anatoly/0000-0002-0047-0606; Zucker, Jeremy/0000-0002-7276-9009; Macdonald, Sandy/0000-0002-4112-0987 FU Biotechnology and Biological Sciences Research Council NR 25 TC 48 Z9 50 U1 3 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1752-0509 J9 BMC SYST BIOL JI BMC Syst. Biol. PD FEB 21 PY 2009 VL 3 AR 24 DI 10.1186/1752-0509-3-24 PG 9 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 421YA UT WOS:000264393000001 PM 19232131 ER PT J AU Roozendaal, R Mempel, TR Pitcher, LA Gonzalez, SF Verschoor, A Mebius, RE von Andrian, UH Carroll, MC AF Roozendaal, Ramon Mempel, Thorsten R. Pitcher, Lisa A. Gonzalez, Santiago F. Verschoor, Admar Mebius, Reina E. von Andrian, Ulrich H. Carroll, Michael C. TI Conduits Mediate Transport of Low-Molecular-Weight Antigen to Lymph Node Follicles SO IMMUNITY LA English DT Article ID FOLLICULAR DENDRITIC CELLS; HUMORAL IMMUNE-RESPONSE; ZONE B-CELLS; COMPLEMENT RECEPTORS 1; IN-VIVO; ANTIBODY-RESPONSES; SUBCAPSULAR SINUS; GERMINAL-CENTERS; MARGINAL ZONE; NETWORKS AB To track drainage of lymph-borne small and large antigens (Ags) into the peripheral lymph nodes and subsequent encounter by B cells and follicular dendritic cells, we used the approach of multiphoton intravital microscopy. We find a system of conduits that extend into the follicles and mediate delivery of small antigens to cognate B cells and follicular dendritic cells. The follicular conduits provide an efficient and rapid mechanism for delivery of small antigens and chemokines such as CXCL13 to B cells that directly contact the conduits. By contrast, large antigens were bound by subcapsular sinus macrophages and subsequently transferred to follicular B cells as previously reported. In summary, the findings identify a unique pathway for the channeling of small lymph-borne antigens and chemoattractants from the subcapsular sinus directly to the B cell follicles. This pathway could be used for enhancing delivery of vaccines or small molecules for improvement of humoral immunity. C1 [Roozendaal, Ramon; Pitcher, Lisa A.; Gonzalez, Santiago F.; Verschoor, Admar; Carroll, Michael C.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Roozendaal, Ramon; Pitcher, Lisa A.; Gonzalez, Santiago F.; Verschoor, Admar; Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Roozendaal, Ramon; Mempel, Thorsten R.; Pitcher, Lisa A.; Gonzalez, Santiago F.; Verschoor, Admar; von Andrian, Ulrich H.; Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Roozendaal, Ramon; Mebius, Reina E.] VU Med Ctr, Dept Mol Cell Biol & Immunol, NL-1081 BT Amsterdam, Netherlands. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@idi.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU Marie Curie Fellowship [008873]; National Institutes of Health [Al 039246] FX We wish to thank D. Vargas for exceptional animal care, R. Yeamans for technical assistance, and N. Barteneva at the IDI Flow and Imaging Cytometry Core facility and M. Ericsson at the Harvard Medical School EM Facility for technical assistance. R.R. is supported by a Marie Curie Fellowship (008873). M.C.C. is supported by a grant from the National Institutes of Health (Al 039246). NR 55 TC 176 Z9 177 U1 2 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB 20 PY 2009 VL 30 IS 2 BP 264 EP 276 DI 10.1016/j.immuni.2008.12.014 PG 13 WC Immunology SC Immunology GA 412FT UT WOS:000263710500013 PM 19185517 ER PT J AU Housley, MP Udeshi, ND Rodgers, JT Shabanowitz, J Puigserver, P Hunt, DF Hart, GW AF Housley, Michael P. Udeshi, Namrata D. Rodgers, Joseph T. Shabanowitz, Jeffrey Puigserver, Pere Hunt, Donald F. Hart, Gerald W. TI A PGC-1 alpha-O-GlcNAc Transferase Complex Regulates FoxO Transcription Factor Activity in Response to Glucose SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID O-GLCNAC TRANSFERASE; LINKED N-ACETYLGLUCOSAMINE; PPAR-GAMMA COACTIVATOR-1; ACTIVATED RECEPTOR-GAMMA; RNA-POLYMERASE-II; INSULIN-RESISTANCE; MASS-SPECTROMETRY; NUCLEOCYTOPLASMIC GLYCOSYLATION; HEPATIC GLUCONEOGENESIS; HEXOSAMINE BIOSYNTHESIS AB Metabolic and stress response gene regulation is crucial for the survival of an organism to a changing environment. Three key molecules that sense nutrients and broadly affect gene expression are the FoxO transcription factors, the transcriptional co-activator PGC-1 alpha, and the dynamic post-translational modification, O-linked beta-N-acetylglucosamine (O-GlcNAc). Here we identify novel post-translational modifications of PGC-1 alpha, including O-GlcNAc, and describe a novel mechanism for how PGC-1 alpha co-activates transcription by FoxOs. In liver, in cultured cells, and in vitro with recombinant proteins, PGC-1 alpha binds to O-GlcNAc transferase and targets the enzyme to FoxOs, resulting in their increased GlcNAcylation and increased transcriptional activity. Furthermore, glucose-enhanced activation of FoxO1 occurs via this PGC-1 alpha-O-GlcNAc transferase-mediated GlcNAcylation. Therefore, one mechanism by which PGC-1 alpha can serve as a co-activator of transcription is by targeting the O-GlcNAc transferase to increase GlcNAcylation of specific transcription factors important to nutrient/stress sensing and energy metabolism. C1 [Housley, Michael P.; Hart, Gerald W.] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. [Udeshi, Namrata D.; Shabanowitz, Jeffrey; Hunt, Donald F.] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. [Hunt, Donald F.] Univ Virginia, Dept Pathol, Charlottesville, VA 22904 USA. [Rodgers, Joseph T.; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Rodgers, Joseph T.; Puigserver, Pere] Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. RP Hart, GW (reprint author), Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. EM gwhart@jhmi.edu RI Hunt, Donald/I-6936-2012 OI Hunt, Donald/0000-0003-2815-6368 FU National Institutes of Health [DK61671, HD13563, GM37537] FX This work was supported, in whole or in part, by National Institutes of Health Grants DK61671 and HD13563 (to G. W. H.) and GM37537 (to D. F. H.). G. W. H. receives a share of royalties on university sales of the CTD110.6 antibody. Arrangement managed by The Johns Hopkins University School conflict of interest policies. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 56 TC 96 Z9 100 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 20 PY 2009 VL 284 IS 8 BP 5148 EP 5157 DI 10.1074/jbc.M808890200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 408DY UT WOS:000263416600045 PM 19103600 ER PT J AU Cohn, MA Kee, Y Haas, W Gygi, SP D'Andrea, AD AF Cohn, Martin A. Kee, Younghoon Haas, Wilhelm Gygi, Steven P. D'Andrea, Alan D. TI UAF1 Is a Subunit of Multiple Deubiquitinating Enzyme Complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; FANCONI-ANEMIA PATHWAY; PROTEIN COMPLEXES; PROTEASOME; UBIQUITIN; REPAIR; UCH37 AB A balance between ubiquitination and deubiquitination regulates numerous cellular processes and pathways, and specific deubiquitinating enzymes often play the decisive role of controlling this balance. We recently reported that the USP1 deubiquitinating enzyme, which regulates the Fanconi anemia pathway by deubiquitinating the central player of the pathway, FANCD2, is activated by the WD40-repeat containing UAF1 protein through formation of a stable USP1/UAF1 protein complex. Here we present the isolation of two novel multisubunit deubiquitinating enzyme complexes containing USP12 and USP46, respectively. Both complexes contain the UAF1 protein as a bona fide subunit. Interestingly, UAF1 regulates the enzymatic activity of both enzyme complexes, suggesting that this activator protein may regulate a subclass of human deubiquitinating enzymes. We postulate that additional WD40-containing proteins may also form complexes with other human deubiquitinating enzymes and thereby regulate their activity and substrate specificity. C1 [Cohn, Martin A.; Kee, Younghoon; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Haas, Wilhelm; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu OI Cohn, Martin/0000-0002-2988-3009 FU National Institutes of Health [5P01CA092584] FX This work was supported, in whole or in part, by National Institutes of Health Grant 5P01CA092584. NR 30 TC 81 Z9 86 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 20 PY 2009 VL 284 IS 8 BP 5343 EP 5351 DI 10.1074/jbc.M808430200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 408DY UT WOS:000263416600064 PM 19075014 ER PT J AU Partridge, AH Winer, EP AF Partridge, Ann H. Winer, Eric P. TI Sharing Study Results With Trial Participants: Time for Action SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CLINICAL-TRIALS; INFORMED-CONSENT; BREAST-CANCER; WANT C1 [Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 15 TC 12 Z9 12 U1 2 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2009 VL 27 IS 6 BP 838 EP 839 DI 10.1200/JCO.2008.20.0865 PG 2 WC Oncology SC Oncology GA 409NR UT WOS:000263513000002 PM 19164202 ER PT J AU Casarett, DJ Fishman, JM Lu, HL O'Dwyer, PJ Barg, FK Naylor, MD Asch, DA AF Casarett, David J. Fishman, Jessica M. Lu, Hien L. O'Dwyer, Peter J. Barg, Frances K. Naylor, Mary D. Asch, David A. TI The Terrible Choice: Re-Evaluating Hospice Eligibility Criteria for Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONJOINT-ANALYSIS; PATIENT PREFERENCES; PALLIATIVE CARE; NURSING-HOMES; HEALTH-CARE; FAMILIES; SERVICES; LIFE; MANAGEMENT; ENROLLMENT AB Purpose To be eligible for the Medicare Hospice Benefit, cancer patients with a life expectancy of 6 months or less must give up curative treatment. Our goal was to determine whether willingness to make this choice identifies patients with greater need for hospice services. Patients and Methods Three hundred patients with cancer and 171 family members were recruited from six oncology practices. Respondents completed conjoint interviews in which their perceived need for five hospice services was calculated from the choices they made among combinations of services. Patients' preferences for treatment were measured, and patients were followed for 6 months or until death. Results Thirty-eight patients (13%) said they would not want cancer treatment even if it offered an almost 100% chance of 6-month survival. These patients, who would have been eligible for hospice, did not have greater perceived need for hospice services compared with other patients (n = 262; mean, 1.75 v 1.98; Wilcoxon rank sum test, P = .46), nor did their family members (mean, 1.95 v 2.04; Wilcoxon rank sum test, P = .80). Instead, independent predictors of patients' perceived need for hospice services included African American ethnicity, less social support, worse functional status, and a greater burden of psychological symptoms. For families, predictors included caregiver burden, worse self-reported health, working outside the home, and caring for a patient with worse functional status. Conclusion The requirement that patients forgo life-sustaining treatment does not identify patients with greater perceived need for hospice services. Other characteristics offer a better way to identify the patients who are most likely to benefit from hospice. C1 [Casarett, David J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Casarett, DJ (reprint author), Univ Penn, Sch Med, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X FU Paul Beeson Physician Faculty Scholars Award [R01CA109540]; Presidential Early Career Award for Scientists and Engineers FX Supported by Grant No. R01CA109540, the Paul Beeson Physician Faculty Scholars Award, and the Presidential Early Career Award for Scientists and Engineers (D.J.C.). NR 39 TC 31 Z9 31 U1 4 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2009 VL 27 IS 6 BP 953 EP 959 DI 10.1200/JCO.2008.17.8079 PG 7 WC Oncology SC Oncology GA 409NR UT WOS:000263513000019 PM 19114698 ER PT J AU Zon, RT Goss, E Vogel, VG Chlebowski, RT Jatoi, I Robson, ME Wollins, DS Garber, JE Brown, P Kramer, BS AF Zon, Robin T. Goss, Elizabeth Vogel, Victor G. Chlebowski, Rowan T. Jatoi, Ismail Robson, Mark E. Wollins, Dana S. Garber, Judy E. Brown, Powel Kramer, Barnett S. TI American Society of Clinical Oncology Policy Statement: The Role of the Oncologist in Cancer Prevention and Risk Assessment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; INVASIVE BREAST-CANCER; BILATERAL PROPHYLACTIC MASTECTOMY; UPPER AERODIGESTIVE TRACT; BRCA2 MUTATION CARRIERS; 2ND PRIMARY TUMORS; COLORECTAL-CANCER; TEACHABLE MOMENT; PROSTATE-CANCER; HEPATOCELLULAR-CARCINOMA AB Oncologists have a critical opportunity to utilize risk assessment and cancer prevention strategies to interrupt the initiation or progression of cancer in cancer survivors and individuals at high risk of developing cancer. Expanding knowledge about the natural history and prognosis of cancers positions oncologists to advise patients regarding the risk of second malignancies and treatment-related cancers. In addition, as recognized experts in the full spectrum of cancer care, oncologists are afforded opportunities for involvement in community-based cancer prevention activities. Although oncologists are currently providing many cancer prevention and risk assessment services to their patients, economic barriers exist, including inadequate or lack of insurance, that may compromise uniform patient access to these services. Additionally, insufficient reimbursement for existing and developing interventions may discourage patient access to these services. The American Society of Clinical Oncology (ASCO), the medical society representing cancer specialists involved in patient care and clinical research, is committed to supporting oncologists in their wide-ranging involvement in cancer prevention. This statement on risk assessment and prevention counseling, although not intended to be a comprehensive overview of cancer prevention describes the current role of oncologists in risk assessment and prevention; provides examples of risk assessment and prevention activities that should be offered by oncologists; identifies potential opportunities for coordination between oncologists and primary care physicians in prevention education and coordination of care for cancer survivors; describes ASCO's involvement in education and training of oncologists regarding prevention; and proposes improvement in the payment environment to encourage patient access to these services. C1 [Wollins, Dana S.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. Turner & Goss LLP, Washington, DC USA. Michiana Hematol Oncol, South Bend, IN USA. Univ Pittsburgh, Inst Canc, Magee UPCI Breast Canc Prevent Program, Pittsburgh, PA USA. Harbor UCLA Med Ctr, Div Hematol & Med Oncol, Torrance, CA 90509 USA. Natl Naval Med Ctr, Breast Care Ctr, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Wollins, DS (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM dana.wollins@asco.org OI Robson, Mark/0000-0002-3109-1692 NR 76 TC 29 Z9 29 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 20 PY 2009 VL 27 IS 6 BP 986 EP 993 DI 10.1200/JCO.2008.16.3691 PG 8 WC Oncology SC Oncology GA 409NR UT WOS:000263513000023 PM 19075281 ER PT J AU Howley, PM Livingston, DM AF Howley, Peter M. Livingston, David M. TI Small DNA tumor viruses: Large contributors to biomedical sciences SO VIROLOGY LA English DT Review DE SV40; Polyoma; HPV; Papillomavirus; BPV; p53 ID HUMAN-PAPILLOMAVIRUS TYPE-16; RETINOBLASTOMA GENE-PRODUCT; SV40 EARLY PROMOTER; REPLICATION INVITRO; POLYOMA-VIRUS; T-ANTIGEN; SV40-TRANSFORMED CELLS; PROTEIN PHOSPHATASE-2A; MESSENGER-RNA; HUMAN CANCER AB Studies of the small DNA tumor viruses (the polyomaviruses, the adenoviruses and the papillomaviruses) have led to fundamental discoveries that have advanced our understanding of basic mammalian cell molecular biology processes such as transcription and DNA replication, uncovered pathways and genes often perturbed in human cancer, and identified bona fide human cancer viruses. In this article we examine the many contributions that have come from the small DNA tumor Virus field and provide a recounting of some of the major landmark discoveries. (C) 2008 Elsevier Inc. All rights reserved. C1 [Howley, Peter M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Livingston, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP Howley, PM (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM peter_howley@hms.harvard.edu FU NCI NIH HHS [P01 CA050661, P01 CA050661-200007] NR 51 TC 36 Z9 36 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 20 PY 2009 VL 384 IS 2 BP 256 EP 259 DI 10.1016/j.virol.2008.12.006 PG 4 WC Virology SC Virology GA 409TG UT WOS:000263528100002 PM 19136134 ER PT J AU DeCaprio, JA AF DeCaprio, James A. TI How the Rb tumor suppressor structure and function was revealed by the study of Adenovirus and SV40 SO VIROLOGY LA English DT Review DE SV40; Adenovirus; Rb; pRb; Retinoblastoma; Tumor suppressor; Transformation; Cell cycle; Large T antigen; E1A ID LARGE-T-ANTIGEN; RETINOBLASTOMA GENE-PRODUCT; SIMIAN-VIRUS-40 LARGE-T; SIMIAN-VIRUS 40; CELLULAR TRANSCRIPTION FACTOR; PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; EARLY REGION-1A POLYPEPTIDES; MOUSE EMBRYO FIBROBLASTS; PRB-RELATED PROTEINS; DNA-BINDING ACTIVITY AB The review recounts the history of how the study of the DNA tumor viruses including polyoma, SV40 and Adenovirus brought key insights into the structure and function of the Retinoblastoma protein (Rb). Knudsen's model of the two-hit hypothesis to explain patterns of hereditary and sporadic retinoblastoma provided the foundation for the tumor suppressor hypothesis that ultimately led to the cloning of the Rb gene. The discovery that SV40 and Adenovirus could cause tumors when inoculated into animals was startling not only because SV40 had contaminated the poliovirus vaccine and Adenovirus was a common cause of viral induced pneumonia but also because they provided an opportunity to study the genetics and biochemistry of cancer. Studies of mutant forms of these viruses led to the identification of the E1A and Large Tantigen (LT) oncogenes and their small transforming elements including the Adenovirus Conserved Regions (CR), the SV40 J domain and the LxCxE motif. The immunoprecipitation studies that initially revealed the size and ultimately the identity of cellular proteins that could bind to these transforming elements were enabled by the widespread development of highly specific monoclonal antibodies against E1A and LT. The identification of Rb as an E1A and LT interacting protein quickly led to the cloning of p107, p130, p300, CBP, p400 and TRRAP and the concept that viral transformation was due, at least in part, to the perturbation of the function of normal cellular proteins. In addition. studies on the ability of E1A to transactivate the Adenovirus E2 promoter led to the cloning of the heterodimeric E2F and DP transcription factor and recognition that Rb repressed transcription of cellular genes required for cell cycle entry and progression. More recent studies have revealed how E1A and LT combine the activity of Rb and the other cellular associated proteins to perturb expression of many genes during viral infection and tumor formation. (C) 2008 Elsevier Inc. All rights reserved. C1 [DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [DeCaprio, James A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [DeCaprio, James A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu FU NCI NIH HHS [P01 CA050661, R01 CA063113] NR 237 TC 53 Z9 54 U1 3 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 20 PY 2009 VL 384 IS 2 BP 274 EP 284 DI 10.1016/j.virol.2008.12.010 PG 11 WC Virology SC Virology GA 409TG UT WOS:000263528100005 PM 19150725 ER PT J AU Schaffhausen, BS Roberts, TM AF Schaffhausen, Brian S. Roberts, Thomas M. TI Lessons from polyoma middle T antigen on signaling and transformation: A DNA tumor virus contribution to the war on cancer SO VIROLOGY LA English DT Review DE Polyoma; Middle T antigen; PI3 kinase; Tyrosine kinase; Signal transduction; Cancer ID PROTEIN PHOSPHATASE 2A; GROWTH-FACTOR RECEPTORS; ROUS-SARCOMA-VIRUS; PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; TYROSINE PHOSPHORYLATION SITES; PHOSPHOTYROSINE-BINDING DOMAIN; MAMMARY EPITHELIAL-CELLS; AVIAN RETROVIRAL VECTOR; HEAT-SHOCK PROTEINS; SOMATIC MOUSE MODEL AB Middle T antigen (MT) is the principal oncogene of murine polyomavirus. Its study has led to the discovery of the roles of tyrosine kinase and phosphoinositide 3-kinase (PI3K) signaling in mammalian growth control and transformation. MT is necessary for viral transformation in tissue culture cells and tumorigenesis in animals. When expressed alone as a transgene, MT causes tumors in a wide variety of tissues. It has no known catalytic activity, but rather acts by assembling cellular signal transduction molecules. Protein phosphatase 2A, protein tyrosine kinases of the src family, PI3K, phospholipase C gamma 1 as well as the Shc/Grb2 adaptors are all assembled on MT Their activation sets off a series of signaling cascades. Analyses of virus mutants as well as transgenic animals have demonstrated that the effects of a given signal depend not only tissue type, but on the genetic background of the host animal. There remain many opportunities as we seek a full molecular understanding of MT and apply some of its lessons to human cancer. (C) 2008 Elsevier Inc. All rights reserved. C1 [Roberts, Thomas M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Schaffhausen, Brian S.] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. [Roberts, Thomas M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM brian.schaffhausen@tufts.edu; thomas_roberts@dfci.harvard.edu FU NIH [PO1-CA50661, RO1-CA34722, RO1-CA30002] FX This article is an overview of MT, not an exhaustive review. We apologize in advance for work not covered here either from lack of space or inadvertent oversight. The work in the authors' laboratories was supported by grants from the NIH (PO1-CA50661 to B.S.S. and T.M.R., RO1-CA34722 to B.S.S., and RO1-CA30002 to T.M.R). NR 236 TC 28 Z9 28 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 0042-6822 J9 VIROLOGY JI Virology PD FEB 20 PY 2009 VL 384 IS 2 BP 304 EP 316 DI 10.1016/j.virol.2008.09.042 PG 13 WC Virology SC Virology GA 409TG UT WOS:000263528100008 PM 19022468 ER PT J AU Fonseca, C Soiffer, R Ho, V Vanneman, M Jinushi, M Ritz, J Neuberg, D Stone, R DeAngelo, D Dranoff, G AF Fonseca, Catia Soiffer, Robert Ho, Vincent Vanneman, Matthew Jinushi, Masahisa Ritz, Jerome Neuberg, Donna Stone, Richard DeAngelo, Dan Dranoff, Glenn TI Protein disulfide isomerases are antibody targets during immune-mediated tumor destruction SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; AUGMENTS ANTITUMOR IMMUNITY; BONE-MARROW TRANSPLANTATION; T-CELLS; METASTATIC MELANOMA; COMBINATION IMMUNOTHERAPY; CTLA-4 BLOCKADE; DENDRITIC CELLS; IN-VIVO; CANCER AB The identification of cancer antigens that contribute to transformation and are linked with immune-mediated tumor destruction is an important goal for immunotherapy. Toward this end, we screened a murine renal cell carcinomac DNA expression library with sera from mice vaccinated with irradiated tumor cells engineered to secrete granulocyte macrophage colony-stimulating factor (GM-CSF). Multiple nonmutated, overexpressed proteins that function in tumor cell migration, protein/nucleic acid homeostasis, metabolism, and stress responses were detected. Among these, the most frequently recognized clone was protein disulfide isomerase (PDI). High titer antibodies to human PDI were similarly induced in an acute myeloid leukemia patient who achieved a complete response after vaccination with irradiated, autologous GMCSF-secreting tumor cells in the setting of nonmyeloablative allogeneic bone marrow transplantation. Moreover, ERp5, a closely related disulfide isomerase involved in major histocompatibility complex (MHC) class I chain-related protein A (MICA) shedding, also evoked potent humoral reactions in diverse solid and hematologic malignancy patients who responded to GM-CSF secreting tumor cell vaccines or antibody blockade of cytotoxic T lymphocyte associated antigen 4 (CTLA-4). Together, these findings reveal the unexpected immunogenicity of PDIs and raise the possibility that these gene products might serve as targets for therapeutic monoclonal antibodies. (Blood. 2009; 113: 1681-1688) C1 [Fonseca, Catia; Soiffer, Robert; Ho, Vincent; Vanneman, Matthew; Jinushi, Masahisa; Ritz, Jerome; Stone, Richard; DeAngelo, Dan; Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fonseca, Catia; Soiffer, Robert; Ho, Vincent; Vanneman, Matthew; Jinushi, Masahisa; Ritz, Jerome; Stone, Richard; DeAngelo, Dan; Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Fonseca, Catia; Soiffer, Robert; Ho, Vincent; Vanneman, Matthew; Jinushi, Masahisa; Ritz, Jerome; Stone, Richard; DeAngelo, Dan; Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fonseca, Catia; Soiffer, Robert; Ho, Vincent; Vanneman, Matthew; Jinushi, Masahisa; Ritz, Jerome; Neuberg, Donna; Stone, Richard; DeAngelo, Dan; Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 520C,44 Binney St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu RI Jinushi, Masahisa/A-4311-2012; OI Ritz, Jerome/0000-0001-5526-4669 FU National Institutes of Health (Bethesda, MD); Leukemia & Lymphoma Society (White Plains, NY); GABBA Graduate Program (Oporto University); Portuguese Foundation for Science and Technology FX We thank the National Institutes of Health (Bethesda, MD), the Leukemia & Lymphoma Society (White Plains, NY), the GABBA Graduate Program (Oporto University), and the Portuguese Foundation for Science and Technology for their educational and financial support. NR 64 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 19 PY 2009 VL 113 IS 8 BP 1681 EP 1688 DI 10.1182/blood-2007-09-114157 PG 8 WC Hematology SC Hematology GA 410GS UT WOS:000263566100010 PM 19008459 ER PT J AU Joshi, I Minter, LM Telfer, J Demarest, RM Capobianco, AJ Aster, JC Sicinski, P Fauq, A Golde, TE Osborne, BA AF Joshi, Ila Minter, Lisa M. Telfer, Janice Demarest, Renee M. Capobianco, Anthony J. Aster, Jon C. Sicinski, Piotr Fauq, Abdul Golde, Todd E. Osborne, Barbara A. TI Notch signaling mediates G(1)/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; KAPPA-B ACTIVITY; CHROMOSOMAL TRANSLOCATIONS; LYMPHOCYTE DEVELOPMENT; PATHWAY; ACTIVATION; DIFFERENTIATION; TRANSCRIPTION; EXPRESSION; PROTEINS AB Notch signaling plays a role in normal lymphocyte development and function. Activating Notch1-mutations, leading to aberrant downstream signaling, have been identified in human T-cell acute lymphoblastic leukemia (T-ALL). While this highlights the contribution of Notch signaling to T-ALL pathogenesis, the mechanisms by which Notch regulates proliferation and survival in normal and leukemic T cells are not fully understood. Our findings identify a role for Notch signaling in G(1)-S progression of cell cycle in T cells. Here we show that expression of the G(1) proteins, cyclin D3, CDK4, and CDK6, is Notch-dependent both in vitro and in vivo, and we outline a possible mechanism for the regulated expression of cyclin D3 in activated T cells via CSL (CBF-1, mammals; suppressor of hairless, Drosophila melanogaster; Lag-1, Caenorhabditis elegans), as well as a noncanonical Notch signaling pathway. While cyclin D3 expression contributes to cell-cycle progression in Notch-dependent human T-ALL cell lines, ectopic expression of CDK4 or CDK6 together with cyclin D3 shows partial rescue from gamma-secretase inhibitor (GSI)-induced G(1) arrest in these cell lines. Importantly, cyclin D3 and CDK4 are highly overexpressed in Notch-dependent T-cell lymphomas, justifying the combined use of cell-cycle inhibitors and GSI in treating human T-cell malignancies. (Blood. 2009; 113: 1689-1698) C1 [Osborne, Barbara A.] Univ Massachusetts, Dept Vet & Anim Sci, Paige Lab 311, Amherst, MA 01003 USA. [Joshi, Ila; Telfer, Janice; Osborne, Barbara A.] Univ Massachusetts, Program Mol & Cell Biol, Amherst, MA 01003 USA. [Demarest, Renee M.; Capobianco, Anthony J.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Aster, Jon C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sicinski, Piotr] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Sicinski, Piotr] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Fauq, Abdul; Golde, Todd E.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. RP Osborne, BA (reprint author), Univ Massachusetts, Dept Vet & Anim Sci, Paige Lab 311, Amherst, MA 01003 USA. EM osborne@vasci.umass.edu RI Minter, Lisa/H-6539-2014 FU National Institutes of Health (NIH) [PO1 AG025531, RO1 AI049361] FX We thank the members of the Osborne laboratory for useful discussions and technical support, especially Rebecca G. Lawlor for help with the tissue culture work. We thank Sripriya Subramanian for help with cell sorting. We also thank Dr Rachit Bakshi for helpful discussions and critical reading of the manuscript. Lastly, we thank Drs Phil Hinds, Dario Vignali, and Suzanne Baker for their generosity in providing plasmids.; This work was supported by National Institutes of Health (NIH) grants PO1 AG025531 and RO1 AI049361. NR 53 TC 82 Z9 85 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 19 PY 2009 VL 113 IS 8 BP 1689 EP 1698 DI 10.1182/blood-2008-03-147967 PG 10 WC Hematology SC Hematology GA 410GS UT WOS:000263566100011 PM 19001083 ER PT J AU Tyner, JW Erickson, H Deininger, MWN Willis, SG Eide, CA Levine, RL Heinrich, MC Gattermann, N Gilliland, DG Druker, BJ Loriaux, MM AF Tyner, Jeffrey W. Erickson, Heidi Deininger, Michael W. N. Willis, Stephanie G. Eide, Christopher A. Levine, Ross L. Heinrich, Michael C. Gattermann, Norbert Gilliland, D. Gary Druker, Brian J. Loriaux, Marc M. TI High-throughput sequencing screen reveals novel, transforming RAS mutations in myeloid leukemia patients SO BLOOD LA English DT Article ID HUMAN COLORECTAL-CANCER; MYELOCYTIC LEUKEMIAS; MYELODYSPLASTIC SYNDROMES; HEMATOPOIETIC-CELLS; KRAS MUTATIONS; PROTEIN-KINASE; POINT MUTATION; GERMLINE KRAS; K-RAS; LEUKEMOGENESIS AB Transforming mutations in NRAS and KRAS are thought to play a causative role in the development of numerous cancers, including myeloid malignancies. Although mutations at amino acids 12, 13, or 61 account for the majority of oncogenic Ras variants, we hypothesized that less frequent mutations at alternate residues may account for disease in some patients with cancer of unexplained genetic etiology. To search for additional, novel RAS mutations, we sequenced all coding exons in NRAS, KRAS, and HRAS in 329 acute myeloid leukemia (AML) patients, 32 chronic myelomonocytic leukemia (CMML) patients, and 96 healthy individuals. We detected 4 "noncanonical" point mutations in 7 patients: N-Ras(G60E), K-Ras(V14I), K-Ras(T74P), and K-Ras(A146T). All 4 Ras mutants exhibited oncogenic properties in comparison with wild-type Ras in biochemical and functional assays. The presence of transforming RAS mutations outside of positions 12, 13, and 61 reveals that alternate mechanisms of transformation by RAS may be overlooked in screens designed to detect only the most common RAS mutations. Our results suggest that RAS mutations may play a greater role in leukemogenesis than currently believed and indicate that high-throughput screening for mutant RAS alleles in cancer should include analysis of the entire RAS coding region. (Blood. 2009; 113: 1749-1755) C1 [Loriaux, Marc M.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Tyner, Jeffrey W.; Erickson, Heidi; Deininger, Michael W. N.; Willis, Stephanie G.; Eide, Christopher A.; Heinrich, Michael C.; Druker, Brian J.; Loriaux, Marc M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Levine, Ross L.; Gilliland, D. Gary] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Levine, Ross L.; Gilliland, D. Gary] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. [Gattermann, Norbert] Univ Dusseldorf, Klin Hamatol Onkol & Klin Immunol, Dusseldorf, Germany. RP Loriaux, MM (reprint author), Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. EM loriauxm@ohsu.edu OI Tyner, Jeffrey/0000-0002-2133-0960 FU Leukemia & Lymphoma Society (White Plains, NY); T. J. Martell Foundation (New York, NY); National Institutes of Health (NIH, Bethesda, MD); VA Merit Review Grant FX M. L. is supported by the Leukemia & Lymphoma Society (White Plains, NY) and the T. J. Martell Foundation (New York, NY). J. W. T. is supported by a cancer biology training grant from the National Institutes of Health (NIH, Bethesda, MD). M. C. H. is supported in part by a VA Merit Review Grant. D. G. G. and B. J. D. are Howard Hughes Medical Institute investigators. NR 33 TC 64 Z9 65 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 19 PY 2009 VL 113 IS 8 BP 1749 EP 1755 DI 10.1182/blood-2008-04-152157 PG 7 WC Hematology SC Hematology GA 410GS UT WOS:000263566100017 PM 19075190 ER PT J AU Grande, D Asch, DA AF Grande, David Asch, David A. TI Commercial versus Social Goals of Tracking What Doctors Do SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Grande, David] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Grande, D (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 2 TC 6 Z9 6 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 19 PY 2009 VL 360 IS 8 BP 747 EP 749 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 408CN UT WOS:000263411300002 PM 19228616 ER PT J AU Cros, D Gonzalez, RG Mark, EJ Han, SW Harris, NL Sheth, KN AF Cros, Didier Gonzalez, R. Gilberto Mark, Eugene J. Han, Sang-Woo (Steve) Harris, Nancy Lee Sheth, Kevin N. TI A Woman with Vertigo, Facial Weakness, and a Generalized Seizure Neurosarcoidosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MEDICAL PROGRESS; LYME-DISEASE; SARCOIDOSIS; DIAGNOSIS; MANIFESTATIONS; MANAGEMENT; LUPUS C1 [Cros, Didier] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Div Neuroradiol, Dept Radiol, Boston, MA 02114 USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cros, Didier] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Cros, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU Bayer; General Electric FX Dr. Gonzalez reports receiving lecture fees from Bayer and General Electric. No other potential conflict of interest relevant to this article was reported. NR 19 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 19 PY 2009 VL 360 IS 8 BP 802 EP 809 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 408CN UT WOS:000263411300012 PM 19228624 ER PT J AU Chen, JJ Cai, X Szostak, JW AF Chen, Jesse J. Cai, Xin Szostak, Jack W. TI N2 '-> P3 ' Phosphoramidate Glycerol Nucleic Acid as a Potential Alternative Genetic System SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CHEMICAL ETIOLOGY; DNA; OLIGODEOXYRIBONUCLEOTIDE; OLIGONUCLEOTIDE; DUPLEX AB Glycerol nucleic acid (GNA) is an interesting base-pairing system with an acyclic, three-carbon backbone. In the present study, GNA analogues with N2'-> P3' phosphoramidate linkages (npGNA) have been synthesized and their base-pairing properties examined. Thermal denaturation and circular dichroism studies show that npGNA can form stable duplexes with itself and with GNA. Furthermore, we show that npGNA can be assembled by template-directed ligation of 3'-imidazole-activated-2'-amino GNA dinucleotides. These results suggest that npGNA is a potential candidate for a self-replicating system based upon phosphoramidate linkages. C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Harvard Origins Initiative; NSF [CHE 0434507]; Howard Hughes Medical Institute FX J.J.C. was supported by a Fellowship from the Harvard Origins Initiative. This work was supported by NSF grant CHE 0434507 to J.W.S. J.W.S is an Investigator of the Howard Hughes Medical Institute. The authors thank Dr. A. Ricardo, Dr. M. Krishnamurthy, Dr. D. Treco, and Dr. B. Heuberger for helpful discussions. NR 17 TC 34 Z9 34 U1 2 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD FEB 18 PY 2009 VL 131 IS 6 BP 2119 EP + DI 10.1021/ja809069b PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 427PW UT WOS:000264792200039 PM 19166350 ER PT J AU Ray, ME Bae, K Hussain, MHA Hanks, GE Shipley, WU Sandler, HM AF Ray, Michael E. Bae, Kyounghwa Hussain, Maha H. A. Hanks, Gerald E. Shipley, William U. Sandler, Howard M. TI Potential Surrogate Endpoints for Prostate Cancer Survival: Analysis of a Phase III Randomized Trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 28-NOV 01, 2007 CL Los Angeles, CA SP Amer Soc Therapeut Radiol & Oncol ID THERAPY ONCOLOGY GROUP; GROUP PROTOCOL 92-02; RADIATION-THERAPY; RADICAL PROSTATECTOMY; ANDROGEN DEPRIVATION; BIOCHEMICAL FAILURE; ADJUVANT THERAPY; COLON-CANCER; RADIOTHERAPY; CARCINOMA AB Background The identification of surrogate endpoints for prostate cancer-specific survival may shorten the length of clinical trials for prostate cancer. We evaluated distant metastasis and general clinical treatment failure as potential surrogates for prostate cancer-specific survival by use of data from the Radiation Therapy and Oncology Group 92-02 randomized trial. Methods Patients (n = 1554 randomly assigned and 1521 evaluable for this analysis) with locally advanced prostate cancer had been treated with 4 months of neoadjuvant and concurrent androgen deprivation therapy with external beam radiation therapy and then randomly assigned to no additional therapy (control arm) or 24 additional months of androgen deprivation therapy (experimental arm). Data from landmark analyses at 3 and 5 years for general clinical treatment failure (defined as documented local disease progression, regional or distant metastasis, initiation of androgen deprivation therapy, or a prostate-specific antigen level of 25 ng/mL or higher after radiation therapy) and/or distant metastasis were tested as surrogate endpoints for prostate cancer-specific survival at 10 years by use of Prentice's four criteria. All statistical tests were two-sided. Results At 3 years, 1364 patients were alive and contributed data for analysis. Both distant metastasis and general clinical treatment failure at 3 years were consistent with all four of Prentice's criteria for being surrogate endpoints for prostate cancer-specific survival at 10 years. At 5 years, 1178 patients were alive and contributed data for analysis. Although prostate cancer-specific survival was not statistically significantly different between treatment arms at 5 years (P=.08), both endpoints were consistent with Prentice's remaining criteria. Conclusions Distant metastasis and general clinical treatment failure at 3 years may be candidate surrogate endpoints for prostate cancer-specific survival at 10 years. These endpoints, however, must be validated in other datasets. J Natl Cancer Inst 2009; 101: 228-236 C1 [Ray, Michael E.] Radiol Associates Appleton, Appleton, WI 54911 USA. [Bae, Kyounghwa] Radiat Therapy Oncol Grp, Dept Stat, Philadelphia, PA USA. [Hussain, Maha H. A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Sandler, Howard M.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Hanks, Gerald E.] Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. [Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Ray, ME (reprint author), Radiol Associates Appleton, 1818 N Meade St, Appleton, WI 54911 USA. EM michael.ray@thedacare.org FU NCI NIH HHS [U10 CA21661, U10 CA32115, U10 CA37422] NR 31 TC 18 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 18 PY 2009 VL 101 IS 4 BP 228 EP 236 DI 10.1093/jnci/djn489 PG 9 WC Oncology SC Oncology GA 559DV UT WOS:000274802600009 PM 19211454 ER PT J AU Spoelgen, R Adams, KW Koker, M Thomas, AV Andersen, OM Hallett, PJ Bercury, KK Joyner, DF Deng, M Stoothoff, WH Strickland, DK Willnow, TE Hyman, BT AF Spoelgen, R. Adams, K. W. Koker, M. Thomas, A. V. Andersen, O. M. Hallett, P. J. Bercury, K. K. Joyner, D. F. Deng, M. Stoothoff, W. H. Strickland, D. K. Willnow, T. E. Hyman, B. T. TI INTERACTION OF THE APOLIPOPROTEIN E RECEPTORS LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN AND sorLA/LR11 SO NEUROSCIENCE LA English DT Article DE LRP; sorLA; LR11; LDL; receptor ID AMYLOID PRECURSOR PROTEIN; RESONANCE ENERGY-TRANSFER; TYROSINE PHOSPHORYLATION; ALPHA-2-MACROGLOBULIN RECEPTOR; ALZHEIMERS-DISEASE; CYTOPLASMIC DOMAIN; MOSAIC RECEPTOR; CELL-SURFACE; LRP; BINDING AB In this study, we examined protein-protein interactions between two neuronal receptors, low density lipoprotein receptor-related protein (LRP) and sorLA/LR11, and found that these receptors interact, as indicated by three independent lines of evidence: co-immunoprecipitation experiments on mouse brain extracts and mouse neuronal cells, surface plasmon resonance analysis with purified human LRP and sorLA, and fluorescence lifetime imaging microscopy (FLIM) on rat primary cortical neurons. Immunocytochemistry experiments revealed widespread co-localization of LRP and sorLA within perinuclear compartments of rat primary neurons, while FLIM analysis showed that LRP-sorLA interactions take place within a subset of these compartments. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Spoelgen, R.; Adams, K. W.; Koker, M.; Thomas, A. V.; Hallett, P. J.; Bercury, K. K.; Joyner, D. F.; Deng, M.; Stoothoff, W. H.; Hyman, B. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimer Unit,MassGen Inst Neurodege, Charlestown, MA 02129 USA. [Andersen, O. M.; Willnow, T. E.] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. [Strickland, D. K.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. [Andersen, O. M.] Aarhus Univ, Dept Med Biochem, MIND Ctr, DK-8000 Aarhus, Denmark. [Hallett, P. J.] Harvard Univ, McLean Hosp, Sch Med, Ctr Neurogenerat Res, Belmont, MA 02478 USA. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimer Unit,MassGen Inst Neurodege, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Hallett, Penelope/0000-0002-8858-9096 FU NHLBI NIH HHS [HL50784, HL54710, P01 HL054710, P01 HL054710-130002, R01 HL050784, R01 HL050784-15]; NIA NIH HHS [R37 AG012406, AG 12406, AG15379, P01 AG015379, P01 AG015379-100003, P50 AG005134, R01 AG012406, R37 AG012406-15] NR 37 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB 18 PY 2009 VL 158 IS 4 BP 1460 EP 1468 DI 10.1016/j.neuroscience.2008.10.061 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 413EN UT WOS:000263775800027 PM 19047013 ER PT J AU Duke-Cohan, JS Wollenick, K Witten, EA Seaman, MS Baden, LR Dolin, R Reinherz, EL AF Duke-Cohan, Jonathan S. Wollenick, Kristin Witten, Elizabeth A. Seaman, Michael S. Baden, Lindsey R. Dolin, Raphael Reinherz, Elllis L. TI The heterogeneity of human antibody responses to vaccinia virus revealed through use of focused protein arrays SO VACCINE LA English DT Article DE Vaccinia; Protein array; Humoral response ID EMERGING INFECTIOUS-DISEASES; SMALLPOX VACCINE; CELL-SURFACE; PROTECTION EFFICACY; NONHUMAN-PRIMATES; ESCHERICHIA-COLI; IMMUNE-RESPONSE; UNITED-STATES; MICE; CHALLENGE AB The renewed interest in strategies to combat infectious agents with epidemic potential has led to a re-examination of vaccination protocols against smallpox. To help define which antigens elicit a human antibody response, we have targeted proteins known OF predicted to be presented on the surface of the intracellular Mature virion (IMV) or the extracellular enveloped virion (EEV). The predicted ectodomains were expressed in a mammalian in vitro coupled transcription/translation reaction using tRNA(lys) precharged with lysine-p-biotin followed by solid phase immobilization on 384-well neutravidin-coated plates. The generated at-ray is highly specific and sensitive in a micro-ELISA format. By comparison of binding of vaccinia-immune sera to the reticulocyte lysate-produced proteins and to secreted post-translationally modified proteins, we demonstrate that for several proteins including the EEV proteins 135 and A33, proper recognition is dependent upon appropriate folding, with little dependence upon glycosylation per se. We further demonstrate that the humoral immune response to vaccinia among different individuals is not uniform in specificity or strength, as different IMV and EEV targets predominate within the group of immunogenic proteins. This heterogeneity likely results from the diversity of HLA Class 11 alleles and CD4 T helper cell epitopes stimulating B cell antibody production. Our findings have important implications both for design of new recombinant subunit vaccines as well as for methods of assaying the human antibody response utilizing recombinant proteins produced in vitro. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Duke-Cohan, Jonathan S.; Wollenick, Kristin; Witten, Elizabeth A.; Reinherz, Elllis L.] Dana Farber Canc Inst, Dept Med Oncol, Immunobiol Lab, Boston, MA 02115 USA. [Duke-Cohan, Jonathan S.; Seaman, Michael S.; Baden, Lindsey R.; Dolin, Raphael; Reinherz, Elllis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Seaman, Michael S.; Dolin, Raphael] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. [Baden, Lindsey R.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Duke-Cohan, JS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Immunobiol Lab, Boston, MA 02115 USA. EM jonathan_duke-cohan@dfci.harvard.edu; ellis_reinherz@dfci.harvard.edu OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU NIH [5U19-AI057330] FX The following reagents were obtained through the NIH Biodefense and Emerging Infections Research Resources Repository, MAID, NIH: Vaccinia Virus (WR) A27L, A33R, B5R and L1R proteins with C-terminal histidine tag produced as recombinant baculovirus proteins. This work was supported by NIH grant 5U19-AI057330 (ELR). NR 56 TC 13 Z9 13 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD FEB 18 PY 2009 VL 27 IS 8 BP 1154 EP 1165 DI 10.1016/j.vaccine.2008.12.035 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 412GH UT WOS:000263712200003 PM 19146908 ER PT J AU Pham, HH O'Malley, AS Bach, PB Saiontz-Martinez, C Schrag, D AF Pham, Hoangmai H. O'Malley, Ann S. Bach, Peter B. Saiontz-Martinez, Cynthia Schrag, Deborah TI Primary Care Physicians' Links to Other Physicians Through Medicare Patients: The Scope of Care Coordination SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PERFORMANCE AB Background: Primary care physicians are expected to coordinate care for their patients. Objective: To assess the number of physician peers providing care to the Medicare patients of a primary care physician. Design: Cross-sectional analysis of claims data. Setting: Fee-for-service Medicare in 2005. Participants: 2284 primary care physicians who responded to the 2004 to 2005 Community Tracking Study Physician Survey. Measurements: Primary patients for each physician were defined as beneficiaries for whom the physician billed for more evaluation and management visits than any other physician in 2005. The number of physician peers for each physician was the sum of other unique physicians that the index physician's primary patients visited plus other unique physicians who served as the primary physician for each of the index physician's nonprimary patients during 2005. Results: The typical primary care physician has 229 (interquartile range, 125 to 340) other physicians working in 117 ( interquartile range, 66 to 175) practices with which care must be coordinated, equivalent to an additional 99 physicians and 53 practices for every 100 Medicare beneficiaries managed by the primary care physician. When only the 31% of a primary care physician's primary patients who had 4 or more chronic conditions was considered, the median number of peers involved was still substantial ( 86 physicians in 36 practices). The number of peers varied with geographic region, practice type, and reliance on Medicaid revenues. Limitations: Estimates are based only on fee-for-service Medicare patients and physician peers, and the number of peers is therefore probably an underestimate. The modest response rate of the Community Tracking Study Physician Survey may bias results in unpredictable directions. Conclusion: In caring for his or her own primary and nonprimary patients during a single year, each primary care physician potentially must coordinate with a large number of individual physician colleagues who also provide care to these patients. C1 [Pham, Hoangmai H.] Ctr Studying Hlth Syst Change, Washington, DC 20024 USA. Mem Sloan Kettering Canc Ctr, Hlth Outcomes Res Grp, New York, NY 10021 USA. Social & Sci Syst, Silver Spring, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pham, HH (reprint author), Ctr Studying Hlth Syst Change, 600 Maryland Ave SW,Suite 550, Washington, DC 20024 USA. EM mpham@hschange.org FU National Institute on Aging; American Medical Group Association; Robert Wood Johnson Foundation FX National Institute on Aging, American Medical Group Association, and the Robert Wood Johnson Foundation. NR 20 TC 86 Z9 86 U1 2 U2 12 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 17 PY 2009 VL 150 IS 4 BP 236 EP U23 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 410FI UT WOS:000263562500002 PM 19221375 ER PT J AU Grinspoon, S AF Grinspoon, Steven TI Diabetes Mellitus, Cardiovascular Risk, and HIV Disease SO CIRCULATION LA English DT Editorial Material DE Editorials; acquired immunodeficiency syndrome; coronary disease; diabetes mellitus; myocardial infarction; risk factors ID REVERSE-TRANSCRIPTASE INHIBITORS; CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; ANTIRETROVIRAL THERAPY; INSULIN-RESISTANCE; INFECTED PATIENTS; CONTROLLED-TRIAL; LIPODYSTROPHY; COHORT; ADULTS C1 [Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Grinspoon, Steven] Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, LON 207,Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org NR 20 TC 18 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 17 PY 2009 VL 119 IS 6 BP 770 EP 772 DI 10.1161/CIRCULATIONAHA.108.835710 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 408JZ UT WOS:000263432600002 PM 19221228 ER PT J AU Ross, JS Gross, CP AF Ross, Joseph S. Gross, Cary P. TI Policy Research Using Evidence to Improve Healthcare Delivery Systems SO CIRCULATION LA English DT Editorial Material DE health policy; delivery of health care; policy ID ACUTE MYOCARDIAL-INFARCTION; COOPERATIVE CARDIOVASCULAR PROJECT; BYPASS GRAFT-SURGERY; ELDERLY MEDICARE BENEFICIARIES; RANDOMIZED CONTROLLED-TRIAL; 30-DAY MORTALITY-RATES; AGE-BASED DISPARITIES; SHORT-TERM MORTALITY; CONFLICT-OF-INTEREST; TO-BALLOON TIMES C1 [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Ross, Joseph S.] James J Peters VA Med Ctr, HSR& Res Enhancement Award Program, Bronx, NY USA. [Ross, Joseph S.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Gross, Cary P.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. [Gross, Cary P.] Yale Univ, Sch Med, Gen Internal Med Sect, Dept Internal Med, New Haven, CT USA. RP Ross, JS (reprint author), Mt Sinai Sch Med, Dept Geriatr & Adult Dev, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM joseph.ross@mssm.edu NR 92 TC 3 Z9 3 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 17 PY 2009 VL 119 IS 6 BP 891 EP 898 DI 10.1161/CIRCULATIONAHA.107.729855 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 408JZ UT WOS:000263432600018 PM 19221232 ER PT J AU Kim, JM Parmar, K Huang, M Weinstock, DM Ruit, CA Kutok, JL D'Andrea, AD AF Kim, Jung Min Parmar, Kalindi Huang, Min Weinstock, David M. Ruit, Carrie Ann Kutok, Jeffrey L. D'Andrea, Alan D. TI Inactivation of Murine Usp1 Results in Genomic Instability and a Fanconi Anemia Phenotype SO DEVELOPMENTAL CELL LA English DT Article ID DNA-REPAIR; HOMOLOGOUS RECOMBINATION; TARGETED DISRUPTION; REDUCED FERTILITY; GENE; MICE; PATHWAY; PROTEIN; FANCD2; HYPERSENSITIVITY AB Fanconi anemia (FA) is a human genetic disease characterized by chromosome instability, cancer predisposition, and cellular hypersensitivity to DNA crosslinking agents. The FA pathway regulates the repair of DNA crosslinks. A critical step in this pathway is the monoubiquitination and deubiquitination of FANCD2. Deubiquitination of FANCD2 Is mediated by the ubiquitin protease, USP1. Here, we demonstrate that targeted deletion of mouse Usp1 results in elevated perinatal lethality, male infertility, crosslinker hypersensitivity, and an FA phenotype. Uspl(-/-) mouse embryonic fibroblasts had heightened levels of monoubiquitinated Fancd2 in chromatin. Usp1(-/-) cells exhibited impaired Fancd2 foci assembly and a defect in homologous recombination repair. Double knockout of Usp1 and Fancd2 resulted in a more severe phenotype than either single knockout. Our results indicate that mouse Usp1 functions downstream in the FA pathway. Deubiquitination is a critical event required for Fancd2 nuclear foci assembly, release from chromatin, and function in DNA repair. C1 [Kim, Jung Min; Parmar, Kalindi; Huang, Min; Ruit, Carrie Ann; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kutok, Jeffrey L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu OI huang, min/0000-0001-6735-1612 FU NIH [RO1DK43889, RO1HL52725, PO1DK50654, U19A1067751] FX We thank Maria Jasin and Hisao Masai for DR-U2OS and for Cre recombinase-expressing adenovirus, respectively. We thank Lisa Moreau for chromosomal breakage analysis, Kenneth Law for immunohistochemistry, Eunmi Park for help in characterization of newborn mice, and Tony Huang for helpful discussions. We thank Patricia Stuckert, Mary Kathryn DeLoach, and Kaya Zhu for technical assistance. This study was supported by NIH grants RO1DK43889, RO1HL52725, PO1DK50654, and U19A1067751. NR 28 TC 120 Z9 122 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD FEB 17 PY 2009 VL 16 IS 2 BP 314 EP 320 DI 10.1016/j.devcel.2009.01.001 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 410PI UT WOS:000263589700019 PM 19217432 ER PT J AU Gostissa, M Ranganath, S Bianco, JM Alt, FW AF Gostissa, Monica Ranganath, Sheila Bianco, Julia M. Alt, Frederick W. TI Chromosomal location targets different MYC family gene members for oncogenic translocations SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nonhomologous end joining; pro-B cell lymphoma; genomic instability; immunoglobulin genes ID B-CELL LYMPHOMA; DNA-LIGASE IV; N-MYC; C-MYC; TRANSGENIC MICE; EMBRYONIC LETHALITY; V(D)J RECOMBINATION; MURINE DEVELOPMENT; RAG COMPLEX; EXPRESSION AB The MYC family of cellular oncogenes includes c-Myc, N-myc, and L-myc, which encode transcriptional regulators involved in the control of cell proliferation and death. Accordingly, these genes become aberrantly activated and expressed in specific types of cancers. For example, c-Myc translocations occur frequently in human B lymphoid tumors, while N-myc gene amplification is frequent in human neuroblastomas. The observed association between aberrations in particular MYC family genes and specific subsets of malignancies might reflect, at least in part, tissue-specific differences in expression or function of a given MYC gene. Since c-Myc and N-myc share substantial functional redundancy, another factor that could influence tumor-specific gene activation would be mechanisms that target aberrations ( e. g., translocations) in a given MYC gene in a particular tumor progenitor cell type. We have previously shown that mice deficient for the DNA Ligase4 (Lig4) nonhomologous DNA end-joining factor and the p53 tumor suppressor routinely develop progenitor (pro)-B cell lymphomas that harbor translocations leading to c-Myc amplification. Here, we report that a modified allele in which the c-Myc coding sequence is replaced by N-myc coding sequence (NCR allele) competes well with the wild-type c-Myc allele as a target for oncogenic translocations and amplifications in the Lig4/p53-deficient pro-B cell lymphoma model. Tumor onset, type, and cytological aberrations are similar in tumors harboring either the wild-type c-Myc gene or the NCR allele. Our results support the notion that particular features of the c-Myc locus select it as a preferential translocation/amplification target, compared to the endogenous N-myc locus, in Lig4/p53-deficient pro-B cell lymphomas. C1 Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Karp Family Res Bldg 1 Blackfan Circle, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU National Institutes of Health [5P01 CA92625]; American Cancer Society and the Dana Farber Cancer Institute Postdoctoral Training Program in Cancer Immunology FX This work was supported by National Institutes of Health Grant 5P01 CA92625 ( to F. W. A.). M. G. is a Leukemia and Lymphoma Society senior fellow. S. R. was supported by a Genentech/IDEC Fellowship from the American Cancer Society and the Dana Farber Cancer Institute Postdoctoral Training Program in Cancer Immunology. F. W. A. is an investigator of theHoward Hughes Medical Institute. NR 39 TC 18 Z9 19 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 17 PY 2009 VL 106 IS 7 BP 2265 EP 2270 DI 10.1073/pnas.0812763106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 409OQ UT WOS:000263516100035 PM 19174520 ER PT J AU Schenten, D Kracker, S Esposito, G Franco, S Klein, U Murphy, M Alt, FW Rajewsky, K AF Schenten, Dominik Kracker, Sven Esposito, Gloria Franco, Sonia Klein, Ulf Murphy, Michael Alt, Frederick W. Rajewsky, Klaus TI Pol zeta ablation in B cells impairs the germinal center reaction, class switch recombination, DNA break repair, and genome stability SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INDUCED CYTIDINE DEAMINASE; IMMUNOGLOBULIN GENE HYPERMUTATION; END-JOINING PATHWAY; DOUBLE-STRAND BREAK; SOMATIC HYPERMUTATION; POLYMERASE-ZETA; CATALYTIC SUBUNIT; EMBRYONIC LETHALITY; CHROMOSOME BREAKS; IMMUNE-RESPONSE AB Pol zeta is an error-prone DNA polymerase that is critical for embryonic development and maintenance of genome stability. To analyze its suggested role in somatic hypermutation (SHM) and possible contribution to DNA double-strand break (DSB) repair in class switch recombination (CSR), we ablated Rev3, the catalytic subunit of Pol zeta, selectively in mature B cells in vivo. The frequency of somatic mutation was reduced in the mutant cells but the pattern of SHM was unaffected. Rev3-deficient B cells also exhibited pronounced chromosomal instability and impaired proliferation capacity. Although the data thus argue against a direct role of Pol zeta in SHM, Pol zeta deficiency directly interfered with CSR in that activated Rev3-deficient B cells exhibited a reduced efficiency of CSR and an increased frequency of DNA breaks in the immunoglobulin H locus. Based on our results, we suggest a nonredundant role of Pol zeta in DNA DSB repair through nonhomologous end joining. C1 [Schenten, Dominik; Kracker, Sven; Franco, Sonia; Murphy, Michael; Alt, Frederick W.; Rajewsky, Klaus] Immune Dis Inst, Boston, MA 02115 USA. [Schenten, Dominik; Kracker, Sven; Franco, Sonia; Alt, Frederick W.; Rajewsky, Klaus] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Esposito, Gloria; Klein, Ulf; Rajewsky, Klaus] Univ Cologne, Inst Genet, D-50674 Cologne, Germany. [Franco, Sonia; Alt, Frederick W.] Childrens Hosp, Boston, MA 02115 USA. [Alt, Frederick W.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Rajewsky, K (reprint author), Immune Dis Inst, Boston, MA 02115 USA. EM rajewsky@idi.med.harvard.edu FU Deutsche Forschungsgemeinschaft [SFB 243]; National Institutes of Health [AI054636, CA092625, AI31541] FX This work was supported by the Deutsche Forschungsgemeinschaft (SFB 243) and the National Institutes of Health (grants AI054636 and CA092625 to K. Rajewsky and AI31541 and CA092625 to F. W. Alt). F. W. Alt is an Investigator of the Howard Hughes Medical Institute. NR 62 TC 42 Z9 43 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 16 PY 2009 VL 206 IS 2 BP 477 EP 490 DI 10.1084/jem.20080669 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 444VP UT WOS:000266008800019 PM 19204108 ER PT J AU Malone, DA Dougherty, DD Rezai, AR Carpenter, LL Friehs, GM Eskandar, EN Rauch, SL Rasmussen, SA Machado, AG Kubu, CS Tyrka, AR Price, LH Stypulkowski, PH Giftakis, JE Rise, MT Malloy, PF Salloway, SP Greenberg, BD AF Malone, Donald A., Jr. Dougherty, Darin D. Rezai, Ali R. Carpenter, Linda L. Friehs, Gerhard M. Eskandar, Emad N. Rauch, Scott L. Rasmussen, Steven A. Machado, Andre G. Kubu, Cynthia S. Tyrka, Audrey R. Price, Lawrence H. Stypulkowski, Paul H. Giftakis, Jonathon E. Rise, Mark T. Malloy, Paul F. Salloway, Stephen P. Greenberg, Benjamin D. TI Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Deep brain stimulation; efficacy; major depression; ventral capsule/ventral striatum ID OBSESSIVE-COMPULSIVE DISORDER; ANTERIOR CAPSULAR STIMULATION; MAJOR DEPRESSION; ELECTROCONVULSIVE-THERAPY; ELECTRICAL-STIMULATION; FOLLOW-UP; OUTCOMES; NEUROSURGERY; NUCLEUS; TRIAL AB Background: We investigated the use of deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) for treatment refractory depression. Methods: Fifteen patients with chronic, severe, highly refractory depression received open-label DBS at three collaborating clinical sites. Electrodes were implanted bilaterally in the VC/VS region. Stimulation was titrated to therapeutic benefit and the absence of adverse effects, All patients received continuous stimulation and were followed for a minimum of 6 months to longer than 4 years. Outcome measures included the Hamilton Depression Rating Scale-24 item (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Global Assessment of Function Scale (GAF). Results: Significant improvements in depressive symptoms were observed during DBS treatment, Mean HDRS scores declined from 33.1 at baseline to 17.5 at 6 months and 14.3 at last follow-up, Similar improvements were seen with the MADRS (34.8, 17.9, and 15.7, respectively) and the GAF (43.4, 55.5, and 61.8, respectively). Responder rates with the HDRS were 40% at 6 months and 53.3% at last follow-up (MADRS: 46.7% and 53.3%, respectively). Remission rates were 20% at 6 months and 40% at last follow-up with the HDRS (MADRS: 26.6% and 33.3%, respectively). The DBS was well-tolerated in this group. Conclusions: Deep brain stimulation of the VC/VS offers promise for the treatment of refractory major depression. C1 [Malone, Donald A., Jr.; Kubu, Cynthia S.] Cleveland Clin, Dept Psychiat & Psychol, Ctr Neurol Restorat, Cleveland, OH 44195 USA. [Rezai, Ali R.; Machado, Andre G.] Cleveland Clin, Dept Neurosurg, Ctr Neurol Restorat, Cleveland, OH 44195 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Carpenter, Linda L.; Rasmussen, Steven A.; Tyrka, Audrey R.; Price, Lawrence H.; Malloy, Paul F.; Salloway, Stephen P.; Greenberg, Benjamin D.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Friehs, Gerhard M.] Brown Med Sch, Div Neurosurg, Dept Clin Neurosci, Providence, RI USA. [Stypulkowski, Paul H.; Giftakis, Jonathon E.; Rise, Mark T.] Medtron, Minneapolis, MN USA. RP Malone, DA (reprint author), Cleveland Clin, Dept Psychiat & Psychol, Ctr Neurol Restorat, 9500 Euclid Ave,Desk P57, Cleveland, OH 44195 USA. EM maloned@ccf.org RI Machado, Andre/B-7572-2014; Tyrka, Audrey/L-2504-2014 OI Machado, Andre/0000-0002-8132-5610; FU Medtronic; Cyberonics; Northstar Neuroscience; Pfizer; Lilly; Forest; McNeil; Bristol-Myers-Squibb; UCB Pharma; Sepracor; Wyeth; Novartis; Neurogen; Elan; Neurochem; Voyager; Cephalon; Athena Diagnostics; Eisai; Johnson. Johnson; Myriad FX Dr. Malone has received research funding and is a consultant to Medtronic. He has received speaking bonoraria from Lilly and Bristol-Myers-Squibb. Dr. Dougberty has received research Support from Medtronic, Cyberonics, Northstar Neuroscience, Pfizer, Lilly, Forest, and McNeil. He has received bonoraria from Cyberonics and McNeil. Dr. Rezai holds the following financial interests in Intelect Medical: Founder and Director, Patent Holder. Chair of the Scientific Advisory Board, and Chief Scientific Officer. He has also received research funding and is a consultant to Medtronic as well as a stockholder of Surgivision. Dr. Carpenter has received research support from Pfizer, UCB Pharma, and Sepracor; consulting fees from Abbott, Bristol-Myers-Squibb, Cyberonics, Medtronic, Novartis, Pfizer, Sepracor, and Wyeth; bonoraria from AstraZeneca, Cyberonics, Pfizer, and Wyeth; and travel support from Neuronetics. Dr. Friebs has received research funding from Medtronic. Dr. Eskandar has received research funding from Medtronic. Dr. Rauch has received research from Cyberonics, Neurogen, Novartis, and Sepracor. and consulting fees from Novartis. Dr. Rasmussen has received research funding and consulting fees from Medtronic. Dr. Machado has received research funding from Medtronic and is a shareholder in Intelect Medical. Dr. Kubu has received research funding from Medtronic. Dr. Tyrka has received grant support from Cephalon, Cyberonics, Medtronic, Pfizer, Sepracor, and UCB Pharma. Dr. Price has received research support from Sepracor, Pfizer and UCB Pharma; consulting fees from Bio Vid, Gerson Lehrman, Oxford Univ Press, Springer and Wiley; and bonoraria from AstraZeneca. Drs. Stypulkowsski, Giftakis, and Rise are employees and shareholders of Medtronic. Dr. Malloy reports no biomedical financial interests or potential conflicts of interest. Dr. Salloway has received research funding from Cephalon, Elan, Neurochem, and Voyager; research support and honoraria from Athena Diagnostics, Eisai, Forest. Johnson. & Johnson, Myriad, and Pfizer; and consulted to Merck and Sanofi-Aventis. Dr. Greenberg has received research funding and honoraria for presentations from Medtronic. He is a consultant for Northstar Neuroscience and Jazz Pharmaceuticals and is on the latter's Speakers' Bureau. NR 39 TC 316 Z9 321 U1 7 U2 42 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 FEB 15 PY 2009 VL 65 IS 4 BP 267 EP 275 DI 10.1016/j.biopsych.2008.08.029 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 405UO UT WOS:000263249900002 PM 18842257 ER PT J AU Friese, CR Neville, BA Edge, SB Hassett, MJ Earle, CC AF Friese, Christopher R. Neville, Bridget A. Edge, Stephen B. Hassett, Michael J. Earle, Craig C. TI Breast Biopsy Patterns and Outcomes in Surveillance, Epidemiology, and End Results-Medicare Data SO CANCER LA English DT Article DE breast; diagnostic techniques and procedures; outcome assessment (healthcare); health services research; SEER program; Medicare ID CORE BIOPSY; CANCER; WOMEN AB BACKGROUND: Despite known benefits to needle biopsy for suspicious breast lesions, variability in the use of this technique has been documented in practice. We sought to study the use of needle biopsy and open surgical biopsy in women with breast cancer, predictors of needle biopsy use, and the effect of biopsy choice on overall number of surgical procedures needed to treat breast cancer. METHODS: We analyzed Surveillance, Epidemiology, and End Results(SEER)-Medicare data for 45,542 women diagnosed between 1991 and 1999 with ductal carcinoma in situ and stage I-II breast cancer. By using diagnosis and procedure codes from 3 months before to 6 months after the SEER diagnosis, we classified the initial biopsy as needle or surgical. By using multivariate logistic regression, we identified patient and tumor characteristics associated with needle biopsy use, and estimated the association between initial biopsy type and likelihood for multiple breast surgeries. RESULTS: Needle biopsy was the initial procedure for 11,073 (24.3%) women. In multivariate analyses, needle biopsy use varied significantly by race, year of diagnosis, and tumor size. After controlling for patient and tumor characteristics, needle biopsy use was associated with a reduced likelihood of multiple breast surgeries (odds ratio, 0.35; 95% confidence interval, 0.34-0.37). CONCLUSIONS: Use of needle biopsy as the initial breast cancer procedure was more common among black women and those with larger tumors, and increased significantly over time. Providers should consider needle biopsy when clinically feasible as the initial breast procedure, because it may reduce the number of surgeries needed to treat breast cancer. Cancer 2009;115:716-24. (C) 2009 American Cancer Society. C1 [Friese, Christopher R.] Univ Michigan, Sch Nursing, AOCN, Div Nursing Business & Hlth Syst, Ann Arbor, MI 48109 USA. [Neville, Bridget A.; Hassett, Michael J.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Dept Breast Surg, Buffalo, NY 14263 USA. [Hassett, Michael J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Earle, Craig C.] Canada Care Ontario, Hlth Serv Res Program, Toronto, ON, Canada. [Earle, Craig C.] Ontario Inst Canc Res, Toronto, ON, Canada. RP Friese, CR (reprint author), Univ Michigan, Sch Nursing, AOCN, Div Nursing Business & Hlth Syst, 400 N Ingalls,Room 4162, Ann Arbor, MI 48109 USA. EM cfriese@umich.edu RI Friese, Christopher/D-2097-2013 OI Friese, Christopher/0000-0002-2281-2056 FU National Cancer Institute, Glorian Sorensen, Principal Investigator [R-25 CA 057711-12] FX This study, used the linked SEER-Medicare database, and the authors acknowledge the efforts of the respective agencies in creating the database. The interpretation and reporting of these data are the sole responsibility of the authors. At the time of the study, the corresponding author (C.R.F.) was research fellow, Center for Outcomes and Policy Research, Dana-Farber Cancer Institute, and Department of Society,, Human Development, and Health, Harvard School of Public Health. NR 18 TC 26 Z9 27 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 2009 VL 115 IS 4 BP 716 EP 724 DI 10.1002/cncr.24085 PG 9 WC Oncology SC Oncology GA 405IQ UT WOS:000263216900006 PM 19152430 ER PT J AU Burga, LN Tung, NM Troyan, SL Bostina, M Konstantinopoulos, PA Fountzilas, H Spentzos, D Miron, A Yassin, YA Lee, BT Wulf, GM AF Burga, Laura N. Tung, Nadine M. Troyan, Susan L. Bostina, Mihnea Konstantinopoulos, Panagiotis A. Fountzilas, Helena Spentzos, Dimitrios Miron, Alexander Yassin, Yosuf A. Lee, Bernard T. Wulf, Gerburg M. TI Altered Proliferation and Differentiation Properties of Primary Mammary Epithelial Cells from BRCA1 Mutation Carriers SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; BASEMENT-MEMBRANE; FAMILIAL BREAST; EXPRESSION; MORPHOGENESIS; CULTURES; MARKER; GLAND; RISK; BETA AB Female BRCA1 mutation carriers have a nearly 80% probability of developing breast cancer during their life-lime. We hypothesized that the breast epithelium at, risk in BRCA1 mutation carriers harbors mammary epithelial cells (MEC) with altered proliferation and differentiation properties. Using a three-dimensional culture technique to grow MECs ex vivo, we found that the ability to form colonies, an indication of clonality. was restricted to the aldehyde dehydrogenase 1-positive fraction in MECs but not in HCC1937 BRCA1-mutant cancer cells. primary MECs from BRCA1 mutation carriers (n = 9) had a 28% greater ability for clonal growth compared with normal controls (n = 6; P = 0.006), and their colonies were significantly larger. Colonies in controls and BRCA1 mutation carriers stained positive for BRCA1 by immunohistochemistry, and 79% of the examined single colonies from BRCA1 carriers retained heterozygosity for BRCA1 (ROH). Colonies from BRCA1 mutation carriers frequently showed high epidermal growth factor receptor (EGFR) expression (71% EGFR positive versus 44% in controls) and were negative for estrogen receptor (ER alpha; 32% ER negative, 44% mixed, 24% ER positive versus 90% ER positive in controls). Expression of CK14 and p63 were not significantly different. Microarray studies revealed that colonies from BRCA1-mutant PMEC, anticipate expression profiles found in BRCA1-related tumors, and that the EGFR pathway is up-regulated. We conclude that. BRCA1 haploin-sufficiency leads to an increased ability for clonal growth and proliferation in the PMECs of BRCA1 mutation carriers, possibly as a result of EGFR pathway activation. These altered growth and differentiation properties may render BRCA1-mutant PMECs vulnerable to transformation and predispose to the development of ER-negative, EGFR-positive breast cancers. [Cancer Res 2009:69(4):1273-8] C1 [Burga, Laura N.; Tung, Nadine M.; Konstantinopoulos, Panagiotis A.; Fountzilas, Helena; Spentzos, Dimitrios; Wulf, Gerburg M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Burga, Laura N.; Wulf, Gerburg M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Canc Biol Program, Boston, MA 02215 USA. [Troyan, Susan L.; Lee, Bernard T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA. [Bostina, Mihnea] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Miron, Alexander; Yassin, Yosuf A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Wulf, GM (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM gwulf@bidmc.harvard.edu RI Lee, Bernard/K-1106-2016 OI Lee, Bernard/0000-0002-5533-3166 FU Susan Komen Foundation [BCTR0601030]; Alternatives Research and Development Foundation; Specialized Programs of Research Excellence; NIH [CA089393, K08-CA093655] FX Grant support: Susan Komen Foundation (BCTR0601030), Alternatives Research and Development Foundation, Specialized Programs of Research Excellence CA089393 (NIH), and K08-CA093655 (NIH: G. Wulf). NR 19 TC 41 Z9 41 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2009 VL 69 IS 4 BP 1273 EP 1278 DI 10.1158/0008-5472.CAN-08-2954 PG 6 WC Oncology SC Oncology GA 407YB UT WOS:000263399100008 PM 19190334 ER PT J AU Liu, BG Zhu, F Xia, XJ Park, E Hu, YL AF Liu, Bigang Zhu, Feng Xia, Xiaojun Park, Eumni Hu, Yinling TI A tale of terminal differentiation IKK alpha, the master keratinocyte regulator SO CELL CYCLE LA English DT Article DE IKK alpha; keratinocyte differentiation and proliferation; Ras; EGFR; tumorigenesis ID KAPPA-B-KINASE; GROWTH-FACTOR RECEPTOR; MICE LACKING; EPIGENETIC INACTIVATION; RAS ONCOGENE; SKIN-CANCER; 14-3-3-SIGMA; CARCINOMAS; EPIDERMIS; MOUSE AB Keratinocyte differentiation is the process of cellular maturation from a mitotic state to a terminally differentiated state during which skin builds up a tough yet soft skin barrier to protect the body. Its irreversibility also allows the shedding of excessive keratinocytes, thereby maintaining skin homeostasis and preventing skin diseases. Although the entire journey of keratinocyte differentiation is intricate and not well understood, it is known that Ras is able to block keratinocyte terminal differentiation and instead induce keratinocyte proliferation and transformation. It appears that uncontrolled proliferation actually interrupts differentiation. However, it has been unclear whether there are any innate surveillants that would be able to induce terminal differentiation by antagonizing excessive mitotic activities. Inhibitor of nuclear factor kappa B kinase-alpha (IKK alpha, previously known as Chuk) emerges as a master regulator in the coordinative control of keratinocyte differentiation and proliferation and as a major tumor suppressor in human and mouse skin squamous cell carcinomas. IKKa does so largely by integrating into the epidermal growth factor receptor (EGFR)/Ras/extracellular signal-regulated kinase (Erk)/EGFR ligand pathways during mitosis and differentiation. We discuss these findings herein to extend our understanding of how IKK alpha-mediated terminal differentiation serves as an innate surveillant in skin. C1 [Hu, Yinling] NCI, Canc & Inflammat Program, NIH, Ctr Canc Res, Frederick, MD 21701 USA. [Liu, Bigang; Zhu, Feng] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX USA. [Xia, Xiaojun] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Park, Eumni] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Hu, YL (reprint author), NCI, Canc & Inflammat Program, NIH, Ctr Canc Res, Frederick, MD 21701 USA. EM huy2@mail.nih.gov FU National Cancer Institute [CA117314, CA102510] FX This work was supported by National Cancer Institute Grants (CA117314 and CA102510 to Hu). We thank the Fellows Editorial Broad in NIH for editing the view. NR 41 TC 9 Z9 10 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD FEB 15 PY 2009 VL 8 IS 4 BP 527 EP 531 PG 5 WC Cell Biology SC Cell Biology GA 408KS UT WOS:000263434500006 PM 19197157 ER PT J AU Haviv, I Polyak, K Qiu, W Hu, M Campbell, I AF Haviv, Izhak Polyak, Kornelia Qiu, Wen Hu, Min Campbell, Ian TI Origin of carcinoma associated fibroblasts SO CELL CYCLE LA English DT Review DE oncology; cancer associated fibroblasts; micro-environment; cancer etiology ID STROMAL-EPITHELIAL INTERACTIONS; OVARIAN SURFACE EPITHELIUM; GROWTH-FACTOR-BETA; MESENCHYMAL STEM-CELLS; HUMAN BREAST-CANCER; TUMOR-STROMA; IN-VIVO; GENETIC ALTERATIONS; SOMATIC MUTATIONS; PROSTATE-CANCER AB Recent evidence on the genomic integrity of non-malignant cells surrounding carcinoma cells has reinvigorated the discussion about the origin of the altered phenotype exhibited by carcinoma associated fibroblasts. Many hypotheses have been proposed for the origin of these altered cells, including standard connective tissue acute phase and stress response, fibroblast senescence, reciprocal interactions with the cancer cells, fibroblast specific somatic mutations, differentiation precursors and infiltrating mesenchymal stem cells. Here we review the definition of CAF phenotype and the evidence for each of those hypotheses, in the context of our current understanding of cancer etiology. C1 [Haviv, Izhak] Baker IDI Inst, Prahran, Vic, Australia. [Haviv, Izhak; Qiu, Wen] Univ Melbourne, Sch Med, Dept Biochem, Melbourne, Vic, Australia. [Campbell, Ian] Univ Melbourne, Sch Med, Dept Pathol, Melbourne, Vic, Australia. [Polyak, Kornelia; Hu, Min] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Polyak, Kornelia; Hu, Min] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Qiu, Wen; Campbell, Ian] Peter MacCallum Canc Ctr, VBCRC Canc Genet Lab, Melbourne, Vic 8006, Australia. RP Campbell, I (reprint author), Peter MacCallum Canc Ctr, VBCRC Canc Res Lab, Locked Bag 1,ABeckett St, Melbourne, Vic 8006, Australia. EM campbellI@petermac.org RI campbell, Ian/F-6006-2011 NR 139 TC 66 Z9 69 U1 3 U2 19 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD FEB 15 PY 2009 VL 8 IS 4 BP 589 EP 595 PG 7 WC Cell Biology SC Cell Biology GA 408KS UT WOS:000263434500016 PM 19182519 ER PT J AU Mitsiades, CS Rouleau, C Echart, C Menon, K Teicher, B Distaso, M Palumbo, A Boccadoro, M Anderson, KC Iacobelli, M Richardson, PG AF Mitsiades, Constantine S. Rouleau, Cecile Echart, Cinara Menon, Krishna Teicher, Beverly Distaso, Maria Palumbo, Antonio Boccadoro, Mario Anderson, Kenneth C. Iacobelli, Massimo Richardson, Paul G. TI Preclinical Studies in Support of Defibrotide for the Treatment of Multiple Myeloma and Other Neoplasias SO CLINICAL CANCER RESEARCH LA English DT Article ID HEPATIC VENOOCCLUSIVE DISEASE; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; MULTICENTER PHASE-I/II; HIGH-RISK POPULATION; IN-VITRO; STROMAL CELLS; SIGNIFICANT TOXICITY; MAMMARY-CARCINOMA; COMPASSIONATE-USE AB Purpose of the Study: Defibrotide, an orally bioavailable polydisperse oligonucleotide, has promising activity in hepatic veno-occlusive disease, a stem cell transplantation - related toxicity characterized by microangiopathy. The antithrombotic properties of defibrotide and its minimal hemorrhagic risk could serve for treatment of cancer-associated thrombotic complications. Given its cytoprotective effect on endothelium, we investigated whether defibrotide protects tumor cells from cytotoxic antitumor agents. Further, given its antiadhesive properties, we evaluated whether defibrotide modulates the protection conferred to multiple myeloma cells by bone marrow stromal cells. Methods-Results: Defibrotide lacks significant single-agent in vitro cytotoxicity on multiple myeloma or solid tumor cells and does not attenuate their in vitro response to dexamethasone, bortezomib, immunomodulatory thalidomide derivatives, and conventional chemotherapeutics, including melphalan and cyclophosphamide. Importantly, defibrotide enhances in vivo chemosensitivity of multiple myeloma and mammary carcinoma xenografts in animal models. In cocultures of multiple myeloma cells with bone marrow stromal cells in vitro, defibrotide enhances the multiple myeloma cell sensitivity to melphalan and dexamethasone, and decreases multiple myeloma-bone marrow stromal cell adhesion and its sequelae, including nuclear factor-kappa B activation in multiple myeloma and bone marrow stromal cells, and associated cytokine production. Moreover, defibrotide inhibits expression and/or function of key mediators of multiple myeloma interaction with bone marrow stromal cell and endothelium, including heparanase, angiogenic cytokines, and adhesion molecules. Conclusion: Defibrotide's in vivo chemosensitizing properties and lack of direct in vitro activity against tumor cells suggest that it favorably modulates antitumor interactions between bone marrow stromal cells and endothelia in the tumor microenvironment. These data support clinical studies of defibrotide in combination with conventional and novel therapies to potentially improve patient outcome in multiple myeloma and other malignancies. C1 [Mitsiades, Constantine S.; Rouleau, Cecile; Menon, Krishna; Teicher, Beverly; Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Mitsiades, Constantine S.; Rouleau, Cecile; Menon, Krishna; Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Echart, Cinara; Distaso, Maria; Iacobelli, Massimo] Gentium SpA, Como, Italy. [Palumbo, Antonio; Boccadoro, Mario] Univ Turin, Div Hematol, Turin, Italy. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM contantine-mitsiadesc@dfci.harvard.edu; paul-richardson@dfci.harvard.edu FU NIH [PO-1 78373]; SPORE [P50 CA100707] FX Grant support: NIH grants PO-1 78373 and SPORE P50 CA100707 (K.C. Anderson); NIH Orphan Drug Grant (P.G. Richardson), the Richard Corman Fund (P.G. Richardson, C.S. Mitsiades) and the Chambers Medical Foundation (P.G. Richardson and C.S. Mitsiades). NR 50 TC 24 Z9 24 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2009 VL 15 IS 4 BP 1210 EP 1221 DI 10.1158/1078-0432.CCR-08-1270 PG 12 WC Oncology SC Oncology GA 410QI UT WOS:000263592600013 PM 19228727 ER PT J AU Mendez, E Houck, JR Doody, DR Fan, WH Lohavanichbutr, P Rue, TC Yueh, B Futran, ND Upton, MP Farwell, DG Heagerty, PJ Zhao, LP Schwartz, SM Chen, C AF Mendez, Eduardo Houck, John R. Doody, David R. Fan, Wenhong Lohavanichbutr, Pawadee Rue, Tessa C. Yueh, Bevan Futran, Neal D. Upton, Melissa P. Farwell, D. Gregory Heagerty, Patrick J. Zhao, Lue Ping Schwartz, Stephen M. Chen, Chu TI A Genetic Expression Profile Associated with Oral Cancer Identifies a Group of Patients at High Risk of Poor Survival SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PLASMINOGEN-ACTIVATOR INHIBITOR; ADVANCED LARYNGEAL-CANCER; GROWTH-FACTOR-BETA; NECK-CANCER; DIAGNOSTIC MARKER; INVASIVE FRONT; HEAD; RECEPTOR; LAMININ-5 AB Purpose: To determine if gene expression signature of invasive oral squamous cell carcinoma (OSCC) can subclassify OSCC based on survival. Experimental Design: We analyzed the expression of 131 genes in 119 OSCC 35 normal, and 17 dysplastic mucosa to identify cluster-defined subgroups. Multivariate Cox regression was used to estimate the association between gene expression and survival. By stepwise Cox regression, the top predictive models of OSCC-specific survival were determined and compared by receiver operating characteristic analysis. Results: The 3-year overall mean +/- SE survival for a cluster of 45 OSCC patients was 38.7 +/- 0.09% compared with 69.1 +/- 0.08% for the remaining patients. Multivariate analysis adjusted for age, sex, and stage showed that the 45 OSCC patient cluster had worse overall and OSCC-specific survival (hazard ratio, 3.31; 95% confidence interval, 1.66-6.58 and hazard ratio, 5.43; 95% confidence interval, 2.32-12.73, respectively). Stepwise Cox regression on the 131 probe sets revealed that a model with a term for LAMC2 (laminin gamma(2)) gene expression best identified patients with worst OSCC-specific survival. We fit a Cox model with a term for a principal component analysis-derived risk score marker and two other models that combined stage with either LAMC2 or PCA. The area under the curve for models combining stage with either LAMC2 or PCA was 0.80 or 0.82, respectively, compared with 0.70 for stage alone (P = 0.013 and 0.008, respectively). Conclusions: Gene expression and stage combined predict survival of OSCC patients better than stage alone. C1 [Mendez, Eduardo; Houck, John R.; Doody, David R.; Lohavanichbutr, Pawadee; Schwartz, Stephen M.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. [Mendez, Eduardo; Futran, Neal D.; Chen, Chu] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Rue, Tessa C.; Heagerty, Patrick J.; Zhao, Lue Ping] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Upton, Melissa P.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Schwartz, Stephen M.; Chen, Chu] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. [Fan, Wenhong; Zhao, Lue Ping] Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, Seattle, WA 98109 USA. [Yueh, Bevan] Univ Minnesota, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA. [Farwell, D. Gregory] Univ Calif Davis, Dept Otolaryngol Head & Neck Surg, Sacramento, CA 95817 USA. RP Chen, C (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, 1100 Fairview Ave N,M5-C800,POB 19024, Seattle, WA 98109 USA. EM cchen@fhcrc.org OI Yueh, Bevan/0000-0003-1380-1053 FU National Cancer Institute; NIH [R01CA095419]; National Center for Research Resources [1KL2RR025015-01]; Fred Hutchinson Cancer Research Center FX National Cancer Institute, NIH grant R01CA095419 (E. Mendez, J. R. Houck, D. R. Doody, W. Fan, P. Lohavanichbutr, B. Yueh, N. D. Futran, M. P. Upton, D.G. Farwell, L.P. Zhao, S.M. Schwartz, and C. Chen), National Center for Research Resources grant 1KL2RR025015-01 (E. Mendez, T.C. Rue, and P.J. Heagerty), and Fred Hutchinson Cancer Research Center institutional funds (C. Chen). NR 36 TC 31 Z9 31 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2009 VL 15 IS 4 BP 1353 EP 1361 DI 10.1158/1078-0432.CCR-08-1816 PG 9 WC Oncology SC Oncology GA 410QI UT WOS:000263592600028 PM 19228736 ER PT J AU Kirkwood, JM Lee, S Moschos, S Albertini, MR Michalak, JC Sander, C Whiteside, T Butterfield, LH Weiner, L AF Kirkwood, John M. Lee, Sandra Moschos, Stergios Albertini, Mark R. Michalak, John C. Sander, Cindy Whiteside, Theresa Butterfield, Lisa H. Weiner, Louis TI Immunogenicity and Antitumor Effects of Vaccination with Peptide Vaccine +/- Granulocyte-Monocyte Colony-Stimulating Factor and/or IFN-alpha 2b in Advanced Metastatic Melanoma: Eastern Cooperative Oncology Group Phase II Trial E1696 SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-DOSE INTERFERON-ALPHA-2B; CYTOLYTIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; HIGH-RISK MELANOMA; DENDRITIC CELLS; ADJUVANT IMMUNOTHERAPY; PERIPHERAL-BLOOD; HLA-A2 MELANOMAS; RANDOMIZED TRIAL; IDENTIFICATION AB Purpose: No therapy has ever shown prolongation of survival in stage IV metastatic melanoma. The association of cytokine-induced autoimmunity with improved prognosis led us to investigate the effect of multi-epitope melanoma vaccines alone and in combination with cytokines in this Eastern Cooperative Oncology Group multicenter phase II trial. Experimental Design: Eligible patients were required to have failed prior therapies and to be HLA-A2 positive. Three HLA class I-restricted lineage antigen epitopes were administered in a factorial 2 x 2 design. Peptide vaccine alone (arm A), or combined with granulocytemonocyte colony-stimulating factor (GM-CSF; Immunex) 250 mu g/d subcutaneously for 14 of 28 days each month (arm 13), or combined with IFN-alpha 2b (Intron A; Schering-Plough) 10 million units/m(2) three times a week (arm C), or combined with both IFN-alpha 2b and GM-CSF (arm D). The primary endpoint was immune response measured by enzyme-linked immunospot assay; secondary endpoints were clinical antitumor response, disease-free survival, and overall survival. Results: One hundred twenty patients enrolled and 115 patients were analyzed. Immune responses to at least one melanoma antigen were observed in 26 of 75 (35%) patients with serial samples. Neither IFN-alpha 2b nor GM-CSF significantly improved immune responses. Six objective clinical responses were documented. At a median follow-up of 25.4 months, the median overall survival of patients with vaccine immune response was significantly longer than that of patients with no immune response (21.3 versus 13.4 months; P = 0.046). Conclusion: Immune response to vaccination correlates with prolonged survival in patients with metastatic melanoma and is not enhanced by immunomodulatory cytokines as tested in this C1 [Kirkwood, John M.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Dept Med,Melanoma & Skin Canc Program, Pittsburgh, PA 15213 USA. [Lee, Sandra] Dana Farber Canc Inst, Boston, MA 02115 USA. [Albertini, Mark R.] Univ Wisconsin, Madison, WI USA. [Michalak, John C.] Siouxland Hematol Oncol Associates, Sioux City, ID USA. [Weiner, Louis] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Kirkwood, JM (reprint author), Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Dept Med,Melanoma & Skin Canc Program, Res Pavilion,Suite 132,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM KirkwoodJM@upmc.edu FU NIH [CA23318, CA66636, CA21115, CA39229]; Schering Plough and Immunex FX NIH grants CA23318, CA66636, CA21115, and CA39229 and research awards to Eastern Cooperative Oncology Group from Schering Plough and Immunex. NR 41 TC 79 Z9 84 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2009 VL 15 IS 4 BP 1443 EP 1451 DI 10.1158/1078-0432.CCR-08-1231 PG 9 WC Oncology SC Oncology GA 410QI UT WOS:000263592600039 PM 19228745 ER PT J AU Lin, NU Dieras, V Paul, D Lossignol, D Christodoulou, C Stemmler, HJ Roche, H Liu, MC Greil, R Ciruelos, E Loibl, S Gori, S Wardley, A Yardley, D Brufsky, A Blum, JL Rubin, SD Dharan, B Steplewski, K Zembryki, D Oliva, C Roychowdhury, D Paoletti, P Winer, EP AF Lin, Nancy U. Dieras, Veronique Paul, Devchand Lossignol, Dominique Christodoulou, Christos Stemmler, Hans-Joachim Roche, Henri Liu, Minetta C. Greil, Richard Ciruelos, Eva Loibl, Sibylle Gori, Stefania Wardley, Andrew Yardley, Denise Brufsky, Adam Blum, Joanne L. Rubin, Stephen D. Dharan, Bernie Steplewski, Klaudia Zembryki, Denise Oliva, Cristina Roychowdhury, Debasish Paoletti, Paolo Winer, Eric P. TI Multicenter Phase II Study of Lapatinib in Patients with Brain Metastases from HER2-Positive Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID NERVOUS-SYSTEM METASTASES; TRASTUZUMAB-BASED THERAPY; CAPECITABINE; CARCINOMA; EFFICACY AB Purpose: Brain metastases develop in one third of patients with advanced HER2+ breast cancer. Effective therapy for patients with central nervous system (CNS) progression after cranial radiation is extremely limited and represents a major clinical challenge. Lapatinib, an epidermal growth factor receptor/HER2 inhibitor, was associated with regressions of CNS lesions in a small phase 2 trial. The current study was done to further evaluate the CNS activity of lapatinib. The study was later amended to allow patients who progressed on lapatinib the option of receiving lapatinib plus capecitabine. Experimental Design: Eligible patients had HER2+ breast cancer, progressive brain metastases, prior trastuzumab, and cranial radiotherapy. The primary end point was CNS objective response, defined as >= 50% volumetric reduction of CNS lesion (s) in the absence of increasing steroid use, progressive neurologic signs and symptoms, or progressive extra-CNS disease. Results: Two-hundred and forty-two patients entered the study. CNS objective responses to lapatinib were observed in 6% of patients. In an exploratory analysis, 21% of patients experienced a >= 20% volumetric reduction in their CNS lesions. An association was observed between volumetric reduction and improvement in progression-free survival and neurologic signs and symptoms. Of the 50 evaluable patients who entered the lapatinib plus capecitabine extension, 20% experienced a CNS objective response and 40% experienced a >= 20% volumetric reduction in their CNS lesions. Conclusions: This study confirms the modest CNS antitumor activity of lapatinib. Additional responses were observed with the combination of lapatinib and capecitabine. Further studies of lapatinib-based regimens for CNS metastases from HER2+ breast cancer are warranted. C1 [Lin, Nancy U.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dieras, Veronique] Inst Curie, Paris, France. [Paul, Devchand] Rocky Mt Canc Ctr, Denver, CO USA. [Lossignol, Dominique] Inst Jules Bordet, B-1000 Brussels, Belgium. [Christodoulou, Christos] Metropolitan Hosp, Athens, Greece. [Stemmler, Hans-Joachim] Klinikum Univ Munchen, Munich, Germany. [Roche, Henri] Inst Claudius Regaud, Toulouse, France. [Liu, Minetta C.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Greil, Richard] Private Med Univ Hosp, Salzburg, Austria. [Ciruelos, Eva] Hosp 12 Octubre, E-28041 Madrid, Spain. [Loibl, Sibylle] Univ Frankfurt Klinikum, D-6000 Frankfurt, Germany. [Gori, Stefania] Azienda Opsedalier Perugia, Perugia, Italy. [Wardley, Andrew] Christie Hosp NHS Fdn Trust, Manchester, Lancs, England. [Yardley, Denise] Sarah Cannon Canc Ctr, Nashville, TN USA. [Brufsky, Adam] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. [Blum, Joanne L.] US Oncol Res, Texas Oncol, Baylor Sammons Canc Ctr, Dallas, TX USA. [Rubin, Stephen D.; Dharan, Bernie; Steplewski, Klaudia; Zembryki, Denise; Roychowdhury, Debasish; Paoletti, Paolo] GlaxoSmithKline Inc, Upper Providence, PA USA. [Paul, Devchand] US Oncol, Denver, CO USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ewiner@partners.org RI Roche, Henri/O-9211-2014; Wardley, ANdrew/N-8135-2015; GORI, Stefania/N-8827-2016; Greil, Richard/C-7673-2017; OI Roche, Henri/0000-0001-7463-205X; Wardley, ANdrew/0000-0002-9639-0888; GORI, Stefania/0000-0001-6320-405X; Greil, Richard/0000-0002-4462-3694; Ciruelos, Eva /0000-0002-2796-1042 FU GlaxoSmith Kline; Breast Cancer Research Foundation; American Society of Clinical Oncology Young Investigator Award and Career Development Award FX GlaxoSmith Kline, Breast Cancer Research Foundation (N.U. Lin and E. P. Winer), and American Society of Clinical Oncology Young Investigator Award and Career Development Award (N.U. Lin). NR 19 TC 260 Z9 267 U1 0 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2009 VL 15 IS 4 BP 1452 EP 1459 DI 10.1158/1078-0432.CCR-08-1080 PG 8 WC Oncology SC Oncology GA 410QI UT WOS:000263592600040 PM 19228746 ER PT J AU Gombart, AF Bhan, I Borregaard, N Tamez, H Camargo, CA Koeffler, HP Thadhani, R AF Gombart, Adrian F. Bhan, Ishir Borregaard, Niels Tamez, Hector Camargo, Carlos A. Koeffler, H. Phillip Thadhani, Ravi TI Low Plasma Level of Cathelicidin Antimicrobial Peptide (hCAP18) Predicts Increased Infectious Disease Mortality in Patients Undergoing Hemodialysis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID VITAMIN-D; 1,25-DIHYDROXYVITAMIN D-3; ANTIBACTERIAL PEPTIDES; HUMAN NEUTROPHILS; ALPHA-DEFENSINS; PROTEIN HCAP18; HOST-DEFENSE; CAMP GENE; LL-37; SURVIVAL AB Background. Human cathelicidin antimicrobial protein (hCAP18) is an antimicrobial and immunomodulatory peptide that has pleiotropic effects and is transcriptionally regulated by vitamin D. Because the administration of vitamin D analogues has been linked to decreased mortality among patients with end-stage renal disease, we hypothesized that low hCAP18 levels would identify those who are at increased risk of death attributable to infection while undergoing hemodialysis. Methods. We performed a case-control study nested in a prospective cohort of patients (n = 10,044) initiating incident hemodialysis. Case patients (n = 81) were those who died of an infectious disease within 1 year; control patients (n = 198) were those who survived at least 1 year while undergoing dialysis. Results. Mean (+/- SD) baseline levels of hCAP18 in case patients and control patients were ng/mL 539 +/- 278 and 650 +/- 353 ng/mL, respectively (P = .006). hCAP18 levels had a modest correlation with 1,25-dihydroxyvitamin D levels (r = 0.23; P = .053) but not with 25-hydroxyvitamin D levels (r = -0.06; P = .44). Patients with hCAP18 levels in the lowest tertile had a 2-fold increased risk (odds ratio, 2.1; 95% confidence interval, 1.2-3.5) of death attributable to infection; after multivariable adjustment, this relationship remained statistically significant (odds ratio, 3.7; 95% confidence interval, 1.2-11.2). Conclusions. In individuals initiating chronic hemodialysis, low baseline levels of hCAP18, a vitamin D regulated antimicrobial protein, are independently associated with an increased risk of death attributable to infection. C1 [Thadhani, Ravi] Massachusetts Gen Hosp, Ctr D Receptor Activat Res, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Gombart, Adrian F.; Koeffler, H. Phillip] Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Dept Med,Div Hematol Oncol, Los Angeles, CA 90095 USA. [Gombart, Adrian F.] Oregon State Univ, Dept Biochem & Biophys, Linus Pauling Inst, Corvallis, OR 97331 USA. [Camargo, Carlos A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Borregaard, Niels] Univ Copenhagen, Rigshosp, Dept Hematol, Granulocyte Res Lab, DK-2100 Copenhagen, Denmark. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Ctr D Receptor Activat Res, Dept Med, Div Nephrol, 55 Fruit St,Bulfinch 127, Boston, MA 02114 USA. EM rthadhani@partners.org FU National Kidney Foundation; National Institutes of Health [5R01AI065604-02] FX Potential conflicts of interest. All authors: no conflicts. NR 40 TC 82 Z9 88 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 15 PY 2009 VL 48 IS 4 BP 418 EP 424 DI 10.1086/596314 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 396IP UT WOS:000262585700008 PM 19133797 ER PT J AU Fulop, T Pawelec, G Castle, S Loeb, M AF Fulop, Tamas Pawelec, Graham Castle, Steven Loeb, Mark TI Immunosenescence and Vaccination in Nursing Home Residents SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LONG-TERM-CARE; RANDOMIZED CONTROLLED-TRIAL; T-CELL DIFFERENTIATION; INFLUENZA VACCINATION; ELDERLY-PEOPLE; CYTOMEGALOVIRUS-INFECTION; SIGNAL-TRANSDUCTION; LIPID RAFTS; AGE; MORTALITY AB The elderly population continues to increase in most countries. Concomitantly, the number of individuals who are institutionalized is also increasing, unfortunately, with more and more individuals being institutionalized at greater ages. These elderly individuals are very different from healthy, community-dwelling elderly individuals, in that many are considered to be frail and have various chronic diseases. It is apparent that the immune response diminishes even in healthy elderly people and that the pathologies that occur in nursing home patients, together with malnutrition, further impair immunity required for an effective vaccine response. Therefore, it is important to take secondary age-related effects, attributable to factors such as chronic diseases, inflammation, frailty, nutrition, functional status, and stress, into account when assessing vaccination strategies. Despite these alterations that can affect immune function and their potential interaction with vaccination, vaccination is still worthwhile and is recommended for elderly nursing home residents. Research efforts should continue attempts to elucidate the immunological basis of impaired immunity in nursing home residents to design improved prevention strategies for this vulnerable group. C1 [Loeb, Mark] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada. [Fulop, Tamas] Univ Sherbrooke, Fac Med, Div Geriatr, Program Immunol,Res Ctr, Quebec City, PQ, Canada. [Loeb, Mark] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8N 3Z5, Canada. [Pawelec, Graham] Univ Tubingen, Sch Med, Med Res Ctr, Tubingen Ageing & Tumour Immunol Grp, Tubingen, Germany. [Castle, Steven] Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Loeb, M (reprint author), McMaster Univ, Dept Pathol & Mol Med, MDCL 3200,1200 Main St W, Hamilton, ON L8N 3Z5, Canada. EM loebm@mcmaster.ca OI Pawelec, Graham/0000-0002-3600-0163 NR 52 TC 29 Z9 29 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 15 PY 2009 VL 48 IS 4 BP 443 EP 448 DI 10.1086/596475 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 396IP UT WOS:000262585700013 PM 19140756 ER PT J AU Parienti, JJ Bangsberg, DR Verdon, R Gardner, EM AF Parienti, Jean-Jacques Bangsberg, David R. Verdon, Renaud Gardner, Edward M. TI Better Adherence with Once-Daily Antiretroviral Regimens: A Meta-Analysis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HIV-INFECTED PATIENTS; VIROLOGICAL FAILURE; VIRAL SUPPRESSION; THERAPY; LAMIVUDINE; EFAVIRENZ; LOPINAVIR/RITONAVIR; EMTRICITABINE; RESISTANCE; OUTCOMES AB Once-daily regimens of antiretroviral therapy are simpler than other regimens, but whether such regimens are associated with better adherence to treatment is controversial. We performed a meta-analysis of 11 randomized, controlled trials (total number of subjects, 3029), which revealed that the adherence rate was better with once-daily regimens (+2.9%; 95% confidence interval, 1.0%-4.8%;) than P < .003 with twice-daily regimens. This modest effect was more pronounced at the time of treatment initiation and for regimens for which all medications were taken once per day. C1 [Parienti, Jean-Jacques] Cote Nacre Univ Hosp, Dept Biostat & Clin Res, F-14033 Caen, France. [Parienti, Jean-Jacques; Verdon, Renaud] Cote Nacre Univ Hosp, Dept Infect Dis, F-14033 Caen, France. [Parienti, Jean-Jacques] Univ Paris 06, Paris, France. [Parienti, Jean-Jacques] INSERM, U707, Paris, France. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. [Gardner, Edward M.] Denver Hlth & Hosp Author, Dept Publ Hlth, Denver, CO USA. RP Parienti, JJ (reprint author), Cote Nacre Univ Hosp, Dept Biostat & Clin Res, Ave Cote Nacre, F-14033 Caen, France. EM parienti-jj@chu-caen.fr FU Cote de Nacre University Hospital; National Institute of Alcohol Abuse and Alcoholism [K-24 015287]; National Institutes of Health [AI067063]; Abbott and Boehringer-Ingelheim; Abbott; Bristol-Myers Squibb; Gilead Sciences FX Potential conflicts of interest. J.-J.P. has received prior grant support from Abbott and Boehringer-Ingelheim. D.R.B. has received prior grant support from Abbott, Bristol-Myers Squibb, and Gilead Sciences. R.V. and E.M. G.: no conflicts. NR 25 TC 129 Z9 131 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 15 PY 2009 VL 48 IS 4 BP 484 EP 488 DI 10.1086/596482 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 396IP UT WOS:000262585700019 PM 19140758 ER PT J AU Musher, DM Logan, N Bressler, AM Johnson, DP Rossignol, JF AF Musher, Daniel M. Logan, Nancy Bressler, Adam M. Johnson, David P. Rossignol, Jean-Francois TI Nitazoxanide versus Vancomycin in Clostridium difficile Infection: A Randomized, Double-Blind Study SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID COLITIS; METRONIDAZOLE; DIARRHEA; DISEASE; OUTBREAK; THERAPY AB Background. Vancomycin is the only US Food and Drug Administration-approved drug for treatment of Clostridium difficile infection (CDI). Metronidazole has been widely used for this purpose but may be inferior to vancomycin, especially for hospitalized patients with severe disease. We report a prospective, double-blind, randomized controlled trial comparing nitazoxanide with vancomycin for treatment of CDI. Methods. Fifty patients with CDI were randomized to receive vancomycin or nitazoxanide for 10 days. An initial response was considered to be the absence of all CDI symptoms between days 11 and 13, and a final response was considered to be lack of symptom recurrence by day 31. Results. One patient fulfilled an exclusion criterion and was removed from the study. Twenty-seven patients received vancomycin, and 23 received nitazoxanide; 23 and 18 patients, respectively, completed the full course of treatment. Initial responses occurred in 20 (74%) of 27 patients treated with vancomycin and in 17 (77%) of 22 patients treated with nitazoxanide (95% confidence interval, -24% to +28%). In those who completed therapy, response rates were 87% ( 20 of 23 patients) in the vancomycin group and 94% ( 17 of 18 patients) in the nitazoxanide group ( 95% confidence interval, -18% to +30%). Times to complete resolution of symptoms were similar in the 2 groups (). Two patients in the vancomycin group and 1 patient in the nitazoxanide group experienced Pp. 55 relapse within 31 days after beginning treatment. Sustained response rates were 78% ( 18 of 23 patients) for the vancomycin group, and 89% ( 16 of 18 patients) for the nitazoxanide group ( 95% confidence interval, -18% to +35%). Conclusions. The small sample precludes conclusions about noninferiority of nitazoxanide to vancomycin. Nevertheless, this is the first recent randomized controlled trial to compare any antimicrobial agent other than metronidazole with vancomycin. Results suggest that nitazoxanide may be as effective as vancomycin in treating CDI. C1 [Musher, Daniel M.; Logan, Nancy] Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Musher, Daniel M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Bressler, Adam M.] Dekalb Med Ctr, Infect Dis Specialists Atlanta, Atlanta, GA USA. [Bressler, Adam M.] Dekalb Med Ctr, Clin Microbiol Lab, Atlanta, GA USA. [Johnson, David P.] Bay Pines Vet Affairs Med Ctr, Div Infect Dis, Bay Pines, FL USA. [Rossignol, Jean-Francois] Romark Inst Med Res, Tampa, FL USA. [Rossignol, Jean-Francois] Stanford Univ, Sch Med, Dept Med, Div Gastroenterol & Hepatol, Palo Alto, CA 94304 USA. RP Musher, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Rm 4B-370,2002 Holcombe Blvd, Houston, TX 77030 USA. EM daniel.musher@med.va.gov FU Department of Veterans Affairs through Merit Review Funding; Romark Laboratories; Infectious Disease Section at Baylor College of Medicine FX Potential conflicts of interest. The academic departments of affiliation for D. M. M., N.L., A. M. B., and D. P. J. received funding from Romark Laboratories for studies of nitazoxanide. The Infectious Disease Section at Baylor College of Medicine has received funds in D. M. M.'s name from Salix for studies of rifaximin; from Genzyme for studies of tolevamer; and from Merck for studies of pneumococcal vaccine. J.-F.R. is an employee and owner of equity interests in Romark Laboratories. NR 19 TC 84 Z9 88 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 15 PY 2009 VL 48 IS 4 BP E41 EP E46 DI 10.1086/596552 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 396IP UT WOS:000262585700027 PM 19133801 ER PT J AU Hochedlinger, K Plath, K AF Hochedlinger, Konrad Plath, Kathrin TI Epigenetic reprogramming and induced pluripotency SO DEVELOPMENT LA English DT Review ID EMBRYONIC STEM-CELLS; PRIMORDIAL GERM-CELLS; HUMAN SOMATIC-CELLS; SMALL-MOLECULE COMPOUNDS; PANCREATIC BETA-CELLS; NUCLEAR TRANSFER; DNA METHYLATION; ES CELLS; MOUSE EMBRYOS; HUMAN FIBROBLASTS AB The cloning of animals from adult cells has demonstrated that the developmental state of adult cells can be reprogrammed into that of embryonic cells by uncharacterized factors within the oocyte. More recently, transcription factors have been identified that can induce pluripotency in somatic cells without the use of oocytes, generating induced pluripotent stem (iPS) cells. iPS cells provide a unique platform to dissect the molecular mechanisms that underlie epigenetic reprogramming. Moreover, iPS cells can teach us about principles of normal development and disease, and might ultimately facilitate the treatment of patients by custom-tailored cell therapy. C1 [Hochedlinger, Konrad] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hochedlinger, Konrad] Harvard Univ, Ctr Regenerat Med, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Boston, MA 02114 USA. [Plath, Kathrin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem,Eli & Edythe Broad Ctr Regenerat M, Jonsson Comprehens Canc Ctr,Mol Biol Inst, Los Angeles, CA 90024 USA. RP Hochedlinger, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu; kplath@mednet.ucla.edu OI Plath, Kathrin/0000-0001-7796-3372 NR 168 TC 344 Z9 361 U1 6 U2 80 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 FEB 15 PY 2009 VL 136 IS 4 BP 509 EP 523 DI 10.1242/dev.020867 PG 15 WC Developmental Biology SC Developmental Biology GA 397WI UT WOS:000262692500001 PM 19168672 ER PT J AU Sharma, SV Settleman, J AF Sharma, Sreenath V. Settleman, Jeffrey TI ErbBs in lung cancer SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE Lung cancer; ErbBs; EGFR; TKIs ID GROWTH-FACTOR-RECEPTOR; NONSMALL CELL LUNG; TYROSINE KINASE INHIBITOR; GENE COPY NUMBER; IN-SITU-HYBRIDIZATION; EXON-19 DELETION MUTATIONS; DRUG-RESISTANCE MUTATION; EML4-ALK FUSION GENE; ACQUIRED-RESISTANCE; EGFR MUTATIONS AB Lung cancer remains the leading cause of cancer deaths worldwide, and advanced stage disease is largely refractory to conventional chemotherapy. Thus, there is an important need for alternative treatment strategies, and the ErbB proteins have emerged as potentially important therapeutic drug targets in this setting, apparently reflecting a state of "oncogene addiction" ill some lung tumors. In this review, we discuss the recent identification of mutations that promote activation of ErbB family proteins in a Subset of lung cancers, and the development of selective inhibitors of these proteins that have demonstrated clinical efficacy. We also discuss the problem of drug resistance, which severely limits the clinical utility of such agents, and has prompted intense efforts to better understand molecular mechanisms underlying drug resistance as well as Strategies to overcome or prevent Such resistance. (C) 2008 Elsevier Inc. All rights reserved. C1 [Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu NR 182 TC 37 Z9 40 U1 1 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD FEB 15 PY 2009 VL 315 IS 4 BP 557 EP 571 DI 10.1016/j.yexcr.2008.07.026 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 407WP UT WOS:000263395300001 PM 18721806 ER PT J AU Naar, AM Thakur, JK AF Naeaer, Anders M. Thakur, Jitendra K. TI Nuclear receptor-like transcription factors in fungi SO GENES & DEVELOPMENT LA English DT Review DE Nuclear receptor; zinc cluster transcription factor; multidrug resistance; Mediator; Gal11p; KIX domain ID PREGNANE-X-RECEPTOR; ZINC CLUSTER PROTEINS; PROLIFERATOR-ACTIVATED RECEPTORS; REV-ERB-ALPHA; SACCHAROMYCES-MAL-ACTIVATOR; PROLINE UTILIZATION PATHWAY; LIGAND-BINDING DOMAINS; MULTIDRUG-RESISTANCE; CANDIDA-GLABRATA; DRUG-RESISTANCE AB Members of the metazoan nuclear receptor superfamily regulate gene expression programs in response to binding of cognate lipophilic ligands. Evolutionary studies using bioinformatics tools have concluded that lower eukaryotes, such as fungi, lack nuclear receptor homologs. Here review recent discoveries suggesting that members of the fungal zinc cluster family of transcription regulators represent functional analogs of metazoan nuclear receptors. These findings indicate that nuclear receptor-like ligand-dependent gene regulatory mechanisms emerged early during eukaryotic evolution, and provide the impetus for further detailed studies of the possible evolutionary and mechanistic relationships of fungal zinc cluster transcription factors and metazoan nuclear receptors. Clinical implications of the discovery of nuclear receptor-like transcription factors in pathogenic fungi will also be discussed. C1 [Naeaer, Anders M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Cell Biol, Charlestown, MA 02129 USA. RP Naar, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM naar@helix.mgh.harvard.edu NR 150 TC 25 Z9 25 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD FEB 15 PY 2009 VL 23 IS 4 BP 419 EP 432 DI 10.1101/gad.1743009 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 410TH UT WOS:000263600700004 PM 19240130 ER PT J AU Soukas, AA Kane, EA Carr, CE Melo, JA Ruvkun, G AF Soukas, Alexander A. Kane, Elizabeth A. Carr, Christopher E. Melo, Justine A. Ruvkun, Gary TI Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans SO GENES & DEVELOPMENT LA English DT Article DE C. elegans; fat metabolism; life span; insulin/IGF; AKT ID AGE-1 PI3 KINASE; C-ELEGANS; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; NERVOUS-SYSTEM; MTOR COMPLEX-2; INSULIN; LONGEVITY; RAPTOR; AKT/PKB AB Rictor is a component of the target of rapamycin complex 2 (TORC2). While TORC2 has been implicated in insulin and other growth factor signaling pathways, the key inputs and outputs of this kinase complex remain unknown. We identified mutations in the Caenorhabditis elegans homolog of rictor in a forward genetic screen for increased body fat. Despite high body fat, rictor mutants are developmentally delayed, small in body size, lay an attenuated brood, and are short-lived, indicating that Rictor plays a critical role in appropriately partitioning calories between long-term energy stores and vital organismal processes. Rictor is also necessary to maintain normal feeding on nutrient-rich food sources. In contrast to wild-type animals, which grow more rapidly on nutrient-rich bacterial strains, rictor mutants display even slower growth, a further reduced body size, decreased energy expenditure, and a dramatically extended life span, apparently through inappropriate, decreased consumption of nutrient-rich food. Rictor acts directly in the intestine to regulate fat mass and whole-animal growth. Further, the high-fat phenotype of rictor mutants is genetically dependent on akt-1, akt-2, and serum and glucocorticoid-induced kinase-1 (sgk-1). Alternatively, the life span, growth, and reproductive phenotypes of rictor mutants are mediated predominantly by sgk-1. These data indicate that Rictor/TORC2 is a nutrient-sensitive complex with outputs to AKT and SGK to modulate the assessment of food quality and signal to fat metabolism, growth, feeding behavior, reproduction, and life span. C1 [Soukas, Alexander A.; Kane, Elizabeth A.; Melo, Justine A.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Soukas, Alexander A.; Kane, Elizabeth A.; Melo, Justine A.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Soukas, Alexander A.] Massachusetts Gen Hosp, Endocrine Div & Diabet Unit, Boston, MA 02114 USA. [Carr, Christopher E.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA. RP Ruvkun, G (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu OI Carr, Christopher/0000-0002-7946-5622 FU NIDDK NIH HHS [F32 DK080607, F32DK080607, R01 DK070147, R01DK070147] NR 55 TC 183 Z9 197 U1 3 U2 27 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 FEB 15 PY 2009 VL 23 IS 4 BP 496 EP 511 DI 10.1101/gad.1775409 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 410TH UT WOS:000263600700010 PM 19240135 ER PT J AU Imamura, T Kikuchi, H Herraiz, MT Park, DY Mizukami, Y Mino-Kenduson, M Lynch, MP Rueda, BR Benita, Y Xavier, RJ Chung, DC AF Imamura, Takaaki Kikuchi, Hirotoshi Herraiz, Maria-Teresa Park, Do-Youn Mizukami, Yusuke Mino-Kenduson, Mari Lynch, Maureen P. Rueda, Bo R. Benita, Yair Xavier, Ramnik J. Chung, Daniel C. TI HIF-1 alpha and HIF-2 alpha have divergent roles in colon cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE colon cancer; HIF; angiogenesis ID HYPOXIA-INDUCIBLE FACTOR; ENDOTHELIAL GROWTH-FACTOR; CELL-CYCLE ARREST; TUMOR ANGIOGENESIS; TRANSCRIPTIONAL RESPONSE; PANCREATIC-CANCER; GENE-EXPRESSION; FACTOR 1-ALPHA; PROTEIN; FACTOR-1-ALPHA AB Hypoxia-inducible factor (HIF)-1 and HIF-2 are heterodimeric transcription factors that mediate the cellular response to hypoxia. Their key regulatory subunits, HIF-1 alpha and HIF-2 alpha are induced similarly by hypoxia, but their functional roles in cancer ill be distinct and isoform-specific. SW480 colon cancer cells with stable expression of siRNA to HIF-1 alpha or HIF-2 alpha or both were established. HIF-1 alpha-deficient cells displayed lower rates of proliferation and migration. but HIF-2 alpha-deficient cells exhibited enhanced anchorage independent growth in a soft agar assay. Xenograft studies revealed that HIF-1 alpha deficiency inhibited overall tumor growth. whereas deficiency of HIF-2 alpha stimulated tumor growth. In human colon cancer tissues, expression of HIF-1 alpha and to a lesser extent. HIF-2 alpha. was linked to upregulation of VEGF and tumor angiogenesis. However. loss of expression of HIF-2 alpha but not HIF-1 alpha was strongly correlated with advanced tumor stage. DNA microarray analysis identified distinct sets of HIF-1 alpha and HIF-2 alpha target genes that may explain these phenotypic differences. Collectively, these findings suggest that HIF isoforms may have differing cellular functions in colon cancer. In particular. HIF-1 alpha promoted the growth of SW480 colon cancer cells but HIF-2 alpha appeared to restrain growth. Consequently, therapeutic approaches that target HIF may need to consider these isoform-specific properties. (c) 2008 Wiley-Liss. Inc. C1 [Imamura, Takaaki; Kikuchi, Hirotoshi; Herraiz, Maria-Teresa; Xavier, Ramnik J.; Chung, Daniel C.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. [Park, Do-Youn; Mino-Kenduson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mizukami, Yusuke] Asahikawa Med Coll, Asahikawa, Hokkaido 078, Japan. [Lynch, Maureen P.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. [Benita, Yair; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, GI Unit, GRJ 825, Boston, MA 02114 USA. EM dchung@partners.org RI Benita, Yair/E-3094-2012 FU NIH [CA92594] FX NIH: Grant number: CA92594. Grant sponsor: Kate J. and Dorothy L. Clapp Fund. NR 57 TC 72 Z9 76 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 15 PY 2009 VL 124 IS 4 BP 763 EP 771 DI 10.1002/ijc.24032 PG 9 WC Oncology SC Oncology GA 396VD UT WOS:000262618400002 PM 19030186 ER PT J AU Brunelle, JK Letai, A AF Brunelle, Joslyn K. Letai, Anthony TI Control of mitochondrial apoptosis by the Bcl-2 family SO JOURNAL OF CELL SCIENCE LA English DT Article ID MEMBRANE PERMEABILIZATION; CELL-DEATH; BH3 DOMAINS; BAX; PROTEINS; GENE; ACTIVATION; DISTINCT; BINDING; MEMBERS C1 [Brunelle, Joslyn K.; Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM Anthony_Letai@dfci.harvard.edu FU NCI NIH HHS [P01 CA068484, R01 CA129974] NR 37 TC 393 Z9 419 U1 2 U2 30 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD FEB 15 PY 2009 VL 122 IS 4 BP 437 EP 441 DI 10.1242/jcs.031682 PG 5 WC Cell Biology SC Cell Biology GA 403GS UT WOS:000263071700001 PM 19193868 ER PT J AU Reynoso, ED Elpek, KG Francisco, L Bronson, R Bellemare-Pelletier, A Sharpe, AH Freeman, GJ Turley, SJ AF Reynoso, Erika D. Elpek, Kutlu G. Francisco, Loise Bronson, Roderick Bellemare-Pelletier, Angelique Sharpe, Arlene H. Freeman, Gordon J. Turley, Shannon J. TI Intestinal Tolerance Is Converted to Autoimmune Enteritis upon PD-1 Ligand Blockade SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL TOLERANCE; MUCOSAL IMMUNE-RESPONSES; MESENTERIC LYMPH-NODES; DENDRITIC CELLS; INDUCED EXPRESSION; CROSS-PRESENTATION; EPITHELIAL-CELLS; SELF-TOLERANCE; DEATH-1 LIGAND; ANTIGEN AB The B7 family member programmed death-1 ligand (PD-L1) has been shown to play an inhibitory role in the regulation of T cell responses in several organs. However, the role of PD-L1 in regulating tolerance to self-Ags of the small intestine has not been previously addressed. In this study, we investigated the role of PD-L1 in CD8(+) T cell tolerance to an intestinal epithelium-specific Ag using the iFABP-tOVA transgenic mouse model, in which OVA is expressed as a self-Ag throughout the small intestine. Using adoptive transfer of naive OVA-specific CD8(+) T cells, we show that loss of PD-1:PD-L1 signaling, by either Ab-mediated PD-L1 blockade or transfer of PD-1(-/-) T cells, leads to considerable expansion of OVA-specific CD8(+) T cells and their differentiation into effector cells capable of producing proinflammatory cytokines. A fatal CD8(+) T cell-mediated inflammatory response develops rapidly against the small bowel causing destruction of the epithelial barrier, severe blunting of intestinal villi, and recruitment and activation of myeloid cells. This response is highly specific because immune destruction selectively targets the small intestine but not other organs. Collectively, these results indicate that loss of the PD-1:PD-L1 inhibitory pathway breaks CD8(+) T cell tolerance to intestinal self-Ag, thus leading to severe enteric autoimmunity. The Journal of Immunology, 2009, 182: 2102-2112. C1 [Reynoso, Erika D.; Elpek, Kutlu G.; Bellemare-Pelletier, Angelique; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Reynoso, Erika D.] Harvard Univ, Sch Med, Div Med Sci, Cambridge, MA 02138 USA. [Francisco, Loise; Bronson, Roderick; Sharpe, Arlene H.; Turley, Shannon J.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Francisco, Loise] Brigham & Womens Hosp, Boston, MA 02115 USA. [Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,Room D1440A, Boston, MA 02115 USA. EM shannon_turley@dfci.harvard.edu FU Claudia Adams Barr Program for Innovative Cancer Research; Baruj Benacerraf Fellowship in Immunology; National Institutes of Health [R01 DK074500, AI56299] FX This work was supported in part by a grant front the Claudia Adams Barr Program for Innovative Cancer Research (to S.J.T.). the Baruj Benacerraf Fellowship in Immunology (to K.G.E.), and National Institutes of Health Grants R01 DK074500 (to S.J.T.) and AI56299 (to A.H.S. and G.J.F.). NR 51 TC 52 Z9 58 U1 1 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 FEB 15 PY 2009 VL 182 IS 4 BP 2102 EP 2112 DI 10.4049/jimmunol.0802769 PG 11 WC Immunology SC Immunology GA 404BS UT WOS:000263126300038 PM 19201863 ER PT J AU Samuvel, DJ Sundararaj, KP Nareika, A Lopes-Virella, MF Huang, Y AF Samuvel, Devadoss J. Sundararaj, Kamala P. Nareika, Alena Lopes-Virella, Maria F. Huang, Yan TI Lactate Boosts TLR4 Signaling and NF-kappa B Pathway-Mediated Gene Transcription in Macrophages via Monocarboxylate Transporters and MD-2 Up-Regulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED INSULIN-RESISTANCE; DIET-INDUCED OBESITY; SKELETAL-MUSCLE; ADIPOSE-TISSUE; MESSENGER-RNA; EXPRESSION; ACTIVATION; TOLL-LIKE-RECEPTOR-4; INFLAMMATION; HYPERLACTATEMIA AB It has been shown that lactate induces insulin resistance. However, the underlying mechanisms have not been well understood. Based on our observation that lactate augments LPS-stimulated inflammatory gene expression, we proposed that lactate may enhance TLR4 signaling in macrophages, which has been shown to play an important role in insulin resistance in adipocytes. In this study, we demonstrated that lactate stimulated NTD-2, a coreceptor for TLR4 signaling activation, NF-kappa B transcriptional activity, and the expression of inflammatory genes in human U937 histiocytes; (resident macrophages). Similar enhancement of the inflammatory gene expression by lactate was also observed in human monocyte-derived macrophages. The essential role of MD-2 in lactate-augmented TLR4 signaling was confirmed by observation that the suppression of MD-2 expression by small interfering RNA led to significant inhibition of inflammatory gene expression. To further elucidate how lactate treatment enhances TLR4 activation, we showed that the augmentation of inflammatory gene expression by lactate was abrogated by antioxidant treatment, suggesting a critical role of reactive oxygen species in the enhancement of TLR4 activation by lactate. Finally, we showed that alpha-cyano-4-hydroxycinnamic acid, a classic inhibitor for monocarboxylate transporters, blocked lactate-augmented inflammatory gene expression and nuclear NF-kappa B activity, indicating that lactate transport through monocarboxylate transporters is required for lactate-enhanced TLR4 activation. Collectively, this study documents that lactate boosts TLR4 activation and NF-kappa B-dependent inflammatory gene expression via monocarboxylate transporters and MD-2 up-regulation. The Journal of Immunology,2009,182:2476-2484. C1 [Lopes-Virella, Maria F.; Huang, Yan] Ralph H Johnson Vet Affairs Med Center, Charleston, SC 29401 USA. [Samuvel, Devadoss J.; Sundararaj, Kamala P.; Nareika, Alena; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Center, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU National Institutes of Health [DE16353]; Department of Veterans Affairs FX This work was supported by National Institutes of Health Grant DE16353 and a Merit Review Grant from the Department of Veterans Affairs (to Y.H.). NR 49 TC 58 Z9 61 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 FEB 15 PY 2009 VL 182 IS 4 BP 2476 EP 2484 DI 10.4049/jimmunol.0802059 PG 9 WC Immunology SC Immunology GA 404BS UT WOS:000263126300078 PM 19201903 ER PT J AU Peleg, AY Monga, D Pillai, S Mylonakis, E Moellering, RC Eliopoulos, GM AF Peleg, Anton Y. Monga, Divya Pillai, Satish Mylonakis, Eleftherios Moellering, Robert C., Jr. Eliopoulos, George M. TI Reduced Susceptibility to Vancomycin Influences Pathogenicity in Staphylococcus aureus Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GALLERIA-MELLONELLA; IN-VIVO; RESISTANT; VIRULENCE; MODEL; BACTEREMIA; EVOLUTION; STRAIN AB In the present study, we demonstrated the utility of the non-mammalian model system Galleria mellonella for studying the pathogenesis of Staphylococcus aureus infection. By use of clinical and laboratory strains that had been exposed to vancomycin, we showed that both agr functional status and vancomycin minimum inhibitory concentration are determinants associated with the virulence of S. aureus in G. mellonella. These results show that G. mellonella can be effectively used to facilitate the in vivo study of S. aureus virulence and, more specifically, the relationship between antibiotic drug resistance and the pathogenesis of infection. C1 [Peleg, Anton Y.; Pillai, Satish; Moellering, Robert C., Jr.; Eliopoulos, George M.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Peleg, Anton Y.; Monga, Divya; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Peleg, Anton Y.; Pillai, Satish; Mylonakis, Eleftherios; Moellering, Robert C., Jr.; Eliopoulos, George M.] Harvard Univ, Sch Med, Boston, MA USA. RP Peleg, AY (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 110 Francis St,LMOB Suite GB, Boston, MA 02215 USA. EM apeleg@bidmc.harvard.edu OI Peleg, Anton/0000-0002-2296-2126 FU National Institutes of Health [AI63084]; Ellison Medical Foundation; Cubist Pharmaceuticals FX Financial support: National Institutes of Health (K08 award AI63084 to E. M.); Ellison Medical Foundation (New Scholar Award in Global Infectious Diseases to E. M.). This work was supported through a research grant from Cubist Pharmaceuticals (grant to G. M. E.). NR 14 TC 81 Z9 82 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 15 PY 2009 VL 199 IS 4 BP 532 EP 536 DI 10.1086/596511 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 399LU UT WOS:000262802200009 PM 19125671 ER PT J AU Sagar, M Laeyendecker, O Lee, S Gamiel, J Wawer, MJ Gray, RH Serwadda, D Sewankambo, NK Shepherd, JC Toma, J Huang, W Quinn, TC AF Sagar, Manish Laeyendecker, Oliver Lee, Sandra Gamiel, Jordyn Wawer, Maria J. Gray, Ronald H. Serwadda, David Sewankambo, Nelson K. Shepherd, James C. Toma, Jonathan Huang, Wei Quinn, Thomas C. TI Selection of HIV Variants with Signature Genotypic Characteristics during Heterosexual Transmission SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 15th Conference on Retroviruses and Opportunistic Infections CY FEB 03-06, 2008 CL Boston, MA ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZING ANTIBODY-RESPONSES; CORECEPTOR TROPISM; SEQUENCE VARIATION; PRIMARY INFECTION; ENVELOPE PROTEIN; AIDS-PREVENTION; COMMUNITY TRIAL; UGANDA; PROGRESSION AB Background. Newly infected subjects acquire a limited number of human immunodeficiency virus type 1 (HIV-1) variants with specific genotypic and phenotypic features from the array of viruses present in a chronically infected transmitting partner. Methods. We examined HIV-1 envelope sequences from the earliest available serum sample after HIV-1 acquisition in 13 newly infected subjects and from their epidemiologically linked HIV-1-infected heterosexual partner. Samples from both members were collected on the same day in the Rakai Community Cohort Study. Results. Ten couples were infected with subtype D HIV-1, and 3 pairs had subtype A HIV-1. Newly infected subjects acquired a subset of the viruses that were circulating in the transmitting partner; transmitted variants had less diversity and divergence and were more closely related to the ancestral sequences. The majority of signature amino acid differences among donor and recipient sequences were in and immediately following the V3 loop. Envelopes from recipients were significantly shorter and had a lower V3 charge than envelopes from donors, but there was no significant difference in the number of potential N-linked glycosylation sites. Conclusion. A minority subset of HIV-1 variants with signature genotypes is favored for transmission in this population. C1 [Sagar, Manish] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lee, Sandra] Dana Farber Canc Inst, Boston, MA 02115 USA. [Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Univ, Immunoregulat Lab, NIAID, NIH, Baltimore, MD USA. [Laeyendecker, Oliver; Gamiel, Jordyn; Shepherd, James C.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Serwadda, David; Sewankambo, Nelson K.] Makerere Univ, Kampala, Uganda. [Toma, Jonathan; Huang, Wei] Monogram Biosci, San Francisco, CA USA. RP Sagar, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 65 Landsdowne St,Rm 447, Cambridge, MA 02139 USA. EM msagar@partners.org RI Laeyendecker, Oliver/B-9331-2009; OI Sagar, Manish/0000-0001-9803-6594; Sewankambo, Nelson/0000-0001-9362-053X; Laeyendecker, Oliver/0000-0002-6429-4760 FU FIC NIH HHS [5D43TW00010, D43 TW000010]; Intramural NIH HHS [Z01 AI000361-25, Z99 AI999999]; NIAID NIH HHS [R01 AI077473-01A2, AI077473, R01 AI077473, R01 AI342650, R01 AI34826]; NICHD NIH HHS [5P30HD06826] NR 42 TC 67 Z9 70 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 15 PY 2009 VL 199 IS 4 BP 580 EP 589 DI 10.1086/596557 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 399LU UT WOS:000262802200017 PM 19143562 ER PT J AU Costello, DJ Kilbride, RD Cole, AJ AF Costello, Daniel J. Kilbride, Ronan D. Cole, Andrew J. TI Cryptogenic New Onset Refractory Status Epilepticus (NORSE) in adults-Infectious or not? SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Epilepsy; New Onset Refractory Status Epilepticus (NORSE); Cryptogenic; Encephalitis ID FOCAL STATUS EPILEPTICUS; LIMBIC ENCEPHALITIS; DE-NOVO AB Introduction: In the majority of cases of New Onset Refractory Status Epilepticus (NORSE) in adults, a cause is discovered. However, some cases of NORSE remain undiagnosed, i.e. cryptogenic. They are usually presumed to be due to infectious encephalitis and typically have devastating consequences. We describe our experience with six adults who presented with NORSE and raise the possibility of non-infectious causes. Methods: Retrospective case series from an epilepsy service in a tertiary care urban hospital. We compare the clinical features of these cases with patients who develop NORSE in the setting of clinically-defined encephalitis from the California Encephalitis Project (most of whom are etiologically cryptogenic) as well as with patients who develop NORSE in the setting of proven infectious encephalitis. Results: We describe 6 previously-normal adults with NORSE where a cause was not established despite an exhaustive search. With an average duration of 36 days (range 6-68), the in-hospital and long-term morbidities were high; one patient died of the propofol infusion syndrome. In contradistinction to NORSE in the setting of etiologically-proven infectious encephalitis, these patients were afebrile and the abnormalities evident during their evaluation could be attributed to the ictal activity itself. Neuropathological examination revealed non-specific findings in 4 patients. Conclusions: Though an underlying etiology remains unproven in these patients, we contend that NORSE is etiologically heterogeneous, with a proportion of cases due to non-infectious causes. Further study of this poorly understood form of status epilepticus is needed. (C) 2008 Elsevier B.V. All rights reserved. C1 [Costello, Daniel J.; Kilbride, Ronan D.; Cole, Andrew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Epilepsy Serv, Boston, MA 02114 USA. RP Costello, DJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, ACC 7, Boston, MA 02114 USA. EM djcostello@partners.org NR 17 TC 29 Z9 29 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD FEB 15 PY 2009 VL 277 IS 1-2 BP 26 EP 31 DI 10.1016/j.jns.2008.10.007 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 404XV UT WOS:000263187200006 PM 19013586 ER PT J AU Wang, YYE Li, B Carlson, JM Streeck, H Gladden, AD Goodman, R Schneidewind, A Power, KA Toth, I Frahm, N Alter, G Brander, C Carrington, M Walker, BD Altfeld, M Heckerman, D Allen, TM AF Wang, Yaoyu E. Li, Bin Carlson, Jonathan M. Streeck, Hendrik Gladden, Adrianne D. Goodman, Robert Schneidewind, Arne Power, Karen A. Toth, Ildiko Frahm, Nicole Alter, Galit Brander, Christian Carrington, Mary Walker, Bruce D. Altfeld, Marcus Heckerman, David Allen, Todd M. TI Protective HLA Class I Alleles That Restrict Acute-Phase CD8(+) T-Cell Responses Are Associated with Viral Escape Mutations Located in Highly Conserved Regions of Human Immunodeficiency Virus Type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID HEPATITIS-C VIRUS; HIV VACCINE DESIGN; LYMPHOCYTE ESCAPE; IMMUNE-RESPONSES; SUBTYPE-C; SEQUENCE POLYMORPHISMS; SIVMAC239 REPLICATION; DISEASE PROGRESSION; PRIMARY INFECTION; RHESUS-MONKEYS AB The control of human immunodeficiency virus type 1 (HIV-1) associated with particular HLA class I alleles suggests that some CD8(+) T-cell responses may be more effective than others at containing HIV-1. Unfortunately, substantial diversities in the breadth, magnitude, and function of these responses have impaired our ability to identify responses most critical to this control. It has been proposed that CD8 responses targeting conserved regions of the virus may be particularly effective, since the development of cytotoxic T-lymphocyte (CTL) escape mutations in these regions may significantly impair viral replication. To address this hypothesis at the population level, we derived near-full-length viral genomes from 98 chronically infected individuals and identified a total of 76 HLA class I-associated mutations across the genome, reflective of CD8 responses capable of selecting for sequence evolution. The majority of HLA-associated mutations were found in p24 Gag, Pol, and Nef. Reversion of HLA-associated mutations in the absence of the selecting HLA allele was also commonly observed, suggesting an impact of most CTL escape mutations on viral replication. Although no correlations were observed between the number or location of HLA-associated mutations and protective HLA alleles, limiting the analysis to mutations selected by acute-phase immunodominant responses revealed a strong positive correlation between mutations at conserved residues and protective HLA alleles. These data suggest that control of HIV-1 may be associated with acute-phase CD8 responses capable of selecting for viral escape mutations in highly conserved regions of the virus, supporting the inclusion of these regions in the design of an effective vaccine. C1 [Wang, Yaoyu E.; Li, Bin; Streeck, Hendrik; Gladden, Adrianne D.; Goodman, Robert; Schneidewind, Arne; Power, Karen A.; Toth, Ildiko; Frahm, Nicole; Alter, Galit; Brander, Christian; Walker, Bruce D.; Altfeld, Marcus; Allen, Todd M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. [Carlson, Jonathan M.; Heckerman, David] Microsoft Res, Redmond, WA USA. [Carrington, Mary] SAIC Frederick Inc, NCI, Lab Genom Divers, Frederick, MD USA. [Allen, Todd M.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Allen, TM (reprint author), CNY 6625, Massachusetts Gen Hosp E, 149 13th St, Charlestown, MA 02129 USA. EM tallen2@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778 FU National Institutes of Health [R01-AI054178]; Bill & Melinda Gates Foundation FX This study was supported by the National Institutes of Health grant R01-AI054178 (T. M. A.) and as part of the Collaboration for AIDS Vaccine Discovery with support from the Bill & Melinda Gates Foundation. NR 85 TC 81 Z9 82 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB 15 PY 2009 VL 83 IS 4 BP 1845 EP 1855 DI 10.1128/JVI.01061-08 PG 11 WC Virology SC Virology GA 400AK UT WOS:000262840200030 PM 19036810 ER PT J AU Lane, R He, YS Morris, C Leverenz, JB Emre, M Ballard, C AF Lane, Roger He, Yunsheng Morris, Christopher Leverenz, James B. Emre, Murat Ballard, Clive TI BuChE-K and APOE epsilon 4 Allele Frequencies in Lewy Body Dementias, and Influence of Genotype and Hyperhomocysteinemia on Cognitive Decline SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease dementia; dementia with Lewy bodies; apolipoprotein E; butyrylcholinesterase ID ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; APOLIPOPROTEIN-E; HOMOCYSTEINE; RIVASTIGMINE; PROGRESSION; DEFICIENCY; DEPOSITION; NEURONS; PLACEBO AB Apolipoprotein E (APOE) epsilon 4 and butyrylcholinesterase-K (BuChE-K) are associated with an increased risk for Alzheimer's disease. The primary objective was to evaluate frequencies of these alleles in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). A secondary objective was to evaluate influences on rate of cognitive decline. This analysis used data from participants consenting to pharmacogenetic testing in placebo-controlled rivastigmine studies. Allele frequencies in DLB and PDD were compared using logistic regression. Within the PDD placebo sample. associations with cognitive decline were evaluated (the DLB sample was too small for these evaluations). Fifty-seven DLB and 323 PDD subjects provided APOE and BuChE data. Allelic frequencies were higher in DLB, relative to PDD subjects, for BuChE-K (P = 0.06), APOE epsilon 4 (P < 0.001), or both alleles together (P < 0.001). More rapid cognitive decline was seen in PDD patients carrying both alleles, compared with other enotypes. Subjects with hyperhomo-cysteinemia were associated with more rapid decline in the presence of BuChE-K, with or without APOE epsilon 4. These results suggest that genetic and biochemical risk factors for AD and PDD pathology may be important in dementia onset and progression in these Lewy body disorders. (C) 2008 Movement Disorder Society C1 [Lane, Roger] Nova Pharmaceut Corp, E Hanover, NJ 07936 USA. [He, Yunsheng] Nova Pharmaceut Corp, Cambridge, MA USA. [Morris, Christopher] Newcastle Gen Hosp, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. [Leverenz, James B.] PADRECC, MIRECC, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Leverenz, James B.] Univ Washington, Seattle, WA 98195 USA. [Emre, Murat] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey. [Ballard, Clive] Kings Coll London, Wolfson Ctr Age Related Dis, London WC2R 2LS, England. RP Lane, R (reprint author), Nova Pharmaceut Corp, 59 Route 10, E Hanover, NJ 07936 USA. EM roger.lane@novartis.com FU Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; Novartis FX This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Novartis sponsored Alpha-Plus Medical Communications Ltd (UK) to provide editorial assistance with the manuscript. NR 22 TC 22 Z9 22 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD FEB 15 PY 2009 VL 24 IS 3 BP 392 EP 400 DI 10.1002/mds.22357 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 412TN UT WOS:000263747200011 PM 19006190 ER PT J AU Luciano, MS Ozelius, L Sims, K Raymond, D Liu, L Saunders-Pullman, R AF Luciano, Marta San Ozelius, Laurie Sims, Katherine Raymond, Deborah Liu, Liu Saunders-Pullman, Rachel TI Responsiveness to Levodopa in Epsilon-Sarcoglycan Deletions SO MOVEMENT DISORDERS LA English DT Article DE myoclonus; dystonia; Epsilon-Sarcoglycan; Levodopa ID MYOCLONUS-DYSTONIA SYNDROME; OBSESSIVE-COMPULSIVE DISORDER; ALCOHOL DEPENDENCE; SODIUM OXYBATE; MUTATIONS; GENE; SGCE; STIMULATION; PHENOTYPE; EFFICACY AB Myoclonus-dystonia (M-D) is characterized by early-onset myoclonus and dystonia, and is often due to mutations in the epsilon-sarcoglycan gene (SCGE) at locus 7q21. The pathogenesis of M-D is poorly understood, and in a murine knockout model, dopaminergic hyperactivity has been postulated as a mechanism. We present two unrelated individuals with M-D due to SCGE deletions who displayed a robust and sustained response to levodopa (L-dopa) treatment. In contrast to using dopamine blocking agents suggested by the hyperdopaminergic knockout model, we propose that a trial of L-dopa may be considered in patients with myoclonus-dystoma. (C) 2009 Movement Disorder Society C1 [Saunders-Pullman, Rachel] Beth Israel Deaconess Med Ctr, Albert Einstein Coll Med, Dept Neurol, New York, NY 10003 USA. [Ozelius, Laurie; Liu, Liu] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Sims, Katherine] Massachusetts Gen Hosp, Dept Pediat Neurol & Neurogenet, Boston, MA 02114 USA. RP Saunders-Pullman, R (reprint author), Beth Israel Deaconess Med Ctr, Albert Einstein Coll Med, Dept Neurol, 10 Union Sq E,Suite 2Q, New York, NY 10003 USA. EM rsaunder@bethisraelny.org FU National Institute of Neurological Disorders and Stroke [K23NS047256]; Thomas J. Hartman Foundation for Parkinson's Research FX We thank the patients and their families who gave so generously their time and effort. We thank Hector Moreno for his technical assistance. NR 24 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD FEB 15 PY 2009 VL 24 IS 3 BP 425 EP 428 DI 10.1002/mds.22375 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 412TN UT WOS:000263747200016 PM 19133653 ER PT J AU Handforth, A Martin, FC Kang, GA Vanek, Z AF Handforth, Adrian Martin, Fredricka C. Kang, Gail A. Vanek, Zeba TI Zonisamide for Essential Tremor: An Evaluator-Blinded Study SO MOVEMENT DISORDERS LA English DT Article DE essential tremor; zonisamide; clinical trial ID PLACEBO-CONTROLLED TRIAL AB In this evaluator-blinded open-treatment trial, subjects with moderate/severe upper limb essential tremor were titrated to 300 mg/day zonisamide, or adjusted to a lesser (lose if symptoms warranted, as monotherapy or as adjunct to stable antitremor medication, followed by a 12-week extension phase. The primary efficacy outcome variables were blinded rater videotaped/drawing tremor score changes at the Treatment and Extension visits compared to Baseline, based on Fahn-Tolosa-Marin and Postural Tremor Scales. Subjects also rated Functional Disabilities. Primary outcomes showed reduced tremor scores at the Treatment (P < 0.00001, n = 25) and Extension (n = 16) visits, at mean doses of 252 and 225 mg/day, respectively. Subject ratings indicated 200 mg/day was superior to 100 mg/day, whereas 300 mg/day produced no additional benefit, but instead was associated with more adverse symptoms, most commonly somnolence, poor energy, imbalance, and altered taste. Future double-blind placebo-controlled trials are warranted. (C) 2008 Movement Disorder Society C1 [Handforth, Adrian] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. [Martin, Fredricka C.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Kang, Gail A.] Vet Affairs San Francisco Med Ctr, Parkinsons Dis Res Educ Clin Ctr, San Francisco, CA USA. [Vanek, Zeba] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Handforth, A (reprint author), VA Greater Los Angeles, Neurol Serv W127, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM charles.handforth@med.va.gov FU Veterans Affairs; Ralph M. Parsons Foundation, Los Angeles FX A.H., F.C.M.. G.A.K. were supported by Veterans Affairs and A.H. by the Ralph M. Parsons Foundation, Los Angeles. The statistical analysis was performed by Jeffrey Gornbein, DrPH, UCLA SBCC/Department of Biomathematics, UCLA David Geffen School of Medicine, Los Angeles. NR 10 TC 23 Z9 23 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD FEB 15 PY 2009 VL 24 IS 3 BP 437 EP 440 DI 10.1002/mds.22418 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 412TN UT WOS:000263747200019 PM 19117357 ER PT J AU Salat, DH Greve, DN Pacheco, JL Quinn, BT Helmer, KG Buckner, RL Fischl, B AF Salat, David H. Greve, Douglas N. Pacheco, Jennifer L. Quinn, Brian T. Helmer, Karl G. Buckner, Randy L. Fischl, Bruce TI Regional white matter volume differences in nondemented aging and Alzheimer's disease SO NEUROIMAGE LA English DT Article ID HUMAN CEREBRAL-CORTEX; AGE-RELATED-CHANGES; MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; BRAIN VOLUME; GRAY-MATTER; CORTICAL SURFACE; IN-VIVO; CEREBROVASCULAR-DISEASE; DEMENTIA SEVERITY AB Accumulating evidence suggests that altered cerebral white matter (WM) influences normal aging, and further that WM degeneration may modulate the clinical expression of Alzheimer's disease (AD). Here we conducted a study of differences in WM volume across the adult age span and in AD employing a newly developed, automated method for regional parcellation of the subcortical WM that uses curvature landmarks and gray matter (GM)/WM surface boundary information. This procedure measures the volume of gyral WM, utilizing a distance constraint to limit the measurements from extending into the centrum semiovale. Regional estimates were first established to be reliable across two scan sessions in 20 young healthy individuals. Next, the method was applied to a large clinically-characterized sample of 299 individuals including 73 normal older adults and 91 age-matched participants with very mild to mild AD. The majority of measured regions showed a decline in volume with increasing age, with strong effects found in bilateral fusiform, lateral orbitofrontal, superior frontal, medial orbital frontal, inferior temporal, and middle temporal WM. The association between WM volume and age was quadratic in many regions suggesting that WM volume loss accelerates in advanced aging. A number of WM regions were further reduced in AD with parahippocampal, entorhinal, inferior parietal and rostral middle frontal WM showing the strongest AD-associated reductions. There were minimal sex effects after correction for intracranial volume, and there were associations between ventricular volume and regional WM volumes in the older adults and AD that were not apparent in the younger adults. Certain results, such as the loss of WM in the fusiform region with aging, were unexpected and provide novel insight into patterns of age associated neural and cognitive decline. Overall, these results demonstrate the utility of automated regional WM measures in revealing the distinct patterns of age and AD associated volume loss that may contribute to cognitive decline. Published by Elsevier Inc. C1 [Salat, David H.] Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Salat, DH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Bldg 149,13th St,Mail Code 149,2301, Charlestown, MA USA. EM salat@nmr.mgh.harvard.edu FU NCRR [P41RR14075]; MIND Institute; Athinoula A. Martinos Center for Biomedical Imaging; NINR [NR010827]; NIA [AG024898, AG05886, AG05681]; HHMI; HBP [NS39581, RR14075] FX This work was supported by NCRR P41RR14075, the MIND Institute, the Athinoula A. Martinos Center for Biomedical Imaging, NINR NR010827, NIA AG024898, AG05886, AG05681, HHMI, HBP NS39581 and RR14075. We thank theWashington University ADRC for making MRI data available. NR 93 TC 130 Z9 132 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 15 PY 2009 VL 44 IS 4 BP 1247 EP 1258 DI 10.1016/j.neuroimage.2008.10.030 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KG UT WOS:000263861800002 PM 19027860 ER PT J AU Hyde, D de Kleine, R MacLaurin, SA Miller, E Brooks, DH Krucker, T Ntziachristos, V AF Hyde, Damon de Kleine, Ruben MacLaurin, Sarah A. Miller, Eric Brooks, Dana H. Krucker, Thomas Ntziachristos, Vasilis TI Hybrid FMT-CT imaging of amyloid-beta plaques in a murine Alzheimer's disease model SO NEUROIMAGE LA English DT Article ID DIFFUSE OPTICAL TOMOGRAPHY; FLUORESCENCE MOLECULAR TOMOGRAPHY; LAPLACIAN-TYPE REGULARIZATION; HUMAN BRAIN-FUNCTION; TRANSGENIC MICE; PRECURSOR PROTEIN; MOUSE MODEL; BORN RATIO; IN-VIVO; RECONSTRUCTION AB The need to study molecular and functional parameters of Alzheimer's disease progression in animal models has led to the development of disease-specific fluorescent markers. However, curved optical interfaces and a highly heterogeneous internal structure make quantitative fluorescence imaging of the murine brain a particularly challenging tomographic problem. We investigated the integration of X-ray computed tomography (CT) information into a state-of-the-art fluorescence molecular tomography (FMT) scheme and establish that the dual-modality approach is essential for high fidelity reconstructions of distributed fluorescence within the murine brain, as compared to conventional fluorescence tomography. We employ this method in vivo using a fluorescent oxazine dye to quantify amyloid-beta plaque burden in transgenic APP23 mice modeling Alzheimer's disease. Multi-modal imaging allows for accurate signal localization and correlation of in vivo findings to ex vivo studies. The results point to FMT-CT as an essential tool for in vivo study of neurodegenerative disease in animal models and potentially humans. (C) 2008 Elsevier Inc. All rights reserved. C1 [Hyde, Damon; de Kleine, Ruben; Ntziachristos, Vasilis] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. [Hyde, Damon; de Kleine, Ruben; Ntziachristos, Vasilis] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [MacLaurin, Sarah A.; Krucker, Thomas] Novartis Inst Biomed Res, Global Imaging Grp, Cambridge, MA 02139 USA. [Hyde, Damon; Brooks, Dana H.] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. [Miller, Eric] Tufts Univ, Dept Elect & Comp Engn, Medford, MA 02155 USA. [Ntziachristos, Vasilis] Tech Univ Munich, Inst Biol & Med Imaging, Munich, Germany. [Ntziachristos, Vasilis] Helmholtz Ctr Munich, Munich, Germany. RP Hyde, D (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. EM dhyde@ece.neu.edu; v.ntziachristos@tum.de RI Miller, Eric/B-2546-2008 OI Miller, Eric/0000-0002-3156-6002 NR 44 TC 69 Z9 69 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD FEB 15 PY 2009 VL 44 IS 4 BP 1304 EP 1311 DI 10.1016/j.neuroimage.2008.10.038 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KG UT WOS:000263861800008 PM 19041402 ER PT J AU Wonderlick, JS Ziegler, DA Hosseini-Varnamkhasti, P Locascio, JJ Bakkour, A Van der Kouwe, A Triantafyllou, C Corkin, S Dickerson, BC AF Wonderlick, J. S. Ziegler, D. A. Hosseini-Varnamkhasti, P. Locascio, J. J. Bakkour, A. Van der Kouwe, A. Triantafyllou, C. Corkin, S. Dickerson, B. C. TI Reliability of MRI-derived cortical and subcortical morphometric measures: Effects of pulse sequence, voxel geometry, and parallel imaging SO NEUROIMAGE LA English DT Article ID MAGNETIC-RESONANCE IMAGES; HUMAN CEREBRAL-CORTEX; THICKNESS; SENSE; SEGMENTATION; BRAIN; RECONSTRUCTION; ACQUISITION; ARRAY; COIL AB Advances in magnetic resonance imaging (MRI) have contributed greatly to the study of neurodegenerative processes, psychiatric disorders, and normal human development, but the effect of such improvements on the reliability of downstream morphometric measures has not been extensively studied. We examined how MRI-derived neurostructural measures are affected by three technological advancements: parallel acceleration, increased spatial resolution, and the use of a high bandwidth multiecho sequence. Test-retest data were collected from 11 healthy participants during 2 imaging sessions occurring approximately 2 weeks apart. We acquired 4 T1-weighted MP-RAGE sequences during each session: a non-accelerated anisotropic sequence (MPR), a non-accelerated isotropic sequence (ISO), an accelerated isotropic sequence (ISH), and an accelerated isotropic high bandwidth multiecho sequence (MEM). Cortical thickness and volumetric measures were computed for each sequence to assess test-retest reliability and measurement bias. Reliability was extremely high for most measures and similar across imaging parameters. Significant measurement bias was observed, however, between MPR and all isotropic sequences for all cortical regions and some subcortical structures. These results suggest that these improvements in MRI acquisition technology do not compromise data reproducibility, but that consistency should be maintained in choosing imaging parameters for structural MRI studies. (C) 2008 Elsevier Inc. All rights reserved. C1 [Wonderlick, J. S.; Ziegler, D. A.; Hosseini-Varnamkhasti, P.; Corkin, S.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Wonderlick, J. S.; Ziegler, D. A.; Hosseini-Varnamkhasti, P.; Triantafyllou, C.; Corkin, S.] MIT, McGovern Inst, Athinoula Martinos Imaging Ctr, Cambridge, MA 02139 USA. [Bakkour, A.; Van der Kouwe, A.; Corkin, S.; Dickerson, B. C.] MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Cambridge, MA USA. [Locascio, J. J.; Dickerson, B. C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. [Bakkour, A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Van der Kouwe, A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. RP Wonderlick, JS (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. EM jswonder@mit.edu RI Triantafyllou, Christina/E-7724-2011; OI Bakkour, Akram/0000-0002-6070-4945 FU NIH [AG021525, T32 GM007484, NIA R01-AG29411, R21-AG29840]; Alzheimer's Association; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery (MIND) Institute; National Alliance for Medical Image Computing (NAMIC) [NIBIB U54 EB005149] FX The Athinoula A. Martinos Center for Biomedical Imaging at MGH is supported by the National Center for Research Resources (P41RR14075), the Mental Illness and Neuroscience Discovery (MIND) Institute, and the National Alliance for Medical Image Computing (NAMIC) (NIBIB U54 EB005149). NR 24 TC 92 Z9 92 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 15 PY 2009 VL 44 IS 4 BP 1324 EP 1333 DI 10.1016/j.neuroimage.2008.10.037 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KG UT WOS:000263861800010 PM 19038349 ER PT J AU Sykes, M AF Sykes, Megan TI Hematopoietic Cell Transplantation for Tolerance Induction: Animal Models to Clinical Trials SO TRANSPLANTATION LA English DT Article DE Tolerance; Thymus; Chimerism; T-cells ID BONE-MARROW-TRANSPLANTATION; RENAL-ALLOGRAFT REJECTION; WHOLE-BODY IRRADIATION; REFRACTORY HEMATOLOGIC MALIGNANCIES; MIXED ALLOGENEIC CHIMERAS; ANTIBODY MAB INJECTIONS; REGULATORY T-CELLS; MONOCLONAL-ANTIBODY; MINIATURE SWINE; COSTIMULATION BLOCKADE AB The induction of donor-specific immune tolerance is the "holy grail" of transplantation, as it would avoid the toxicities of chronic immunosuppressive therapies while preventing acute and chronic graft rejection. A large number of approaches to tolerance induction have been described in the experimental literature, but only hematopoietic cells transplantation has shown preliminary Success for intentional tolerance induction in pilot clinical trials. This review summarizes the conditions that allow progress to be made in moving strategies for tolerance induction from the bench to the bedside and discuss the mechanisms by which tolerance may be achieved through hematopoietic cell transplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Surg Serv,Sch Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Surg Serv,Sch Med, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NCI NIH HHS [P01 CA111519-030001, P01 CA111519, P01 CA111519-01A2, P01 CA111519-01A20001, P01 CA111519-02, P01 CA111519-020001, P01 CA111519-03, R01 CA079989, R01 CA079989-06, R01 CA079989-07, R01 CA079989-08, R01 CA079989-09]; NHLBI NIH HHS [P01 HL018646, P01 HL018646-26A10014, P01 HL018646-270014, P01 HL018646-280014, P01 HL018646-290014, P01 HL018646-300014, R01 HL049915, R01 HL049915-10, R01 HL049915-11, R01 HL049915-12, R01 HL049915-13A1]; NIAID NIH HHS [N01AI15416, P01 AI045897, P01 AI045897-060007, P01 AI045897-070007, P01 AI045897-080007, P01 AI045897-090007, P01 AI045897-100007] NR 92 TC 41 Z9 41 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 15 PY 2009 VL 87 IS 3 BP 309 EP 316 DI 10.1097/TP.0b013e31819535c2 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 407XK UT WOS:000263397400001 PM 19202432 ER PT J AU Scholtysek, C Krukiewicz, AA Alonso, JL Sharma, KP Sharma, PC Goldmann, WH AF Scholtysek, Carina Krukiewicz, Aleksandra A. Alonso, Jose-Luis Sharma, Karan P. Sharma, Pal C. Goldmann, Wolfgang H. TI Characterizing components of the Saw Palmetto Berry Extract (SPBE) on prostate cancer cell growth and traction SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Phytosterol; Prostate cancer cells; DU-145; Cell growth; Cell traction; p21; p27; p53 ID BETA-SITOSTEROL; SERENOA-REPENS; SCID MICE; F-ACTIN; P53; PHYTOSTEROLS; INHIBITION; APOPTOSIS AB Saw Palmetto Berry Extract (SPBE) is applied for prostate health and treatment of urinary tract infections. nonbacterial prostitis and Benign Prostatic Hyperplasia (BPH) in man. An assumption is that SPBE affects tumor cell progression and migration in breast and prostate tissue. In this work, DU-145 cells were used to demonstrate that SPBE and its sterol components, p-sitosterol and stigmasterol, inhibit prostate cancer growth by increasing p53 protein expression and also inhibit carcinoma development by decreasing p21 and p27 protein expression. In the presence of cholesterol. these features are not only reversed but increased significantly. The results Show for the first time the potential of SPBE, beta-sitosterol and stigmasterol as potential anti-tumor agents. Since the protein p53 is also regarded as nuclear matrix protein facilitating actin cytoskeletal binding, 2D tractions were measured. The cell adhesion strength in the presence of SPBE, beta-sitosterol and cholesterol and the observation was that the increase in p53 expression triggered an increase in the intracellular force generation. The results Suggest a dual function of p53 in cells. (c) 2008 Elsevier Inc. All rights reserved. C1 [Scholtysek, Carina; Krukiewicz, Aleksandra A.; Goldmann, Wolfgang H.] Univ Erlangen Nurnberg, Biophys Grp, Ctr Med Phys & Technol, D-91052 Erlangen, Germany. [Alonso, Jose-Luis] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Sharma, Karan P.; Sharma, Pal C.] Boston BioProd Inc, Worcester, MA 01604 USA. RP Goldmann, WH (reprint author), Univ Erlangen Nurnberg, Biophys Grp, Ctr Med Phys & Technol, Henke Str 91, D-91052 Erlangen, Germany. EM wgoldmann@biomed.uni-erlangen.de RI Alonso, Jose Luis/G-7961-2012; Goldmann, Wolfgang/H-5572-2013 FU BFHZ; BaCaTec; DAAD FX We thank Gerold Diez, Anna H. Klemm, and Christine Albert for excellent technical assistance and Dr. Ben Fabry for helpful discussions and Dr. James Smith for proof-reading and copy-editing of this manuscript. This work was supported by grants from BFHZ, BaCaTec and DAAD to WHG. NR 23 TC 18 Z9 19 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 13 PY 2009 VL 379 IS 3 BP 795 EP 798 DI 10.1016/j.bbrc.2008.11.114 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 405XS UT WOS:000263258100029 PM 19059205 ER PT J AU Klemm, AH Diez, G Alonso, JL Goldmann, WH AF Klemm, Anna H. Diez, Gerold Alonso, Jose-Luis Goldmann, Wolfgang H. TI Comparing the mechanical influence of vinculin, focal adhesion kinase and p53 in mouse embryonic fibroblasts SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Mouse embryonic fibroblasts; Vinculin; Focal adhesion kinase; p53; Cell Stiffness; Binding strength; Diffusivity ID CELLS; ACTIN; PRESTRESS; STIFFNESS; DYNAMICS; MATRIX; FORCE AB Cytoskeletal reorganization is an ongoing process when cells adhere, move or invade extracellular substrates. The cellular force generation and transmission are determined by the intactness of the actomy-osin-(focal adhesion complex)-integrin connection. We investigated the intracellular course of action in mouse embryonic fibroblasts deficient in the focal adhesion proteins vinculin and focal adhesion kinase (FAK) and the nuclear matrix protein p53 using magnetic tweezer and nanoparticle tracking techniques. Results show that the lack of these proteins decrease cellular stiffness and affect cell theological behavior. The decrease in cellular binding strength was higher in FAK- to Vinculin-deficient cells, whilst p53-deficient cells showed no effect compared to wildtype cells. The intracellular cytoskeletal activity was lowest in wildtype cells, but increased in the following order when cells lacked FAK+p53 > p53 > Vinculin. In summary, cell mechanical processes are differently affected by the focal adhesion proteins vinculin and FAK than by the nuclear matrix protein, p53. (c) 2009 Elsevier Inc. All rights reserved. C1 [Klemm, Anna H.; Diez, Gerold; Goldmann, Wolfgang H.] Univ Erlangen Nurnberg, Biophys Grp, Ctr Med Phys & Technol, D-91052 Erlangen, Germany. [Alonso, Jose-Luis] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Goldmann, WH (reprint author), Univ Erlangen Nurnberg, Biophys Grp, Ctr Med Phys & Technol, D-91052 Erlangen, Germany. EM wgoldmann@biomed.uni-erlangen.de RI Alonso, Jose Luis/G-7961-2012; Goldmann, Wolfgang/H-5572-2013 FU BFHZ; BaCaTec; DAAD FX We thank Dr. Eileen Adamson for the kind gift of the MEF cells, Christine Albert for excellent technical assistance and Philip Kollmannsberger, Claudia T. Mierke, Ben Fabry for helpful discussions and James Smith for reviewing this manuscript. This work was Supported by BFHZ, BaCaTec and DAAD. NR 21 TC 11 Z9 11 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 13 PY 2009 VL 379 IS 3 BP 799 EP 801 DI 10.1016/j.bbrc.2008.12.124 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 405XS UT WOS:000263258100030 PM 19126403 ER PT J AU Thakur, JK Arthanari, H Yang, FJ Chau, KH Wagner, G Naar, AM AF Thakur, Jitendra K. Arthanari, Haribabu Yang, Fajun Chau, Katherine H. Wagner, Gerhard Naeaer, Anders M. TI Mediator Subunit Gal11p/MED15 Is Required for Fatty Acid-dependent Gene Activation by Yeast Transcription Factor Oaf1p SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENCODING PEROXISOMAL PROTEINS; NUCLEAR RECEPTOR SUPERFAMILY; RNA-POLYMERASE-II; SACCHAROMYCES-CEREVISIAE; BETA-OXIDATION; TRANSACTIVATION DOMAIN; X-RECEPTOR; METABOLISM; INDUCTION; COMPLEX AB The yeast zinc cluster transcription factor Oaf1p activates transcription of target genes in response to direct binding of fatty acids in a manner analogous to the vertebrate nuclear receptor peroxisome proliferator-activated receptor alpha(PPAR alpha). PPARs and other metazoan nuclear receptors productively engage several distinct LXXLL motif-containing co-activators, including p160 family members and the TRAP220/MED1 subunit of the Mediator coactivator, to promote ligand-dependent gene activation. Yeast, however, does not appear to harbor LXXLL motif co-activators, and the mechanism of fatty acid-dependent gene activation by the yeast PPAR alpha analog Oaf1p is unknown. Here we show that the yeast Mediator subunit Gal11p/MED15 and its activator-targeted KIX domain plays a critical role in fatty acid-dependent transcriptional regulation of fatty acid beta-oxidation and peroxisomal genes by Oaf1p and for the ability of yeast to utilize fatty acids as a sole carbon source. Moreover, structural studies by NMR spectroscopy reveal that the Oaf1p activation domain interacts with the Gal11p/MED15 KIX domain in a manner similar to the yeast zinc cluster family member and xenobiotic receptor Pdr1p, revealing that the Gal11p/MED15 KIX domain is a key target of several ligand-dependent transcription factors in yeast. Together with previous work showing that the Caenorhabditis elegans Gal11p/MED15 homolog MDT-15 plays a critical role in regulation of fatty acid metabolism by the nematode PPAR-like nuclear receptor NHR-49, the findings presented here provide evidence for an ancient and essential role of a Mediator co-activator subunit in regulation of fatty acid metabolism by nuclear receptor-like transcription factors in eukaryotes. C1 [Thakur, Jitendra K.; Yang, Fajun; Naeaer, Anders M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Thakur, Jitendra K.; Yang, Fajun; Naeaer, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Charlestown, MA 02129 USA. [Arthanari, Haribabu; Chau, Katherine H.; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Naar, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Rm 7407,Bldg 149,13th St, Charlestown, MA 02129 USA. EM naar@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA127990] NR 33 TC 43 Z9 43 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 13 PY 2009 VL 284 IS 7 BP 4422 EP 4428 DI 10.1074/jbc.M808263200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 404ET UT WOS:000263134400042 PM 19056732 ER PT J AU Roy, SS Madesh, M Davies, E Antonsson, B Danial, N Hajnoczky, G AF Roy, Soumya Sinha Madesh, Muniswamy Davies, Erika Antonsson, Bruno Danial, Nika Hajnoczky, Gyoergy TI Bad Targets the Permeability Transition Pore Independent of Bax or Bak to Switch between Ca2+-Dependent Cell Survival and Death SO MOLECULAR CELL LA English DT Article ID MITOCHONDRIAL OUTER-MEMBRANE; CYTOCHROME-C RELEASE; BCL-2 FAMILY-MEMBERS; PROTEIN-KINASE; ENDOPLASMIC-RETICULUM; DEPENDENT APOPTOSIS; CERAMIDE CHANNELS; CALCIUM SIGNALS; BH3 DOMAINS; BCL-X(L) AB Calcium oscillations exert physiological control on mitochondrial energy metabolism and can also lead to mitochondrial membrane permeabilization and cell death. The outcome of the mitochondrial calcium signaling is altered by stress factors such as ceramide or staurosporine. However, the mechanism of this proapoptotic switch remains unclear. Using genetic, biochemical, pharmacological, and functional approaches, we here show that ceramide and staurosporine target PP2A and protein kinases A and C, respectively, in a mitochondria-associated signaling complex to induce dephosphorylation of the BH3-only protein Bad. Dephosphorylated Bad sensitizes the mitochondrial permeability transition pore (PTP) to Ca2+ through a Bcl-xL-sensitive and VDAC-mediated process. Furthermore, the Bad-induced sensitization of the PTP to Ca2+ does not require Bax or Bak. Thus, phospho-regulatory mechanisms converge on Bad to switch between the survival and apoptotic functions of mitochondrial calcium signaling by activating a mechanism whereby a BH3-only protein bypasses Bax/Bak and engages the PTP. C1 [Roy, Soumya Sinha; Madesh, Muniswamy; Davies, Erika; Hajnoczky, Gyoergy] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. [Antonsson, Bruno] Merck Serono Int SA, Geneva Res Ctr, CH-1202 Geneva, Switzerland. [Danial, Nika] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Danial, Nika] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Hajnoczky, G (reprint author), Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. EM gyorgy.hajnoczky@jefferson.edu FU NIH [KO1CA10659, GM59419]; Burroughs Welcome Fund Career Award in Biomedical Sciences FX The authors thank Eric Smith for creation of the scheme in Figure 7E. This work was supported by an NIH grant (KO1CA10659) and a Burroughs Welcome Fund Career Award in Biomedical Sciences to N.D. and an NIH grant (GM59419) to G.H. NR 67 TC 84 Z9 87 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD FEB 13 PY 2009 VL 33 IS 3 BP 377 EP 388 DI 10.1016/j.molcel.2009.01.018 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 407XE UT WOS:000263396800010 PM 19217411 ER PT J AU Vidarsson, H Westergren, R Heglind, M Blomqvist, SR Breton, S Enerback, S AF Vidarsson, Hilmar Westergren, Rickard Heglind, Mikael Blomqvist, Sandra Rodrigo Breton, Sylvie Enerback, Sven TI The Forkhead Transcription Factor Foxi1 Is a Master Regulator of Vacuolar H+-ATPase Proton Pump Subunits in the Inner Ear, Kidney and Epididymis SO PLOS ONE LA English DT Article AB The vacuolar H+-ATPase dependent transport of protons across cytoplasmic membranes in FORE (forkhead related) cells ofendolymphatic epithelium in the inner ear, intercalated cells of collecting ducts in the kidney and in narrow and clear cells of epididymis require expression of several subunits that assemble into a functional multimeric proton pump. We demonstrate that expression of four such subunits A1, B1, E2 and a4 all co-localize with the forkhead transcription factor Foxi1 in a subset of epithelial cells at these three locations. In cells, of such epithelia, that lack Foxi1 we fail to identify any expression of A1, B1, E2 and a4 demonstrating an important role for the transcription factor Foxi1 in regulating subunit availability. Promoter reporter experiments, electrophoretic mobility shift assays (EMSA) and site directed mutagenesis demonstrate that a Foxi1 expression vector can trans-activate an a4-promoter reporter construct in a dose dependent manner. Furthermore, we demonstrate using chromatin immunoprecipitation (ChIP) assays that Foxi1-dependent activation to a large extent depends on cis-elements at position -561/-547 in the a4 promoter. Thus, we provide evidence that Foxi1 is necessary for expression of at least four subunits in three different epithelia and most likely is a major determinant for proper assembly of a functional vacuolar H+-ATPase complex at these locations. C1 [Vidarsson, Hilmar; Westergren, Rickard; Heglind, Mikael; Blomqvist, Sandra Rodrigo; Enerback, Sven] Univ Gothenburg, Ctr Med Genet, Inst Biomed, Sahlgrenska Acad, Gothenburg, Sweden. [Breton, Sylvie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nephrol Div, Ctr Syst Biol, Program Membrane Biol, Boston, MA USA. RP Vidarsson, H (reprint author), Univ Gothenburg, Ctr Med Genet, Inst Biomed, Sahlgrenska Acad, Gothenburg, Sweden. EM sven.enerback@medgen.gu.se FU Swedish Research Council [K2005-32BI-15324-01A]; EU [QLK3-CT-2002-02149, LSHM-CT-2003-503041]; The Arne and IngaBritt Foundation; The Soderberg Foundation; NIH [HD040793] FX SE's laboratory is supported from the Swedish Research Council (grant K2005-32BI-15324-01A), EU grants (QLK3-CT-2002-02149) and (LSHM-CT-2003-503041), The Arne and IngaBritt Foundation and The Soderberg Foundation. SB's laboratory is supported by NIH grant HD040793. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 20 TC 42 Z9 42 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 13 PY 2009 VL 4 IS 2 AR e4471 DI 10.1371/journal.pone.0004471 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437JR UT WOS:000265484300010 PM 19214237 ER PT J AU Raab, MS Breitkreutz, I Tonon, G Zhang, J Hayden, PJ Nguyen, T Fruehauf, JH Lin, BK Chauhan, D Hideshima, T Munshi, NC Anderson, KC Podar, K AF Raab, Marc S. Breitkreutz, Iris Tonon, Giovanni Zhang, Jing Hayden, Patrick J. Nguyen, Thu Fruehauf, Johannes H. Lin, Boris K. Chauhan, Dharminder Hideshima, Teru Munshi, Nikhil C. Anderson, Kenneth C. Podar, Klaus TI Targeting PKC: a novel role for beta-catenin in ER stress and apoptotic signaling SO BLOOD LA English DT Article ID PROTEIN-KINASE-C; MULTIPLE-MYELOMA CELLS; ENDOPLASMIC-RETICULUM; IN-VIVO; COLON-CARCINOMA; PLASMA-CELLS; AKT PATHWAY; DNA-DAMAGE; CYCLIN D1; ACTIVATION AB Targeting protein kinase C (PKC) isoforms by the small molecule inhibitor enzastaurin has shown promising preclinical activity in a wide range of tumor cells. We further delineated its mechanism of action in multiple myeloma (MM) cells and found a novel role of beta-catenin in regulating growth and survival of tumor cells. Specifically, inhibition of PKC leads to rapid accumulation of beta-catenin by preventing the phosphorylation required for its proteasomal degradation. Microarray analysis and small-interfering RNA (siRNA)-mediated gene silencing in MM cells revealed that accumulated beta-catenin activates early endoplasmic reticulum stress signaling via eIF2 alpha, C/EBP-homologous protein (CHOP), and p21, leading to immediate growth inhibition. Furthermore, accumulated beta-catenin contributes to enzastaurin-induced cell death. Sequential knockdown of beta-catenin, c-Jun, and p73, as well as overexpression of beta-catenin or p73 confirmed that accumulated beta-catenin triggers c-Jun-dependent induction of p73, thereby conferring MM cell apoptosis. Our data reveal a novel role of beta-catenin in endoplasmic reticulum (ER) stress-mediated growth inhibition and anew proapoptotic mechanism triggered by beta-catenin on inhibition of PKC isoforms. Moreover, we identify p73 as a potential novel therapeutic target in MM. Based on these and previous data, enzastaurin is currently under clinical investigation in a variety of hematologic malignancies, including MM. (Blood. 2009; 113: 1513-1521) C1 [Raab, Marc S.; Breitkreutz, Iris; Zhang, Jing; Hayden, Patrick J.; Chauhan, Dharminder; Hideshima, Teru; Munshi, Nikhil C.; Anderson, Kenneth C.; Podar, Klaus] Harvard Univ, Dept Med Oncol, LeBow Inst Myeloma Therapeut, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [Raab, Marc S.; Breitkreutz, Iris; Zhang, Jing; Hayden, Patrick J.; Chauhan, Dharminder; Hideshima, Teru; Munshi, Nikhil C.; Anderson, Kenneth C.; Podar, Klaus] Harvard Univ, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [Tonon, Giovanni] Harvard Univ, Dept Med Oncol, Center Appl Canc Sci, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [Nguyen, Thu; Fruehauf, Johannes H.] Harvard Univ, Sch Med, Beth Israel Med Ctr, Skip Ackerman Ctr Mol Therapeut,Div Gastroenterol, Boston, MA 02115 USA. [Lin, Boris K.] Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Raab, MS (reprint author), Harvard Univ, Dept Med Oncol, LeBow Inst Myeloma Therapeut, Dana Farber Canc Inst,Med Sch, 44 Binney St, Boston, MA 02115 USA. EM marc_raab@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU Fritz-Thyssen Foundation; Multiple Myeloma Research Foundation (MMRF) Senior Research; Dunkin Donuts Rising Stars Award; National Institutes of Health [RO CA50947, PO-1 CA78378, P50 CA100707]; LeBow Fund FX This work was supported by a fellowship grant of the Fritz-Thyssen Foundation (M. S. R.), a Multiple Myeloma Research Foundation (MMRF) Senior Research grant award and a Dunkin Donuts Rising Stars Award (K. P.), the National Institutes of Health (grants RO CA50947, PO-1 CA78378, and P50 CA100707), and the LeBow Fund to Cure Myeloma (K. C. A.). NR 63 TC 44 Z9 44 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 12 PY 2009 VL 113 IS 7 BP 1513 EP 1521 DI 10.1182/blood-2008-05-157040 PG 9 WC Hematology SC Hematology GA 406SY UT WOS:000263316400017 PM 19018094 ER PT J AU Bashey, A Medina, B Corringham, S Pasek, M Carrier, E Vrooman, L Lowy, I Solomon, SR Morris, LE Holland, HK Mason, JR Alyea, EP Soiffer, RJ Ball, ED AF Bashey, Asad Medina, Bridget Corringham, Sue Pasek, Mildred Carrier, Ewa Vrooman, Linda Lowy, Israel Solomon, Scott R. Morris, Lawrence E. Holland, H. Kent Mason, James R. Alyea, Edwin P. Soiffer, Robert J. Ball, Edward D. TI CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation SO BLOOD LA English DT Article ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; VERSUS-HOST-DISEASE; METASTATIC MELANOMA; ANTIBODY BLOCKADE; CLINICAL-RESPONSE; TUMOR-REGRESSION; CANCER; AUTOIMMUNITY; IMMUNOTHERAPY; ANTI-CTLA-4 AB Relapse of malignancy after allogeneic hematopoietic cell transplantation (allo-HCT) remains a therapeutic challenge. Blockade of the CTLA4 molecule can effectively augment antitumor immunity mediated by autologous effector T cells. We have assessed the safety and preliminary efficacy of a neutralizing, human anti-CTLA4 monoclonal antibody, ipilimumab, in stimulating the graft-versus-malignancy (GVM) effect after allo-HCT. Twenty-nine patients with malignancies that were recurrent or progressive after allo-HCT, received ipilimumab as a single infusion at dose cohorts between 0.1 and 3.0 mg/kg. Dose-limiting toxicity was not encountered, and ipilimumab did not induce graft-versus-host disease (GVHD) or graft rejection. Organ-specific immune adverse events (IAE) were seen in 4 patients (grade 3 arthritis, grade 2 hyperthyroidism, recurrent grade 4 pneumonitis). Three patients with lymphoid malignancy developed objective disease responses following ipilimumab: complete remission (CR) in 2 patients with Hodgkin disease and partial remission (PR) in a patient with refractory mantle cell lymphoma. At the 3.0 mg/kg dose, active serum concentrations of ipilimumab were maintained for more than 30 days after a single infusion. Ipilimumab, as administered in this clinical trial, does not induce or exacerbate clinical GVHD, but may cause organ-specific IAE and regression of malignancy. This study is registered at http://clinicaltrials.gov under NCI protocol ID P6082. (Blood. 2009; 113: 1581-1588) C1 [Bashey, Asad; Pasek, Mildred; Vrooman, Linda; Solomon, Scott R.; Morris, Lawrence E.; Holland, H. Kent] Northside Hosp, Blood & Marrow Transplant Grp Georgia, Atlanta, GA 30342 USA. [Bashey, Asad; Medina, Bridget; Corringham, Sue; Carrier, Ewa; Ball, Edward D.] Univ Calif, San Diego Moores Canc Ctr, Div Blood & Marrow Transplantat, La Jolla, CA USA. [Lowy, Israel] Medarex, Bloomsbury, NJ USA. [Mason, James R.] Scripps Clin, BMT, La Jolla, CA USA. [Alyea, Edwin P.; Soiffer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bashey, A (reprint author), Northside Hosp, Blood & Marrow Transplant Grp Georgia, 5670 Peachtree Dunwoody Rd NE,Suite 1000, Atlanta, GA 30342 USA. EM abashey@bmtga.com FU National Institutes of Health (NIH); [RO1 CA 9389-01A1] FX We acknowledge the contribution of Howard Streicher, MD, Pharmaceutical Management Branch, National Cancer Institute (NCI; Bethesda, MD) during the design and analysis of the study. Minya Pu and Karen Messer from the Biostatistics Core at the Moores Cancer Center, University of California, San Diego helped with the statistical analysis.; This study was supported by National Institutes of Health (NIH) award RO1 CA 9389-01A1 (A. B.). NR 24 TC 127 Z9 130 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD FEB 12 PY 2009 VL 113 IS 7 BP 1581 EP 1588 DI 10.1182/blood-2008-07-168468 PG 8 WC Hematology SC Hematology GA 406SY UT WOS:000263316400026 PM 18974373 ER PT J AU Volpp, KG Troxel, AB Pauly, MV Glick, HA Puig, A Asch, DA Galvin, R Zhu, JS Wan, F DeGuzman, J Corbett, E Weiner, J Audrain-McGovern, J AF Volpp, Kevin G. Troxel, Andrea B. Pauly, Mark V. Glick, Henry A. Puig, Andrea Asch, David A. Galvin, Robert Zhu, Jingsan Wan, Fei DeGuzman, Jill Corbett, Elizabeth Weiner, Janet Audrain-McGovern, Janet TI A Randomized, Controlled Trial of Financial Incentives for Smoking Cessation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LONG-TERM ABSTINENCE; PREGNANT SMOKERS; TOBACCO USE; HEALTH; PERFORMANCE; PROGRAMS AB Background Smoking is the leading preventable cause of premature death in the United States. Previous studies of financial incentives for smoking cessation in work settings have not shown that such incentives have significant effects on cessation rates, but these studies have had limited power, and the incentives used may have been insufficient. Methods We randomly assigned 878 employees of a multinational company based in the United States to receive information about smoking- cessation programs ( 442 employees) or to receive information about programs plus financial incentives ( 436 employees). The financial incentives were $ 100 for completion of a smoking- cessation program, $ 250 for cessation of smoking within 6 months after study enrollment, as confirmed by a biochemical test, and $ 400 for abstinence for an additional 6 months after the initial cessation, as confirmed by a biochemical test. Individual participants were stratified according to work site, heavy or nonheavy smoking, and income. The primary end point was smoking cessation 9 or 12 months after enrollment, depending on whether initial cessation was reported at 3 or 6 months. Secondary end points were smoking cessation within the first 6 months after enrollment and rates of participation in and completion of smoking- cessation programs. Results The incentive group had significantly higher rates of smoking cessation than did the information- only group 9 or 12 months after enrollment (14.7% vs. 5.0%, P< 0.001) and 15 or 18 months after enrollment (9.4% vs. 3.6%, P< 0.001). Incentive- group participants also had significantly higher rates of enrollment in a smoking- cessation program (15.4% vs. 5.4%, P< 0.001), completion of a smoking- cessation program (10.8% vs. 2.5%, P< 0.001), and smoking cessation within the first 6 months after enrollment (20.9% vs. 11.8%, P< 0.001). Conclusions In this study of employees of one large company, financial incentives for smoking cessation significantly increased the rates of smoking cessation. (ClinicalTrials. gov number, NCT00128375.). C1 [Volpp, Kevin G.; Pauly, Mark V.; Glick, Henry A.; Puig, Andrea; Asch, David A.] Univ Penn, Sch Med, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Pauly, Mark V.; Glick, Henry A.; Puig, Andrea; Asch, David A.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Troxel, Andrea B.; Wan, Fei] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Troxel, Andrea B.; Wan, Fei] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Troxel, Andrea B.; Pauly, Mark V.; Glick, Henry A.; Asch, David A.; Zhu, Jingsan; DeGuzman, Jill; Weiner, Janet] Univ Penn, Ctr Hlth Incent, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Glick, Henry A.; Asch, David A.; Zhu, Jingsan; DeGuzman, Jill; Corbett, Elizabeth] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Audrain-McGovern, Janet] Univ Penn, Sch Med, Transdisciplinary Tobacco Use Res Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. [Galvin, Robert] Gen Elect, Fairfield, CT USA. [Galvin, Robert] Yale Univ, Sch Med, New Haven, CT USA. RP Volpp, KG (reprint author), Univ Penn, Sch Med, Div Gen Internal Med, 1232 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu OI Weiner, Janet/0000-0001-5810-5807; Corbett, Elizabeth/0000-0002-3552-3181 FU Centers for Disease Control and Prevention [RO1 DP000100-01, RO1 DP001168-01]; Pennsylvania Department of Health; Aetna; Pfizer; General Electric; America's Health Insurance Plans; Merck; MedStar FX Supported by grants from the Centers for Disease Control and Prevention (RO1 DP000100-01 and RO1 DP001168-01) and from the Pennsylvania Department of Health, which specifically disclaims responsibility for any analyses, interpretations, or conclusions.; Dr. Volpp reports receiving lecture fees from Aetna and grant support from Aetna and Pfizer and owning equity in General Electric; Dr. Pauly, being a board member of Independent Health, owning equity in General Electric, receiving lecture fees from America's Health Insurance Plans, and receiving grant support from Merck and MedStar; Dr. Glick, owning equity in General Electric; and Dr. Galvin, owning equity in General Electric. No other potential conflict of interest relevant to this article was reported.; We thank Quincy Greene for his contributions to the analyses for this article and Donna Tomlinson, M. D., for assistance in implementing this study. NR 27 TC 263 Z9 264 U1 3 U2 41 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 12 PY 2009 VL 360 IS 7 BP 699 EP 709 DI 10.1056/NEJMsa0806819 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 405YQ UT WOS:000263260500007 PM 19213683 ER PT J AU Kroshinsky, D Stone, JH Bloch, DB Sepehr, A Harris, NL Seton, M Robinson, D AF Kroshinsky, Daniela Stone, John H. Bloch, Donald B. Sepehr, Alireza Harris, Nancy Lee Seton, Margaret Robinson, Dwight TI A Woman with a Rash and Numbness and Pain in the Legs Lymphocyte-mediated vasculopathy, with fibrin microthrombi and vascular hyalinization (livedoid vasculopathy), secondary to SLE. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; ANTIPHOSPHOLIPID SYNDROME; AUTOANTIBODIES; PATIENT; UPDATE C1 [Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Stone, John H.; Bloch, Donald B.] Massachusetts Gen Hosp, Dept Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Sepehr, Alireza] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kroshinsky, Daniela] Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. [Stone, John H.; Bloch, Donald B.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Sepehr, Alireza] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Kroshinsky, D (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. FU Merck; ZymoGenetics FX Dr. Stone reports receiving consulting fees from Merck and ZymoGenetics. No other potential conflict of interest relevant to this article was reported. NR 28 TC 18 Z9 21 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 12 PY 2009 VL 360 IS 7 BP 711 EP 720 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 405YQ UT WOS:000263260500010 PM 19213685 ER PT J AU Tartar, JL Ward, CP Cordeira, JW Legare, SL Blanchette, AJ McCarley, RW Strecker, RE AF Tartar, Jaime L. Ward, Christopher P. Cordeira, Joshua W. Legare, Steven L. Blanchette, Amy J. McCarley, Robert W. Strecker, Robert E. TI Experimental sleep fragmentation and sleep deprivation in rats increases exploration in an open field test of anxiety while increasing plasma corticosterone levels SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Sleep deprivation; Sleep fragmentation; Anxiety; Corticosterone; Rat ID ELEVATED PLUS-MAZE; STRESS; RESPONSES; BEHAVIOR; MOOD; PERFORMANCE; MODEL; MICE AB Sleep deprivation alters mood and anxiety in man. In rats, 24 h of treadmill-induced total sleep deprivation or sleep fragmentation increased exploratory behavior in an open field test of anxiety compared to cage or exercise controls. Plasma corticosterone (CORT) levels of sleep disturbed and exercise control rats were elevated compared to cage controls, suggesting that the increased exploration observed in the sleep disturbed rats was not due to a hypothalamic-pituitary-adrenal (HPA) stress response. (C) 2008 Elsevier B.V. All rights reserved. C1 [Tartar, Jaime L.; Ward, Christopher P.; Cordeira, Joshua W.; Legare, Steven L.; Blanchette, Amy J.; McCarley, Robert W.; Strecker, Robert E.] Harvard Med Sch, Dept Psychiat & Res, Brockton, MA 02301 USA. [Tartar, Jaime L.; Ward, Christopher P.; Cordeira, Joshua W.; Legare, Steven L.; Blanchette, Amy J.; McCarley, Robert W.; Strecker, Robert E.] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Tartar, Jaime L.] Nova SE Univ, Farquhar Coll Arts & Sci, Div Social & Behav Sci, Ft Lauderdale, FL 33321 USA. [Ward, Christopher P.] Univ Houston Clear Lake, Dept Psychol, Houston, TX 77058 USA. RP Tartar, JL (reprint author), Harvard Med Sch, Dept Psychiat & Res, Res 151-C,940 Belmont St, Brockton, MA 02301 USA. EM tartar@nova.edu; wardchris@uhcl.edu; joshua.cordeira@gmail.com; steve7883@gmail.com; amyblanch@gmail.com; robert_mccarley@hms.harvard.edu; robert_strecker@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Ward, Christopher/0000-0001-9932-3894; Tartar, Jaime/0000-0002-3452-0579 FU Department of Veterans Affairs Medical Research Service; NHLBI [P50 HL060292, T32 HL07901] FX We thank John Franco for care of the animals. This research was supported by: Department of Veterans Affairs Medical Research Service Award to R.E.S., NHLBI - P50 HL060292 (R.E.S. and R.W.M.), NHLBI - T32 HL07901 ULT.). NR 30 TC 35 Z9 37 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD FEB 11 PY 2009 VL 197 IS 2 BP 450 EP 453 DI 10.1016/j.bbr.2008.08.035 PG 4 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 402MT UT WOS:000263018500024 PM 18805441 ER PT J AU Li, HL Zhang, HL Zheng, MY Luo, J Kang, L Liu, XF Wang, XC Jiang, HL AF Li, Honglin Zhang, Hailei Zheng, Mingyue Luo, Jie Kang, Ling Liu, Xiaofeng Wang, Xicheng Jiang, Hualiang TI An effective docking strategy for virtual screening based on multi-objective optimization algorithm SO BMC BIOINFORMATICS LA English DT Article ID PROTEIN-LIGAND INTERACTIONS; AUTOMATED MOLECULAR DOCKING; GENETIC ALGORITHM; SCORING FUNCTIONS; FLEXIBLE DOCKING; DRUG DISCOVERY; COMBINATORIAL LIBRARIES; STRUCTURAL BASIS; ACTIVE-SITES; BINDING-SITE AB Background: Development of a fast and accurate scoring function in virtual screening remains a hot issue in current computer-aided drug research. Different scoring functions focus on diverse aspects of ligand binding, and no single scoring can satisfy the peculiarities of each target system. Therefore, the idea of a consensus score strategy was put forward. Integrating several scoring functions, consensus score re-assesses the docked conformations using a primary scoring function. However, it is not really robust and efficient from the perspective of optimization. Furthermore, to date, the majority of available methods are still based on single objective optimization design. Results: In this paper, two multi-objective optimization methods, called MOSFOM, were developed for virtual screening, which simultaneously consider both the energy score and the contact score. Results suggest that MOSFOM can effectively enhance enrichment and performance compared with a single score. For three different kinds of binding sites, MOSFOM displays an excellent ability to differentiate active compounds through energy and shape complementarity. EFMOGA performed particularly well in the top 2% of database for all three cases, whereas MOEA_Nrg and MOEA_Cnt performed better than the corresponding individual scoring functions if the appropriate type of binding site was selected. Conclusion: The multi-objective optimization method was successfully applied in virtual screening with two different scoring functions that can yield reasonable binding poses and can furthermore, be ranked with the potentially compromised conformations of each compound, abandoning those conformations that can not satisfy overall objective functions. C1 [Li, Honglin; Jiang, Hualiang] E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China. [Li, Honglin; Zheng, Mingyue; Liu, Xiaofeng; Jiang, Hualiang] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China. [Li, Honglin; Kang, Ling; Wang, Xicheng] Dalian Univ Technol, Dept Engn Mech, State Key Lab Struct Analyses Ind Equipment, Dalian 116023, Peoples R China. [Zhang, Hailei] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhang, Hailei] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Luo, Jie] E China Univ Sci & Technol, Sch Informat Sci & Engn, Shanghai 200237, Peoples R China. RP Li, HL (reprint author), E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China. EM hlli@mail.shcnc.ac.cn; hailei_zhang@dfci.harvard.edu; myzheng@mail.shcnc.ac.cn; luojie1985sh@gmail.com; klxju@163.com; xxffliu@gmail.com; guixum@dlut.edu.cn; hljiang@mail.shcnc.ac.cn RI Li, Honglin/F-2606-2010; Zheng, Mingyue/B-4860-2010 OI Zheng, Mingyue/0000-0002-3323-3092 NR 73 TC 11 Z9 11 U1 2 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD FEB 11 PY 2009 VL 10 AR 58 DI 10.1186/1471-2105-10-58 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 439CG UT WOS:000265603900001 PM 19210777 ER PT J AU Buckner, RL Sepulcre, J Talukdar, T Krienen, FM Liu, HS Hedden, T Andrews-Hanna, JR Sperling, RA Johnson, KA AF Buckner, Randy L. Sepulcre, Jorge Talukdar, Tanveer Krienen, Fenna M. Liu, Hesheng Hedden, Trey Andrews-Hanna, Jessica R. Sperling, Reisa A. Johnson, Keith A. TI Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE connectivity; cognition; Alzheimer's disease; fMRI; cortex; cingulate ID PITTSBURGH COMPOUND-B; DEFAULT-MODE NETWORK; BOLD SIGNAL FLUCTUATIONS; CONSCIOUS RESTING STATE; HUMAN BRAIN; CEREBRAL-CORTEX; LOW-FREQUENCY; GRAPHICAL ANALYSIS; PREFRONTAL CORTEX; CINGULATE CORTEX AB Recent evidence suggests that some brain areas act as hubs interconnecting distinct, functionally specialized systems. These nexuses are intriguing because of their potential role in integration and also because they may augment metabolic cascades relevant to brain disease. To identify regions of high connectivity in the human cerebral cortex, we applied a computationally efficient approach to map the degree of intrinsic functional connectivity across the brain. Analysis of two separate functional magnetic resonance imaging datasets (each n = 24) demonstrated hubs throughout heteromodal areas of association cortex. Prominent hubs were located within posterior cingulate, lateral temporal, lateral parietal, and medial/lateral prefrontal cortices. Network analysis revealed that many, but not all, hubs were located within regions previously implicated as components of the default network. A third dataset (n = 12) demonstrated that the locations of hubs were present across passive and active task states, suggesting that they reflect a stable property of cortical network architecture. To obtain an accurate reference map, data were combined across 127 participants to yield a consensus estimate of cortical hubs. Using this consensus estimate, we explored whether the topography of hubs could explain the pattern of vulnerability in Alzheimer's disease (AD) because some models suggest that regions of high activity and metabolism accelerate pathology. Positron emission tomography amyloid imaging in AD (n = 10) compared with older controls (n = 29) showed high amyloid-beta deposition in the locations of cortical hubs consistent with the possibility that hubs, while acting as critical way stations for information processing, may also augment the underlying pathological cascade in AD. C1 [Buckner, Randy L.; Sepulcre, Jorge; Krienen, Fenna M.; Hedden, Trey; Andrews-Hanna, Jessica R.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Buckner, Randy L.; Sepulcre, Jorge; Talukdar, Tanveer; Liu, Hesheng; Hedden, Trey; Sperling, Reisa A.; Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Buckner, Randy L.; Sepulcre, Jorge; Krienen, Fenna M.; Hedden, Trey; Andrews-Hanna, Jessica R.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.; Talukdar, Tanveer; Krienen, Fenna M.; Liu, Hesheng; Hedden, Trey; Andrews-Hanna, Jessica R.; Sperling, Reisa A.] Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Sperling, Reisa A.; Johnson, Keith A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Buckner, RL (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St,William James Hall 2nd Floor, Cambridge, MA 02138 USA. EM randy_buckner@harvard.edu OI Liu, Hesheng/0000-0002-7233-1509 FU National Institute on Aging [AG-021910, AG-027435-S1]; Howard Hughes Medical Institute FX This work was supported by the National Institute on Aging (Grants AG-021910 and AG-027435-S1) and the Howard Hughes Medical Institute. We thank Avi Snyder, Itamar Kahn, Brad Dickerson, and Marc Raichle for insightful comments and discussion. Yun-Ching Kao and Gagan Wig generously provided fMRI data. Larry Wald, Mary Foley, and the Athinoula A. Martinos Center MRI Core provided assistance with MRI imaging. The Molecular Imaging PET Core provided assistance with amyloid imaging. Bill Klunk and Chet Mathis provided assistance with PiB. Dorene Rentz and the Massachusetts ADRC provided assistance with characterization of the patient cohorts. NR 94 TC 1005 Z9 1029 U1 13 U2 101 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 11 PY 2009 VL 29 IS 6 BP 1860 EP 1873 DI 10.1523/JNEUROSCI.5062-08.2009 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 406NC UT WOS:000263301200028 PM 19211893 ER PT J AU Azzone, V Frank, RG Pakes, JR Earle, CC Hassett, MJ AF Azzone, Vanessa Frank, Richard G. Pakes, Juliana R. Earle, Craig C. Hassett, Michael J. TI Behavioral Health Services for Women Who Have Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MEDICAID CARVE-OUT; MENTAL-HEALTH; MANAGED CARE; COMORBIDITY INDEX; PROPENSITY SCORE; DIAGNOSIS; COSTS; DEPRESSION; SURVIVAL; MASSACHUSETTS AB Purpose To explore whether the use of behavioral health services (BHS) among women with breast cancer is influenced by how insurance plans administer these services, we compared utilization of psychotherapy and psychotherapeutic medications among women with breast cancer who received BHS coverage through a carve-out versus integrated arrangement. Patients and Methods We analyzed insurance claims, enrollment data, and benefit design data from the MarketScan Commercial Claims & Encounters Research Database for the years 1998 to 2002 for women <= 63 years old with newly diagnosed breast cancer. We compared the probability of receiving psychotherapy, the likelihood of receiving antidepressant/antianxiety/hypnotic medications, and the number of psychotherapy sessions used during the year after a breast cancer diagnosis among women whose behavioral health services were provided through carve-out versus integrated arrangements. Results Women enrolled in carve-outs were significantly less likely to receive any psychotherapy visits compared with women in integrated arrangements (odds ratio, 0.68; P < .01). Conditional on having received psychotherapy, however, women in carve-out arrangements used more psychotherapy visits than women in integrated arrangements. The use of antianxiety/hypnotic drugs was significantly higher for women in carve-out arrangements versus women in integrated arrangements (36.1% v 32.6%, P < .05). Moreover, women who received psychotherapy were significantly more likely to received antidepressants and antianxiety/hypnotic medications (five and three times more likely, respectively). Conclusion The type of BHS arrangement was associated with the utilization of psychotherapy and psychotherapeutic medications among women with breast cancer. C1 [Azzone, Vanessa] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. NYU, Steinhardt Sch Educ, New York, NY USA. RP Azzone, V (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM azzone@hcp.med.harvard.edu FU Agency for Healthcare Research and Quality [PO1 HS10803-03] FX Supported by Grant No. PO1 HS10803-03 (Structuring Markets and Competition in Health Care) from the Agency for Healthcare Research and Quality. NR 41 TC 13 Z9 13 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 FEB 10 PY 2009 VL 27 IS 5 BP 706 EP 712 DI 10.1200/JCO.2008.16.3006 PG 7 WC Oncology SC Oncology GA 404GR UT WOS:000263139800010 PM 19114705 ER PT J AU Freedman, RA He, YL Winer, EP Keating, NL AF Freedman, Rachel A. He, Yulei Winer, Eric P. Keating, Nancy L. TI Trends in Racial and Age Disparities in Definitive Local Therapy of Early-Stage Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2008 CL Chicago, IL SP Amer Soc Clin Oncol ID RANDOMIZED-TRIAL; FOLLOW-UP; RADIOTHERAPY; IRRADIATION; SURGERY; WOMEN; OLDER; LUMPECTOMY; MASTECTOMY; TAMOXIFEN AB Purpose Guidelines recommend breast-conserving surgery (BCS) with radiation or mastectomy for definitive local therapy of stage I/II breast cancers. We assessed receipt of definitive local therapy for early-stage breast cancer by race/ethnicity and age and examined trends over time. Patients and Methods We calculated rates of definitive local therapy (mastectomy or BCS with radiation) for 375,547 adult women with stage I or II breast cancer diagnosed during 1988 to 2004 using Surveillance, Epidemiology, and End Results registry data. We assessed the probability of definitive local therapy and trends over time using multivariate logistic regression. Results Overall, 85.8% of women had definitive local therapy. As mastectomy rates decreased (76.5% in 1988 to 38.0% in 2004; P < .001), definitive local therapy rates also decreased (95.2% in 1988 to 79.2% in 2004; P < .001). In adjusted analyses, rates of definitive local therapy were modestly lower for black and Hispanic (v white) women and higher for Asian women. Differences for black and Asian women were stable over time (P = .61 and P = .35 for interaction), but increased for Hispanic women (P = .0003). Although age differences narrowed over time, women older than 70 years and women <= 60 years had lower rates of definitive local therapy than women 61 to 70 years throughout the study period. Conclusion As breast conservation has increasingly substituted mastectomy, our findings suggest fewer women are receiving definitive local breast cancer therapy, with persistent disparities for black and Hispanic women as well as women age <= 60 and older than 70 years. Interventions to assure receipt of radiation after BCS are needed to eliminate these disparities. C1 [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Internal Med, 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 NR 29 TC 93 Z9 95 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 FEB 10 PY 2009 VL 27 IS 5 BP 713 EP 719 DI 10.1200/JCO.2008.17.9234 PG 7 WC Oncology SC Oncology GA 404GR UT WOS:000263139800011 PM 19103731 ER PT J AU Blumenthal, DT Won, M Mehta, MP Curran, WJ Souhami, L Michalski, JM Rogers, CL Corn, BW AF Blumenthal, Deborah T. Won, Minhee Mehta, Minesh P. Curran, Walter J. Souhami, Luis Michalski, Jeff M. Rogers, C. Leland Corn, Benjamin W. TI Short Delay in Initiation of Radiotherapy May Not Affect Outcome of Patients With Glioblastoma: A Secondary Analysis From the Radiation Therapy Oncology Group Database SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 11th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 16-19, 2006 CL Orlando, FL SP Soc Neuro Oncol ID SQUAMOUS-CELL CARCINOMA; POSITIVE BREAST-CANCER; POSTOPERATIVE RADIOTHERAPY; PHASE-II; MALIGNANT GLIOMA; LOCAL-CONTROL; WAITING TIME; EARLY-STAGE; PROGNOSTIC-FACTORS; LUNG-CANCER AB Purpose To analyze the Radiation Therapy Oncology Group (RTOG) database of patients with glioblastoma and appraise whether outcome was influenced by time to initiation of radiation therapy (RT). Patients and Methods From 1974 through 2003, adult patients with histologically confirmed supratentorial glioblastoma were enrolled onto 16 RTOG studies. Of 3,052 enrolled patients, 197 patients (6%) were either initially rendered ineligible or had insufficient chronologic data, leaving a cohort of 2,855 patients for the present analysis. We selected four patient groups based on the interval from surgery to the start of RT: <= 2 weeks, 2 to 3 weeks, 3 to 4 weeks, more than 4 weeks to the protocol eligibility limit of 6 weeks. Survival times were estimated by the Kaplan-Meier method. Multivariate analysis incorporated variables of time interval, recursive partitioning analysis (RPA) class, and treatment regimen. Results No decrement in survival could be identified with increasing time to initiation of RT. Among our four temporal groupings, median survival time was unexpectedly and significantly greater in the group with the longest interval (> 4 weeks) than in those with the shortest delay (<= 2 weeks): respectively, 12.5 months versus 9.2 months (P < .0001). On multivariate analysis, with overall survival as the end point, time interval more than 4 weeks and lower RPA class were both significant predictors of improved outcome. Treatment regimen was not a significant factor. Conclusion There is no evident reduction in survival by delaying initiation of RT within the relatively narrow constraint of 6 weeks. An unanticipated yet significantly superior outcome was identified for patients for whom RT was delayed beyond 4 weeks from surgery. C1 Tel Aviv Med Ctr & Sch Med, Dept Oncol, Tel Aviv, Israel. Tel Aviv Med Ctr & Sch Med, Dept Neurooncol Serv, Tel Aviv, Israel. Tel Aviv Med Ctr & Sch Med, Dept Radiat Oncol, Tel Aviv, Israel. Thomas Jefferson Univ Hosp, Dept Radiat Oncol, Radiat Therapy Oncol Grp, Stat Unit, Philadelphia, PA 19107 USA. Univ Wisconsin, Dept Radiat Oncol, Madison, WI USA. Mayo Clin, Rochester, MN USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Gamma W Radiat Therapy, Dept Radiat Oncol, Salt Lake City, UT USA. McGill Univ, Dept Radiat Oncol, Montreal, PQ H3A 2T5, Canada. RP Blumenthal, DT (reprint author), Tel Aviv Sourasky Med Ctr, Dept Oncol, 6 Weizman St, Tel Aviv, Israel. EM deborahblumenthal@gmail.com OI mehta, minesh/0000-0002-4812-5713 NR 43 TC 43 Z9 46 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 10 PY 2009 VL 27 IS 5 BP 733 EP 739 DI 10.1200/JCO.2008.18.9035 PG 7 WC Oncology SC Oncology GA 404GR UT WOS:000263139800014 PM 19114694 ER PT J AU Walsh, CT Fischbach, MA AF Walsh, Christopher T. Fischbach, Michael A. TI Repurposing libraries of eukaryotic protein kinase inhibitors for antibiotic discovery SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID CARBOXYLASE C1 [Walsh, Christopher T.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Fischbach, Michael A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Walsh, CT (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM christopher_walsh@hms.harvard.edu NR 9 TC 17 Z9 17 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 10 PY 2009 VL 106 IS 6 BP 1689 EP 1690 DI 10.1073/pnas.0813405106 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 405VO UT WOS:000263252500004 PM 19193851 ER PT J AU Jones, TR Carpenter, AE Lamprecht, MR Moffat, J Silver, SJ Grenier, JK Castoreno, AB Eggert, US Root, DE Golland, P Sabatini, DM AF Jones, Thouis R. Carpenter, Anne E. Lamprecht, Michael R. Moffat, Jason Silver, Serena J. Grenier, Jennifer K. Castoreno, Adam B. Eggert, Ulrike S. Root, David E. Golland, Polina Sabatini, David M. TI Scoring diverse cellular morphologies in image-based screens with iterative feedback and machine learning SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE high-content screening; high-throughput image analysis; phenotype ID SUBCELLULAR STRUCTURES; HUMAN-CELLS; MUTATIONS; PATTERNS; CYCLE; RECOGNITION; MICROSCOPY; DROSOPHILA; ZEBRAFISH; GENES AB Many biological pathways were first uncovered by identifying mutants with visible phenotypes and by scoring every sample in a screen via tedious and subjective visual inspection. Now, automated image analysis can effectively score many phenotypes. In practical application, customizing an image-analysis algorithm or finding a sufficient number of example cells to train a machine learning algorithm can be infeasible, particularly when positive control samples are not available and the phenotype of interest is rare. Here we present a supervised machine learning approach that uses iterative feedback to readily score multiple subtle and complex morphological phenotypes in high-throughput, image-based screens. First, automated cytological profiling extracts hundreds of numerical descriptors for every cell in every image. Next, the researcher generates a rule (i.e., classifier) to recognize cells with a phenotype of interest during a short, interactive training session using iterative feedback. Finally, all of the cells in the experiment are automatically classified and each sample is scored based on the presence of cells displaying the phenotype. By using this approach, we successfully scored images in RNA interference screens in 2 organisms for the prevalence of 15 diverse cellular morphologies, some of which were previously intractable. C1 [Jones, Thouis R.; Carpenter, Anne E.; Silver, Serena J.; Grenier, Jennifer K.; Root, David E.; Sabatini, David M.] MIT & Harvard, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Jones, Thouis R.; Carpenter, Anne E.; Lamprecht, Michael R.; Moffat, Jason; Sabatini, David M.] MIT, Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. [Jones, Thouis R.; Golland, Polina] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Castoreno, Adam B.; Eggert, Ulrike S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Castoreno, Adam B.; Eggert, Ulrike S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Carpenter, AE (reprint author), MIT & Harvard, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM anne@broad.mit.edu RI Carpenter, Anne/C-4982-2008 OI Carpenter, Anne/0000-0003-1555-8261 FU Broad Institute; RNAi Consortium; Life Sciences Research Foundation; Society for Biomolecular Screening Academic grant; L'Oreal for Women in Science fellowship; Massachusetts Institute of Technology; National Institutes of Health [DK070069- 01]; National Science Foundation [0642971]; National Institute of General Medical Sciences [R01 GM0725555]; National Institute of Allergy and Infectious Diseases [RO1 AI047389] FX We thank InHan Kang (Massachusetts Institute of Technology) for creating the CellProfiler Analyst software infrastructure and engineering some of the machine learning functionality; the RNAi Consortium and the Broad Institute RNAi Platform for investment of time and resources in the project; the Broad Institute Imaging Platform members for image analysis, statistical analysis, and software engineering(especially Adam Fraser, Adam Papallo, and Martha Vokes); Shomit Sengupta for microscopy and assay guidance; Aviv Regev and Eric Lander for helpful comments on the manuscript; and David Bonnett, Renee Butterfield, Dan Card, Dianne Carpenter, Seth Carpenter, Christopher Lewis, and Themba Nyathi for scoring images for the project. This work was supported by the Broad Institute, the RNAi Consortium, a Novartis fellowship from the Life Sciences Research Foundation (to A. E. C.), a Society for Biomolecular Screening Academic grant (to A. E. C.), a L'Oreal for Women in Science fellowship (to A. E. C.), the Massachusetts Institute of Technology Department of Electrical Engineering and Computer Science/Whitehead/Broad Training Program in Computational Biology, National Institutes of Health Grant DK070069- 01 (to T. R. J.), National Science Foundation CAREER Award 0642971 (to P. G.), National Institute of General Medical Sciences Grant R01 GM0725555 (to D. M. S.) and National Institute of Allergy and Infectious Diseases Grant RO1 AI047389 (to D. M. S.). NR 36 TC 166 Z9 166 U1 0 U2 20 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 10 PY 2009 VL 106 IS 6 BP 1826 EP 1831 DI 10.1073/pnas.0808843106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 405VO UT WOS:000263252500029 PM 19188593 ER PT J AU Butcher, RA Ragains, JR Li, WQ Ruvkun, G Clardy, J Mak, HY AF Butcher, Rebecca A. Ragains, Justin R. Li, Weiqing Ruvkun, Gary Clardy, Jon Mak, Ho Yi TI Biosynthesis of the Caenorhabditis elegans dauer pheromone SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ascaroside; daf-22; dhs-28 ID C-ELEGANS; LARVAL DEVELOPMENT; LIFE-SPAN; ASCARIS LUMBRICOIDES; ENVIRONMENTAL CUES; NUCLEAR RECEPTOR; GENE; ENCODES; INSULIN; LONGEVITY AB To sense its population density and to trigger entry into the stress-resistant dauer larval stage, Caenorhabditis elegans uses the dauer pheromone, which consists of ascaroside derivatives with short, fatty acid-like side chains. Although the dauer pheromone has been studied for 25 years, its biosynthesis is completely uncharacterized. The daf-22 mutant is the only known mutant defective in dauer pheromone production. Here, we show that daf-22 encodes a homolog of human sterol carrier protein SCPx, which catalyzes the final step in peroxisomal fatty acid beta-oxidation. We also show that dhs-28, which encodes a homolog of the human D-bifunctional protein that acts just upstream of SCPx, is also required for pheromone production. Long-term daf-22 and dhs-28 cultures develop dauer-inducing activity by accumulating less active, long-chain fatty acid ascaroside derivatives. Thus, daf-22 and dhs-28 are required for the biosynthesis of the short-chain fatty acid-derived side chains of the dauer pheromone and link dauer pheromone production to metabolic state. C1 [Butcher, Rebecca A.; Ragains, Justin R.; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Li, Weiqing] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. [Ruvkun, Gary] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Mak, Ho Yi] Stowers Inst Med Res, Kansas City, MO 64110 USA. [Mak, Ho Yi] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA. RP Mak, HY (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM jon_clardy@hms.harvard.edu; hym@stowers.org OI Mak, Ho Yi/0000-0002-1500-5328 FU National Institutes of Health National Center for Research Resources [CA24487]; Stowers Institute for Medical Research; National Research Service Award Postdoctoral Fellowship [GM077943] FX We thank Donald Riddle for unpublished information; Jason Crawford and Dong-Chan Oh for discussion; and Andy Fire (Stanford University School of Medicine), Jihong Bai (Harvard Medical School), and Jeremy Dittman (Weill Cornell Medical College) for vectors. Some worm strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health National Center for Research Resources. This work was supported by Grant CA24487 (to J. C.) and by the Stowers Institute for Medical Research (H. Y. M.). R. A. B. was supported by National Research Service Award Postdoctoral Fellowship GM077943. NR 33 TC 74 Z9 77 U1 1 U2 20 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 10 PY 2009 VL 106 IS 6 BP 1875 EP 1879 DI 10.1073/pnas.0810338106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 405VO UT WOS:000263252500038 PM 19174521 ER PT J AU Rajimehra, R Young, JC Tootell, RBH AF Rajimehra, Reza Young, Jeremy C. Tootell, Roger B. H. TI An anterior temporal face patch in human cortex, predicted by macaque maps SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE face processing; fMRI; inferotemporal cortex; macaque-human homology ID INFEROTEMPORAL CORTEX; VISUAL-CORTEX; CORTICAL CONNECTIONS; CONTRAST AGENT; RHESUS-MONKEY; OBJECT AREAS; PERCEPTION; LOBE; FMRI; ORGANIZATION AB Increasing evidence suggests that primate visual cortex has a specialized architecture for processing discrete object categories such as faces. Human fMRI studies have described a localized region in the fusiform gyrus [ the fusiform face area (FFA)] that responds selectively to faces. In contrast, in nonhuman primates, electrophysiological and fMRI studies have instead revealed 2 apparently analogous regions of face representation: the posterior temporal face patch ( PTFP) and the anterior temporal face patch ( ATFP). An earlier study suggested that human FFA is homologous to the PTFP in macaque. However, in humans, no obvious homologue of the macaque ATFP has been demonstrated. Here, we used fMRI to map face-selective sites in both humans and macaques, based on equivalent stimuli in a quantitative topographic comparison. This fMRI evidence suggests that such a face-selective area exists in human anterior inferotemporal cortex, comprising the apparent homologue of the fMRI-defined ATFP in macaques. C1 [Rajimehra, Reza; Young, Jeremy C.; Tootell, Roger B. H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Martinos Ctr, Charlestown, MA 02129 USA. [Rajimehra, Reza] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. RP Rajimehra, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Martinos Ctr, Charlestown, MA 02129 USA. EM reza@nmr.mgh.harvard.edu FU National Institutes of Health [R01 MH67529, R01 EY017081]; Martinos Center for Biomedical Imaging, National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery Institute FX We thank Wim Vanduffel for help in the monkey surgery and monkey fMRI setup, Mukund Balasubramanian for providing cortical flattening code, David Van Essen for help in the Caret analysis, and 2 anonymous reviewers for their scientific input on an earlier version of this manuscript. This work was supported by the National Institutes of Health Grants R01 MH67529 and R01 EY017081 ( to R. B. H. T.), the Martinos Center for Biomedical Imaging, National Center for Research Resources Grant P41RR14075, and the Mental Illness and Neuroscience Discovery Institute. NR 50 TC 125 Z9 125 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 10 PY 2009 VL 106 IS 6 BP 1995 EP 2000 DI 10.1073/pnas.0807304106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 405VO UT WOS:000263252500059 PM 19179278 ER PT J AU Varkey, AB Manwell, LB Williams, ES Ibrahim, SA Brown, RL Bobula, JA Horner-Ibler, BA Schwartz, MD Konrad, TR Wiltshire, JC Linzer, M AF Varkey, Anita B. Manwell, Linda Baier Williams, Eric S. Ibrahim, Said A. Brown, Roger L. Bobula, James A. Horner-Ibler, Barbara A. Schwartz, Mark D. Konrad, Thomas R. Wiltshire, Jacqueline C. Linzer, Mark CA Memo Investigators TI Separate and Unequal Clinics Where Minority and Nonminority Patients Receive Primary Care SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 27-29, 2006 CL Los Angeles, CA SP Soc Gen Internal Med ID PHYSICIANS; HEALTH; SATISFACTION; VALIDITY; MODELS AB Background: Few studies have examined the influence of physician workplace conditions on health care disparities. We compared 96 primary care clinics in New York, New York, and in the upper Midwest serving various proportions of minority patients to determine differences in workplace organizational characteristics. Methods: Cross-sectional data are from surveys of 96 clinic managers, 388 primary care physicians, and 1701 of their adult patients with hypertension, diabetes mellitus, or congestive heart failure participating in the Minimizing Error, Maximizing Outcome (MEMO) study. Data from 27 clinics with at least 30% minority patients were contrasted with data from 69 clinics with less than 30% minority patients. Results: Compared with clinics serving less than 30% minority patients, clinics serving at least 30% minority patients have less access to medical supplies (2.7 vs 3.4, P < .001), referral specialists (3.0 vs 3.5, P < .005) on a scale of 1 (none) to 4 (great), and examination rooms per physician (2.2 vs 2.7, P = .002). Their patients are more frequently depressed (22.8% vs 12.1%), are more often covered by Medicaid (30.2% vs 11.4%), and report lower health literacy (3.7 vs 4.4) on a scale of 1 (low) to 5 (high) (P < .001 for all). Physicians from clinics serving higher proportions of minority populations perceive their patients as frequently speaking little or no English (27.1% vs 3.4%, P = .004), having more chronic pain (24.1% vs 12.9%, P < .001) and substance abuse problems (15.1% vs 10.1%, P = .005), and being more medically complex (53.1% vs 39.9%) and psychosocially complex (44.9% vs 28.2%) (P < .001 for both). In regression analyses, clinics with at least 30% minority patients are more likely to have chaotic work environments (odds ratio, 4.0; P = .003) and to have fewer physicians reporting high work control (0.2; P = .003) or high job satisfaction (0.4; P = .01). Conclusion: Clinics serving higher proportions of minority patients have more challenging workplace and organizational characteristics. C1 [Varkey, Anita B.] John H Stroger Jr Hosp Cook Cty, Dept Med, Chicago, IL USA. [Varkey, Anita B.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Varkey, Anita B.] Loyola Univ, Med Ctr, Chicago, IL 60611 USA. [Manwell, Linda Baier; Bobula, James A.] Univ Wisconsin, Dept Family Med, Madison, WI USA. [Linzer, Mark] Univ Wisconsin, Dept Med, Madison, WI USA. [Wiltshire, Jacqueline C.] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI USA. [Brown, Roger L.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Brown, Roger L.] Univ Wisconsin, Sch Nursing, Madison, WI USA. [Horner-Ibler, Barbara A.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Williams, Eric S.] Univ Alabama, Culverhouse Coll Commerce & Business Adm, Dept Management & Mkt, Tuscaloosa, AL USA. [Ibrahim, Said A.] Univ Pittsburgh, Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Ibrahim, Said A.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Schwartz, Mark D.] NYU, Sch Med, Dept Med, New York, NY USA. [Schwartz, Mark D.] Vet Affairs New York Harbor Hlth Care Syst, New York, NY USA. [Konrad, Thomas R.] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC USA. RP Varkey, AB (reprint author), Loyola Univ, Med Ctr, Dept Med, 2160 S 1st Ave, Maywood, IL 60153 USA. EM avarkey@lumc.edu OI Konrad, Thomas R/0000-0002-5269-0440 FU AHRQ HHS [5R01 HS 011955] NR 25 TC 52 Z9 52 U1 3 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 9 PY 2009 VL 169 IS 3 BP 243 EP 250 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 405DK UT WOS:000263202600006 PM 19204215 ER PT J AU Isaac, T Weissman, JS Davis, RB Massagli, M Cyrulik, A Sands, DZ Weingart, SN AF Isaac, Thomas Weissman, Joel S. Davis, Roger B. Massagli, Michael Cyrulik, Adrienne Sands, Daniel Z. Weingart, Saul N. TI Overrides of Medication Alerts in Ambulatory Care SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PHYSICIAN-ORDER ENTRY; ADVERSE DRUG EVENTS; ERRORS; SYSTEMS; IMPACT AB Background: Electronic prescribing systems with decision support may improve patient safety in ambulatory care by offering drug allergy and drug interaction alerts. However, preliminary studies show that clinicians override most of these alerts. Methods: We performed a retrospective analysis of 233 537 medication safety alerts generated by 2872 clinicians in Massachusetts, New Jersey, and Pennsylvania who used a common electronic prescribing system from January 1, 2006, through September 30, 2006. We used multivariate techniques to examine factors associated with alert acceptance. Results: A total of 6.6% of electronic prescription attempts generated alerts. Clinicians accepted 9.2% of drug interaction alerts and 23.0% of allergy alerts. High-severity interactions accounted for most alerts (61.6%); clinicians accepted high-severity alerts slightly more often than moderate- or low-severity interaction alerts (10.4%, 7.3%, and 7.1%, respectively; P < .001). Clinicians accepted 2.2% to 43.1% of high-severity interaction alerts, depending on the classes of interacting medications. In multivariable analyses, we found no difference in alert acceptance among clinicians of different specialties (P = .16). Clinicians were less likely to accept a drug interaction alert if the patient had previously received the alerted medication (odds ratio, 0.03; 95% confidence interval, 0.03-0.03). Conclusion: Clinicians override most medication alerts, suggesting that current medication safety alerts may be inadequate to protect patient safety. C1 [Isaac, Thomas; Davis, Roger B.; Sands, Daniel Z.; Weingart, Saul N.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Weissman, Joel S.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Isaac, Thomas; Weingart, Saul N.] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA USA. [Isaac, Thomas; Weissman, Joel S.; Davis, Roger B.; Weingart, Saul N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Massagli, Michael] PatientsLikeMe Inc, Cambridge, MA USA. [Sands, Daniel Z.] Cisco Syst, San Jose, CA USA. RP Isaac, T (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave, Boston, MA 02215 USA. EM tisaac@bidmc.harvard.edu FU Physicians' Foundation for Health Systems Excellence FX This study was supported by a grant from the Physicians' Foundation for Health Systems Excellence. NR 25 TC 143 Z9 145 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 9 PY 2009 VL 169 IS 3 BP 305 EP 311 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 405DK UT WOS:000263202600014 PM 19204222 ER PT J AU Foley, JE Yeh, JRJ Maeder, ML Reyon, D Sander, JD Peterson, RT Joung, JK AF Foley, Jonathan E. yeh, Jing-Ruey J. Maeder, Morgan L. Reyon, Deepak Sander, Jeffry D. Peterson, Randall T. Joung, J. Keith TI Rapid Mutation of Endogenous Zebrafish Genes Using Zinc Finger Nucleases Made by Oligomerized Pool ENgineering (OPEN) SO PLOS ONE LA English DT Article AB Background: Customized zinc finger nucleases (ZFNs) form the basis of a broadly applicable tool for highly efficient genome modification. ZFNs are artificial restriction endonucleases consisting of a non-specific nuclease domain fused to a zinc finger array which can be engineered to recognize specific DNA sequences of interest. Recent proof-of-principle experiments have shown that targeted knockout mutations can be efficiently generated in endogenous zebrafish genes via non-homologous end-joining-mediated repair of ZFN-induced DNA double-stranded breaks. The Zinc Finger Consortium, a group of academic laboratories committed to the development of engineered zinc finger technology, recently described the first rapid, highly effective, and publicly available method for engineering zinc finger arrays. The Consortium has previously used this new method (known as OPEN for Oligomerized Pool ENgineering) to generate high quality ZFN pairs that function in human and plant cells. Methodology/Principal Findings: Here we show that OPEN can also be used to generate ZFNs that function efficiently in zebrafish. Using OPEN, we successfully engineered ZFN pairs for five endogenous zebrafish genes: tfr2, dopamine transporter, telomerase, hif1aa, and gridlock. Each of these ZFN pairs induces targeted insertions and deletions with high efficiency at its endogenous gene target in somatic zebrafish cells. In addition, these mutations are transmitted through the germline with sufficiently high frequency such that only a small number of fish need to be screened to identify founders. Finally, in silico analysis demonstrates that one or more potential OPEN ZFN sites can be found within the first three coding exons of more than 25,000 different endogenous zebrafish gene transcripts. Conclusions and Significance: In summary, our study nearly triples the total number of endogenous zebrafish genes successfully modified using ZFNs (from three to eight) and suggests that OPEN provides a reliable method for introducing targeted mutations in nearly any zebrafish gene of interest. C1 [Foley, Jonathan E.; Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA USA. [Foley, Jonathan E.; Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Comput & Integrat Biol, Charlestown, MA USA. [yeh, Jing-Ruey J.; Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [yeh, Jing-Ruey J.; Peterson, Randall T.] MIT, Broad Inst, Cambridge, MA USA. [yeh, Jing-Ruey J.; Peterson, Randall T.] Harvard Univ, Cambridge, MA USA. [Reyon, Deepak; Sander, Jeffry D.] Iowa State Univ, Dept Genet Dev & Cell Biol, Interdept Grad Program Bioinformat & Comp Biol, Ames, IA 50011 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Foley, JE (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA USA. EM jjoung@partners.org FU NIH [R01 GM069906, R21 HL091808, R01 HL79267, R33-GM066387]; MGH Department of Pathology; National Institute of Aging [K01 AG031300]; Claflin Distinguished Scholar Award; Pioneer-Hi-Bred International, Inc [2008 Graduate Fellowship]; ISU CIAG FX J.E.F., M.L.M., and J.K.J. are supported by the NIH (R01 GM069906 and R21 HL091808) and the MGH Department of Pathology. J.-R.J.Y. is supported by the National Institute of Aging (K01 AG031300) and by a Claflin Distinguished Scholar Award. J.-R.J.Y. and R.T.P. are supported by the NIH (R01 HL79267). J.D.S is supported by Pioneer-Hi-Bred International, Inc 2008 Graduate Fellowship, NIH R33-GM066387, and ISU CIAG. D.R is supported by ISU CIAG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 155 Z9 168 U1 1 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 9 PY 2009 VL 4 IS 2 AR e4348 DI 10.1371/journal.pone.0004348 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437JN UT WOS:000265483900001 PM 19198653 ER PT J AU Trinacty, CM Adams, AS Soumerai, SB Zhang, F Meigs, JB Piette, JD Ross-Degnan, D AF Trinacty, Connie M. Adams, Alyce S. Soumerai, Stephen B. Zhang, Fang Meigs, James B. Piette, John D. Ross-Degnan, Dennis TI Racial differences in long-term adherence to oral antidiabetic drug therapy: a longitudinal cohort study SO BMC HEALTH SERVICES RESEARCH LA English DT Article CT 67th Annual Meeting of the American-Diabetes-Association CY JUN 22-26, 2007 CL Chicago, IL SP Amer Diabet Assoc ID DIABETES SELF-MANAGEMENT; GLYCEMIC CONTROL; BLOOD-GLUCOSE; POPULATION; CARE; HEALTH; US; RECOMMENDATIONS; ORGANIZATION; MEDICATION AB Background: Adherence to oral antidiabetic medications is often suboptimal. Adherence differences may contribute to health disparities for black diabetes patients, including higher microvascular event rates, greater complication-related disability, and earlier mortality. Methods: In this longitudinal retrospective cohort study, we used 10 years of patient-level claims and electronic medical record data (1/1/1992 - 12/31/2001) to assess differences in short- and long-term adherence to oral antidiabetic medication among 1906 newly diagnosed adults with diabetes (26% black, 74% white) in a managed care setting in which all members have prescription drug coverage. Four main outcome measures included: (1) time from diabetes diagnosis until first prescription of oral antidiabetic medication; (2) primary adherence (time from first prescription to prescription fill); (3) time until discontinuation of oral antidiabetic medication from first prescription; and (4) long-term adherence (amount dispensed versus amount prescribed) over a 24-month follow-up from first oral antidiabetic medication prescription. Results: Black patients were as likely as whites to initiate oral therapy and fill their first prescription, but experienced higher rates of medication discontinuation (HR: 1.8, 95% CI: 1.2, 2.7) and were less adherent over time. These black-white differences increased over the first six months of therapy but stabilized thereafter for patients who initiated on sulfonylureas. Significant black-white differences in adherence levels were constant throughout follow-up for patients initiated on metformin therapy. Conclusion: Racial differences in adherence to oral antidiabetic drug therapy persist even with equal access to medication. Early and continued emphasis on adherence from initiation of therapy may reduce persistent racial differences in medication use and clinical outcomes. C1 [Trinacty, Connie M.; Adams, Alyce S.; Soumerai, Stephen B.; Zhang, Fang; Meigs, James B.; Ross-Degnan, Dennis] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. [Trinacty, Connie M.; Adams, Alyce S.; Soumerai, Stephen B.; Zhang, Fang; Ross-Degnan, Dennis] Harvard Pilgrim Hlth Care, Boston, MA USA. [Adams, Alyce S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Gen Med Unit, Boston, MA USA. [Piette, John D.] Univ Michigan, VA Ctr Clin Management Res, Hlth Care Syst, Ann Arbor, MI 48109 USA. [Piette, John D.] Univ Michigan, Div Gen Med, Hlth Care Syst, Ann Arbor, MI 48109 USA. RP Trinacty, CM (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. EM connie_trinacty@hphc.org; alyce.s.adams@nsmtp.kp.org; ssoumerai@hms.harvard.edu; fang_zhang@hphc.org; jmeigs@partners.org; jpiette@umich.edu; drossdeg@hms.harvard.edu FU NIDDK NIH HHS [P60 DK020572, P30 DK020572, DK020572] NR 31 TC 35 Z9 36 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD FEB 7 PY 2009 VL 9 AR 24 DI 10.1186/1472-6963-9-24 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 418LC UT WOS:000264148700001 PM 19200387 ER PT J AU Dattoli, G Guiot, C Delsanto, PP Ottaviani, PL Pagnutti, S Deisboeck, TS AF Dattoli, G. Guiot, C. Delsanto, P. P. Ottaviani, P. L. Pagnutti, S. Deisboeck, T. S. TI Cancer metabolism and the dynamics of metastasis SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE General theory and mathematical aspects ID TUMOR-GROWTH; MODEL; DISSEMINATION; CARCINOMA AB Cancer growth dynamics, commonly simulated with a Compertzian model, is analyzed in the framework of a more recent and realistic model. In particular, we consider the setting of a tumor embedded in a host organ and investigate their interaction. We assume that, at least in some cases, tumor metastasis may be triggered by an 'energetic crisis', when the tumor exceeds the 'carrying capacity' of the host organ. As a consequence, dissemination of clusters of cancer cells is set in motion, with a statistical probability given by a Poisson distribution. The model, although still at a preclinical level, is fully quantitative and is applied, as an example, to the case of prostate cancer. The results confirm that, at least for the more aggressive cancers, metastasis starts very early during tumorigenesis and a quantitative link is found between the tumor's doubling time, its 'aggressiveness' and the metastatic potential., (c) 2008 Elsevier Ltd. All rights reserved. C1 [Dattoli, G.] Ctr Ric Frascati, Unita Fis Teor & Matemat Applicata, Dip FIM, ENEA, I-00044 Frascati, Italy. [Guiot, C.] Univ Turin, Dipartimento Neurosci, Turin, Italy. [Delsanto, P. P.] Politecn Turin, Dipartimento Fis, Turin, Italy. [Ottaviani, P. L.; Pagnutti, S.] Ctr Ric Bologna, Dip FIM, ENEA, Bologna, Italy. [Deisboeck, T. S.] Massachusetts Gen Hosp, Athinoula A Martino Ctr Biomed Imaging, Harvard MIT HST, Complex Biosyst Modeling Lab, Charlestown, MA 02129 USA. RP Dattoli, G (reprint author), Ctr Ric Frascati, Unita Fis Teor & Matemat Applicata, Dip FIM, ENEA, I-00044 Frascati, Italy. EM dattoli@frascati.enea.it RI guiot, caterina/C-6708-2009; OI guiot, caterina/0000-0001-8529-1625 FU NCI NIH HHS [CA 113004] NR 29 TC 9 Z9 9 U1 0 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD FEB 7 PY 2009 VL 256 IS 3 BP 305 EP 310 DI 10.1016/j.jtbi.2008.10.008 PG 6 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 403IU UT WOS:000263077100001 PM 18996401 ER PT J AU Chen, AE Egli, D Niakan, K Deng, J Akutsu, H Yamaki, M Cowan, C Fitz-Gerald, C Zhang, K Melton, DA Eggan, K AF Chen, Alice E. Egli, Dieter Niakan, Kathy Deng, Jie Akutsu, Hidenori Yamaki, Mariko Cowan, Chad Fitz-Gerald, Claire Zhang, Kun Melton, Douglas A. Eggan, Kevin TI Optimal Timing of Inner Cell Mass Isolation Increases the Efficiency of Human Embryonic Stem Cell Derivation and Allows Generation of Sibling Cell Lines SO CELL STEM CELL LA English DT Article ID HUMAN BLASTOCYSTS; IN-VITRO; DIFFERENTIATION; CULTURE C1 [Cowan, Chad; Melton, Douglas A.; Eggan, Kevin] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Cowan, Chad; Eggan, Kevin] Harvard Univ, Stowers Med Inst, Cambridge, MA 02138 USA. [Melton, Douglas A.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Chen, Alice E.; Egli, Dieter; Niakan, Kathy; Yamaki, Mariko; Fitz-Gerald, Claire; Melton, Douglas A.; Eggan, Kevin] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Akutsu, Hidenori] Natl Res Inst Child Hlth & Dev, Setagaya Ku, Tokyo 1578535, Japan. [Cowan, Chad] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Deng, Jie; Zhang, Kun] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. RP Melton, DA (reprint author), Harvard Univ, Harvard Stem Cell Inst, 7 Divin Ave, Cambridge, MA 02138 USA. EM dmelton@harvard.edu; eggan@mcb.harvard.edu FU Jane Coffin Childs Memorial Fund for Medical Research; Merck Research Laboratories; Health and Labour Sciences Research Grants, Japan; University of California, San Diego; Harvard Stem Cell Institute; Stowers Medical Institute; Howard Hughes Medical Institute FX We thank E. Trish for technical assistance, K. Osafune for help with ESC culture, and J. Sprague and G. Hardiman for assistance in microarray analysis. A.E.C. is a fellow of the Jane Coffin Childs Memorial Fund for Medical Research and Merck Research Laboratories. H.A. is funded by Health and Labour Sciences Research Grants, Japan. K.E. is a fellow of the John D. and Catherine T. MacArthur Foundation. K.Z. and J.D. are funded by the University of California, San Diego new faculty startup fund. J.D. is a California Institute for Regenerative Medicine postdoctoral fellow. This work was supported by the Harvard Stem Cell Institute as well as the Stowers Medical Institute and Howard Hughes Medical Institute. NR 23 TC 91 Z9 92 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD FEB 6 PY 2009 VL 4 IS 2 BP 103 EP 106 DI 10.1016/j.stem.2008.12.001 PG 4 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 405HI UT WOS:000263213400005 PM 19200798 ER PT J AU Sowden, GL Huffman, JC AF Sowden, Gillian L. Huffman, Jeff C. TI The impact of mental illness on cardiac outcomes: A review for the cardiologist SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Review DE Cardiovascular disease; Depression; Anxiety disorders; Bipolar disorder; Schizophrenia ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; MAJOR DEPRESSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; SEROTONIN REUPTAKE INHIBITORS; CARDIOVASCULAR RISK-FACTORS; PLACEBO-CONTROLLED TRIAL; C-REACTIVE PROTEIN; BIPOLAR DISORDER; ARTERY-DISEASE AB Traditional cardiac risk factors, such as smoking, hypertension and obesity, are widely accepted contributors to the onset and progression of cardiovascular disease (CVD), one of the foremost causes of morbidity and mortality worldwide. Largely overlooked, however, is the impact of mental health on cardiac disease. From extensive MEDLINE and PsycINFO searches, we have reviewed the association between specific psychiatric disorders and CVD-related morbidity and mortality, the efficacy and safety of their treatments, and plausible behavioral and biological mechanism through which these associations may occur. The preponderance of evidence suggests that depression, anxiety disorders, bipolar disorder and schizophrenia are all important cardiac risk factors, and patients with these disorders are at significantly higher risk for cardiac morbidity and mortality than are their counterparts in the general population. Antidepressants, antipsychotics, mood stabilizers and benzodiazepines are effective therapeutic interventions, and many are safe to use in cardiac populations. Some, such as selective serotonin reuptake inhibitors and atypical antipsychotics, may even improve cardiac outcomes in healthy individuals and patients with CVD, although more work is needed to confirm this hypothesis. A combination of behavioral and biological mechanisms underlies the association between cardiac disease and mental illness, many of which are shared across disorders. With further research, it may be learned that psychiatric treatments definitively reverse the detrimental effects of mental illness on cardiac health. Currently, however, the challenge lies in raising awareness of mental health issues in cardiac patients, so that basic but critical treatments may be initiated in this population. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Sowden, Gillian L.] Harvard Univ, Sch Med, TMEC, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sowden, GL (reprint author), Harvard Univ, Sch Med, TMEC, 260 Longwood Ave, Boston, MA 02115 USA. EM gillian_sowden@hms.harvard.edu RI Langan Martin, Julie/M-4658-2015 NR 135 TC 38 Z9 42 U1 6 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD FEB 6 PY 2009 VL 132 IS 1 BP 30 EP 37 DI 10.1016/j.ijcard.2008.10.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 401YD UT WOS:000262978900004 PM 19004512 ER EF