FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Pope, C Davis, BH AF Pope, Charlene Davis, Boyd H. TI Finding a balance: The Carolinas Conversation Collection SO CORPUS LINGUISTICS AND LINGUISTIC THEORY LA English DT Article DE sociolinguistics; health; chronic disease; Alzheimer's disease; ONZE Miner; ethnic groups; social determinants of health ID VISTA-CLINICAL-TRIAL; ALZHEIMERS-DISEASE; CULTURAL COMPETENCE; VERBAL REPETITION; INFORMATION; HEALTH; GALANTAMINE; PEOPLE; COMMUNICATION; DEMENTIA AB The Carolinas Conversations Collection is a password-protected digital collection of transcribed audio and video recordings of conversations about health, supported by the National Libraries of Medicine. It has two cohorts: 125 unimpaired multiethnic older speakers with any of 12 chronic conditions and a longitudinal set of 400 conversations with 125 persons having dementia. Information about health literacy, health status, and cognitive function requires high standards for privacy and confidentiality, and restricted data use agreements. Since contents are housed in an adaptation of the well-established ONZE Miner, users can search and perform online analysis of sound, word or syntax with increasing specificity. C1 [Pope, Charlene] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Pope, Charlene] Ralph H Johnson Vet Affairs VA Med Ctr, Charleston, SC USA. [Davis, Boyd H.] Univ N Carolina Charlotte, Charlotte, NC USA. RP Pope, C (reprint author), Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. EM popec@musc.edu; boydhdavis@yahoo.com OI Davis, Boyd/0000-0003-4773-7715 NR 64 TC 3 Z9 3 U1 0 U2 3 PU MOUTON DE GRUYTER PI BERLIN PA GENTHINER STRASSE 13, 10785 BERLIN, GERMANY SN 1613-7027 J9 CORPUS LINGUIST LING JI Corpus Linguist. Linguist. Theo. PD MAY PY 2011 VL 7 IS 1 SI SI BP 143 EP 161 DI 10.1515/CLLT.2011.007 PG 19 WC Linguistics; Language & Linguistics SC Linguistics GA 776MK UT WOS:000291539000007 ER PT J AU Bell, PD Fitzgibbon, W Sas, K Stenbitt, AE Amria, M Houston, A Reichert, R Gilley, S Siegal, GP Bissler, J Bilgen, M Chou, PCT Guay-Woodford, L Yoder, B Haycraft, CJ Siroky, B AF Bell, P. Darwin Fitzgibbon, Wayne Sas, Kelli Stenbitt, Antine E. Amria, May Houston, Amber Reichert, Ryan Gilley, Sandra Siegal, Gene P. Bissler, John Bilgen, Mehmet Chou, Peter Cheng-te Guay-Woodford, Lisa Yoder, Brad Haycraft, Courtney J. Siroky, Brian TI Loss of Primary Cilia Upregulates Renal Hypertrophic Signaling and Promotes Cystogenesis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; REVERSIBLE COMPENSATORY HYPERTROPHY; PLANAR CELL POLARITY; CYST FORMATION; TUBULOGLOMERULAR FEEDBACK; UNILATERAL NEPHRECTOMY; RAT KIDNEYS; SLOW-ONSET; ADULT MICE; PKD1 AB Primary cilia dysfunction alters renal tubular cell proliferation and differentiation and associates with accelerated cyst formation in polycystic kidney disease. However, the mechanism leading from primary ciliary dysfunction to renal cyst formation is unknown. We hypothesize that primary cilia prevent renal cyst formation by suppressing pathologic tubular cell hypertrophy and proliferation. Unilateral nephrectomy initiates tubular cell hypertrophy and proliferation in the contralateral kidney and provides a tool to examine primary cilia regulation of renal hypertrophy. Conditional knockout of the primary cilia ift88 gene leads to delayed, adult-onset renal cystic disease, which provides a window of opportunity to conduct unilateral nephrectomy and examine downstream kinetics of renal hypertrophy and cyst formation. In wild-type animals, unilateral nephrectomy activated the mTOR pathway and produced appropriate structural and functional hypertrophy without renal cyst formation. However, in ift88 conditional knockout animals, unilateral nephrectomy triggered increased renal hypertrophy and accelerated renal cyst formation, leading to renal dysfunction. mTOR signaling also increased compared with wild-type animals, suggesting a mechanistic cascade starting with primary ciliary dysfunction, leading to excessive mTOR signaling and renal hypertrophic signaling and culminating in cyst formation. These data suggest that events initiating hypertrophic signaling, such as structural or functional loss of renal mass, may accelerate progression of adult polycystic kidney disease toward end-stage renal disease. C1 [Bell, P. Darwin; Fitzgibbon, Wayne; Sas, Kelli; Stenbitt, Antine E.; Amria, May; Houston, Amber; Reichert, Ryan; Gilley, Sandra; Haycraft, Courtney J.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Bell, P. Darwin] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Siegal, Gene P.; Yoder, Brad] Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. [Siegal, Gene P.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Guay-Woodford, Lisa] Univ Alabama, Dept Genet, Birmingham, AL USA. [Bissler, John; Siroky, Brian] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH USA. [Bilgen, Mehmet; Chou, Peter Cheng-te] Univ Malaya, Fac Med, Med Ctr, Dept Biomed Imaging, Kuala Lumpur, Malaysia. RP Bell, PD (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 173 Ashley Ave,210 CRI, Charleston, SC 29425 USA. EM Bellpd@musc.edu FU VA Merit Grants [P30DK074038, DK32032, P30 AR 46031, P30 DK 079337, DK35534, DK065655, DK061458]; Dialysis Clinic, Inc. FX This project was supported by VA Merit Grants (P.D.B.), P30DK074038 (L.G.W.), DK32032 (P.D.B.), P30 AR 46031 (Siegal Core PI), and P30 DK 079337 (Siegal Core PI), DK35534 (L.G.W.), DK065655 (B.Y.) and DK061458 (J.B.) in addition to funds from Dialysis Clinic, Inc. NR 40 TC 28 Z9 28 U1 0 U2 1 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 MAY PY 2011 VL 22 IS 5 BP 839 EP 848 DI 10.1681/ASN.2010050526 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 776FI UT WOS:000291519500011 PM 21493775 ER PT J AU Raina, D Kosugi, M Ahmad, R Panchamoorthy, G Rajabi, H Alam, M Shimamura, T Shapiro, GI Supko, J Kharbanda, S Kufe, D AF Raina, Deepak Kosugi, Michio Ahmad, Rehan Panchamoorthy, Govind Rajabi, Hasan Alam, Maroof Shimamura, Takeshi Shapiro, Geoffrey I. Supko, Jeffrey Kharbanda, Surender Kufe, Donald TI Dependence on the MUC1-C Oncoprotein in Non-Small Cell Lung Cancer Cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BETA-CATENIN; PHOSPHOINOSITIDE 3-KINASE; ACQUIRED-RESISTANCE; KINASE INHIBITOR; REGULATORY LOOP; C-SRC; GROWTH; RECEPTOR; MUTATIONS; PATHWAYS AB Non-small cell lung cancer (NSCLC) cells are often associated with constitutive activation of the phosphoinositide 3-kinase (PI3K) -> Akt -> mTOR pathway. The mucin 1 (MUC1) heterodimeric glycoprotein is aberrantly overexpressed in NSCLC cells and induces gene signatures that are associated with poor survival of NSCLC patients. The present results show that the MUC1 C-terminal subunit (MUC1-C) cytoplasmic domain associates with PI3K p85 in NSCLC cells. We show that inhibition of MUC1-C with cell-penetrating peptides blocks this interaction with PI3K p85 and suppresses constitutive phosphorylation of Akt and its downstream effector, mTOR. In concert with these results, treatment of NSCLC cells with the MUC1-C peptide inhibitor GO-203 was associated with downregulation of PI3K -> Akt signaling and inhibition of growth. GO-203 treatment was also associated with increases in reactive oxygen species (ROS) and induction of necrosis by a ROS-dependent mechanism. Moreover, GO-203 treatment of H1975 (EGFR L858R/T790M) and A549 (K-Ras G12S) xenografts growing in nude mice resulted in tumor regressions. These findings indicate that NSCLC cells are dependent on MUC1-C both for activation of the PI3K -> Akt pathway and for survival. Mol Cancer Ther; 10(5); 806-16. (C) 2011 AACR. C1 [Kosugi, Michio; Ahmad, Rehan; Rajabi, Hasan; Alam, Maroof; Shimamura, Takeshi; Shapiro, Geoffrey I.; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Supko, Jeffrey] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Raina, Deepak; Panchamoorthy, Govind; Kharbanda, Surender] Genus Oncol Boston, Boston, MA USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Dana 830, Boston, MA 02115 USA. EM Donald_Kufe@dfci.harvard.edu FU Lung Cancer Research Foundation; National Cancer Institute [CA97098, CA42802]; Genus Oncology FX This study was supported by Lung Cancer Research Foundation and National Cancer Institute grants CA97098 and CA42802. J. Supko received research support from Genus Oncology. NR 49 TC 77 Z9 82 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2011 VL 10 IS 5 BP 806 EP 816 DI 10.1158/1535-7163.MCT-10-1050 PG 11 WC Oncology SC Oncology GA 774ZY UT WOS:000291427000010 PM 21421804 ER PT J AU Scaltriti, M Serra, V Normant, E Guzman, M Rodriguez, O Lim, AR Slocum, KL West, KA Rodriguez, V Prudkin, L Jimenez, J Aura, C Baselga, J AF Scaltriti, Maurizio Serra, Violeta Normant, Emmanuel Guzman, Marta Rodriguez, Olga Lim, Alice R. Slocum, Kelly L. West, Kip A. Rodriguez, Varenka Prudkin, Ludmila Jimenez, Jose Aura, Claudia Baselga, Jose TI Antitumor Activity of the Hsp90 Inhibitor IPI-504 in HER2-Positive Trastuzumab-Resistant Breast Cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID FACTOR-I RECEPTOR; SHOCK-PROTEIN 90; METASTATIC BREAST; MONOCLONAL-ANTIBODY; PHASE-II; 1ST-LINE TREATMENT; SINGLE-AGENT; CELLS; GROWTH; EFFICACY AB Hsp90 facilitates the maturation and stability of numerous oncoproteins, including HER2. The aim of this study was to assess the antitumor activity of the Hsp90 inhibitor IPI-504 in trastuzumab-resistant, HER2-overexpressing breast cancer cells. Therapy with trastuzumab, IPI-504, and the combination of trastuzumab and IPI-504 was evaluated in trastuzumab-sensitive and trastuzumab-resistant cells. Inhibition of protein targets, cell proliferation, and tumor growth was assessed in vitro and in xenograft models. IPI-504 inhibited proliferation of both trastuzumab-sensitive and trastuzumab-resistant cells. Administration of IPI-504 markedly reduced total levels of HER2 and Akt, as well as phosphorylated Akt and mitogen-activated protein kinase (MAPK), to an equal extent in trastuzumab-sensitive and trastuzumab-resistant cells. IPI-504, used as single agent or in combination with trastuzumab, also inhibited in vivo the growth of both trastuzumab-sensitive and -resistant tumor xenografts. As a mechanism for the observed antitumor activity, IPI-504 resulted in a marked decrease in the levels of HER2, Akt, p-Akt, and p-MAPK in trastuzumab-resistant xenografts as early as 12 hours after a single dose of IPI-504. IPI-504-mediated Hsp90 inhibition may represent a novel therapeutic approach in trastuzumab refractory HER2-positive breast cancer. Mol Cancer Ther; 10(5); 817-24. (C) 2011 AACR. C1 [Scaltriti, Maurizio; Baselga, Jose] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Scaltriti, Maurizio; Serra, Violeta; Guzman, Marta; Rodriguez, Olga; Baselga, Jose] VHIO, Dept Med Oncol, Barcelona, Spain. [Prudkin, Ludmila; Jimenez, Jose; Aura, Claudia] VHIO, Dept Mol Pathol, Barcelona, Spain. [Baselga, Jose] Univ Autonoma Barcelona, Fac Med, E-08193 Barcelona, Spain. [Normant, Emmanuel; Lim, Alice R.; Slocum, Kelly L.; West, Kip A.; Rodriguez, Varenka] Infin Pharmaceut, Cambridge, MA USA. RP Baselga, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol & Oncol, 10 N Grove St,LH-108, Boston, MA 02114 USA. EM jbaselga@partners.org FU Breast Cancer Research Foundation; European Research Council [AdG09 250244] FX The work was supported by the Breast Cancer Research Foundation and the European Research Council (AdG09 250244). NR 40 TC 26 Z9 26 U1 4 U2 6 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 MAY PY 2011 VL 10 IS 5 BP 817 EP 824 DI 10.1158/1535-7163.MCT-10-0966 PG 8 WC Oncology SC Oncology GA 774ZY UT WOS:000291427000011 PM 21383049 ER PT J AU Iwamoto, FM Lamborn, KR Kuhn, JG Wen, PY Yung, WKA Gilbert, MR Chang, SM Lieberman, FS Prados, MD Fine, HA AF Iwamoto, Fabio M. Lamborn, Kathleen R. Kuhn, John G. Wen, Patrick Y. Yung, W. K. Alfred Gilbert, Mark R. Chang, Susan M. Lieberman, Frank S. Prados, Michael D. Fine, Howard A. TI A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03 SO NEURO-ONCOLOGY LA English DT Article DE glioblastoma; glioma; histone deacetylase inhibitor; romidepsin ID DEPSIPEPTIDE FR901228; PROGNOSTIC-FACTORS; FK228; PHARMACOKINETICS; GLIOBLASTOMA; CELLS; CYTOCHROME-P450; IDENTIFICATION; PROGRESSION; EXPRESSION AB Romidepsin, a potent histone deacetylase inhibitor, has shown activity in preclinical glioma models. The primary objectives of this trial were to determine the pharmacokinetics of romidepsin in patients with recurrent glioma on enzyme-inducing antiepileptic drugs (EIAEDs) and to evaluate the antitumor efficacy of romidepsin in patients with recurrent glioblastoma who were not receiving EIAEDs. Two dose cohorts were studied in the phase I component of the trial (13.3 and 17.7 mg/m(2)/d). Patients in the phase II component were treated with intravenous romidepsin at a dosage of 13.3 mg/m(2)/day on days 1, 8, and 15 of each 28-day cycle. Eight patients were treated on the phase I component. A similar romidepsin pharmacokinetic profile was demonstrated between patients receiving EIAEDs to those not receving EIAEDs. Thirty-five patients with glioblastoma were accrued to the phase II component. There was no objective radiographic response. The median progression-free survival (PFS) was 8 weeks and only 1 patient had a PFS time >= 6 months (PFS6 = 3%). To date, 34 patients (97%) have died, with a median survival duration of 34 weeks. Despite in vitro studies showing that romidepsin is primarily metabolized by CYP3A4, no decrease in exposure to romidepsin was seen in patients receiving potent CYP3A4 inducers. Romidepsin, at its standard dose and schedule, was ineffective for patients with recurrent glioblastomas. C1 [Iwamoto, Fabio M.; Fine, Howard A.] NCI, Neurooncol Branch, Natl Inst Neurol Disorder & Stroke, NIH, Bethesda, MD 20892 USA. [Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Houston, TX USA. [Yung, W. K. Alfred; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Lieberman, Frank S.] Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA USA. RP Fine, HA (reprint author), NCI, Neurooncol Branch, Natl Inst Neurol Disorder & Stroke, NIH, 9030 Old Georgetown Rd,Bloch Bldg 82,Room 225, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU National Institutes of Health ("The North American Brain Tumor Consortium") [CA 062399] FX National Institutes of Health (CA 062399; "The North American Brain Tumor Consortium"). NR 29 TC 41 Z9 43 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAY PY 2011 VL 13 IS 5 BP 509 EP 516 DI 10.1093/neuonc/nor017 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 775HS UT WOS:000291450200005 PM 21377994 ER PT J AU Jack, CR Albert, MS Knopman, DS McKhann, GM Sperling, RA Carrillo, MC Thies, B Phelps, CH AF Jack, Clifford R., Jr. Albert, Marilyn S. Knopman, David S. McKhann, Guy M. Sperling, Reisa A. Carrillo, Maria C. Thies, Bill Phelps, Creighton H. TI Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Diagnostic criteria; Biomarkers; Imaging; Cerebrospinal fluid ID MILD COGNITIVE IMPAIRMENT; NEUROFIBRILLARY TANGLES; PROGRESSIVE APHASIA; AMYLOID DEPOSITION; CLINICAL DEMENTIA; SYNAPSE LOSS; LEWY BODIES; CONSORTIUM; NEUROPATHOLOGY; DEGENERATION AB Background: Criteria for the clinical diagnosis of Alzheimer's disease (AD) were established in 1984. A broad consensus now exists that these criteria should be revised to incorporate state-of-the-art scientific knowledge. Methods: The National Institute on Aging (NIA) and the Alzheimer's Association sponsored a series of advisory round table meetings in 2009 whose purpose was to establish a process for revising diagnostic and research criteria for AD. The recommendation from these advisory meetings was that three separate work groups should be formed with each assigned the task of formulating diagnostic criteria for one phase of the disease: the dementia phase; the symptomatic, pre-dementia phase; and the asymptomatic, preclinical phase of AD. Results: Two notable differences from the AD criteria published in 1984 are incorporation of biomarkers of the underlying disease state and formalization of different stages of disease in the diagnostic criteria. There was a broad consensus within all three workgroups that much additional work is needed to validate the application of biomarkers for diagnostic purposes. In the revised NIA-Alzheimer's Association criteria, a semantic and conceptual distinction is made between AD pathophysiological processes and clinically observable syndromes that result, whereas this distinction was blurred in the 1984 criteria. Conclusions: The new criteria for AD are presented in three documents. The core clinical criteria of the recommendations regarding AD dementia and MCI due to AD are intended to guide diagnosis in the clinical setting. However, the recommendations of the preclinical AD workgroup are intended purely for research purposes. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Jack, Clifford R., Jr.; Knopman, David S.] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. [Albert, Marilyn S.; McKhann, Guy M.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Med Sch, Boston, MA 02115 USA. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Phelps, Creighton H.] NIA, Div Neurosci, Baltimore, MD 21224 USA. RP Jack, CR (reprint author), Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. EM jack.clifford@mayo.edu RI Jack, Clifford/F-2508-2010 OI Jack, Clifford/0000-0001-7916-622X FU Baxter; Pfizer Inc; GE Healthcare; Elan Pharmaceuticals; Forest Pharmaceuticals; Baxter Healthcare FX Clifford Jack serves as a consultant for Eli Lilly, Eisai, and Elan; is an investigator in clinical trials sponsored by Baxter and Pfizer Inc; and owns stock in Johnson and Johnson. Marilyn Albert serves as a consultant to Genentech and Eli Lilly and receives grants to her institution from GE Healthcare. David Knopman serves on a Data Safety Monitoring Board for Lilly Pharmaceuticals; is an investigator for clinical trials sponsored by Elan Pharmaceuticals, Forest Pharmaceuticals, and Baxter Healthcare; and is deputy editor of Neurology and receives compensation for editorial activities. Guy McKhann serves on a Data Safety Monitoring Board for Merck. Reisa Sperling has served as a site investigator and/or consultant to several companies developing imaging biomarkers and pharmacological treatments for early AD, including Avid, Bayer, Bristol-Myers-Squibb, Elan, Eisai, Janssen, Pfizer, and Wyeth. Maria Carrillo is an employee of the Alzheimer's Association and reports no conflicts. Bill Thies is an employee of the Alzheimer's Association and reports no conflicts. Creighton Phelps is an employee of the U.S. Government and reports no conflicts. NR 50 TC 458 Z9 477 U1 7 U2 82 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 257 EP 262 DI 10.1016/j.jalz.2011.03.004 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600002 PM 21514247 ER PT J AU McKhann, GM Knopman, DS Chertkow, H Hyman, BT Jack, CR Kawas, CH Klunk, WE Koroshetz, WJ Manly, JJ Mayeux, R Mohs, RC Morris, JC Rossor, MN Scheltens, P Carrillo, MC Thies, B Weintraub, S Phelps, CH AF McKhann, Guy M. Knopman, David S. Chertkow, Howard Hyman, Bradley T. Jack, Clifford R., Jr. Kawas, Claudia H. Klunk, William E. Koroshetz, Walter J. Manly, Jennifer J. Mayeux, Richard Mohs, Richard C. Morris, John C. Rossor, Martin N. Scheltens, Philip Carrillo, Maria C. Thies, Bill Weintraub, Sandra Phelps, Creighton H. TI The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Dementia; Diagnosis; Magnetic resonance brain imaging; Positron emission tomography; Cerebrospinal fluid ID FRONTOTEMPORAL DEMENTIA; WORK GROUP; CRITERIA; BIOMARKERS; CONSENSUS; ATROPHY AB The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [McKhann, Guy M.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [McKhann, Guy M.] Johns Hopkins Univ, Zanvyl Krieger Mind Brain Inst, Baltimore, MD 21205 USA. [Knopman, David S.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Chertkow, Howard] McGill Univ, Dept Neurol, Sch Med, Montreal, PQ H3A 2T5, Canada. [Chertkow, Howard] Lady Davis Inst, Bloomfield Ctr Res Aging, Montreal, PQ, Canada. [Hyman, Bradley T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Kawas, Claudia H.] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Kawas, Claudia H.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA. [Kawas, Claudia H.] Univ Calif Irvine, Alzheimer Dis Res Ctr, Irvine, CA USA. [Klunk, William E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA. [Manly, Jennifer J.; Mayeux, Richard] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. [Manly, Jennifer J.; Mayeux, Richard] Columbia Univ, Gertrude H Sergievsky Ctr, Med Ctr, New York, NY 10027 USA. [Manly, Jennifer J.; Mayeux, Richard] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Mohs, Richard C.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Rossor, Martin N.] UCL, Dementia Res Ctr, Dept Neurodegenerat, UCL Inst Neurol, London, England. [Scheltens, Philip] Vrije Univ Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands. [Scheltens, Philip] Vrije Univ Amsterdam, Alzheimer Ctr, Med Ctr, Amsterdam, Netherlands. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Weintraub, Sandra] NW Feinberg Sch Med, Dept Psychiat, Chicago, IL USA. [Weintraub, Sandra] NW Feinberg Sch Med, Dept Neurol, Chicago, IL USA. [Phelps, Creighton H.] NIA, Alzheimers Dis Ctr Program, Bethesda, MD 20892 USA. RP McKhann, GM (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RI Jack, Clifford/F-2508-2010; Morris, John/A-1686-2012; OI Jack, Clifford/0000-0001-7916-622X; Klunk, William/0000-0001-5512-0251 FU Elan Pharmaceuticals; Forest Pharmaceuticals; Baxter Healthcare; Pfizer Canada; NIH; Alzheimer's Association; Fidelity Biosciences; Baxter; Pfizer Inc.; Avid Radiopharmaceuticals; Eli Lilly and Co. FX Guy McKhann serves on a Data Safety Monitoring Board for Merck. David Knopman serves on a Data Safety Monitoring Board for Lilly Pharmaceuticals and is an investigator for clinical trials sponsored by Elan Pharmaceuticals, Forest Pharmaceuticals, and Baxter Healthcare; he is deputy editor of Neurology and receives compensation for editorial activities. Howard Chertkow serves as a consultant to Pfizer Canada, Lundbeck Canada, Janssen Ortho, Novartis Canada, and Bristol Myers Squibb; he receives a research grant from Pfizer Canada. Bradley Hyman serves as a consultant to EMD Serrano, Janssen, Takeda, BMS, Neurophage, Pfizer, Quanterix, foldrx, Elan, and Link, and receives funding from the NIH, the Alzheimer's Association, and Fidelity Biosciences. Clifford Jack serves as a consultant for Eli Lilly, Eisai, and Elan; he is an investigator in clinical trials sponsored by Baxter and Pfizer Inc., and owns stock in Johnson and Johnson. Claudia Kawas serves on a Data Safety Monitoring Board for Lilly Pharmaceuticals, Elan Pharmaceuticals, and Lundbeck; she is an investigator in a trial sponsored by Avid Radiopharmaceuticals. William Klunk serves as a consultant to GE Healthcare and receives research grants from the same; he also receives royalties from GE Healthcare for PiB PET technology and owns stock or options in Neuroptix, a company seeking to commercialize detection of amyloid in the eye. Walter Koroshetz are employees of the U.S. Government and report no conflicts. Jennifer Manly reports no conflicts of interests. Richard Mayeux serves on scientific advisory board of Psycho-Genics. Richard Mohs is a full-time employee of Eli Lilly and Company and holds stock in Lilly. Avid Radiopharmaceuticals is a wholly owned subsidiary of Eli Lilly and Co. John Morris serves as a consultant to Astra Zeneca, Bristol-Myers Squibb, Eisai, Janssen, Genetic, Eli Lilly, Merck, Novartis, Otsuka, Pfizer, and Schering Plough. University College London receives payment for Martin Rossor serving on the Safety Monitoring Committees for Janssen and Servier trials in AD. Philip Scheltens serves as a consultant to Pfizer Pharmaceuticals, Genetech, Danone Research, Lundbeck Pharmaceuticals, GE Healthcare, Roche, and Novartis; he also serves on a speakers bureau for Lundbeck Pharmaceuticals. Maria Carrillo and Bill Thies are employees of the Alzheimer's Association and reports no conflicts. Sandra Weintraub reports no conflicts of interest and Creighton Phelps. NR 24 TC 2377 Z9 2459 U1 85 U2 564 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 263 EP 269 DI 10.1016/j.jalz.2011.03.005 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600003 PM 21514250 ER PT J AU Sperling, RA Aisen, PS Beckett, LA Bennett, DA Craft, S Fagan, AM Iwatsubo, T Jack, CR Kaye, J Montine, TJ Park, DC Reiman, EM Rowe, CC Siemers, E Stern, Y Yaffe, K Carrillo, MC Thies, B Morrison-Bogorad, M Wagster, MV Phelps, CH AF Sperling, Reisa A. Aisen, Paul S. Beckett, Laurel A. Bennett, David A. Craft, Suzanne Fagan, Anne M. Iwatsubo, Takeshi Jack, Clifford R., Jr. Kaye, Jeffrey Montine, Thomas J. Park, Denise C. Reiman, Eric M. Rowe, Christopher C. Siemers, Eric Stern, Yaakov Yaffe, Kristine Carrillo, Maria C. Thies, Bill Morrison-Bogorad, Marcelle Wagster, Molly V. Phelps, Creighton H. TI Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Preclinical Alzheimer's disease; Biomarker; Amyloid; Neurodegeneration; Prevention ID MILD COGNITIVE IMPAIRMENT; AMYLOID DEPOSITION; OLDER-ADULTS; A-BETA; NONDEMENTED INDIVIDUALS; COMMUNITY POPULATION; BIOMARKER SIGNATURE; CSF BIOMARKERS; GENETIC RISK; DECLINE AB The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Dept Neurol,Med Sch, Boston, MA 02115 USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Beckett, Laurel A.] Univ Calif Davis, Div Biostat, Sch Med, Davis, CA 95616 USA. [Bennett, David A.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA. [Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Ctr Geriatr Res Educ & Clin, Seattle, WA 98195 USA. [Fagan, Anne M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Iwatsubo, Takeshi] Univ Tokyo, Grad Sch Sci, Dept Neuropathol, Tokyo 113, Japan. [Jack, Clifford R., Jr.] Mayo Clin Minnesota, Dept Radiol, Rochester, MN USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Biomed Engn, Layton Aging & Alzheimers Dis Ctr, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Kaye, Jeffrey] Portland VA Med Ctr, Portland, OR USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Park, Denise C.] Univ Texas Dallas, Ctr Vital Longev, Dallas, TX 75230 USA. [Siemers, Eric] Banner Alzheimers Inst, Phoenix, AZ USA. [Rowe, Christopher C.] Univ Melbourne, Melbourne, Vic, Australia. [Siemers, Eric] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Stern, Yaakov] Columbia Univ, Coll Phys & Surg, Cognit Neurosci Div, Taub Inst, New York, NY USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Carrillo, Maria C.; Thies, Bill] Alzheimers Assoc, Chicago, IL USA. [Morrison-Bogorad, Marcelle; Wagster, Molly V.; Phelps, Creighton H.] NIA, Div Neurosci, Bethesda, MD 20892 USA. RP Sperling, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Dept Neurol,Med Sch, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu RI Jack, Clifford/F-2508-2010; OI Jack, Clifford/0000-0001-7916-622X; Beckett, Laurel/0000-0002-2418-9843; Kaye, Jeffrey/0000-0002-9971-3478 FU Pfizer Inc.; Baxter International Inc.; Baxter; Avid Pharmaceuticals; Bayer; Janssen; Eli Lilly; Elan FX Reisa Sperling has served as a site investigator and/or consultant to several companies developing imaging biomarkers and pharmacological treatments for early AD, including Avid, Bayer, Bristol-Myers-Squibb, Elan, Eisai, Janssen, Pfizer, and Wyeth. Paul Aisen serves on a scientific advisory board for NeuroPhage; serves as a consultant to Elan Corporation, Wyeth, Eisai Inc., Bristol-Myers Squibb, Eli Lilly and Company, NeuroPhage, Merck & Co., Roche, Amgen, Abbott, Pfizer Inc., Novartis, Bayer, Astellas, Dainippon, Biomarin, Solvay, Otsuka, Daiichi, AstraZeneca, Janssen, and Medivation Inc.; receives research support from Pfizer Inc. and Baxter International Inc.; and has received stock options from Medivation Inc. and NeuroPhage. Clifford Jack serves as a consultant for Eli Lilly, Eisai, and Elan; is an investigator in clinical trials sponsored by Baxter and Pfizer Inc.; and owns stock in Johnson and Johnson. Denise Park has received research support from Avid Pharmaceuticals. Eric Siemers is an employee of Eli Lilly and Company, which acquired Avid Pharmaceuticals. Yaakov Stern has consulted to Bayer Pharmaceuticals and has received research support from Bayer, Janssen, Eli Lilly, and Elan. Maria Carrillo is an employee of the Alzheimer's Association and reports no conflicts. Bill Thies is an employee of the Alzheimer's Association and reports no conflicts. Creighton Phelps is an employee of the U.S. Government and reports no conflicts. NR 71 TC 1680 Z9 1721 U1 45 U2 278 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 280 EP 292 DI 10.1016/j.jalz.2011.03.003 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600005 PM 21514248 ER PT J AU Marshall, GA Rentz, DM Frey, MT Locascio, JJ Johnson, KA Sperling, RA AF Marshall, Gad A. Rentz, Dorene M. Frey, Meghan T. Locascio, Joseph J. Johnson, Keith A. Sperling, Reisa A. CA Alzheimer's Dis Neuroimaging TI Executive function and instrumental activities of daily living in mild cognitive impairment and Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Executive function; Instrumental activities of daily living; Memory; Mild cognitive impairment ID OLDER-ADULTS; CLINICAL DEMENTIA; DYSFUNCTION; ASSOCIATION; DIAGNOSIS; COMMUNITY; AD AB Background: Impairment in instrumental activities of daily living (IADL) leads to early loss in productivity and adds significant burden to caregivers. Executive dysfunction is thought to be an important contributor to functional impairment. The objective of this study was to investigate the relationship between executive function and IADL in a large cohort of well-characterized normal older controls, mild cognitive impairment (MCI), and patients with mild Alzheimer's disease, separately as well as across the entire sample, while accounting for demographic, cognitive, and behavioral factors. Methods: Subjects with baseline clinical datasets (n = 793) from the Alzheimer's Disease Neuroimaging Initiative study (228 normal older controls, 387 MCI, 178 Alzheimer's disease) were included in the analysis. A multiple regression model was used to assess the relationship between executive function and IADL. Results: A multiple regression model, including diagnosis, global cognitive impairment, memory performance, and other covariates demonstrated a significant relationship between executive dysfunction and IADL impairment across all subjects (R(2) = .60, P < .0001 for model; Digit Symbol, partial beta = -.044, P = .005; Trailmaking Test B-A, quadratic relation, P = .01). Similarly, an analysis using MCI subjects only yielded a significant relationship (R(2) = .16, P < .0001 for model; Digit Symbol, partial beta = -.08, P = .001). Conclusions: These results suggest that executive dysfunction is a key contributor to impairment in IADL. This relationship was evident even after accounting for degree of memory deficit across the continuum of cognitive impairment and dementia. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Marshall, Gad A.; Rentz, Dorene M.; Frey, Meghan T.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Sch Med, Boston, MA 02115 USA. [Marshall, Gad A.; Rentz, Dorene M.; Frey, Meghan T.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. [Marshall, Gad A.; Rentz, Dorene M.; Locascio, Joseph J.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Marshall, GA (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Sch Med, Boston, MA 02115 USA. EM gamarshall@partners.org RI Scharre, Douglas/E-4030-2011 FU Rosalinde; Arthur Gilbert Foundation; Massachusetts Alzheimer's Disease Research Center [P50 AG005134-24]; ADNI; National Institutes of Health (NIH); [R01 AG027435]; [1K23AG033634-01A1] FX This study was supported by R01 AG027435, 1K23AG033634-01A1, the Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134-24), and ADNI. The Foundation for the National Institutes of Health (www.fnih.org) coordinates the private sector participation of the $60 million ADNI public-private partnership that was begun by the National Institute on Aging (NIA) and supported by the National Institutes of Health (NIH). To date, more than $27 million has been provided to the Foundation for NIH by Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Co., Merck & Co., Inc., Novartis AG, Pfizer Inc., F. Hoffmann-La Roche, Schering-Plough, Synarc Inc., and Wyeth, as well as non-profit partners the Alzheimer's Association and the Institute for the Study of Aging. NR 42 TC 84 Z9 86 U1 3 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2011 VL 7 IS 3 BP 300 EP 308 DI 10.1016/j.jalz.2010.04.005 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 772NC UT WOS:000291239600007 PM 21575871 ER PT J AU Almandoz, JED Su, HS Schaefer, PW Goldstein, JN Pomerantz, SR Lev, MH Gonzalez, RG Romero, JM AF Almandoz, J. E. Delgado Su, H. S. Schaefer, P. W. Goldstein, J. N. Pomerantz, S. R. Lev, M. H. Gonzalez, R. G. Romero, J. M. TI Frequency of Adequate Contrast Opacification of the Major Intracranial Venous Structures with CT Angiography in the Setting of Intracerebral Hemorrhage: Comparison of 16- and 64-Section CT Angiography Techniques SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID SPOT SIGN; HEMATOMA EXPANSION; HIGHEST RISK; EXTRAVASATION; THROMBOSIS; ETIOLOGY; SCORE AB BACKGROUND AND PURPOSE: DVST is an important cause of ICH because its treatment may require anticoagulation or mechanical thrombectomy. We aimed to determine the frequency of adequate contrast opacification of the major intracranial venous structures in CTAs performed for ICH evaluation, which is an essential factor in excluding DVST as the ICH etiology. MATERIALS AND METHODS: Two readers retrospectively reviewed CTAs performed in 170 consecutive patients with ICH who presented to our emergency department during a 1-year period to determine by consensus whether qualitatively, contrast opacification in each of the major intracranial venous structures was adequate to exclude DVST. "Adequate contrast opacification" was defined as homogeneous opacification of the venous structure examined. "Inadequate contrast opacification" was defined as either inhomogeneous opacification or nonopacification of the venous structure examined. Delayed scans, if obtained, were reviewed by the same readers blinded to the first-pass CTAs to determine the adequacy of contrast opacification in the venous structures according to the same criteria. In patients who did not have an arterial ICH etiology, the same readers determined if thrombosis of an inadequately opacified intracranial venous structure could have potentially explained the ICH by correlating the presumed venous drainage path of the ICH with the presence of inadequate contrast opacification within the venous structure draining the venous territory of the ICH. CTAs were performed in 16- or 64-section CT scanners with bolus-tracking, scanning from Cl to the vertex. Patients with a final diagnosis of DVST were excluded. We used the Pearson chi(2) test to determine the significance of the differences in the frequency of adequate contrast opacification within each of the major intracranial venous structures in scans obtained using either a 16- or 64-section MDCTA technique. RESULTS: Fifty-eight patients were evaluated with a 16-section MDCTA technique (34.1%) and 112 with a 64-section technique (65.9%). Adequate contrast opacification within all major noncavernous intracranial venous structures was significantly less frequent in first-pass CTAs performed with a 64-section technique (33%) than in those performed with a 16-section technique (60%, P value <.0001). Delayed scans were obtained in 50 patients, all of which demonstrated adequate contrast opacification in the major noncavernous intracranial venous structures. In 142 patients with supratentorial or cerebellar ICH without an underlying arterial etiology, we found that thrombosis of an inadequately opacified major intracranial venous structure could have potentially explained the ICH in 38 patients (26.8%), most examined with a 64-section technique (86.8%). CONCLUSIONS: Inadequate contrast pacification of the major intracranial venous structures is common in first-pass CTAs performed for ICH evaluation, particularly if performed with a 64-section technique. Acquiring delayed scans appears necessary to confidently exclude DVST when there is strong clinical or radiologic suspicion. C1 [Almandoz, J. E. Delgado] Washington Univ, Div Neuroradiol, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Almandoz, J. E. Delgado; Su, H. S.; Schaefer, P. W.; Pomerantz, S. R.; Lev, M. H.; Gonzalez, R. G.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Neuroradiol, Boston, MA 02115 USA. [Goldstein, J. N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Almandoz, JED (reprint author), Washington Univ, Div Neuroradiol, Mallinckrodt Inst Radiol, Campus Box 8131,510 S Kingshighway Blvd, St Louis, MO 63110 USA. EM delgadoj@mir.wustl.edu RI Goldstein, Joshua/H-8953-2016 FU National Institute of Neurological Disorders and Stroke [K23NS059774] FX This work was supported, in part, by the National Institute of Neurological Disorders and Stroke grant K23NS059774. NR 15 TC 3 Z9 3 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 2011 VL 32 IS 5 BP 839 EP 845 DI 10.3174/ajnr.A2388 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 770VW UT WOS:000291117600010 ER PT J AU Mui, K Yoo, AJ Verduzco, L Copen, WA Hirsch, JA Gonzalez, RG Schaefer, PW AF Mui, K. Yoo, A. J. Verduzco, L. Copen, W. A. Hirsch, J. A. Gonzalez, R. G. Schaefer, P. W. TI Cerebral Blood Flow Thresholds for Tissue Infarction in Patients with Acute Ischemic Stroke Treated with Intra-Arterial Revascularization Therapy Depend on Timing of Reperfusion SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID APPARENT DIFFUSION-COEFFICIENT; PERFUSION MAGNETIC-RESONANCE; HYPERACUTE STROKE; WEIGHTED MRI; ARTERY OCCLUSION; WHITE-MATTER; PENUMBRA; THROMBOLYSIS; PREDICTION; CT AB BACKGROUND AND PURPOSE: MR perfusion CBF values can distinguish hypoperfused penumbral tissue likely to infarct from that which is likely to recover. Our aim was to determine if CBF thresholds for tissue infarction depend on the timing of recanalization in patients with acute stroke treated with IAT. MATERIALS AND METHODS: Twenty-six patients with acute proximal anterior circulation strokes underwent DWI and PWI before IAT. rCBF was obtained in the following areas: 1) C with abnormal DWI, reduced CBF, follow-up infarction; 2) PI with normal DWI, reduced CBF, follow-up infarction and 3) PNI with normal DWI, reduced CBF, normal follow-up. rCBF in tissue reperfused at <6 hours (early recanalizers), in tissue reperfused at >6 hours (late RC), and in NRC was compared. RESULTS: For C, mean rCBF was 0.13 (SEM, 0.002), 0.29 (0.007), and 0.21 (0.004) for early recanalizers, late recanalizers, and nonrecanalizers, respectively (P < .001, for all comparisons). For PI, mean rCBF was 0.34 (0.006), 0.38 (0.008), and 0.39 (0.005) for early recanalizers, late recanalizers, and nonrecanalizers, respectively (P < .001 for early-versus-late recanalizers and versus nonrecanalizers; P > .05 for late recanalizers versus nonrecanalizers). For PNI, the mean rCBF was 0.38 (0.002), 0.48 (0.003), and 0.48 (0.004) for early recanalizers, late recanalizers, and nonrecanalizers, respectively (P < .001 for early-versus-late recanalizers and nonrecanalizers; P>.05 for late recanalizers versus nonrecanalizers). ROC analyzis demonstrated optimal rCBF thresholds for tissue infarction of 0.27 (sensitivity, 80%; specificity, 87%), 0.44 (sensitivity, 77%; specificity, 75%), and 0.41 (sensitivity, 78%; specificity, 77%) for early recanalizers, late recanalizers, and nonrecanalizers, respectively. CONCLUSIONS: CBF thresholds for tissue infarction in patients with acute stroke are lower in tissue that is reperfused at earlier time points. This information may be important in selecting patients who might benefit from reperfusion therapy. C1 [Schaefer, P. W.] Harvard Univ, Dept Radiol, Div Neuroradiol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Schaefer, PW (reprint author), Harvard Univ, Dept Radiol, Div Neuroradiol, Massachusetts Gen Hosp,Med Sch, Gray 273A,55 Fruit St, Boston, MA 02114 USA. EM pschaefer@partners.org NR 33 TC 9 Z9 9 U1 0 U2 5 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 2011 VL 32 IS 5 BP 846 EP 851 DI 10.3174/ajnr.A2415 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 770VW UT WOS:000291117600011 PM 21474633 ER PT J AU Schutz, FAB Jardim, DLF Je, YJ Choueiri, TK AF Schutz, Fabio A. B. Jardim, Denis L. F. Je, Youjin Choueiri, Toni K. TI Haematologic toxicities associated with the addition of bevacizumab in cancer patients SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Bevacizumab; Meta-analysis; Haematologic toxicities; Bone marrow toxicities; Anaemia; Neutropenia; Thrombocytopenia; Febrile neutropenia ID PHASE-III TRIAL; CELL LUNG-CANCER; METASTATIC BREAST-CANCER; ADVANCED PANCREATIC-CANCER; COLORECTAL-CANCER; HEMATOPOIETIC-CELLS; 1ST-LINE TREATMENT; PLUS GEMCITABINE; TUMOR-GROWTH; STEM-CELLS AB Background: Bevacizumab is currently approved for the treatment of several malignancies. Haematologic toxicities are not among the main concerns associated with bevacizumab, but they have been occasionally reported. We performed a meta-analysis to determine the incidence and risk of haematologic toxicities associated with bevacizumab. Methods: Pubmed databases from 1966 to September 2010 were searched for studies reported, as well as American Society of Clinical Oncology meetings. Bevacizumab randomised clinical trials with adequate safety data profile were included. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR) and 95% confidence intervals (CI). Results: 15,263 patients were included. The incidence of bevacizumab-associated all-grade and high-grade haematologic toxicities were, respectively: anaemia: 18.7% and 3.9%; neutropenia: 25.0% and 18.5%; and thrombocytopenia: 13.9% and 3.4%. Febrile neutropenia incidence was 3.8%. Compared to placebo/control arms, bevacizumab was associated with a decreased risk of all-grade (RR = 0.81; 95%CI 0.68-0.96; p =.016) and high-grade (RR = 0.73; 95%CI 0.60-0.89; p = .002) anaemia, and increased risks of all-grade (RR = 1.15; 95%CI 1.01-1.30; p = .033) and high-grade (RR = 1.08; 95%CI 1.02-1.13; p = .005) neutropenia, all-grade thrombocytopenia (RR = 1.22; 95%CI 1.00-1.48; p = .047) and febrile neutropenia (RR = 1.31; 95%CI 1.08-1.58; p = .006). Conclusions: Bevacizumab is associated with a lower risk of anaemia and increased risks of neutropenia, thrombocytopenia and febrile neutropenia. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Kidney Canc Ctr,Dana Farber Canc Inst, Boston, MA 02115 USA. [Schutz, Fabio A. B.; Jardim, Denis L. F.; Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Je, Youjin] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Jardim, Denis L. F.] Hosp Sirio Libanes, Sao Paulo, Brazil. RP Choueiri, TK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Kidney Canc Ctr,Dana Farber Canc Inst, 44 Binney St,Dana 1230, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu FU philanthropic Trust Family Research Fund for Kidney Cancer FX This study was funded by the philanthropic Trust Family Research Fund for Kidney Cancer. The funding source did not have any role in this study. The authors had access to all the data and had the final responsibility for the decision to submit the manuscript for publication. NR 55 TC 14 Z9 14 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD MAY PY 2011 VL 47 IS 8 BP 1161 EP 1174 DI 10.1016/j.ejca.2011.03.005 PG 14 WC Oncology SC Oncology GA 772KI UT WOS:000291232400006 PM 21470847 ER PT J AU Fuller, BE Rodriguez, VL Linke, A Sikirica, M Dirani, R Hauser, P AF Fuller, Bret E. Rodriguez, Veronica L. Linke, Alex Sikirica, Mirko Dirani, Riad Hauser, Peter TI Prevalence of liver disease in veterans with bipolar disorder or schizophrenia SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Liver disease; Veterans; Bipolar disorder; Schizophrenia ID SUBSTANCE USE DISORDERS; SEVERE MENTAL-ILLNESS; HEPATITIS-C; UNITED-STATES; PSYCHIATRIC-DISORDERS; CARE; COMORBIDITY; MANAGEMENT; INFECTION; HEALTH AB Objective: To assess the prevalence of three liver diseases [hepatitis C virus (HCV), nonalcoholic fatty liver disease and alcohol-induced cirrhosis] in patients (veterans) with/without schizophrenia/schizoaffective disorder and bipolar disorder. Methods: A retrospective electronic chart review of Veterans Integrated Services Network 20 facilities from January 1, 2001 to December 21, 2006 selected patients to one of two groups: schizophrenia/schizoaffective disorder or bipolar disorder. Patients in both groups were compared with veterans in an equal-sized random sample from the same data set of veterans without psychiatric diagnoses. Logistic regression models evaluated risk for overall liver diseases as well as HCV, nonalcoholic fatty liver disease and alcoholic-induced cirrhosis. Results: Patients with schizophrenia (n=6521) had a higher prevalence of liver disease [22.4% versus 3.2%; odds ratio (OR)=8.73]; HCV (16.5% versus 1.9%; OR=10.21); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=4.09) than matched controls. Patients with bipolar disorder (n=5319) had a higher prevalence of liver disease (21.5% versus 3.5%; OR=7.58); HCV (15.5% versus 2.1%; OR=8.60); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=3.82) than matched controls. Risk factors for liver disease in patients with schizophrenia (versus matched controls) included diabetes (OR=1.29), hypertension (OR=1.27), HIV (OR=3.54), substance use disorder (SUD) (OR=2.28), alcohol use disorder (OR=3.05) and schizophrenia (OR=2.74). Risk factors for development of liver disease for patients with bipolar disorder: diabetes (OR=1.40), HIV (OR=3.66), SUD (OR=2.68), alcohol use disorder (OR=3.22) and bipolar disorder (OR=2.27). Conclusions: This study in veterans shows that the presence of mental illness and its comorbidities represents a significant risk factor for the diagnosis of liver disease, including HCV and alcohol-related cirrhosis. Published by Elsevier Inc. C1 [Fuller, Bret E.; Rodriguez, Veronica L.; Linke, Alex] Portland VA Med Ctr, Portland, OR 97210 USA. [Sikirica, Mirko; Dirani, Riad] Ortho McNeil Janssen Sci Affairs LLC, Titusville, NJ USA. [Fuller, Bret E.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Hauser, Peter] Long Beach Vet Affairs Med Ctr, Vet Integrated Serv Network 22, Network Off, Long Beach, CA USA. RP Fuller, BE (reprint author), Portland VA Med Ctr, 3170 SW US Vet Pk Rd,Mailcode P3MHDC, Portland, OR 97210 USA. EM bret.fuller@va.gov FU Ortho-McNeil Janssen Scientific Affairs FX This study was funded by a grant from Ortho-McNeil Janssen Scientific Affairs. NR 24 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAY-JUN PY 2011 VL 33 IS 3 BP 232 EP 237 DI 10.1016/j.genhosppsych.2011.03.006 PG 6 WC Psychiatry SC Psychiatry GA 773IR UT WOS:000291300700004 PM 21601719 ER PT J AU Roffman, JL AF Roffman, Joshua L. TI SPECIAL ISSUE Biomarkers and Personalized Psychiatry Introduction SO HARVARD REVIEW OF PSYCHIATRY LA English DT Editorial Material C1 Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Med School, Cambridge, MA 02138 USA. RP Roffman, JL (reprint author), Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Med School, Cambridge, MA 02138 USA. EM jroffman@partners.org NR 6 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2011 VL 19 IS 3 SI SI BP 99 EP 101 DI 10.3109/10673229.2011.586547 PG 3 WC Psychiatry SC Psychiatry GA 771MJ UT WOS:000291162300001 PM 21631156 ER PT J AU Iosifescu, DV AF Iosifescu, Dan Vlad TI Electroencephalography-Derived Biomarkers of Antidepressant Response SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE antidepressant; EEG source localization; electroencephalography; event-related potentials; major depressive disorder; predictor; quantitative electroencephalography; response ID MAJOR DEPRESSIVE DISORDER; EVENT-RELATED POTENTIALS; STAR-ASTERISK-D; ANTERIOR CINGULATE CORTEX; LOUDNESS DEPENDENCE; CLINICAL-RESPONSE; NORADRENERGIC ANTIDEPRESSANTS; PERCEPTUAL ASYMMETRY; INTENSITY DEPENDENCE; ELECTRICAL-ACTIVITY AB Recent meta-analyses point to the relatively low efficacy of commonly used antidepressant medications. Selecting the most effective medications for depressed subjects having failed previous treatments is especially difficult. There is a clear need for objective biomarkers that could assist and optimize such treatment selection. We will review here a growing body of evidence suggesting that several electroencephalography (EEG)-based methods may be useful for predicting antidepressant response and eventually for guiding clinical treatment decisions. While most of these methods are based on resting-state EEGs (e. g., alpha-and theta-band EEG abnormalities, the combined Antidepressant Response Index (ATR), cordance, referenced EEG), others include EEG source localization and evoked potentials. The limitations of these technologies and the potential clinical uses will also be outlined. (HARV REV PSYCHIATRY 2011;19:144-154.) C1 [Iosifescu, Dan Vlad] Harvard Univ, Dept Psychiat, Mt Sinai Sch Med, Sch Med, New York, NY 10029 USA. [Iosifescu, Dan Vlad] Harvard Univ, Dept Neurosci, Mt Sinai Sch Med, Sch Med, New York, NY 10029 USA. [Iosifescu, Dan Vlad] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Iosifescu, DV (reprint author), Harvard Univ, Dept Psychiat, Mt Sinai Sch Med, Sch Med, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM dan.iosifescu@mssm.edu NR 65 TC 18 Z9 22 U1 4 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2011 VL 19 IS 3 SI SI BP 144 EP 154 DI 10.3109/10673229.2011.586549 PG 11 WC Psychiatry SC Psychiatry GA 771MJ UT WOS:000291162300005 PM 21631160 ER PT J AU Borairi, S Dougherty, DD AF Borairi, Sahar Dougherty, Darin D. TI The Use of Neuroimaging to Predict Treatment Response for Neurosurgical Interventions for Treatment-Refractory Major Depression and Obsessive-Compulsive Disorder SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE biological markers; major depressive disorder; neuroimaging; neurosurgery; neurotherapy; obsessive-compulsive disorder ID MEDIAL PREFRONTAL CORTEX; DEEP BRAIN-STIMULATION; TREATMENT-RESISTANT DEPRESSION; SUBGENUAL CINGULATE CORTEX; GLUCOSE-METABOLISM; POTENTIAL PREDICTORS; ANTERIOR CINGULOTOMY; UNIPOLAR DEPRESSION; BEHAVIORAL-THERAPY; SLEEP-DEPRIVATION AB Neuroimaging has contributed profoundly to our understanding of the pathophysiology of psychiatric disorders but has had little impact on treatment. An important goal in neuroscience research is identifying biological markers that predict subsequent response to given treatments. This approach may be especially valuable when considering high-risk and high-cost treatments such as psychiatric neurosurgery. Here, we review neuroimaging findings pertaining to treatment-refractory major depression and obsessive-compulsive disorder, and imaging markers that predict response to neurotherapeutic interventions. Thus far, studies conducted with neurotherapeutic interventions have found patterns of predictive brain activity that are similar to those conducted with pharmacological treatments. The predictive neural correlates are concordant with pathophysiological models of major depressive and obsessive-compulsive disorder. These promising findings should motivate additional work establishing the reliability and cost-effectiveness of neuroimaging to predict treatment response across psychiatric diagnoses and interventions. (HARV REV PSYCHIATRY 2011;19:155-161.) C1 [Borairi, Sahar] York Univ, Dept Psychol, Boston, MA USA. [Dougherty, Darin D.] Harvard Univ, Sch Med, Boston, MA USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,Room 2612, Charlestown, MA 02129 USA. EM ddougherty@partners.org FU NIMH NIH HHS [P50 MH086400] NR 50 TC 2 Z9 2 U1 2 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2011 VL 19 IS 3 SI SI BP 155 EP 161 DI 10.3109/10673229.2011.581888 PG 7 WC Psychiatry SC Psychiatry GA 771MJ UT WOS:000291162300006 PM 21631161 ER PT J AU Riess, H AF Riess, Helen TI Biomarkers in the Psychotherapeutic Relationship: The Role of Physiology, Neurobiology, and Biological Correlates of EMPATHY SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE biomarkers; empathy; neural correlates of empathy; patient-doctor relationship; psychophysiology; psychotherapy; therapeutic alliance ID COGNITIVE-BEHAVIORAL-THERAPY; HUMAN CINGULATE CORTEX; NEURAL BASIS; INTERPERSONAL PSYCHOTHERAPY; MAGNETIC STIMULATION; EMOTIONAL EXPERIENCE; FACIAL EXPRESSIONS; BLOOD-FLOW; DEPRESSION; ALLIANCE AB Emerging biomarker research could powerfully influence the practice of psychotherapy, a standard treatment that is as strongly rooted in brain plasticity as are psychopharmacologic interventions. Psychotherapy is associated with measurable changes in central and peripheral neurophysiology. These markers could be harnessed to aid informed, personalized recommendations for specific psychosocial treatments, to guide a course of treatment, and to predict treatment outcomes, in lieu of relying on costly, trial-and-error approaches. Psychotherapy and empathy research also demonstrate that the patient-doctor relationship has important neurophysiological correlates that can be salient to treatment outcomes, as illustrated in a case example. These correlates include autonomic nervous system arousal manifested by heart rate, respiration rate, muscle tension, and galvanic skin resistance; electroencephalography; and brain-imaging markers. While additional biomarker research is unfolding, there are specific neurobiologically based clinical and subclinical observations, organized by using the E.M.P.A.T.H.Y. mnemonic, that may guide and enhance psychotherapy. Empathic attunement to patients is equally relevant for psychopharmacologic interventions and psychotherapy, and for all patient-doctor relationships. (HARV REV PSYCHIATRY 2011;19:162-174.) C1 [Riess, Helen] Harvard Univ, Sch Med, Boston, MA USA. [Riess, Helen] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Riess, H (reprint author), Wang ACC, Dept Psychiat, Suite 812,15 Parkman St, Boston, MA 02114 USA. EM HRIESS@PARTNERS.ORG NR 107 TC 7 Z9 7 U1 2 U2 31 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2011 VL 19 IS 3 SI SI BP 162 EP 174 DI 10.3109/08941939.2011.581915 PG 13 WC Psychiatry SC Psychiatry GA 771MJ UT WOS:000291162300007 PM 21631162 ER PT J AU Villarreal, G Oh, DJ Kang, MH Rhee, DJ AF Villarreal, Guadalupe, Jr. Oh, Dong-Jin Kang, Min Hyung Rhee, Douglas J. TI Coordinated Regulation of Extracellular Matrix Synthesis by the MicroRNA-29 Family in the Trabecular Meshwork SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; AQUEOUS-HUMOR; VISUAL IMPAIRMENT; OUTFLOW FACILITY; GENE-EXPRESSION; SMAD PROTEINS; TGF-BETA; INTRAOCULAR-PRESSURE; HUMAN EYES; CELLS AB PURPOSE. The microRNA-29 (miR-29) family has emerged, in various tissues, as a key modulator of extracellular matrix (ECM) homeostasis. In this study, the authors investigate the role of the miR-29 family in the regulation of ECM synthesis in the trabecular meshwork (TM) under basal and TGF-beta 2 stimulatory conditions. METHODS. Human TM cells were incubated with 2.5 ng/mL activated, recombinant human TGF-beta 2 for 24, 48, and 72 hours. A specific pharmacologic inhibitor was used to block SMAD3 function in the context of TGF-beta 2 stimulation. Changes in the expression of the miR-29 family were assessed by real-time PCR. The effect of miR-29 molecules and inhibitors on ECM levels was determined by immunoblot analysis. RESULTS. All three members of the miR-29 family were expressed in cultured TM cells. Although the incubation of TM cells with TGF-beta 2 induced miR-29a and suppressed miR-29b levels, no significant effect was observed on miR-29c expression. Additional studies revealed that SMAD3 modulates miR-29b expression under basal and TGF-beta 2 conditions. Subsequent gain-and loss-of-function experiments demonstrated that the miR-29 family functions as a critical suppressor of various ECM proteins under basal and TGF-beta 2 stimulatory conditions. CONCLUSIONS. The findings derived from this study identify the miR-29 family as a critical regulator of ECM expression in the TM and suggest that its modulation by TGF-beta 2 may be important in controlling ECM synthesis. Together, these data provide further insight into the complex regulatory mechanisms mediating TGF-beta 2 signaling and ECM production in the TM. (Invest Ophthalmol Vis Sci. 2011;52:3391-3397) DOI:10.1167/iovs.10-6165 C1 [Villarreal, Guadalupe, Jr.; Oh, Dong-Jin; Kang, Min Hyung; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Rhee, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com FU Fight for Sight; National Eye Institute [EY 019654-01, EY 014104] FX Supported by a Fight for Sight Summer Student Fellowship (GV) and by National Eye Institute Grants EY 019654-01 (DJR) and EY 014104 (MEEI Vision-Core Grant). NR 59 TC 45 Z9 46 U1 0 U2 5 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 MAY PY 2011 VL 52 IS 6 BP 3391 EP 3397 DI 10.1167/iovs.10-6165 PG 7 WC Ophthalmology SC Ophthalmology GA 770PN UT WOS:000291100800067 PM 21330653 ER PT J AU Iovieno, N Dalton, ED Fava, M Mischoulon, D AF Iovieno, Nadia Dalton, Elizabeth D. Fava, Maurizio Mischoulon, David TI Second-tier natural antidepressants: Review and critique SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE Complementary and Alternative Medicine; Depression; Rhodiola rosea; Chromium; 5-Hydroxytryptophan; Inositol ID ROSEA L. EXTRACT; OBSESSIVE-COMPULSIVE DISORDER; LOW-DOSE REGIMEN; RHODIOLA-ROSEA; DOUBLE-BLIND; ALTERNATIVE MEDICINE; CHROMIUM PICOLINATE; INOSITOL TREATMENT; RESONANCE-SPECTROSCOPY; DEPRESSION RESISTANT AB The use of Complementary and Alternative Medicine (CAM) for physical and mental problems has increased significantly in the US over the past two decades, and depression is one of the leading indications for the use of CAM. This article reviews some of the lesser-known natural products with potential psychiatric applications that are starting to emerge with some scientific and clinical evidence and may constitute a next wave of natural antidepressants: Rhodiola rosea, chromium, 5-Hydroxytryptophan (5-HTP) and inositol. Background information, efficacy data, proposed mechanisms of action, recommended doses, side effects, and precautions are reviewed. We found some encouraging data for the use of these natural products in specific populations of depressed patients. R.rosea is an adaptogen plant that can be especially helpful in treating asthenic or lethargic depression, and may be combined with conventional antidepressants to alleviate some of their common side effects. Chromium has a beneficial effect on eating-related atypical symptoms of depression, and may be a valuable agent in treating atypical depression and seasonal affective disorder. Inositol may be useful in the treatment of bipolar depression when combined with mood stabilizers. Evidence for the clinical efficacy of 5-HTP is also promising but still preliminary. Although more well-designed and larger controlled studies are needed before any substantive conclusions can be drawn, the available evidence is compelling and these natural products deserve further investigation as a possibly significant addition to the antidepressant armamentarium. (C) 2010 Elsevier B.V. All rights reserved. C1 [Iovieno, Nadia; Dalton, Elizabeth D.; Fava, Maurizio; Mischoulon, David] Harvard Univ, Depress Clin & Res Program, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Iovieno, Nadia] Univ Pisa, Dept Psychiat, Pisa, Italy. RP Iovieno, N (reprint author), Harvard Univ, Depress Clin & Res Program, Sch Med, Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA. EM niovieno@partners.org FU Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bio Research; BrainCells, Inc.; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions; Eli Lilly Company; Forest Pharmaceuticals Inc.; Ganeden; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis; Organon Inc.; PamLab; LLC; Pfizer Inc.; Pharmavite; Roche; Sanofi-Aventis; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories; Laxdale (Amarin); Nordic Naturals; SwissMedica FX Dr. M. Fava has served has an advisor/consultant for Abbott Laboratories, Amarin, Aspect Medical Systems, Astra-Zeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc, Biovail Pharmaceuticals, Inc., BrainCells, Inc, Bristol-Myers Squibb Company, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly & Company, EPIX Pharmaceuticals, Fabre-Kramer, Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, Grunenthal GmBH Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante Inc. Merck, Methylation Sciences. Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc., PharmaStar, Pharmavite, Precision Human Biolaboratory, Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay Pharmaceuticals Inc., Somaxon, Somerset Pharmaceuticals, Synthelabo, Takeda, Tetragenex, Transcept Pharmaceuticals, Vanda Pharmaceuticals Inc., Wyeth-Ayerst Laboratories; has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, Bio Research, BrainCells, Inc., Bristol-Myers Squibb Company, Cephalon, Clinical Trial Solutions, Eli Lilly & Company, Forest Pharmaceuticals Inc., Ganeden, GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc., Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, Wyeth-Ayerst Laboratories; has served as a speaker for Advanced Meeting Partners, American Psychiatric Association, Astra-Zeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb Company, Cephalon. Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, Imedex, Novartis, Organon Inc., Pfizer Inc., PharmaStar, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed-Elsevier, UBC, Wyeth-Ayerst Laboratories; has equity Holdings in Compellis; and has patent applications for SPCD and for a combination of azapirones and bupropion in MDD, copyright royalties for the MGH CPFQ SFI, ATRQ DESS, and SAFER.; Dr. D. Mischoulon has served as a consultant for Bristol-Myers Squibb Company and PamLab; has received research support from Laxdale (Amarin), Nordic Naturals, Ganeden, SwissMedica; has received honoraria from MGH Psychiatry Academy/Reed Medical Education; has served as a speaker for Pamlab, Virbac; Nordic Naturals; and has royalties for Back Bay Scientific for PMS Escape (patent application pending). NR 116 TC 18 Z9 18 U1 3 U2 32 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 MAY PY 2011 VL 130 IS 3 BP 343 EP 357 DI 10.1016/j.jad.2010.06.010 PG 15 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 771WT UT WOS:000291192100001 PM 20579741 ER PT J AU Mischoulon, D Eddy, KT Keshaviah, A Dinescu, D Ross, SL Kass, AE Franko, DL Herzog, DB AF Mischoulon, David Eddy, Kamryn T. Keshaviah, Aparna Dinescu, Diana Ross, Stephanie L. Kass, Andrea E. Franko, Debra L. Herzog, David B. TI Depression and eating disorders: Treatment and course SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Major depressive disorder; Eating disorders; Anorexia nervosa; Bulimia nervosa; Antidepressants ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; SUICIDE ATTEMPTS; FLUOXETINE; PLACEBO; OBSESSIONALITY; PSYCHOTHERAPY; COMORBIDITY; RECOVERY; ANXIETY AB Background: We examined the course of major depressive disorder (MDD) and predictors of MOD recovery and relapse in a longitudinal sample of women with eating disorders (ED). Methods: 246 Boston-area women with DSM-IV anorexia nervosa-restricting (ANR; n = 51), AN-binge/purge (ANBP; n = 85), and bulimia nervosa (BN; n = 110) were recruited between 1987 and 1991 and interviewed using the Eating Disorders Longitudinal Interval Follow-up Evaluation (LIFE-EAT-II) every 6-12 months for up to 12 years. 100 participants had MDD at study intake and 45 developed MOD during the study. Psychological functioning and treatment were assessed. Results: Times to MDD onset (1 week-4.3 years), recovery (8 weeks-8.7 years), and relapse (1 week-5.2 years) varied. 70% recovered from MOD, but 65% subsequently relapsed. ANR patients were significantly less likely to recover from MDD than ANBP patients (p = 0.029). Better psychological functioning and history of MDD were associated with higher chance of MDD recovery. Higher baseline depressive severity and full recovery from ED were associated with greater likelihood of MDD relapse; increased weight loss was somewhat protective. Adequate antidepressant treatment was given to 72% of patients with MDD and generally continued after MDD recovery. Time on antidepressants did not predict MOD recovery (p = 0.27) or relapse (p = 0.26). Limitations: Small ED diagnostic subgroups; lack of non-ED control group. Conclusions: The course of MDD in EDs is protracted; MOD recovery may depend on ED type. Antidepressants did not impact likelihood of MOD recovery, nor protect against relapse, which may impact on treatment strategies for comorbid MOD and EDs. (C) 2010 Elsevier B.V. All rights reserved. C1 [Mischoulon, David] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Eddy, Kamryn T.; Dinescu, Diana; Ross, Stephanie L.; Kass, Andrea E.; Franko, Debra L.; Herzog, David B.] Massachusetts Gen Hosp, Harris Ctr Educ & Advocacy Eating Disorders, Dept Psychiat, Boston, MA 02114 USA. [Eddy, Kamryn T.; Herzog, David B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Keshaviah, Aparna] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Franko, Debra L.] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. RP Mischoulon, D (reprint author), 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmischoulon@partners.org FU National Institute of Mental Health [5R01 MH 38333 05]; Rubenstein Charitable Foundation, Boston MA; Laxdale (Amarin); Nordic Naturals; Ganeden; SwissMedica FX This work was supported by the National Institute of Mental Health grant 5R01 MH 38333 05 (DBH) and the Rubenstein Charitable Foundation, Boston MA. Sponsors had no further role in the study design, collection, analysis and interpretation of data, writing of the report, and the decision to submit the paper for publication.; Dr. Mischoulon has received research support from Laxdale (Amarin), Nordic Naturals, Ganeden, and SwissMedica. He has served as a consultant to Bristol-Meyers-Squibb Company. He has received speaking honoraria from Pamlab, Virbac, and Nordic Naturals. He has received writing honoraria from Pamlab. He has received royalties from Back Bay Scientific for PMS Escape, and royalties from Lippincott Williams & Wilkins, for textbook "Natural Medications for Psychiatric Disorders: Considering the Alternatives" (David Mischoulon and Jerrold F Rosenbaum, Eds.). He has received honoraria from Reed Medical Education (a company working as a logistics collaborator for the MGH Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were supported through Independent Medical Education (IME) grants from pharmaceutical companies co-supporting programs along with participant tuition. Commercial entities currently supporting the MGH Psychiatry Academy are listed on the Academy's website www.mghcme.org. NR 38 TC 33 Z9 33 U1 1 U2 13 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 MAY PY 2011 VL 130 IS 3 BP 470 EP 477 DI 10.1016/j.jad.2010.10.043 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 771WT UT WOS:000291192100015 PM 21109307 ER PT J AU La Fountaine, MF Gossett, JD De Meersman, RE Bauman, WA AF La Fountaine, Michael F. Gossett, James D. De Meersman, Ronald E. Bauman, William A. TI Increased QT Interval Variability in 3 Recently Concussed Athletes: An Exploratory Observation SO JOURNAL OF ATHLETIC TRAINING LA English DT Article DE autonomic nervous system; heart; cardiovascular system; return to play ID HEART-RATE-VARIABILITY; AUTONOMIC NERVOUS-SYSTEM; POWER SPECTRAL-ANALYSIS; SUDDEN CARDIAC DEATH; EXERCISE; MODULATION; CASCADE; RISK AB Context: The QT interval variability index (QTVI) is a noninvasive measure of beat-to-beat fluctuations of the QT interval as seen from a single electrocardiographic lead. It represents the relationship between the respective variabilities of the QT and R-R intervals. Recently, the QTVI was demonstrated to be an index of vagal cardiac autonomic modulation in resting conditions. Objective: To determine whether QTVI varied in athletes at 48 hours, 1 week, and 2 weeks after a concussive head injury. Design: Case series. Setting: Testing facility. Patients or Other Participants: Three athletes with recent concussions and 3 uninjured athletes with similar demographic factors. Main Outcome Measure(s): Continuous 3-lead electrocardiograms were obtained in a seated, resting position over 2 successive weeks. Separate, unpaired t tests were performed to determine whether group-visit differences were present in the QTVI at 48 hours, 1 week, or 2 weeks. Results: No demographic differences were present between groups. At 48 hours, the QTVI was greater in the concussion group than in the matched controls. At weeks 1 and 2, the QTVI in the concussion group was lower than at 48 hours and not different from that of the control group. Conclusions: Vagal cardiac autonomic modulation, as quantified by the QTVI, appeared to be negatively affected in concussed athletes within 48 hours of injury, resolved within 1 week, and remained at control group levels 2 weeks later. Serial assessments of QTVI may be of clinical utility in identifying suspected cases of acute concussion and may provide helpful information for determining when an athlete can return to play safely. C1 [La Fountaine, Michael F.; Bauman, William A.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [La Fountaine, Michael F.; Bauman, William A.] James J Peters VA Med Ctr, SCI Serv, Bronx, NY 10468 USA. [La Fountaine, Michael F.; Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Gossett, James D.] Columbia Univ, Dept Sports Med, New York, NY USA. [De Meersman, Ronald E.] Columbia Univ, Teachers Coll, Dept Biobehav Sci, New York, NY 10027 USA. [Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP La Fountaine, MF (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Room 7A-13M,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM michael.lafountaine@va.gov NR 32 TC 5 Z9 5 U1 0 U2 5 PU NATL ATHLETIC TRAINERS ASSOC INC PI DALLAS PA 2952 STEMMONS FREEWAY, DALLAS, TX 75247 USA SN 1062-6050 J9 J ATHL TRAINING JI J. Athl. Train. PD MAY-JUN PY 2011 VL 46 IS 3 BP 230 EP 233 PG 4 WC Sport Sciences SC Sport Sciences GA 770YC UT WOS:000291123400002 PM 21669090 ER PT J AU Smith, EG Craig, TJ Ganoczy, D Walters, HM Valenstein, M AF Smith, Eric G. Craig, Thomas J. Ganoczy, Dara Walters, Heather M. Valenstein, Marcia TI Treatment of Veterans With Depression Who Died by Suicide: Timing and Quality of Care at Last Veterans Health Administration Visit SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PSYCHOLOGICAL AUTOPSY; MENTAL-HEALTH; UNITED-STATES; ANTIDEPRESSANTS; CONTACT; SWEDEN; PEOPLE; ACCESS; PRESCRIPTION; PREVENTION AB Objective: To examine the recency and quality of the last Veterans Health Administration (VHA) visit for patients with depression who died by suicide. Method: We obtained services and pharmacy data for all 1,843 VHA patients with diagnosed depressive disorders (DSM-IV criteria) who died by suicide from April 1999 through September 2004. We ascertained the location and timing of their final VHA visit. For visits occurring within 30 days of suicide, we examined 3 quality indicators: (1) evidence that mental illness was a focus of the final visit, (2) adequacy of antidepressant dosage, and (3) recent receipt of mental health services. Results: Just over half of the patients (51%) with depression diagnoses had a VHA visit within 30 days of suicide. A minority of these patients (43%) died by suicide within 30 days of a final visit with mental health services, although 64% had received such services within 91 days of their suicide. Among the 57% of patients who died by suicide within 30 days and who were seen in non-mental health settings for their final visit, only 34% had a mental health condition coded at the final visit, and only 41% were receiving adequate dosages of antidepressant (versus 55% for those last seen by mental health services) (P <. 0005). Conclusions: Veterans Health Administration patients with depression who died by suicide within 30 days of their final visit received relatively high rates of mental health services, but most final visits still occurred in non-mental health settings. Increased referrals to mental health services, attention to mental health issues in non-mental health settings, and focus on antidepressant treatment adequacy by all providers might have reduced suicide risks for these patients. J Clin Psychiatry 2011;72(5):622-629 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Smith, Eric G.] Vet Hlth Adm VHA Hlth Serv Res & Dev Ctr Hlth Qua, Bedford, MA USA. [Smith, Eric G.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Craig, Thomas J.] US Dept Vet Affairs, Washington, DC USA. [Ganoczy, Dara; Walters, Heather M.; Valenstein, Marcia] Serious Mental Illness Treatment Resource & Evalu, Ann Arbor Ctr Excellence COE, Dept Vet Affairs, Ann Arbor, MI USA. [Valenstein, Marcia] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. RP Smith, EG (reprint author), Edith Nourse Rogers Mem VA Hosp, Room B-29,Bldg 70,200 Springs Rd, Bedford, MA 01730 USA. EM Eric.Smith5@va.gov FU Forest Research Institute, an affiliate of Forest Laboratories, a manufacturer of antidepressants (among other medications); Department of Veterans Affairs [IIR 04-211]; National Institute of Mental Health [R01 MH078698]; Serious Mental Illness Treatment Resource and Evaluation Center; Ann Arbor; VHA Health Services Research and Development [RCD 98-350] FX Dr Smith receives grant funding from Forest Research Institute, an affiliate of Forest Laboratories, a manufacturer of antidepressants (among other medications), for unrelated investigator-initiated research concerning the safety of antidepressants. Dr Smith declares that he received no funds from this grant during the period of preparation of this article and that the grant did not influence this article in any way. Drs Craig and Valenstein and Mss Ganoczy and Walters have no competing financial interests to disclose.\; Supported by Department of Veterans Affairs grant IIR 04-211, by National Institute of Mental Health grant R01 MH078698, and by the Serious Mental Illness Treatment Resource and Evaluation Center, Ann Arbor, Michigan. Dr Smith receives salary support through VHA Health Services Research and Development Center of Excellence funding to the Center for Health Quality, Outcomes, and Economic Research, Bedford, Massachusetts. Support for database and research provided by VHA Health Services Research and Development grant RCD 98-350 (Dr Valenstein, principal investigator). NR 39 TC 14 Z9 14 U1 0 U2 6 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 MAY PY 2011 VL 72 IS 5 BP 622 EP 629 DI 10.4088/JCP.09m05608b1u PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 772NM UT WOS:000291240600008 PM 20868636 ER PT J AU Gitlin, MJ Mintz, J Sokolski, K Hammen, C Altshuler, LL AF Gitlin, Michael J. Mintz, Jim Sokolski, Kenneth Hammen, Constance Altshuler, Lori L. TI Subsyndromal Depressive Symptoms After Symptomatic Recovery From Mania Are Associated With Delayed Functional Recovery SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PROSPECTIVE FOLLOW-UP; BIPOLAR-II DISORDER; LONG-TERM COURSE; PSYCHOSOCIAL DISABILITY; NATURAL-HISTORY; RATING-SCALE; IMPAIRMENT; HOSPITALIZATION; REMISSION; IMPACT AB Objective: This study examined whether the presence of subsyndromal depressive symptoms predicted functional recovery after an acute manic episode. Method: Subjects with bipolar I disorder (according to the Structured Clinical Interview for DSM-IV) who, at the time of symptomatic recovery from an acute manic or hypomanic episode, had a concomitant functional recovery (n = 52) were compared on demographic variables and mood symptoms to those who had symptomatically recovered but not functionally recovered (n = 33). Demographic and mood variables were examined in the nonfunctionally recovered group to assess predictors of time to functional recovery. The primary functional outcome measure used was the Life Functioning Questionnaire, a 5-minute, gender-neutral self-report scale to measure role function in 4 domains: workplace, duties at home, leisure time with family, and leisure time with friends. Participants in the study were recruited from July 2000 through February 2005. Results: Depressive symptoms, even at a subsyndromal level, were significantly associated with persisting functional impairment after symptomatic recovery from a manic episode (P<.02). Subsyndromal depressive symptoms also significantly predicted a slower time to functional recovery over the next 9 months (P=.006). Conclusion: The presence of even mild subsyndromal depressive symptoms may interfere with functional recovery in patients with bipolar disorder after symptomatic recovery from a manic or hypomanic episode. J Clin Psychiatry 2011;72(5):692-697 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Gitlin, Michael J.; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA. [Sokolski, Kenneth] Vet Affairs VA Long Beach Healthcare Syst, Mental Hlth Care Grp, Long Beach, CA USA. [Sokolski, Kenneth] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine Sch Med, Irvine, CA 92717 USA. [Hammen, Constance] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Gitlin, MJ (reprint author), 300 UCLA Med Plaza,Ste 2200, Los Angeles, CA 90095 USA. EM mgitlin@mednet.ucla.edu FU National Institute of Mental Health, Bethesda, Maryland [1R01MH057762]; Abbott Laboratories, Abbott Park, Illinois FX Funding for this study was provided by the National Institute of Mental Health (1R01MH057762) (Dr Altshuler), Bethesda, Maryland. Abbott Laboratories (Dr Altshuler), Abbott Park, Illinois, provided funding to obtain divalproex sodium levels at the UCLA laboratory and provided divalproex sodium for some study subjects. NR 39 TC 18 Z9 18 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2011 VL 72 IS 5 BP 692 EP 697 DI 10.4088/JCP.09m05291gre PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 772NM UT WOS:000291240600016 PM 20673560 ER PT J AU Sachs, GS Dupuy, JM Wittmann, CW AF Sachs, Gary S. Dupuy, Jamie M. Wittmann, Curtis W. TI The Pharmacologic Treatment of Bipolar Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; TREATMENT ENHANCEMENT PROGRAM; LITHIUM MAINTENANCE TREATMENT; RELEASE CARBAMAZEPINE CAPSULES; MANIC-DEPRESSIVE DISORDERS; CONTROLLED 18-MONTH TRIAL; NOS MAJOR DEPRESSION; DOUBLE-BLIND TRIAL; OPEN-LABEL TRIAL; I-DISORDER AB Over the past half century, substantial clinical trial data have accumulated to guide clinical management of bipolar disorder, and 13 medications have gained US Food and Drug Administration approval for the treatment of mania or bipolar depression or the maintenance treatment of bipolar disorder. While the number of studies has grown and many controversies related to pharmacologic treatment of bipolar disorder are not yet resolved, the task of transforming the accumulated evidence into useful guidance for clinical practice becomes more manageable and less error prone by limiting consideration to the highest quality studies. Therefore, this article emphasizes points of relative clarity by highlighting findings supported by double-blind, placebo-controlled clinical trials with samples of at least 100 subjects. A MEDLINE search was conducted and augmented by a manual search of bibliographies, textbooks, and abstracts from recent scientific meetings for randomized controlled trials published in English between 1950 and April 2010 with at least 100 subjects. Keywords used in the search included randomized controlled trial, mania, hypomania, depression, relapse prevention, placebo, antidepressant, switch, and maintenance treatment of bipolar disorder. A paradigm for implementing evidence-based treatment is offered along with consideration of patterns emerging across clinical trials. J Clin Psychiatry 2011;72(5):704-715 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Sachs, Gary S.] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Bipolar Clin, Boston, MA 02114 USA. [Sachs, Gary S.; Dupuy, Jamie M.; Wittmann, Curtis W.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Sachs, Gary S.] United BioSource Corp, Lexington, MA USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Bipolar Clin, WACC 815,50 Staniford St, Boston, MA 02114 USA. EM sachsg@aol.com FU National Institute of Mental Health and Repligen FX Dr Sachs is an employee of United BioSource Corporation; has been a consultant for Forest, Merck, Sunovion, and Takeda; has received grant/research support from the National Institute of Mental Health and Repligen; has been on the speakers/advisory boards of AstraZeneca, Pfizer, and Otsuka; and is a stock shareholder in Concordant Rater Systems. Drs Dupuy and Wittmann report no financial or other relationships relevant to the subject of this article. NR 157 TC 12 Z9 12 U1 3 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2011 VL 72 IS 5 BP 704 EP 715 DI 10.4088/JCP.10m06523 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 772NM UT WOS:000291240600018 PM 21658351 ER PT J AU Berlin, HA Koran, LM Jenike, MA Shapira, NA Chaplin, W Pallanti, S Hollander, E AF Berlin, Heather A. Koran, Lorrin M. Jenike, Michael A. Shapira, Nathan A. Chaplin, William Pallanti, Stefano Hollander, Eric TI Double-Blind, Placebo-Controlled Trial of Topiramate Augmentation in Treatment-Resistant Obsessive-Compulsive Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COMORBID TOURETTES-SYNDROME; TRANSGENIC MODEL; TRANSPORTER GENE; ASSOCIATION; PAROXETINE; SEROTONIN; RECEPTOR; SCALE; OCD; SLC1A1/EAAC1 AB Background: From 40% to 60% of obsessive-compulsive disorder (OCD) patients fail to tolerate or respond to selective serotonin reuptake inhibitors (SSRIs). Preclinical and neuroimaging studies have shown abnormally high glutamatergic concentrations in OCD patients and an association between decreased caudate glutamatergic concentrations and reduced OCD symptom severity after SSRI treatment. Topiramate inhibits glutamatergic conduction. Method: Thirty-six adult patients with DSM-IV-defined OCD were randomly assigned to topiramate (n = 18) and placebo (n = 18) groups in this 12-week, double-blind, placebo-controlled, parallel-groups trial. Subjects were taking the maximum SSRI dose they could tolerate for at least 12 weeks and their current dose for at least 6 weeks, which was maintained throughout the study. Primary outcome measures were changes in the Yale-Brown Obsessive Compulsive Scale (YBOCS) total score and compulsions and obsessions subscores. Patients were recruited and followed up between April 1, 2003, and April 13, 2006. Results: Using mixed regression models (time [weeks] x treatment), we found a significant treatment effect on the YBOCS compulsions (P=.014) subscale, but not the obsessions (P=.99) subscale or the total score (P=.11). Over the 12-week trial, the topiramate group (mean endpoint dose =177.8 +/- 134.2 mg/d; range, 50-400 mg/d) showed an average linear decrease of 5.38 points on the compulsions subscale compared to 0.6 points in the placebo group. Thirteen topiramate and 14 placebo subjects completed the study. Topiramate was not well tolerated in this trial: 28% (5/18) of the subjects discontinued the drug for adverse effects, and 39% (7/18) had a dose reduction for this reason. Conclusions: The results of this first double-blind, placebo-controlled trial of topiramate augmentation for treatment-resistant OCD suggest that topiramate may be beneficial for compulsions, but not obsessions. Modifications in glutamatergic function may be responsible, at least in part, for the improved response in compulsions seen with topiramate. C1 [Berlin, Heather A.; Pallanti, Stefano] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Koran, Lorrin M.] Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Jenike, Michael A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Jenike, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shapira, Nathan A.] Emory Univ, Dept Psychiat & Behav Sci, Sch Med, Atlanta, GA USA. [Chaplin, William] St Johns Univ, Dept Psychol, New York, NY USA. [Hollander, Eric] Albert Einstein Coll Med, Dept Psychiat, Montefiore Med Ctr, Univ Hosp, New York, NY USA. RP Berlin, HA (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM heather.berlin@mssm.edu FU Eli Lilly; Forest; Ortho-McNeil Neurologics; Somaxon; Ortho-McNeil Janssen; Ortho-McNeil Janssen Scientific Affairs, LLC FX Dr Koran chaired the American Psychiatric Association (APA) Workgroup that wrote the Practice Guideline for OCD; has received research grants from Eli Lilly, Forest, Ortho-McNeil Neurologics, and Somaxon; and is on the speakers bureau for Forest. Dr Shapira is named on a patent application (No. 11/830,906) relating to this study. Dr Hollander received research grants from and has been a consultant for Ortho-McNeil Janssen and served on the APA Workgroup that wrote the Practice Guideline for OCD and on the DSM-V Anxiety Disorders workgroup. Drs Berlin, Jenike, Chaplin, and Pallanti report no biomedical financial interests or potential conflicts of interest.; This study was funded by Ortho-McNeil Janssen Scientific Affairs, LLC. NR 56 TC 41 Z9 43 U1 1 U2 11 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2011 VL 72 IS 5 BP 716 EP 721 DI 10.4088/JCP.09m05266gre PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 772NM UT WOS:000291240600019 PM 20816027 ER PT J AU Gilbertson, MW Pitman, RK AF Gilbertson, Mark W. Pitman, Roger K. TI Does Combat Trauma Cause a Majority of PTSD Symptoms in Combat Veterans? Reply SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter ID POSTTRAUMATIC-STRESS-DISORDER C1 [Gilbertson, Mark W.] Manchester VA Med Ctr, Manchester, NH USA. [Pitman, Roger K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gilbertson, Mark W.; Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA USA. RP Gilbertson, MW (reprint author), Manchester VA Med Ctr, Manchester, NH USA. EM mark.gilbertson@va.gov NR 2 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2011 VL 72 IS 5 BP 725 EP 725 DI 10.4088/JCP.11lr06851a PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 772NM UT WOS:000291240600026 ER PT J AU Ding, A Abujudeh, H Novelline, RA AF Ding, Alexander Abujudeh, Hani Novelline, Robert A. TI DIAGNOSING CERVICAL SPINE INSTABILITY: ROLE OF THE POST-COMPUTED TOMOGRAPHY SCAN OUT-OF-COLLAR LATERAL RADIOGRAPH SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE cervical spine CT; spine trauma; out-of-collar radiograph; cervical instability; emergency radiology ID BLUNT TRAUMA PATIENTS; CLEARANCE; INJURY; RULE; CT AB Background: Cervical spine injuries may have devastating neurological consequences, which makes accurate diagnosis of injury a key part of the trauma evaluation. Imaging plays a significant role in making the diagnosis and guiding management. Current American College of Radiology Appropriateness Criteria guidelines recommend computed tomography (CT) of the cervical spine with multi-planar reformats as the highest-rated imaging examination for patients meeting clinical criteria, without subsequent need for further imaging with a negative scan in a neurologically intact and non-obtunded patient. Although CT is fast and accurate for evaluation of bony injury, it may overlook ligamentous injury. Objective and Case Report: We report a case in which ligamentous instability was demonstrated as subluxation with an out-of-collar lateral radiograph after a CT scan showed no subluxation or fracture in a patient without neurological deficits. Our Radiology Department routinely performs an out-of-collar lateral radiograph after a negative CT scan, and this case suggests that there may be an important role for this practice. Conclusion: Magnetic resonance is the optimal study for soft tissue and ligamentous evaluation; however, a simple lateral out-of-collar radiograph after CT clearance, in an otherwise neurologically intact and non-obtunded patient, may be a quick and cost-effective means to assess for instability of the cervical spine. (C) 2011 Elsevier Inc. C1 [Ding, Alexander; Abujudeh, Hani; Novelline, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Ding, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,FND-216, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2011 VL 40 IS 5 BP 518 EP 521 DI 10.1016/j.jemermed.2010.11.039 PG 4 WC Emergency Medicine SC Emergency Medicine GA 771BN UT WOS:000291132300007 PM 21269791 ER PT J AU Platz, E Liteplo, A Hurwitz, S Hwang, J AF Platz, Elke Liteplo, Andrew Hurwitz, Shelley Hwang, James TI ARE LIVE INSTRUCTORS REPLACEABLE? COMPUTER VS. CLASSROOM LECTURES FOR EFAST TRAINING SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency ultrasound; EFAST; education; e-learning; blended learning ID FOCUSED ASSESSMENT; SONOGRAPHY; ULTRASOUND; EDUCATION AB Background: The EFAST (extended focused assessment with sonography for trauma) is part of the recommended curriculum for Emergency Medicine and Surgery residents. Computer-based lectures may represent a time-efficient alternative to traditional lectures. Objectives: Our hypothesis was that computer lectures in basic ultrasound and the EFAST are not inferior to classroom lectures in test score improvement for residents with or without prior training. Methods: First-year Emergency Medicine and Surgery residents were enrolled and completed a pre-test. Subjects were then randomized into a classroom group, which attended traditional lectures, and a computer group, which listened to narrated lectures on computers. After the didactic training, all subjects completed a post-test. Results: Forty-four subjects completed the study: 64% were General Surgery residents, 66% were male. Overall, mean test score improvements were higher in the classroom than in the computer group (28.0% vs. 18.4%). In 25 residents without prior training, mean improvements in the computer and classroom groups were 25% and 27%, respectively. The 95% confidence limit around the difference was 9%, falling within the a priori non-inferiority range of 10%, and consistent with non inferiority of computer-based lectures. In 19 residents with prior training, mean test score improvements for the computer and classroom groups were 13% and 29%, respectively. The 95% confidence limit of 24% exceeded the noninferiority range, consistent with inferiority of computer-based lectures. Conclusions: Computer-based lectures are not inferior to classroom lectures and may represent a worthwhile substitution in subjects without prior ultrasound education. Our data suggest that didactic ultrasound training through classroom lectures is more effective than computer-based lectures in individuals with prior training. (C) 2011 Elsevier Inc. C1 [Platz, Elke; Hwang, James] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Platz, Elke; Liteplo, Andrew; Hurwitz, Shelley; Hwang, James] Harvard Univ, Sch Med, Boston, MA USA. [Liteplo, Andrew] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hurwitz, Shelley] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Platz, E (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville House, Boston, MA 02115 USA. FU Department of Emergency Medicine, Brigham; Women's Hospital, Boston, Massachusetts FX This study was generously supported by two faculty seed grants from the Department of Emergency Medicine, Brigham and Women's Hospital, Boston, Massachusetts. NR 11 TC 12 Z9 12 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2011 VL 40 IS 5 BP 534 EP 538 DI 10.1016/j.jemermed.2009.08.030 PG 5 WC Emergency Medicine SC Emergency Medicine GA 771BN UT WOS:000291132300010 PM 19892506 ER PT J AU Hayes, JP LaBar, KS McCarthy, G Selgrade, E Nasser, J Dolcos, F Morey, RA AF Hayes, Jasmeet Pannu LaBar, Kevin S. McCarthy, Gregory Selgrade, Elizabeth Nasser, Jessica Dolcos, Florin Morey, Rajendra A. CA VISN 6 Mid-Atlantic MIRECC Workgrp TI Reduced hippocampal and amygdala activity predicts memory distortions for trauma reminders in combat-related PTSD SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE fMRI; Gist; Contextual memory; Military; Subsequent memory paradigm; Precuneus ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; CORTICOLIMBIC BLOOD-FLOW; SCRIPT-DRIVEN IMAGERY; MEDIAL TEMPORAL-LOBE; FUZZY-TRACE THEORY; FALSE RECOGNITION; AUTOBIOGRAPHICAL MEMORY; NEURAL SYSTEMS; FMRI AB Neurobiological models of posttraumatic stress disorder (PTSD) suggest that altered activity in the medial temporal lobes (MTL) during encoding of traumatic memories contribute to the development and maintenance of the disorder. However, there is little direct evidence in the PTSD literature to support these models. The goal of the present study was to examine MTL activity during trauma encoding in combat veterans using the subsequent memory paradigm. Fifteen combat veterans diagnosed with PTSD and 14 trauma-exposed control participants viewed trauma-related and neutral pictures while undergoing event-related fMRI. Participants returned one week after scanning for a recognition memory test. Region-of-interest (ROI) and voxel-wise whole brain analyses were conducted to examine the neural correlates of successful memory encoding. Patients with PTSD showed greater false alarm rates for novel lures than the trauma-exposed control group, suggesting reliance on gist-based representations in lieu of encoding contextual details. Imaging analyses revealed reduced activity in the amygdala and hippocampus in PTSD patients during successful encoding of trauma-related stimuli. Reduction in left hippocampal activity was associated with high arousal symptoms on the Clinician-Administered PTSD Scale (CAPS). The behavioral false alarm rate for traumatic stimuli co-varied with activity in the bilateral precuneus. These results support neurobiological theories positing reduced hippocampal activity under conditions of high stress and arousal. Reduction in MTL activity for successfully encoded Stimuli and increased precuneus activity may underlie reduced stimulus-specific encoding and greater gist memory in patients with PTSD, leading to maintenance of the disorder. Published by Elsevier Ltd. C1 [Morey, Rajendra A.] Duke Univ, Med Ctr, Duke UNC Brain Imaging & Anal Ctr, Durham, NC 27710 USA. [Hayes, Jasmeet Pannu] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Hayes, Jasmeet Pannu] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Hayes, Jasmeet Pannu; Morey, Rajendra A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Hayes, Jasmeet Pannu; McCarthy, Gregory; Selgrade, Elizabeth; Nasser, Jessica; Morey, Rajendra A.] Durham VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Durham, NC USA. [McCarthy, Gregory] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [LaBar, Kevin S.] Duke Univ, Ctr Cognit Neurosci, Durham, NC 27710 USA. [Dolcos, Florin] Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. [Dolcos, Florin] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA. RP Morey, RA (reprint author), Duke Univ, Med Ctr, Duke UNC Brain Imaging & Anal Ctr, Box 3918, Durham, NC 27710 USA. EM Rajendra.morey@duke.edu FU Department of Veterans Affairs, Mental Illness Research Education and Clinical Center (MIRECC) [K23 MH073091, K23 MH084013]; U.S. National Institutes of Health [2 P01 NS041328] FX This work was supported by the Department of Veterans Affairs, Mental Illness Research Education and Clinical Center (MIRECC) Grant for Post-Deployment Mental Health, National Institute of Mental Health Grants K23 MH073091 and K23 MH084013, and U.S. National Institutes of Health grant 2 P01 NS041328. These funding sources had no further role in the study design, collection, analysis, interpretation of the data, writing of the report, or the decision to submit the paper for publication. NR 76 TC 47 Z9 50 U1 5 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD MAY PY 2011 VL 45 IS 5 BP 660 EP 669 DI 10.1016/j.jpsychires.2010.10.007 PG 10 WC Psychiatry SC Psychiatry GA 771OR UT WOS:000291171100012 PM 21047644 ER PT J AU Martin, LF Olincy, A Ross, RG Du, YPP Singel, D Shatti, S Tregellas, JR AF Martin, Laura Frances Olincy, Ann Ross, Randy G. Du, Yiping P. Singel, Debra Shatti, Shireen Tregellas, Jason R. TI Cerebellar hyperactivity during smooth pursuit eye movements in bipolar disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Magnetic resonance imaging; Uvula; Cerebellum; Hippocampus; Affective symptoms; Depression ID REGIONAL CEREBRAL METABOLISM; COGNITIVE-AFFECTIVE SYNDROME; SCHIZOPHRENIC-PATIENTS; NEUROLEPTIC TREATMENT; UNAFFECTED RELATIVES; UNIPOLAR DEPRESSION; GLUCOSE-METABOLISM; PSYCHOTIC-PATIENTS; MAJOR DEPRESSION; BRAIN ACTIVATION AB Introduction: Smooth pursuit eye movements (SPEM) are abnormal in individuals with schizophrenia and individuals with bipolar disorder. Functional imaging methods have revealed greater hippocampal activity and less frontotemporal, visual, and posterior cerebellar activity in individuals with schizophrenia when performing a SPEM task. The underlying neurobiology of SPEM deficits in bipolar disorder is unknown. Methods: Functional magnetic resonance imaging at 3T was performed on fourteen subjects with bipolar disorder and 14 subjects without psychiatric illness during a block design SPEM task. Clinical measures were assessed on the day of testing and related to imaging measures. Results: Subjects with bipolar disorder had greater hemodynamic response than control subjects in cerebellar vermis. Responses were associated with levels of depressive symptoms on the day of study. Discussion: Increased cerebellar vermis activity during the smooth pursuit eye movement task in individuals with bipolar disorder further implicates cerebellar involvement in bipolar disorder. Increased hemodynamic response within the hippocampus was not seen in these individuals and may be a finding specific to schizophrenia. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Martin, Laura Frances; Olincy, Ann; Ross, Randy G.; Du, Yiping P.; Singel, Debra; Shatti, Shireen; Tregellas, Jason R.] Univ Colorado Denver, Sch Med, Aurora, CO 80045 USA. [Tregellas, Jason R.] Eastern Colorado Hlth Care Syst, Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80220 USA. RP Martin, LF (reprint author), Univ Colorado Denver, Sch Med, Mail Stop F546,13001 E 17th Pl, Aurora, CO 80045 USA. EM laura.martin@ucdenver.edu RI Tregellas, Jason/J-3637-2015 FU Research Service of the Denver VAMC; NARSAD; [829/RCD- 006-05S] FX This work was supported by the Research Service of the Denver VAMC and Program/Study No: 829/RCD- 006-05S (LFM, JRT) and NARSAD (LFM). Neither the Department of Veterans Affairs nor NARSAD had any further role in study design, data collection, data analysis, manuscript preparation or decision to publish the manuscript. NR 97 TC 4 Z9 4 U1 8 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD MAY PY 2011 VL 45 IS 5 BP 670 EP 677 DI 10.1016/j.jpsychires.2010.09.015 PG 8 WC Psychiatry SC Psychiatry GA 771OR UT WOS:000291171100013 PM 20950824 ER PT J AU Garbelotti, K AF Garbelotti, Kelly TI PHANTOM LIMB PAIN RELIEVED WITH PULSED RADIO FREQUENCY ENERGY (PRFE) THERAPY SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 [Garbelotti, Kelly] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM kelly.garbelotti@va.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2011 VL 38 IS 3 SU S MA 5426 BP S83 EP S83 PG 1 WC Nursing SC Nursing GA 772LI UT WOS:000291235000232 ER PT J AU McCarthy, MW Giannino, K AF McCarthy, Maureen W. Giannino, Kerri TI COMPLEX ABDOMINAL WOUNDS SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 [McCarthy, Maureen W.; Giannino, Kerri] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mmccarthy29@partners.org; KmGiannino@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 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2011 VL 38 IS 3 SU S MA 5148 BP S26 EP S26 PG 1 WC Nursing SC Nursing GA 772LI UT WOS:000291235000067 ER PT J AU Zulkowski, K Ayello, EA Berlowitz, D Parker, VA Lukas, CV Niederhauser, A AF Zulkowski, Karen Ayello, Elizabeth A. Berlowitz, Dan Parker, Victoria A. Lukas, Carol VanDeusen Niederhauser, Andrea TI PREVENTING PRESSURE ULCERS IN HOSPITALS: DEVELOPMENT OF A QUALITY IMPROVEMENT TOOLKIT SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 [Zulkowski, Karen] Montana State Univ Bozeman, Red Lodge, MT 59068 USA. [Ayello, Elizabeth A.] Excelsior Coll Sch Nursing, New York, NY USA. [Berlowitz, Dan] Bedford VA, Bedford, MA USA. [Parker, Victoria A.] Boston Univ, Boston, MA 02215 USA. [Lukas, Carol VanDeusen; Niederhauser, Andrea] VA Boston Healthcare Syst, Boston, MA USA. EM KarenZ@montatta.edu; elizabeth@ayello.com; Dan.Berlowitz@va.gov; vparker@bu.edu; Carol.VanDeusenLukas@va.gov; anieder@bu.edu NR 1 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2011 VL 38 IS 3 SU S MA 5261 BP S51 EP S51 PG 1 WC Nursing SC Nursing GA 772LI UT WOS:000291235000141 ER PT J AU Lorch, JH Goloubeva, O Posner, MR AF Lorch, Jochen H. Goloubeva, Olga Posner, Marshall R. TI How does TPF improve survival over PF? reply SO LANCET ONCOLOGY LA English DT Letter C1 [Lorch, Jochen H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goloubeva, Olga] Univ Maryland, Med Sch Teaching Facil, Div Biostat, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Posner, Marshall R.] Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol Med Oncol, New York, NY USA. RP Lorch, JH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jochen_lorch@dfci.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2011 VL 12 IS 5 BP 421 EP 422 PG 2 WC Oncology SC Oncology GA 771FQ UT WOS:000291143000012 ER PT J AU Belov, VV Bonab, AA Fischman, AJ Heartlein, M Calias, P Papisov, MI AF Belov, Vasily V. Bonab, Ali A. Fischman, Alan J. Heartlein, Michael Calias, Pericles Papisov, Mikhail I. TI Iodine-124 as a Label for Pharmacological PET Imaging SO MOLECULAR PHARMACEUTICS LA English DT Article DE Iodine-124; Positron Emission Tomography; Pharmacology; Pharmacokinetics; Biopharmaceuticals; Macromolecules ID POSITRON-EMISSION-TOMOGRAPHY; PERFORMANCE EVALUATION; SPATIAL-RESOLUTION; SCANNER; SYSTEM; SENSITIVITY; EMITTERS AB With the growing number of biotechnology products and drug delivery systems entering preclinical and clinical studies, pharmacological imaging studies with PET play an increasingly significant role. Such studies often require investigation of slow and complex pharmacokinetics (PK). This suggests labeling of the drug candidate with radionuclides that have long physical half-lives. Among the currently available PET positron emitters, (124)1 has the longest physical half-life (4.2 days). This, combined with the well-investigated behavior of iodine in vivo, makes (124)I very attractive for pharmacological studies. However, the high energy of the positrons emitted by (124)I and the presence of single photons in the (124)I emission can potentially introduce limitations in the quantitative analysis of the images. The objective of this research was to determine whether the use of (124)I as a PET label provides data quality suitable for PK studies. The study was carried out using MicroPET P4 scanner (Siemens/Concorde Microsystems). Spatial resolution, count-rate performance, sensitivity and scatter fraction were measured using a line source and a cylindrical phantom. Model animal studies in rats and cynomolgus monkeys were carried out using human recombinant proteins. The proteins were labeled with (124)I, up to 185 MBq/mg. The transaxial and axial spatial resolutions in the center of the camera were satisfactory and higher for OSEM3D/MAP than FORE-2DFBP (FWHM 2.52 vs 3.31 mm, and 3.10 vs 3.69 mm). Linearity of the true coincidence count-rate was observed up to 44 MBq. Animal studies demonstrated excellent delineation and resolution of even very small organs. At optimal doses, 2-10 MBq per animal for rodents and 4-10 MBq per kg of body weight for larger animals, the quality of numerical data was appropriate for PK analysis in all experimental timeframes from minutes (dynamic studies) to 10 days. Overall, the data suggest that (124)I is an excellent label for quantitative pharmacological PET imaging studies. C1 [Belov, Vasily V.; Bonab, Ali A.; Papisov, Mikhail I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Belov, Vasily V.; Bonab, Ali A.; Fischman, Alan J.; Papisov, Mikhail I.] Harvard Univ, Sch Med, Boston, MA USA. [Belov, Vasily V.; Bonab, Ali A.; Fischman, Alan J.; Papisov, Mikhail I.] Shriners Burns Hosp Boston, Boston, MA USA. [Heartlein, Michael; Calias, Pericles] Shire Human Genet Therapy, Lexington, MA USA. RP Papisov, MI (reprint author), Massachusetts Gen Hosp, Dept Radiol, Bartlett Hall 500R,55 Fruit St, Boston, MA 02114 USA. EM papisov@helix.mgh.harvard.edu OI Papisov, Mikhail/0000-0003-4716-2122 FU Shire HGT (Cambridge, MA) FX This work was supported in part by Shire HGT (Cambridge, MA), which also provided model proteins. NR 34 TC 19 Z9 19 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD MAY-JUN PY 2011 VL 8 IS 3 BP 736 EP 747 DI 10.1021/mp100358f PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 772KW UT WOS:000291233800011 PM 21361362 ER PT J AU Hong, IH Jeong, YW Shin, T Hyun, SH Park, JK Ki, MR Han, SY Park, SI Lee, JH Lee, EM Kim, AY You, SY Hwang, WS Jeong, KS AF Hong, Il-Hwa Jeong, Yeon-Woo Shin, Taeyoung Hyun, Sang-Hwan Park, Jin-Kyu Ki, Mi-Ran Han, Seon-Young Park, Se-Il Lee, Ji-Hyun Lee, Eun-Mi Kim, Ah-Young You, Sang-Young Hwang, Woo-Suk Jeong, Kyu-Shik TI Morphological Abnormalities, Impaired Fetal Development and Decrease in Myostatin Expression Following Somatic Cell Nuclear Transfer in Dogs SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article ID BECKWITH-WIEDEMANN-SYNDROME; SKELETAL-MUSCLE; MAMMALIAN DEVELOPMENT; GROWTH-HORMONE; IN-VITRO; CATTLE; DIFFERENTIATION; EMBRYOS; CLONING; MICE AB Several mammals, including dogs, have been successfully cloned using somatic cell nuclear transfer (SCNT), but the efficiency of generating normal, live offspring is relatively low. Although the high failure rate has been attributed to incomplete reprogramming of the somatic nuclei during the cloning process, the exact cause is not fully known. To elucidate the cause of death in cloned offspring, 12 deceased offspring cloned by SCNT were necropsied. The clones were either stillborn just prior to delivery or died with dyspnea shortly after birth. On gross examination, defects in the anterior abdominal wall and increased heart and liver sizes were found. Notably, a significant increase in muscle mass and macroglossia lesions were observed in deceased SCNT-cloned dogs. Interestingly, the expression of myostatin, a negative regulator of muscle growth during embryogenesis, was down-regulated at the mRNA level in tongues and skeletal muscles of SCNT-cloned dogs compared with a normal dog. Results of the present study suggest that decreased expression of myostatin in SCNT-cloned dogs may be involved in morphological abnormalities such as increased muscle mass and macroglossia, which may contribute to impaired fetal development and poor survival rates. C1 [Hong, Il-Hwa; Park, Jin-Kyu; Ki, Mi-Ran; Han, Seon-Young; Park, Se-Il; Lee, Eun-Mi; Kim, Ah-Young; You, Sang-Young; Jeong, Kyu-Shik] Kyungpook Natl Univ, Coll Vet Med, Taegu, South Korea. [Jeong, Yeon-Woo; Shin, Taeyoung; Hwang, Woo-Suk] SooAm Biotech Res Fdn, Seoul, South Korea. [Hyun, Sang-Hwan] Chungbuk Natl Univ, Coll Vet Med, Lab Vet Biotechnol, Cheongju, South Korea. [Lee, Ji-Hyun] Harvard Univ, Sch Med, Dept Genet, Ctr Human Genet Res,Massachusetts Gen Hosp, Boston, MA USA. [Jeong, Kyu-Shik] Kyungpook Natl Univ, Stem Cell Therapeut Res Inst, Taegu, South Korea. RP Jeong, KS (reprint author), Kyungpook Natl Univ, Coll Vet Med, Taegu, South Korea. EM hwangws@sooam.org; jeongks@knu.ac.kr FU H Bion, Republic of Korea FX This research was supported by a grant from H Bion, Republic of Korea. NR 38 TC 9 Z9 9 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD MAY PY 2011 VL 78 IS 5 BP 337 EP 346 DI 10.1002/mrd.21309 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 772CY UT WOS:000291210200005 PM 21520324 ER PT J AU Finch, TH Chae, SR Shafaee, MN Siegel, KR Ali, MK Tomei, R Panjabi, R Kishore, SP AF Finch, Thomas H. Chae, Sae-Rom Shafaee, Maryam N. Siegel, Karen R. Ali, Mohammed K. Tomei, Rachelle Panjabi, Rajesh Kishore, Sandeep P. TI Role of Students in Global Health Delivery SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article ID EXPERIENCE AB What role do students have in global health activities? On one hand, students have much to offer, including innovative ideas, fresh knowledge and perspective, and inspiring energy. At the same time, students lack technical credentials and may drain resources from host communities. Here, we examine the dynamic, contemporary roles of students in global health activities, including health delivery. We focus on 3 themes that guide engagement: (I) fostering an enabling policy environment (eg, toward greater health equity); (2) understanding and working within the local context and governments' needs; and (3) leading bidirectional partnerships. We next study the implications of short-term exposure and long-term engagement programs. We conclude with 4 recommendations on how to better equip students to engage in the next frontier of global health education and future action. Mt Sinai J Med 78:373-381, 2011. (C) 2011 Mount Sinai School of Medicine C1 [Kishore, Sandeep P.] Weill Cornell Rockefeller Sloan Kettering Triinst, New York, NY USA. [Finch, Thomas H.] Weill Cornell Med Coll, New York, NY USA. [Chae, Sae-Rom] Univ Illinois, Coll Med, Chicago, IL USA. [Shafaee, Maryam N.] New York Presbyterian Hosp, Dept Med, New York, NY USA. [Siegel, Karen R.] Emory Univ, Laney Grad Sch, Atlanta, GA 30322 USA. [Siegel, Karen R.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Ali, Mohammed K.] Emory Univ, Dept Global Hlth, Atlanta, GA 30322 USA. [Tomei, Rachelle] Weill Cornell Med Coll, Surg Phys Assistant Program, New York, NY USA. [Panjabi, Rajesh] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Panjabi, Rajesh] Tiyatien Hlth Liberia, Boston, MA USA. RP Kishore, SP (reprint author), Weill Cornell Rockefeller Sloan Kettering Triinst, New York, NY USA. EM sunny.kishore@gmail.com FU NIGMS NIH HHS [T32 GM007739] NR 27 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD MAY-JUN PY 2011 VL 78 IS 3 BP 373 EP 381 DI 10.1002/msj.20254 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 772LW UT WOS:000291236400008 PM 21598264 ER PT J AU Weintraub, D Burn, DJ AF Weintraub, Daniel Burn, David J. TI Parkinson's Disease: The Quintessential Neuropsychiatric Disorder SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's; dementia; neuropsychiatric; depression; psychosis ID DEEP-BRAIN-STIMULATION; IMPULSE CONTROL DISORDERS; SLEEP BEHAVIOR DISORDER; RANDOMIZED CONTROLLED-TRIAL; VOXEL-BASED MORPHOMETRY; SUBTHALAMIC NUCLEUS STIMULATION; EXCESSIVE DAYTIME SLEEPINESS; MILD COGNITIVE IMPAIRMENT; PLACEBO-CONTROLLED TRIAL; DRUG-INDUCED PSYCHOSIS AB Although diagnosed by characteristic motor features, Parkinson's disease may be preceded, and is frequently accompanied by, a wide range of cognitive and neuropsychiatric features. In addition to the most commonly studied disorders of dementia, depression, and psychosis, other relatively common and clinically significant psychiatric complications include impulse control disorders, anxiety symptoms, disorders of sleep and wakefulness, and apathy. These problems may be underrecognized and are frequently under-treated. The emergent focus on nonmotor aspects of Parkinson's disease over the past quarter of a century is highlighted by a nonlinear increase in the number of articles published devoted to this topic. Although the development of newer antidepressants, atypical antipsychotics, and cholinesterase inhibitors in recent years has had a positive benefit on the management of these troublesome and distressing symptoms, responses are frequently suboptimal, and this remains an area of major unmet therapeutic need. (C) 2011 Movement Disorder Society C1 [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr PADRECC & MIRE, Philadelphia, PA USA. [Burn, David J.] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Burn, David J.] Newcastle Univ, Clin Ageing Res Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU NIMH NIH HHS [K23 MH067894] NR 186 TC 115 Z9 117 U1 6 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2011 VL 26 IS 6 BP 1022 EP 1031 DI 10.1002/mds.23664 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 774AO UT WOS:000291353900011 PM 21626547 ER PT J AU Shoulson, I Young, AB AF Shoulson, Ira Young, Anne B. TI Milestones in Huntington Disease SO MOVEMENT DISORDERS LA English DT Review DE Huntington disease; experimental therapeutics; review ID PREIMPLANTATION GENETIC DIAGNOSIS; HISTONE DEACETYLASE INHIBITORS; CAG REPEAT LENGTH; AGE-OF-ONSET; MUTANT HUNTINGTIN; COENZYME Q(10); PREDICT-HD; PROJECTION NEURONS; FUNCTIONAL-ANATOMY; DEPENDENT MANNER AB There have been extraordinary advances in our knowledge of the underlying gene, the protein it encodes, various models of disease, and potential targets for effective therapies for Huntington disease. Huntington disease research has increased exponentially in the past 25 years, and we now understand many of the molecular mechanisms underlying the disease. Still, more work needs to be done before we have a full understanding of the pathophysiology of the disease. Clinical research on biomarkers and clinical trials on potential neuroprotective agents are underway. Here we review our progress in these areas over the last 25 years and speculate on what the next 25 years may hold. (C) 2011 Movement Disorder Society C1 [Shoulson, Ira] Georgetown Univ, Program Regulatory Sci & Med, Washington, DC USA. [Young, Anne B.] Harvard Univ, Sch Med, Boston, MA USA. [Young, Anne B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shoulson, I (reprint author), 1351 Mt Hope Ave,Suite 218, Rochester, NY 14620 USA. EM Ira.Shoulson@ctcc.rochester.edu NR 81 TC 36 Z9 37 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2011 VL 26 IS 6 BP 1127 EP 1133 DI 10.1002/mds.23685 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 774AO UT WOS:000291353900020 PM 21626556 ER PT J AU Kim, YW Grossmann, TN Verdine, GL AF Kim, Young-Woo Grossmann, Tom N. Verdine, Gregory L. TI Synthesis of all-hydrocarbon stapled alpha-helical peptides by ring-closing olefin metathesis SO NATURE PROTOCOLS LA English DT Article ID HYDROGEN-BOND SURROGATE; COUPLING REAGENTS; BH3 HELIX; ASYMMETRIC-SYNTHESIS; EFFICIENT SYNTHESIS; HIGHLY EFFICIENT; CONFORMATION; INHIBITOR; ACTIVATION; 6-CL-HOBT AB This protocol provides a detailed procedure for the preparation of stapled alpha-helical peptides, which have proven their potential as useful molecular probes and as next-generation therapeutics. Two crucial features of this protocol are (i) the construction of peptide substrates containing hindered alpha-methyl, alpha-alkenyl amino acids and (ii) the ring-closing olefin metathesis (RCM) of the resulting resin-bound peptide substrates. The stapling systems described in this protocol, namely bridging one or two turns of an alpha-helix, are highly adaptable to most peptide sequences, resulting in favorable RCM kinetics, helix stabilization and promotion of cellular uptake. C1 [Kim, Young-Woo; Grossmann, Tom N.; Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Kim, Young-Woo; Grossmann, Tom N.; Verdine, Gregory L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Kim, Young-Woo; Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. [Verdine, Gregory L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. EM gregory_verdine@harvard.edu RI Grossmann, Tom/A-4175-2015 OI Grossmann, Tom/0000-0003-0179-4116 FU Harvard and Dana-Farber Program in Cancer Chemical Biology; Deutsche Akademie der Naturforscher Leopoldina [LPDS 2009-2] FX This research was supported by the Harvard and Dana-Farber Program in Cancer Chemical Biology. T.N.G. is grateful for a fellowship from Deutsche Akademie der Naturforscher Leopoldina (LPDS 2009-2). NR 40 TC 127 Z9 127 U1 6 U2 68 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD MAY PY 2011 VL 6 IS 6 BP 761 EP 771 DI 10.1038/nprot.2011.324 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 772EZ UT WOS:000291218300004 PM 21637196 ER PT J AU Zhao, J Wu, H Khosravi, M Cui, HJ Qian, XX Kelly, JA Kaufman, KM Langefeld, CD Williams, AH Comeau, ME Ziegler, JT Marion, MC Adler, A Glenn, SB Alarcon-Riquelme, ME Pons-Estel, BA Harley, JB Bae, SC Bang, SY Cho, SK Jacob, CO Vyse, TJ Niewold, TB Gaffney, PM Moser, KL Kimberly, RP Edberg, JC Brown, EE Alarcon, GS Petri, MA Ramsey-Goldman, R Vila, LM Reveille, JD James, JA Gilkeson, GS Kamen, DL Freedman, BI Anaya, JM Merrill, JT Criswell, LA Scofield, RH Stevens, AM Guthridge, JM Chang, DM Song, YW Park, JA Lee, EY Boackle, SA Grossman, JM Hahn, BH Goodship, THJ Cantor, RM Yu, CY Shen, N Tsao, BP AF Zhao, Jian Wu, Hui Khosravi, Melanie Cui, Huijuan Qian, Xiaoxia Kelly, Jennifer A. Kaufman, Kenneth M. Langefeld, Carl D. Williams, Adrienne H. Comeau, Mary E. Ziegler, Julie T. Marion, Miranda C. Adler, Adam Glenn, Stuart B. Alarcon-Riquelme, Marta E. Pons-Estel, Bernardo A. Harley, John B. Bae, Sang-Cheol Bang, So-Young Cho, Soo-Kyung Jacob, Chaim O. Vyse, Timothy J. Niewold, Timothy B. Gaffney, Patrick M. Moser, Kathy L. Kimberly, Robert P. Edberg, Jeffrey C. Brown, Elizabeth E. Alarcon, Graciela S. Petri, Michelle A. Ramsey-Goldman, Rosalind Vila, Luis M. Reveille, John D. James, Judith A. Gilkeson, Gary S. Kamen, Diane L. Freedman, Barry I. Anaya, Juan-Manuel Merrill, Joan T. Criswell, Lindsey A. Scofield, R. Hal Stevens, Anne M. Guthridge, Joel M. Chang, Deh-Ming Song, Yeong Wook Park, Ji Ah Lee, Eun Young Boackle, Susan A. Grossman, Jennifer M. Hahn, Bevra H. Goodship, Timothy H. J. Cantor, Rita M. Yu, Chack-Yung Shen, Nan Tsao, Betty P. CA BIOLUPUS Network GENLES Network TI Association of Genetic Variants in Complement Factor H and Factor H-Related Genes with Systemic Lupus Erythematosus Susceptibility SO PLOS GENETICS LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; DENSE DEPOSIT DISEASE; MACULAR DEGENERATION; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; ALLOTYPIC VARIANT; INFLUENCES RISK; CFH; C3; HAPLOTYPE; POLYMORPHISMS AB Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, P(meta) = 6.6x10(-8), OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, P(meta) = 2.9x10(-7), OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a similar to 146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1 Delta), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1D (P(meta) = 3.2x10(-7), OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (P(meta) = 3.5x10(-4), OR = 1.14). These results suggested that the CFHR3-1D deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE. C1 [Zhao, Jian; Wu, Hui; Khosravi, Melanie; Grossman, Jennifer M.; Hahn, Bevra H.; Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA. [Cui, Huijuan; Qian, Xiaoxia; Shen, Nan] Inst Hlth Sci, Joint Mol Rheumatol Lab, Shanghai, Peoples R China. [Cui, Huijuan; Qian, Xiaoxia; Shen, Nan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Biol Sci, Shanghai Renji Hosp, Shanghai 200030, Peoples R China. [Cui, Huijuan; Qian, Xiaoxia; Shen, Nan] Chinese Acad Sci, Shanghai, Peoples R China. [Kelly, Jennifer A.; Kaufman, Kenneth M.; Adler, Adam; Glenn, Stuart B.; Alarcon-Riquelme, Marta E.; Gaffney, Patrick M.; Moser, Kathy L.; James, Judith A.; Scofield, R. Hal; Guthridge, Joel M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Kaufman, Kenneth M.; Scofield, R. Hal] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Langefeld, Carl D.; Williams, Adrienne H.; Comeau, Mary E.; Ziegler, Julie T.; Marion, Miranda C.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Wake Forest, NC USA. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta Andalucia, Ctr Genom & Oncol Res, Granada, Spain. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Bae, Sang-Cheol; Bang, So-Young; Cho, Soo-Kyung] Hanyang Univ Hosp Rheumat Dis, Dept Rheumatol, Seoul, South Korea. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Vyse, Timothy J.] Kings Coll London, Div Genet & Mol Med, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Immunol, London WC2R 2LS, England. [Niewold, Timothy B.] Univ Chicago, Rheumatol Sect, Chicago, IL 60637 USA. [Niewold, Timothy B.] Univ Chicago, Gwen Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA. [Kimberly, Robert P.; Edberg, Jeffrey C.; Brown, Elizabeth E.; Alarcon, Graciela S.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. [Petri, Michelle A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Ramsey-Goldman, Rosalind] Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Chicago, IL 60611 USA. [Vila, Luis M.] Univ Puerto Rico Med Sci Campus, Dept Med, Div Rheumatol, San Juan, PR USA. [Reveille, John D.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [James, Judith A.; Scofield, R. Hal] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Gilkeson, Gary S.; Kamen, Diane L.] Med Univ S Carolina, Div Rheumatol, Charleston, SC 29425 USA. [Freedman, Barry I.] Wake Forest Univ Hlth Sci, Dept Internal Med, Winston Salem, NC USA. [Anaya, Juan-Manuel] Univ Rosario, Ctr Autoimmune Dis Res, Bogota, Colombia. [Merrill, Joan T.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Criswell, Lindsey A.] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA. [Stevens, Anne M.] Univ Washington, Dept Pediat, Div Rheumatol, Seattle, WA 98195 USA. [Stevens, Anne M.] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA. [Chang, Deh-Ming] Natl Def Med Ctr, Taipei, Taiwan. [Song, Yeong Wook; Park, Ji Ah; Lee, Eun Young] Seoul Natl Univ, Div Rheumatol, Seoul, South Korea. [Boackle, Susan A.] Univ Colorado Denver, Sch Med, Div Rheumatol, Aurora, CO USA. [Adler, Adam; Goodship, Timothy H. J.] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Cantor, Rita M.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA. [Yu, Chack-Yung] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. RP Zhao, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90095 USA. EM btsao@mednet.ucla.edu RI Yu, Chack-Yung/E-4360-2011; Song, Yeong Wook/J-2765-2012; Lee, Eun Young/J-5594-2012; Zhao, Jian/E-6292-2012; D'Alfonso, Sandra/K-7295-2014; Anaya, Juan-Manuel/J-1960-2016; OI Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154; Niewold, Timothy/0000-0003-3532-6660; D'Alfonso, Sandra/0000-0002-3983-9925; Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario, Biblioteca/0000-0003-3491-9392; Kimberly, Robert/0000-0002-5330-3086; Silva, Berta/0000-0001-6579-5068 FU US National Institutes of Health [R01AR043814, R01AR043274, R01AI063274, N01AR62277, R37AI024717, R01AR042460, P01AI083194, P20RR020143, P01AR049084, R01AR33062, K08AI083790, LRPAI071651, R01CA141700, RC1AR058621, UL1RR024999, R01AR051545-01A2, P30AR053483, AR43727, UL1RR025005, K24AR002138, P602AR30692, P01AR49084, UL1RR025741, P20RR015577, RC1AR058554, U19AI082714, N01AI50026, R21AI070304, P60AR053308, M01RR00079, UL1RR029882, P60AR049459, R01AR054459]; Arthritis National Research Foundation; Ministry for Health and Welfare, Republic of Korea [A080588]; MKE/KEIT [10035615]; US Department of Veterans Affairs; US Department of Defense [PR094002]; Lupus Research Institute; Alliance for Lupus Research; Arthritis Foundation; Lupus Foundation; Swedish Research Council; Swedish Association Against Rheumatism; King Gustaf Vth 80th Jubilee; Fundacion Instituto de Salud Carlos III [PS0900129]; Consejeria de Salud de Andalucia [PI-0012]; Welcome Trust; Arthritis Research UK; UK Medical Research Council [G0701325]; CTSA [I ULI RR025014-02]; National Center for Research Resources (NCRR); Kirkland Scholar Award; Federico Wilhelm Agricola Foundation; Networking Programmers European Science Foundation; ESF FX ` Support for this work was obtained from the US National Institutes of Health grants: R01AR043814 (BP Tsao), R01AR043274 (KL Moser), R01AI063274 (PM Gaffney), N01AR62277 (JB Harley), R37AI024717 (JB Harley), R01AR042460 (JB Harley), P01AI083194 (JB Harley), P20RR020143 (JB Harley), P01AR049084 (RP Kimberly), R01AR33062 (RP Kimberly, EE Brown), K08AI083790 (TB Niewold), LRPAI071651 (TB Niewold), R01CA141700 (ME Alarcon-Riquelme), RC1AR058621 (ME Alarcon-Riquelme) and UL1RR024999 (TB Niewold), R01AR051545-01A2 (AM Stevens), P30AR053483 (JA James and JM Guthridge), AR43727 (MA Petri), UL1RR025005 (MA Petri), K24AR002138 (R Ramsey-Goldman), P602AR30692 (R Ramsey-Goldman), P01AR49084 (R Ramsey-Goldman), UL1RR025741 (R Ramsey-Goldman), P20RR015577 (JA James), RC1AR058554 (JA James), U19AI082714 (JA James), N01AI50026 (JA James and JM Guthridge), R21AI070304 (SA Boackle), P60AR053308 (LA Criswell), M01RR00079 (LA Criswell), UL1RR029882 (GS Gilkeson and DL Kamen), P60AR049459 (GS Gilkeson and DL Kamen), and R01AR054459 (C-Y Yu). The first author (J Zhao) is an Eng Tan Scholar supported by the Arthritis National Research Foundation. This study was also supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (A080588; S-C Bae), Korean R&D Program of MKE/KEIT (10035615; YW Song), the Merit Award from the US Department of Veterans Affairs (JB Harley and GS Gilkeson), the US Department of Defense PR094002 (JB Harley), Lupus Research Institute (BP Tsao, AM Stevens, and TB Niewold), The Alliance for Lupus Research (KL Moser, TB Niewold, LA Criswell, and CO Jacob), the Arthritis National Research Foundation Eng Tan Scholar Award (TB Niewold), the Arthritis Foundation (AM Stevens and PM Gaffney), and the Lupus Foundation (AM Stevens). Additional funding awarded from the Swedish Research Council, Swedish Association Against Rheumatism, and the King Gustaf Vth 80th Jubilee. Foundation and the Fundacion Instituto de Salud Carlos III PS0900129 and the Consejeria de Salud de Andalucia PI-0012 (ME Alarcon-Riquelme), the Welcome Trust (TJ Vyse), Arthritis Research UK (TJ Vyse), UK Medical Research Council grant (G0701325; THJ Goodship), CTSA Grant Number I ULI RR025014-02 (AM Stevens) from the National Center for Research Resources (NCRR), Kirkland Scholar Award (LA Criswell and JA James), and Federico Wilhelm Agricola Foundation Research Grant (BA Pons-Estel). The work reported on in this publication has been in part financially supported by the ESF, in the framework of the Research Networking Programmers European Science Foundation - The Identification of Novel Genes and Biomarkers for Systemic Lupus Erythematosus (BIOLUPUS)-RNP-083. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 68 Z9 69 U1 3 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2011 VL 7 IS 5 AR e1002079 DI 10.1371/journal.pgen.1002079 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 769LI UT WOS:000291014600024 PM 21637784 ER PT J AU Tsai, AC Rosenlicht, NZ Jureidini, JN Parry, PI Spielmans, GI Healy, D AF Tsai, Alexander C. Rosenlicht, Nicholas Z. Jureidini, Jon N. Parry, Peter I. Spielmans, Glen I. Healy, David TI Aripiprazole in the Maintenance Treatment of Bipolar Disorder: A Critical Review of the Evidence and Its Dissemination into the Scientific Literature SO PLOS MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIALS; CLINICAL-PRACTICE GUIDELINES; CONTROLLED 18-MONTH TRIAL; CONFLICT-OF-INTEREST; I-DISORDER; DOUBLE-BLIND; LONG-TERM; MOOD STABILIZERS; PHARMACOLOGICAL-TREATMENT; PHARMACEUTICAL-INDUSTRY AB Background: Aripiprazole, a second-generation antipsychotic medication, has been increasingly used in the maintenance treatment of bipolar disorder and received approval from the U.S. Food and Drug Administration for this indication in 2005. Given its widespread use, we sought to critically review the evidence supporting the use of aripiprazole in the maintenance treatment of bipolar disorder and examine how that evidence has been disseminated in the scientific literature. Methods and Findings: We systematically searched multiple databases to identify double-blind, randomized controlled trials of aripiprazole for the maintenance treatment of bipolar disorder while excluding other types of studies, such as open-label, acute, and adjunctive studies. We then used a citation search to identify articles that cited these trials and rated the quality of their citations. Our evidence search protocol identified only two publications, both describing the results of a single trial conducted by Keck et al., which met criteria for inclusion in this review. We describe four issues that limit the interpretation of that trial as supporting the use of aripiprazole for bipolar maintenance: (1) insufficient duration to demonstrate maintenance efficacy; (2) limited generalizability due to its enriched sample; (3) possible conflation of iatrogenic adverse effects of abrupt medication discontinuation with beneficial effects of treatment; and (4) a low overall completion rate. Our citation search protocol yielded 80 publications that cited the Keck et al. trial in discussing the use of aripiprazole for bipolar maintenance. Of these, only 24 (30%) mentioned adverse events reported and four (5%) mentioned study limitations. Conclusions: A single trial by Keck et al. represents the entirety of the literature on the use of aripiprazole for the maintenance treatment of bipolar disorder. Although careful review identifies four critical limitations to the trial's interpretation and overall utility, the trial has been uncritically cited in the subsequent scientific literature. C1 [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. [Rosenlicht, Nicholas Z.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Rosenlicht, Nicholas Z.] San Francisco VA Med Ctr, San Francisco, CA USA. [Jureidini, Jon N.] Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia. [Parry, Peter I.] Flinders Univ S Australia, Div Mental Hlth, Child & Adolescent Mental Hlth Serv, Adelaide, SA 5001, Australia. [Spielmans, Glen I.] Metropolitan State Univ, Dept Psychol, St Paul, MN USA. [Healy, David] Cardiff Univ, Dept Psychol Med, Cardiff, S Glam, Wales. RP Tsai, AC (reprint author), Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. EM nicholas.rosenlicht@ucsf.edu RI Parry, Peter/G-7663-2015; OI Parry, Peter/0000-0003-1086-0138; Tsai, Alexander/0000-0001-6397-7917 FU Harvard University; Robert Wood Johnson Foundation Health and Society; Vanguard Healthcare FX The authors received no specific funding for this study. ACT received salary support as a Robert Wood Johnson Health and Society Scholar at Harvard University. No funding bodies had any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.; ACT receives salary support through the Robert Wood Johnson Foundation Health and Society Scholars Program. The Robert Wood Johnson Foundation's stated mission is to improve the health and health care of all Americans. NZR is a member of the National Physicians Alliance, a not-for-profit organisation whose stated primary goal is to restore physicians' primary emphasis on the core values of service, integrity, and advocacy. The National Physicians Alliance rejects funding from commercial health care interests and encourages its members to do the same. NZR, JNJ, and PIP are members of Healthy Skepticism, an international not-for-profit organisation whose stated aim is to improve health by reducing harm from misleading drug promotion; GIS joined Healthy Skepticism after this article was accepted for publication. GIS is a current shareholder (<$10,000) in a mutual fund, Vanguard Healthcare, that invests heavily in pharmaceutical companies. DH reports no links to pharmaceutical companies in the past 5 years. ACT is a former board member of the ethics committee, and former member, of the National Physicians Alliance. ACT and NZR are former members of No Free Lunch, a not-for-profit organisation whose stated mission was to encourage health care providers to practice medicine on the basis of scientific evidence rather than on the basis of pharmaceutical promotion. JNJ was engaged by the law firm of Baum, Hedlund, Aristei & Goldman to provide an independent analysis of the data in Glaxo SmithKline's Study 329 of paroxetine in adolescents. DH has been an expert witness in ten legal cases involving antidepressant medications and one case involving the patent on olanzapine (Zyprexa). NR 117 TC 15 Z9 15 U1 5 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD MAY PY 2011 VL 8 IS 5 AR e1000434 DI 10.1371/journal.pmed.1000434 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 771IW UT WOS:000291151400001 PM 21559324 ER PT J AU Farmer, P Almazor, CP Bahnsen, ET Barry, D Bazile, J Bloom, BR Bose, N Brewer, T Calderwood, SB Clemens, JD Cravioto, A Eustache, E Jerome, G Gupta, N Harris, JB Hiatt, HH Holstein, C Hotez, PJ Ivers, LC Kerry, VB Koenig, SP LaRocque, RC Leandre, F Lambert, W Lyon, E Mekalanos, JJ Mukherjee, JS Oswald, C Pape, JW Prosper, AG Rabinovich, R Raymonville, M Rejouit, JR Ronan, LJ Rosenberg, ML Ryan, ET Sachs, JD Sack, DA Surena, C Suri, AA Ternier, R Waldor, MK Walton, D Weigel, JL AF Farmer, Paul Almazor, Charles Patrick Bahnsen, Emily T. Barry, Donna Bazile, Junior Bloom, Barry R. Bose, Niranjan Brewer, Thomas Calderwood, Stephen B. Clemens, John D. Cravioto, Alejandro Eustache, Eddy Jerome, Gregory Gupta, Neha Harris, Jason B. Hiatt, Howard H. Holstein, Cassia Hotez, Peter J. Ivers, Louise C. Kerry, Vanessa B. Koenig, Serena P. LaRocque, Regina C. Leandre, Fernet Lambert, Wesler Lyon, Evan Mekalanos, John J. Mukherjee, Joia S. Oswald, Cate Pape, Jean-William Prosper, Anany Gretchko Rabinovich, Regina Raymonville, Maxi Rejouit, Jean-Renold Ronan, Laurence J. Rosenberg, Mark L. Ryan, Edward T. Sachs, Jeffrey D. Sack, David A. Surena, Claude Suri, Arjun A. Ternier, Ralph Waldor, Matthew K. Walton, David Weigel, Jonathan L. TI Meeting Cholera's Challenge to Haiti and the World: A Joint Statement on Cholera Prevention and Care SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID ORAL REHYDRATION SOLUTION; PRIMARY-HEALTH-CARE; PROTECTIVE EFFICACY; B-SUBUNIT; EPIDEMIC CHOLERA; WATER-TREATMENT; HERD-IMMUNITY; FIELD TRIAL; VACCINE; DIARRHEA AB This joint statement argues for a comprehensive, integrated cholera response in Haiti. The cholera epidemic in Haiti is particularly devastating because of the vulnerability of Haiti's population after the January 12, 2010, earthquake, the long-standing weakness of its health, water, and sanitation systems, and the observed virulence of the El Tor hybrid strain. From October 19, 2010-when the first cases were confirmed in the National Public Health Laboratory-to April 4, 2011, 274,418 cases of cholera and 4,787 deaths related to cholera had been reported across all ten departments of Haiti [1]. The Haitian Ministere de la Sante Publique et de la Population (MSPP, the Ministry of Health) and the Direction Nationale de l'Eau Potable et de l'Assainissement (DINEPA, the government body charged with water and sanitation) have, with the support of many nongovernmental and international groups, made great strides against cholera. Case-fatality rates have dropped to 2.1% from 7% at the outset of the epidemic (and up to 10% in certain regions); incidence has also declined across Haiti, according to recent reports [1]. But fewer cases in the dry season (November-April) should not lead to complacency: seasonal variation is expected in epidemics of waterborne disease. Some have raised doubts about the sustainability of free water distribution within internally displaced persons (IDP) camps. But we believe that such efforts are an essential service that has contributed to the relatively few cases of cholera in the camps (as compared to other urban and rural areas). Given the likelihood of case resurgence and endemicity of cholera in Haiti, this document argues for a comprehensive, integrated strategy for cholera prevention and care in Haiti. We must reduce suffering and preventable death in the short term, and we must build effective water, sanitation, and health delivery infrastructure to fortify Haiti against cholera and other diseases of poverty in the long term. The document identifies three principal goals. First, we must continue aggressive case finding and scale up treatment efforts, including oral rehydration therapy, intravenous rehydration, antibiotic therapy (for moderate and severe cases), and complementary supplementation with zinc and vitamin A. Second, we must shore up Haiti's water infrastructure by building systems for consistent chlorination and filtration at public water sources and by distributing point-of-use water purification technologies. We must also strengthen sanitation infrastructure by improving and expanding waste management facilities (such as sewage systems and latrines) and waste monitoring. Third, we must link prevention to care by bolstering surveillance, education campaigns (about hand-washing, for example), and water, sanitation, and hygiene (WASH) efforts. Prevention must also include advocacy for scaled-up production of cholera vaccine and the development of a vaccine strategy for Haiti. A vaccination campaign should be implemented if adequate vaccine and resources can be mobilized without undermining efforts to treat acutely ill patients or strengthen water and sanitation infrastructure. This document identifies key challenges and outlines the components of a comprehensive cholera response to aid medical and public health practitioners in Haiti and elsewhere. With leadership from the Haitian government, we must work together to bolster responses to the acute problem of cholera today and strengthen Haiti's health, water, and sanitation infrastructure to prevent similar outbreaks in the future. C1 [Farmer, Paul; Bahnsen, Emily T.; Gupta, Neha; Hiatt, Howard H.; Holstein, Cassia; Ivers, Louise C.; Kerry, Vanessa B.; Koenig, Serena P.; Mukherjee, Joia S.; Suri, Arjun A.; Walton, David; Weigel, Jonathan L.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02215 USA. [Farmer, Paul; Barry, Donna; Hiatt, Howard H.; Ivers, Louise C.; Koenig, Serena P.; Mukherjee, Joia S.; Walton, David] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Farmer, Paul; Bahnsen, Emily T.; Holstein, Cassia; Ivers, Louise C.; Koenig, Serena P.; Leandre, Fernet; Lyon, Evan; Mukherjee, Joia S.; Walton, David; Weigel, Jonathan L.] Partners Hlth, Boston, MA USA. [Almazor, Charles Patrick; Bazile, Junior; Eustache, Eddy; Jerome, Gregory; Leandre, Fernet; Lambert, Wesler; Oswald, Cate; Prosper, Anany Gretchko; Raymonville, Maxi; Rejouit, Jean-Renold; Ternier, Ralph] Zanmi Lasante Partners Hlth, Cange, Haiti. [Bloom, Barry R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bose, Niranjan; Brewer, Thomas; Rabinovich, Regina] Bill & Melinda Gates Fdn, Global Hlth Program, Seattle, WA USA. [Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Calderwood, Stephen B.; Mekalanos, John J.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Calderwood, Stephen B.; Harris, Jason B.; LaRocque, Regina C.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Clemens, John D.] Int Vaccine Inst, Seoul, South Korea. [Cravioto, Alejandro] Int Ctr Diarrhoeal Dis Res ICDDR B, Dhaka, Bangladesh. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Hotez, Peter J.] Amer Soc Trop Med & Hyg, Deerfield, IL USA. [Hotez, Peter J.] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA. [Hotez, Peter J.] PLoS Neglected Trop Dis, San Francisco, CA USA. [Hotez, Peter J.] Sabin Vaccine Inst, Washington, DC USA. [Kerry, Vanessa B.; Ronan, Laurence J.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Pape, Jean-William] Weill Cornell Med Coll, Ctr Global Hlth, New York, NY USA. [Pape, Jean-William] GHESKIO Ctr, Port Au Prince, Haiti. [Rosenberg, Mark L.] Task Force Global Hlth, Decatur, GA USA. [Ryan, Edward T.] Massachusetts Gen Hosp, Trop & Geog Med Ctr, Boston, MA 02114 USA. [Sachs, Jeffrey D.] Columbia Univ, Earth Inst, New York, NY USA. [Sack, David A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Surena, Claude] Haitian Med Assoc, Port Au Prince, Haiti. [Waldor, Matthew K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Waldor, Matthew K.] HHMI, Boston, MA USA. RP Farmer, P (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02215 USA. EM paul_farmer@hms.harvard.edu OI Hotez, Peter/0000-0001-8770-1042 FU NIAID NIH HHS [R37 AI042347] NR 123 TC 32 Z9 34 U1 10 U2 113 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2011 VL 5 IS 5 AR e1145 DI 10.1371/journal.pntd.0001145 PG 13 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 770OZ UT WOS:000291099100024 PM 21655350 ER PT J AU Friedman, NDB Shedlack, KJ AF Friedman, Nora D. B. Shedlack, Karen J. TI Assessment and Management of Patients with Intellectual Disabilities by Psychiatric Consultants SO PSYCHOSOMATICS LA English DT Review ID MENTAL-RETARDATION; CHALLENGING BEHAVIOR; DEVELOPMENTAL-DISABILITIES; PSYCHOTROPIC MEDICATION; ADULTS; RISPERIDONE; DISORDERS; SYMPTOMS; PEOPLE; INDIVIDUALS AB Background: Although most individuals with intellectual disability (ID) currently reside in the community and receive their health care in general medical settings, there is no specific literature on psychiatric consultation to those requiring inpatient medical or surgical care. Objective: The authors discuss the specialized features of the consultation-liaison (C-L) evaluation and common requests for psychiatric consultation in the hospitalized ID population. Method: This article reviews the literature on general psychiatric care in this population and presents the experience of practitioners in the ID-Psychiatry field who have followed their patients through episodes of inpatient non-psychiatric care. Results: The C-L clinician must adapt the interview to accommodate a patient's cognitive, sensory, and language capacities; integrate information from collateral sources; and serve as a liaison between multiple parties. Discussion: ID should not be a barrier to the delivery of appropriate health care. This article provides evidence and recommendations on C-L assessment, management, and liaison for hospitalized individuals with ID. (Psychosomatics 2011; 52:210-217) C1 [Friedman, Nora D. B.] Harvard Univ, Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Sch Med, Boston, MA 02114 USA. [Shedlack, Karen J.] Harvard Univ, Sch Med, McLean Hosp, Boston, MA 02114 USA. [Shedlack, Karen J.] Harvard Univ, Sch Med, State MA Dept Dev Serv, Boston, MA 02114 USA. [Shedlack, Karen J.] Harvard Univ, Sch Med, Riverside Community Care Inc, Boston, MA 02114 USA. [Shedlack, Karen J.] Harvard Univ, Sch Med, Behav Treatment Serv, Boston, MA 02114 USA. RP Friedman, NDB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Sch Med, 55 Fruit St,Yawkey 6A, Boston, MA 02114 USA. EM ndfriedman@partners.org NR 48 TC 2 Z9 3 U1 5 U2 12 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 MAY-JUN PY 2011 VL 52 IS 3 BP 210 EP 217 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 771UU UT WOS:000291187000002 PM 21565592 ER PT J AU Marques, L LeBlanc, N Robinaugh, D Weingarden, H Keshaviah, A Wilhelm, S AF Marques, Luana LeBlanc, Nicole Robinaugh, Donald Weingarden, Hilary Keshaviah, Aparna Wilhelm, Sabine TI Correlates of Quality of Life and Functional Disability in Individuals with Body Dysmorphic Disorder SO PSYCHOSOMATICS LA English DT Article ID ANXIETY STRESS SCALES; OBSESSIVE-COMPULSIVE DISORDER; MAJOR DEPRESSIVE DISORDER; LARGE NONCLINICAL SAMPLE; CLINICAL CHARACTERISTICS; PSYCHIATRIC-INPATIENTS; COMMUNITY SAMPLE; NORMATIVE DATA; HEALTH; PREVALENCE AB Objective: Body dysmorphic disorder (BDD) is a chronic mental illness characterized by low quality of life and functional disability across multiple domains. Despite the clinical importance of understanding impairment in BDD, there has been little research examining the factors that contribute to these constructs. The present study was designed to examine sociodemographic and clinical correlates of quality of life and disability (work, social, and family) in a sample of individuals with moderately severe BDD symptoms. Method: Participants completed an internet survey with questions about demographics, BDD phenomenology, treatment, and impairment. Only participants who completed all study measures and received a score >= 16 on the 10-item Yale-Brown Obsessive Compulsive Scale, Modified fur BDD (BDD-YBOCS), indicating the presence of clinical BDD symptoms, were included in the analysis (n = 256). Multivariate regression with backwards variable selection was used to identify significant predictors of quality of life and functional disability, assessed with the Quality of Life Enjoyment and Satisfaction Scale-Short Form (QLESQ-SF) and the Sheehan Disability Scale (SDS), respectively Results: BDD symptom severity was inversely associated with quality of life and directly associated with disability in all domains. After controlling statistically for BDD symptom severity, sociodemographic and clinical factors such as age, gender, ethnicity, marital status, insurance, body parts of concern, depression symptoms, and anxiety symptoms were significantly associated with impairment. Conclusion: Results suggest a multidimensional nature of quality of life and functional disability and underscore the importance of developing holistic treatment strategies to address impairment in BDD. (Psychosomatics 2011; 52:245-254) C1 [Marques, Luana; LeBlanc, Nicole; Robinaugh, Donald; Weingarden, Hilary; Keshaviah, Aparna; Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Marques, Luana; LeBlanc, Nicole; Robinaugh, Donald; Weingarden, Hilary; Keshaviah, Aparna; Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA USA. [LeBlanc, Nicole; Weingarden, Hilary] Tufts Univ, Medford, MA 02155 USA. RP Marques, L (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq, Boston, MA 02114 USA. EM lmarques@partners.org FU Massachusetts General Hospital, Boston, MA FX The authors acknowledge the David Judah Fund-Internal Donor Funding donated for research purposes at the Massachusetts General Hospital, Boston, MA. NR 50 TC 11 Z9 11 U1 0 U2 5 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 MAY-JUN PY 2011 VL 52 IS 3 BP 245 EP 254 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 771UU UT WOS:000291187000006 PM 21565596 ER PT J AU Beach, SR Stem, TA AF Beach, Scott R. Stem, Theodore A. TI Malingering Involving Insurance Fraud: When it Pays to be Ill SO PSYCHOSOMATICS LA English DT Article C1 [Beach, Scott R.; Stem, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Beach, SR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 605, Boston, MA 02114 USA. EM sbeach1@partners.org NR 6 TC 1 Z9 1 U1 1 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 MAY-JUN PY 2011 VL 52 IS 3 BP 280 EP 282 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 771UU UT WOS:000291187000010 PM 21565600 ER PT J AU DeBonis, K Pierre, JM AF DeBonis, Katrina Pierre, Joseph M. TI Psychosis, Ivermectin Toxicity, and "Morgellons Disease" SO PSYCHOSOMATICS LA English DT Letter C1 [DeBonis, Katrina] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. W Los Angeles VA Med Ctr, Dept Psychiat, Los Angeles, CA USA. RP DeBonis, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. NR 6 TC 2 Z9 2 U1 0 U2 5 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 MAY-JUN PY 2011 VL 52 IS 3 BP 295 EP 296 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 771UU UT WOS:000291187000015 PM 21565604 ER PT J AU Boland, GWL AF Boland, Giles W. L. TI Adrenal Imaging: From Addison to Algorithms SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Adrenal lesion; Hyperfunctioning; Computed tomography; Characterization; Algorithm ID DELAYED ENHANCED CT; F-18-FDG PET/CT; INITIAL-EXPERIENCE; UNENHANCED CT; MASSES; ADENOMAS; LESIONS; BENIGN; PHEOCHROMOCYTOMAS; CANCER AB Despite their small size, pathologic condition of the adrenal glands is often far from insignificant. Imagers should therefore be familiar with the principles and techniques that underpin the ability of imaging to characterize most lesions. Ignorance of these techniques fails to deliver the necessary imaging value to referrers and patients alike. This article, outlines the range of possible abnormalities encountered in the adrenal gland, the imaging modalities and specialized techniques used to detect and characterize them, the principles based on which these techniques are used, and finally a working imaging algorithm that can be readily used in daily practice. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, White Bldg 270C,55 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org NR 47 TC 7 Z9 9 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 2011 VL 49 IS 3 BP 511 EP + DI 10.1016/j.rcl.2011.02.010 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 770XC UT WOS:000291120800010 PM 21569908 ER PT J AU Sanz, F Restrepo, MI Fernandez, E Mortensen, EM Aguar, MC Cervera, A Chiner, E Blanquer, J AF Sanz, Francisco Restrepo, Marcos I. Fernandez, Estrella Mortensen, Eric M. Carmen Aguar, Maria Cervera, Angela Chiner, Eusebi Blanquer, Jose CA Neumonia Adquirida Comunidad TI Hypoxemia Adds to the CURB-65 Pneumonia Severity Score in Hospitalized Patients With Mild Pneumonia SO RESPIRATORY CARE LA English DT Article DE hypoxemia; prognosis; pneumonia; CURB-65; outcomes; oxygenation ID COMMUNITY-ACQUIRED PNEUMONIA; LOW-RISK PATIENTS; PREDICTION RULE; MORTALITY; VALIDATION; DISEASE; ABNORMALITIES; OXYGENATION; GUIDELINES; MANAGEMENT AB BACKGROUND: Hypoxemia may influence the prognosis of patients with mild pneumonia, regardless of the initial CURB-65 score (confusion, blood urea nitrogen > 20 mg/dL, respiratory rate > 30 breaths/min, blood pressure < 90/60 mm Hg, and age >= 65 y). OBJECTIVE: To determine the risk factors associated with hypoxemia and the influence of hypoxemia on clinical outcomes in hospitalized patients with mild pneumonia. METHODS: We performed a multicenter prospective cohort study of 585 consecutive hospitalized patients with mild pneumonia (CURB-65 groups 0 and 1). We stratified the patients according to the presence of hypoxemia, defined as a P(aO2)/F(IO2) < 300 mm Hg on admission. We assessed the risk factors associated with hypoxemia, hypoxemia's influence on the course of pneumonia, and clinical outcomes (mortality, hospital stay, and need for intensive care unit admission), with multivariable regression. RESULTS: Fifty percent of the patients (294 cases) had hypoxemia on admission. The risk factors independently associated with hypoxemia were: bilateral radiological involvement (odds ratio 2.8, 95% CI 1.1-7.5), history of COPD (odds ratio 2.5, 95% CI 1.4-4.3), and hypoalbuminemia (odds ratio 2.0, 95% CI 1.1-3.5). The hypoxemic patients had longer hospital stay, higher intensive care unit admission rate, higher rate of severe sepsis, and higher mortality than the non-hypoxemic patients. CONCLUSIONS: Hypoxemia in patients with mild pneumonia is independently associated with several adverse clinical and radiological variables, and the hypoxemic patients had worse clinical outcomes than the non-hypoxemic patients. Therefore, additional attention should be paid to the presence of hypoxemia, regardless of a low CURB-65 score. C1 [Sanz, Francisco] Univ Valencia, Consorci Hosp Gen, Serv Neumol, Valencia 46014, Spain. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pulm & Crit Care Med, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. [Fernandez, Estrella; Cervera, Angela] Hosp Univ Doctor Peset Valencia, Serv Neumol, Valencia, Spain. [Mortensen, Eric M.] S Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX USA. [Carmen Aguar, Maria] Hosp Arnau Vilanova, Serv Neumol, Valencia, Spain. [Chiner, Eusebi] Hosp St Joan, Serv Neumol, Alacant, Spain. [Blanquer, Jose] Hosp Clin Univ Valencia, Serv Med Intens, Valencia, Spain. RP Sanz, F (reprint author), Univ Valencia, Consorci Hosp Gen, Serv Neumol, Tres Cruces 2, Valencia 46014, Spain. EM sanz_fraher@gva.es RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU Department of Veteran Affairs Veterans Integrated Service Network [17]; National Institutes of Health [KL2 RR025766]; Clinical and Translational Science Award [KL2 RR025766/VISN-17] FX Dr Restrepo was partly supported by a Department of Veteran Affairs Veterans Integrated Service Network 17 new faculty grant, by National Institutes of Health grant KL2 RR025766, and by Clinical and Translational Science Award KL2 RR025766/VISN-17. Dr Restrepo has disclosed relationships with Johnson & Johnson, CR Bard, Pfizer, Covidien, Ortho McNeil-Janssen, Whyeth, Theravan. Dr Mortensen EM has disclosed a relationship with the United States National Institutes of Health. The other authors have disclosed no conflicts of interest. The organizations that supported this research had no role in conducting the study or preparing, reviewing, or approving this paper. NR 31 TC 11 Z9 11 U1 0 U2 1 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 MAY PY 2011 VL 56 IS 5 BP 612 EP 618 DI 10.4187/respcare.00853 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771XO UT WOS:000291194200008 PM 21276314 ER PT J AU MacIntyre, NR Nava, S DiBlasi, RM Restrepo, RD Hess, DR AF MacIntyre, Neil R. Nava, Stefano DiBlasi, Robert M. Restrepo, Ruben D. Hess, Dean R. TI Respiratory Care Year in Review 2010: Part 2. Invasive Mechanical Ventilation, Noninvasive Ventilation, Pediatric Mechanical Ventilation, Aerosol Therapy SO RESPIRATORY CARE LA English DT Review DE aerosol therapy; airway pressure release ventilation; high-frequency oscillatory ventilation; inhaled bronchodilator; inhaled corticosteroid; mechanical ventilation; noninvasive ventilation ID POSITIVE AIRWAY PRESSURE; ACUTE LUNG INJURY; END-EXPIRATORY PRESSURE; FREQUENCY PERCUSSIVE VENTILATION; RANDOMIZED CONTROLLED-TRIAL; EXTREMELY PRETERM INFANTS; DISTRESS-SYNDROME; RELEASE VENTILATION; CYSTIC-FIBROSIS; TIDAL VOLUMES AB The purpose of this paper is to review the recent literature related to invasive mechanical ventilation, NIV, pediatric mechanical ventilation, and aerosol therapy. Topics covered related to invasive mechanical ventilation topics include the role of PEEP in providing lung protection during mechanical ventilation, unconventional modes for severe hypoxemia, and strategies to improve patient-ventilator interactions. Topics covered related to NIV include real-life NIV use, NIV and extubation failure, and NIV and pandemics. For pediatric mechanical ventilation, the topics addressed are NIV, invasive respiratory support, and inhaled nitric oxide. Topics covered related to aerosol therapy include short-acting beta-adrenergic agents, long-acting beta-adrenergic agents, long-acting antimuscarinic agents, inhaled corticosteroid therapy, phosphodiesterase type 4 (PDE4) inhibitors, long-acting beta-adrenergic plus inhaled corticosteroid, long-acting antimuscarinic plus inhaled corticosteroid, nebulized hypertonic saline, inhaled mannitol, and inhaled antibiotic therapy. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of RESPIRATORY CARE. C1 [Hess, Dean R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [MacIntyre, Neil R.] Duke Univ, Med Ctr, Div Pulm & Crit Care Med, Durham, NC USA. [Nava, Stefano] St Orsola & Malpighi Hosp, Resp & Crit Care Unit, Bologna, Italy. [DiBlasi, Robert M.] Seattle Childrens Hosp, Resp Care Dept, Seattle, WA USA. [DiBlasi, Robert M.] Seattle Childrens Res Inst, Ctr Dev Therapeut, Seattle, WA USA. [Restrepo, Ruben D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Resp Care, San Antonio, TX 78229 USA. RP Hess, DR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 77 TC 3 Z9 4 U1 1 U2 9 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD MAY PY 2011 VL 56 IS 5 BP 667 EP 680 DI 10.4187/respcare.01310 PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771XO UT WOS:000291194200014 PM 21669105 ER PT J AU Barnes, TA Kacmarek, RM Kageler, WV Morris, MJ Durbin, CG AF Barnes, Thomas A. Kacmarek, Robert M. Kageler, Woody V. Morris, Michael J. Durbin, Charles G., Jr. TI Transitioning the Respiratory Therapy Workforce for 2015 and Beyond SO RESPIRATORY CARE LA English DT Article DE respiratory care; respiratory therapist; manpower; education; training; competency; licensure; credentialing; accreditation; credentials; specialty; protocols ID MECHANICAL VENTILATION; CARDIAC-ARREST; EDUCATION; CARE AB The American Association for Respiratory Care established a task force in late 2007 to identify likely new roles and responsibilities of respiratory therapists (RTs) in the year 2015 and beyond. A series of 3 conferences was held between 2008 and 2010. The first task force conference affirmed that the healthcare system is in the process of dramatic change, driven by the need to improve health while decreasing costs and improving quality. This will be facilitated by application of evidence-based care, prevention and management of disease, and closely integrated interdisciplinary care teams. The second task force conference identified specific competencies needed to assure safe and effective execution of RT roles and responsibilities in the future. The third task force conference was charged with creating plans to change the professional education process so that RTs are able to achieve the needed skills, attitudes, and competencies identified in the previous conferences. Transition plans were developed by participants after review and discussion of the outcomes of the first two conferences and 1,011 survey responses from RT department managers and RT education program directors. This is a report of the recommendations of the third task force conference held July 12-14, 2010, on Marco Island, Florida. The participants, who represented groups concerned with RT education, licensure, and practice, proposed, discussed, and accepted that to be successful in the future a baccalaureate degree must be the minimum entry level for respiratory care practice. Also accepted was the recommendation that the Certified Respiratory Therapist examination be retired, and instead, passing of the Registered Respiratory Therapist examination will be required for beginning clinical practice. A date of 2020 for achieving these changes was proposed, debated, and accepted. Recommendations were approved requesting resources be provided to help RT education programs, existing RT workforce, and state societies work through the issues raised by these changes. C1 [Barnes, Thomas A.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Boston, MA USA. [Kageler, Woody V.] Tarrant Cty Coll, Dept Hlth Sci, Ft Worth, TX USA. [Morris, Michael J.] Brooke Army Med Ctr, Dept Internal Med, San Antonio, TX USA. [Durbin, Charles G., Jr.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA. RP Barnes, TA (reprint author), Northeastern Univ, Dept Hlth Sci, 316 Robinson Hall,360 Huntington Ave, Boston, MA 02115 USA. EM tbarnes@neu.edu NR 29 TC 14 Z9 15 U1 1 U2 4 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 MAY PY 2011 VL 56 IS 5 BP 681 EP 690 DI 10.4187/respcare.01169 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771XO UT WOS:000291194200015 PM 21276324 ER PT J AU Hess, DR AF Hess, Dean R. TI How Much PEEP? Do We Need Another Meta-Analysis? SO RESPIRATORY CARE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; VENTILATION STRATEGY; MECHANICAL VENTILATION; TIDAL VOLUMES; RECRUITMENT; PULMONARY; MORTALITY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Boston, MA 02114 USA. RP Hess, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 23 TC 6 Z9 6 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 EI 1943-3654 J9 RESP CARE JI Respir. Care PD MAY PY 2011 VL 56 IS 5 BP 710 EP 713 DI 10.4187/respcare.01315 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771XO UT WOS:000291194200021 PM 21669106 ER PT J AU Bajwa, EK AF Bajwa, Ednan K. TI Acute Lung Injury: Time to Find a Way That Works SO RESPIRATORY CARE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; VENTILATION C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Bajwa, EK (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. EM ebajwa@partners.org NR 7 TC 0 Z9 0 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 MAY PY 2011 VL 56 IS 5 BP 714 EP 715 DI 10.4187/respcare.01350 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771XO UT WOS:000291194200022 PM 21669107 ER PT J AU Stone, WS Giuliano, AJ Tsuang, MT Braff, DL Cadenhead, KS Calkins, ME Dobie, DJ Faraone, SV Freedman, R Green, MF Greenwood, TA Gur, RE Gur, RC Light, GA Mintz, J Nuechterlein, KH Olincy, A Radant, AD Roe, AH Schork, NJ Siever, LJ Silverman, JM Swerdlow, NR Thomas, AR Tsuang, DW Turetsky, BI Seidman, LJ AF Stone, William S. Giuliano, Anthony J. Tsuang, Ming T. Braff, David L. Cadenhead, Kristin S. Calkins, Monica E. Dobie, Dorcas J. Faraone, Stephen V. Freedman, Robert Green, Michael F. Greenwood, Tiffany A. Gur, Raquel E. Gur, Ruben C. Light, Gregory A. Mintz, Jim Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Roe, Andrea H. Schork, Nicholas J. Siever, Larry J. Silverman, Jeremy M. Swerdlow, Neal R. Thomas, Alison R. Tsuang, Debby W. Turetsky, Bruce I. Seidman, Larry J. TI Group and site differences on the California Verbal Learning Test in persons with schizophrenia and their first-degree relatives: Findings from the Consortium on the Genetics of Schizophrenia (COGS) SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Verbal declarative memory; Schizophrenia; Endophenotype ID ANTISACCADE PERFORMANCE; NONPSYCHOTIC RELATIVES; 1ST-EPISODE SCHIZOPHRENIA; BIOLOGICAL RELATIVES; COGNITIVE DEFICITS; MEMORY IMPAIRMENTS; DECLARATIVE MEMORY; WORKING-MEMORY; METAANALYSIS; ENDOPHENOTYPES AB Genetic studies of schizophrenia focus increasingly on putative endophenotypes because their genetic etiology may be simpler than clinical diagnosis. The Consortium on the Genetics of Schizophrenia (COGS), a multisite family study, aims to identify the genetic basis of several endophenotypes including verbal declarative memory (VDM), a neurocognitive function that shows robust impairment in schizophrenia. We present data on one type of measure of VDM, the California Verbal Learning Test, Second Edition (CVLT-II), in schizophrenia probands (n = 305), their full biological siblings (n = 449) and parents (n = 232), and in community comparison subjects (CCS: n = 509) across seven sites. Probands performed more poorly on each of five CVLT-II measures compared to related sibling and parent groups and CCS. Siblings and parents performed significantly worse than CCS on one measure (Discriminability), but with smaller effect sizes and less impairment than observed previously. The results raise questions about the homogeneity of VDM as an endophenotype, about methodological issues related to sampling, and about psychometric issues that impact the utility of the CVLT for detecting VDM deficits in nonpsychotic relatives of persons with schizophrenia. (C) 2011 Elsevier B.V. All rights reserved. C1 [Stone, William S.; Giuliano, Anthony J.; Roe, Andrea H.; Thomas, Alison R.; Seidman, Larry J.] Harvard Univ, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr, Publ Psychiat Div,Med Sch, Boston, MA 02215 USA. [Stone, William S.; Tsuang, Ming T.; Seidman, Larry J.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Tsuang, Ming T.; Braff, David L.; Cadenhead, Kristin S.; Greenwood, Tiffany A.; Light, Gregory A.; Schork, Nicholas J.; Swerdlow, Neal R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Med Genet Res Program, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Dobie, Dorcas J.; Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Dobie, Dorcas J.; Radant, Allen D.; Tsuang, Debby W.] Dept Vet Affairs VISN 20 Mental Illness Res Educ, Seattle, WA USA. [Green, Michael F.; Mintz, Jim; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Freedman, Robert; Olincy, Ann] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.] James J Peters VA & VISN3 Mental Illness Res Educ, Bronx, NY USA. RP Stone, WS (reprint author), Harvard Univ, Sch Med, Dept Psychiat BIDMC, 2nd Floor E,401 Pk Dr, Boston, MA 02215 USA. EM wstone@bidmc.harvard.edu; dbraff@ncsd.edu RI Greenwood, Tiffany/F-6356-2012; Tsuang, Debby/L-7234-2016; OI Greenwood, Tiffany/0000-0002-6080-6503; Tsuang, Debby/0000-0002-4716-1894; Faraone, Stephen/0000-0002-9217-3982 FU NIMH [RO1 -MH065562]; Mount Sinai School of Medicine [RO1-MH065554]; University of California Los Angeles [RO1-MH65707]; University of California San Diego [RO1-MH065571]; University of Colorado [RO1-MH65588]; University of Pennsylvania [RO1-MH65578]; University of Washington [RO1-MH65558] FX This work was supported by the NIMH through grants to Harvard University (RO1 -MH065562), Mount Sinai School of Medicine (RO1-MH065554), University of California Los Angeles (RO1-MH65707), University of California San Diego (RO1-MH065571), University of Colorado (RO1-MH65588), University of Pennsylvania (RO1-MH65578) and the University of Washington (RO1-MH65558). NR 46 TC 17 Z9 17 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2011 VL 128 IS 1-3 BP 102 EP 110 DI 10.1016/j.schres.2011.01.005 PG 9 WC Psychiatry SC Psychiatry GA 771QL UT WOS:000291175700018 PM 21288694 ER PT J AU Goldstein, JM Cherkerzian, S Seidman, LJ Petryshen, TL Fitzmaurice, G Tsuang, MT Buka, SL AF Goldstein, Jill M. Cherkerzian, Sara Seidman, Larry J. Petryshen, Tracey L. Fitzmaurice, Garrett Tsuang, Ming T. Buka, Stephen L. TI Sex-specific rates of transmission of psychosis in the New England high-risk family study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Psychosis; Genetic transmission; Sex differences; High risk; X-linked inheritance ID BIPOLAR AFFECTIVE-DISORDER; X-CHROMOSOME MARKERS; HOPA(12BP) POLYMORPHISM; COMMON VARIANTS; GENETIC-LINKAGE; WORKING-MEMORY; GENOME SCAN; SCHIZOPHRENIA; ILLNESS; BRAIN AB Recent molecular genetic studies have demonstrated X-chromosome abnormalities in the transmission of psychosis, a finding that may contribute to understanding sex differences in the disorder. Using our family high risk paradigm, we tested the hypothesis that there are sex-specific patterns of transmission of psychosis and whether there is specificity comparing nonaffective- with affective-type psychoses. We identified 159 parents with psychoses (schizophrenia psychosis spectrum disorders (SPS, n = 59) and affective (AP, n = 100)) and 114 comparable, healthy control parents. 203 high risk (HR) and 147 control offspring were diagnostically assessed (185 females: 165 males). We compared the proportion of male:female offspring with psychoses by affected parent sex and the consistency for SPS compared to AP parents, and tested (using exact logistic regression) whether the male:female ratio for affected offspring differed significantly between affected mothers and affected fathers. Risk of psychosis in offspring was a function of the sex of the parent and offspring. Among ill mothers, 18.8% of their male offspring developed psychosis compared with 9.5% of their daughters. In contrast, among ill fathers, 3.1% of their male offspring developed psychosis compared with 15.2% of their daughters. The male: female ratio for affected offspring differed significantly (p < 0.05) between affected mothers and fathers. Similar patterns held for SPS and AP. Results demonstrated sex-specific transmission of psychosis regardless of psychosis-type and suggest X-linked inheritance. This has important implications for molecular genetic studies of psychoses underscoring the impact of one's gender on gene-brain-behavior phenotypes of SCZ. (C) 2011 Elsevier B.V. All rights reserved. C1 [Goldstein, Jill M.; Cherkerzian, Sara] Brigham & Womens Hosp, Div Womens Hlth, Dept Psychiat, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02120 USA. [Goldstein, Jill M.; Cherkerzian, Sara] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, Jill M.; Cherkerzian, Sara] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goldstein, Jill M.; Cherkerzian, Sara] Brigham & Womens Hosp, Div Womens Hlth, Dept Med, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02120 USA. [Goldstein, Jill M.; Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci, Boston, MA 02114 USA. [Seidman, Larry J.; Tsuang, Ming T.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Dept Psychiat, Div Publ Psychiat, Boston, MA 02115 USA. [Petryshen, Tracey L.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Petryshen, Tracey L.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA. [Fitzmaurice, Garrett] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, San Diego, CA 92103 USA. [Tsuang, Ming T.] Harvard Univ, Sch Publ Hlth, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. [Buka, Stephen L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RP Goldstein, JM (reprint author), Brigham & Womens Hosp, Div Womens Hlth, Dept Psychiat, Connors Ctr Womens Hlth & Gender Biol, 1 Brigham Circle,1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU NIMH [RO1 MHSO647, RO1 MH56956, RO1 MH63951]; Stanley Medical Research Institute; NARSAD FX This work was primarily funded by NIMH RO1 MHSO647 (1999-2003, Tsuang, P.I.; 2003-2006, Goldstein, P.I.) and NIMH RO1 MH56956 (Goldstein, PI). Additional funding included NIMH RO1 MH63951 (LJS), Stanley Medical Research Institute (SB, LJS), and NARSAD (LJS). NIMH had no further role in the study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication. NR 62 TC 16 Z9 16 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2011 VL 128 IS 1-3 BP 150 EP 155 DI 10.1016/j.schres.2011.01.019 PG 6 WC Psychiatry SC Psychiatry GA 771QL UT WOS:000291175700025 PM 21334180 ER PT J AU Hermes, E Nasrallah, H Davis, V Meyer, J McEvoy, J Goff, D Davis, S Stroup, TS Swartz, M Lieberman, J Rosenheck, R AF Hermes, Eric Nasrallah, Henry Davis, Vicki Meyer, Jonathan McEvoy, Joseph Goff, Donald Davis, Sonia Stroup, T. Scott Swartz, Marvin Lieberman, Jeffrey Rosenheck, Robert TI The association between weight change and symptom reduction in the CATIE schizophrenia trial SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Antipsychotic agents; Weight gain; Lipids; Schizophrenia; Treatment outcome; Body mass index ID 2ND-GENERATION ANTIPSYCHOTICS; ATYPICAL ANTIPSYCHOTICS; RANDOMIZED-TRIAL; GAIN; OLANZAPINE; CLOZAPINE; IMPROVEMENT; EFFICACY; DRUGS; PANSS AB Background: Weight gain and changes in metabolic indicators associated with some antipsychotics may be related to symptom improvement and thus an unavoidable correlate of clinical benefit. Methods: Data from the CATIE schizophrenia trial comparing the effectiveness of perphenazine, olanzapine, risperidone, quetiapine and ziprasidone in a randomized, double-blind, trial over 18 months were used to evaluate the relationship between percent change in body mass index (BMI) and change in total serum cholesterol and triglycerides with the Positive and Negative Syndrome Scale (PANSS) score. Analysis of covariance for observations at 3 months and a mixed effects model for all observations up to 18 months adjusted for potentially confounding variables were used to examine these associations. Results: In both models, there was a significant association (p = 0.001) between change in PANSS total score and percent change in BMI, equating to a 0.28 and 0.21 point decrease in PANSS total score (range 30-210) per 1% increase in BMI respectively. Change in BMI accounted for 3% or less of variance for change in PANSS scores. There was no evidence that the association of symptoms and weight gain differed across medications in spite of substantial differences in weight gain and other metabolic measures. Neither total serum cholesterol nor triglyceride levels displayed a significant association with change in PANSS. Conclusion: The magnitude of the relationship between change in BMI and PANSS was too small to be clinically important, indicating that switching medications to one with less metabolic risk is unlikely to result in meaningful loss of clinical benefit. (C) 2011 Elsevier B.V. All rights reserved. C1 [Hermes, Eric; Rosenheck, Robert] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Nasrallah, Henry] Univ Cincinnati, Dept Psychiat & Behav Sci, Cincinnati, OH 45267 USA. [Davis, Vicki] NeuroCog Trials Inc, Durham, NC 27707 USA. [Meyer, Jonathan] Univ Calif San Diego, Dept Psychiat, VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [McEvoy, Joseph] Duke Univ, Dept Psychiat & Behav Sci, Butner, NC 27509 USA. [McEvoy, Joseph] John Umstead Hosp, Butner, NC 27509 USA. [Goff, Donald] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat,Med Sch,Lindemann Mental Hlth Ctr, Schizophrenia Program,Freedom Trail Clin, Boston, MA 02114 USA. [Davis, Sonia] Quintiles Inc, Morrisville, NC 27560 USA. [Stroup, T. Scott] New York State Psychiat Inst & Hosp, Program Intervent Effectiveness Res, New York, NY 10032 USA. [Swartz, Marvin] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Lieberman, Jeffrey] Columbia Univ, Inst Psychiat, Dept Psychiat, New York, NY 10032 USA. [Rosenheck, Robert] VA New England Mental Illness Res Educ & Clin Ctr, West Haven, CT 06516 USA. RP Hermes, E (reprint author), Yale Univ, Sch Med, Dept Psychiat, 300 George St,Ste 901, New Haven, CT 06511 USA. EM Eric.Hermes@yale.edu; NASRALHA@ucmail.uc.edu; Vicki.Davis@NeuroCogTrials.com; jmmeyer@ucsd.edu; jpmcevoy@duke.edu; goff@psych.mgh.harvard.edu; sonia.davis@quintiles.com; stroups@pi.cpmc.columbia.edu; marvin.swartz@duke.edu; JL2616@columbia.edu; Robert.Rosenheck@yale.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU New England Mental Illness Research and Education Center; Janssen Pharmaceutics Products; Wyeth Pharmaceuticals; AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb; GlaxoSmithKline; Pfizer Inc; Novartis; Solvay; Forest Pharmaceutical Company; Wyeth; Jannsen; Lilly; Pfizer; Sanofi; Cephalon; Dainippon Sumitomo; Solvay/Wyeth; Organon; Vanda; Eli Lilly FX This analysis was supported by the New England Mental Illness Research and Education Center. The funding source had no role in the design, analysis or interpretation of data or in the preparation of the report or decision to publish.; Dr. Rosenheck has received research support from Janssen Pharmaceutics Products and Wyeth Pharmaceuticals within the last year in addition to AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, and Eli Lilly and Co. in the past. He has received consulting fees from Bristol-Myers Squibb, Eli Lilly and Co., Roche Pharmaceuticals and Janssen Pharmaceutica Products. He is a testifying expert in Jones ex rel. the State of Texas v. Janssen Pharmaceutica Products.; Dr. Lieberman reports having received research funding from AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Pharmaceutics Products, and Pfizer Inc.; and consulting and educational fees from AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Eli Lilly and Co., Forest Pharmaceutical Company, GlaxoSmithKline, Janssen Pharmaceutica Products, Novartis, Pfizer Inc., and Solvay.; Dr. McEvoy reports having received research funding from AstraZeneca, Forest Research Institute, Eli Lilly and Co., Janssen Pharmaeutica, and Pfizer Inc.; consulting or advisory board fees from Pfizer Inc. and Bristol-Myers Squibb; and lecture fees from Janssen Pharmaceutics, and Bristol-Myers Squibb.; Dr. Swartz reports having received research funding from Eli Lilly and Co., and consulting and educational fees from AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Eli Lilly and Co., and Pfizer Inc.; Dr. Meyer reports having received research support from Bristol-Myers Squibb and Pfizer, Inc., and has received speaking or advising fees from Bristol-Myers Squibb, Janssen Pharmaceutica, Pfizer, Inc., and Wyeth.; Dr. Nasrallah has received grants/research support from AstraZeneca, GSK, Jannsen, Lilly, Pfizer and Sanofi; has been a consultant, an advisory board member and served on the speakers' bureau for Abbott, AstraZeneca, Janssen, Pfizer and Shire.; Dr. Goff has received grants/research support from Pfizer. Cephalon and Janssen, has received consulting, advisory board or lecture fees from Dainippon Sumitomo, Solvay/Wyeth, Bristol-MyerSquibb, Organon, Vanda and Eli Lilly. NR 26 TC 23 Z9 23 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2011 VL 128 IS 1-3 BP 166 EP 170 DI 10.1016/j.schres.2011.01.022 PG 5 WC Psychiatry SC Psychiatry GA 771QL UT WOS:000291175700028 PM 21334853 ER PT J AU Alter, G Altfeld, M AF Alter, Galit Altfeld, Marcus TI Mutiny or scrutiny: NK cell modulation of DC function in HIV-1 infection SO TRENDS IN IMMUNOLOGY LA English DT Review ID NATURAL-KILLER-CELLS; MHC CLASS-I; PLASMACYTOID-DENDRITIC-CELLS; IMMUNE-RESPONSES; VIRUS-INFECTION; INNATE IMMUNITY; LYMPH-NODES; IFN-GAMMA; HLA-B; ACTIVATION AB Accumulating data suggest that natural killer (NK) cells are involved not only in the innate antiviral response following infection, but also in shaping the quality of the adaptive immune response by modulating the functional properties of myeloid dendritic cells (DC) during the acute immune response to infection. In this role, NK cells ensure that only fully mature, immunogenic DCs gain access to inductive sites, where they might prime effective antiviral adaptive immune responses. However, increasing evidence now suggests that several aspects of this cross-talk between NK cells and DCs are compromised during HIV infection, potentially contributing to immune dysfunction. C1 [Altfeld, Marcus] MIT, Ragon Inst MGH, Charlestown, MA 02120 USA. Massachusetts Gen Hosp, Charlestown, MA 02120 USA. RP Altfeld, M (reprint author), MIT, Ragon Inst MGH, 149 13th St, Charlestown, MA 02120 USA. EM maltfeld@partners.org FU NIAID NIH HHS [P01 AI074415, R01 AI067031, R01 AI067031-05, P01 AI074415-04] NR 69 TC 17 Z9 18 U1 0 U2 4 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 MAY PY 2011 VL 32 IS 5 BP 219 EP 224 DI 10.1016/j.it.2011.02.003 PG 6 WC Immunology SC Immunology GA 771CX UT WOS:000291135900006 PM 21411368 ER PT J AU Greulich, H Pollock, PM AF Greulich, Heidi Pollock, Pamela M. TI Targeting mutant fibroblast growth factor receptors in cancer SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID TYROSINE KINASE INHIBITOR; DYSPLASIA TYPE-I; IMMUNOGLOBULIN-LIKE DOMAIN; UROTHELIAL CELL-CARCINOMA; LETHAL SKELETAL DYSPLASIA; POTENT ANTITUMOR-ACTIVITY; GENOME-WIDE ASSOCIATION; MULTIPLE-MYELOMA; FGFR3 MUTATIONS; ACTIVATING MUTATIONS AB Fibroblast growth factor receptors (FGFRs) play diverse roles in the control of cell proliferation, cell differentiation, angiogenesis and development. Activating the mutations of FGFRs in the germline has long been known to cause a variety of skeletal developmental disorders, but it is only recently that a similar spectrum of somatic FGFR mutations has been associated with human cancers. Many of these somatic mutations are gain-of-function and oncogenic and create dependencies in tumor cell lines harboring such mutations. A combination of knockdown studies and pharmaceutical inhibition in preclinical models has further substantiated genomically altered FGFR as a therapeutic target in cancer, and the oncology community is responding with clinical trials evaluating multikinase inhibitors with anti-FGFR activity and a new generation of specific pan-FGFR inhibitors. C1 [Greulich, Heidi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Greulich, Heidi] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Greulich, Heidi] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Greulich, Heidi] Broad Inst, Cambridge, MA 02142 USA. [Pollock, Pamela M.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Kelvin Grove, Qld 4059, Australia. RP Greulich, H (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM heidig@broadinstitute.org; pamela.pollock@qut.edu.au FU NCI NIH HHS [P50 CA134254] NR 103 TC 56 Z9 59 U1 1 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD MAY PY 2011 VL 17 IS 5 BP 283 EP 292 DI 10.1016/j.molmed.2011.01.012 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 773GL UT WOS:000291294900007 PM 21367659 ER PT J AU Somarouthu, B Rabinov, J Wong, WC Kalva, SP AF Somarouthu, Bhanusupriya Rabinov, James Wong, Waichi Kalva, Sanjeeva P. TI Stent-Assisted Coil Embolization of an Intraparenchymal Renal Artery Aneurysm in a Patient With Neurofibromatosis SO VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE Renal artery aneurysm; neurofibromatosis; stent-assisted coil embolization AB True renal artery aneurysms are rare. They are generally asymptomatic, however, a few may present with hypertension, rupture, or renal dysfunction secondary to distal embolization. Indications for intervention include aneurysm of >= 2.0 cm in diameter, renovascular hypertension, enlarging aneurysm, associated dissection /rupture, and aneurysms in women of child-bearing age/pregnancy. Endovascular therapy through coil embolization or stent graft exclusion is the recommended management. Coil embolization of the first and second order branch aneurysms is often associated with distal parenchymal loss and current stent graft technology prohibits use of these endoprostheses in the branch renal arteries. In this report, we describe successful stent-assisted coil embolization of an intraparenchymal aneurysm while preserving the distal parenchyma in a young woman with Neurofibromatosis type I. C1 [Somarouthu, Bhanusupriya; Rabinov, James; Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Somarouthu, Bhanusupriya; Rabinov, James; Wong, Waichi; Kalva, Sanjeeva P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wong, Waichi] Massachusetts Gen Hosp, Dept Nephrol, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB 297,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 7 TC 4 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1538-5744 J9 VASC ENDOVASC SURG JI Vasc. Endovasc. Surg. PD MAY PY 2011 VL 45 IS 4 BP 368 EP 371 DI 10.1177/1538574411403327 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 771LX UT WOS:000291160600012 PM 21527466 ER PT J AU Perrin, JM Dewitt, TG AF Perrin, James M. Dewitt, Thomas G. TI Future of Academic General Pediatrics-Areas of Opportunity SO ACADEMIC PEDIATRICS LA English DT Article ID HEALTH-CARE NEEDS; MEDICAL HOME; CHILDREN; CHALLENGES; PHYSICIANS; EDUCATION C1 [Perrin, James M.] Harvard Univ, Sch Med, MGH Ctr Child & Adolescent Hlth Policy, MassGen Hosp Children, Boston, MA USA. [Dewitt, Thomas G.] Univ Cincinnati, Coll Med, Div Gen & Community Pediat, Cincinnati Childrens Hosp, Cincinnati, OH USA. RP Perrin, JM (reprint author), 50 Staniford St,901, Boston, MA 02114 USA. EM jperrin@partners.org NR 34 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2011 VL 11 IS 3 BP 181 EP 188 PG 8 WC Pediatrics SC Pediatrics GA 768IV UT WOS:000290928500003 PM 21570003 ER PT J AU Co, JPT Sternberg, SB Homer, CJ AF Co, John Patrick T. Sternberg, Scot B. Homer, Charles J. TI Measuring Patient and Family Experiences of Health Care for Children SO ACADEMIC PEDIATRICS LA English DT Article DE patient centeredness; patient experience; quality of care; surveys ID PEDIATRIC AMBULATORY-CARE; QUALITY-OF-CARE; PSYCHOMETRIC PROPERTIES; PHYSICIAN COMMUNICATION; CONSUMER ASSESSMENT; TECHNICAL QUALITY; SYSTEM PROVISION; CORE SURVEY; PLANS; SERVICES AB BACKGROUND: The Institute of Medicine considers patient centeredness a core dimension of quality. Several patient/family surveys exist to assess pediatric health care. The Children's Health Insurance Program Reauthorization Act mandates strengthening quality measurement for children, including for patient/family experience of care. OBJECTIVES: The aim of this study was to determine what instruments exist for measuring patient/family experience of pediatric health care and which should be included in the core measurement set for assessing Medicaid and the Children's Health Insurance Program (CHIP) programs; to identify gaps in measurement; and to provide recommendations for measure development. METHODS: We developed a conceptual framework for measuring patient/family experience of care. We conducted a review of national measure clearinghouses and of the literature to assess validity, reliability, and feasibility of existing measures, and how these measures address the conceptual framework. RESULTS: We found valid and reliable instruments for measuring patient/family experience of care include the Consumer Assessment of Healthcare Providers and Systems (CAHPS (R)) instruments, Promoting Healthy Development Survey (PHDS), Young Adult Health Care Survey (YAHCS), and the National Research Corporation Picker Pediatric Inpatient Survey (NRC Picker). We identified the need for matching patients with providers and groups as a barrier for widespread use of the CAHPS (R) pediatric clinician & group instrument. CONCLUSIONS: We recommended to the National Advisory Council for Healthcare Research and Quality Subcommittee on Children's Healthcare Quality Measures for Medicaid and Child Health Insurance Programs (SNAC) the CAHPS (R) Child Medicaid 4.0 and pediatric Clinician & Group Survey for inclusion in the initial recommended list of core measures for voluntary use by Medicaid and CHIP. The Clinician and Group Survey was not included in the list posted for public comment due to concerns at that time (December 2009) about feasibility. We also recommended that development of a child version of the CAHPS (R) behavioral and mental health survey now used in the adult population and of a pediatric hospital CAHPS (R) measure be considered high priorities for development in the next phase of Children's Health Insurance Program Reauthorization Act measurement activity. This phase should also explore methods to increase response rates and lower costs of obtaining consumer feedback. C1 [Co, John Patrick T.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Co, John Patrick T.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Sternberg, Scot B.; Homer, Charles J.] Natl Initiat Childrens Healthcare Qual, Boston, MA USA. [Co, John Patrick T.; Homer, Charles J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Co, JPT (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM jco@partners.org FU US Department of Health and Human Services Agency for Healthcare Research and Quality [HHSP233200900801P]; Centers for Medicare & Medicaid Services FX Funding for this report was provided through purchase order HHSP233200900801P by the US Department of Health and Human Services Agency for Healthcare Research and Quality, with funds provided by its Centers for Medicare & Medicaid Services. NR 59 TC 12 Z9 12 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2011 VL 11 IS 3 SU S BP S59 EP S67 PG 9 WC Pediatrics SC Pediatrics GA 768IX UT WOS:000290928700007 PM 21570018 ER PT J AU Kuhlthau, KA AF Kuhlthau, Karen A. TI Measures of Availability of Health Care Services for Children SO ACADEMIC PEDIATRICS LA English DT Article DE availability; health care; pediatric; provider density ID NEONATAL INTENSIVE-CARE; UNITED-STATES; MANAGED CARE; ACCESS; NEEDS; ACCESSIBILITY; ENVIRONMENT; PHYSICIAN AB OBJECTIVE: The Children's Health Insurance Program Reauthorization Act (CHIPRA) mandates that measures of availability of child health services be included in the recommended core measurement set. The objective of this work was to review and evaluate measures of availability of child health services for potential inclusion in the initial core set of health care quality measures as mandated by CHIPRA. METHODS: To find measures, I searched the published literature, measurement sets, and recommended articles to identify existing measures of availability. I comment on the use of these measures as well as their reliability and validity (where available). RESULTS: I identified measures of geographic availability (n = 11), timeliness (n = 7), and barriers (n = 4). Geographic measures range from counts of the number of providers in a specific area to measures that account for whether providers are open to caring for patients with public insurance and distance. Measures of timeliness address whether patients can see a provider quickly. Barriers measure the ease with which providers can be seen. CONCLUSIONS: Of potential use to the CHIPRA measurement initiative are objective measures of provider density and some existing parent survey questions about timeliness and ease of use. Other measures include more refined measures of density or distance, perhaps looking at providers who are taking new Medicaid and State Children's Health Insurance Program patients and more detailed questions about the timeliness and ease with which patients can get care. However, more work is needed on the validity and reliability of existing measures; more work is also needed to expand measures of availability beyond existing domains of providers and conditions. C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. RP Kuhlthau, KA (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Ste 901, Boston, MA 02114 USA. EM kkuhlthau@partners.org FU US HHS AHRQ [HESP233200900701P]; HHS Centers for Medicare & Medicaid Services FX Funding for this report was provided through Purchase Order HESP233200900701P by the US HHS AHRQ, with funds provided by the HHS Centers for Medicare & Medicaid Services. NR 35 TC 4 Z9 4 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2011 VL 11 IS 3 SU S BP S42 EP S48 PG 7 WC Pediatrics SC Pediatrics GA 768IX UT WOS:000290928700005 PM 21570016 ER PT J AU Sternberg, SB Co, JPT Homer, CJ AF Sternberg, Scot B. Co, John Patrick T. Homer, Charles J. TI Review of Quality Measures of the Most Integrated Health Care Settings for Children and the Need for Improved Measures: Recommendations for Initial Core Measurement Set for CHIPRA SO ACADEMIC PEDIATRICS LA English DT Review DE integrated health care; medical home ID PEDIATRIC PRIMARY-CARE; MEDICAL HOME; EXPERIENCES; IMPLEMENTATION; PATIENT; IMPACT AB OBJECTIVE: To identify, assess, and make recommendations for inclusion of measures that assess the domain of "most integrated health care setting," with a specific focus on measures of the medical home, one particular mechanism for integrating care, to identify gaps in measurement; and to make recommendations for new measure development. METHODS: We developed a conceptual framework for care integration and reviewed literature on measures assessing the presence and quality of the medical home to determine their validity, reliability, and feasibility as a proxy for care integration. RESULTS: We identified 2 broad approaches to assessing the extent to which patients receive care that fulfills the aims of the medical home: I) organizational assessment of practice systems and processes thought associated with achieving these desired aims (viz, the National Committee for Quality Assurance Physician Practice Connections Patient Centered Medical Home measure and the Medical Home Index, and 2) direct assessment by patients/families of their experience of care in targeted dimensions. Based on concerns about the absence of reliability data and the feasibility of applying the-practice audit/self-assessment approach on a population level for the purpose of state reporting, as well as the limited data linking performance on the specific measures with important child outcomes, we did not recommend any of the measures of organizational assessments of practice systems for inclusion in the core set as an indicator of care integration. In contrast, measures of the medical home based on items from the National Survey of Child Health on a population level of or the Consumer Assessment of Healthcare Providers and Systems for practice- and state-level assessment are more feasible, have known reliability and performance characteristics, and more closely reflect the aims of the medical home, including care integration. CONCLUSIONS: Measures of health care integration as captured by the experience of care in a medical home can best be assessed for state-level performance through patient/family experience surveys. Better measures of care integration, care coordination, and integration of mental, developmental, and physical health into a comprehensive care system are high-priority topics for measure development. C1 [Co, John Patrick T.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Co, John Patrick T.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Sternberg, Scot B.; Homer, Charles J.] Natl Initiat Childrens Healthcare Qual, Boston, MA USA. RP Sternberg, SB (reprint author), Beth Israel Deaconess Med Ctr, Stoneman Ctr Qual Improvement, 330 Brookline Ave, Boston, MA 02215 USA. EM Scot.Sternberg@gmail.com FU US Department of Health and Human Services (HHS) AHRQ [HHSP233200900799P]; HHS CMS FX Funding for this report was provided through Purchase Order HHSP233200900799P by the US Department of Health and Human Services (HHS) AHRQ with funds provided by the HHS CMS. NR 41 TC 8 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2011 VL 11 IS 3 SU S BP S49 EP S58 PG 10 WC Pediatrics SC Pediatrics GA 768IX UT WOS:000290928700006 PM 21570017 ER PT J AU Mylonakis, E AF Mylonakis, Eleftherios TI The Need to Redefine Antimicrobial Drug Discovery SO CURRENT PHARMACEUTICAL DESIGN LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St,Gray Jackson 5,Room GRJ-504, Boston, MA 02114 USA. EM emylonakis@partners.org NR 13 TC 3 Z9 3 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2011 VL 17 IS 13 BP 1223 EP 1224 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768QU UT WOS:000290952300001 PM 21470109 ER PT J AU Anastassopoulou, CG Fuchs, BB Mylonakis, E AF Anastassopoulou, Cleo G. Fuchs, Beth Burgwyn Mylonakis, Eleftherios TI Caenorhabditis elegans-based Model Systems for Antifungal Drug Discovery SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Invertebrate model hosts; non-mammalian animal models; systemic mycoses; Candida albicans; high-throughput in vivo screening; drug bioaccumulation model; Caenorhabditis elegans ID HOST-PATHOGEN INTERACTIONS; ANIMAL INFECTION MODEL; INTENSIVE-CARE-UNIT; CANDIDA-ALBICANS; CRYPTOCOCCUS-NEOFORMANS; C-ELEGANS; FUNGAL-INFECTIONS; INNATE IMMUNITY; IN-VITRO; ANTILEISHMANIAL ACTIVITY AB The substantial morbidity and mortality associated with invasive fungal infections constitute undisputed tokens of their severity. The continued expansion of susceptible population groups (such as immunocompromised individuals, patients undergoing extensive surgery, and those hospitalized with serious underlying diseases especially in the intensive care unit) and the limitations of current antifungal agents due to toxicity issues or to the development of resistance, mandate the development of novel antifungal drugs. Currently, drug discovery is transitioning from the traditional in vitro large-scale screens of chemical libraries to more complex bioassays, including in vivo studies on whole animals; invertebrates, such as Caenorhabditis elegans, are thus gaining momentum as screening tools. Key pathogenesis features of fungal infections, including filament formation, are expressed in certain invertebrate and mammalian hosts; among the various potential hosts, C. elegans provides an attractive platform both for the study of host-pathogen interactions and the identification of new antifungal agents. Advantages of compound screening in this facile, relatively inexpensive and not as ethically challenged whole-animal context, include the simultaneous assessment of antifungal efficacy and toxicity that could result in the identification of compounds with distinct mechanisms of action, for example by promoting host immune responses or by impeding fungal virulence factors. With the recent advent of using predictive models to screen for compounds with improved chances of bioavailability in the nematode a priori, high-throughput screening of chemical libraries using the C. elegans-C. albicans antifungal discovery assay holds even greater promise for the identification of novel antifungal agents in the near future. C1 [Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Gray Jackson 5,Room GRJ-504, Boston, MA 02114 USA. EM emylonakis@partners.org FU NIH [P01 AI 083214, R01 AI075286, R21 AI079569]; Astellas Pharma Inc. FX This work was supported by NIH grants P01 AI 083214, R01 AI075286 and R21 AI079569 to E.M.; E.M. has served in an Advisory Board and received research support from Astellas Pharma Inc. C. G. A. and B. B. F. report no potential conflicts of interest. NR 113 TC 17 Z9 18 U1 2 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2011 VL 17 IS 13 BP 1225 EP 1233 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768QU UT WOS:000290952300002 PM 21470110 ER PT J AU Tegos, GP Haynes, M Strouse, J Khan, MMT Bologa, CG Oprea, TI Sklar, LA AF Tegos, George P. Haynes, Mark Strouse, Jacob Khan, Mohiuddin Md. T. Bologa, Cristian G. Oprea, Tudor I. Sklar, Larry A. TI Microbial Efflux Pump Inhibition: Tactics and Strategies SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Multidrug resistance; efflux pump substrates and inhibitors; natural antimicrobials; high-throughput screening ID RESISTANT STAPHYLOCOCCUS-AUREUS; GRAM-NEGATIVE BACTERIA; PSEUDOMONAS-AERUGINOSA BIOFILMS; KLEBSIELLA-PNEUMONIAE STRAINS; ARGININE-BETA-NAPHTHYLAMIDE; CANDIDA-ALBICANS BIOFILMS; MULTIDRUG TRANSPORTER BMR; MEDIATED DRUG-RESISTANCE; LARGE PERIPLASMIC LOOPS; ESCHERICHIA-COLI AB Traditional antimicrobials are increasingly suffering from the emergence of multidrug resistance among pathogenic microorganisms. To overcome these deficiencies, a range of novel approaches to control microbial infections are under investigation as potential alternative treatments. Multidrug efflux is a key target of these efforts. Efflux mechanisms are broadly recognized as major components of resistance to many classes of chemotherapeutic agents as well as antimicrobials. Efflux occurs due to the activity of membrane transporter proteins widely known as Multidrug Efflux Systems (MES). They are implicated in a variety of physiological roles other than efflux and identifying natural substrates and inhibitors is an active and expanding research discipline. One plausible alternative is the combination of conventional antimicrobial agents/antibiotics with small molecules that block MES known as multidrug efflux pump inhibitors (EPIs). An array of approaches in academic and industrial research settings, varying from high-throughput screening (HTS) ventures to bioassay guided purification and determination, have yielded a number of promising EPIs in a series of pathogenic systems. This synergistic discovery platform has been exploited in translational directions beyond the potentiation of conventional antimicrobial treatments. This venture attempts to highlight different tactical elements of this platform, identifying the need for highly informative and comprehensive EPI-discovery strategies. Advances in assay development genomics, proteomics as well as the accumulation of bioactivity and structural information regarding MES facilitates the basis for a new discovery era. This platform is expanding drastically. A combination of chemogenomics and chemoinformatics approaches will integrate data mining with virtual and physical HTS ventures and populate the chemical-biological interface with a plethora of novel chemotypes. This comprehensive step will expedite the preclinical development of lead EPIs. C1 [Tegos, George P.; Haynes, Mark; Strouse, Jacob; Khan, Mohiuddin Md. T.; Bologa, Cristian G.; Oprea, Tudor I.; Sklar, Larry A.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Tegos, George P.; Sklar, Larry A.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Tegos, George P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. [Bologa, Cristian G.; Oprea, Tudor I.] Univ New Mexico, Hlth Sci Ctr, Div Biocomp, Albuquerque, NM 87131 USA. RP Tegos, GP (reprint author), 2325 Camino de Salud, CRF 217A MSC 07-4025, Albuquerque, NM 87131 USA. EM gtegos@salud.unm.edu RI Oprea, Tudor/A-5746-2011; OI Oprea, Tudor/0000-0002-6195-6976; Bologa, Cristian/0000-0003-2232-4244 FU Massachusetts Technology Transfer Center (MTTC) [U54, MH084690, R01GM59903, R01AI050875] FX Funding for part of the research presented in this review was provided for by Massachusetts Technology Transfer Center (MTTC) to George Tegos NIH (U54, MH084690 Molecular Libraries Probe Production Centers Network, to George Tegos and Larry Sklar) and (R01GM59903, K. Lewis) and (R01AI050875, M. R. Hamblin). The authors will like to thank Melissa Brown & Laura Piddock for permission to use the MES scheme in Fig. 1 and to Martyn Symmons for kindly providing the PDB model of the AcrAB-TolC efflux pump. NR 184 TC 30 Z9 30 U1 2 U2 40 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2011 VL 17 IS 13 BP 1291 EP 1302 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768QU UT WOS:000290952300009 PM 21470111 ER PT J AU Sharma, SK Dai, TH Kharkwal, GB Huang, YY Huang, LY De Arce, VJB Tegos, GP Hamblin, MR AF Sharma, Sulbha K. Dai, Tianhong Kharkwal, Gitika B. Huang, Ying-Ying Huang, Liyi De Arce, Vida J. Bil Tegos, George P. Hamblin, Michael R. TI Drug Discovery of Antimicrobial Photosensitizers Using Animal Models SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Antimicrobial photodynamic therapy; cationic tetrapyrroles; phenothiazinium dyes; reactive oxygen species; mouse models of localized infections; bioluminescence imaging; drug discovery ID RESISTANT STAPHYLOCOCCUS-AUREUS; GRAM-POSITIVE BACTERIA; MESOSUBSTITUTED CATIONIC PORPHYRINS; TARGETED PHOTODYNAMIC THERAPY; CANDIDA-ALBICANS; IN-VITRO; ESCHERICHIA-COLI; METHYLENE-BLUE; EFFICIENT PHOTOSENSITIZERS; PHOTOBACTERICIDAL ACTIVITY AB Antimicrobial photodynamic therapy (aPDT) is an emerging alternative to antibiotics motivated by growing problems with multi-drug resistant pathogens. aPDT uses non-toxic dyes or photosensitizers (PS) in combination with harmless visible of the correct wavelength to be absorbed by the PS. The excited state PS can form a long-lived triplet state that can interact with molecular oxygen to produce reactive oxygen species such as singlet oxygen and hydroxyl radical that kill the microbial cells. To obtain effective PS for treatment of infections it is necessary to use cationic PS with positive charges that are able to bind to and penetrate different classes of microbial cells. Other drug design criteria require PS with high absorption coefficients in the red/near infra-red regions of the spectrum where light penetration into tissue is maximum, high photostability to minimize photobleaching, and devising compounds that will selectively bind to microbial cells rather than host mammalian cells. Several molecular classes fulfill many of these requirements including phenothiazinium dyes, cationic tetrapyrroles such as porphyrins, phthalocyanines and bacteriochlorins, cationic fullerenes and cationic derivatives of other known PS. Larger structures such as conjugates between PS and cationic polymers, cationic nanoparticles and cationic liposomes that contain PS are also effective. In order to demonstrate in vivo efficacy it is necessary to use animal models of localized infections in which both PS and light can be effectively delivered into the infected area. This review will cover a range of mouse models we have developed using bioluminescent pathogens and a sensitive low light imaging system to non-invasively monitor the progress of the infection in real time. Effective aPDT has been demonstrated in acute lethal infections and chronic biofilm infections; in infections caused by Gram-positive, Gram-negative bacteria and fungi; in infections in wounds, third degree burns, skin abrasions and soft-tissue abscesses. This range of animal models also represents a powerful aid in antimicrobial drug discovery. C1 [Sharma, Sulbha K.; Dai, Tianhong; Kharkwal, Gitika B.; Huang, Ying-Ying; Huang, Liyi; De Arce, Vida J. Bil; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Kharkwal, Gitika B.; Huang, Ying-Ying; Huang, Liyi; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning, Peoples R China. [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM Hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01A1050875, R01CA/AI838801, R01CA137108]; US Air Force MFEL Program [FA9550-04-1-0079]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program in TBI [W81XWH-09-1-0514] FX Research in the Hamblin laboratory is supported by NIH grants (R01A1050875 and R01CA/AI838801 to MRH; R01CA137108 to Long Y Chiang), US Air Force MFEL Program (FA9550-04-1-0079), Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514). NR 95 TC 42 Z9 44 U1 2 U2 47 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2011 VL 17 IS 13 BP 1303 EP 1319 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 768QU UT WOS:000290952300010 PM 21504410 ER PT J AU Wain, RM Wilbourne, PL Harris, KW Pierson, H Teleki, J Burling, TA Lovett, S AF Wain, R. Morgan Wilbourne, Paula L. Harris, Keith W. Pierson, Heather Teleki, Jasmine Burling, Thomas A. Lovett, Steven TI Motivational interview improves treatment entry in homeless veterans SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Motivational interview; Homeless veterans; Treatment retention; Wait-list attrition ID SUBSTANCE-ABUSE TREATMENT; BRIEF INTERVENTIONS; RANDOMIZED-TRIAL; CLINICAL-TRIALS; USE DISORDERS; DRUG; EFFICACY; SERVICES; OUTCOMES; LENGTH AB Motivational Interviewing (MI) has successfully been used to facilitate entry and compliance in drug and alcohol treatment programs. Some questions have been raised as to the effectiveness of MI in severely distressed populations. This study aims to assess the effectiveness of MI in a population of homeless, unemployed, and substance dependent veterans who are being wait-listed for entry into a residential treatment program. Seventy-five veterans placed on a wait-list were randomized to receive a single MI or standard (Std) intake interview. Outcomes assessed were entry, and length of stay (LOS). Secondary outcomes assessed included program completion and rates of graduation. Readiness to change and self-efficacy were assessed before and after the interview. Significantly more participants entered the program in the MI group (95%) than in the Std group (71%). Although those in the MI group remained in the program longer, and had higher program completion and graduation rates, these differences were not statistically significant. No significant between-group or within-group differences were found in readiness or self-efficacy. This study demonstrates that a single, easily administered intervention can increase program entry. Also based on the study findings, further research into the question of whether MI can increase program retention, in a severely distressed population, is warranted. Published by Elsevier Ireland Ltd. C1 [Harris, Keith W.] VHA Off Mental Hlth Serv, Homeless & Residential Rehabil Treatment Program, Fremont, CA 94538 USA. [Wilbourne, Paula L.] VA Palo Alto Hlth Care Syst, Addict Treatment Serv, Menlo Pk, CA 94025 USA. [Pierson, Heather] VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. [Teleki, Jasmine] Behav Med Clin, Stanford, CA 94304 USA. [Lovett, Steven] VA Palo Alto Hlth Care Syst, Psychol Serv 116B, Palo Alto, CA 94304 USA. RP Harris, KW (reprint author), VHA Off Mental Hlth Serv, Homeless & Residential Rehabil Treatment Program, 39199 Liberty St, Fremont, CA 94538 USA. EM Keith.Harris@va.gov NR 39 TC 8 Z9 8 U1 3 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY 1 PY 2011 VL 115 IS 1-2 BP 113 EP 119 DI 10.1016/j.drugalcdep.2010.11.006 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 770IE UT WOS:000291079400018 PM 21145181 ER PT J AU Wang, JH Cao, ZX Zhao, LL Li, SQ AF Wang, Jihua Cao, Zanxia Zhao, Liling Li, Shuqiang TI Novel Strategies for Drug Discovery Based on Intrinsically Disordered Proteins (IDPs) SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE intrinsically disordered proteins; sequence characterizations; structural characterizations; interaction networks; drug-discovery ID BOUND ALPHA-SYNUCLEIN; UNSTRUCTURED TRANSACTIVATION DOMAIN; NATIVELY UNFOLDED PROTEINS; EXTENDED-HELIX; FUNCTIONAL ANTHOLOGY; INTERACTION NETWORKS; ALPHA-SYN12 PEPTIDE; PARKINSONS-DISEASE; MOLECULAR-DYNAMICS; ALZHEIMERS-DISEASE AB Intrinsically disordered proteins (IDPs) are proteins that usually do not adopt well-defined native structures when isolated in solution under physiological conditions. Numerous IDPs have close relationships with human diseases such as tumor, Parkinson disease, Alzheimer disease, diabetes, and so on. These disease-associated IDPs commonly play principal roles in the disease-associated protein-protein interaction networks. Most of them in the disease datasets have more interactants and hence the size of the disease-associated IDPs interaction network is simultaneously increased. For example, the tumor suppressor protein p53 is an intrinsically disordered protein and also a hub protein in the p53 interaction network; a-synuclein, an intrinsically disordered protein involved in Parkinson diseases, is also a hub of the protein network. The disease-associated IDPs may provide potential targets for drugs modulating protein-protein interaction networks. Therefore, novel strategies for drug discovery based on IDPs are in the ascendant. It is dependent on the features of IDPs to develop the novel strategies. It is found out that IDPs have unique structural features such as high flexibility and random coil-like conformations which enable them to participate in both the. one to many. and. many to one. interaction. Accordingly, in order to promote novel strategies for drug discovery, it is essential that more and more features of IDPs are revealed by experimental and computing methods. C1 [Wang, Jihua; Cao, Zanxia; Zhao, Liling] Shandong Prov Key Lab Funct Macromol Biophys, Dezhou 253023, Peoples R China. [Wang, Jihua; Cao, Zanxia; Zhao, Liling] Dezhou Univ, Dept Phys, Dezhou 253023, Peoples R China. [Li, Shuqiang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wang, JH (reprint author), Shandong Prov Key Lab Funct Macromol Biophys, Dezhou 253023, Peoples R China. EM jhwyh@yahoo.com.cn; qiayilai@mail.ustc.edu.cn; zll2008@mail.ustc.edu.cn; shuqiang_li@dfci.harvard.edu FU Chinese Natural Science Foundation; Shandong Natural Science Foundation [30970561, 31000324, 2009ZRA14027, 2009ZRA14028] FX We thank the financial support from the Chinese Natural Science Foundation and Shandong Natural Science Foundation (grant number 30970561, 31000324, 2009ZRA14027 and 2009ZRA14028). NR 92 TC 14 Z9 15 U1 3 U2 35 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD MAY PY 2011 VL 12 IS 5 BP 3205 EP 3219 DI 10.3390/ijms12053205 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 768QP UT WOS:000290951800032 PM 21686180 ER PT J AU Jang, IK AF Jang, Ik-Kyung TI Optical Coherence Tomography or Intravascular Ultrasound? SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE intravascular ultrasound; optical coherence tomography (OCT); plaque burden; thin capped fibroatheroma (TCFA) ID ATHEROSCLEROTIC PLAQUE; REFLOW AB Intravascular ultrasound (IVUS) has been an important modality in understanding the in vivo pathophysiology of coronary artery disease and in predicting outcome of percutaneous coronary intervention (PCI). The IVUS features associated with acute coronary syndromes include positive remodeling, large plaque burden, ruptured plaque, and intracoronary thrombus. Plaque burden, lesion site calcium, and positive remodeling have been reported to be associated with no-reflow phenomenon and periprocedural myocardial necrosis after PCI (1,2). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 8 TC 5 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 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD MAY PY 2011 VL 4 IS 5 BP 492 EP 494 DI 10.1016/j.jcin.2011.02.004 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 769KR UT WOS:000291012500003 PM 21596320 ER PT J AU Rumsfeld, JS Allen, LA AF Rumsfeld, John S. Allen, Larry A. TI Reducing Readmission Rates Does Coronary Artery Bypass Graft Surgery Provide Clarity? SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material DE coronary artery bypass graft surgery; outcomes; quality measures; readmission; rehospitalization ID HEART-FAILURE AB Because hospital readmissions are costly and potentially avoidable, reducing hospital readmission rates has been touted as a means to improve quality and reduce costs. Cardiovascular disease is a natural focus for this because of overall costs of treatment and frequency of readmission (e.g., nearly 1 in 4 Medicare patients is readmitted within 30 days after hospitalization for heart failure) (1). Since 2009, hospital-level 30-day risk-standardized readmission rates for acute myocardial infarction and heart failure have been publicly reported for Medicare patients (1). C1 [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Rumsfeld, John S.; Allen, Larry A.] Colorado Cardiovasc Outcomes Res Consortium, Denver, CO USA. [Rumsfeld, John S.; Allen, Larry A.] Univ Colorado, Div Cardiol, Aurora, CO USA. RP Rumsfeld, JS (reprint author), VA Eastern Colorado Hlth Care Syst, Cardiol 111B,1055 Clermont St, Denver, CO 80220 USA. EM john.rumsfeld@va.gov NR 8 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD MAY PY 2011 VL 4 IS 5 BP 577 EP 578 DI 10.1016/j.jcin.2011.04.002 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 769KR UT WOS:000291012500015 PM 21596332 ER PT J AU Goldfarb, JW Bittner, EA George, E Welch, C Schmidt, U AF Goldfarb, Jeremy W. Bittner, Edward A. George, Edward Welch, Charles Schmidt, Ulrich TI Successful management of a morbidly obese patient for electroconvulsive therapy with elective tracheostomy SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material DE Elective tracheostomy; Electroconvulsive therapy; Morbid obesity ID PERCUTANEOUS TRACHEOSTOMY; SLEEP-APNEA; SUCCINYLCHOLINE; ANESTHESIA; POSITION AB Electroconvulsive therapy (ECT) is a treatment for affective catatonia and requires multiple general anesthetics. Morbid obesity is an increasingly prevalent condition that may complicate the standard anesthetic management of a patient undergoing ECT. We report the successful airway management of a morbidly obese ECT patient via elective tracheostomy. (C) 2011 Elsevier Inc. All rights reserved. C1 [Goldfarb, Jeremy W.; Bittner, Edward A.; George, Edward; Schmidt, Ulrich] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. [Welch, Charles] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Goldfarb, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. EM jwgoldfarb@partners.org NR 28 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD MAY PY 2011 VL 23 IS 3 BP 241 EP 243 DI 10.1016/j.jclinane.2010.05.009 PG 3 WC Anesthesiology SC Anesthesiology GA 770IN UT WOS:000291080300015 PM 21507618 ER PT J AU Balboni, MJ Babar, A Dillinger, J Phelps, AC George, E Block, SD Kachnic, L Hunt, J Peteet, J Prigerson, HG VanderWeele, TJ Balboni, TA AF Balboni, Michael J. Babar, Amenah Dillinger, Jennifer Phelps, Andrea C. George, Emily Block, Susan D. Kachnic, Lisa Hunt, Jessica Peteet, John Prigerson, Holly G. VanderWeele, Tyler J. Balboni, Tracy A. TI "It Depends": Viewpoints of Patients, Physicians, and Nurses on Patient-Practitioner Prayer in the Setting of Advanced Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Prayer; spirituality; religion; spiritual care; end-of-life care; palliative care ID QUALITY-OF-LIFE; SPIRITUAL CARE; RELIGIOUS CHARACTERISTICS; NEAR-DEATH; BELIEFS; ATTITUDES; ASSOCIATIONS; PREFERENCES; MEDICINE; WANT AB Context. Although prayer potentially serves as an important practice in offering religious/spiritual support, its role in the clinical setting remains disputed. Few data exist to guide the role of patient-practitioner prayer in the setting of advanced illness. Objectives. To inform the role of prayer in the setting of life-threatening illness, this study used mixed quantitative-qualitative methods to describe the viewpoints expressed by patients with advanced cancer, oncology nurses, and oncology physicians concerning the appropriateness of clinician prayer. Methods. This is a cross-sectional, multisite, mixed-methods study of advanced cancer patients (n = 70), oncology physicians (n = 206), and oncology nurses (n = 115). Semistructured interviews were used to assess respondents' attitudes toward the appropriate role of prayer in the context of advanced cancer. Theme extraction was performed based on interdisciplinary input using grounded theory. Results. Most advanced cancer patients (71%), nurses (83%), and physicians (65%) reported that patient-initiated patient-practitioner prayer was at least occasionally appropriate. Furthermore, clinician prayer was viewed as at least occasionally appropriate by the majority of patients (64%), nurses (76%), and physicians (59%). Of those patients who could envision themselves asking their physician or nurse for prayer (61%), 86% would find this form of prayer spiritually supportive. Most patients (80%) viewed practitioner-initiated prayer as spiritually supportive. Open-ended responses regarding the appropriateness of patient-practitioner prayer in the advanced cancer setting revealed six themes shaping respondents' viewpoints: necessary conditions for prayer, potential benefits of prayer, critical attitudes toward prayer, positive attitudes toward prayer, potential negative consequences of prayer, and prayer alternatives. Conclusion. Most patients and practitioners view patient-practitioner prayer as at least occasionally appropriate in the advanced cancer setting, and most patients view prayer as spiritually supportive. However, the appropriateness of patient-practitioner prayer is case specific, requiring consideration of multiple factors. J Pain Symptom Manage 2011; 41:836-847. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Balboni, Michael J.; Phelps, Andrea C.; Block, Susan D.; Hunt, Jessica; Peteet, John; Prigerson, Holly G.; Balboni, Tracy A.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02120 USA. [Balboni, Michael J.; Phelps, Andrea C.; Block, Susan D.; Peteet, John; Prigerson, Holly G.; Balboni, Tracy A.] Dana Farber Canc Inst, Dept Psychooncol, Boston, MA 02120 USA. [Balboni, Michael J.; Phelps, Andrea C.; Block, Susan D.; Peteet, John; Prigerson, Holly G.; Balboni, Tracy A.] Dana Farber Canc Inst, Dept Palliat Care, Boston, MA 02120 USA. [Dillinger, Jennifer] Dana Farber Canc Inst, Dept Chaplaincy, Boston, MA 02120 USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02120 USA. [Balboni, Michael J.] Boston Univ, Sch Theol, Boston, MA 02215 USA. [Babar, Amenah] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [George, Emily] Boston Med Ctr, Dept Med Oncol, Boston, MA USA. [Kachnic, Lisa] Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. [Block, Susan D.; Peteet, John; Prigerson, Holly G.; Balboni, Tracy A.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Balboni, MJ (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 44 Binney St, Boston, MA 02120 USA. EM michael_balboni@dfci.harvard.edu FU American Society of Clinical Oncology FX This research was supported in part by an American Society of Clinical Oncology Young Investigator Award to Dr. Tracy Balboni. NR 35 TC 15 Z9 15 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 2011 VL 41 IS 5 BP 836 EP 847 DI 10.1016/j.jpainsymman.2010.07.008 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 768NQ UT WOS:000290942200007 PM 21276700 ER PT J AU Goebel, JR Compton, P Zubkoff, L Lanto, A Asch, SM Sherbourne, CD Shugarman, L Lorenz, KA AF Goebel, Joy R. Compton, Peggy Zubkoff, Lisa Lanto, Andy Asch, Steven M. Sherbourne, Cathy D. Shugarman, Lisa Lorenz, Karl A. TI Prescription Sharing, Alcohol Use, and Street Drug Use to Manage Pain Among Veterans SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Prescription sharing; substance use disorders; substance misuse; street drugs; mental health; pain management; symptoms; quality of life; spiritual well-being ID SUBSTANCE USE DISORDERS; CHRONIC NONCANCER PAIN; PHYSICAL-DEPENDENCE; ANALGESIC THERAPY; NONMALIGNANT PAIN; OPIOID MISUSE; PRIMARY-CARE; ABUSE; PSEUDOADDICTION; PREVALENCE AB Context. Efforts to promote awareness and management of chronic pain have been accompanied by a troubling increase in prescription medication abuse. At the same time, some patients may misuse substances in an effort to manage chronic pain. Objectives. This study examines self-reported substance misuse for pain management among veterans and identifies the contributing factors. Methods. We analyzed cross-sectional data from the Help Veterans Experience Less Pain study. Results. Of 343 veterans, 35.3% reported an aberrant pain management behavior (24% reported using alcohol, 11.7% reported using street drugs, and 16.3% reported sharing prescriptions to manage pain). Poorer mental health, younger age, substance use disorders (SUDs), number of nonpain symptoms, and greater pain severity and interference were associated with aberrant pain management behaviors. In multivariate analysis, SUDs (odds ratio [OR]: 3.9, 95% confidence interval [CI]: 2.3-6.7, P < 0.000) and poorer mental health (OR: 2.3, 95% CI: 1.3-4.3, P = 0.006) were associated with using alcohol or street drugs to manage pain; SUDs (OR: 2.4, 95% CI: 1.3-4.4, P - 0.006) and pain interference (OR: 1.1, 95% CI: 1.0-1.2, P = 0.047) were associated with prescription sharing; and SUDs (OR: 3.6, 95% CI: 2.2-6.1, P < 0.000) and number of nonpain symptoms (OR: 6.5, 95% CI: 1.2-35.4, P = 0.031) were associated with any aberrant pain management behavior. Conclusion. Veterans with a history of SUDs, greater pain interference, more nonpain symptoms, and mental health concerns should be carefully managed to deter substance misuse for pain management. J Pain Symptom Manage 2011; 41:848-858. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Goebel, Joy R.] Calif State Univ Long Beach, Sch Nursing, Long Beach, CA 90840 USA. [Compton, Peggy] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Asch, Steven M.; Lorenz, Karl A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Zubkoff, Lisa] Vet Affairs Med Ctr, New England HealthCare Engn Partnership, White River Jct, VT USA. [Lanto, Andy; Asch, Steven M.; Lorenz, Karl A.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven M.; Sherbourne, Cathy D.; Shugarman, Lisa; Lorenz, Karl A.] RAND Corp, Santa Monica, CA USA. RP Goebel, JR (reprint author), Calif State Univ Long Beach, Sch Nursing, 1250 Bellflower Blvd, Long Beach, CA 90840 USA. EM jgoebel@csulb.edu FU Department of Veterans Affairs Health Services Research Development [IIR 03-152] FX This study was funded by the Department of Veterans Affairs Health Services Research & Development Merit Award IIR 03-152. K. L. is the recipient of a VA HSR&D Advanced Career Development Award. The authors declare no conflicts of interest. NR 69 TC 16 Z9 16 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 2011 VL 41 IS 5 BP 848 EP 858 DI 10.1016/j.jpainsymman.2010.07.009 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 768NQ UT WOS:000290942200008 PM 21256706 ER PT J AU Conley, DM Singer, SJ Edmondson, L Berry, WR Gawande, AA AF Conley, Dante M. Singer, Sara J. Edmondson, Lizabeth Berry, William R. Gawande, Atul A. TI Effective Surgical Safety Checklist Implementation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID TECHNOLOGY; MORTALITY AB BACKGROUND: Research suggests that surgical safety checklists can reduce mortality and other postoperative complications. The real world impact of surgical safety checklists on patient outcomes, however, depends on the effectiveness of hospitals' implementation processes. STUDY DESIGN: We studied implementation processes in 5 Washington State hospitals by conducting semistructured interviews with implementation leaders and surgeons from September to December 2009. Interviews were transcribed, analyzed, and compared with findings from previous implementation research to identify factors that distinguish effective implementation. RESULTS: Qualitative analysis suggested that effectiveness hinges on the ability of implementation leaders to persuasively explain why and adaptively show how to use the checklist. Coordinated efforts to explain why the checklist is being implemented and extensive education regarding its use resulted in buy-in among surgical staff and thorough checklist use. When implementation leaders did not explain why or show how the checklist should be used, staff neither understood the rationale behind implementation nor were they adequately prepared to use the checklist, leading to frustration, disinterest, and eventual abandonment despite a hospital-wide mandate. CONCLUSIONS: The impact of surgical safety checklists on patient outcomes is likely to vary with the effectiveness of each hospital's implementation process. Further research is needed to confirm these findings and reveal additional factors supportive of checklist implementation. (J Am Coll Surg 2011;212:873-879. (C) 2011 by the American College of Surgeons) C1 [Conley, Dante M.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Conley, Dante M.] Univ Washington, Seattle, WA 98195 USA. [Singer, Sara J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Edmondson, Lizabeth; Gawande, Atul A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Conley, DM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave,Kresge Bldg,Room 112, Boston, MA 02115 USA. EM cdante@uw.edu OI Gawande, Atul/0000-0002-1824-9176 NR 12 TC 98 Z9 101 U1 2 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAY PY 2011 VL 212 IS 5 BP 873 EP 879 DI 10.1016/j.jamcollsurg.2011.01.052 PG 7 WC Surgery SC Surgery GA 768RU UT WOS:000290956000017 PM 21398154 ER PT J AU Raval, MV Wang, X Cohen, ME Ingraham, AM Bentrem, DJ Dimick, JB Flynn, T Hall, BL Ko, CY AF Raval, Mehul V. Wang, Xue Cohen, Mark E. Ingraham, Angela M. Bentrem, David J. Dimick, Justin B. Flynn, Timothy Hall, Bruce L. Ko, Clifford Y. TI The Influence of Resident Involvement on Surgical Outcomes SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; RISK ADJUSTMENT; PATIENT SAFETY; NONTEACHING HOSPITALS; TEACHING HOSPITALS; INPATIENT SURGERY; MEDICARE PATIENTS; AMERICAN-COLLEGE; GENERAL-SURGERY; MORTALITY AB BACKGROUND: Although the training of surgical residents is often considered in national policy addressing complications and safety, the influence of resident intraoperative involvement on surgical outcomes has not been well studied. STUDY DESIGN: We identified 607,683 surgical cases from 234 hospitals from the 2006 to 2009 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). Outcomes were compared by resident involvement for all general and vascular cases as well as for specific general surgical procedures. RESULTS: After typical ACS NSQIP comorbidity risk adjustment and further adjustment for hospital teaching status and operative time in modeling, resident intraoperative involvement was associated with slightly increased morbidity when assessing overall general or vascular procedures (odds ratio [OR] 1.06; 95% CI 1.04 to 1.09), pancreatectomy or esophagectomy (OR 1.26; 95% CI 1.08 to 1.45), and colorectal resections (OR 1.15; 95% CI 1.09 to 1.22). In contrast, for mortality, resident intraoperative involvement was associated with reductions for overall general and vascular procedures (OR 0.91; 95% CI 0.84 to 0.99), colorectal resections (OR 0.88; 95% CI 0.78 to 0.99), and abdominal aortic aneurysm repair (OR 0.71; 95% CI 0.53 to 0.95). Results were moderated somewhat after hierarchical modeling was performed to account for hospital-level variation, with mortality results no longer reaching significance (overall morbidity OR 1.07; 95% CI 1.03 to 1.10, overall mortality OR 0.97; 95% CI 0.90 to 1.05). Based on risk-adjusted event rates, resident intraoperative involvement is associated with approximately 6.1 additional morbidity events but 1.4 fewer deaths per 1,000 general and vascular surgery procedures. CONCLUSIONS: Resident intraoperative participation is associated with slightly higher morbidity rates but slightly decreased mortality rates across a variety of procedures and is minimized further after taking into account hospital-level variation. These clinically small effects may serve to reassure patients and others that resident involvement in surgical care is safe and possibly protective with regard to mortality. (J Am Coll Surg 2011;212:889-898. (C) 2011 by the American College of Surgeons) C1 [Raval, Mehul V.; Wang, Xue; Cohen, Mark E.; Ingraham, Angela M.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Raval, Mehul V.; Bentrem, David J.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Bentrem, David J.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Ingraham, Angela M.] Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 USA. [Dimick, Justin B.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Flynn, Timothy] Univ Florida, Gainesville, FL USA. Washington Univ, Dept Surg, John Cochran Vet Affairs Med Ctr, St Louis, MO USA. Barnes Jewish Hosp, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO 63130 USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO 63130 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Raval, MV (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM m-raval@md.northwestern.edu OI Raval, Mehul/0000-0002-1527-2661 FU John Gray Research Fellowship; Daniel F and Ada L Rice Foundation; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FX Drs Raval and Ingraham participate in the American College of Surgeons Clinical Scholars in Residence Program. Dr Raval is supported by the John Gray Research Fellowship and the Daniel F and Ada L Rice Foundation. Dr Bentrem is supported by a career development award from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service. Dr Hall assists with the conduct of the ACS NSQIP nationally. NR 46 TC 101 Z9 101 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAY PY 2011 VL 212 IS 5 BP 889 EP 898 DI 10.1016/j.jamcollsurg.2010.12.029 PG 10 WC Surgery SC Surgery GA 768RU UT WOS:000290956000019 PM 21398151 ER PT J AU Filley, CM Brodtmann, A AF Filley, Christopher M. Brodtmann, Amy TI Lacunes and cognitive decline Little things matter SO NEUROLOGY LA English DT Editorial Material ID SMALL VESSEL DISEASE; DEMENTIA; ATROPHY; MRI C1 [Filley, Christopher M.] Univ Colorado, Dept Neurol, Sch Med, Aurora, CO USA. [Filley, Christopher M.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Brodtmann, Amy] Univ Melbourne, Florey Neurosci Inst, Melbourne, Vic, Australia. RP Filley, CM (reprint author), Behav Neurol Sect, 12631 E 17th Ave,POB 6511, Aurora, CO 80045 USA. EM filley@ucdenver.edu NR 15 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2011 VL 76 IS 22 BP 1856 EP 1857 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 769WN UT WOS:000291049100005 PM 21543732 ER PT J AU Walcott, BP Kahle, KT Wain, JC Borges, LF AF Walcott, Brian P. Kahle, Kristopher T. Wain, John C. Borges, Lawrence F. TI Giant thoracic meningocele associated with neurofibromatosis 1 SO NEUROLOGY LA English DT Editorial Material RP Borges, LF (reprint author), Massachusetts Gen Hosp, Neurosurg Stereoscop Dimens Video Lab 3, Neurosurg Spine Serv, White 1205,55 Fruit St, Boston, MA 02114 USA. EM LBorges@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2011 VL 76 IS 22 BP 1943 EP 1943 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 769WN UT WOS:000291049100019 PM 21624995 ER PT J AU Groessl, EJ Weingart, KR Gifford, AL Asch, SM Ho, SB AF Groessl, Erik J. Weingart, Kimberly R. Gifford, Allen L. Asch, Steven M. Ho, Samuel B. TI Development of the Hepatitis C Self-Management Program SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Patient self-management; Cognitive/behavioral interventions; Hepatitis C ID QUALITY-OF-LIFE; PRIMARY-CARE PATIENTS; VIRUS-INFECTION; ANTIVIRAL THERAPY; WEIGHT-REDUCTION; CHRONIC DISEASE; PLUS RIBAVIRIN; UNITED-STATES; HEALTH-CARE; VETERANS AB Objective: Chronic hepatitis C infection (HCV) is a major health problem that disproportionately affects people with limited resources. Many people with HCV are ineligible or refuse antiviral treatment, but less curative treatment options exist. These options include adhering to follow-up health visits, lifestyle changes, and avoiding hepatotoxins like alcohol. Herein, we describe a recently developed self-management program designed to assist HCV-infected patients with adherence and improve their health-related quality of life (HRQOL). Methods: The development of the Hepatitis C Self-Management Program (HCV-SMP) was informed by scientific literature, qualitative interviews with HCV-infected patients, self-management training, and feedback from HCV clinical experts. Results: The Hepatitis C Self-Management Program (HCV-SMP) is a multi-faceted program that employs cognitive-behavioral principles and is designed to provide HCV-infected people with knowledge and skills for improving their HRQOL. The program consists of six 2-h workshop sessions which are held weekly. The sessions consist of a variety of group activities, including disease-specific information dissemination, action planning, and problem-solving. Conclusion: The intervention teaches skills for adhering to challenging treatment recommendations using a validated theoretical model. A randomized trial will test the efficacy of this novel HCV self-management program for improving HRQOL in a difficult to reach population. Published by Elsevier Ireland Ltd. C1 [Groessl, Erik J.; Weingart, Kimberly R.; Ho, Samuel B.] VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Groessl, Erik J.; Ho, Samuel B.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Gifford, Allen L.] Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Gifford, Allen L.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Asch, Steven M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven M.] Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA 90024 USA. RP Groessl, EJ (reprint author), VA San Diego Healthcare Syst, 3350 La Jolla Village Dr 111 N-1, San Diego, CA 92161 USA. EM egroessl@ucsd.edu FU VA HSRD [IAC 05-067] FX This study is funded by a research grant from the VA HSR&D, Project # IAC 05-067. NR 41 TC 5 Z9 5 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD MAY PY 2011 VL 83 IS 2 BP 252 EP 255 DI 10.1016/j.pec.2010.06.006 PG 4 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 768JC UT WOS:000290929200020 PM 20638216 ER PT J AU McTigue, KM Bhargava, T Bryce, CL Conroy, M Fischer, GS Hess, R Simkin-Silverman, LR Zickmund, S AF McTigue, Kathleen M. Bhargava, Tina Bryce, Cindy L. Conroy, Molly Fischer, Gary S. Hess, Rachel Simkin-Silverman, Laurey R. Zickmund, Susan TI Patient perspectives on the integration of an intensive online behavioral weight loss intervention into primary care SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Primary health care; Internet; Obesity; Counseling; Preventive medicine ID LIFE-STYLE INTERVENTION; OBESITY; PHYSICIANS; HEALTH; MANAGEMENT; ADULTS; PREVENTION; ATTITUDES; INTERNET; ADVICE AB Objective: To examine patients' perception of how a referral-based online lifestyle intervention contributed to primary care medicine. Methods: We invited 50 adults to complete a semi-structured interview after a 1-year online behavioral weight loss intervention (average weight change: -4.79 kg). We developed an iterative codebook using content analysis. Two coders independently coded all transcripts (kappa = 0.895). We analyzed responses regarding the integration of the program with primary care. Results: Among the 35 participants who completed the interview, 46% described a positive experience between the program and their routine medical care; 14% noted it was fine/OK; 9% reported no effect, 3% were negative, 11% said that the program was unrelated to their medical care, and 14% that the only connection was the referral. Factors such as physician feedback and support, coordination with routine health care, and improved cardiovascular risk factors were cited in support of a positive experience. Physician feedback was reported by 89%, and 80% stated that the program helped them to follow their physician's advice. Conclusion: Physician referral to online education and counseling may facilitate the integration of evidence-based behavioral counseling with primary care. Practice implications: Internet technology may enable improved access to evidence-based counseling for chronic health problems. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [McTigue, Kathleen M.; Bhargava, Tina; Bryce, Cindy L.; Conroy, Molly; Fischer, Gary S.; Hess, Rachel; Zickmund, Susan] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [McTigue, Kathleen M.; Conroy, Molly; Hess, Rachel; Simkin-Silverman, Laurey R.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Bhargava, Tina] Univ Pittsburgh, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15213 USA. [Zickmund, Susan] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP McTigue, KM (reprint author), Univ Pittsburgh, Dept Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM kmm34@pitt.edu; tdb11@pitt.edu; brycecl@upmc.edu; conroymb@upmc.edu; fischerg@upmc.edu; rah67@pitt.edu; lrs@pitt.edu; Susan.Zickmund@va.gov OI Bryce, Cindy/0000-0001-6356-6675; Simkin-Silverman, Lauren/0000-0003-1572-8726 FU Department of Defense through University of Pittsburgh Diabetes Institute [USAMRAA W81XWH-04-2-0030] FX This project was supported with a grant from the Department of Defense [USAMRAA W81XWH-04-2-0030 Siminerio (PI)]. through the University of Pittsburgh Diabetes Institute. While the University of Pittsburgh has licensed the online program's contents to DPS Health, the authors have assigned the copyright to the University and receive no personal royalties from its commercial use. Support for Dr. Zickmund was provided in part by the Veteran's Administration Health Services Research and Development Merit Review funds. NR 33 TC 7 Z9 7 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD MAY PY 2011 VL 83 IS 2 BP 261 EP 264 DI 10.1016/j.pec.2010.05.009 PG 4 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 768JC UT WOS:000290929200022 PM 21459256 ER PT J AU Chen, YX Gelfond, J McManus, LM Shireman, PK AF Chen, Yongxin Gelfond, Jonathan McManus, Linda M. Shireman, Paula K. TI Temporal microRNA expression during in vitro myogenic progenitor cell proliferation and differentiation: regulation of proliferation by miR-682 SO PHYSIOLOGICAL GENOMICS LA English DT Article DE muscle regeneration; muscle differentiation; muscle regeneration; satellite cell ID MUSCLE SATELLITE CELLS; SKELETAL-MUSCLE; GENE-EXPRESSION; MICROARRAY DATA; STEM-CELLS; REGENERATION; GROWTH; REPRESSION; APOPTOSIS; MIR-206 AB Chen Y, Gelfond J, McManus LM, Shireman PK. Temporal microRNA expression during in vitro myogenic progenitor cell proliferation and differentiation: regulation of proliferation by miR-682. Physiol Genomics 43: 621-630, 2011. First published September 14, 2010; doi:10.1152/physiolgenomics.00136.2010.MicroRNAs (miRNAs) regulate gene expression by repressing target genes at the posttranscriptional level. Since miRNAs have unique expression profiles in different tissues, they provide pivotal regulation of many biological processes. The present study defined miRNA expression during murine myogenic progenitor cell (MPC) proliferation and differentiation to identify miRNAs involved in muscle regeneration. Muscle-related gene expression analyses revealed that the time course and expression of myosin heavy chain (MHC) and transcription factors (Myf5, MyoD, myogenin, and Pax7) were similar during in vitro MPC proliferation/differentiation and in vivo muscle regeneration. Comprehensive profiling revealed that 139 or 16 miRNAs were significantly changed more than twofold [false discovery rate (FDR) < 0.05] during MPC differentiation or proliferation, respectively; cluster analyses revealed five distinct patterns of miRNA expression during the time course of MPC differentiation. Not unexpectedly, the largest miRNA changes occurred in muscle-specific miRNAs (miR-1, -133a, and -499), which were upregulated > 10-fold during MPC differentiation (FDR < 0.01). However, several previously unreported miRNAs were differentially expressed, including miR-10b, -335-3p, and -682. Interestingly, the temporal patterns of miR-1, -499, and -682 expression during in vitro MPC proliferation/differentiation were remarkably similar to those observed during in vivo muscle regeneration. Moreover, in vitro inhibition of miR-682, the only miRNA upregulated in proliferating compared with quiescent MPC, led to decreased MPC proliferation, further validating our in vitro assay system for the identification of miRNAs involved in muscle regeneration. Thus the differentially expressed miRNAs identified in the present study could represent new regulatory elements in MPC proliferation and differentiation. C1 [Chen, Yongxin; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Gelfond, Jonathan] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Chen, Yongxin; Shireman, Paula K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Chen, YX (reprint author), 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cheny4@uthscsa.edu FU Department of Veterans Affairs; National Institutes of Health [R01-HL-074236, T32-HL-07446, KL2-RR-025766] FX These studies were supported, in part, by a Department of Veterans Affairs Merit Review grant and National Institutes of Health Grants R01-HL-074236, T32-HL-07446, and KL2-RR-025766. NR 63 TC 29 Z9 30 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 EI 1531-2267 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD MAY PY 2011 VL 43 IS 10 BP 621 EP 630 DI 10.1152/physiolgenomics.00136.2010 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 769LK UT WOS:000291014800013 PM 20841498 ER PT J AU Sohn, Y Choi, MK Ahn, YY Lee, J Jeong, J AF Sohn, Yunkyu Choi, Myung-Kyu Ahn, Yong-Yeol Lee, Junho Jeong, Jaeseung TI Topological Cluster Analysis Reveals the Systemic Organization of the Caenorhabditis elegans Connectome SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID GRAPH-THEORETICAL ANALYSIS; COMPLEX BRAIN NETWORKS; SMALL-WORLD NETWORKS; C-ELEGANS; ARCHITECTURE; CIRCUIT; PROTEIN AB The modular organization of networks of individual neurons interwoven through synapses has not been fully explored due to the incredible complexity of the connectivity architecture. Here we use the modularity-based community detection method for directed, weighted networks to examine hierarchically organized modules in the complete wiring diagram (connectome) of Caenorhabditis elegans (C. elegans) and to investigate their topological properties. Incorporating bilateral symmetry of the network as an important cue for proper cluster assignment, we identified anatomical clusters in the C. elegans connectome, including a body-spanning cluster, which correspond to experimentally identified functional circuits. Moreover, the hierarchical organization of the five clusters explains the systemic cooperation (e. g., mechanosensation, chemosensation, and navigation) that occurs among the structurally segregated biological circuits to produce higher-order complex behaviors. C1 [Sohn, Yunkyu; Jeong, Jaeseung] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea. [Sohn, Yunkyu] Univ Calif San Diego, Dept Polit Sci, San Diego, CA 92103 USA. [Choi, Myung-Kyu; Lee, Junho] Seoul Natl Univ, Inst Mol Biol & Genet, Sch Biol Sci, Res Ctr Cellul,Dept Biophys & Chem Biol, Seoul, South Korea. [Ahn, Yong-Yeol] Northeastern Univ, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA. [Ahn, Yong-Yeol] Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Sohn, Y (reprint author), Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea. EM jsjeong@kaist.ac.kr RI Jeong, Jaeseung /C-1620-2011; OI Ahn, Yong-Yeol/0000-0002-4352-4301 FU CHUNG MoonSoul Research Center for BioInformation and BioElectronics (CMSC) in KAIST; Korea government (MOST) [R01-2007-000-21094-0, M10644000028-06N4400-02810]; Ministry of Science and Technology, the Republic of Korea [M103KV010018-08K2201-01810] FX This work was supported by CHUNG MoonSoul Research Center for BioInformation and BioElectronics (CMSC) in KAIST, the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (No. R01-2007-000-21094-0 and No. M10644000028-06N4400-02810) (J. Jeong). This work was also supported in part by a grant (M103KV010018-08K2201-01810) from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea (J. Lee). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 22 Z9 22 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAY PY 2011 VL 7 IS 5 AR e1001139 DI 10.1371/journal.pcbi.1001139 PG 10 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 769LT UT WOS:000291015800013 PM 21625578 ER PT J AU Ranasinghe, SRF Kramer, HB Wright, C Kessler, BM di Gleria, K Zhang, YH Gillespie, GM Blais, ME Culshaw, A Pichulik, T Simmons, A Rowland-Jones, SL McMichael, AJ Dong, T AF Ranasinghe, Srinika R. F. Kramer, Holger B. Wright, Cynthia Kessler, Benedikt M. di Gleria, Katalin Zhang, Yonghong Gillespie, Geraldine M. Blais, Marie-Eve Culshaw, Abigail Pichulik, Tica Simmons, Alison Rowland-Jones, Sarah L. McMichael, Andrew J. Dong, Tao TI The Antiviral Efficacy of HIV-Specific CD8(+) T-Cells to a Conserved Epitope Is Heavily Dependent on the Infecting HIV-1 Isolate SO PLOS PATHOGENS LA English DT Article ID MHC-CLASS-I; IMMUNODEFICIENCY-VIRUS TYPE-1; CELLULAR IMMUNE-RESPONSES; ANTIGEN PRESENTATION; LYMPHOCYTE ESCAPE; VIRAL LOAD; VACCINE; PROTEASOME; NEF; HLA AB A major challenge to developing a successful HIV vaccine is the vast diversity of viral sequences, yet it is generally assumed that an epitope conserved between different strains will be recognised by responding T-cells. We examined whether an invariant HLA-B8 restricted Nef(90-97) epitope FL8 shared between five high titre viruses and eight recombinant vaccinia viruses expressing Nef from different viral isolates (clades A-H) could activate antiviral activity in FL8-specific cytotoxic T-lymphocytes (CTL). Surprisingly, despite epitope conservation, we found that CTL antiviral efficacy is dependent on the infecting viral isolate. Only 23% of Nef proteins, expressed by HIV-1 isolates or as recombinant vaccinia-Nef, were optimally recognised by CTL. Recognition of the HIV-1 isolates by CTL was independent of clade-grouping but correlated with virus-specific polymorphisms in the epitope flanking region, which altered immunoproteasomal cleavage resulting in enhanced or impaired epitope generation. The finding that the majority of virus isolates failed to present this conserved epitope highlights the importance of viral variance in CTL epitope flanking regions on the efficiency of antigen processing, which has been considerably underestimated previously. This has important implications for future vaccine design strategies since efficient presentation of conserved viral epitopes is necessary to promote enhanced anti-viral immune responses. C1 [Ranasinghe, Srinika R. F.; di Gleria, Katalin; Zhang, Yonghong; Gillespie, Geraldine M.; Blais, Marie-Eve; Culshaw, Abigail; Pichulik, Tica; Simmons, Alison; Rowland-Jones, Sarah L.; McMichael, Andrew J.; Dong, Tao] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC,Human Immunol Unit, Oxford OX3 9DU, England. [Kramer, Holger B.; Wright, Cynthia; Kessler, Benedikt M.] Univ Oxford, Nuffield Dept Clin Med, Oxford OX3 9DU, England. [Zhang, Yonghong] BeiJing Capital Univ, BeiJing YouAn Hosp, Beijing, Peoples R China. RP Ranasinghe, SRF (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. EM srinika.ranasinghe@bnc.oxon-org; tao.dong@imm.ox.ac.uk OI Kessler, Benedikt/0000-0002-8160-2446 FU MRC FX SRFR was supported by an MRC-funded PhD studentship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 12 Z9 12 U1 0 U2 2 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 MAY PY 2011 VL 7 IS 5 AR e1001341 DI 10.1371/journal.ppat.1001341 PG 16 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 769LC UT WOS:000291014000006 PM 21589893 ER PT J AU Scioli, A Ricci, M Nyugen, T Scioli, ER AF Scioli, Anthony Ricci, Michael Than Nyugen Scioli, Erica R. TI Hope: Its Nature and Measurement SO PSYCHOLOGY OF RELIGION AND SPIRITUALITY LA English DT Article DE hope; depression; anxiety; health; measurement ID PSYCHOLOGY; VALIDATION AB Hope is a powerful emotion that has been largely neglected by the social sciences. In this paper, we introduce a theory of hope drawn from multiple disciplines, including psychology, philosophy, theology, and medicine. Our integrative approach features four components: the attachment, mastery, and survival motives, as well as spiritual beliefs. In addition, we describe four different empirical analyses aimed at the development and refinement of a comprehensive set of scales for measuring state and trait hope. C1 [Scioli, Anthony; Ricci, Michael; Than Nyugen] Keene State Coll, Dept Psychol, Keene, NH 03435 USA. [Scioli, Erica R.] VA Boston Healthcare Syst, Boston, MA USA. RP Scioli, A (reprint author), Keene State Coll, Dept Psychol, Keene, NH 03435 USA. EM tscioli@keene.edu NR 69 TC 20 Z9 21 U1 3 U2 19 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1941-1022 J9 PSYCHOL RELIG SPIRIT JI Psychol. Relig. Spiritual. PD MAY PY 2011 VL 3 IS 2 BP 78 EP 97 DI 10.1037/a0020903 PG 20 WC Psychology, Multidisciplinary; Religion SC Psychology; Religion GA 768YP UT WOS:000290976200002 ER PT J AU Da Silva, N Cortez-Retamozo, V Reinecker, HC Wildgruber, M Hill, E Brown, D Swirski, FK Pittet, MJ Breton, S AF Da Silva, Nicolas Cortez-Retamozo, Virna Reinecker, Hans-Christian Wildgruber, Moritz Hill, Eric Brown, Dennis Swirski, Filip K. Pittet, Mikael J. Breton, Sylvie TI A dense network of dendritic cells populates the murine epididymis SO REPRODUCTION LA English DT Article ID IMMUNO-COMPETENT CELLS; REGULATORY T-CELLS; RAT EPIDIDYMIS; LUMINAL ACIDIFICATION; PERIPHERAL TOLERANCE; DEPENDENT MECHANISM; REPRODUCTIVE-TRACT; HIV-1 TRANSMISSION; MOUSE EPIDIDYMIS; LANGERHANS CELLS AB One of the most intriguing aspects of male reproductive physiology is the ability to generate spermatogenic cells - which are 'foreign' to the host - without triggering immune activation. After leaving the testis, spermatozoa enter the epididymis where they mature and are stored. In this study, we report a previously unrecognized dense network of dendritic cells (DCs) located at the base of the epididymal epithelium. This network was detected in transgenic mice expressing CD11c-EYFP and CX3CR1-GFP reporters. Epididymal DCs (eDCs) establish intimate interactions with the epithelium and project long dendrites between epithelial cells toward the lumen. We show that isolated eDCs express numerous leukocyte markers described previously in other organs that are in contact with the external environment, and present and cross-present ovalbumin to T cells in vitro. eDCs are, therefore, strategically positioned to regulate the complex interplay between immune tolerance and activation, a balance that is fundamental to male fertility. Reproduction (2011) 141 653-663 C1 [Da Silva, Nicolas; Hill, Eric; Brown, Dennis; Breton, Sylvie] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Da Silva, Nicolas] Massachusetts Gen Hosp, Ctr Syst Biol, Div Nephrol, Boston, MA 02114 USA. [Reinecker, Hans-Christian] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Reinecker, Hans-Christian] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Da Silva, N (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. EM dasilva.nicolas@mgh.harvard.edu FU National Institutes of Health [DK085715, DK38452]; MGH Center for the Study of Inflammatory Bowel Disease (CSIBD) [DK43351, CA086355, AI084880, R01HL095612]; Boston Area Diabetes and Endocrinology Research Center [DK57521] FX This study was supported by National Institutes of Health grants DK085715 and DK38452 (S Breton), MGH Center for the Study of Inflammatory Bowel Disease (CSIBD) pilot feasibility grant (DK43351, N Da Silva), CA086355 and AI084880 (M J Pittet), R01HL095612 (F K Swirski). The Microscopy Core facility of the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center (DK57521) and the CSIBD (DK43351). NR 76 TC 37 Z9 37 U1 1 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD MAY PY 2011 VL 141 IS 5 BP 653 EP 663 DI 10.1530/REP-10-0493 PG 11 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 768DC UT WOS:000290910700011 PM 21310816 ER PT J AU Spencer, J Amin, J Wang, MH Packham, G Alwi, SSS Tizzard, GJ Coles, SJ Paranal, RM Bradner, JE Heightman, TD AF Spencer, John Amin, Jahangir Wang, Minghua Packham, Graham Alwi, Sharifah S. Syed Tizzard, Graham J. Coles, Simon J. Paranal, Ronald M. Bradner, James E. Heightman, Tom D. TI Synthesis and Biological Evaluation of JAHAs: Ferrocene-Based Histone Deacetylase Inhibitors SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Ferrocene; HDAC inhibitor; bioinorganic; anticancer; hydroxamic acid ID HDAC INHIBITORS; CANCER-THERAPY; IN-VITRO; VORINOSTAT; COMPLEXES; ANALOGS; ACID AB N-1-Hydroxy-N-8-ferrocenyloctanediamide, JAHA (7), an organometallic analogue of SAHA containing a ferrocenyl group as a phenyl bioisostere, displays nanomolar inhibition of class I HDACs, excellent selectivity over class ha HDACs, and anticancer action in intact cells (IC50 = 2.4 mu M, MCF7 cell line). Molecular docking studies of 7 in HDAC8 (a,b) suggested that the ferrocenyl moiety in 7 can overlap with the aryl cap of SAHA and should display similar HDAC inhibition, which was borne out in an in vitro assay (IC50 values against HDAC8 (mu M, SD in parentheses): SAHA, 1.41 (0.15); 7, 1.36 (0.16). Thereafter, a small library of related JAHA analogues has been synthesized, and preliminary SAR studies are presented. IC50 values as low as 90 pM toward HDAC6 (class IIb) have been determined, highlighting the excellent potential of JAHAs as bioinorganic probes. C1 [Spencer, John; Amin, Jahangir] Univ Greenwich, Sch Sci Medway, Chatham ME4 4TB, Kent, England. [Packham, Graham; Alwi, Sharifah S. Syed] Univ Southampton, Canc Res UK Ctr, Fac Med, Southampton Gen Hosp, Southampton SO16 6YD, Hants, England. [Tizzard, Graham J.; Coles, Simon J.] Univ Southampton, UK Natl Crystallog Serv, Sch Chem, Southampton SO17 1BJ, Hants, England. [Paranal, Ronald M.; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wang, Minghua; Heightman, Tom D.] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, England. RP Spencer, J (reprint author), Univ Greenwich, Sch Sci Medway, Chatham ME4 4TB, Kent, England. EM j.spencer@gre.ac.uk RI Coles, Simon/A-1795-2009; spencer, john/C-2156-2008; Tizzard, Graham/D-1227-2010 OI Coles, Simon/0000-0001-8414-9272; spencer, john/0000-0001-5231-8836; FU RSC; Greenwich University; CRUK; Malaysian Government; Canadian Institutes for Hearth Research [1097737]; Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Merck Co Inc.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation or Strategic Research; Wellcome Trust FX The RSC (Research Fund) and Greenwich University (GRE and the Alumni fund) are thanked for financial assistance (J.S. and J.A., for equipment) as well as CRUK (G.P.) and the Malaysian Government (S.S.S.A.).; The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Hearth Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation or Strategic Research, and the Wellcome Trust. NR 27 TC 43 Z9 43 U1 2 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD MAY PY 2011 VL 2 IS 5 BP 358 EP 362 DI 10.1021/ml100295v PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 765GE UT WOS:000290691400007 PM 21572592 ER PT J AU Deng, XM Wang, JH Zhang, JM Sim, T Kim, ND Sasaki, T Luther, W George, RE Janne, PA Gray, NS AF Deng, Xianming Wang, Jinhua Zhang, Jianming Sim, Taebo Kim, Nam Doo Sasaki, Takaaki Luther, William, II George, Rani E. Jaenne, Pasi A. Gray, Nathanael S. TI Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE ALK; 3,5-diamino-1,2,4-triazole urea ID CELL LUNG-CANCER; INFLAMMATORY MYOFIBROBLASTIC TUMOR; EML4-ALK FUSION GENE; EXPERIMENTAL-MODELS; THERAPEUTIC TARGET; ANTITUMOR-ACTIVITY; ALK; NEUROBLASTOMA; IDENTIFICATION; PATHOGENESIS AB A series of novel 3,5-diamino-1,2,4-triazole benzyl ureas was identified as having potent anaplastic lymphoma kinase (ALK) inhibition exemplified by 15a, 20a, and 23a, which exhibited antiproliferative IC50 values of 70, 40, and 20 nM in Tel-ALK transformed Ba/F3 cells, respectively. Moreover, 15a and 23a potently inhibited the growth and survival of NPM-ALK positive anaplastic large cell lymphoma cell (SU-DHL-1) and neuroblastoma cell lines (KELLY, SH-SY5Y) containing the F1174L ALK mutation. These compounds provide novel leads for the development of small-molecule ALK inhibitors for cancer therapy. C1 [Deng, Xianming; Wang, Jinhua; Zhang, Jianming; Sim, Taebo; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Deng, Xianming; Wang, Jinhua; Zhang, Jianming; Sim, Taebo; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kim, Nam Doo] Yonsei Univ, Dept Biotechnol, Seoul 120749, South Korea. [Sasaki, Takaaki; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Luther, William, II; George, Rani E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA. EM Nathanael_Gray@dfci.harvard.edu OI Sasaki, Takaaki/0000-0002-6505-8786 FU NCI [1 R01 CA136851-01A1, 1 R01 CA148688-01A1] FX This work was supported by an NCI Grant 1 R01 CA136851-01A1 (N.S.G. and P.A.J.) and 1 R01 CA148688-01A1 (R.E.G.). NR 27 TC 17 Z9 17 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD MAY PY 2011 VL 2 IS 5 BP 379 EP 384 DI 10.1021/ml200002a PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 765GE UT WOS:000290691400011 PM 21572589 ER PT J AU Weisbord, SD Palevsky, PM AF Weisbord, Steven D. Palevsky, Paul M. TI Iodinated Contrast Media and the Role of Renal Replacement Therapy SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Contrast media; Acute kidney injury; Dialysis; Hemofiltration ID RADIOCONTRAST-INDUCED NEPHROPATHY; RANDOMIZED CONTROLLED-TRIAL; OXYGEN-FREE-RADICALS; DIURESIS DVD TRIAL; PROPHYLACTIC HEMODIALYSIS; IOPROMIDE ELIMINATION; CORONARY-ANGIOGRAPHY; DIALYSIS; PREVENTION; FAILURE AB Iodinated contrast media are among the most commonly used pharmacologic agents in medicine. Although generally highly safe, iodinated contrast media are associated with several adverse effects, most significantly the risk of acute kidney injury, particularly in patients with underlying renal dysfunction. By virtue of their pharmacokinetic characteristics, these contrast agents are efficiently cleared by hemodialysis and to a lesser extent, hemofiltration. This has led to research into the capacity for renal replacement therapies to prevent certain adverse effects of iodinated contrast. This review examines the molecular and pharmacokinetic characteristics of iodinated contrast media and critically analyzes data from past studies on the role of renal replacement therapy to prevent adverse effects of these diagnostic agents. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. C1 [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Renal Sect, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Dept Med, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Ctr Hlth Equ Res & Promot, Univ Dr Div,7 East,Room 120 111F U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU VA Health Services Research and Development Career Development Transition Award [RCD 03-176] FX Dr. Weisbord is the recipient of a VA Health Services Research and Development Career Development Transition Award (RCD 03-176). NR 49 TC 3 Z9 4 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD MAY PY 2011 VL 18 IS 3 BP 199 EP 206 DI 10.1053/j.ackd.2010.11.008 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 765KC UT WOS:000290703500008 PM 21531326 ER PT J AU Franek, KJ Butler, J Johnson, J Simensen, R Friez, MJ Bartel, F Moss, T DuPont, B Berry, K Bauman, M Skinner, C Stevenson, RE Schwartz, CE AF Franek, Karl J. Butler, Julia Johnson, John Simensen, Richard Friez, Michael J. Bartel, Frank Moss, Tonya DuPont, Barbara Berry, Katherine Bauman, Margaret Skinner, Cindy Stevenson, Roger E. Schwartz, Charles E. TI Deletion of the Immunoglobulin Domain of IL1RAPL1 Results in Nonsyndromic X-Linked Intellectual Disability Associated With Behavioral Problems and Mild Dysmorphism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE IL1RAPL1; non-syndromic XLID; deletion; behavior problems ID IDIOPATHIC MENTAL-RETARDATION; ACCESSORY PROTEIN-LIKE; ADRENAL HYPOPLASIA; GENE; FAMILY; CHROMOSOME; INACTIVATION; MUTATIONS; INVERSION; AUTISM AB X-Linked intellectual disability accounts for a significant fraction of males with cognitive impairment. Many of these males present with a non-syndromic phenotype and presently mutations in 17 X-linked genes are associated with these patients. Mutations in IL1RAPL1 have been found in multiple families with non-syndromic X-linked intellectual disability. All of the published mutations predict loss of function of the protein. We have identified an additional two families with deletions of a portion of the gene that give rise to cognitive impairment, as well as some behavioral problems and mild dysmorphism. Our clinical findings better delineate the phenotypic spectrum associated with IL1RAPL1 mutations. (C) 2011 Wiley-Liss, Inc. C1 [Franek, Karl J.; Butler, Julia; Simensen, Richard; Friez, Michael J.; Bartel, Frank; Moss, Tonya; DuPont, Barbara; Skinner, Cindy; Stevenson, Roger E.; Schwartz, Charles E.] Greenwood Genet Ctr, JC Self Res Inst Human Genet, Ctr Mol Studies, Greenwood, SC 29646 USA. [Johnson, John; Berry, Katherine] Shodair Childrens Hosp, Dept Med Genet, Helena, MT USA. [Bauman, Margaret] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schwartz, CE (reprint author), Greenwood Genet Ctr, JC Self Res Inst Human Genet, Ctr Mol Studies, 113 Gregor Mendel Circle, Greenwood, SC 29646 USA. EM ceschwartz@ggc.org FU NICHD [R01HD26208]; South Carolina Department of Disabilities and Special Needs (SCDDSN) FX We thank the members of the families for their participation in this study. This work was supported by a NICHD grant (R01HD26208) to C.E.S. and in part by a grant from the South Carolina Department of Disabilities and Special Needs (SCDDSN). This article is dedicated to the memory of Ethan Francis Schwartz 1996-1998. NR 23 TC 21 Z9 22 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY PY 2011 VL 155A IS 5 BP 1109 EP 1114 DI 10.1002/ajmg.a.33833 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 765OB UT WOS:000290716700023 PM 21484992 ER PT J AU Lysack, C Lichtenberg, P Schneider, B AF Lysack, Cathy Lichtenberg, Peter Schneider, Brooke TI Effect of a DVD Intervention on Therapists' Mental Health Practices With Older Adults SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE clinical competence; depression; education, continuing; educational measurement; mental health services ID LATE-LIFE DEPRESSION; HOME-CARE; OCCUPATIONAL-THERAPY; TREATING DEPRESSION; RECOGNITION; COMPETENCE; SCALE AB PURPOSE. We tested the effectiveness of an educational intervention in DVD format aimed at strengthening the mental health practices of occupational therapists working with older adults. METHOD. The DVD intervention was tested in a pretest-posttest design. Occupational therapists (n = 30) completed a brief knowledge and attitude questionnaire; a chart review (n = 383) of therapists' (n = 20) patients at 3 mo before and 3 mo after DVD training was also conducted. RESULTS. Questionnaire data showed that the percentage of therapists with correct answers increased 20%-30% for 5 of the 11 knowledge items. Chart review data showed therapists spoke more often with their older patients about mood, depression, and cognitive impairment; screened more often for depression and cognitive impairment; and reported findings more often to the treatment team after training. CONCLUSION. Educational interventions can significantly improve therapists' mental health practice with older adults. C1 [Lysack, Cathy; Lichtenberg, Peter] Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA. [Schneider, Brooke] W Los Angeles Vet Affairs Med Ctr, Psychol Serv, Los Angeles, CA 90073 USA. RP Lysack, C (reprint author), Wayne State Univ, Inst Gerontol, Room 231,Knapp Bldg,87 E Ferry St, Detroit, MI 48202 USA. EM c.lysack@wayne.edu NR 30 TC 5 Z9 5 U1 1 U2 2 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD MAY-JUN PY 2011 VL 65 IS 3 SI SI BP 297 EP 305 DI 10.5014/ajot.2011.001354 PG 9 WC Rehabilitation SC Rehabilitation GA 765KQ UT WOS:000290704900008 PM 21675335 ER PT J AU Schechter-Perkins, EM Mitchell, PM Murray, KA Rubin-Smith, JE Weir, S Gupta, K AF Schechter-Perkins, Elissa M. Mitchell, Patricia M. Murray, Kate A. Rubin-Smith, Julia E. Weir, Susan Gupta, Kalpana TI Prevalence and Predictors of Nasal and Extranasal Staphylococcal Colonization in Patients Presenting to the Emergency Department SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID AUREUS COLONIZATION; UNITED-STATES; RISK-FACTORS; HOSPITAL ADMISSION; HAND HYGIENE; CARE; INFECTIONS; SKIN; SURVEILLANCE; POPULATIONS AB Study objective: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of skin and soft tissue infections in patients presenting to the emergency department (ED). The prevalence of asymptomatic MRSA colonization in ED patients is less well described, particularly in the absence of a skin and soft tissue infection related complaint. The goals of this study are to assess the prevalence of nasal and extranasal staphylococcal colonization in ED patients, evaluate risk factors, and molecularly characterize the strains. Methods: We performed active surveillance for methicillin-susceptible S aureus (MSSA) and MRSA colonization in 400 subjects presenting to an urban ED. Risk factor assessment was performed and culture testing was conducted on anterior nares, oropharynx, palms, groin, perirectal area, wounds, and catheter insertion sites. Multiplex polymerase chain reaction was used to identify the USA300/400 clonal types. Results: The prevalence of colonization with MSSA was 39% (95% confidence interval 34.2% to 44.0%), and prevalence of colonization with MRSA was 5% (95% confidence interval 3.1% to 7.6%). Among MRSA-colonized subjects, an extranasal site tested positive in 80% of subjects, and 45% had exclusive extranasal colonization. USA300 was identified in 55% of MRSA-colonized subjects. The main risk factors for MRSA colonization included HIV infection, diabetes, and participation in contact sports. Conclusion: The overall prevalence of MRSA colonization in this ED population was lower than that reported in other high-risk ambulatory care settings. However, extranasal colonization was present in more than half of MRSA-colonized subjects, and USA300 was the predominant clonal type. [Ann Emerg Med. 2011;57:492-499.] C1 [Gupta, Kalpana] Boston Vet Affairs Hlth Care Syst, Boston, MA USA. [Schechter-Perkins, Elissa M.; Mitchell, Patricia M.; Murray, Kate A.; Rubin-Smith, Julia E.] Boston Univ, Sch Med, Dept Emergency Med, Boston, MA 02118 USA. [Weir, Susan; Gupta, Kalpana] Boston Univ, Sch Med, Dept Internal Med, Boston, MA 02118 USA. RP Gupta, K (reprint author), VA Boston HCS, 1400 VFW Pkwy,111 Med, W Roxbury, MA 02132 USA. EM kalpana.gupta@va.gov FU Boston University Department of Medicine; Boston University Clinical and Translational Science Institute (NIH) [UL1RR025771] FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. The study was supported in part by a pilot grant award from the Boston University Department of Medicine and the Boston University Clinical and Translational Science Institute (NIH Award UL1RR025771). NR 41 TC 25 Z9 25 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAY PY 2011 VL 57 IS 5 BP 492 EP 499 DI 10.1016/j.annemergmed.2010.11.024 PG 8 WC Emergency Medicine SC Emergency Medicine GA 764CQ UT WOS:000290606400014 PM 21239081 ER PT J AU Smith, H Hutson, HR Geoffley, A Strote, J AF Smith, Hayden Hutson, H. Range Geoffley, Alpert Strote, Jared TI Emergency Physician Watchdogs for Law Enforcement: If We Are the Hammer, Everything Will Look Like a Nail Reply SO ANNALS OF EMERGENCY MEDICINE LA English DT Letter C1 [Smith, Hayden; Geoffley, Alpert] Univ S Carolina, Dept Criminol & Criminal Justice, Columbia, SC 29208 USA. [Hutson, H. Range] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Strote, Jared] Univ Washington, Div Emergency Med, Seattle, WA 98195 USA. RP Smith, H (reprint author), Univ S Carolina, Dept Criminol & Criminal Justice, Columbia, SC 29208 USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAY PY 2011 VL 57 IS 5 BP 543 EP 544 DI 10.1016/j.annemergmed.2010.11.005 PG 2 WC Emergency Medicine SC Emergency Medicine GA 764CQ UT WOS:000290606400028 ER PT J AU Hutson, HR Anglin, D Strote, J AF Hutson, H. Range Anglin, Deirdre Strote, Jared TI Regarding Use of Force Reply SO ANNALS OF EMERGENCY MEDICINE LA English DT Letter ID EMERGENCY PHYSICIANS; POLICE C1 [Hutson, H. Range] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Anglin, Deirdre] Univ So Calif, Cty USC Med Ctr, Dept Emergency Med, Los Angeles, CA USA. [Strote, Jared] Univ Washington, Univ Washington Med Ctr, Div Emergency Med, Seattle, WA 98195 USA. RP Hutson, HR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAY PY 2011 VL 57 IS 5 BP 546 EP 546 DI 10.1016/j.annemergmed.2010.12.026 PG 1 WC Emergency Medicine SC Emergency Medicine GA 764CQ UT WOS:000290606400031 ER PT J AU Filipits, M Hills, M Salter, J Dafni, U Gelber, RD Piccart, M Gnant, M Smith, BR Leyland-Jones, B Dowsett, M AF Filipits, M. Hills, M. Salter, J. Dafni, U. Gelber, R. D. Piccart, M. Gnant, M. Smith, B. R. Leyland-Jones, B. Dowsett, M. TI TRANSHERA: ANALYSIS OF PTEN, IGF-1R AND STATHMIN AS PUTATIVE PROGNOSTIC/PREDICTIVE MARKERS IN HER2-POSITIVE EARLY BREAST CANCER (BC) PATIENTS TREATED WITH 1-YEAR OF TRASTUZUMAB SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Conference on Improving Care and Knowledge through Translational Research (IMPAKT) Breast Cancer CY MAY 05-07, 2011 CL Brussels, BELGIUM C1 [Filipits, M.] Med Univ Vienna, Dept Med 1, Vienna, Austria. [Hills, M.; Salter, J.] Royal Marsden Hosp, London SW3 6JJ, England. [Dafni, U.] Frontier Sci Fdn, Athens, Greece. [Gelber, R. D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. [Piccart, M.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. [Gnant, M.] Med Univ Vienna, Dept Surg, Vienna, Austria. [Smith, B. R.] VM Inst Res, Montreal, PQ, Canada. [Leyland-Jones, B.] Emory Univ, Atlanta, GA 30322 USA. [Dowsett, M.] Royal Marsden NHS Trust, Breakthrough Res Ctr, London, England. 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 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 2 BP 45 EP 45 PG 1 WC Oncology SC Oncology GA 764EB UT WOS:000290610100077 ER PT J AU Chren, MM Torres, JS Stuart, SE Bertenthal, D Labrador, RJ Boscardin, J AF Chren, Mary-Margaret Torres, Jeanette S. Stuart, Sarah E. Bertenthal, Daniel Labrador, Remedios J. Boscardin, John TI Recurrence After Treatment of Nonmelanoma Skin Cancer A Prospective Cohort Study SO ARCHIVES OF DERMATOLOGY LA English DT Article ID BASAL-CELL CARCINOMA; MOHS MICROGRAPHIC SURGERY; FACE AB Objective: To determine long-term tumor recurrence rates after treatment of primary nonmelanoma skin cancer (NMSC). Data are currently insufficient to permit evidence-based choices among treatments for NMSC. Design: Prospective study of an inception cohort observed for a median of 6.6 years after treatment. Setting: Dermatology clinic at a Veterans Affairs hospital. Care was provided by dermatology resident or attending physicians. Patients: Consecutive sample of all 495 patients with 616 primary NMSCs diagnosed in 1999 and 2000 and treated with electrodessication and curettage (ED&C), excision, or Mohs surgery. Follow-up was available for 608 tumors (99%). Main Outcome Measure: Tumor recurrence, deter-mined by medical record review, with validation by clinical examination. Results: The mean age at diagnosis was 71 years; 97% were men. Overall, 127 tumors were treated with ED&C (20.9%); 309 with excision (50.8%); and 172 with Mohs surgery (28.3%). Over the course of the study, 21 tumors recurred (3.5% [95% confidence interval (CI), 2.2%-5.2%]): 2 after ED&C (1.6% [95% CI, 0.2%-5.6%]), 13 after excision (4.2% [95% CI, 2.2%-7.1%]), and 6 after Mohs surgery (3.5% [95% CI, 1.3%-7.4%]). Conclusions: Recurrence of primary NMSC after treatment occurred in less than 5% of tumors. The recurrence rate after ED&C was lower than expected, and the recurrence rate after Mohs surgery was higher than expected. These findings may be related to the risk for recurrence in the treatment groups. C1 [Chren, Mary-Margaret; Torres, Jeanette S.; Stuart, Sarah E.; Bertenthal, Daniel; Labrador, Remedios J.; Boscardin, John] San Francisco VA Med Ctr, Res Enhancement Award Program, Hlth Serv Res & Dev Serv, Dept Vet Affairs, San Francisco, CA USA. [Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Boscardin, John] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Boscardin, John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Chren, MM (reprint author), San Francisco VA Med Ctr 151R, 4150 Clement St, San Francisco, CA 94121 USA. EM chrenm@derm.ucsf.edu FU Investigator-Initiated Research Grant [IIR 04-043-3]; Health Services Research and Development Service of the Department of Veterans Affairs; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [K24 AR052667, R01 AR 054983] FX This work was supported by Investigator-Initiated Research Grant IIR 04-043-3 and the San Francisco Research Enhancement Award Program (REAP) of the Health Services Research and Development Service of the Department of Veterans Affairs, and by grants K24 AR052667 and R01 AR 054983 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. NR 16 TC 35 Z9 38 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 2011 VL 147 IS 5 BP 540 EP 546 PG 7 WC Dermatology SC Dermatology GA 764LX UT WOS:000290632100004 PM 21576572 ER PT J AU Hadlock, TA Malo, JS Cheney, ML Henstrom, DK AF Hadlock, Tessa A. Malo, Juan S. Cheney, Mack L. Henstrom, Douglas K. TI Free Gracilis Transfer for Smile in Children The Massachusetts Eye and Ear Infirmary Experience in Excursion and Quality-of-Life Changes SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID FACIAL-NERVE PARALYSIS; FREE MUSCLE TRANSFER; NECK RECONSTRUCTION; FREE FLAPS; REANIMATION; HEAD; FACE; TRANSPLANTATION; VALIDATION; EXPRESSION AB Background: Free muscle transfer for facial reanimation has become the standard of care in recent decades and is now the cornerstone intervention for dynamic smile reanimation. We sought to quantify smile excursion and quality-of-life (QOL) changes in our pediatric free gracilis recipients following reanimation. Methods: We quantified gracilis muscle excursion in 17 pediatric patients undergoing 19 consecutive pediatric free gracilis transplantation operations, using our validated SMILE program, as an objective measure of functional outcome. These were compared against excursion measured the same way in a cohort of 17 adults with 19 free gracilis operations. In addition, we prospectively evaluated QOL outcomes in these children using the Facial Clinimetric Evaluation (FaCE) instrument. Results: The mean gracilis excursion in our pediatric free gracilis recipients was 8.8 mm +/- 5.0 mm, which matched adult results, but with fewer complete failures of less than 2-mm excursion, with 2 (11%) and 4 (21%), respectively. Quality-of-life measures indicated statistically significant improvements following dynamic smile reanimation (P = .01). Conclusions: Dynamic facial reanimation using free gracilis transfer in children has an acceptable success rate, yields improved commissure excursion, and improves QOL in the pediatric population. It should be considered first-line therapy for children with lack of a meaningful smile secondary to facial paralysis. C1 [Hadlock, Tessa A.; Malo, Juan S.; Cheney, Mack L.; Henstrom, Douglas K.] Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 23 TC 33 Z9 33 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD MAY-JUN PY 2011 VL 13 IS 3 BP 190 EP 194 PG 5 WC Surgery SC Surgery GA 764MA UT WOS:000290632400009 PM 21576665 ER PT J AU Sachs, DH AF Sachs, David H. TI Transplant Tolerance Bench to Bedside 26th Annual Samuel Jason Mixter Lecture SO ARCHIVES OF SURGERY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; REGULATORY T-CELLS; LARGE-ANIMAL-MODEL; MIXED CHIMERISM; PREPARATIVE REGIMEN; ALLOGRAFT TOLERANCE; INDUCTION; KIDNEY; MAINTENANCE; MECHANISMS AB Ever since the first demonstration that transplant tolerance can be induced in neonatal mice by injection of donor bone marrow cells shortly after birth, 1 the establishment of tolerance for organ transplants has been a major goal in the field of transplantation immunology. Indeed, an understanding of tolerance has both theoretical and practical implications for transplantation: from a theoretical point of view, an understanding of tolerance is basic to the requirement for self-/nonself-discrimination in the immune system; from a practical point of view, the induction of tolerance could relieve patients from the need for long-term immunosuppressant medications, thereby avoiding the adverse effects and complications that are a major limitation to the success of clinical transplant at present. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA. EM david.sachs@tbrc.mgh.harvard.edu FU NIAID NIH HHS [N01AI15416, N01 AI015416] NR 22 TC 2 Z9 2 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 501 EP 505 PG 5 WC Surgery SC Surgery GA 764MH UT WOS:000290633100001 PM 21576601 ER PT J AU Cosimi, AB AF Cosimi, A. Benedict TI Modern Day Bloodletting Is That Laboratory Test Necessary? INVITED CRITIQUE SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Cosimi, AB (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM cosimi@partners.org NR 2 TC 2 Z9 2 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 527 EP 527 PG 1 WC Surgery SC Surgery GA 764MH UT WOS:000290633100009 PM 21739650 ER PT J AU Fikry, K Velmahos, GC Bramos, A Janjua, S de Moya, M King, DR Alam, HB AF Fikry, Karim Velmahos, George C. Bramos, Athanasios Janjua, Sumbal de Moya, Marc King, David R. Alam, Hasan B. TI Successful Selective Nonoperative Management of Abdominal Gunshot Wounds Despite Low Penetrating Trauma Volumes SO ARCHIVES OF SURGERY LA English DT Article ID CONSERVATIVE MANAGEMENT; ROUTINE LAPAROTOMY; STAB WOUNDS; INJURIES; ABDOMEN; MORBIDITY; OPERATION; BACK AB Objective: To determine whether selective nonoperative management of abdominal gunshot wounds (AGSW) is safe in trauma centers with a low volume of penetrating trauma. Design: Retrospective study. Setting: Academic level 1 trauma center with approximately 10% penetrating trauma. Patients: All patients with anterior and posterior AGSW (January 1, 1999, through December 31, 2009), excluding tangential injuries, transfers, and deaths in the emergency department. Patients with hemodynamic instability or peritonitis received an urgent laparotomy. The remaining patients had selective nonoperative management. A delayed laparotomy was offered for worsening symptoms or worrisome computed tomography findings. Main Outcome Measures: Hospital stay, complications, and mortality. Results: Of 125 AGSW patients, 38 (30%) were initially managed by selective nonoperative management (25 of 99 anterior and 13 of 26 posterior AGSW patients). Seven selective nonoperative management patients received delayed laparotomy as late as 11 hours after admission. At the end, 30 of the 125 patients (24%) were successfully managed without an operation (20 of 99 anterior and 10 of 26 posterior AGSW patients). There were no predictors of delayed laparotomy and no complications or mortality attributed to it. Ten patients (8%) had a nontherapeutic laparotomy, and 3 of them developed complications. Conclusions: Selective nonoperative management of AGSW is feasible and safe in trauma centers with low penetrating trauma volumes. Nearly 1 in 4 AGSW patients does not need a laparotomy, and nontherapeutic laparotomies are associated with complications. The volume of AGSW per se should not be an excuse for routine laparotomies. These data become particularly important because penetrating trauma volumes are decreasing around the country. C1 [Fikry, Karim] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fikry, K (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM kfikry@partners.org NR 29 TC 9 Z9 11 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 528 EP 532 PG 5 WC Surgery SC Surgery GA 764MH UT WOS:000290633100010 PM 21576606 ER PT J AU Haynes, AB Deshpande, V Ingkakul, T Vagefi, PA Szymonifka, J Thayer, SP Ferrone, CR Wargo, JA Warshaw, AL Fernandez-del Castillo, C AF Haynes, Alex B. Deshpande, Vikram Ingkakul, Thun Vagefi, Parsia A. Szymonifka, Jackie Thayer, Sarah P. Ferrone, Cristina R. Wargo, Jennifer A. Warshaw, Andrew L. Fernandez-del Castillo, Carlos TI Implications of Incidentally Discovered, Nonfunctioning Pancreatic Endocrine Tumors Short-term and Long-term Patient Outcomes SO ARCHIVES OF SURGERY LA English DT Article ID GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS; ISLET CELL TUMORS; NEOPLASMS; EXPERIENCE; MANAGEMENT; SYSTEM AB Objectives: To describe the characteristics and outcomes after resection of incidentally discovered, nonfunctioning pancreatic endocrine tumors (PETs). Design: Case series. Setting: Academic hospital. Patients: Consecutive patients with an incidentally identified, nonfunctioning PET resected from May 1, 1977, through July 31, 2009. Main Outcome Measures: Operative morbidity and survival after resection. Results: A total of 139 patients with median age of 56 years (range, 21-85 years) underwent resection; tumor size ranged from 0.4 to 17.0 cm, with median size of 3.0 cm. No perioperative deaths were reported. Sixty-one patients (43.9%) experienced a perioperative complication. Twenty-six tumors (18.7%) were classified as benign, 39 (28.1%) as malignant, and 72 (51.8%) as uncertain. We were unable to confidently classify 2 tumors due to lack of information regarding mitotic rate in the pathology report. Complete follow-up was available for 112 patients (80.6%) (median, 34.2 months). Five-year actuarial survival rates were 88.8% for patients with benign disease, 92.5% for patients with tumors of uncertain biology, and 49.8% for those with malignant tumors (P=.01). Late metastasis, tumor recurrence, or disease progression were seen in 1 patient (3.8%) with tumors initially classified as benign, 8 patients (11.1%) with uncertain tumors, and 15 patients (38.5%) with tumors classified as malignant (P<.001). Of the 39 patients with tumors 2 cm or smaller, 3 (7.7%) had late metastases or recurrence. When compared with patients with symptomatic, nonfunctioning PETs, no large difference was observed in tumor size, patient age, disease, or survival. Conclusions: Incidentally detected, nonfunctioning PETs can display aggressive behavior, even when small. Although patients with malignant disease had diminished survival and increased rates of recurrence, benign histologic findings did not eliminate the possibility of progression. Patients with incidentally discovered, nonfunctioning PETs should undergo tumor resection and careful postoperative surveillance, even if surgical pathologic findings suggest benign disease. C1 [Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr 460, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Szymonifka, Jackie] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Vagefi, Parsia A.] Univ Calif San Francisco, Sch Med, Dept Surg, San Francisco, CA 94143 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org FU NCI NIH HHS [P01 CA117969, P01 CA117969-04S1, P01 CA117969-05, P01 CA117969-06, P50 CA127003, P50 CA127003-03]; NIDDK NIH HHS [K08 DK071329, K08 DK071329-05] NR 16 TC 69 Z9 71 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 534 EP 538 PG 5 WC Surgery SC Surgery GA 764MH UT WOS:000290633100012 PM 21576607 ER PT J AU Salinas, HM Dursun, A Klos, CL Shellito, P Sylla, P Berger, D Bordeianou, L AF Salinas, Harry M. Dursun, Abdulmetin Klos, Coen L. Shellito, Paul Sylla, Patricia Berger, David Bordeianou, Liliana TI Determining the Need for Radical Surgery in Patients With T1 Rectal Cancer SO ARCHIVES OF SURGERY LA English DT Article ID LYMPH-NODE METASTASIS; LOCAL EXCISION; PREOPERATIVE RADIOTHERAPY; TRANSANAL EXCISION; ADJUVANT THERAPY; UNITED-STATES; RISK; CARCINOMA; RESECTION; ADENOCARCINOMA AB Hypothesis: In the era of modern preoperative staging of patients with rectal cancer, lymph node metastases can be reliably predicted by the histological features of the tumor and preoperative imaging. Local resection can then be safely offered to the patients who are at low risk of having malignant lymph nodes. Design: We reviewed the records of 109 consecutive patients with preoperative imaging results suggestive of T1N0 or T2N0 disease who underwent total mesorectal excision. All patients underwent preoperative endorectal ultrasonography or magnetic resonance imaging and computed tomography, with or without positron emission tomography. Final pathologic investigation identified T3 disease in 27 patients. History, physical examination results, and radiologic and pathologic data were evaluated for predictors of positive nodes in the remaining 82 patients. Setting: Tertiary care referral center. Patients: Patients with preoperative imaging suggestive of T1N0 or T2N0 rectal cancer. Main Outcome Measures: To evaluate different clinical and pathologic tumor features as predictors of positive lymph nodes in T1 and T2 rectal cancers with negative radiographic nodes. Background: Local resection of T1 and T2 rectal cancer results in lower morbidity compared with radical resection. However, recurrence rates after local resection are higher, likely owing to unresected nodal metastasis. Reports on predictors of lymph node metastasis remain inconsistent in the literature. Although local resection may be appropriate for some rectal cancers, selection criteria remain unclear. Results: Despite indications of negative nodes on radiographic examination, 4 of 35 patients with T1 disease (11%) and 13 of 47 with T2 disease (28%) had positive nodes. On univariate analysis, the only significant predictor was depth of invasion: 24 of 65 patients with negative nodes (37%) vs 13 of 17 patients with positive nodes (76%) had tumors invading the lower third of the submucosa and beyond (P=.02). On logistic regression analysis accounting for depth of invasion (lower third of the submucosa and beyond), size, distance from anal verge, differentiation, and lymphovascular and small-vessel invasion, only depth of invasion remained a significant predictor. Conclusions: In all, 89% of patients with T1 disease (31 of 35) and 72% of those with T2 disease (34 of 47) underwent unnecessary radical resection. Endorectal ultrasonography or magnetic resonance imaging and computed tomography, with or without positron emission tomography, for preoperative staging could not identify these patients reliably. In addition, histologic markers of aggressive disease were not helpful. Thus, local resection for T2 rectal cancer is not justified. Local resection should be offered only to patients with superficial T1 tumors who will adhere to aggressive postoperative surveillance. C1 [Bordeianou, Liliana] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Salinas, Harry M.; Dursun, Abdulmetin; Shellito, Paul; Sylla, Patricia; Berger, David; Bordeianou, Liliana] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Klos, Coen L.] Univ Amsterdam, Amsterdam, Netherlands. RP Bordeianou, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@partners.org NR 24 TC 10 Z9 11 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 540 EP 543 PG 4 WC Surgery SC Surgery GA 764MH UT WOS:000290633100014 PM 21576608 ER PT J AU Velmahos, GC AF Velmahos, George C. TI Surprise, Surprise! More Surgery in Rural Areas Than in Cities INVITED CRITIQUE SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 [Velmahos, George C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Velmahos, George C.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2011 VL 146 IS 5 BP 584 EP 584 PG 1 WC Surgery SC Surgery GA 764MH UT WOS:000290633100023 PM 21739655 ER PT J AU Kuil, J Buckle, T Yuan, HS van den Berg, NS Oishi, S Fujii, N Josephson, L van Leeuwen, FWB AF Kuil, Joeri Buckle, Tessa Yuan, Hushan van den Berg, Nynke S. Oishi, Shinya Fujii, Nobutaka Josephson, Lee van Leeuwen, Fijs W. B. TI Synthesis and Evaluation of a Bimodal CXCR4 Antagonistic Peptide SO BIOCONJUGATE CHEMISTRY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; CANCER; T140; FLUORESCENCE; EXPRESSION; DTPA AB The antagonistic Ac-TZ14011 peptide, which binds to the chemokine receptor 4, has been labeled with a multifunctional single attachment point reagent that contains a DTPA chelate and a fluorescent dye with Cy5.5 spectral properties. Flow cytometry and confocal microscopy showed that the bimodal labeled peptide gave a specific receptor binding that is similar to monofunctionalized peptide derivatives, Therefore, the newly developed bimodal peptide derivative can be used in multimodal imaging applications. C1 [Kuil, Joeri; Buckle, Tessa; van den Berg, Nynke S.; van Leeuwen, Fijs W. B.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Diagnost Oncol, NL-1066 CX Amsterdam, Netherlands. [Yuan, Hushan; Josephson, Lee] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Yuan, Hushan; Josephson, Lee] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Oishi, Shinya; Fujii, Nobutaka] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Bioorgan Med Chem, Kyoto, Japan. RP van Leeuwen, FWB (reprint author), Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Diagnost Oncol, NL-1066 CX Amsterdam, Netherlands. EM fw.v.leeuwen@nki.nl RI Oishi, Shinya/C-1350-2011; OI Oishi, Shinya/0000-0002-2833-2539; van leeuwen, Fijs/0000-0002-6844-4025; Buckle, Tessa/0000-0003-2980-6895 FU KWF [PGF 2009-4344]; Centre for Translational Molecular Medicine [030-104] FX This research is supported, in part, by a KWF-translational research award (Grant No. PGF 2009-4344; FvL), and within the framework of CTMM, the Centre for Translational Molecular Medicine (http://www.ctmm.nl), project Breast CARE (grant 030-104; JK). NR 32 TC 32 Z9 32 U1 1 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY PY 2011 VL 22 IS 5 BP 859 EP 864 DI 10.1021/bc2000947 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 765GF UT WOS:000290691600002 PM 21480671 ER PT J AU Petryshen, TL AF Petryshen, Tracey L. TI Characterizing the Role of Ankyrin 3 in Regulating Bipolar-Related Behaviors SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Petryshen, Tracey L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 10 BP 4S EP 4S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800011 ER PT J AU Milad, MR AF Milad, Mohammed R. TI Sex Differences and Influence of Sex Hormones on Fear Extinction in Rats and Humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Milad, Mohammed R.] Massachusetts Gen Hosp, Charlestown, MA USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 103 BP 27S EP 28S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800088 ER PT J AU Bymaster, F Skolnick, P Huang, NY Bradshaw, M McKinney, A Manthis, J Fava, M Tran, P AF Bymaster, F. Skolnick, P. Huang, N. Y. Bradshaw, M. McKinney, A. Manthis, J. Fava, M. Tran, P. TI Efficacy and Safety of EB-1010, a Triple Reuptake Inhibitor, in the Treatment of Patients with Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Skolnick, P.] DOV Pharmaceut, Clin, Somerset, NJ USA. [Huang, N. Y.] QRx Pharma, Clin, Bedminster, NJ USA. [Bradshaw, M.] Global Consulting Partners, Clin, Princeton, NJ USA. [Fava, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 136 BP 37S EP 38S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800121 ER PT J AU Howland, RH Wisniewski, S Balasubramani, GK Fava, M Trivedi, M Rush, AJ AF Howland, Robert H. Wisniewski, Stephen Balasubramani, G. K. Fava, Maurizo Trivedi, Madukar Rush, A. John TI Thyroid Disease, Major Depression, and Treatment Outcome in the COMED Trial SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Howland, Robert H.] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. [Wisniewski, Stephen; Balasubramani, G. K.] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15213 USA. [Fava, Maurizo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Trivedi, Madukar] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Rush, A. John] Singapore Duke NUS, Grad Sch Med, Singapore, Singapore. RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 NR 0 TC 0 Z9 0 U1 0 U2 5 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 138 BP 38S EP 38S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800123 ER PT J AU Ripoll, LH Zaki, J Perez-Rodriguez, M New, AS AF Ripoll, Luis H. Zaki, Jamil Perez-Rodriguez, Mercedes New, Antonia S. TI Empathic Accuracy and Social Cognition in Personality Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Ripoll, Luis H.; New, Antonia S.] James J Peters VA Med Ctr, MIRECC, Bronx, NY USA. [Zaki, Jamil] Harvard Univ, Dept Psychol, Boston, MA 02115 USA. [Perez-Rodriguez, Mercedes] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 8 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 177 BP 50S EP 50S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800162 ER PT J AU Bevilacqua, L Hadjulis, M Enoch, MA New, AS Hodgkinson, CA Yuan, QP Shen, PH Siever, LJ Roy, A Goldman, D AF Bevilacqua, Laura Hadjulis, Michael Enoch, Mary-Anne New, Antonia S. Hodgkinson, Colin A. Yuan, Qiaoping Shen, Pei-Hong Siever, Larry J. Roy, Alec Goldman, David TI An HTR2B Low-expression Haplotype Predicts Risk of Cocaine Dependence and Aggression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Bevilacqua, Laura; Enoch, Mary-Anne; Hodgkinson, Colin A.; Yuan, Qiaoping; Shen, Pei-Hong; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. [Hadjulis, Michael; New, Antonia S.; Siever, Larry J.] Mt Sinai Sch Med, New York, NY USA. [Hadjulis, Michael; New, Antonia S.; Siever, Larry J.] James J Peters VA Med Ctr, New York, NY USA. [Roy, Alec] New Jersey VA Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 211 BP 60S EP 61S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800196 ER PT J AU Tsareva, A Lebron-Milad, K Pitman, RK Milad, MR AF Tsareva, Alina Lebron-Milad, Kelimer Pitman, Roger K. Milad, Mohammed R. TI Influence of Selective Serotonin Reuptake Inhibitors on Fear Extinction SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 312 BP 93S EP 93S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800297 ER PT J AU Milad, MR AF Milad, Mohammed R. TI Fear Extinction in Post-Traumatic Stress, Obsessive-Compulsive Disorder and Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Milad, Mohammed R.] Massachusetts Gen Hosp, Charlestown, MA USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 7 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 383 BP 113S EP 113S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800360 ER PT J AU Spencer, KM AF Spencer, Kevin M. TI Oscillatory Brain Dynamics in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Spencer, Kevin M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 405 BP 120S EP 120S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800382 ER PT J AU Maussion, G Ernst, C Yang, JN Turecki, G AF Maussion, Gilles Ernst, Carl Yang, Jennie Turecki, Gustavo TI Differential DNA Methylation in Frontal Cortex of Suicide Completers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Maussion, Gilles; Ernst, Carl; Yang, Jennie; Turecki, Gustavo] Douglas Hosp, Mental Hlth Univ Inst, Dept Psychiat, Montreal, PQ, Canada. [Ernst, Carl] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 446 BP 133S EP 133S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800423 ER PT J AU Rabany, L Levkovitz, Y Harel, EV Zangen, A AF Rabany, Liron Levkovitz, Yechiel Harel, Eiran Vadim Zangen, Abraham TI Deep Transcranial Magnetic Stimulation (deep-TMS) Add-on for Treatment of Negative Symptoms and Cognitive Deficits of Schizophrenia: A Feasibility Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Rabany, Liron; Levkovitz, Yechiel; Harel, Eiran Vadim] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Rabany, Liron; Levkovitz, Yechiel; Harel, Eiran Vadim] Shalvata Mental Hlth Care Ctr, Emot Cognit Res Ctr, Hod Hasharon, Israel. [Rabany, Liron] Tel Aviv Univ, Gordon Fac Social Sci, IL-69978 Tel Aviv, Israel. [Levkovitz, Yechiel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Zangen, Abraham] Weitzman Inst Sci, Dept Neurobiol, Rehovot, Israel. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 456 BP 136S EP 136S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800433 ER PT J AU Alexander, PR Garrett, CT Fisher, M Vinogradov, S AF Alexander, Phillip R. Garrett, Coleman T. Fisher, Melissa Vinogradov, Sophia TI Insight into Cognition Predicts Response to Cognitive Training in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Alexander, Phillip R.; Garrett, Coleman T.; Fisher, Melissa; Vinogradov, Sophia] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Alexander, Phillip R.; Garrett, Coleman T.; Fisher, Melissa; Vinogradov, Sophia] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 485 BP 145S EP 145S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800462 ER PT J AU Tyrka, AR Price, LH Marsit, C Walters, C Wilkinson, CW Carpenter, LL AF Tyrka, Audrey R. Price, Lawrence H. Marsit, Carmen Walters, Chris Wilkinson, Charles W. Carpenter, Linda L. TI Epigenetic Modulation of Leukocyte Glucocorticoid Receptor in Healthy Adults: Effects of Childhood Parenting Experiences SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Tyrka, Audrey R.; Price, Lawrence H.; Marsit, Carmen; Carpenter, Linda L.] Brown Med Sch, Providence, RI USA. [Walters, Chris] Butler Hosp, Mood Disorders Res Program, Providence, RI 02906 USA. [Wilkinson, Charles W.] Univ Washington, Dept Psychiat & Behav Sci, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 517 BP 154S EP 155S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800493 ER PT J AU Yao, JK Condray, R Dougherty, GG Keshavan, MS Montrose, DM Matson, WR McEvoy, J Kaddurah-Daouk, R Reddy, RD AF Yao, Jeffrey K. Condray, Ruth Dougherty, George G. Keshavan, Matcheri S. Montrose, Debra M. Matson, Wayne R. McEvoy, Joseph Kaddurah-Daouk, Rima Reddy, Ravinder D. TI Associations between Purine Metabolites and Clinical Symptoms in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Yao, Jeffrey K.; Condray, Ruth; Dougherty, George G.; Reddy, Ravinder D.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Yao, Jeffrey K.; Condray, Ruth; Dougherty, George G.; Keshavan, Matcheri S.; Montrose, Debra M.; Reddy, Ravinder D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr 4, Dept Psychiat, Boston, MA USA. [Keshavan, Matcheri S.] Harvard Univ, Boston, MA 02115 USA. [Matson, Wayne R.] Bedford VA Med Ctr, Med Res Serv, Bedford, MA USA. [McEvoy, Joseph; Kaddurah-Daouk, Rima] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 530 BP 158S EP 158S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800506 ER PT J AU Yao, JK Condray, R Reddy, RD Montrose, DM Keshavan, MS AF Yao, Jeffrey K. Condray, Ruth Reddy, Ravinder D. Montrose, Debra M. Keshavan, Matcheri S. TI Defective Purine Catabolism in High Risk Relatives of Patients with Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Yao, Jeffrey K.; Condray, Ruth; Reddy, Ravinder D.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Yao, Jeffrey K.; Condray, Ruth; Reddy, Ravinder D.; Montrose, Debra M.; Keshavan, Matcheri S.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Keshavan, Matcheri S.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 529 BP 158S EP 158S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800505 ER PT J AU Pousada-Casal, A Thermenos, HW Juelich, RJ Goldstein, JM Gabrieli, SW Makris, N Tsuang, MT Buka, SL Seidman, LJ AF Pousada-Casal, Andrea Thermenos, Heidi W. Juelich, Richard J. Goldstein, Jill M. Gabrieli, Susan W. Makris, Nikos Tsuang, Ming T. Buka, Stephen L. Seidman, Larry J. TI An fMRI Study of Verbal Encoding in Persons with Bipolar Disorder or at Genetic Risk for Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Pousada-Casal, Andrea; Thermenos, Heidi W.; Goldstein, Jill M.; Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Thermenos, Heidi W.; Juelich, Richard J.; Makris, Nikos; Seidman, Larry J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02215 USA. [Goldstein, Jill M.] Harvard Univ, Sch Med, Div Womens Hlth,Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02215 USA. [Gabrieli, Susan W.] MIT, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. [Tsuang, Ming T.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Buka, Stephen L.] Brown Univ, Providence, RI 02912 USA. RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 571 BP 172S EP 172S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800547 ER PT J AU Thermenos, H Whitfield-Gabrieli, S Makris, N Brown, AB Giuliano, AJ Lee, EH Faraone, SV Tsuang, MT Seidman, LJ AF Thermenos, H. Whitfield-Gabrieli, S. Makris, N. Brown, A. B. Giuliano, A. J. Lee, E. H. Faraone, S. V. Tsuang, M. T. Seidman, L. J. TI Default Network Activity Differentiates Adolescent and Young Adult Relatives of Persons With Bipolar Disorder and Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Thermenos, H.; Giuliano, A. J.; Lee, E. H.; Seidman, L. J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Boston, MA 02215 USA. [Thermenos, H.; Makris, N.; Seidman, L. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Whitfield-Gabrieli, S.; Brown, A. B.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, S.; Brown, A. B.] MIT, Poitras Ctr Affect Disorders Res, Cambridge, MA 02139 USA. [Makris, N.] Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. [Brown, A. B.] Harvard Univ, Sch Med, MIT, Massachusetts Gen Hosp,Martinos Ctr Biomed Imagin, Charlestown, MA USA. [Faraone, S. V.] SUNY Upstate Med Univ, Syracuse, NY USA. [Tsuang, M. T.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 587 BP 177S EP 177S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800563 ER PT J AU Houston, JP Kohler, J Ostbye, KM Heinloth, AN Perlis, R AF Houston, John P. Kohler, Jared Ostbye, Katherine M. Heinloth, Alexandra N. Perlis, Roy TI Association of Additional Common Variants in COMT with Duloxetine Efficacy in Patients with Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Houston, John P.] Lilly USA LLC, Neurosci, Indianapolis, IN USA. [Kohler, Jared; Ostbye, Katherine M.] BioStat Solut Inc, Genom, Mt Airy, MD USA. [Heinloth, Alexandra N.] I3 Statprobe, Sci Commun, Ann Arbor, MI USA. [Perlis, Roy] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 610 BP 184S EP 184S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800586 ER PT J AU Bartzokis, G Lu, PH Raven, EP Amar, CP DeTore, NR Altshuler, LL Mintz, J Ventura, J Casaus, LR Luo, JS Subotnik, KL Nuechterlein, KH AF Bartzokis, George Lu, Po H. Raven, Erika P. Amar, Chetan P. DeTore, Nicole R. Altshuler, Lori L. Mintz, Jim Ventura, Joseph Casaus, Laurie R. Luo, John S. Subotnik, Kenneth L. Nuechterlein, Keith H. TI Abnormal Trajectory of Intracortical Myelination in Schizophrenia Implicates White Matter in Treatment Response and Outcomes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Bartzokis, George; Lu, Po H.; Raven, Erika P.; Amar, Chetan P.; DeTore, Nicole R.; Altshuler, Lori L.; Ventura, Joseph; Casaus, Laurie R.; Luo, John S.; Subotnik, Kenneth L.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Los Angeles, CA USA. [Lu, Po H.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RI Bartzokis, George/K-2409-2013; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 3 Z9 3 U1 0 U2 2 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 611 BP 185S EP 185S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800587 ER PT J AU Levenson, JM Gibson, HE Richardson, KA Ghorashi, S Whitford, TJ Mears, RP Spencer, KM Gerber, D Levin, ME AF Levenson, Jonathan M. Gibson, Helen E. Richardson, Kristen A. Ghorashi, Shahab Whitford, Thomas J. Mears, Ryan P. Spencer, Kevin M. Gerber, David Levin, Margaret E. TI Gamma Oscillation Correlates of Cognition Shared Between Mouse and Man SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Levenson, Jonathan M.; Gibson, Helen E.; Richardson, Kristen A.; Gerber, David; Levin, Margaret E.] Galenea Corp, Target Validat, Cambridge, MA USA. [Ghorashi, Shahab; Whitford, Thomas J.; Mears, Ryan P.; Spencer, Kevin M.] VA Boston Healthcare, Neural Dynam Lab, Boston, MA USA. [Ghorashi, Shahab; Whitford, Thomas J.; Mears, Ryan P.; Spencer, Kevin M.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 631 BP 191S EP 191S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800607 ER PT J AU Simon, N AF Simon, Naomi TI Theory and Evidence for Telomere Shortening in Depression Modeled as a Chronic Stress-related Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Simon, Naomi] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 644 BP 195S EP 195S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800620 ER PT J AU Holtzheimer, PE Dougherty, DD Schlaepfer, T Mayberg, H AF Holtzheimer, Paul E. Dougherty, Darin D. Schlaepfer, Thomas Mayberg, Helen TI Acute Effects of Deep Brain Stimulation for Treatment-Resistant Depression: Using Variability Across Targets to Inform on the Neurobiology of Mood Regulation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Holtzheimer, Paul E.; Mayberg, Helen] Emory Univ, Atlanta, GA 30322 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Charlestown, MA USA. [Schlaepfer, Thomas] Univ Bonn, D-5300 Bonn, Germany. RI Holtzheimer, Paul/B-6212-2015 OI Holtzheimer, Paul/0000-0002-3552-3296 NR 0 TC 1 Z9 1 U1 0 U2 1 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 668 BP 202S EP 203S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800644 ER PT J AU Siever, LJ AF Siever, Larry J. TI 5-HT2b Alleles, Frontal Activation, and Aggressive Behavior SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Siever, Larry J.] James J Peters VAMC, Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 667 BP 202S EP 202S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800643 ER PT J AU Xie, PX Kranzler, HR Krauthammer, M Oslin, D Anton, RF Zhao, HY Farrer, LA Gelernter, J AF Xie, Pingxing Kranzler, Henry R. Krauthammer, Michael Oslin, David Anton, Raymond F. Zhao, Hongyu Farrer, Lindsay A. Gelernter, Joel TI Protective Effect of Rare Nonsynonymous Variants In the Alpha-4 Subunit of Nicotinic Acetylcholine Receptor Gene (chrna4) for Nicotine Dependence SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Xie, Pingxing] Yale Univ, Dept Genet, West Haven, CT USA. [Xie, Pingxing; Gelernter, Joel] VA CT Healthcare Ctr, West Haven, CT USA. [Kranzler, Henry R.; Oslin, David] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Kranzler, Henry R.; Oslin, David] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Krauthammer, Michael] Yale Univ, Dept Pathol, New Haven, CT USA. [Anton, Raymond F.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Zhao, Hongyu] Yale Univ, Dept Genet, New Haven, CT USA. [Farrer, Lindsay A.] Boston Univ, Dept Med, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Genet & Genom, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Epidemiol & Biostat, Boston, MA 02215 USA. [Gelernter, Joel] Yale Univ, Dept Genet & Psychiat, West Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 671 BP 203S EP 204S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800647 ER PT J AU Siever, LJ AF Siever, Larry J. TI Schizophrenia Susceptibility Genes and Intermediate Phenotypes in Schizotypal Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Siever, Larry J.] James J Peters VAMC, Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 694 BP 209S EP 209S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800663 ER PT J AU Raskind, MA Redila, VA Olson, VG AF Raskind, Murray A. Redila, Van A. Olson, Valerie G. TI Prazosin Blocks Development of Ethanol, Morphine and Cocaine Conditioned Place Preference in Mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Raskind, Murray A.; Olson, Valerie G.] VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA USA. [Redila, Van A.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 745 BP 223S EP 223S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800706 ER PT J AU Frid, SA Pavlidis, P Dracheya, S Byne, W AF Frid, Simon A. Pavlidis, Paul Dracheya, Stella Byne, William TI Differential Gene Expression in Schizophrenia and Bipolar Disorder in the Corpus Collosum SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Frid, Simon A.; Dracheya, Stella; Byne, William] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Pavlidis, Paul] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Dracheya, Stella; Byne, William] Bronx Vet Affairs Med Ctr, Dept Psychiat, New York, NY USA. RI Pavlidis, Paul/H-8406-2013 OI Pavlidis, Paul/0000-0002-0426-5028 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 756 BP 226S EP 226S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800717 ER PT J AU Ghorashi, S Spencer, KM AF Ghorashi, Shahab Spencer, Kevin M. TI Oscillatory Correlates of Face Gestalt Processing in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Ghorashi, Shahab; Spencer, Kevin M.] VA Boston Healthcare Syst, Boston, MA USA. [Ghorashi, Shahab; Spencer, Kevin M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 773 BP 231S EP 231S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800734 ER PT J AU Kuperberg, GR Eddy, M AF Kuperberg, Gina R. Eddy, Marianna TI Seeing The Wood for the Trees: Feedforward Visual Deficits Do Not Fully Explain Semantic Deficits in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Kuperberg, Gina R.] Massachusetts Gen Hosp, Charlestown, MA USA. [Kuperberg, Gina R.] Tufts Univ, Charlestown, MA USA. [Eddy, Marianna] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 781 BP 233S EP 234S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800742 ER PT J AU Mears, RP Spencer, KM AF Mears, Ryan P. Spencer, Kevin M. TI Auditory Cortex Neuroplasticity in Schizophrenia: An ERP Assessment of Stimulus-Specific Plasticity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Mears, Ryan P.; Spencer, Kevin M.] VA Boston Healthcare System, Boston, MA USA. [Mears, Ryan P.; Spencer, Kevin M.] Harvard Univ, Dept Psychiat, Sch Med, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 783 BP 234S EP 234S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800744 ER PT J AU Radant, AD Braff, D Calkins, M Cadenhead, K Dobie, D Freedman, R Green, M Greenwood, T Gur, R Gur, R Horan, W Light, G Meichle, S Millard, S Olincy, A Nuechterlein, K Seidman, L Siever, L Silverman, J Stone, W Sprock, J Swerdlow, N Tsuang, M Turetsky, B Tsuang, D AF Radant, Allen D. Braff, David Calkins, Monica Cadenhead, Kristin Dobie, Dorcas Freedman, Robert Green, Michael Greenwood, Tiffany Gur, Raquel Gur, Ruben Horan, William Light, Gregory Meichle, Sean Millard, Steve Olincy, Ann Nuechterlein, Keith Seidman, Larry Siever, Larry Silverman, Jeremy Stone, William Sprock, Joyce Swerdlow, Neal Tsuang, Ming Turetsky, Bruce Tsuang, Debby TI Influence of Duration of Schizophrenia on Antisaccade Performance SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Radant, Allen D.; Dobie, Dorcas; Meichle, Sean; Millard, Steve; Tsuang, Debby] Puget Sound Hlth Care Syst, Vet Adm, Educ & Clin Ctr, Mental Illness Res,Seattle Div, Seattle, WA USA. [Radant, Allen D.; Meichle, Sean; Millard, Steve; Tsuang, Debby] Univ Washington, Seattle, WA 98195 USA. [Braff, David; Cadenhead, Kristin; Greenwood, Tiffany; Sprock, Joyce; Swerdlow, Neal; Tsuang, Ming] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Calkins, Monica; Gur, Raquel; Gur, Ruben; Turetsky, Bruce] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Freedman, Robert; Olincy, Ann] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. [Green, Michael; Horan, William; Nuechterlein, Keith] Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. [Green, Michael; Horan, William; Nuechterlein, Keith] Greater Angeles Hlth Care Syst, Vet Adm, Los Angeles Div, Los Angeles, CA USA. [Seidman, Larry; Stone, William] Harvard Univ, Sch Med, Dept Psychiat, MA Mental Hlth Ctr Publ Psychiat Div,Beth Israel, Boston, MA 02115 USA. [Siever, Larry; Silverman, Jeremy] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry; Silverman, Jeremy] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 791 BP 237S EP 237S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800752 ER PT J AU Wiste, A McGrath, LM Lee, PH Smoller, JW AF Wiste, Anna McGrath, Lauren M. Lee, Phil H. Smoller, Jordan W. TI Genome-Wide Association Study of Smoking Behavior Among Schizophrenics: Preliminary Results SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Wiste, Anna; Smoller, Jordan W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wiste, Anna; McGrath, Lauren M.; Lee, Phil H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Wiste, Anna; McGrath, Lauren M.; Lee, Phil H.; Smoller, Jordan W.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 834 BP 250S EP 251S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800795 ER PT J AU Goldstein, KE Alloy, LB Drabick, DAG New, AS Siever, LJ Hazlett, EA AF Goldstein, Kim E. Alloy, Lauren B. Drabick, Deborah A. G. New, Antonia S. Siever, Larry J. Hazlett, Erin A. TI Cingulum Integrity in Schizotypal Personality Disorder and Borderline Personality Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Goldstein, Kim E.; Alloy, Lauren B.; Drabick, Deborah A. G.] Temple Univ, Philadelphia, PA 19122 USA. [New, Antonia S.; Siever, Larry J.; Hazlett, Erin A.] Mt Sinai Sch Med, New York, NY USA. [New, Antonia S.; Siever, Larry J.; Hazlett, Erin A.] James J Peters VAMC, Mental Illness Res & Clin Ctr MIRECC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 851 BP 256S EP 256S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800812 ER PT J AU Hazlett, EA Goodman, M Carpenter, D Avedon, J Goldstein, KE New, AS Siever, LJ AF Hazlett, Erin A. Goodman, Marianne Carpenter, David Avedon, Jennifer Goldstein, Kim E. New, Antonia S. Siever, Larry J. TI Exaggerated Amygdala and Startle Response Predicts Positive Dialectical Behavior Therapy Outcome in Borderline Patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Hazlett, Erin A.; Goodman, Marianne; Carpenter, David; Avedon, Jennifer; Goldstein, Kim E.; New, Antonia S.; Siever, Larry J.] Mt Sinai Sch Med, New York, NY USA. [Hazlett, Erin A.; Goodman, Marianne; New, Antonia S.; Siever, Larry J.] James J Peters VAMC, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 7 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 852 BP 256S EP 256S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800813 ER PT J AU Levitt, J Pelavin, PE Alvarado, JL McCarley, RW Shenton, ME AF Levitt, James Pelavin, Paula E. Alvarado, Jorge L. McCarley, Robert W. Shenton, Martha E. TI Regionally Selective Differential Effects of Atypical Neuroleptic Medication on Dorsal but not Ventral Striatum in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Levitt, James; McCarley, Robert W.; Shenton, Martha E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. [Levitt, James; Pelavin, Paula E.; Alvarado, Jorge L.; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 870 BP 262S EP 263S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800831 ER PT J AU Seidman, LJ Thermenos, HW Juelich, R Valera, E Brown, AB Huang, S Salwen, KK Makris, N Whitfield-Gabrieli, S Biederman, J Faraone, SV Tsuang, MT AF Seidman, Larry J. Thermenos, Heidi W. Juelich, Richard Valera, Eve Brown, Ariel B. Huang, Samantha Salwen, Kathryn K. Makris, Nikos Whitfield-Gabrieli, Susan Biederman, Joseph Faraone, Stephen V. Tsuang, Ming T. TI Distinct Pattern of Brain Functioning Underlies Working Memory in ADHD and Individuals at Familial Risk for Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Seidman, Larry J.; Thermenos, Heidi W.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Dept Psychiat, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.; Thermenos, Heidi W.; Brown, Ariel B.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Seidman, Larry J.; Thermenos, Heidi W.; Juelich, Richard; Valera, Eve; Brown, Ariel B.; Huang, Samantha; Salwen, Kathryn K.; Makris, Nikos; Biederman, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Brown, Ariel B.; Makris, Nikos; Whitfield-Gabrieli, Susan] Harvard Mit Div Hlth Sci & Technol, Massachusetts Inst Technol, Dept Brain & Cognit Sci, Boston, MA USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA 02114 USA. [Makris, Nikos] Massachusetts Gen Hosp, Dept Radiol, Ctr Morphometr Anal, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 880 BP 266S EP 267S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800841 ER PT J AU Seidman, LJ Goldstein, JM Cherkerzian, S Agnew-Blais, J Tsuang, MT Buka, S AF Seidman, Larry J. Goldstein, Jill M. Cherkerzian, Sara Agnew-Blais, Jessica Tsuang, Ming T. Buka, Stephen TI Was Kraepelin Right? A 30 Year Follow-Up of Neurocognitive Deterioration in Schizophrenia vs Bipolar Psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Seidman, Larry J.; Goldstein, Jill M.; Tsuang, Ming T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.; Goldstein, Jill M.; Tsuang, Ming T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Goldstein, Jill M.; Cherkerzian, Sara] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Agnew-Blais, Jessica] Harvard Univ, Sch Publ Hlth, Dept Psychiat, Boston, MA 02115 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Buka, Stephen] Brown Univ, Dept Psychiat, Providence, RI 02912 USA. RI Buka, Stephen/H-7335-2014; Agnew-Blais, Jessica/L-9236-2015 OI Buka, Stephen/0000-0002-8578-9308; Agnew-Blais, Jessica/0000-0002-0755-6867 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 879 BP 266S EP 266S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800840 ER PT J AU Fryer, SL Watson, TD Jorgensen, KW Yetter, EJ Krystal, JH Mathalon, DH AF Fryer, Susanna L. Watson, Todd D. Jorgensen, Kasper W. Yetter, Elizabeth J. Krystal, John H. Mathalon, Daniel H. TI Cue Reactivity across Stages of Alcohol Dependence: FMRI Reveals Evidence of Altered Attentional Functioning SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Fryer, Susanna L.; Jorgensen, Kasper W.; Yetter, Elizabeth J.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fryer, Susanna L.; Jorgensen, Kasper W.; Yetter, Elizabeth J.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Watson, Todd D.] Lewis & Clark Coll, Portland, OR 97219 USA. [Krystal, John H.; Mathalon, Daniel H.] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 897 BP 272S EP 272S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800858 ER PT J AU Rabany, L Weiser, M Levkovitz, Y AF Rabany, Liron Weiser, Mark Levkovitz, Yechiel TI Assessment of Depression in Negative Symptoms of Schizophrenia: Revising the Structure of the Calgary Depression Scale for Schizophrenia (CDSS) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Rabany, Liron; Levkovitz, Yechiel] Shalvata Mental Hlth Ctr, Emot Cognit Res Ctr, Hod Hasharon, Israel. [Rabany, Liron] Tel Aviv Univ, Gordon Fac Social Sci, IL-69978 Tel Aviv, Israel. [Rabany, Liron; Weiser, Mark; Levkovitz, Yechiel] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Weiser, Mark] Chaim Sheba Med Ctr, Dept Psychiat, IL-52621 Tel Hashomer, Israel. [Levkovitz, Yechiel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 915 BP 278S EP 278S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800876 ER PT J AU Dutra, SJ Stoeckel, LE Carlini, SV Pizzagalli, DA Evins, AE AF Dutra, Sunny J. Stoeckel, Luke E. Carlini, Sara V. Pizzagalli, Diego A. Evins, A. Eden TI Varenicline as a Smoking Cessation Aid in Schizophrenia Patients: Effects on Smoking Behavior and Reward Sensitivity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Dutra, Sunny J.] Yale Univ, New Haven, CT USA. [Stoeckel, Luke E.; Carlini, Sara V.; Evins, A. Eden] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pizzagalli, Diego A.] McLean Hosp, Belmont, MA 02178 USA. [Pizzagalli, Diego A.; Evins, A. Eden] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 MAY 1 PY 2011 VL 69 IS 9 SU S MA 921 BP 280S EP 280S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800882 ER PT J AU Bashyal, R Malchau, H Nimkin, K Holmes, LB AF Bashyal, R. Malchau, H. Nimkin, K. Holmes, L. B. TI Malformed Pelvis, Hip Dysplasia, and Genital Anomalies: An Association SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Bashyal, R.; Malchau, H.; Nimkin, K.; Holmes, L. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2011 VL 91 IS 5 SI SI BP 342 EP 342 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 762QQ UT WOS:000290494900068 ER PT J AU Thomas, EG Westgate, MN Holmes, LB AF Thomas, E. G. Westgate, M-N Holmes, L. B. TI The Effect of Elective Terminations for Fetal Anomalies on Spectrum of Birth Defects in Liveborn Infants SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Thomas, E. G.; Westgate, M-N; Holmes, L. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thomas, E. G.; Westgate, M-N; Holmes, L. B.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2011 VL 91 IS 5 SI SI BP 354 EP 354 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 762QQ UT WOS:000290494900088 ER PT J AU Han, TH Martyn, JAJ AF Han, T. -H. Martyn, J. A. J. TI Neuromuscular pharmacodynamics of mivacurium in adults with major burns SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE neuromuscular relaxants, mivacurium; pharmacodynamics; trauma, burns ID DUCHENNE MUSCULAR-DYSTROPHY; ACETYLCHOLINE-RECEPTORS; THERMAL-INJURY; ATRACURIUM; PHARMACOKINETICS; ADOLESCENTS; CHILDREN; CHLORIDE; THERAPY; PATIENT AB Background. Mivacurium is metabolized by plasma pseudocholinesterase (PChE) enzyme, which is decreased in burns. We tested whether the decreased metabolism of mivacurium due to decreased PChE activity can overcome the pharmacodynamic resistance to non-depolarizing relaxants previously seen in major burns. Methods. Thirty adults with 35 (13)% [mean (SD)] burn were studied at 5-91 post-burn days and 31 non-burns matched controls. Mivacurium 0.2 mg kg(-1) was administered as a single bolus. Neuromuscular block was monitored with single-twitch response using TOF-Watch (TM). Onset time (drug administration to maximal twitch suppression) and spontaneous recovery were measured. Results. Onset time was significantly prolonged in burns when compared with non-burns (115 vs 90 s; P < 0.001). The PChE levels were lower in burns [1432 (916) vs 2866 (731) IU litre 21; P < 0.001] and the neuromuscular recovery to 50% of baseline twitch height was prolonged in burns (41 vs 26 min; P < 0.001). There was a significant correlation between PChE and time to 50% recovery for the whole group together (r= -20.6; P < 0.001). The dibucaine numbers were not different. Conclusions. The prolonged onset time suggests resistance to neuromuscular effects, whereas the prolonged recovery suggests increased sensitivity. This divergent response can be explained by qualitative and quantitative changes in acetylcholine receptor expression causing resistance and decreased PChE activity causing sensitivity. Despite using a relatively large dose of mivacurium (0.2 mg kg(-1)) in the presence of decreased PChE levels, this did not overcome the resistance resulting from up-regulated receptors. C1 [Han, T. -H.] Univ Iowa Hosp & Clin, Roy J & Lucille A Carver Coll Med, Dept Anesthesia JCP 6505 3, Iowa City, IA 52242 USA. [Martyn, J. A. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Martyn, J. A. J.] Shriners Hosp Children, Boston, MA 02114 USA. RP Han, TH (reprint author), Univ Iowa Hosp & Clin, Roy J & Lucille A Carver Coll Med, Dept Anesthesia JCP 6505 3, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM anthony-han@uiowa.edu FU Korean Health Industry Development Institute, Seoul, Korea [A06-0093-B41104-06N1-00040B]; National Institute of Health, Bethesda, MD, USA [GM 05882]; Shriners Hospital Research Philanthropy FX T.-H. H. was supported in part by grants from the Korean Health Industry Development Institute, Seoul, Korea A06-0093-B41104-06N1-00040B). J.A.J.M. was supported in part by a grant from the National Institute of Health, Bethesda, MD, USA (GM 05882), and grants from Shriners Hospital Research Philanthropy. NR 25 TC 1 Z9 1 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD MAY PY 2011 VL 106 IS 5 BP 675 EP 679 DI 10.1093/bja/aer023 PG 5 WC Anesthesiology SC Anesthesiology GA 763MP UT WOS:000290562800008 PM 21354998 ER PT J AU Salemi, VMC Rochitte, CE Shiozaki, AA Andrade, JM Parga, JR de Avila, LF Benvenuti, LA Cestari, IN Picard, MH Kim, RJ Mady, C AF Salemi, Vera M. C. Rochitte, Carlos E. Shiozaki, Afonso A. Andrade, Joalbo M. Parga, Jose R. de Avila, Luiz F. Benvenuti, Luiz A. Cestari, Ismar N. Picard, Michael H. Kim, Raymond J. Mady, Charles TI Late Gadolinium Enhancement Magnetic Resonance Imaging in the Diagnosis and Prognosis of Endomyocardial Fibrosis Patients SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE myocardial cardiomyopathy disease; endomyocardial fibrosis; restrictive cardiomyopathy; heart failure; magnetic resonance imaging; gadolinium; prognosis ID DELAYED-ENHANCEMENT; IN-VIVO; DISEASE; CARDIOMYOPATHIES; VISUALIZATION; THROMBI; MARKER AB Background-Endocardial fibrous tissue (FT) deposition is a hallmark of endomyocardial fibrosis (EMF). Echocardiography is a first-line and the standard technique for the diagnosis of this disease. Although late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) allows FT characterization, its role in the diagnosis and prognosis of EMF has not been investigated. Methods and Results-Thirty-six patients (29 women; age, 54 +/- 12 years) with EMF diagnosis after clinical evaluation and comprehensive 2-dimensional Doppler echocardiography underwent cine-CMR for assessing ventricular volumes, ejection fraction and mass, and LGE-CMR for FT characterization and quantification. Indexed FT volume (FT/body surface area) was calculated after planimetry of the 8 to 12 slices obtained in the short-axis view at end-diastole (mL/m(2)). Surgical resection of FT was performed in 16 patients. In all patients, areas of LGE were confined to the endocardium, frequently as a continuous streak from the inflow tract extending to the apex, where it was usually most prominent. There was a relation between increased FT/body surface area and worse New York Heart Association functional class and with increased probability of surgery (P<0.05). The histopathologic examination of resected FT showed typical features of EMF with extensive endocardial fibrous thickening, proliferation of small vessels, and scarce inflammatory infiltrate. In multivariate analysis, the patients with FT/body surface area >19 mL/m(2) had an increased mortality rate, with a relative risk of 10.8. Conclusions-Our study provides evidence that LGE-CMR is useful in the diagnosis and prognosis of EMF through quantification of the typical pattern of FT deposition. (Circ Cardiovasc Imaging. 2011;4:304-311.) C1 [Salemi, Vera M. C.; Mady, Charles] Univ Sao Paulo, Heart Inst InCor, Fac Med, Cardiomyopathy Unit, Sao Paulo, Brazil. [Rochitte, Carlos E.; Shiozaki, Afonso A.; Andrade, Joalbo M.; Parga, Jose R.; de Avila, Luiz F.] Univ Sao Paulo, Heart Inst InCor, Fac Med, Magnet Resonance Sect, Sao Paulo, Brazil. [Benvenuti, Luiz A.] Univ Sao Paulo, Heart Inst InCor, Fac Med, Pathol Lab, Sao Paulo, Brazil. [Cestari, Ismar N.] Univ Sao Paulo, Heart Inst InCor, Fac Med, Biomed Technol Ctr, Sao Paulo, Brazil. [Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Picard, Michael H.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Picard, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Raymond J.] Duke Univ, Med Ctr, Duke Cardiovasc Magnet Resonance Ctr, Dept Med, Durham, NC USA. [Kim, Raymond J.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC USA. RP Salemi, VMC (reprint author), Av Jandira 185 Apt 41B Indianopolis, BR-04080000 Sao Paulo, Brazil. EM verasalemi@uol.com.br RI Cestari, Ismar /B-7286-2012; Kim, Raymond/B-1426-2008; Benvenuti, Luiz/C-6614-2014; Mady, Charles/C-8870-2012; Salemi, Vera/C-9104-2013; OI Mady, Charles/0000-0002-8838-199X; Salemi, Vera/0000-0002-7152-1810; Picard, Michael/0000-0002-9264-3243 NR 26 TC 23 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2011 VL 4 IS 3 BP 304 EP U163 DI 10.1161/CIRCIMAGING.110.950675 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 765NU UT WOS:000290715800016 PM 21415124 ER PT J AU Truong, QA Murphy, SA McCabe, CH Armani, A Cannon, CP AF Truong, Quynh A. Murphy, Sabina A. McCabe, Carolyn H. Armani, Annemarie Cannon, Christopher P. CA TIMI Study Grp TI Benefit of Intensive Statin Therapy in Women Results From PROVE IT-TIMI 22 SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE hydroxymethylglutaryl-CoA reductase inhibitors; sex; acute coronary syndrome; prognosis; secondary prevention ID ACUTE CORONARY SYNDROMES; C-REACTIVE PROTEIN; CARDIOVASCULAR EVENTS; HEART-DISEASE; PRIMARY-PREVENTION; MYOCARDIAL-INFARCTION; CHOLESTEROL LEVELS; CONTROLLED TRIAL; PRAVASTATIN; ATORVASTATIN AB Background-Despite the known benefit of intensive statin therapy for reducing future cardiovascular events, its effectiveness in women has been questioned by some. Methods and Results-In the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial, 911 (21.9%) women and 3251 (78.1%) men were randomized to intensive statin (atorvastatin 80 mg) versus standard therapy (pravastatin 40 mg) therapy for a median duration of 2.1 years. The primary end point was death, myocardial infarction, unstable angina; revascularization (occurring after 30 days); or stroke. Safety end points included elevations in liver function tests, creatine kinase, and myalgias/myositis. Women had a reduction in low-density lipoprotein (LDL) of 42.8% from baseline at 30 days (to a median of 60 mg/dL) in the intensive therapy arm, with 88.8% reaching the LDL goal of <100 mg/dL and 65.0% of <70 mg/dL, compared with a 16.8% reduction in LDL (to a median of 88 mg/dL) in the standard therapy arm. Women receiving intensive statin therapy had a significant 25% relative reduction over standard dose (hazard ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04) for the primary composite end point compared with a 14% reduction for men (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P=0.04; P-interaction, 0.38). No differences were observed between sexes for safety (all P-interaction >= 0.11). Conclusions-This trial provides evidence that both women and men derived benefit from intensive statin therapy after acute coronary syndrome, and thus, sex should not be a factor in determining who should be treated with intensive statin therapy. C1 [Murphy, Sabina A.; McCabe, Carolyn H.; Armani, Annemarie; Cannon, Christopher P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. [Truong, Quynh A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM cpcannon@partners.org FU Bristol Myers Squibb, Princeton, NJ; Sankyo, Parsippany, NJ; National Institutes of Health [L30HL093896, K23HL098370]; AstraZeneca; Bristol-Myers Squibb/Sanofi Partnership; GlaxoSmithKline; Merck; Accumetrics; Intekrin Therapeutics; Takeda FX The trial was funded by Bristol Myers Squibb, Princeton, NJ, and Sankyo, Parsippany, NJ.; Dr Truong received research grant support from National Institutes of Health grants L30HL093896 and K23HL098370. Ms McCabe received research grant support from AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, and Merck. Dr Cannon received research grant support from Accumetrics, AstraZeneca, GlaxoSmithKline, Merck, Intekrin Therapeutics, and Takeda; has served on advisory boards for Bristol-Myers Squibb/Sanofi-Aventis and Novartis (but funds donated to charity); and reports having equity ownership in Automedics Medical Systems. NR 34 TC 30 Z9 32 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2011 VL 4 IS 3 BP 328 EP 336 DI 10.1161/CIRCOUTCOMES.110.957720 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 765NX UT WOS:000290716100014 PM 21487089 ER PT J AU Attumi, TA Graham, DY AF Attumi, Taraq A. Graham, David Y. TI Follow-up Testing After Treatment of Helicobacter Pylori Infections: Cautions, Caveats, and Recommendations SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID STOOL ANTIGEN TEST; UREA BREATH TESTS; DIAGNOSIS; GASTRITIS; ANTRUM; CORPUS C1 [Attumi, Taraq A.; Graham, David Y.] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Attumi, TA (reprint author), Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. FU NCI NIH HHS [CA116845]; NIDDK NIH HHS [DK56338, DK067366] NR 13 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAY PY 2011 VL 9 IS 5 BP 373 EP 375 DI 10.1016/j.cgh.2010.12.025 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 764TV UT WOS:000290657200010 PM 21195791 ER PT J AU LiVolsi, VA Abrosimov, AA Bogdanova, T Fadda, G Hunt, JL Ito, M Rosai, J Thomas, GA Williams, ED AF LiVolsi, V. A. Abrosimov, A. A. Bogdanova, T. Fadda, G. Hunt, J. L. Ito, M. Rosai, J. Thomas, G. A. Williams, E. D. TI The Chernobyl Thyroid Cancer Experience: Pathology SO CLINICAL ONCOLOGY LA English DT Article DE Iodine; papillary cancer; radiation; subtypes; thyroid cancer ID BIOLOGIC BEHAVIOR; CARCINOMA; PAPILLARY; ACCIDENT; CHILDREN; GLAND; CHILDHOOD; PROGNOSIS; EXPOSURE; DISEASES AB The Chernobyl accident was followed by a large increase in the incidence of thyroid carcinoma in the areas exposed to high levels of fallout. The Chernobyl Tumor Bank was set up in 1998 to make tumours available for study internationally, and a pathology panel reviewed all the tumours and established an agreed diagnosis. The thyroid tumours that were discovered after the Chernobyl nuclear accident were virtually all (95%) of the papillary carcinoma type. Rare examples of other tumour types were identified. Within the papillary group, several subtypes were noted, including classical or usual type, follicular variant, solid variant and mixed patterns Diffuse sclerosis variant, cribriform/morular type and Warthin-like variant were rare. No tall cell or columnar cell variants were identified. The tumours examined by the Pathology Panel of the Chernobyl Tumor Bank constitute a large representative sample (estimated at about 50%) of the tumours that developed in this population. This overview describes the method adopted by the panel and the different diagnostic categories adopted; illustrates the pathology of these neoplasms; compares the pathological characteristics of the early lesions with those identified after long latency periods and the institution of screening programmes and outlines the possible associated causes for the various morphological patterns seen. (C) 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [LiVolsi, V. A.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Abrosimov, A. A.] Fed State Inst, Med Radiol Res Ctr, Obninsk, Kaluga Region, Russia. [Bogdanova, T.] Ukraine Acad Med Sci, Inst Endocrinol & Metab, Kiev, Ukraine. [Fadda, G.] Univ Cattolica Sacro Cuore, Div Anat Pathol, I-00168 Rome, Italy. [Hunt, J. L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ito, M.] Natl Nagasaki Med Ctr, Res Lab, Omura, Japan. [Rosai, J.] Ctr Diagnost Italiano CDI, Ctr Consulenze Anat Patol Oncol, Milan, Italy. [Thomas, G. A.] Hammersmith Hosp, Div Surg & Canc, London, England. [Williams, E. D.] Strangeways Res Lab, Thyroid Carcinogenesis Res Unit, Cambridge CB1 4RN, England. RP LiVolsi, VA (reprint author), Univ Penn, Dept Pathol & Lab Med, 3400 Spruce St, Philadelphia, PA 19104 USA. EM linus@mail.med.upenn.edu RI Abrosimov, A/H-3382-2015 OI Abrosimov, A/0000-0001-8284-9996 NR 31 TC 20 Z9 21 U1 1 U2 9 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PD MAY PY 2011 VL 23 IS 4 SI SI BP 261 EP 267 DI 10.1016/j.clon.2011.01.160 PG 7 WC Oncology SC Oncology GA 767GE UT WOS:000290842500005 PM 21333507 ER PT J AU Li, A Zhou, C Moore, J Zhang, P Tsai, TH Lee, HC Romano, DM Mckee, ML Schoenfeld, DA Serra, MJ Raygor, K Cantiello, HF Fujimoto, JG Tanzi, RE AF Li, A. Zhou, C. Moore, J. Zhang, P. Tsai, T. -H. Lee, H. -C. Romano, D. M. McKee, M. L. Schoenfeld, D. A. Serra, M. J. Raygor, K. Cantiello, H. F. Fujimoto, J. G. Tanzi, R. E. TI Changes in the Expression of the Alzheimer's Disease-Associated Presenilin Gene in Drosophila Heart Leads to Cardiac Dysfunction SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Alzheimer's disease; calcium channel; cardiomyopathy; Drosophila; heart; presenilin ID OPTICAL COHERENCE TOMOGRAPHY; IDIOPATHIC DILATED CARDIOMYOPATHY; AMYLOID PRECURSOR PROTEIN; BETA-CATENIN; GAMMA-SECRETASE; INTRAMEMBRANE PROTEOLYSIS; APOLIPOPROTEIN-E; IN-VIVO; MUTATIONS; MELANOGASTER AB Mutations in the presenilin genes cause the majority of early-onset familial Alzheimer's disease. Recently, presenilin mutations have been identified in patients with dilated cardiomyopathy (DCM), a common cause of heart failure and the most prevalent diagnosis in cardiac transplantation patients. However, the molecular mechanisms, by which presenilin mutations lead to either AD or DCM, are not yet understood. We have employed transgenic Drosophila models and optical coherence tomography imaging technology to analyze cardiac function in live adult Drosophila. Silencing of Drosophila ortholog of presenilins (dPsn) led to significantly reduced heart rate and remarkably age-dependent increase in end-diastolic vertical dimensions. In contrast, overexpression of dPsn increased heart rate. Either overexpression or silencing of dPsn resulted in irregular heartbeat rhythms accompanied by cardiomyofibril defects and mitochondrial impairment. The calcium channel receptor activities in cardiac cells were quantitatively determined via real-time RT-PCR. Silencing of dPsn elevated dIP(3)R expression, and reduced dSERCA expression; overexprerssion of dPsn led to reduced dRyR expression. Moreover, overexpression of dPsn in wing disc resulted in loss of wing phenotype and reduced expression of wingless. Our data provide novel evidence that changes in presenilin level leads to cardiac dysfunction, owing to aberrant calcium channel receptor activities and disrupted Wnt signaling transduction, indicating a pathogenic role for presenilin mutations in DCM pathogenesis. C1 [Li, A.; Moore, J.; Romano, D. M.; Raygor, K.; Tanzi, R. E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Li, A.; Moore, J.; Zhang, P.; Romano, D. M.; McKee, M. L.; Serra, M. J.; Raygor, K.; Cantiello, H. F.; Tanzi, R. E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Zhou, C.; Tsai, T. -H.; Lee, H. -C.; Fujimoto, J. G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Zhang, P.; Serra, M. J.; Cantiello, H. F.] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. [McKee, M. L.] Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. [Schoenfeld, D. A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, 114,16th St, Charlestown, MA 02129 USA. EM jgfuji@mit.edu; tanzi@helix.mgh.harvard.edu RI Zhou, Chao/A-1327-2007; OI Tsai, Tsung-Han/0000-0002-2306-2269 FU Cure Alzheimer's Fund; National Institute of Health [R01AG014713, R01MH60009, R01CA75289, R01HL095717]; Air Force Office of Scientific Research [FA9550-07-1-0014]; Neuroscience Education and Research Foundation; Boston Area Diabetes and Endocrinology Research Center [DK 57521]; Center for the Study of Inflammatory Bowel Disease [DK 43351] FX We wish to thank Mark E. Fortini for kindly providing Drosophila stocks and helpful suggestion, and Brett E. Bouma, Michael A. Choma, Gary Tearney, and Steven N. Fry for their helpful advice and technical assistance. This work was supported by the Cure Alzheimer's Fund [to R.E.T], National Institute of Health [R01AG014713 and R01MH60009 to R.E.T; R01CA75289 and R01HL095717 to J.G.F], Air Force Office of Scientific Research [FA9550-07-1-0014 to J.G.F], and the Neuroscience Education and Research Foundation [to A.L.]. The Microscopy Core Facility at the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center [DK 57521] and the Center for the Study of Inflammatory Bowel Disease [DK 43351]. NR 52 TC 12 Z9 12 U1 3 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD MAY PY 2011 VL 8 IS 3 BP 313 EP 322 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 768BA UT WOS:000290905100012 PM 21524270 ER PT J AU Rosenbaum, JF AF Rosenbaum, Jerrold F. TI Recollections from the ADAA President SO DEPRESSION AND ANXIETY LA English DT Editorial Material C1 [Rosenbaum, Jerrold F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosenbaum, JF (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. EM JRosenbaum@partners.org NR 1 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAY PY 2011 VL 28 IS 5 BP 355 EP 357 DI 10.1002/da.20813 PG 3 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 761RN UT WOS:000290416200001 PM 21449007 ER PT J AU Davis, BH Pope, C Mason, PR Magwood, G Jenkins, CM AF Davis, Boyd H. Pope, Charlene Mason, Peyton R. Magwood, Gayenell Jenkins, Carolyn M. TI "It's a Wild Thing, Waiting to Get Me": Stance Analysis of African Americans With Diabetes SO DIABETES EDUCATOR LA English DT Article ID SELF-MANAGEMENT; EDUCATION; CULTURE; HEALTH; CARE; COMMUNICATION AB Purpose This mixed methods study uses a unique approach from social science and linguistics methodologies, a combination of positioning theory and stance analysis, to examine how 20 African Americans with type 2 diabetes make sense of the practices that led to recurrent emergency department visits to identify needs for more effective intervention. Methods In a purposive sample of postemergency department visit interviews with a same-race interviewer, people responded to open-ended questions reflecting on the decision to seek emergency department care. As applied to diabetes education, positioning theory explains that people use their language to position themselves toward their disease, their medications, and the changes in their lives. Transcriptions were coded using discourse analysis to categorize themes. As a form of triangulation, stance analysis measured language patterns using factor analysis to see when and how speakers revealed affect, attitude, and agentive choices for action. Conclusion Final analysis revealed that one third of the sample exhibited high scores for positive agency or capacity for decision-making and self-management, while the rest expressed less control and more negative emotions and fears that may preclude self-management. This approach suggests a means to tailor diabetes education considering alternative approaches focused on communication for those facing barriers. C1 [Pope, Charlene; Magwood, Gayenell; Jenkins, Carolyn M.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Davis, Boyd H.] Univ N Carolina, Dept English Appl Linguist, Charlotte, NC 28223 USA. [Pope, Charlene] Charleston REAP, Ralph H Johnson Dept, Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Mason, Peyton R.] Next Generat Mkt Insights, Charlotte, NC USA. RP Pope, C (reprint author), Med Univ S Carolina, Coll Nursing, 99 Jonathan Lucas St, Charleston, SC 29425 USA. EM popec@musc.edu OI Davis, Boyd/0000-0003-4773-7715 FU Medical University of South Carolina Center for Health Disparities Research; [NIH/NINR 1 R15 NR009486-01A1] FX This study was supported by Grant #NIH/NINR 1 R15 NR009486-01A1, 2006, entitled "Emergency Department Use-African American with Diabetes," (Dr Carolyn Jenkins, principal investigator), and an intramural grant from the Medical University of South Carolina Center for Health Disparities Research, 2008 (Dr Charlene Pope, principal investigator). Dr Pope's contribution is the result of work supported with resources and the use of facilities at the Charleston, SC, Ralph H. Johnson VAMC, and the HSR&D REAP Center for Disease Prevention and Health Interventions for Diverse Populations (REA 08-261). Disclaimer: The views expressed in this article are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. NR 38 TC 2 Z9 2 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2011 VL 37 IS 3 BP 409 EP 418 DI 10.1177/0145721711404439 PG 10 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 764US UT WOS:000290660500007 PM 21515541 ER PT J AU Wander, PL Boyko, EJ Leonetti, DL McNeely, MJ Kahn, SE Fujimoto, WY AF Wander, P. L. Boyko, E. J. Leonetti, D. L. McNeely, M. J. Kahn, S. E. Fujimoto, W. Y. TI Greater hand-grip strength predicts a lower risk of developing type 2 diabetes over 10 years in leaner Japanese Americans SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Epidemiology; Muscle; Hand strength; Japanese-American ID BODY-COMPOSITION; MUSCLE STRENGTH; LIFETIME RISK; GRIP STRENGTH; MELLITUS; CLASSIFICATION; DIAGNOSIS; ADULTS; HEALTH AB Aims: Much is known about body composition and type 2 diabetes risk but less about body function such as strength. We assessed whether hand-grip strength predicted incident diabetes. Methods: We followed 394 nondiabetic Japanese-American subjects (mean age 51.9) for the development of diabetes. We fit a logistic regression model to examine the association between hand-grip strength at baseline and type 2 diabetes risk over 10 years, adjusted for age, sex, and family history. Results: A statistically significant (p = 0.008) and negative (coefficient -0.208) association was observed between hand-grip strength and diabetes risk that diminished at higher BMI levels. Adjusted ORs for a 10-pound hand-grip strength increase with BMI set at the 25th, 50th or 75th percentiles were 0.68, 0.79, and 0.98, respectively. Conclusions: Among leaner individuals, greater hand-grip strength was associated with lower risk of type 2 diabetes, suggesting it may be a useful marker of risk in this population. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Wander, P. L.; Boyko, E. J.; McNeely, M. J.; Kahn, S. E.; Fujimoto, W. Y.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Boyko, E. J.; Kahn, S. E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Leonetti, D. L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Wander, PL (reprint author), Univ Washington, Dept Med, 1959 NE Pacific St,Box 356421, Seattle, WA 98195 USA. EM lwander@u.washington.edu OI Wander, Pandora/0000-0003-3671-1464; Kahn, Steven/0000-0001-7307-9002 FU National Institutes of Health [DK-31170, HL-49293, DK-02654]; Diabetes and Endocrinology Research Center [DK-17047]; Clinical Nutrition Research Unit [DK-35816]; General Clinical Research Center at the University of Washington [RR-00037]; VA Puget Sound Health Care System; King County Japanese-American Community FX This work was supported by National Institutes of Health Grants DK-31170, HL-49293, and DK-02654; by facilities and services provided by the Diabetes and Endocrinology Research Center (DK-17047), Clinical Nutrition Research Unit (DK-35816), and the General Clinical Research Center (RR-00037) at the University of Washington. VA Puget Sound Health Care System provides support for Drs. Boyko and Kahn's involvement in this research. We are grateful to the King County Japanese-American Community for support and cooperation. NR 15 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD MAY PY 2011 VL 92 IS 2 BP 261 EP 264 DI 10.1016/j.diabres.2011.01.007 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 764ER UT WOS:000290612200020 PM 21281974 ER PT J AU Badr, CE Niers, JM Morse, D Koelen, JA Vandertop, P Noske, D Wurdinger, T Zalloua, PA Tannous, BA AF Badr, C. E. Niers, J. M. Morse, D. Koelen, J. A. Vandertop, P. Noske, D. Wurdinger, T. Zalloua, P. A. Tannous, B. A. TI Suicidal gene therapy in an NF-kappa B-controlled tumor environment as monitored by a secreted blood reporter SO GENE THERAPY LA English DT Article DE suicidal gene therapy; cytosine deaminase; uracil phosphoribosyltransferase; nuclear factor-kappa B; Gaussia luciferase; blood reporter ID CYTOSINE DEAMINASE GENE; ENZYME-PRODRUG THERAPY; CELL LUNG-CANCER; IN-VIVO; URACIL PHOSPHORIBOSYLTRANSFERASE; COLORECTAL-CANCER; OVARIAN-CANCER; EXPRESSION; 5-FLUOROCYTOSINE; ACTIVATION AB The nuclear factor-kappa B (NF-kappa B) is known to be activated in many cancer types including lung, ovarian, astrocytomas, melanoma, prostate as well as glioblastoma, and has been shown to correlate with disease progression. We have cloned a novel NF-kappa B-based reporter system (five tandem repeats of NF-kappa B responsive genomic element (NF; 14 bp each)) to drive the expression cassette for both a fusion between the yeast cytosine deaminase and uracil phosphoribosyltransferase (CU) as a therapeutic gene and the secreted Gaussia luciferase (Gluc) as a blood reporter, separated by an internal ribosomal entry site (NE-CU-IGIuc). We showed that malignant tumor cells have high expression of Gluc, which correlates to high activation of NF-kappa B. When NF-kappa B was further activated by tumor necrosis factor-a in these cells, we observed up to 10-fold increase in Gluc levels and therefore transgene expression in human glioma cells served to greatly enhance the sensitization of these cells to the prodrug, 5-fluorocytosine both in cultured cells and in vivo subcutaneous tumor xenograft model. This inducible system provides a tool to enhance the expression of imaging and therapeutic genes for cancer therapy. Gene Therapy (2011) 18, 445-451; doi:10.1038/gt.2010.156; published online 9 December 2010 C1 [Badr, C. E.; Niers, J. M.; Morse, D.; Koelen, J. A.; Tannous, B. A.] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Boston, MA 02129 USA. [Badr, C. E.; Niers, J. M.; Morse, D.; Koelen, J. A.; Tannous, B. A.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Badr, C. E.; Niers, J. M.; Vandertop, P.; Noske, D.; Wurdinger, T.] Canc Ctr Amsterdam, VU Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Koelen, J. A.] Univ Utrecht, Grad Sch Life Sci, Utrecht, Netherlands. [Zalloua, P. A.] Lebanese Amer Univ, Sch Med, Chouran Beirut, Lebanon. [Tannous, B. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU National Cancer Institute [P50 CA86355]; National Institute of Neurological Disorders [P30 NS045776]; Frem Foundation FX This work was supported by grants from the National Cancer Institute (P50 CA86355), the National Institute of Neurological Disorders (P30 NS045776) as well as the Frem Foundation. We would like to thank: Mr Neemat Frem (Indevco Group Sal, Lebanon) for providing guidance throughout the multiple design phases of the project; Miss Lee-Ann Tjon-Kon-Fat and Lisa Pike for technical assistance; Dr Miguel Sena-Esteves for help with designing the lentivirus vector; and Dr Xandra Breakefield for advice and critical reading of this manuscript. NR 52 TC 11 Z9 11 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAY PY 2011 VL 18 IS 5 BP 445 EP 451 DI 10.1038/gt.2010.156 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 765XK UT WOS:000290742500004 PM 21150937 ER PT J AU Bell-McGuinn, KM Matthews, CM Ho, SN Barve, M Gilbert, L Penson, RT Lengyel, E Palaparthy, R Gilder, K Vassos, A McAuliffe, W Weymer, S Barton, J Schilder, RJ AF Bell-McGuinn, Katherine M. Matthews, Carolyn M. Ho, Steffan N. Barve, Minal Gilbert, Lucy Penson, Richard T. Lengyel, Ernst Palaparthy, Rameshraja Gilder, Kye Vassos, Artemios McAuliffe, William Weymer, Sara Barton, Jeremy Schilder, Russell J. TI A phase II, single-arm study of the anti-alpha 5 beta 1 integrin antibody volociximab as monotherapy in patients with platinum-resistant advanced epithelial ovarian or primary peritoneal cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Volociximab; Ovarian cancer; Platinum resistant; alpha 5 beta 1 integrin ID CIRCULATING TUMOR-CELLS; ALPHA(5)BETA(1) INTEGRIN; LIPOSOMAL DOXORUBICIN; ONCOLOGY-GROUP; BEVACIZUMAB; THERAPY; ANGIOGENESIS; CHEMOTHERAPY; CISPLATIN; FIBRONECTIN AB Objective. This phase II, multicenter, single-arm, two-stage study in platinum-resistant, advanced epithelial ovarian or primary peritoneal cancer evaluated the efficacy, safety, and tolerability of weekly single-agent volociximab. Pharmacokinetic/pharmacodynamic (PK/PD) studies were also performed. Methods. Sixteen patients were enrolled in Stage 1. Volociximab was administered at 15 mg/kg IV qwk until progression of disease or drug intolerability. Tumor response was assessed every 8 weeks. Serum samples for PK or whole blood for the evaluation of circulating tumor cells, endothelial cells, and endothelial progenitor cells were obtained on Days 1, 8, 15, 29, and 50. Ascites from one patient was collected for volociximab concentration analysis. Archived tumor tissue was analyzed by immunohistochemistry (IHC) for alpha 5 integrin expression. Results. Safety data are available on all 16 patients; 14 were evaluable for efficacy. One patient had stable disease at 8 weeks. The remaining 13 progressed on treatment. Twelve patients (75%) experienced study-related adverse events (AEs); the most common (>= 20%) were headache and fatigue. Three patients experienced possible study-related serious AEs (SAEs): reversible posterior leukoencephalopathy syndrome, pulmonary embolism, and hyponatremia. Peak serum concentrations of volociximab increased 2-3 fold from Day 1 to Day 50. Clinically relevant trough levels were achieved (> 150 mu g/mL). IHC analysis of archived tumor sections showed low-to-moderate expression of alpha 5 integrin on all ovarian cancer tissue evaluated. Conclusion. Despite insufficient clinical activity in this refractory patient population to continue the study, weekly volociximab was well tolerated, and the gained understanding of the mechanism of action of volociximab will inform future development efforts. (C) 2011 Elsevier Inc. All rights reserved. C1 [Bell-McGuinn, Katherine M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Matthews, Carolyn M.] Mary Crowley Med Res Ctr, Dallas, TX USA. [Ho, Steffan N.; Palaparthy, Rameshraja; Gilder, Kye; Vassos, Artemios; McAuliffe, William; Weymer, Sara; Barton, Jeremy] Biogen Idec Inc, San Diego, CA USA. [Barve, Minal] Texas Oncol Presbyterian, Dallas, TX USA. [Gilbert, Lucy] McGill Univ Hosp, Montreal, PQ, Canada. [Penson, Richard T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lengyel, Ernst] Univ Chicago, Chicago, IL 60637 USA. [Schilder, Russell J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Bell-McGuinn, KM (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM bell-mck@mskcc.org RI Lengyel, Ernst/D-9220-2014 OI Lengyel, Ernst/0000-0001-8624-1507 FU PDL Biopharma Inc.; PDL FX Richard T. Penson: Research funds from PDL Biopharma Inc.; Ernst lengyel: Received funding from PDL for experiments with the antibody. (Cancer Res. 2008 Apr 1;68(7):2329-39.) NR 34 TC 48 Z9 49 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 MAY 1 PY 2011 VL 121 IS 2 BP 273 EP 279 DI 10.1016/j.ygyno.2010.12.362 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AD UT WOS:000290292100007 PM 21276608 ER PT J AU Farley, J Sill, MW Birrer, M Walker, J Schilder, RJ Thigpen, JT Coleman, RL Miller, BE Rose, PG Lankes, HA AF Farley, John Sill, Michael W. Birrer, Michael Walker, Joan Schilder, Russell J. Thigpen, J. Tate Coleman, Robert L. Miller, Brigitte E. Rose, Peter G. Lankes, Heather A. TI Phase II study of cisplatin plus cetuximab in advanced, recurrent, and previously treated cancers of the cervix and evaluation of epidermal growth factor receptor immunohistochemical expression: A Gynecologic Oncology Group study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Cisplatin; Cetuximab; Cervical cancer ID SQUAMOUS-CELL CARCINOMA; MONOCLONAL-ANTIBODY C225; K-RAS ACTIVATION; UTERINE CERVIX; EXPLORATORY CELIOTOMY; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER; CLINICAL-TRIALS; 2-STAGE DESIGNS; LUNG-CANCER AB Background. The purpose of this study was to evaluate the safety and efficacy of cetuximab (C225), an antibody that inhibits epidermal growth factor receptor (EGFR) activity, with cisplatin and to explore associations between EGFR protein expression with patient demographics or clinical outcome. Methods. Women with advanced, persistent, or recurrent carcinoma of the cervix were eligible. The women received cisplatin at 30 mg/m(2) on days 1 and 8 with a loading dose of cetuximab at 400 mg/m(2) followed by 250 mg/m(2) on days 1, 8, and 15 in a 21 day cycle. Adverse events were assessed with CTCAE v 3.0. Primary measure of efficacy was tumor response by RECIST. The study was stratified by prior chemotherapy (CT). EGFR protein expression in pre-treatment tumor was analyzed by immunohistochemistry. Results. Between September 2004 and March 2008, 76 patients were enrolled. Of these, 69 were eligible and evaluable: 44 (64%) received prior chemotherapy. There were 4 responses in each group, prior chemotherapy and no chemotherapy, 9% and 16%, respectively. Grade 4 toxicities included anemia (1), allergy (1), metabolic (1), and vascular (1). The most common grade 3 toxicities were metabolic (15), dermatologic (8), fatigue (6), and gastrointestinal (6). EGFR protein was expressed in 47/48 (98%) of tumors analyzed with a median cellular expression of 81%. Exploratory analyses revealed a trend between the percentage of cells expressing EGFR protein and PFS (hazard ratio = 1.76, 95% confidence interval = 0.96-3.21). Conclusions. The combination of cetuximab with cisplatin was adequately tolerated but did not indicate additional benefit beyond cisplatin therapy. Published by Elsevier Inc. C1 [Farley, John] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Sill, Michael W.; Lankes, Heather A.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Sill, Michael W.] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA. [Birrer, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Joan] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet Gynecol, Oklahoma City, OK 73190 USA. [Schilder, Russell J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Thigpen, J. Tate] Univ Mississippi, Med Ctr, Dept Med Oncol, Jackson, MS 39216 USA. [Coleman, Robert L.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77230 USA. [Miller, Brigitte E.] Wake Forest Univ, Dept Obstet Gynecol, Winston Salem, NC 27157 USA. [Rose, Peter G.] Cleveland Clin Fdn, Dept Obstet Gynecol, Cleveland, OH 44195 USA. [Rose, Peter G.] Case Western Reserve Univ, Cleveland, OH 44195 USA. RP Farley, J (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, 4301 Jones Bridge Rd, Bethesda, MD 20832 USA. EM john.farley@us.army.mil FU National Cancer Institute [CA 27469, CA 37517] FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517). This trial was registered at www.clinicaltrials.gov, NCT 10101192. The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: University of Mississippi Medical Center, Indiana University School of Medicine, Wake Forest University School of Medicine, The Cleveland Clinic Foundation, MD Anderson Cancer Center, Fox Chase Cancer Center, University of Oklahoma, University of Texas - Galveston and Gynecologic Oncology Network. NR 46 TC 35 Z9 39 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY 1 PY 2011 VL 121 IS 2 BP 303 EP 308 DI 10.1016/j.ygyno.2011.01.030 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AD UT WOS:000290292100012 PM 21329967 ER PT J AU Farley, J Smith, LM Darcy, KM Brady, MF Bell, J McGuire, W Birrer, MJ AF Farley, John Smith, Leia M. Darcy, Kathleen M. Brady, Mark F. Bell, Jeffrey McGuire, William Birrer, Michael J. TI Nuclear P27 expression in benign, borderline (LMP) and invasive tumors of the ovary and its association with prognosis: A gynecologic oncology group study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE p27; Ovary; Carcinogenesis; Prognostic; Immunohistochemistry ID DEPENDENT KINASE INHIBITOR; CELL-CYCLE REGULATORS; BREAST-CANCER CELLS; P27(KIP1) EXPRESSION; GROWTH ARREST; SUBCELLULAR-LOCALIZATION; SURVIVAL; D1; MALIGNANCY; MUTATIONS AB Objective. Nuclear p27 expression was examined in non-invasive and invasive ovarian tumors from a cross-sectional study, and clinical relevance of p27 was evaluated in the primary tumors from women participating in two randomized phase III treatment trials. Methods. An immunohistochemistry assay was used to detect p27 in formalin-fixed paraffin-embedded ovarian tumors from 3 distinct sources. Results. Among the initial 91 ovarian tumors tested, low p27 expression (< 50% positive cells) was observed in 5.4% of non-invasive tumors versus 42.6% of invasive tumors (p < 0.001). In 145 ovarian cancers with high-risk early stage disease, 16.5% exhibited low p27 expression, and categorized p27 was not associated with age, race, or performance status. Low expression of p27 was common in poorly differentiated tumors (35.7%) compared to moderately (15.0%) and well (9.5%) differentiated tumors (p = 0.024) and rare in clear cell carcinomas (2.4%) compared to other histologies (p = 0.014). In the 139 cancers with advanced disease, 60% displayed low p27 expression, and categorized p27 expression was not associated with age, race, performance status, tumor grade, histologic subtype, measurable disease status or survival. Exploratory analyses revealed an association of cyclin E to p27 ratio > 1.0 with an increased risk of death (hazard ratio = 1.53; p = 0.017). Conclusions. Low p27 expression could be associated with malignant transformation of the ovarian epithelium and FIGO stage. A cyclin E to p27 ratio > 1.0 may be associated with shorter survival in these patients. Further study is required to confirm the trend for increased recurrences with low p27 expression in early stage disease. (C) 2010 Published by Elsevier Inc. C1 [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Farley, John] Walter Reed Army Med Ctr, Dept Obstet Gynecol, Div Gynecol Oncol, Washington, DC 20307 USA. [Smith, Leia M.] Seattle Genet Inc, Seattle, WA 98021 USA. [Darcy, Kathleen M.; Brady, Mark F.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Bell, Jeffrey] Riverside Methodist Hosp, Columbus, OH 43214 USA. [McGuire, William] Franklin Sq Hosp, Baltimore, MD 21237 USA. [Birrer, Michael J.] Harvard Canc Ctr, Boston, MA 02114 USA. [Birrer, Michael J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Birrer, MJ (reprint author), Massachusetts Gen Hosp, Yawkey 9,55 Fruit St, Boston, MA 02114 USA. EM mbirrer@partners.org FU National Cancer Institute; GOG Tissue Bank [CA 27469]; GOG Statistical and Data Center [CA 37517]; National Cancer Institute of the National Institute of Health FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and the GOG Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and the Intramural Research Program of the National Cancer Institute of the National Institute of Health. The following GOG member institutions participated in this study: University of Alabama at Birmingham, Oregon Health Sciences University, Abington Memorial Hospital, University of Rochester Medical Center, Walter Reed Army Medical Center, Wayne State University, University of Southern California at Los Angeles, Colorado Gynecologic Oncology Group, PC, University of California at Los Angeles, University of Washington, Milton S. Hershey Medical Center, Georgetown University Hospital, Wake Forest University School of Medicine, University of California Medical Center at Irvine, Stanford University Medical Center, University of Kentucky, The Cleveland Clinic Foundation, Johns Hopkins Oncology Center, East:ern Pennsylvania GYN/ONC Center, PC, Washington University School of Medicine, Cooper Hospital/University Medical Center, Columbus Cancer Council, University of Massachusetts Medical Center, University of Oklahoma, and Tacoma General Hospital. NR 39 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY 1 PY 2011 VL 121 IS 2 BP 395 EP 401 DI 10.1016/j.ygyno.2010.11.023 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AD UT WOS:000290292100029 PM 21310472 ER PT J AU Olden, K Freudenberg, N Dowd, J Shields, AE AF Olden, Kenneth Freudenberg, Nicholas Dowd, Jennifer Shields, Alexandra E. TI ANALYSIS & COMMENTARY Discovering How Environmental Exposures Alter Genes Could Lead To New Treatments For Chronic Illnesses SO HEALTH AFFAIRS LA English DT Article ID HUMAN-DISEASE; PHENOTYPIC PLASTICITY; DIABETES-MELLITUS; MONOZYGOTIC TWINS; HUMAN GENOME; EPIGENETICS; PATHOGENESIS; ASSOCIATION; METABOLISM; EPIGENOME AB Emerging research demonstrates that diet, pollution, and other environmental triggers can alter both the function and expression of human genes and lead to a heightened disease risk. These environment-gene interactions can cause so-called epigenetic changes in gene expression-patterns of which genes are switched "on" or "off"-that may account for the rising mortality from chronic diseases in industrialized nations. In this paper, we call for a new transdisciplinary approach to public health that would examine how environmental exposures, both physical and social, influence gene expression and a person's susceptibility to chronic disease. This initiative could lead to new ways to prevent and treat such illnesses. C1 [Olden, Kenneth; Freudenberg, Nicholas; Dowd, Jennifer] CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10021 USA. [Shields, Alexandra E.] Harvard Massachusetts Gen Hosp, Ctr Gen Vulnerable Populat & Hlth Dispar, Boston, MA USA. [Shields, Alexandra E.] Harvard Univ, Sch Med, Boston, MA USA. RP Olden, K (reprint author), CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10021 USA. EM kolden@hunter.cuny.edu RI Dowd, Jennifer/C-1127-2012 OI Dowd, Jennifer/0000-0003-2006-5656 FU National Institutes of Health [P30CA06516-43] FX This work was supported by a Nodal Award grant from the Dana-Farber/Harvard Cancer Center as part of the center's grant from the National Institutes of Health (P30CA06516-43). NR 46 TC 14 Z9 14 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 MAY PY 2011 VL 30 IS 5 BP 833 EP 841 DI 10.1377/hlthaff.2011.0078 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 761WD UT WOS:000290430800005 PM 21555469 ER PT J AU Kharfan-Dabaja, MA Cutler, CS AF Kharfan-Dabaja, Mohamed A. Cutler, Corey S. TI Rituximab for prevention and treatment of graft-versus-host disease SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Rituximab; Allogeneic hematopoietic cell transplantation; Acute graft-versus-host disease; Chronic graft-versus-host disease ID MONOCLONAL-ANTIBODY TREATMENT; STEM-CELL TRANSPLANTATION; REFRACTORY CHRONIC GVHD; T-CELLS; HEMATOPOIETIC TRANSPLANTATION; ADOPTIVE IMMUNOTHERAPY; B-CELLS; LYMPHOMA; SURVIVAL; EXPRESSION AB Growing understanding of the important role of B lymphocytes in alloreactivity has paved the way for evaluating anti-B cell therapy with rituximab in patients undergoing allogeneic hematopoietic cell transplantation. Data suggesting a beneficial reduction in incidence and severity of acute graft-versus-host disease (GVHD) are limited to non-randomized studies from single institutions using higher than conventional doses of rituximab. Additionally, rituximab is used as an effective treatment of corticosteroid-refractory chronic GVHD with good responses, particularly in cases of dermatologic and mucosal involvement. Post-transplant administration of rituximab appears to reduce the rate of chronic GVHD in preliminary studies. C1 [Cutler, Corey S.] Harvard Univ, Sch Med, Div Hematol Malignancies, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02215 USA. [Kharfan-Dabaja, Mohamed A.] Amer Univ Beirut, Dept Internal Med, Div Hematol Oncol & Bone Marrow Transplantat, Beirut, Lebanon. RP Cutler, CS (reprint author), Harvard Univ, Sch Med, Div Hematol Malignancies, Dept Med Oncol,Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM corey_cutler@dfci.harvard.edu NR 35 TC 19 Z9 20 U1 0 U2 1 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD MAY PY 2011 VL 93 IS 5 BP 578 EP 585 DI 10.1007/s12185-011-0855-2 PG 8 WC Hematology SC Hematology GA 765TZ UT WOS:000290732800003 PM 21547615 ER PT J AU Davies, JK AF Davies, Jeffrey K. TI Costimulatory blockade with monoclonal antibodies to induce alloanergy in donor lymphocytes SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Allogeneic hematopoietic transplantation; Graft-versus-Host Disease; Costimulatory blockade; Anergy; Donor lymphocyte infusion ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; ALLOREACTIVE T-CELLS; BONE-MARROW-TRANSPLANTATION; ADOPTIVE IMMUNOTHERAPY; IMMUNE RECONSTITUTION; SELECTIVE DEPLETION; REGULATORY CELL; LEUKEMIA; ANERGY AB Alloreactive donor T cells are central to the pathogenesis of Graft-versus-Host Disease (GvHD). Non-specific T cell depletion of donor grafts reduces GvHD, but increases infection and disease relapse. Several strategies are, therefore, in development to selectively remove alloreactive donor T cells prior to transplant while retaining beneficial donor T cells. An alternative approach is ex vivo alloanergization of donor T cells via allostimulation and blockade of costimulatory signals with fusion proteins or monoclonal antibodies. This strategy, which selectively inactivates alloreactive donor T cells, has been tested with some success in previous clinical trials of HLA-mismatched bone marrow transplantation. To build on the findings of these early trials, the strategy is now being tested in a multi-center clinical study of alloanergized donor lymphocyte infusion after HLA-mismatched stem cell transplantation. Recent advances in the understanding of alloanergization include the recognition of the central role played by CD4(+) regulatory T cells and new applications include the combination of alloanergization with T cell redirection to maximize anti-tumor activity. This mini-review will give an overview of the immunological basis for alloanergization, the previous and current clinical applications, and how new pre-clinical data have helped to create exciting new avenues of translational research in this area. C1 [Davies, Jeffrey K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Davies, JK (reprint author), Queen Mary Univ London, Ctr Haematooncol, Barts Canc Inst, John Vane Sci Ctr, London EC1M 6BQ, England. EM j.k.davies@qmul.ac.uk FU Leukemia and Lymphoma Society; American Society for Blood and Marrow Transplantation FX The author thanks Eva Guinan, Lee Nadler and Laurence Cooper. The author was funded by a Leukemia and Lymphoma Society Career Development Award and a New Investigator award from the American Society for Blood and Marrow Transplantation. NR 37 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD MAY PY 2011 VL 93 IS 5 BP 594 EP 601 DI 10.1007/s12185-011-0819-6 PG 8 WC Hematology SC Hematology GA 765TZ UT WOS:000290732800005 PM 21475951 ER PT J AU Quesnel, AM Lee, GS Nuss, RKC Volk, MS Jones, DT Rahbar, R AF Quesnel, Alicia M. Lee, Gi Soo Nuss, Roger K. C. Volk, Mark S. Jones, Dwight T. Rahbar, Reza TI Minimally invasive endoscopic management of subglottic stenosis in children: Success and failure SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Subglottic stenosis; Endoscopic; Minimally invasive; Airway; Laryngotracheal reconstruction ID PEDIATRIC LARYNGOTRACHEAL RECONSTRUCTION; DIOXIDE LASER-SURGERY; TRACHEAL STENOSIS; MITOMYCIN-C; SINGLE; COMPLICATIONS; LARYNGEAL; OUTCOMES; STAGE AB Objective: To assess the efficacy and safety of endoscopic management of subglottic stenosis both as a primary and as an adjunctive treatment in the pediatric population. Methods: Retrospective review of pediatric patients with subglottic stenosis undergoing endoscopic airway procedures at a tertiary care pediatric medical center. Outcomes were assessed by systematic review to determine the success and failure of the endoscopic approach. Results: Forty patients (22 male, 18 female) underwent endoscopic interventions for a diagnosis of subglottic airway stenosis between 2003 and 2000. Age ranged from 22 days old to 20 years old. Recorded degree of subglottic stenosis ranged from 10% to 99%. Fifty-three percent (21/40) had a history of prematurity, and 40% (16/40) had secondary airway diagnoses. Twenty-four patients underwent an endoscopic intervention initially (including laser or dilation, with or without topical mitomycin treatment), including four patients who underwent tracheostomy prior to the first endoscopic intervention. Sixteen underwent laryngotracheoplasty initially, including ten patients who underwent tracheostomy prior to the laryngotracheoplasty. Endoscopic treatment resulted in resolution of symptoms, and/or decannulation, and no further need for an open procedure in 58% of patients. Of the 24 patients undergoing endoscopic interventions initially, 14 patients underwent two or more endoscopic interventions, and 10 patients subsequently required tracheostomy or laryngotracheoplasty. When endoscopic procedures were used as an adjunct to laryngotracheoplasty, 60% (12/20) had resolution of symptoms, underwent decannulation, and did not require tracheostomy or revision laryngotracheoplasty. Conclusions: The endoscopic approach can be successful in the management of properly selected patients with subglottic stenosis, either as the initial treatment modality or as an adjunctive treatment in cases of re-stenosis after open airway surgery. The likelihood of success with a minimally invasive procedure as the primary treatment decreases with worsening initial grade of subglottic stenosis. (C) 2011 Published by Elsevier Ireland Ltd. C1 [Quesnel, Alicia M.; Lee, Gi Soo; Nuss, Roger K. C.; Volk, Mark S.; Jones, Dwight T.; Rahbar, Reza] Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA. [Quesnel, Alicia M.; Lee, Gi Soo; Nuss, Roger K. C.; Volk, Mark S.; Jones, Dwight T.; Rahbar, Reza] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Quesnel, Alicia M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Rahbar, R (reprint author), Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, 300 Longwood Ave, Boston, MA 02115 USA. EM reza.rahbar@childrens.harvard.edu OI Volk, Mark/0000-0001-5708-5808 NR 23 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD MAY PY 2011 VL 75 IS 5 BP 652 EP 656 DI 10.1016/j.ijporl.2011.02.002 PG 5 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 767UF UT WOS:000290882900009 PM 21377219 ER PT J AU Schlett, CL Banerji, D Siegel, E Bamberg, F Lehman, SJ Ferencik, M Brady, TJ Nagurney, JT Hoffmann, U Truong, QA AF Schlett, Christopher L. Banerji, Dahlia Siegel, Emily Bamberg, Fabian Lehman, Sam J. Ferencik, Maros Brady, Thomas J. Nagurney, John T. Hoffmann, Udo Truong, Quynh A. TI Prognostic Value of CT Angiography for Major Adverse Cardiac Events in Patients With Acute Chest Pain From the Emergency Department 2-Year Outcomes of the ROMICAT Trial SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE computed tomography angiography; coronary artery disease; emergency department; long-term outcome; major adverse cardiac events ID CORONARY-ARTERY-DISEASE; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; ALL-CAUSE MORTALITY; TIMI RISK SCORE; DIAGNOSTIC PERFORMANCE; METAANALYSIS; PREDICTION; POPULATION; DECISION AB OBJECTIVES The aim of this study was to determine the 2-year prognostic value of cardiac computed tomography (CT) for predicting major adverse cardiac events (MACE) in patients presenting to the emergency department (ED) with acute chest pain. BACKGROUND CT has high potential for early triage of acute chest pain patients. However, there is a paucity of data regarding the prognostic value of CT in this ED cohort. METHODS We followed 368 patients from the ROMICAT (Rule Out Myocardial Infarction Using Computer Assisted Tomography) trial (age 53 +/- 12 years; 61% male) who presented to the ED with acute chest pain, negative initial troponin, and a nonischemic electrocardiogram for 2 years. Contrast-enhanced 64-slice CT was obtained during index hospitalization, and caregivers and patients remained blinded to the results. CT was assessed for the presence of plaque, stenosis (> 50% luminal narrowing), and left ventricular regional wall motion abnormalities (RWMA). The primary endpoint was MACE, defined as composite cardiac death, nonfatal myocardial infarction, or coronary revascularization. RESULTS Follow-up was completed in 333 patients (90.5%) with a median follow-up period of 23 months. At the end of the follow-up period, 25 patients (6.8%) experienced 35 MACE (no cardiac deaths, 12 myocardial infarctions, and 23 revascularizations). Cumulative probability of 2-year MACE increased across CT strata for coronary artery disease (CAD) (no CAD 0%; nonobstructive CAD 4.6%; obstructive CAD 30.3%; log-rank p < 0.0001) and across combined CT strata for CAD and RWMA (no stenosis or RWMA 0.9%; 1 feature-either RWMA [15.0%] or stenosis [10.1%], both stenosis and RWMA 62.4%; log-rank p < 0.0001). The c statistic for predicting MACE was 0.61 for clinical Thrombolysis In Myocardial Infarction risk score and improved to 0.84 by adding CT CAD data and improved further to 0.91 by adding RWMA (both p < 0.0001). CONCLUSIONS CT coronary and functional features predict MACE and have incremental prognostic value beyond clinical risk score in ED patients with acute chest pain. The absence of CAD on CT provides a 2-year MACE-free warranty period, whereas coronary stenosis with RWMA is associated with the highest risk of MACE. (J Am Coll Cardiol Img 2011;4:481-91) (C) 2011 by the American College of Cardiology Foundation C1 [Schlett, Christopher L.; Banerji, Dahlia; Siegel, Emily; Lehman, Sam J.; Ferencik, Maros; Brady, Thomas J.; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Cardiac MR PET CT Program, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Bamberg, Fabian] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-8000 Munich, Germany. [Ferencik, Maros; Truong, Quynh A.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Nagurney, John T.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Truong, QA (reprint author), Harvard Univ, Cardiac MR PET CT Program, Dept Radiol, Massachusetts Gen Hosp,Med Sch, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM qtruong@partners.org FU National Institutes of Health (NIH) [R01 HL080053, K23HL098370, L30HL093896]; Siemens Medical Solutions; GE Healthcare FX This work was supported by the National Institutes of Health (NIH) R01 HL080053 and in part supported by Siemens Medical Solutions and GE Healthcare. Dr. Truong was supported by NIH grants K23HL098370 and L30HL093896. All other authors have reported that they have no relationships to disclose. NR 39 TC 69 Z9 72 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2011 VL 4 IS 5 BP 481 EP 491 DI 10.1016/j.jcmg.2010.12.008 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 765MT UT WOS:000290712100006 PM 21565735 ER PT J AU Gewirtz, H AF Gewirtz, Henry TI PET Measurement of Absolute Myocardial Blood Flow and LV Function in Dilated Cardiomyopathy SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material C1 Harvard Univ, Cardiac Unit, Massachusetts Gen Hosp, Dept Med,Cardiol Div,Med Sch, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Harvard Univ, Cardiac Unit, Massachusetts Gen Hosp, Dept Med,Cardiol Div,Med Sch, Yawkey 5E,55 Fruit St, Boston, MA 02114 USA. EM hgewirtz@partners.org NR 2 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2011 VL 4 IS 5 BP 557 EP 560 DI 10.1016/j.jcmg.2010.06.020 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 765MT UT WOS:000290712100016 PM 21565745 ER PT J AU Suvak, MK Litz, BT Sloan, DM Zanarini, MC Barrett, LF Hofmann, SG AF Suvak, Michael K. Litz, Brett T. Sloan, Denise M. Zanarini, Mary C. Barrett, Lisa Feldman Hofmann, Stefan G. TI Emotional Granularity and Borderline Personality Disorder SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE borderline personality disorder; emotional processing; emotional granularity; affective dysregulation ID CONFIRMATORY FACTOR-ANALYSIS; AFFECT INTENSITY MEASURE; NEGATIVE AFFECT; INDIVIDUAL-DIFFERENCES; INTERPERSONAL PROBLEMS; MEASUREMENT MODEL; COMMUNITY SAMPLE; MOOD AWARENESS; VALENCE FOCUS; YOUNG-ADULTS AB This study examined the affective dysregulation component of borderline personality disorder (BPD) from an emotional granularity perspective, which refers to the specificity in which one represents emotions. Forty-six female participants meeting criteria for BPD and 51 female control participants without BPD and Axis I pathology completed tasks that assessed the degree to which participants incorporated information about valence (pleasant-unpleasant) and arousal (calm-activated) in their semantic/conceptual representations of emotions and in using labels to represent emotional reactions. As hypothesized, participants with BPD emphasized valence more and arousal less than control participants did when using emotion terms to label their emotional reactions. Implications and future research directions are discussed. C1 [Suvak, Michael K.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA 02130 USA. [Litz, Brett T.] Boston Univ, Dept Psychol, Sch Med, Boston, MA 02215 USA. [Litz, Brett T.; Sloan, Denise M.] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. [Zanarini, Mary C.] McLean Hosp, Belmont, MA 02178 USA. [Zanarini, Mary C.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA USA. [Barrett, Lisa Feldman] Harvard Univ, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Suvak, MK (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, 116B3,150 S Huntington Ave, Boston, MA 02130 USA. EM Michael.Suvak@VA.GOV RI Hofmann, Stefan/B-8769-2014; OI Hofmann, Stefan/0000-0002-3548-9681; Sloan, Denise/0000-0002-0962-478X FU NIH HHS [DP1OD003312, DP1 OD003312]; NIMH NIH HHS [F31 MH078426, F31 MH078426-02, F31MH078426] NR 60 TC 25 Z9 25 U1 6 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2011 VL 120 IS 2 BP 414 EP 426 DI 10.1037/a0021808 PG 13 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 763YP UT WOS:000290595900013 PM 21171723 ER PT J AU Hosseini, A Gill, TJ Van de Velde, SK Li, GA AF Hosseini, Ali Gill, Thomas J. Van de Velde, Samuel K. Li, Guoan TI Estimation of In Vivo ACL Force Changes in Response to Increased Weightbearing SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE anterior cruciate ligament (ACL); in vivo ACL force changes; knee ID ANTERIOR CRUCIATE-LIGAMENT; GEOMETRIC IMAGE DISTORTION; SITU FORCES; KNEE FLEXION; ANTEROMEDIAL BAND; STRAIN BEHAVIOR; TIBIAL LOADS; KINEMATICS; JOINT; ELONGATION AB Accurate knowledge of in vivo anterior cruciate ligament (ACL) forces is instrumental for understanding normal ACL function and improving surgical ACL reconstruction techniques. The objective of this study was to estimate the change in ACL forces under in vivo loading conditions using a noninvasive technique. A combination of magnetic resonance and dual fluoroscopic imaging system was used to determine ACL in vivo elongation during controlled weightbearing at discrete flexion angles, and a robotic testing system was utilized to determine the ACL force-elongation data in vitro. The in vivo ACL elongation data were mapped to the in vitro ACL force-elongation curve to estimate the change in in vivo ACL forces in response to full body weightbearing using a weighted mean statistical method. The data demonstrated that by assuming that there was no tension in the ACL under zero weightbearing, the changes in in vivo ACL force caused by full body weightbearing were 131.4 +/- 16.8 N at 15 deg, 106.7 +/- 11.2 N at 30 deg, and 34.6 +/- 4.5 N at 45 deg of flexion. However, when the assumed tension in the ACL under zero weightbearing was over 20 N, the change in the estimated ACL force in response to the full body weightbearing approached an asymptotic value. With an assumed ACL tension of 40 N under zero weightbearing, the full body weight caused an ACL force increase in 202.7 +/- 27.6 N at 15 deg, 184.9 +/- 22.5 N at 30 deg, and 98.6 +/- 11.7 N at 45 deg of flexion. The in vivo ACL forces were dependent on the flexion angle with higher force changes at low flexion angles. Under full body weightbearing, the ACL may experience less than 250 N. These data may provide a valuable insight into the biomechanical behavior of the ACL under in vivo loading conditions. [DOI: 10.1115/1.4003780] C1 [Hosseini, Ali; Gill, Thomas J.; Van de Velde, Samuel K.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. [Hosseini, Ali] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. EM hosseini@alum.mit.edu; tgill@partners.org; svandevelde@partners.org; gli1@partners.org FU National Institutes of Health [R21 AR051078, R01 AR055612]; Department of Orthopaedic Surgery at the Massachusetts General Hospital FX The authors would like to gratefully acknowledge the financial support of the National Institutes of Health (Grant Nos. R21 AR051078 and R01 AR055612) and the Department of Orthopaedic Surgery at the Massachusetts General Hospital. The technical assistance of Michal Kozanek is greatly appreciated. NR 44 TC 10 Z9 11 U1 0 U2 4 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 MAY PY 2011 VL 133 IS 5 AR 051004 DI 10.1115/1.4003780 PG 9 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 765EQ UT WOS:000290686600004 PM 21599095 ER PT J AU Jackson, LT Aubin, PM Cowley, MS Sangeorzan, BJ Ledoux, WR AF Jackson, Lyle T. Aubin, Patrick M. Cowley, Matthew S. Sangeorzan, Bruce J. Ledoux, William R. TI A Robotic Cadaveric Flatfoot Analysis of Stance Phase SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE pes planus; flatfoot; foot structure; cadaver; stance phase; robot ID DEFORMITY; JOINTS AB The symptomatic flatfoot deformity (pes planus with peri-talar subluxation) can be a debilitating condition. Cadaveric flatfoot models have been employed to study the etiology of the deformity, as well as invasive and noninvasive surgical treatment strategies, by evaluating bone positions. Prior cadaveric flatfoot simulators, however, have not leveraged industrial robotic technologies, which provide several advantages as compared with the previously developed custom fabricated devices. Utilizing a robotic device allows the researcher to experimentally evaluate the flatfoot model at many static instants in the gait cycle, compared with most studies, which model only one to a maximum of three instances. Furthermore, the cadaveric tibia can be statically positioned with more degrees of freedom and with a greater accuracy, and then a custom device typically allows. We created a six degree of freedom robotic cadaveric simulator and used it with a flatfoot model to quantify static bone positions at ten discrete instants over the stance phase of gait. In vivo tibial gait kinematics and ground reaction forces were averaged from ten flatfoot subjects. A fresh frozen cadaveric lower limb was dissected and mounted in the robotic gait simulator (RGS). Biomechanically realistic extrinsic tendon forces, tibial kinematics, and vertical ground reaction forces were applied to the limb. In vitro bone angular position of the tibia, calcaneus, talus, navicular, medial cuneiform, and first metatarsal were recorded between 0% and 90% of stance phase at discrete 10% increments using a retroreflective six-camera motion analysis system. The foot was conditioned flat through ligament attenuation and axial cyclic loading. Post-flat testing was repeated to study the pes planus deformity. Comparison was then made between the pre-flat and post-flat conditions. The RGS was able to recreate ten gait positions of the in vivo pes planus subjects in static increments. The in vitro vertical ground reaction force was within +/- 1 standard deviation (SD) of the in vivo data. The in vitro sagittal, coronal, and transverse plane tibial kinematics were almost entirely within +/- 1 SD of the in vivo data. The model showed changes consistent with the flexible flatfoot pathology including the collapse of the medial arch and abduction of the forefoot, despite unexpected hindfoot inversion. Unlike previous static flatfoot models that use simplified tibial degrees of freedom to characterize only the midpoint of the stance phase or at most three gait positions, our simulator represented the stance phase of gait with ten discrete positions and with six tibial degrees of freedom. This system has the potential to replicate foot function to permit both noninvasive and surgical treatment evaluations throughout the stance phase of gait, perhaps eliciting unknown advantages or disadvantages of these treatments at other points in the gait cycle. [DOI: 10.1115/1.4003869] C1 [Jackson, Lyle T.; Aubin, Patrick M.; Cowley, Matthew S.; Sangeorzan, Bruce J.; Ledoux, William R.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Jackson, Lyle T.] Univ Washington, Sch Med, Seattle, WA USA. [Aubin, Patrick M.] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU VA Rehabilitation Research and Development Service [A2661C, A4843C]; University of Washington FX The authors thank the VA Rehabilitation Research and Development Service Grant Nos. A2661C and A4843C and the University of Washington Medical Student Research Training Program. NR 14 TC 5 Z9 5 U1 2 U2 8 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 MAY PY 2011 VL 133 IS 5 AR 051005 DI 10.1115/1.4003869 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 765EQ UT WOS:000290686600005 PM 21599096 ER PT J AU Jessup, M Albert, NM Lanfear, DE Lindenfeld, J Massie, BM Walsh, MN Zucker, MJ AF Jessup, Mariell Albert, Nancy M. Lanfear, David E. Lindenfeld, Joann Massie, Barry M. Walsh, Mary Norine Zucker, Mark J. CA Aha Heart Failure Transplantation Heart Failure Soc Amer TI ACCF/AHA/HFSA 2011 Survey Results: Current Staffing Profile of Heart Failure Programs, Including Programs That Perform Heart Transplant and Mechanical Circulatory Support Device Implantation SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE ACCF/AHA/HFSA Survey Report; heart failure; heart transplant; mechanical circulatory support device; staffing profile ID TASK-FORCE; MANAGEMENT; CARDIOLOGY; GUIDELINES; STATEMENT; OUTCOMES; SOCIETY AB Objectives: There have been no published recommendations about staffing needs for a heart failure (HF),clinic or an office setting focused on heart transplant. The goal of this survey was to understand the current staffing environment of HF, transplant, and mechanical circulatory support device (MCSD) programs in the United States and abroad. This report identifies current staffing patterns but does not endorse a particular staffing model. Methods: An online survey, jointly sponsored by the American College of Cardiology Foundation (ACCF), American Heart Association (AHA), and the Heart Failure Society of America (HFSA), was sent to the members of all 3 organizations who had identified themselves as interested in HF, heart transplant, or both, between March 12, 2009, and May 12, 2009. Results: The overall response rate to the 1,823 e-mail surveys was 23%. There were 257 unique practices in the United States (81% of total sites) and 58 international sites (19%); approximately 30% of centers were in a cardiovascular group practice and 30% in a medical school hospital setting. The large majority of practices delivered HF care in both an inpatient and outpatient environment, and slightly more centers were implanting MCSDs (47%) than performing cardiac transplantation (39%). Most practices (43%) were small, with <4 staff members, or small- to medium-sized (34%), with 4 to 10 staff members, with only 23% being medium (11-20 staff) or large programs (> 20 staff). On average, a U.S. HF practice cared for 1,641 outpatients annually. An average HF program with transplant performed 10 transplants. Although larger programs were able to perform more transplants and see more outpatient HF visits, their clinician staffing volume tended to double for approximately every 500 to 700 additional HF visits annually. The average staffing utilization was 2.65 physician full-time equivalents (FTEs), 2.21 nonphysician practitioner (nurse practitioner or physician assistant) FTEs, and 2.61 nurse coordinator FTEs annually. Conclusions: The HF patient population is growing in number in the United States and internationally, and the clinicians who provide the highly skilled and time-consuming care to this population are under intense scrutiny as a result of focused quality improvement initiatives and reduced financial resources. Staffing guidelines should be developed to ensure that an adequate number of qualified professionals are hired for a given practice volume. These survey results are an initial step in developing such standards. (J Cardiac Fail 2011;17:349-358) C1 [Jessup, Mariell] Univ Penn, Philadelphia, PA 19104 USA. [Albert, Nancy M.] Cleveland Clin, Cleveland, OH USA. [Lindenfeld, Joann] Univ Colorado, Boulder, CO 80309 USA. [Massie, Barry M.] UCSF, San Francisco VAMC, San Francisco, CA USA. [Zucker, Mark J.] Newark Beth Israel Med Ctr, Newark, NJ USA. RP Jessup, M (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 15 TC 3 Z9 4 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD MAY PY 2011 VL 17 IS 5 BP 349 EP 358 DI 10.1016/j.cardfail.2011.04.001 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 766JE UT WOS:000290777600001 PM 21549290 ER PT J AU Blanchfield, BB Gazelle, GS Khaliif, M Arocha, IS Hacker, K AF Blanchfield, Bonnie B. Gazelle, G. Scott Khaliif, Mursal Arocha, Izabel S. Hacker, Karen TI A Framework to Identify the Costs of Providing Language Interpretation Services SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Interpreters; language services; cost effectiveness; costs ID HEALTH-CARE; BARRIERS; IMPACT; QUALITY AB The availability of language services for patients with limited English proficiency has become a standard of care in the United States. Finding the resources to pay for language programs is challenging for providers, payers, and policymakers. There is no federal payment policy and states are developing policies using different methodologies for determining costs and reimbursement rates. This paper establishes a conceptual framework that identifies program costs, can be used across health care entities, and can be understood by administrators, researchers, and policymakers to guide research and analysis and establish a common ground for informed strategic discussion of payment and reimbursement policy. Using case study methods, a framework was established to identify costs and included determining the perspective of the cost analysis as well as distinguishing between the financial accounting costs (direct, indirect, and overheard costs) and the economic opportunity and subsequent utilization costs. C1 [Blanchfield, Bonnie B.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Khaliif, Mursal; Arocha, Izabel S.; Hacker, Karen] Cambridge Hlth Alliance, Cambridge, MA USA. RP Blanchfield, BB (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,Suite 10th Floor, Boston, MA 02114 USA. EM gsmbbb@gmail.com NR 15 TC 2 Z9 2 U1 0 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2011 VL 22 IS 2 BP 523 EP 531 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 762GB UT WOS:000290461800013 PM 21551931 ER PT J AU Meo, N Hwang, U Morrison, RS AF Meo, Nicholas Hwang, Ula Morrison, R. Sean TI Resident Perceptions of Palliative Care Training in the Emergency Department SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID END-OF-LIFE; EDUCATION AB Objectives: To characterize the level of formal training and perceived educational needs in palliative care of emergency medicine (EM) residents. Methods: This descriptive study used a 16-question survey administered at weekly resident didactic sessions in 2008 to EM residency programs in New York City. Survey items asked residents to: (1) respond to Likert-scaled statements about the role of palliative care in the emergency department (ED); (2) quantify their level of formal training and personal comfort in symptom management, discussion of bad news and prognosis, legal issues, and withdrawing/withholding therapy; and (3) express their interest in future palliative care training. Results: Of 228 total residents, 159 (70%) completed the survey. Of those surveyed, 50% completed some palliative care training before residency; 71.1% agreed or strongly agreed that palliative care was an important competence for an EM physician. However, only 24.3% reported having a "clear idea of the role of palliative care in EM." The highest self-reported level of formal training was in the area of advanced directives or legal issues at the end of life; the lowest levels were in areas of patient management at the end of life. The highest level of self-reported comfort was in giving bad news and the lowest was in withholding/withdrawing therapy. A slight majority of residents (54%) showed positive interest in receiving future training in palliative care. Conclusions: New York City EM residents reported palliative care as an important competency for emergency medicine physicians, yet also reported low levels of formal training in palliative care. The majority of residents surveyed favored additional training. C1 [Meo, Nicholas; Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA. [Meo, Nicholas; Hwang, Ula; Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Care, New York, NY 10029 USA. [Hwang, Ula; Morrison, R. Sean] James J Peters Vet Affairs Med Ctr, REAP, Bronx, NY USA. [Hwang, Ula; Morrison, R. Sean] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, Gustave L Levy Pl,Box 1620, New York, NY 10029 USA. EM ula.hwang@mountsinai.org FU American Federation on Aging Research (AFAR); National Institute on Aging (NIA) [K23 AG031218, K24 AG022345] FX Nicholas Meo was supported by a Medical Student Training on Aging Research summer program award from the American Federation on Aging Research (AFAR). Ula Hwang is supported by a National Institute on Aging (NIA) K23 career development award (K23 AG031218). R. Sean Morrison is supported by a NIA K24 mid-career mentoring award (K24 AG022345). NR 19 TC 25 Z9 25 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAY PY 2011 VL 14 IS 5 BP 548 EP 555 DI 10.1089/jpm.2010.0343 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 766CE UT WOS:000290756700007 PM 21291326 ER PT J AU Zerzan, J Lee, CA Haverhals, LM Nowels, CT AF Zerzan, Judy Lee, Courtney A. Haverhals, Leah M. Nowels, Carolyn T. TI Exploring Physician Decisions about End-of-Life Opiate Prescribing: A Qualitative Study SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID HEALTH-CARE PROVIDERS; PAIN MANAGEMENT; KNOWLEDGE; ATTITUDES; COMMUNICATION; BARRIERS; STATE AB Background: Opiates are commonly used for symptoms at the end of life (EOL). Little is known about the decision-making process physicians go through when deciding to prescribe opiates for their EOL patients. The study's objective was to explore physician factors affecting EOL opiate prescribing. Methods: Qualitative study of 38 physicians in the Denver area in the specialties of outpatient and inpatient medicine, geriatrics, oncology, and palliative care. Semi-structured qualitative interviews by trained interviewers asked physicians about their knowledge, attitudes, and experiences in prescribing opiates, reasons for prescribing opiates, barriers to prescribing opiates, changes in prescribing habits, and perceived patient factors that influence prescribing. Interviews were analyzed using ATLAS.ti qualitative analysis software and independently coded by two reviewers. Results: We found a spectrum of beliefs ranging from the viewpoint that opiates are underused at EOL to overused. We found five key themes: practices in when and how to use opiates, barriers to prescribing, personal experiences drive prescribing, social meaning of opiates, and differences in the role of physician. Physicians interviewed described experiences, both personal and professional, that influenced their opiate-prescribing habits. All respondents expressed positive experiences with prescribing opiates in being able to ease patients' suffering at EOL and to improve their functionality and quality of life. Conclusions: Differences in prescribing habits, attitudes, and experiences of physicians influence opiate prescribing, which may lead to over- and underprescribing. Knowledge, barriers, and fears about EOL opiate prescribing need to be addressed to ensure EOL patients are receiving appropriate symptom relief. C1 [Zerzan, Judy; Nowels, Carolyn T.] Univ Colorado Denver, Div Gen Internal Med, Aurora, CO 80045 USA. [Lee, Courtney A.] Univ Colorado Denver, Dept Hlth & Behav Sci, Aurora, CO 80045 USA. [Haverhals, Leah M.] Eastern Colorado Hlth Care Syst, US Dept Vet Affairs, Denver, CO USA. RP Zerzan, J (reprint author), Univ Colorado Denver, Div Gen Internal Med, 12631 E 17th Ave,Mail Stop B180, Aurora, CO 80045 USA. EM Judy.Zerzan@ucdenver.edu FU University of Colorado Denver FX The results of this study were presented at the 32nd SGIM Annual Meeting in May 2009. This study was funded from the University of Colorado Denver General Internal Medicine Small Grants Program. NR 14 TC 3 Z9 3 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAY PY 2011 VL 14 IS 5 BP 567 EP 572 DI 10.1089/jpm.2010.0505 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 766CE UT WOS:000290756700011 PM 21413855 ER PT J AU Malin, JL O'Neill, SM Asch, SM Dy, SM Walling, AM Tisnado, D Antonio, AL Lorenz, KA AF Malin, Jennifer L. O'Neill, Sean M. Asch, Steven M. Dy, Sydney M. Walling, Anne M. Tisnado, Diana Antonio, Anna Liza Lorenz, Karl A. TI Quality of Supportive Care for Patients with Advanced Cancer in a VA Medical Center SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID EVIDENCE-BASED RECOMMENDATIONS; SYMPTOM PREVALENCE; TELEHEALTH; MANAGEMENT; LIFE AB Purpose: Using the Assessing Symptoms Side Effects and Indicators of Supportive Treatment (ASSIST) quality indicators (QIs), we conducted a comprehensive evaluation of the quality of care provided in our institution to patients diagnosed with advanced cancer in 2006. Methods: Patients diagnosed with a Stage IV solid tumor were identified from the hospital's cancer registry. Using data abstracted from medical records, care was assessed using 41 explicit QIs. Mean percent adherence to QIs was calculated overall, as well as across five clinical domains: (1) Pain, (2) Depression and Psychosocial Distress, (3) Dyspnea, (4) Treatment Toxicity, (5) Other Symptoms, and (6) Information and Care Planning. Results: The study cohort (n = 118) was almost all male (2% female) and mean age was 65.9 years (standard deviation [SD] 9.9 years). The most common cancers were lung and head and neck cancer (23% each); 17% had prostate cancer; 13% had colorectal cancer; and the rest (24%) had breast, esophageal, stomach, genitourinary, liver/biliary, or pancreas cancer. Patients received 51% (95% confidence interval [CI] 48%-54%) of recommended care. Adherence to recommended care within domains ranged from 38% (95% CI 35%-42%) for Other Symptoms to 79% (95% CI 73%-86%) for Information and Care Planning. Conclusions: This study suggests that the quality of supportive care for patients with advanced cancer can be greatly improved. Future efforts should use the ASSIST indicators to evaluate the quality of supportive care in larger and more diverse cohorts of advanced cancer patients. C1 [Malin, Jennifer L.] Univ Calif Los Angeles, Div Hematol Oncol 111H, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med,RAND Hlth, Los Angeles, CA 90073 USA. [O'Neill, Sean M.] Northwestern Univ, Feinberg Sch Med, Pardee RAND Grad Sch, Chicago, IL 60611 USA. [Dy, Sydney M.] Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. [Dy, Sydney M.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Dy, Sydney M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Walling, Anne M.; Tisnado, Diana] Univ Calif Los Angeles, VA Greater Los Angeles, Div Gen Internal Med & Hlth Serv Res, Sch Publ Hlth, Los Angeles, CA 90073 USA. RP Malin, JL (reprint author), Univ Calif Los Angeles, Div Hematol Oncol 111H, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med,RAND Hlth, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jennifer.malin@va.gov OI O'Neill, Sean/0000-0001-7759-8942 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [SHP 08-196] FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service SHP 08-196. The authors are solely responsible for its content and the views do not necessarily represent the views of the Department of Veterans Affairs. NR 17 TC 9 Z9 9 U1 0 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAY PY 2011 VL 14 IS 5 BP 573 EP 577 DI 10.1089/jpm.2010.0464 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 766CE UT WOS:000290756700012 PM 21413885 ER PT J AU Jackson, V Arnold, RM AF Jackson, Vicki Arnold, Robert M. TI The Joys and Complications of Working on a Team SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 [Jackson, Vicki] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jackson, V (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM VJackson@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAY PY 2011 VL 14 IS 5 BP 649 EP 649 DI 10.1089/jpm.2011.9697 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 766CE UT WOS:000290756700022 PM 21592032 ER PT J AU Sylvia, LG Nierenberg, AA Stange, JP Peckham, AD Deckersbach, T AF Sylvia, Louisa G. Nierenberg, Andrew A. Stange, Jonathan P. Peckham, Andrew D. Deckersbach, Thilo TI Development of an Integrated Psychosocial Treatment to Address the Medical Burden Associated with Bipolar Disorder SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE bipolar disorder; psychosocial treatment; diet; exercise; cognitive-behavioral therapy ID NEUROPSYCHIATRIC INTERVIEW MINI; RANDOMIZED CONTROLLED-TRIAL; PHYSICAL-ACTIVITY; I-DISORDER; BEHAVIORAL-THERAPY; RELAPSE PREVENTION; COGNITIVE THERAPY; MAJOR DEPRESSION; MENTAL-DISORDERS; BLOOD-PRESSURE AB We developed an integrated psychosocial treatment for bipolar disorder to decrease the disproportionate medical burden associated with this illness. Three treatment modules, Nutrition/weight loss, Exercise, and Wellness Treatment (NEW Tx) were administered in twelve 60-minute group sessions over 14 weeks. After the first group (N = 4) had completed the treatment, it was revised, and then a second group (N = 6) completed the revised treatment. Participants completed all of the study assessments and attended 82% of the sessions. Both groups added over 100 minutes of weekly exercise to their baseline duration. Participants in the second group showed improvements in their quality of life, depressive symptoms, and weight. It appears that NEW Tx may be a feasible intervention with promising pilot data for reducing the medical burden in bipolar disorder, but future research is needed to further evaluate the efficacy of NEW Tx. (Journal of Psychiatric Practice 2011; 17: 224-232) C1 [Sylvia, Louisa G.; Nierenberg, Andrew A.; Peckham, Andrew D.; Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sylvia, Louisa G.; Nierenberg, Andrew A.; Deckersbach, Thilo] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Stange, Jonathan P.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. RP Sylvia, LG (reprint author), Bipolar Clin & Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM lsylvia2@partners.org FU NIMH NIH HHS [K23 MH091182] NR 55 TC 19 Z9 19 U1 3 U2 7 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 MAY PY 2011 VL 17 IS 3 BP 224 EP 232 DI 10.1097/01.pra.0000398419.82362.32 PG 9 WC Psychiatry SC Psychiatry GA 765QX UT WOS:000290724800012 PM 21587004 ER PT J AU Htoon, J Nadig, A Hughes, T Yavuz, S Direskenel, H Saruhan-Direskeneli, G Sawalha, AH AF Htoon, Jasmine Nadig, Ajay Hughes, Travis Yavuz, Sule Direskenel, Haner Saruhan-Direskeneli, Guher Sawalha, Amr H. TI IL18 Polymorphism Is Associated with Behcet's Disease But Not Lupus in Patients from Turkey SO JOURNAL OF RHEUMATOLOGY LA English DT Letter ID PROMOTER POLYMORPHISMS; INTERLEUKIN-18 LEVELS; SERUM INTERLEUKIN-18; GENE POLYMORPHISMS; ERYTHEMATOSUS; IL-18; CRITERIA C1 [Htoon, Jasmine; Nadig, Ajay; Hughes, Travis; Sawalha, Amr H.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Yavuz, Sule; Direskenel, Haner] Marmara Univ, Dept Rheumatol, Sch Med, Istanbul, Turkey. [Saruhan-Direskeneli, Guher] Istanbul Univ, Istanbul Sch Med, Dept Physiol, Istanbul, Turkey. [Sawalha, Amr H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Sawalha, Amr H.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Sawalha, AH (reprint author), 825 NE 13th St,MS 24, Oklahoma City, OK 73104 USA. EM amr-sawalha@omrf.ouhsc.edu FU NCRR NIH HHS [P20RR020143, P20 RR020143]; NIAID NIH HHS [R03 AI076729, R03AI076729, R03 AI076729-01, R03 AI076729-02]; NIAMS NIH HHS [P30 AR053483, P30AR053483] NR 14 TC 12 Z9 12 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2011 VL 38 IS 5 BP 962 EP 963 DI 10.3899/jrheum.101202 PG 2 WC Rheumatology SC Rheumatology GA 766KJ UT WOS:000290780700028 PM 21532063 ER PT J AU Sisto, R Moleti, A Botti, T Bertaccini, D Shera, CA AF Sisto, Renata Moleti, Arturo Botti, Teresa Bertaccini, Daniele Shera, Christopher A. TI Distortion products and backward-traveling waves in nonlinear active models of the cochlea SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID OTOACOUSTIC EMISSIONS; REVERSE PROPAGATION; BASILAR-MEMBRANE; FINE-STRUCTURE; AMPLIFICATION; REFLECTION; SOUND; EAR AB This study explores the phenomenology of distortion products in nonlinear cochlear models, predicting their amplitude and phase along the basilar membrane. The existence of a backward-traveling wave at the distortion-product frequency, which has been recently questioned by experiments measuring the phase of basilar-membrane vibration, is discussed. The effect of different modeling choices is analyzed, including feed-forward asymmetry, micromechanical roughness, and breaking of scaling symmetry. The experimentally observed negative slope of basilar-membrane phase is predicted by numerical simulations of nonlinear cochlear models under a wide range of parameters and modeling choices. In active models, positive phase slopes are predicted by the quasi-linear analytical computations and by the fully nonlinear numerical simulations only if the distortion-product sources are localized apical to the observation point and if the stapes reflectivity is unrealistically small. The results of this study predict a negative phase slope whenever the source is distributed over a reasonably wide cochlear region and/or a reasonably high stapes reflectivity is assumed. Therefore, the above-mentioned experiments do not contradict "classical" models of cochlear mechanics and of distortion-product generation. (C) 2011 Acoustical Society of America. [DOI:10.1121/1.3569700] C1 [Moleti, Arturo] Univ Roma Tor Vergata, Dipartimento Fis, I-00133 Rome, Italy. [Sisto, Renata] INAIL, Dipartimento Igiene Lavoro, I-00040 Monte Porzio Catone, Italy. [Botti, Teresa] Univ Insubria, Dipartimento Fis & Matemat, I-22100 Como, Italy. [Bertaccini, Daniele] Univ Roma Tor Vergata, Dipartimento Matemat, I-00133 Rome, Italy. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Shera, Christopher A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Moleti, A (reprint author), Univ Roma Tor Vergata, Dipartimento Fis, Via Ric Sci 1, I-00133 Rome, Italy. EM moleti@roma2.infn.it RI Moleti, Arturo/P-6812-2016; OI Moleti, Arturo/0000-0002-2465-8849; BERTACCINI, Daniele/0000-0002-3662-278X; Renata, Sisto/0000-0002-5086-7003 FU PRIN [20083KLJEZ] FX The contribution of D. Bertaccini has been partially supported by PRIN Grant 20083KLJEZ. NR 33 TC 12 Z9 12 U1 1 U2 4 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2011 VL 129 IS 5 BP 3141 EP 3152 DI 10.1121/1.3569700 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 762CR UT WOS:000290450400048 PM 21568417 ER PT J AU Pugh, MJ Tabares, J Finley, E Bollinger, M Tortorice, K VanCott, AC AF Pugh, Mary Jo Tabares, Jeffrey Finley, Erin Bollinger, Mary Tortorice, Kathy VanCott, Anne C. TI CHANGES IN ANTIEPILEPTIC DRUG CHOICE FOR OLDER VETERANS WITH NEW-ONSET EPILEPSY: 2002 TO 2006 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 [Pugh, Mary Jo; Tabares, Jeffrey; Finley, Erin; Bollinger, Mary] VERDICT REAP, S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Tortorice, Kathy] Hines Vet Affairs, Pharm Benefits Management Strateg Hlth Grp, Hines, IL USA. [VanCott, Anne C.] Univ Pittsburgh, Dept Neurol, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. RP Pugh, MJ (reprint author), VERDICT REAP, S Texas Vet Hlth Care Syst, San Antonio, TX USA. OI Pugh, Mary Jo/0000-0003-4196-7763; Finley, Erin/0000-0003-4497-7721 FU NINR NIH HHS [R01-NR010828] NR 6 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2011 VL 59 IS 5 BP 955 EP 956 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 763RZ UT WOS:000290578700038 PM 21568976 ER PT J AU Freedman, RA Garber, JE AF Freedman, Rachel A. Garber, Judy E. TI Family Cancer History: Healthy Skepticism Required SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; POPULATION; VALIDATION; ACCURACY C1 [Freedman, Rachel A.; Garber, Judy E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Garber, JE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,SM210, Boston, MA 02115 USA. EM jegarber@partners.org NR 16 TC 2 Z9 2 U1 1 U2 1 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 MAY PY 2011 VL 103 IS 10 BP 776 EP U84 DI 10.1093/jnci/djr142 PG 2 WC Oncology SC Oncology GA 766VA UT WOS:000290813400001 PM 21562244 ER PT J AU Smith, BD Pan, IW Shih, YCT Smith, GL Harris, JR Punglia, R Pierce, LJ Jagsi, R Hayman, JA Giordano, SH Buchholz, TA AF Smith, Benjamin D. Pan, I-Wen Shih, Ya-Chen T. Smith, Grace L. Harris, Jay R. Punglia, Rinaa Pierce, Lori J. Jagsi, Reshma Hayman, James A. Giordano, Sharon H. Buchholz, Thomas A. TI Adoption of Intensity-Modulated Radiation Therapy for Breast Cancer in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID IN-FIELD TECHNIQUE; CLINICAL COMORBIDITY INDEX; ACTIVE BREATHING CONTROL; CONFORMAL RADIOTHERAPY; RANDOMIZED-TRIALS; CLAIMS DATA; IRRADIATION; MEDICARE; IMRT; COST AB Background Although intensity modulation of the radiation beam has been shown to lower toxic effects for patients receiving whole-breast irradiation, relatively simple techniques may suffice. It is thus controversial whether such treatment justifies billing for intensity-modulated radiation therapy (IMRT). Methods We used the claims data to determine billing for IMRT from Surveillance, Epidemiology, and End Results-Medicare records from 2001 to 2005 for 26 163 women aged 66 years or older with nonmetastatic breast cancer treated with surgery and radiotherapy. The impact of individual covariates (demographic, health services, tumor, and treatment factors) on cost of treatment was assessed using the Wilcoxon two-sample test. Two-sided multivariable logistic regression was used to identify predictors for IMRT use. Cost of radiation was calculated in 2005 dollars. All statistical tests were two-sided. Results The number of patients with IMRT billing claims increased from 0.9% (49 of 5196) of patients diagnosed in 2001 to 11.2% (564 of 5020) in 2005. In multivariable analysis, IMRT billing was more likely for patients with left-sided tumors (odds ratio [OR] = 1.30, 95% confidence interval [CI] = 1.16 to 1.45), for those residing in a health service area with high radiation oncologist density (OR = 2.32, 95% CI = 1.47 to 3.68), for those treated at freestanding radiation centers (OR = 1.36, 95% CI = 1.20 to 1.53), or for those residing in regions where the Medicare intermediary allowed breast IMRT (OR = 10.87, 95% CI = 9.26 to 12.76, all P <.001). The mean cost of radiation was $7179 without IMRT and $15 230 with IMRT. IMRT adoption contributed to an increase in the mean cost of breast radiation from $6334 in 2001 to $8473 in 2005. Conclusions IMRT billing increased 10-fold from 2001 through 2005, contributing to a 33% increase in the cost of breast radiation. These findings suggest that reimbursement policy and practice setting strongly influenced adoption of IMRT billing for breast cancer. C1 [Smith, Benjamin D.; Smith, Grace L.; Buchholz, Thomas A.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Pan, I-Wen; Shih, Ya-Chen T.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Giordano, Sharon H.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Harris, Jay R.; Punglia, Rinaa] Dept Radiat Oncol, Brigham, Cumbria, England. [Harris, Jay R.; Punglia, Rinaa] Womens Hosp Med Ctr, Boston, MA USA. [Harris, Jay R.; Punglia, Rinaa] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pierce, Lori J.; Jagsi, Reshma; Hayman, James A.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. RP Smith, BD (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 1202, Houston, TX 77030 USA. EM bsmith3@mdanderson.org OI Jagsi, Reshma/0000-0001-6562-1228; Smith, Benjamin/0000-0001-7866-1093; Pan, Iwen/0000-0002-2781-2629 FU Department of Radiation Oncology at the University of Texas M. D. Anderson Cancer Center; American Cancer Society [MRSG-09-145-01]; Cancer Prevention and Research Institute of Texas [RP101207]; Agency for Healthcare Research and Quality [R01 HS018535] FX This work was supported in part by a research grant from Varian Medical Equipment to the Department of Radiation Oncology at the University of Texas M. D. Anderson Cancer Center. T. A. B. was the principal investigator for a portion of this grant. This work was also supported in part by a Mentored Research Scholar Grant from the American Cancer Society (MRSG-09-145-01 to R.J.), the Cancer Prevention and Research Institute of Texas (RP101207 to B. D. S.), and the Agency for Healthcare Research and Quality (R01 HS018535 to Y.T.S.). NR 42 TC 61 Z9 63 U1 0 U2 15 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 MAY PY 2011 VL 103 IS 10 BP 798 EP 809 DI 10.1093/jnci/djr100 PG 12 WC Oncology SC Oncology GA 766VA UT WOS:000290813400008 PM 21525437 ER PT J AU Kuklina, EV Bateman, BT AF Kuklina, Elena V. Bateman, Brian T. TI Pregnancy Complications and Prevention of Cardiovascular Disease in Women: Stay Tuned SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material ID GENDER-SPECIFIC ASPECTS; C-REACTIVE PROTEIN; RISK-FACTORS; PREECLAMPSIA C1 [Kuklina, Elena V.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Kuklina, EV (reprint author), Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway NE,MS K-37, Atlanta, GA 30341 USA. EM ekuklina@cdc.gov NR 22 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2011 VL 20 IS 5 BP 657 EP 659 DI 10.1089/jwh.2011.2827 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 766MF UT WOS:000290785800003 PM 21599426 ER PT J AU Meltzer, EO Hamilos, DL AF Meltzer, Eli O. Hamilos, Daniel L. TI Rhinosinusitis Diagnosis and Management for the Clinician: A Synopsis of Recent Consensus Guidelines SO MAYO CLINIC PROCEEDINGS LA English DT Review ID PLACEBO-CONTROLLED TRIAL; FUROATE NASAL SPRAY; ACUTE MAXILLARY SINUSITIS; RANDOMIZED CONTROLLED-TRIAL; CILIARY-BEAT FREQUENCY; ACUTE BACTERIAL RHINOSINUSITIS; APPROPRIATE ANTIBIOTIC USE; DOUBLE-BLIND; FLUTICASONE PROPIONATE; MUCOCILIARY CLEARANCE AB Rhinosinusitis (RS) affects approximately 1 in 7 adults In the United States, and its effect on quality of life, productivity, and finances Is substantial. During the past 10 years, several expert panels from authoritative bodies have published evidence-based guidelines for the diagnosis and management of RS and its subtypes, Including acute viral RS, acute bacterial RS, chronic RS (CRS) without nasal polyposis, CRS with nasal polyposis, and allergic fungal RS. This review examines and compares the recommendations of the Rhinosinusitis initiative, the Joint Task Force on Practice Parameters, the Clinical Practice Guideline: Adult Sinusitis, the European Position Paper on Rhinosinusitis and Nasal Polyps 2007, and the British Society for Allergy and Clinical immunology. Points of consensus and divergent opinions expressed In these guidelines regarding classification, diagnosis, and management of adults with acute RS (ARS) and CRS and their various subtypes are highlighted for the practicing clinician. Key points of agreement regarding therapy in the guidelines for ARS include the efficacy of symptomatic treatment, such as intranasal corticosteroids, and the importance of reducing the unnecessary use of antibiotics in ARS; however, guidelines do not agree precisely regarding when antibiotics should be considered as a reasonable treatment strategy. Although the guidelines diverge markedly on the management of CRS, the diagnostic utility of nasal airway examination is acknowledged by all. Important and relevant data from MEDLINE-Indexed articles published since the most recent guidelines were issued are also considered, and needs for future research are discussed. C1 [Meltzer, Eli O.] Allergy & Asthma Med Grp & Res Ctr, San Diego, CA 92123 USA. [Hamilos, Daniel L.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Meltzer, EO (reprint author), Allergy & Asthma Med Grp & Res Ctr, 9610 Granite Ridge Dr,Ste B, San Diego, CA 92123 USA. EM eomeltzer@aol.com FU Alcon; Alexza Pharmaceuticals; Amgen; Antigen Labs; Apotex; Astellas; AstraZeneca; Boehringer Ingelheim; Forest; GlaxoSmithKline; Johnson Johnson; MAP; MEDA; Medimmune; Merck; Novartis; Proctor Gamble; Schering-Plough; Sepracor; Teva; UCB; Schering Corp, now Merck Co. FX Dr Meltzer has received grant/research support from Alcon, Alexza Pharmaceuticals, Amgen, Antigen Labs, Apotex, Astellas, AstraZeneca, Boehringer Ingelheim, Forest, GlaxoSmithKline, Johnson & Johnson, MAP, MEDA, Medimmune, Merck, Novartis, Proctor & Gamble, Schering-Plough, Sepracor, Teva, and UCB. He has served as a consultant/speaker for Alcon, Alexza Pharmaceuticals, Amgen, AstraZeneca, Boehringer Ingelheim, Capnia, Dainippon Sumitomo, Dey, GlaxoSmithKline, ISTA, Johnson & Johnson, Kalypsys, MAR Meda, Merck, Sandoz, sanofi-aventis, Schering-Plough, Sepracor, SRxA, Stallergenes, Teva, VentiRx, Wockhardt, and Wyeth. Dr. Hamilos has received book royalties from UpToDate and lnforma. Editorial assistance for the submitted manuscript was funded by Schering Corp, now Merck & Co. NR 161 TC 83 Z9 90 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAY PY 2011 VL 86 IS 5 BP 427 EP 443 DI 10.4065/mcp.2010.0392 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 763IF UT WOS:000290549300009 PM 21490181 ER PT J AU Tsiamas, P Seco, J Han, Z Bhagwat, M Maddox, J Kappas, C Theodorou, K Makrigiorgos, M Marcus, K Zygmanski, P AF Tsiamas, P. Seco, J. Han, Z. Bhagwat, M. Maddox, J. Kappas, C. Theodorou, K. Makrigiorgos, M. Marcus, K. Zygmanski, P. TI A modification of flattening filter free linac for IMRT SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo; flattening filter free; electron beam modification; peripheral dose; IMRT ID MODULATED RADIATION-THERAPY; FREE CLINICAL ACCELERATOR; MULTILEAF COLLIMATOR TRANSMISSION; MEDICAL LINEAR-ACCELERATOR; DOSE CALCULATION ALGORITHM; UNFLATTENED PHOTON BEAMS; MONTE-CARLO-SIMULATION; STOPPING-POWER RATIOS; STEREOTACTIC RADIOTHERAPY; SPATIAL DEPENDENCE AB Purpose: This study investigates the benefits of a modified flattening filter free (FFF) linac over the standard (STD) linac equipped with the flattening filter. Energy and angular spread of the electron beam of the FFF linac were modified. Modification of FFF beam parameters is explored to maximize the monitor unit efficiency and to minimize the head scatter in IMRT delivery for large target volumes or targets lying away from the central axis. Methods: The EGSnrc code is used to model FFF and STD linacs and study basic beam properties for both linac types in various beam configurations. Increasing energy of FFF linac results in similar beam attenuation properties and maximized dose rate compared to STD linac. Matching beam attenuation properties allows a more direct exploration of beam flatness of FFF linac in regard to IMRT delivery, especially away from the central axis where the effective dose rate is considerably smaller than the one at the central axis. Flatness of open beam dose profile of FFF linac is improved by increasing the angular spread of the electron beam. The resulting dose rate within the treatment field and outside of the field (peripheral dose) are characterized and compared to the unmodified FFF and STD linacs. Results: In order to match beam penetration properties, the energy of FFF is adjusted from 6.5 to 8.0 MeV for small to medium field sizes and from 6.5 to 8.5 MeV for larger ones. Dose rate of FFF vs STD linac increased by a factor of 1.9 (6.5 MeV) and 3.4-4.1 (8.0-8.5 MeV). Adjusting the mean angular spread of the electron beam from 0 degrees to 5 degrees-10 degrees resulted in complete flattening of photon beam for field sizes between 10 x 10 cm(2) and 15 x 15 cm(2) and partial flattening for field sizes from 15 x 15 cm(2) to 30 x 30 cm(2). Values of angular spread >= 14 degrees are not recommended as they exceed the opening of the primary collimator, affecting the area at the edges of the field. FFF fields of sizes smaller than 6 x 6 cm(2) are already flat and beam flattening is not necessary. Overall, the angular spread of 5 degrees-10 degrees is sufficient and can satisfactorily flatten open beam dose profiles even for larger field sizes. Increasing the electron beam angular spread amounts to a slight decrease of dose rate of FFF linac. However, for angular spread, 5 degrees-10 degrees dose rate factor of FFF vs STD is still about 1.6-2.6, depending on the field size (and the adjusted energy). Similarly, in case of peripheral dose, a moderate increase in dose can be observed for angular spread of 5 degrees-10 degrees and for field sizes 10 x 10 cm(2) to 30 x 30 cm(2). Lastly, beam flatness of not modified FFF linac can be conveniently described by an analytical function representing a ratio of STD vs FFF doses: 1 + b vertical bar r vertical bar(n). Conclusions: A modified FFF beamline with increased energy and electron beam angular spread results in satisfactory flattened beam and high dose rate within the field. Peripheral dose remaining at similar (or smaller) level than that of STD linac for the same delivered dose within the treatment field. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3571419] C1 [Tsiamas, P.; Han, Z.; Bhagwat, M.; Maddox, J.; Makrigiorgos, M.; Marcus, K.; Zygmanski, P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tsiamas, P.; Han, Z.; Bhagwat, M.; Maddox, J.; Makrigiorgos, M.; Marcus, K.; Zygmanski, P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tsiamas, P.; Kappas, C.; Theodorou, K.] Univ Thessaly, Sch Med, Dept Med Phys, Larisa 4100, Greece. [Seco, J.] Massachusetts Gen Hosp, Boston, MA 02138 USA. [Seco, J.] Harvard Med, Boston, MA 02138 USA. RP Marcus, K (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM kmarcus@lroc.harvard.edu; pzygmanski@lroc.harvard.edu NR 45 TC 12 Z9 12 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 MAY PY 2011 VL 38 IS 5 BP 2342 EP 2352 DI 10.1118/1.3571419 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 764JL UT WOS:000290625700007 PM 21776768 ER PT J AU Kalamarides, M Stemmer-Rachamimov, AO Niwa-Kawakita, M Chareyre, F Taranchon, E Han, ZY Martinelli, C Lusis, EA Hegedus, B Gutmann, DH Giovannini, M AF Kalamarides, M. Stemmer-Rachamimov, A. O. Niwa-Kawakita, M. Chareyre, F. Taranchon, E. Han, Z-Y Martinelli, C. Lusis, E. A. Hegedus, B. Gutmann, D. H. Giovannini, M. TI Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes SO ONCOGENE LA English DT Article DE neurofibromatosis type 2; arachnoid; brain tumours ID PROSTAGLANDIN-D SYNTHASE; BETA-TRACE; NATURAL-HISTORY; INCIDENTAL MENINGIOMAS; CHOROID-PLEXUS; SKULL BASE; ADULT-RAT; IN-VIVO; NF2; MICE AB Meningiomas are among the most common primary central nervous system tumours in adults. Studies focused on the molecular basis for meningioma development are hampered by a lack of information with regard to the cell of origin for these brain tumours. Herein, we identify a prostaglandin D synthase-positive meningeal precursor as the cell of origin for murine meningioma, and show that neurofibromatosis type 2 (Nf2) inactivation in prostaglandin D2 synthase (PGDS) (+) primordial meningeal cells, before the formation of the three meningeal layers, accounts for the heterogeneity of meningioma histological subtypes. Using a unique PGDSCre strain, we define a critical embryonic and early postnatal developmental window in which biallelic Nf2 inactivation in PGDS (+) progenitor cells results in meningioma formation. Moreover, we identify differentially expressed markers that characterize the two major histological meningioma subtypes both in human and mouse tumours. Collectively, these findings establish the cell of origin for these common brain tumours as well as a susceptible developmental period in which signature genetic mutations culminate in meningioma formation. Oncogene (2011) 30, 2333-2344; doi: 10.1038/onc.2010.609; published online 17 January 2011 C1 [Giovannini, M.] House Ear Res Inst, Ctr Neural Tumor Res, Los Angeles, CA 90057 USA. [Kalamarides, M.; Niwa-Kawakita, M.; Chareyre, F.; Taranchon, E.; Han, Z-Y; Martinelli, C.; Giovannini, M.] INSERM, U674, Paris, France. [Kalamarides, M.; Niwa-Kawakita, M.; Chareyre, F.; Taranchon, E.; Han, Z-Y; Martinelli, C.; Giovannini, M.] Univ Paris 07, Inst Univ Hematol, Paris, France. [Kalamarides, M.] Hop Beaujon, AP HP, Serv Neurochirurg, Clichy, France. [Stemmer-Rachamimov, A. O.] Massachusetts Gen Hosp, Mol Neurooncol & Pathol Dept, Boston, MA 02114 USA. [Stemmer-Rachamimov, A. O.] Harvard Univ, Sch Med, Boston, MA USA. [Lusis, E. A.] Washington Univ, Sch Med, Dept Neurosurg, St Louis, MO USA. [Hegedus, B.; Gutmann, D. H.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Giovannini, M (reprint author), House Ear Res Inst, Ctr Neural Tumor Res, 2100W 3rd St, Los Angeles, CA 90057 USA. EM mgiovannini@hei.org RI Hegedus, Balazs/B-6076-2008 OI Hegedus, Balazs/0000-0002-4341-4153 FU US Army Medical Research and Materiel Command [DAMD17-02-1-0645]; James S McDonnell Foundation; Association Neurofibromatoses et Recklinghausen; Vincent Buono Research Fund; Inserm FX We thank A Berns for p16Ink4a and p53flox mutant mice; S Dufour and JP Thiery for HtPACre mice; Y Urade for the PGDS genomic fragment; M Pla and staff of the Institut Universitaire d'Hematologie (IUH), Universite Paris 7, for mouse housing; N Karboul for technical assistance; and M Catala and W Van Furth for helpful discussions. This work was supported by Grants from the US Army Medical Research and Materiel Command (DAMD17-02-1-0645 to MG), James S McDonnell Foundation (to DHG and MG), Association Neurofibromatoses et Recklinghausen, the Vincent Buono Research Fund (to DHG and MG) and Inserm. NR 44 TC 32 Z9 33 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 2011 VL 30 IS 20 BP 2333 EP 2344 DI 10.1038/onc.2010.609 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 766NF UT WOS:000290789200005 PM 21242963 ER PT J AU Tavernier, SS Beck, SL Clayton, MF Pett, MA Berry, DL AF Tavernier, Susan S. Beck, Susan L. Clayton, Margaret F. Pett, Marjorie A. Berry, Donna L. TI Validity of the Patient Generated Index as a Quality-of-Life Measure in Radiation Oncology SO ONCOLOGY NURSING FORUM LA English DT Article ID DISTRESS THERMOMETER; CANCER-PATIENTS; CLINICAL-TRIALS; CENTERED ASSESSMENT; RESPONSE SHIFT; QUESTIONNAIRE; INSTRUMENTS; VALIDATION; DISORDERS AB Purpose/Objectives: To evaluate psychometric properties of an instrument designed to measure individualized health-related quality of life (HRQOL). Design: Repeated measures of self-reported quality of life. Setting: An outpatient radiation therapy department in the western part of the United States. Sample: 86 adults with cancer receiving their first course of radiation therapy. Methods: The Patient Generated Index (PGI), the National Comprehensive Cancer Network's Distress Thermometer (DT), and the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core30 (QLQ-C30). Main Research Variables: Convergent validity, responsiveness, sensitivity, and response shift. Findings: PGI scores were inversely correlated with scores on the DT (r = -0.49, -0.55, -0.44; p < 0.001), as well as the role (r = 0.31, 0.4, 0.38; p < 0.01), emotional (r = 0.33, 0.41, 0.33; p < 0.01), social functioning (r = 0.27, 0.49, 0.42; p < 0.05), pain (r = -0.29, -0.39, -0.39; p < 0.01), and fatigue (r = -0.35, -0.25, -0.47; p < 0.05) QLQ-C30 subscales at all measurement times. The PGI was responsive to those reporting high or low DT scores (t = 4.42, 3.32, 2.9; p < 0.05). A small-to-moderate effect size was detected in those who had an increase (effect size = 0.51) or decrease (effect size = 0.38) in HRQOL over time. Participants reconceptualized HRQOL over time. Conclusions: Data supported the PGI as a valid measure of individualized HRQOL. Implications for Nursing: The PGI potentially provides a more patient-centered measure of HRQOL in patients with cancer. Additional testing is needed in larger, more diverse groups. C1 [Tavernier, Susan S.] St Alphonsus Reg Med Ctr, Boise, ID 83706 USA. [Beck, Susan L.; Clayton, Margaret F.; Pett, Marjorie A.] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Berry, Donna L.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. RP Tavernier, SS (reprint author), St Alphonsus Reg Med Ctr, Boise, ID 83706 USA. EM susatave@sarmc.org FU National Cancer Institute [R25 CA093831]; Sigma Theta Tau Mu Gamma Chapter; University of Utah FX Susan S. Tavernier, PhD, RN, APRN-CNS, AOCN (R), is an oncology clinical nurse specialist at Saint Alphonsus Regional Medical Center in Boise, ID when this article was written; Susan L. Beck, PhD, APRN, AOCN (R), FAAN, is a professor, Margaret F. Clayton, PhD, RN, FNP-CS, is an assistant professor, and Marjorie A. Pett, MStat, DSW, is a research professor, all in the College of Nursing at the University of Utah in Salt Lake City; and Donna L. Berry, PhD, RN, AOCN (R), FAAN, is the director of the Phyllis F. Cantor Center for Research in Nursing and Patient Care Services at the Dana-Farber Cancer Institute in Boston, MA. This article presents findings from the lead author's dissertation and was funded in part by a National Cancer Institute training grant (R25 CA093831 [K. Mooney, principal investigator]), Sigma Theta Tau Mu Gamma Chapter, and the University of Utah George S. and Dolores Dore Eccles Scholarship Fund. Tavernier can be reached at susatave@sarmc.org, with copy to the editor at ONFEditor@ons.org. (Submitted April 2010. Accepted for publication April 26, 2010). NR 46 TC 4 Z9 4 U1 1 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2011 VL 38 IS 3 BP 319 EP 329 DI 10.1188/11.ONF.319-329 PG 11 WC Oncology; Nursing SC Oncology; Nursing GA 761TL UT WOS:000290423800013 PM 21531682 ER PT J AU Sheldon, LK Hilaire, D Berry, DL AF Sheldon, Lisa Kennedy Hilaire, Dany Berry, Donna L. TI Provider Verbal Responses to Patient Distress Cues During Ambulatory Oncology Visits SO ONCOLOGY NURSING FORUM LA English DT Article ID COMMUNICATION-SKILLS; CANCER-PATIENTS; NURSES; ANXIETY AB Purpose/Objectives: To explore healthcare provider cue-responding behaviors to patient cues of distress and socioemotional concerns during ambulatory, on-treatment oncology visits. Design: Descriptive secondary analysis of a data set of audio recordings of oncology visits and reports of symptoms and quality of life recorded with an electronic self-report assessment-cancer (ESRA-C) tool. Setting: Comprehensive cancer center, ambulatory care. Sample: 31 randomly selected cases from an existing data set (with one used as a training tool) of 590 audio recordings of patient-provider communication. Methods: Patients were placed in Group 1 (n = 20) and Group 2 (n = 10) to explore differences in patient-provider communication and decrease coder bias. Both groups completed the ESRA-C questionnaire prior to the visit. Providers in Group 2 received a printed ESRA-C summary report for use during the visit. Audio files of the visit were coded using the Medical Interview Aural Rating System (MIARS). Main Research Variables: Patient cues of distress and provider cue-responding behaviors. Findings: Patient cues of distress and socioemotional concerns ranged from 0-13 cues per visit, with a mean of 4.6 cues per visit. Providers acknowledged 57% of patient cues, but only acknowledged and explored 22% of all patient cues. Providers in Group 2 acknowledged patient concerns more often but explored the concerns less frequently. The number of patient cues distanced from by providers was lower in Group 2 and the overall provider score for responsiveness to patient cues of distress was higher, indicating more responsiveness than from Group 1. Conclusions: The use of a summary report of patient concerns may have enhanced provider responsiveness, in general. Distancing behaviors by providers in response to patient verbal cues may indicate a lack of knowledge, time limitations, or a lack of confidence. Implications for Nursing: To effectively support patients with cancer through active therapy, a greater level of acknowledgment, exploration, and responsive action by providers is indicated. These findings have implications for provider education, with regard to appropriate responses, and for researchers to test methods that best prompt and support effective provider behaviors, ultimately improving patient outcomes. C1 [Sheldon, Lisa Kennedy; Hilaire, Dany] Univ Massachusetts, Boston, MA 02125 USA. [Sheldon, Lisa Kennedy] St Joseph Hosp, Nashua, NH USA. [Sheldon, Lisa Kennedy] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Berry, Donna L.] Dana Farber Canc Inst, Cantor Ctr Res Nursing & Patient Care Serv, Boston, MA USA. [Berry, Donna L.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Sheldon, LK (reprint author), Univ Massachusetts, Boston, MA 02125 USA. EM lisa.kennedysheldon@umb.edu OI Sheldon, Lisa Kennedy/0000-0002-5958-8529 NR 30 TC 11 Z9 11 U1 1 U2 3 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2011 VL 38 IS 3 BP 369 EP 375 DI 10.1188/11.ONF.369-375 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA 761TL UT WOS:000290423800019 ER PT J AU Dighe, MK Wieseler, KM Bhargava, P Kanal, KM Vaidya, S Stewart, BK AF Dighe, Manjiri K. Wieseler, Karen M. Bhargava, Puneet Kanal, Kalpana M. Vaidya, Sandeep Stewart, Brent K. TI Re: More Cautions on Imaging of Pregnant Patients Response SO RADIOGRAPHICS LA English DT Letter C1 [Dighe, Manjiri K.; Wieseler, Karen M.; Bhargava, Puneet; Kanal, Kalpana M.; Vaidya, Sandeep; Stewart, Brent K.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] Vet Affairs Puget Sound Healthcare Syst, Dept Radiol, Seattle, WA USA. [Vaidya, Sandeep] Univ Washington, Harborview Med Ctr, Dept Radiol, Seattle, WA 98104 USA. RP Dighe, MK (reprint author), Univ Washington, Med Ctr, Dept Radiol, Box 357115,1959 NE Pacific St, Seattle, WA 98195 USA. EM dighe@u.washington.edu RI Bhargava, Puneet /F-1330-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2011 VL 31 IS 3 BP 891 EP 892 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 763WN UT WOS:000290590500023 ER PT J AU Quillard, T Croce, K Jaffer, FA Weissleder, R Libby, P AF Quillard, Thibaut Croce, Kevin Jaffer, Farouc A. Weissleder, Ralph Libby, Peter TI Molecular imaging of macrophage protease activity in cardiovascular inflammation in vivo SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Proteases; imaging; macrophage ID MATRIX-METALLOPROTEINASE ACTIVITY; ABDOMINAL AORTIC-ANEURYSMS; CARDIAC ALLOGRAFT-REJECTION; MAGNETIC-RESONANCE; ATHEROSCLEROTIC PLAQUES; MYOCARDIAL-INFARCTION; VASCULAR INFLAMMATION; SCAVENGER RECEPTOR; TREATMENT RESPONSE; ENZYME-ACTIVITY AB Macrophages contribute pivotally to cardiovascular diseases (CVD), notably to atherosclerosis. Imaging of macrophages in vivo could furnish new tools to advance evaluation of disease and therapies. Proteolytic enzymes serve as key effectors of many macrophage contributions to CVD. Therefore, intravital imaging of protease activity could aid evaluation of the progress and outcome of atherosclerosis, aortic aneurysm formation, or rejection of cardiac allografts.Among the large families of proteases, matrix metalloproteinases (MMPs) and cysteinyl cathepsins have garnered the most interest because of their participation in extracellular matrix remodelling. These considerations have spurred the development of dedicated imaging agents for protease activity detection. Activatable fluorescent probes, radiolabelled inhibitors, and nanoparticles are currently under exploration for this purpose. While some agents and technologies may soon see clinical use, others will require further refinement. Imaging of macrophages and protease activity should provide an important adjunct to understanding pathophysiology in vivo, evaluating the effects of interventions, and ultimately aiding clinical care. C1 [Quillard, Thibaut; Croce, Kevin; Libby, Peter] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Div Cardiovasc Med, Boston, MA 02115 USA. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Cardiol Div, Boston, MA 02115 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02115 USA. RP Libby, P (reprint author), Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Div Cardiovasc Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM plibby@rics.bwh.harvard.edu RI Quillard, Thibaut/K-8150-2015; OI Quillard, Thibaut/0000-0002-8096-2597; Jaffer, Farouc/0000-0001-7980-384X FU National Institutes of Health [R01 -HL080472]; Translational Program of Excellence in Nanotechnology (TPEN) [U01 HL080731]; American Heart Association FX We thank our colleagues affiliated with the Donald W. Reynolds Clinical Cardiovascular Research Center at Harvard Medical School, who contributed to our efforts to develop molecular imaging of atherosclerosis and cardiovascular diseases. We also acknowledge the National Institutes of Health (R01 -HL080472), the Translational Program of Excellence in Nanotechnology (TPEN) (U01 HL080731), and the American Heart Association for their support. NR 93 TC 26 Z9 27 U1 3 U2 15 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 MAY PY 2011 VL 105 IS 5 SI SI BP 828 EP 836 DI 10.1160/TH10-09-0589 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 767TE UT WOS:000290878400014 PM 21225096 ER PT J AU Porter, MP Kerrigan, MC Donato, BMK Ramsey, SD AF Porter, Michael P. Kerrigan, Matthew C. Donato, Bonnie M. K. Ramsey, Scott D. TI Patterns of use of systemic chemotherapy for Medicare beneficiaries with urothelial bladder cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Bladder neoplasms; Drug therapy; Delivery of health care; SEER program; Medicare ID NEOADJUVANT CHEMOTHERAPY; ELDERLY-PATIENTS; CARCINOMA; METHOTREXATE; METAANALYSIS; CARBOPLATIN; PACLITAXEL; MANAGEMENT; TRIAL AB Objectives: Examine the association between clinical, demographic, and socioeconomic factors and the receipt of systemic chemotherapy for bladder cancer. Examine factors influencing the use of combination chemotherapy plus cystectomy and use of specific chemotherapy drugs over time for bladder cancer. Materials and methods: Data from the SEER-Medicare database were analyzed for patients diagnosed with urothelial carcinoma of the bladder between 1992 and 2002. Cox proportional hazards regression analyses were used to assess differences in use of systemic chemotherapy based on demographic and clinical factors, site of care, and year of diagnosis. We assessed the proportion of patients who received chemotherapy in the adjuvant and neoadjuvant settings as well as use of chemotherapy in the monotherapy setting. We estimated the proportion of claims made for several commonly used chemotherapy agents in the outpatient setting by year. Results: During follow-up, 13%, 28%, 37%, and 57% of patients with stages 1 through 4, respectively, received systemic chemotherapy for bladder cancer. Chemotherapy use in the neoadjunvant or adjuvant settings within 6 months of diagnosis was not commonly found. Neoadjuvant chemotherapy was delivered to 1.4% Of stage 2 patients and 11% of stage 4 patients. In 2003, the most frequent claims for intravenous chemotherapy were for gemcitabine, carboplatin, and placlitaxel. Conclusions: Chemotherapy was not generally used as recommended for persons with invasive bladder cancer in this patient population. Studies to clarify potential underutilization and variation in patterns of;administration are warranted. (C) 2011 Elsevier Inc. All rights reserved. C1 [Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Porter, Michael P.] Univ Washington, Dept Urol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Kerrigan, Matthew C.] GlaxoSmithKline Inc, Philadelphia, PA 19102 USA. [Donato, Bonnie M. K.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. EM sramsey@fhcrc.org FU Bristol-Myers Squibb FX This study was funded by Bristol-Myers Squibb. The study has been approved by the Fred Hutchinson Cancer Research Center Institutional Review Board and by the SEER Medicare Institutional Review Board. NR 22 TC 57 Z9 58 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 MAY-JUN PY 2011 VL 29 IS 3 BP 252 EP 258 DI 10.1016/j.urolonc.2009.03.021 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 766JW UT WOS:000290779400005 PM 19450992 ER PT J AU Nguyen, PL Lin, DI Lei, JY Fiorentino, M Mueller, E Weinstein, MH Pagano, M Loda, M AF Nguyen, Paul L. Lin, Douglas I. Lei, Junyi Fiorentino, Michelangelo Mueller, Elke Weinstein, Michael H. Pagano, Michele Loda, Massimo TI The impact of Skp2 overexpression on recurrence-free survival following radical prostatectomy SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Skp2; Biomarker; Prostate cancer; Recurrence ID KINASE INHIBITOR P27(KIP1); LIGASE SUBUNIT SKP2; HUMAN BREAST-CANCER; UBIQUITIN LIGASE; PROTEIN EXPRESSION; P27; DEGRADATION; RADIOTHERAPY; ANTIGEN; CELLS AB Background: In several human cancers, overexpression of Skp2 (S-phase kinase associated protein 2), which targets p27 for degradation, portends a poorer prognosis. We examined whether Skp2 overexpression is associated with recurrence following radical prostatectomy (RP) for prostate cancer. Methods: Immunohistochemical staining for Skp2, p27, and MIB-1 was performed on 109 men with node-negative prostate cancer surgically managed from 1985-1996. Associations between the stains were tested and Cox regression was used to determine the association between Skp2 expression and time to biochemical recurrence following RP. Results: The 12 tumors (11%) with Skp2 overexpression all had correspondingly low p27 expression (P = 0.006), and a similar inverse Skp2/p27 relationship was seen in vitro in LNCap cells. Skp2 overexpression in tissue was associated with higher Gleason score (P = 0.002), more advanced pathological stage (P = 0.01), and higher MIB-1 index (P = 0.03), but a more favorable PSA profile (P = 0.04). Five men received a TURP. Among 104 who received RP, median follow-up was 67 months (range: 0.2-218). After adjusting for PSA, pathologic stage, and Gleason score, Skp2 overexpression remained significantly associated with a shorter time to biochemical recurrence (adjusted hazard ratio 4.8 (95% C.I. 1.6-14, P = 0.004)). The median time to recurrence with high vs. low Skp2 was 4 vs. 54 months. Conclusions: Skp2 overexpression was seen in a significant minority of surgically-managed men and was independently associated with a higher risk of recurrence, raising the possibility that Skp2 could be useful as a prognostic biomarker and as a potential molecular target for novel systemic agents in prostate cancer. (C) 2011 Elsevier Inc. All rights reserved. C1 [Nguyen, Paul L.; Lin, Douglas I.; Lei, Junyi; Fiorentino, Michelangelo; Mueller, Elke; Weinstein, Michael H.; Pagano, Michele; Loda, Massimo] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dana Farber Canc Inst, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu OI pagano, michele/0000-0003-3210-2442 FU NCI NIH HHS [R01 CA076584] NR 18 TC 9 Z9 11 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 MAY-JUN PY 2011 VL 29 IS 3 BP 302 EP 308 DI 10.1016/j.urolonc.2009.03.022 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 766JW UT WOS:000290779400014 PM 19450994 ER PT J AU Caposio, P Orloff, SL Streblow, DN AF Caposio, Patrizia Orloff, Susan L. Streblow, Daniel N. TI The role of cytomegalovirus in angiogenesis SO VIRUS RESEARCH LA English DT Article DE Angiogenesis; Cytomegalovirus; Endothelial cell ID SMOOTH-MUSCLE-CELLS; TRANSPLANT VASCULAR SCLEROSIS; APOE KNOCKOUT MICE; ENDOTHELIAL-CELLS; CHRONIC REJECTION; EXTRACELLULAR-MATRIX; ADHESION MOLECULES; ALTERED EXPRESSION; CORONARY-ARTERIES; HEART-TRANSPLANTS AB Human cytomegalovirus (HCMV) infection has been associated with the acceleration of vascular disease including atherosclerosis and transplant associated vasculopathy in solid organ transplants. HCMV promotes vascular disease at many of the different stages of the disease development. These include the initial injury phase, enhancing the response to injury and inflammation, as well as by increasing SMC hyperplasia and foamy macrophage cell formation. Angiogenesis is a critical process involved in the development of vascular diseases. Recently, HCMV has been shown to induce angiogenesis and this process is thought to contribute to HCMV-accelerated vascular disease and may also be important for HCMV-enhanced tumor formation. This review will highlight the role of HCMV in promoting angiogenesis. (C) 2010 Elsevier B.V. All rights reserved. C1 [Caposio, Patrizia; Orloff, Susan L.; Streblow, Daniel N.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Caposio, Patrizia; Orloff, Susan L.; Streblow, Daniel N.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97239 USA. [Orloff, Susan L.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97239 USA. [Orloff, Susan L.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Streblow, DN (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, 505 SW 185th, Beaverton, OR 97006 USA. EM streblow@ohsu.edu FU National Institutes of Health [HL 083194, HL 085451, HL 088603] FX This work was supported by research grants from the National Institutes of Health to D.N. Streblow (HL 083194), S.L. Orloff (HL 085451) and J.A. Nelson (HL 088603). NR 89 TC 33 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD MAY PY 2011 VL 157 IS 2 SI SI BP 204 EP 211 DI 10.1016/j.virusres.2010.09.011 PG 8 WC Virology SC Virology GA 767WM UT WOS:000290889500010 PM 20869406 ER PT J AU Hwang, U McCarthy, ML Aronsky, D Asplin, B Crane, PW Craven, CK Epstein, SK Fee, C Handel, DA Pines, JM Rathlev, NK Schafermeyer, RW Zwemer, FL Bernstein, SL AF Hwang, Ula McCarthy, Melissa L. Aronsky, Dominik Asplin, Brent Crane, Peter W. Craven, Catherine K. Epstein, Stephen K. Fee, Christopher Handel, Daniel A. Pines, Jesse M. Rathlev, Niels K. Schafermeyer, Robert W. Zwemer, Frank L., Jr. Bernstein, Steven L. TI Measures of Crowding in the Emergency Department: A Systematic Review SO ACADEMIC EMERGENCY MEDICINE LA English DT Review ID LENGTH-OF-STAY; PATIENT FLOW; REAL-TIME; OVERCROWDING SCALE; SAFETY NET; MODELS; SIMULATION; MORTALITY; VARIABLES; CAPACITY AB Objectives: Despite consensus regarding the conceptual foundation of crowding, and increasing research on factors and outcomes associated with crowding, there is no criterion standard measure of crowding. The objective was to conduct a systematic review of crowding measures and compare them in conceptual foundation and validity. Methods: This was a systematic, comprehensive review of four medical and health care citation databases to identify studies related to crowding in the emergency department (ED). Publications that "describe the theory, development, implementation, evaluation, or any other aspect of a 'crowding measurement/definition' instrument (qualitative or quantitative)" were included. A "measurement/definition" instrument is anything that assigns a value to the phenomenon of crowding in the ED. Data collected from papers meeting inclusion criteria were: study design, objective, crowding measure, and evidence of validity. All measures were categorized into five measure types (clinician opinion, input factors, throughput factors, output factors, and multidimensional scales). All measures were then indexed to six validation criteria (clinician opinion, ambulance diversion, left without being seen (LWBS), times to care, forecasting or predictions of future crowding, and other). Results: There were 2,660 papers identified by databases; 46 of these papers met inclusion criteria, were original research studies, and were abstracted by reviewers. A total of 71 unique crowding measures were identified. The least commonly used type of crowding measure was clinician opinion, and the most commonly used were numerical counts (number or percentage) of patients and process times associated with patient care. Many measures had moderate to good correlation with validation criteria. Conclusions: Time intervals and patient counts are emerging as the most promising tools for measuring flow and nonflow (i.e., crowding), respectively. Standardized definitions of time intervals (flow) and numerical counts (nonflow) will assist with validation of these metrics across multiple sites and clarify which options emerge as the metrics of choice in this "crowded" field of measures. ACADEMIC EMERGENCY MEDICINE 2011; 18:527-538 (C) 2011 by the Society for Academic Emergency Medicine C1 [Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. [Hwang, Ula] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [McCarthy, Melissa L.] Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD USA. [Craven, Catherine K.] Johns Hopkins Univ, Sch Med, William H Welch Med Lib, Baltimore, MD USA. [Aronsky, Dominik] Vanderbilt Univ, Med Ctr, Dept Biomed Informat & Emergency Med, Nashville, TN USA. [Asplin, Brent] Mayo Clin, Dept Emergency Med, Rochester, MN USA. [Crane, Peter W.] Univ Rochester, Dept Emergency Med, Rochester, NY USA. [Epstein, Stephen K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Emergency Med, Boston, MA 02215 USA. [Fee, Christopher] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Handel, Daniel A.] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. [Pines, Jesse M.] George Washington Univ, Med Ctr, Dept Emergency Med, Washington, DC 20037 USA. [Pines, Jesse M.] George Washington Univ, Med Ctr, Dept Hlth Policy, Washington, DC 20037 USA. [Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Schafermeyer, Robert W.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. [Zwemer, Frank L., Jr.] Virginia Commonwealth Univ, Dept Emergency Med, McGuire VA Med Ctr, Richmond, VA USA. [Bernstein, Steven L.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. EM ula.hwang@mountsinai.org NR 77 TC 60 Z9 66 U1 9 U2 60 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2011 VL 18 IS 5 BP 526 EP 537 DI 10.1111/j.1553-2712.2011.01054.x PG 12 WC Emergency Medicine SC Emergency Medicine GA 763SJ UT WOS:000290579700011 PM 21569171 ER PT J AU Ginde, AA Camargo, CA Shapiro, NI AF Ginde, Adit A. Camargo, Carlos A., Jr. Shapiro, Nathan I. TI Vitamin D Insufficiency and Sepsis Severity in Emergency Department Patients With Suspected Infection SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID SYSTEM; CARE AB Objectives: Vitamin D is increasingly recognized as an important mediator of immune function and may have a preventive role in the pathogenesis of sepsis. We sought to evaluate the association between vitamin D status and sepsis severity and hypothesized that vitamin D insufficiency would be associated with increased sepsis severity. Methods: This was a pilot study of emergency department (ED) patients age >= 18 years evaluated for suspected infection at an urban, teaching hospital. The authors measured illness severity using the following assessments at baseline and 24 hours: 1) severe sepsis, defined as suspected infection plus two or more elements of systemic inflammatory response syndrome criteria and acute dysfunction of one or more organ systems; 2) Acute Physiology Age Chronic Health Evaluation (APACHE) II scores; and 3) Sepsis-related Organ Failure Assessment (SOFA) scores. Vitamin D insufficiency was defined as baseline serum 25-hydroxyvitamin D (25OHD) levels <75 nmol/L. Results: Eighty-one patients were enrolled, with a median age of 62 years (interquartile range [IQR] = 48-76 years), 47% were female, and 77% were white. At baseline, 64 (79%) had 25OHD levels of <75 nmol/L, and 43 (53%) had severe sepsis. At 24 hours, 48 (59%) had severe sepsis. Patients with baseline 25OHD levels of <75 nmol/L, compared to patients with 25OHD levels of >= 75 nmol/L, were more likely to have severe sepsis (61% vs. 24%; p = 0.006) and SOFA scores >= 2 (44% vs. 18%; p = 0.049). Additionally, at 24 hours, those with 25OHD levels of <75 nmol/L were more likely to have severe sepsis (67% vs. 29%; p = 0.005), dysfunction of two or more organ systems (50% vs. 18%; p = 0.02), APACHE II score of >= 25 (19% vs. 0%; p = 0.06), and SOFA scores of >= 2 (63% vs. 29%; p = 0.02). Additionally, all four patients who died during the index hospitalization had 25OHD levels of <75 nmol/L. Conclusions: Vitamin D insufficiency was associated with higher sepsis severity in ED patients hospitalized for suspected infection. Larger observational studies, mechanistic studies, and ultimately randomized controlled trials are needed to determine causation and to evaluate if vitamin D supplementation can reduce the risk of sepsis as a preventive or therapeutic strategy. ACADEMIC EMERGENCY MEDICINE 2011; 18:551-554 (C) 2011 by the Society for Academic Emergency Medicine C1 [Ginde, Adit A.] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Shapiro, Nathan I.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Emergency Med, Sch Med, Boston, MA 02215 USA. RP Ginde, AA (reprint author), Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. EM adit.ginde@ucdenver.edu RI Shapiro, Nathan/F-1718-2016; Siry, Bonnie/D-7189-2017 NR 12 TC 42 Z9 46 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2011 VL 18 IS 5 BP 550 EP 553 DI 10.1111/j.1553-2712.2011.01047.x PG 4 WC Emergency Medicine SC Emergency Medicine GA 763SJ UT WOS:000290579700015 PM 21518095 ER PT J AU Gibson, CM Mega, JL Burton, P Goto, S Verheugt, F Bode, C Plotnikov, A Sun, X Cook-Bruns, N Braunwald, E AF Gibson, C. Michael Mega, Jessica L. Burton, Paul Goto, Shinya Verheugt, Freek Bode, Christoph Plotnikov, Alexei Sun, Xiang Cook-Bruns, Nancy Braunwald, Eugene TI Rationale and design of the Anti-Xa Therapy to Lower cardiovascular events in Addition to standard therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 (ATLAS-ACS 2 TIMI 51) trial: A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rivaroxaban in subjects with acute coronary syndrome SO AMERICAN HEART JOURNAL LA English DT Article ID TOTAL KNEE ARTHROPLASTY; ST-SEGMENT ELEVATION; HIP-ARTHROPLASTY; ASPIRIN; ENOXAPARIN; THROMBOPROPHYLAXIS; CLOPIDOGREL; PHARMACODYNAMICS; PHARMACOKINETICS; METAANALYSIS AB Background Although therapy with aspirin or aspirin plus a thienopyridine reduces the incidence of long-term adverse cardiovascular events among patients with acute coronary syndrome (ACS), there remains a significant residual risk of cardiovascular death, recurrent myocardial infarction (MI), and stroke. In a phase 2 trial (ClinicalTrials.gov NCT00402597) in which the addition of the factor Xa inhibitor rivaroxaban was compared with placebo, among ACS patients receiving either aspirin alone or dual-antiplatelet therapy with aspirin and a thienopyridine, the end point of death, MI, or stroke compared with placebo was reduced (87/2331 [3.9%] vs 62/1160 [5.5%]; hazard ratio 0.69, [95% CI 0.50-0.96], P = .027). Two candidate doses of rivaroxaban were selected for further evaluation in a pivotal phase 3. Design The second ATLAS-ACS 2 TIMI 51 Trial is an international, randomized, double-blind, event-driven (n = 983) phase 3 trial involving more than 15,570 patients hospitalized with ACS (ClinicalTrials.gov NCT00809965). All patients are treated with a background of standard therapy including low-dose aspirin, and patients are stratified by the administration of a thienopyridine (clopidogrel or ticlopidine; stratum 2) or not (stratum 1). Within each stratum, patients are randomly assigned in a 1: 1: 1 ratio to receive rivaroxaban 2.5 mg twice daily, or rivaroxaban 5 mg twice daily, or placebo twice daily. The primary efficacy end point is the composite of cardiovascular death, MI, or stroke. The primary safety end point is thrombolysis in MI major bleeding not associated with coronary artery bypass graft surgery. Summary The ATLAS-ACS 2 TIMI 51 is testing the hypothesis that anticoagulation with the oral factor Xa inhibitor rivaroxaban reduces cardiovascular death, MI, and stroke among patients with ACS treated with guideline-based therapies for ACS. (Am Heart J 2011;161:815-821.e6.) C1 [Gibson, C. Michael; Mega, Jessica L.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Burton, Paul; Plotnikov, Alexei; Sun, Xiang] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med, Kanagawa 2591100, Japan. [Verheugt, Freek] Onze Lieve Vrouw Hosp, Dept Cardiol, Amsterdam, Netherlands. [Bode, Christoph] Univ Freiburg, Freiburg, Germany. [Cook-Bruns, Nancy] Bayer Schering Pharma, Berlin, Germany. RP Gibson, CM (reprint author), 185 Pilgrim Rd,Deaconess 319, Boston, MA 02215 USA. EM mgibson@perfuse.org RI Verheugt, F.W.A./H-8105-2014 FU Johnson and Johnson; Bayer Inc. FX All authors received research grant support from the sponsors of the trial (Johnson and Johnson and Bayer Inc.). Dr. Gibson reports receiving consulting monies from Johnson and Johnson and Bayer Inc. Dr. Mega reports receiving honoraria from Bayer Inc. Drs. Burton, Plotnikov and Sun are employees of Johnson and Johnson. Dr. Bruns is an employee of Bayer Inc. NR 16 TC 41 Z9 43 U1 1 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2011 VL 161 IS 5 BP 815 EP + DI 10.1016/j.ahj.2011.01.026 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 763LV UT WOS:000290559300009 PM 21570509 ER PT J AU Kontos, MC Diercks, DB Ho, PM Wang, TY Chen, AY Roe, MT AF Kontos, Michael C. Diercks, Debra B. Ho, P. Michael Wang, Tracy Y. Chen, Anita Y. Roe, Matthew T. TI Treatment and outcomes in patients with myocardial infarction treated with acute beta-blocker therapy: Results from the American College of Cardiology's NCDR (R) SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; INTERNATIONAL TRIAL; HEART-DISEASE; ELEVATION; THROMBOLYSIS; PREDICTORS; METOPROLOL; MORTALITY AB Background Although beta-blockers (BBs) reduce long-term mortality in patients after myocardial infarction (MI), data regarding acute usage are conflicting. Methods We examined acute (<= 24 hours) BB use in 34,661 patients with ST-elevation MI (STEMI) and non-ST-segment MI (NSTEMI) included in the NCDR (R) ACTION Registry (R)-GWTG (TM) (291 US hospitals) between January 2007 and June 2008. Patients with contraindications or did not receive BBs or with missing data were excluded. We analyzed the use and impact of BB stratified by variables associated with increased risk for shock specified in the recent guidelines: age > 70 years, symptoms > 12 hours (STEMI patients), systolic blood pressure < 120 mm Hg, and heart rate > 110 beat/min on presentation. Results Among patients without contraindications, at least 1 high-risk variable was found in 45% of STEMI and 63% of NSTEMI patients. In-hospital complications including cardiogenic shock, mortality, and the composite outcome of shock or mortality were significantly increased with more shock risk factors in both STEMI and NSTEMI patients. Very early use in the emergency department was associated with a significantly increased risk of shock for both STEMI and NSTEMI patients compared to patients treated later but within 24 hours. Conclusions Risk factors for shock are common in STEMI and NSTEMI patients treated with early BBs. Increasing numbers of risk factors were associated with increased risk for shock or death in patients treated with BBs. These results are consistent with current recommendations for avoiding early BB treatment for patients with acute MI. (Am Heart J 2011;161:864-70.) C1 [Kontos, Michael C.] Virginia Commonwealth Univ, Dept Internal Med, Div Cardiol, Pauley Heart Ctr, Richmond, VA USA. [Diercks, Debra B.] Univ Calif Davis, Sacramento, CA 95817 USA. [Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. [Wang, Tracy Y.; Chen, Anita Y.; Roe, Matthew T.] Duke Clin Res Inst, Durham, NC USA. RP Kontos, MC (reprint author), Rm 285,Gateway Bldg,2nd Floor,POB 980051,1200 E M, Richmond, VA 23298 USA. EM mkontos@mcvh-vcu.edu NR 24 TC 23 Z9 23 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2011 VL 161 IS 5 BP 864 EP 870 DI 10.1016/j.ahj.2011.01.006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 763LV UT WOS:000290559300015 PM 21570515 ER PT J AU Sawaya, H Sebag, IA Plana, JC Januzzi, JL Ky, B Cohen, V Gosavi, S Carver, JR Wiegers, SE Martin, RP Picard, MH Gerszten, RE Halpern, EF Passeri, J Kuter, I Scherrer-Crosbie, M AF Sawaya, Heloisa Sebag, Igal A. Plana, Juan Carlos Januzzi, James L. Ky, Bonnie Cohen, Victor Gosavi, Sucheta Carver, Joseph R. Wiegers, Susan E. Martin, Randolph P. Picard, Michael H. Gerszten, Robert E. Halpern, Elkan F. Passeri, Jonathan Kuter, Irene Scherrer-Crosbie, Marielle TI Early Detection and Prediction of Cardiotoxicity in Chemotherapy-Treated Patients SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HIGH-DOSE CHEMOTHERAPY; BREAST-CANCER PATIENTS; ADJUVANT THERAPY; CARDIAC TOXICITY; TRASTUZUMAB; ANTHRACYCLINE; DYSFUNCTION; DOXORUBICIN; PACLITAXEL AB As breast cancer survival increases, cardiotoxicity associated with chemotherapeutic regimens such as anthracyclines and trastuzumab becomes a more significant issue. Assessment of the left ventricular (LV) ejection fraction fails to detect subtle alterations in LV function. The objective of this study was to evaluate whether more sensitive echocardiographic measurements and biomarkers could predict future cardiac dysfunction in chemotherapy-treated patients. Forty-three patients diagnosed with breast cancer who received anthracyclines and trastuzumab therapy underwent echocardiography and blood sampling at 3 time points (baseline and 3 and 6 months during the course of chemotherapy). The LV ejection fraction; peak systolic myocardial longitudinal, radial, and circumferential strain; echocardiographic markers of diastolic function; N-terminal pro B-type natriuretic peptide; and high-sensitivity cardiac troponin I were measured. Nine patients (21%) developed cardiotoxicity (1 at 3 months and 8 at 6 months) as defined by the Cardiac Review and Evaluation Committee reviewing trastuzumab. A decrease in longitudinal strain from baseline to 3 months and detectable high-sensitivity cardiac troponin I at 3 months were independent predictors of the development of cardiotoxicity at 6 months. The LV ejection fraction, parameters of diastolic function, and N-terminal pro B-type natriuretic peptide did not predict cardiotoxicity. In conclusion, cardiac troponin plasma concentrations and longitudinal strain predict the development of cardiotoxicity in patients treated with anthracyclines and trastuzumab. The 2 parameters may be useful to detect chemotherapy-treated patients who may benefit from alternative therapies, potentially decreasing the incidence of cardio toxicity and its associated morbidity and mortality. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1375-1380) C1 [Sawaya, Heloisa; Januzzi, James L.; Gosavi, Sucheta; Picard, Michael H.; Gerszten, Robert E.; Passeri, Jonathan; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Sawaya, Heloisa; Januzzi, James L.; Gosavi, Sucheta; Picard, Michael H.; Gerszten, Robert E.; Passeri, Jonathan; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kuter, Irene] Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Sebag, Igal A.] Sir Mortimer B Davis Jewish Hosp, Echocardiog Lab, Montreal, PQ, Canada. [Cohen, Victor] Sir Mortimer B Davis Jewish Hosp, Dept Med, Div Cardiol, Montreal, PQ, Canada. [Cohen, Victor] Sir Mortimer B Davis Jewish Hosp, Abramson Canc Ctr, Montreal, PQ, Canada. McGill Univ, Montreal, PQ, Canada. [Plana, Juan Carlos] Univ Texas MD Anderson Canc Ctr, Div Cardiol, Houston, TX 77030 USA. [Ky, Bonnie; Carver, Joseph R.; Wiegers, Susan E.] Hosp Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Martin, Randolph P.] Piedmont Heart Inst, Atlanta, GA USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. EM marielle@crosbie.com OI Picard, Michael/0000-0002-9264-3243 FU Susan G. Komen for the Cure Foundation, Dallas, Texas; Claflin Distinguished Scholar Award; Clinical Innovation Award, Boston, Massachusetts; Kynett Focus Junior Faculty Investigator Award, Philadelphia, Pennsylvania; Roche Diagnostics GmbH, Mannheim, Germany; Siemens Medical Systems, Erlangen, Germany; Critical Diagnostics, San Diego, California FX Dr. Seherrer-Crosbie was supported by an investigator-initiated grant from the Susan G. Komen for the Cure Foundation, Dallas, Texas, a Claflin Distinguished Scholar Award, and a Clinical Innovation Award, Boston, Massachusetts. Dr. Ky was supported by the Kynett Focus Junior Faculty Investigator Award, Philadelphia, Pennsylvania.; Dr. Januzzi has received grant support from Roche Diagnostics GmbH, Mannheim, Germany, Siemens Medical Systems, Erlangen, Germany, and Critical Diagnostics, San Diego, California. Dr. Plana is on the speaker's bureau of GE Healthcare, Milwaukee, Wisconsin. NR 16 TC 182 Z9 190 U1 2 U2 19 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2011 VL 107 IS 9 BP 1375 EP 1380 DI 10.1016/j.amjcard.2011.01.006 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 764CI UT WOS:000290605600020 PM 21371685 ER PT J AU Chen, JC Goetz, MB Feld, JE Taylor, A Anaya, H Burgess, J Flores, RD Gidwani, RA Knapp, H Ocampo, EH Asch, SM AF Chen, Jennifer C. Goetz, Matthew Bidwell Feld, Jamie E. Taylor, Anne Anaya, Henry Burgess, Jane Flores, Richard de Mesa Gidwani, Risha A. Knapp, Herschel Ocampo, Elizabeth H. Asch, Steven M. TI A provider participatory implementation model for HIV testing in an ED SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID FOR-DISEASE-CONTROL; EMERGENCY-DEPARTMENT; MISSED OPPORTUNITIES; PREVALENCE AREA; CARE SETTINGS; INFECTION; HEALTH; RECOMMENDATIONS; DIAGNOSIS; WOMEN AB Background: The Centers for Disease Control and Prevention recommends routine HIV screening for adults. Objectives: Community-based participatory research incorporates subjects in the design and conduct of research. We included nurses and physicians in the implementation of HIV rapid test use in the emergency department (ED). We explored the process, facilitators, and barriers. Methods: We identified clinical champions and trained staff. Physicians obtained consent and ordered HIV testing; nurses performed rapid testing. Testing rates were tracked by electronic medical record. We conducted regular meetings between staff and researchers. Semistructured qualitative interviews with providers were conducted at 3 months. Results: By week 15, we administered 121 tests. After the eligibility protocol evolved to incorporate ED nursing concerns regarding staffing limitations from a random sampling model to one focused on testing during nonpeak hours, the weekly number of tests increased. Eighteen percent of providers favored nontargeted HIV screening, 27% favored the current model of testing at nonpeak hours, 32% supported diagnostic testing, and 18% favored no testing or "other." Barriers include written consent, electronic documentation, time constraints, and belief that screening is not a core ED duty. Facilitators include ease of test administration, belief that ED patients are at higher risk, and flexibility to tailor screening efforts according to patient volume. Conclusions: The ED-based HIV testing is feasible within a Veterans Hospital Administration setting. Involvement of nursing in a community-based participatory research implementation model may facilitate staff acceptance of nontargeted HIV screening and be a mechanism to initiate administration of clinical preventive services to ED patients with limited primary care contact. Published by Elsevier Inc. C1 [Chen, Jennifer C.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Chen, Jennifer C.; Goetz, Matthew Bidwell; Asch, Steven M.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Gidwani, Risha A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Chen, JC (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. OI Chen, Jennifer/0000-0002-4801-5397; Goetz, Matthew/0000-0003-4542-992X NR 24 TC 14 Z9 14 U1 2 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAY PY 2011 VL 29 IS 4 BP 418 EP 426 DI 10.1016/j.ajem.2009.11.016 PG 9 WC Emergency Medicine SC Emergency Medicine GA 763QK UT WOS:000290574600010 PM 20825814 ER PT J AU Rosenthal, RA Fish, B Hill, RP Huffman, KD Lazarova, Z Mahmood, J Medhora, M Molthen, R Moulder, JE Sonis, ST Tofilon, PJ Doctrow, SR AF Rosenthal, Rosalind A. Fish, Brian Hill, Richard P. Huffman, Karl D. Lazarova, Zelmira Mahmood, Javed Medhora, Meetha Molthen, Robert Moulder, John E. Sonis, Stephen T. Tofilon, Philip J. Doctrow, Susan R. TI Salen Mn Complexes Mitigate Radiation Injury in Normal Tissues SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Article DE Salen manganese complex; radiation injury; radiation mitigation; catalytic antioxidant ID SUPEROXIDE DISMUTASE/CATALASE MIMETICS; CHRONIC OXIDATIVE STRESS; INDUCED ORAL MUCOSITIS; IONIZING-RADIATION; CATALYTIC SCAVENGERS; CATALASE MIMETICS; GENE-EXPRESSION; REDOX CONTROL; NITRIC-OXIDE; MICE AB Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusing on several tissues of therapeutic interest, namely kidney, lung, skin, and oral mucosa. These studies have demonstrated suppression of delayed radiation injury in animals treated with EUK-189 and/or EUK-207. While an antioxidant mechanism of action is postulated, it is likely that the mechanisms of radiation mitigation by these compounds in vivo are complex and may differ in the various target tissues. Indicators of oxidative stress are increased in lung and skin radiation injury models, and suppressed by salen Mn complexes. The role of oxidative stress in the renal injury model is unclear, though EUK-207 does mitigate. In certain experimental models, salen Mn complexes have shown "mito-protective" properties, that is, attenuating mitochondrial injury. Consistent with this, EUK-134 suppresses effects of ionizing radiation on mitochondrial function in rat astrocyte cultures. In summary, salen Mn complexes could be useful to mitigate delayed radiation injury to normal tissues following radiation therapy, accidental exposure, or radiological terrorism. Optimization of their mode of delivery and other key pharmaceutical properties, and increasing understanding of their mechanism(s) of action as radiation mitigators, are key issues for future study. C1 [Rosenthal, Rosalind A.; Huffman, Karl D.; Doctrow, Susan R.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. [Sonis, Stephen T.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Sonis, Stephen T.] Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA. [Sonis, Stephen T.] Brigham & Womens Hosp, Div Dent, Boston, MA 02115 USA. [Sonis, Stephen T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fish, Brian; Medhora, Meetha; Moulder, John E.] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Lazarova, Zelmira] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. [Molthen, Robert] Med Coll Wisconsin, Dept Pulm Med, Milwaukee, WI 53226 USA. [Hill, Richard P.; Mahmood, Javed] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Tofilon, Philip J.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Doctrow, SR (reprint author), Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. EM sdoctrow@bu.edu RI Moulder, John/E-6799-2012 FU [AI067734]; [AI81294]; [CA72156] FX Development of the salen Mn complexes, including EUK-207, was funded in part by GM57770 (SRD). Renal, cutaneous, and pulmonary studies and further compound development were supported by AI067734 (JEM), including a pilot grant (RAR) to study EUK-400 compounds. Some pulmonary studies were also supported by AI81294 (MM). The mucositis study was performed by Biomodels, LLC. (Wellesley, MA) under the direction of STS. The mitochondrial injury studies were supported by CA72156 (PJT). NR 106 TC 31 Z9 32 U1 1 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5206 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PD MAY PY 2011 VL 11 IS 4 BP 359 EP 372 PG 14 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA 764FL UT WOS:000290614400005 PM 21453241 ER PT J AU Atri, A O'Brien, JL Sreenivasan, A Rastegar, S Salisbury, S DeLuca, AN O'Keefe, KM LaViolette, PS Rentz, DM Locascio, JJ Sperling, RA AF Atri, Alireza O'Brien, Jacqueline L. Sreenivasan, Aishwarya Rastegar, Sarah Salisbury, Sibyl DeLuca, Amy N. O'Keefe, Kelly M. LaViolette, Peter S. Rentz, Dorene M. Locascio, Joseph J. Sperling, Reisa A. TI Test-Retest Reliability of Memory Task Functional Magnetic Resonance Imaging in Alzheimer Disease Clinical Trials SO ARCHIVES OF NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; RANDOMIZED CONTROLLED-TRIAL; CHOLINERGIC ENHANCEMENT; HIPPOCAMPAL ACTIVATION; PHARMACOLOGICAL FMRI; MRI; AD; DONEPEZIL; DEMENTIA; MODERATE AB Objective: To examine the feasibility and test-retest reliability of encoding-task functional magnetic resonance imaging (fMRI) in mild Alzheimer disease (AD). Design: Randomized, double-blind, placebocontrolled study. Setting: Memory clinical trials unit. Participants: We studied 12 patients with mild AD (mean [SEM] Mini-Mental State Examination score, 24.0 [0.7]; mean Clinical Dementia Rating score, 1.0) who had been taking donepezil hydrochloride for more than 6 months from the placebo arm of a larger 24-week study (n = 24, 4 scans on weeks 0, 6, 12, and 24, respectively). Interventions: Placebo and 3 face-name, paired-associate encoding, block-design blood oxygenation level-dependent fMRI scans in 12 weeks. Main Outcome Measures: We performed whole-brain t maps (P < .001, 5 contiguous voxels) and hippocampal regions-of-interest analyses of extent (percentage of active voxels) and magnitude (percentage of signal change) for novel-greater-than-repeated face-name contrasts. We also calculated intraclass correlation coefficients and power estimates for hippocampal regions of interest. Results: Task tolerability and data yield were high (95 of 96 scans yielded favorable-quality data). Whole brain maps were stable. Right and left hippocampal regions-of-interest intraclass correlation coefficients were 0.59 to 0.87 and 0.67 to 0.74, respectively. To detect 25.0% to 50.0% changes in week-0 to week-12 hippocampal activity using left-right extent or right magnitude with 80.0% power (2-sided alpha = .05) requires 14 to 51 patients. Using left magnitude requires 125 patients because of relatively small signal to variance ratios. Conclusions: Encoding-task fMRI was successfully implemented in a single-site, 24-week, AD randomized controlled trial. Week 0 to 12 whole-brain t maps were stable, and test-retest reliability of hippocampal fMRI measures ranged from moderate to substantial. Right hippocampal magnitude may be the most promising of these candidate measures in a leveraged context. These initial estimates of test-retest reliability and power justify evaluation of encoding-task fMRI as a potential biomarker for signal of effect in exploratory and proof-of-concept trials in mild AD. Validation of these results with larger sample sizes and assessment in multisite studies is warranted. C1 [Atri, Alireza] Massachusetts Gen Hosp, Memory Disorders Unit, Boston, MA 02114 USA. [Sreenivasan, Aishwarya; Rastegar, Sarah; LaViolette, Peter S.; Locascio, Joseph J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [O'Brien, Jacqueline L.; Salisbury, Sibyl; DeLuca, Amy N.; O'Keefe, Kelly M.; Rentz, Dorene M.; Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Atri, Alireza; Rentz, Dorene M.; Locascio, Joseph J.; Sperling, Reisa A.] Martinos Ctr Biomed Imaging, Boston, MA USA. [Atri, Alireza; Rentz, Dorene M.; Locascio, Joseph J.; Sperling, Reisa A.] Harvard Univ, Sch Med, Boston, MA USA. [Atri, Alireza] Bedford Med Ctr, Vet Hlth Adm, Geriatr Res Educ & Clin Ctr, Bedford, MA USA. RP Atri, A (reprint author), Massachusetts Gen Hosp, Memory Disorders Unit, 15 Parkman St,Wang Ambulatory Care Ctr 715, Boston, MA 02114 USA. EM atri@nmr.mgh.harvard.edu OI Atri, Alireza/0000-0003-4405-6973 FU National Institute on Aging [1K23 AG027171, RO1 AG027435]; Harvard-Massachusetts Institute of Technology Health Sciences and Technology Pfizer-Merck; National Institutes of Health; Forest Pharmaceuticals Inc; Harvard Center for Neurodegeneration and Repair; Clinical, Neuroimaging, and Statistics Cores of the Massachusetts Alzheimer's Disease Research Center (National Institute on Aging ) [5 P50AG05134]; Geriatric Research Education and Clinical Center at the Edith Nourse Rogers Memorial Veterans Administration Bedford Medical Center FX The study was supported by National Institute on Aging grants 1K23 AG027171 (Dr Atri) and RO1 AG027435 (Dr Sperling); the Harvard-Massachusetts Institute of Technology Health Sciences and Technology Pfizer-Merck Clinical Investigator Training Program (Dr Atri); the National Institutes of Health loan repayment program (Dr Atri); Investigator-Initiated Research Grants from Forest Pharmaceuticals Inc and the Harvard Center for Neurodegeneration and Repair; the Clinical, Neuroimaging, and Statistics Cores of the Massachusetts Alzheimer's Disease Research Center (National Institute on Aging grant 5 P50AG05134 to Dr Growdon and Bradley T. Hyman, MD, PhD); and the Geriatric Research Education and Clinical Center at the Edith Nourse Rogers Memorial Veterans Administration Bedford Medical Center. Less than 30% of this research was supported by an Investigator-Initiated Research Grant from Forest Pharmaceuticals Inc. NR 46 TC 16 Z9 17 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2011 VL 68 IS 5 BP 599 EP 606 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 761YB UT WOS:000290438000008 PM 21555634 ER PT J AU Berson, EL Rosner, B Sandberg, MA Weigel-DiFranco, C Willett, WC AF Berson, Eliot L. Rosner, Bernard Sandberg, Michael A. Weigel-DiFranco, Carol Willett, Walter C. TI Letter From the DSMC Regarding a Clinical Trial of Lutein in Patients With Retinitis Pigmentosa reply SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID RECEIVING VITAMIN-A; RANDOMIZED-TRIAL; ASPIRIN C1 [Berson, Eliot L.; Rosner, Bernard; Sandberg, Michael A.; Weigel-DiFranco, Carol] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab, Boston, MA USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Berson, EL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM linda_berard@meei.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 2011 VL 129 IS 5 BP 675 EP 676 PG 6 WC Ophthalmology SC Ophthalmology GA 761XU UT WOS:000290437100030 ER PT J AU Bartels, CM Kind, AJH Everett, C Mell, M McBride, P Smith, M AF Bartels, Christie M. Kind, Amy J. H. Everett, Christine Mell, Matthew McBride, Patrick Smith, Maureen TI Low Frequency of Primary Lipid Screening Among Medicare Patients With Rheumatoid Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; POSITIVE PREDICTIVE-VALUE; PRIMARY-CARE PHYSICIANS; QUALITY-OF-CARE; MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK; ADMINISTRATIVE DATA; ORTHOPEDIC-SURGERY; ISCHEMIC-STROKE; CLAIMS AB Objective. Although studies have demonstrated suboptimal preventive care in RA patients, performance of primary lipid screening (i.e., testing before cardiovascular disease [CVD], CVD risk equivalents, or hyperlipidemia is evident) has not been systematically examined. The purpose of this study was to examine associations between primary lipid screening and visits to primary care providers (PCPs) and rheumatologists among a national sample of older RA patients. Methods. This retrospective cohort study examined a 5% Medicare sample that included 3,298 RA patients without baseline CVD, diabetes mellitus, or hyperlipidemia, who were considered eligible for primary lipid screening during the years 2004-2006. The outcome was probability of lipid screening by the relative frequency of primary care and rheumatology visits, or seeing a PCP at least once each year. Results. Primary lipid screening was performed in only 45% of RA patients. Overall, 65% of patients received both primary and rheumatology care, and 50% saw a rheumatologist as often as a PCP. Any primary care predicted more lipid screening than lone rheumatology care (26% [95% confidence interval (95% CI) 21-32]). As long as a PCP was involved, performance of lipid screening was similar regardless of the balance between primary and rheumatology visits (44-48% [95% CI 41-51]). Not seeing a PCP at least annually decreased screening by 22% (adjusted risk ratio 0.78 [95% CI 0.71-0.84]). Conclusion. Primary lipid screening was performed in fewer than half of eligible RA patients, highlighting a key target for CVD risk reduction efforts. Annual visits to a PCP improved lipid screening, although performance remained poor (51%). Half of RA patients saw their rheumatologist as often or more often than they saw a PCP, illustrating the need to study optimal partnerships between PCPs and rheumatologists for screening patients for CVD risks. C1 [Bartels, Christie M.] Univ Wisconsin, Sch Med & Publ Hlth, Clin Sci Ctr H6, Madison, WI 53792 USA. [Kind, Amy J. H.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Mell, Matthew] Stanford Univ, Palo Alto, CA 94304 USA. RP Bartels, CM (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Clin Sci Ctr H6, Box 3244,600 Highland Ave, Madison, WI 53792 USA. EM cb4@medicine.wisc.edu FU University of Wisconsin Institute for Clinical and Translational Research from National Center for Research Resources, NIH [1UL1-RR-025011]; University of Wisconsin Institute for Clinical and Translational Research (NIH) [5KL2-RR-025012-02] FX Supported by the Health Innovation Program and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (grant 1UL1-RR-025011 from the Clinical and Translational Science Award program of the National Center for Research Resources, NIH) and by the University of Wisconsin Institute for Clinical and Translational Research (NIH training grant 5KL2-RR-025012-02). NR 49 TC 20 Z9 22 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2011 VL 63 IS 5 BP 1221 EP 1230 DI 10.1002/art.30239 PG 10 WC Rheumatology SC Rheumatology GA 764DY UT WOS:000290609800009 PM 21305507 ER PT J AU Castelino, FV Seiders, J Bain, G Brooks, SF King, CD Swaney, JS Lorrain, DS Chun, J Luster, AD Tager, AM AF Castelino, Flavia V. Seiders, Jon Bain, Gretchen Brooks, Sarah F. King, Christopher D. Swaney, James S. Lorrain, Daniel S. Chun, Jerold Luster, Andrew D. Tager, Andrew M. TI Amelioration of Dermal Fibrosis by Genetic Deletion or Pharmacologic Antagonism of Lysophosphatidic Acid Receptor 1 in a Mouse Model of Scleroderma SO ARTHRITIS AND RHEUMATISM LA English DT Article ID TGF-BETA ACTIVATION; GROWTH-FACTOR; INCREASED EXPRESSION; SYSTEMIC-SCLEROSIS; PULMONARY-FIBROSIS; TISSUE-REPAIR; FIBROBLASTS; SKIN; MYOFIBROBLAST; DISEASE AB Objective. Scleroderma (systemic sclerosis [SSc]), is characterized by progressive multiorgan fibrosis. We recently implicated lysophosphatidic acid (LPA) in the pathogenesis of pulmonary fibrosis. The purpose of the present study was to investigate the roles of LPA and two of its receptors, LPA(1) and LPA(2), in dermal fibrosis in a mouse model of SSc. Methods. Wild type (WT), and LPA(1)-knockout (KO) and LPA(2)-KO mice were injected subcutaneously with bleomycin or phosphate buffered saline (PBS) once daily for 28 days. Dermal thickness, collagen content, and numbers of cells positive for alpha-smooth muscle actin (alpha-SMA) or phospho-Smad2 were determined in bleomycin-injected and PBS-injected skin. In separate experiments, a novel selective LPA(1) antagonist AM095 or vehicle alone was administered by oral gavage to C57BL/6 mice that were challenged with 28 daily injections of bleomycin or PBS. AM095 or vehicle treatments were initiated concurrently with, or 7 or 14 days after, the initiation of bleomycin and PBS injections and continued to the end of the experiments. Dermal thickness and collagen content were determined in injected skin. Results. The LPA(1)-KO mice were markedly resistant to bleomycin-induced increases in dermal thickness and collagen content, whereas the LPA(2)-KO mice were as susceptible as the WT mice. Bleomycin-induced increases in dermal alpha-SMA+ and phospho-Smad2+ cells were abrogated in LPA(1)-KO mice. Pharmacologic antagonism of LPA(1) with AM095 significantly attenuated bleomycin-induced dermal fibrosis when administered according to either a preventive regimen or two therapeutic regimens. Conclusion. These results suggest that LPA/LPA(1) pathway inhibition has the potential to be an effective new therapeutic strategy for SSc, and that LPA(1) is an attractive pharmacologic target in dermal fibrosis. C1 [Castelino, Flavia V.; Brooks, Sarah F.; Luster, Andrew D.; Tager, Andrew M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Castelino, Flavia V.; Brooks, Sarah F.; Luster, Andrew D.; Tager, Andrew M.] Harvard Univ, Sch Med, Boston, MA USA. [Seiders, Jon; Bain, Gretchen; King, Christopher D.; Swaney, James S.; Lorrain, Daniel S.] Amira Pharmaceut, San Diego, CA USA. [Chun, Jerold] Scripps Res Inst, La Jolla, CA 92037 USA. RP Tager, AM (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St,Room 8301, Charlestown, MA 02129 USA. EM amtager@partners.org FU American College of Rheumatology Research and Education Foundation; NIH [R01-DA-019674, R01-NS-048478, R01-DC-009505, T32-AR-007258-32, R01-HL-095732]; Scleroderma Research Foundation; Amira Pharmaceuticals FX Supported by an American College of Rheumatology Research and Education Foundation Physician Scientist Development Award to Dr. Castelino, by NIH grants R01-DA-019674, R01-NS-048478, and R01-DC-009505 to Dr. Chun, T32-AR-007258-32 to Dr. Luster, and R01-HL-095732 to Dr. Tager, and by a Scleroderma Research Foundation grant to Dr. Tager.; Drs. Seiders, Bain, King, Swaney, Lorrain, and Chun own stock or stock options in Amira Pharmaceuticals. Drs. Chun and Tager have received consulting fees and/or honoraria from Amira Pharmaceuticals (less than $ 10,000 each) and serve as members of the company's Scientific Advisory Board. Drs. Luster and Tager have filed a patent cooperation treaty application on lysophosphatidic acid receptor targeting in lung disease. NR 43 TC 74 Z9 75 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2011 VL 63 IS 5 BP 1405 EP 1415 DI 10.1002/art.30262 PG 11 WC Rheumatology SC Rheumatology GA 764DY UT WOS:000290609800030 PM 21305523 ER PT J AU Morita, Y Chu, CQ AF Morita, Yoshiaki Chu, Cong-Qiu TI Is transforming growth factor beta always necessary for generation of pathogenic Th17 cells in autoimmune disease? Comment on the article by Morita et al Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID TGF-BETA; T-CELLS; INTERLEUKIN-23 PROMOTES; DIFFERENTIATION; DISTINCT; LINEAGE; INFLAMMATION C1 [Morita, Yoshiaki] Astellas Pharma, Tsukuba, Ibaraki, Japan. [Chu, Cong-Qiu] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Chu, Cong-Qiu] Portland VA Med Ctr, Portland, OR USA. RP Morita, Y (reprint author), Astellas Pharma, Tsukuba, Ibaraki, Japan. NR 9 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2011 VL 63 IS 5 BP 1467 EP 1468 DI 10.1002/art.30304 PG 2 WC Rheumatology SC Rheumatology GA 764DY UT WOS:000290609800040 ER PT J AU Hausmann, LRM Hanusa, BH Kresevic, DM Zickmund, S Ling, BS Gordon, HS Kwoh, CK Mor, MK Hannon, MJ Cohen, PZ Grant, R Ibrahim, SA AF Hausmann, Leslie R. M. Hanusa, Barbara H. Kresevic, Denise M. Zickmund, Susan Ling, Bruce S. Gordon, Howard S. Kwoh, C. Kent Mor, Maria K. Hannon, Michael J. Cohen, Peter Z. Grant, Richard Ibrahim, Said A. TI Orthopedic Communication About Osteoarthritis Treatment: Does Patient Race Matter? SO ARTHRITIS CARE & RESEARCH LA English DT Article ID INTERACTION ANALYSIS SYSTEM; INFORMED DECISION-MAKING; TOTAL KNEE REPLACEMENT; PRIMARY-CARE VISITS; JOINT REPLACEMENT; PHYSICIAN COMMUNICATION; ETHNIC-DIFFERENCES; AFRICAN-AMERICANS; RACIAL DISPARITIES; UNITED-STATES AB Objective. To understand racial disparities in the use of total joint replacement, we examined whether there were racial differences in patient-provider communication about treatment of chronic knee and hip osteoarthritis in a sample of African American and white patients referred to Veterans Affairs orthopedic clinics. Methods. Audio recorded visits between patients and orthopedic surgeons were coded using the Roter Interaction Analysis System and the Informed Decision-Making model. Racial differences in communication outcomes were assessed using linear regression models adjusted for study design, patient characteristics, and clustering by provider. Results. The sample (n = 402) included 296 white and 106 African American patients. Most patients were men (95%) and ages 50-64 years (68%). Almost half (41%) reported an income <$20,000. African American patients were younger and reported lower incomes than white patients. Visits with African American patients contained less discussion of biomedical topics (beta = -9.14; 95% confidence interval [95% CI] -16.73, -1.54) and more rapport-building statements (beta = 7.84; 95% CI 1.85, 13.82) than visits with white patients. However, no racial differences were observed with regard to length of visit, overall amount of dialogue, discussion of psychosocial issues, patient activation/engagement statements, physician verbal dominance, display of positive affect by patients or providers, or discussion related to informed decision making. Conclusion. In this sample, communication between orthopedic surgeons and patients regarding the management of chronic knee and hip osteoarthritis did not, for the most part, vary by patient race. These findings diminish the potential role of communication in Veterans Affairs orthopedic settings as an explanation for well-documented racial disparities in the use of total joint replacement. C1 [Hausmann, Leslie R. M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15206 USA. [Hausmann, Leslie R. M.; Hanusa, Barbara H.; Zickmund, Susan; Ling, Bruce S.; Kwoh, C. Kent; Mor, Maria K.; Hannon, Michael J.] Univ Pittsburgh, Pittsburgh, PA USA. [Kresevic, Denise M.; Grant, Richard] Univ Hosp Case Med Ctr, Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Gordon, Howard S.] Univ Illinois, Coll Med, Chicago, IL USA. [Gordon, Howard S.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Cohen, Peter Z.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Hausmann, LRM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM leslie.hausmann@gmail.com RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [IIR 04-137]; VA Health Services Research and Development Career Development [RCD 06-287, ER 0280-1]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [1K24AR055259-01]; Harold Amos Robert Wood Johnson Scholar FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (study IIR 04-137). Dr. Hausmann's work was supported by the VA Health Services Research and Development Career Development Program (awards RCD 06-287 and ER 0280-1). Dr. Ibrahim's work was supported in part by a K24 Award (grant 1K24AR055259-01) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and is recipient of a VA Health Services Research Career Development Award and the Harold Amos Robert Wood Johnson Scholar Award. NR 43 TC 7 Z9 7 U1 3 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD MAY PY 2011 VL 63 IS 5 BP 635 EP 642 DI 10.1002/acr.20429 PG 8 WC Rheumatology SC Rheumatology GA 761ZK UT WOS:000290441800001 PM 21225676 ER PT J AU Cutler, C Stevenson, K Kim, HT Brown, J McDonough, S Herrera, M Reynolds, C Liney, D Kao, G Ho, V Armand, P Koreth, J Alyea, E Dey, BR Attar, E Spitzer, T Boussiotis, VA Ritz, J Soiffer, R Antin, JH Ballen, K AF Cutler, C. Stevenson, K. Kim, H. T. Brown, J. McDonough, S. Herrera, M. Reynolds, C. Liney, D. Kao, G. Ho, V. Armand, P. Koreth, J. Alyea, E. Dey, B. R. Attar, E. Spitzer, T. Boussiotis, V. A. Ritz, J. Soiffer, R. Antin, J. H. Ballen, K. TI Double umbilical cord blood transplantation with reduced intensity conditioning and sirolimus-based GVHD prophylaxis SO BONE MARROW TRANSPLANTATION LA English DT Article DE umbilical cord blood; graft-vs-host disease; sirolimus ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; EPSTEIN-BARR-VIRUS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; BONE-MARROW; THYMIC FUNCTION; IMMUNE RECONSTITUTION; LYMPHOID MALIGNANCIES; UNRELATED DONORS; RISK-FACTORS AB The main limitations to umbilical cord blood (UCB) transplantation (UCBT) in adults are delayed engraftment, poor immunological reconstitution and high rates of non-relapse mortality (NRM). Double UCBT (DUCBT) has been used to circumvent the issue of low cell dose, but acute GVHD remains a significant problem. We describe our experience in 32 subjects, who underwent DUCBT after reduced-intensity conditioning with fludarabine/melphalan/antithymocyte globulin and who received sirolimus and tacrolimus to prevent acute GVHD. Engraftment of neutrophils occurred in all patients at a median of 21 days, and platelet engraftment occurred at a median of 42 days. Three subjects had grade II-IV acute GVHD (9.4%) and chronic GVHD occurred in four subjects (cumulative incidence 12.5%). No deaths were caused by GVHD and NRM at 100 days was 12.5%. At 2 years, NRM, PFS and OS were 34.4, 31.2 and 53.1%, respectively. As expected, immunologic reconstitution was slow, but PFS and OS were associated with reconstitution of CD4(+) and CD8(+) lymphocyte subsets, suggesting that recovery of adaptive immunity is required for the prevention of infection and relapse after transplantation. In summary, sirolimus and tacrolimus provide excellent GVHD prophylaxis in DUCBT, and this regimen is associated with low NRM after DUCBT. Bone Marrow Transplantation (2011) 46, 659-667; doi:10.1038/bmt.2010.192; published online 9 August 2010 C1 [Cutler, C.; McDonough, S.; Herrera, M.; Reynolds, C.; Liney, D.; Kao, G.; Ho, V.; Armand, P.; Koreth, J.; Alyea, E.; Ritz, J.; Soiffer, R.; Antin, J. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stevenson, K.; Kim, H. T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Brown, J.; Boussiotis, V. A.] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol & Canc Biol, Boston, MA 02215 USA. [Dey, B. R.; Attar, E.; Spitzer, T.; Ballen, K.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Cutler, C (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D1B13, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU NCI [P01 CA142106, R01 CA123855]; Jock and Bunny Adams Research and Education Fund; Eileen Pasquarello Research Fund; Astellas, Inc; Genzyme, Inc.; Stem Cell Cyclists of the Pan Mass Challenge FX Supported by NCI P01 CA142106, NCI R01 CA123855, the Jock and Bunny Adams Research and Education Fund, and the Ted and Eileen Pasquarello Research Fund. Funded in part by unrestricted research grants from Astellas, Inc and Genzyme, Inc. CC is supported by the Stem Cell Cyclists of the Pan Mass Challenge. NR 32 TC 55 Z9 58 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2011 VL 46 IS 5 BP 659 EP 667 DI 10.1038/bmt.2010.192 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 762JM UT WOS:000290472500005 PM 20697368 ER PT J AU Brown, JR AF Brown, Jennifer R. TI Insulin Receptor Activation in Deletion 11q Chronic Lymphocytic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID B-CELL RECEPTOR; SURVIVAL; INHIBITOR; CAL-101; SIGNALS AB The chromosomal abnormalities characteristic of chronic lymphocytic leukemia (CLL) are well studied, but the mechanisms underlying their contribution to pathogenesis are only partially elucidated. Integrated genomic profiling, focused on deletion 11q, has identified elevated expression of the insulin receptor in a subgroup of CLLs and associated it with worse outcomes. Clin Cancer Res; 17(9); 2605-7. (C) 2011 AACR. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Jennifer_Brown@dfci.harvard.edu NR 12 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2011 VL 17 IS 9 BP 2605 EP 2607 DI 10.1158/1078-0432.CCR-11-0295 PG 3 WC Oncology SC Oncology GA 757NH UT WOS:000290093600001 PM 21427241 ER PT J AU Pettersson, F Yau, C Dobocan, MC Culjkovic-Kraljacic, B Retrouvay, H Puckett, R Flores, LM Krop, IE Rousseau, C Cocolakis, E Borden, KLB Benz, CC Miller, WH AF Pettersson, Filippa Yau, Christina Dobocan, Monica C. Culjkovic-Kraljacic, Biljana Retrouvay, Helene Puckett, Rachel Flores, Ludmila M. Krop, Ian E. Rousseau, Caroline Cocolakis, Eftihia Borden, Katherine L. B. Benz, Christopher C. Miller, Wilson H., Jr. TI Ribavirin Treatment Effects on Breast Cancers Overexpressing eIF4E, Biomarker with Prognostic Specificity for Luminal B-Type Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID INITIATION-FACTOR 4E; MAMMARY EPITHELIAL-CELLS; TRANSLATION FACTOR EIF4E; CAP-BINDING PROTEIN; MESSENGER-RNA CAP; GENE-EXPRESSION; ONCOGENIC TRANSFORMATION; SIGNALING PATHWAY; MTOR INHIBITION; TUMOR-GROWTH AB Purpose: We have evaluated the eukaryotic translation initiation factor 4E (eIF4E) as a potential biomarker and therapeutic target in breast cancer. eIF4E facilitates nuclear export and translation of specific, growth-stimulatory mRNAs and is frequently overexpressed in cancer. Experimental Design: Breast cancer cells were treated with ribavirin, an inhibitor of eIF4E, and effects on cell proliferation and on known mRNA targets of eIF4E were determined. eIF4E expression was assessed, at the mRNA and protein level, in breast cancer cell lines and in skin biopsies from patients with metastatic disease. Additionally, pooled microarray data from 621 adjuvant untreated, node-negative breast cancers were analyzed for eIF4E expression levels and correlation with distant metastasis-free survival (DMFS), overall and within each intrinsic breast cancer subtype. Results: At clinically relevant concentrations, ribavirin reduced cell proliferation and suppressed clonogenic potential, correlating with reduced mRNA export and protein expression of important eIF4E targets. This effect was suppressed by knockdown of eIF4E. Although eIF4E expression is elevated in all breast cancer cell lines, variability in ribavirin responsiveness was observed, indicating that other factors contribute to an eIF4E-dependent phenotype. Assessment of the prognostic value of high eIF4E mRNA in patient tumors found that significant discrimination between good and poor outcome groups was observed only in luminal B cases, suggesting that a specific molecular profile may predict response to eIF4E-targeted therapy. Conclusions: Inhibition of eIF4E is a potential breast cancer therapeutic strategy that may be especially promising against specific molecular subtypes and in metastatic as well as primary tumors. Clin Cancer Res; 17(9); 2874-84. (C) 2011 AACR. C1 [Pettersson, Filippa; Dobocan, Monica C.; Retrouvay, Helene; Rousseau, Caroline; Cocolakis, Eftihia; Miller, Wilson H., Jr.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. [Pettersson, Filippa; Dobocan, Monica C.; Retrouvay, Helene; Rousseau, Caroline; Cocolakis, Eftihia; Miller, Wilson H., Jr.] McGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Montreal, PQ H3T 1E2, Canada. [Culjkovic-Kraljacic, Biljana; Borden, Katherine L. B.] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ, Canada. [Culjkovic-Kraljacic, Biljana; Borden, Katherine L. B.] Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ, Canada. [Yau, Christina; Puckett, Rachel; Benz, Christopher C.] Buck Inst Age Res, Novato, CA USA. [Flores, Ludmila M.; Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Miller, WH (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst, 3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM wmiller@jgh.mcgill.ca FU BCRF-AACR; Canadian Institute for Health Research [CIHR MOP-12863, MOP-43979]; National Cancer Institute of Canada (NCIC ) [19202]; [NIH-P50-CA58207]; [RL1-AG032113]; [U24-CA14358]; [NIH-98571] FX This research was supported in part by a BCRF-AACR Grant for Translational Breast Cancer Research (W. H. Miller). Other financial support was received from the Canadian Institute for Health Research (CIHR MOP-12863, W. H. Miller and F. Pettersson; MOP-43979, W. H. Miller), National Cancer Institute of Canada (NCIC #19202, W. H. Miller), NIH-P50-CA58207, RL1-AG032113, and U24-CA14358 (C. C. Benz and C. Yau), and NIH-98571 (K. L. B. Borden). W. H. Miller is a Chercheur National of Fonds de la Recherche en Sante du Quebec (FRSQ) and K. L. B. Borden holds a Canada Research Chair. NR 48 TC 42 Z9 46 U1 0 U2 2 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 MAY 1 PY 2011 VL 17 IS 9 BP 2874 EP 2884 DI 10.1158/1078-0432.CCR-10-2334 PG 11 WC Oncology SC Oncology GA 757NH UT WOS:000290093600028 PM 21415224 ER PT J AU Amrein, PC Attar, EC Takvorian, T Hochberg, EP Ballen, KK Leahy, KM Fisher, DC LaCasce, AS Jacobsen, ED Armand, P Hasserjian, RP Werner, L Neuberg, D Brown, JR AF Amrein, Philip C. Attar, Eyal C. Takvorian, Tak Hochberg, Ephraim P. Ballen, Karen K. Leahy, Kathleen M. Fisher, David C. LaCasce, Ann S. Jacobsen, Eric D. Armand, Philippe Hasserjian, Robert P. Werner, Lillian Neuberg, Donna Brown, Jennifer R. TI Phase II Study of Dasatinib in Relapsed or Refractory Chronic Lymphocytic Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID GNAS1 T393C POLYMORPHISM; CHRONIC MYELOID-LEUKEMIA; B-CELL RECEPTOR; KINASE INHIBITOR; TYROSINE KINASE; IN-VITRO; APOPTOSIS; FLUDARABINE; RESISTANCE; ACTIVATION AB Purpose: Chronic lymphocytic leukemia (CLL) cells treated with dasatinib in vitro undergo apoptosis via inhibition of Lyn kinase. Thus, in this study we tested the activity of dasatinib in patients with relapsed CLL. Experimental Design: Patients were eligible for this phase II trial if they had documented CLL/SLL and had failed at least 1 prior therapy with a fludarabine-containing regimen and if they required therapy according to NCI-WG criteria. The starting dose of dasatinib was 140 mg daily. Results: Fifteen patients were enrolled, with a median age of 59 and a median of 3 prior regimens. All patients had received fludarabine, and 5 were fludarabine-refractory. Eleven of the 15 (73%) had high risk del(11q) or del(17p) cytogenetics. The primary toxicity was myelosuppression, with grade 3 or 4 neutropenia and thrombocytopenia in 10 and 6 patients, respectively. Partial responses by NCI-WG criteria were achieved in 3 of the 15 patients (20%; 90% CI: 6-44). Among the remaining 12 patients, 5 had nodal responses by physical exam, and 1 patient had a nodal and lymphocyte response but with severe myelosuppression. Pharmacodynamic studies indicated apoptosis in peripheral blood CLL cells within 3 to 6 hours after dasatinib administration, associated with downregulation of Syk (spleen tyrosine kinase) mRNA. Conclusions: Dasatinib as a single agent has activity in relapsed and refractory CLL. Clin Cancer Res; 17(9); 2977-86. (C) 2011 AACR. C1 [Amrein, Philip C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Werner, Lillian; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Amrein, Philip C.; Attar, Eyal C.; Takvorian, Tak; Hochberg, Ephraim P.; Ballen, Karen K.; Fisher, David C.; LaCasce, Ann S.; Jacobsen, Eric D.; Armand, Philippe; Brown, Jennifer R.] Harvard Univ, Sch Med, Boston, MA USA. RP Amrein, PC (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7-942, Boston, MA 02114 USA. EM pamrein@partners.org FU Bristol Myers Squibb [205309]; Celgene; Genzyme; NIH [K23 CA115682] FX This study is an investigator-initiated study supported by per patient funding from Bristol Myers Squibb, which also supplied dasatinib. P. C. Amrein received $1,500 for attending a Bristol-Myers Squibb Advisory Board Meeting regarding Hematologic Malignancies in 2007. J. R. Brown served as a consultant for Calistoga, Celgene, and Genentech and received research funding from Celgene and Genzyme. The other authors have no conflict-of-interest to report.; This work was supported in part by grant 205309 from Bristol-Myers Squibb (to help support the management of data and the processing of blood and bone marrow samples). J. R. Brown was supported in part by NIH K23 CA115682. NR 32 TC 77 Z9 77 U1 0 U2 10 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 MAY 1 PY 2011 VL 17 IS 9 BP 2977 EP 2986 DI 10.1158/1078-0432.CCR-10-2879 PG 10 WC Oncology SC Oncology GA 757NH UT WOS:000290093600038 PM 21402714 ER PT J AU Leleu, X Xie, WL Bagshaw, M Banwait, R Leduc, R Roper, N Weller, E Ghobrial, IM AF Leleu, Xavier Xie, Wanling Bagshaw, Meghan Banwait, Ranjit Leduc, Renee Roper, Nitin Weller, Edie Ghobrial, Irene M. TI The Role of Serum Immunoglobulin Free Light Chain in Response and Progression in Waldenstrom Macroglobulinemia SO CLINICAL CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA; IMMUNOFIXATION ELECTROPHORESIS; INTERNATIONAL WORKSHOP; RECOMMENDATIONS; DIAGNOSIS; CRITERIA; ASSAYS AB Introduction: The serum free light chain (sFLC) has been widely used in the assessment of response in patients with multiple myeloma and other plasma cell dyscrasias. However, its use in Waldenstrom macroglobulinemia (WM) has not been previously assessed. We sought to examine the role of sFLC in response and progression of patients with WM. Methods: This study was conducted in a cohort of 48 patients with a diagnosis of WM, untreated (n = 20) or relapsed/refractory (n = 28), prospectively treated on a bortezomib and rituximab trial. Results: Involved FLC (iFLC) response occurred in 79% patients versus 60% by M-spike protocol criteria. The median time to response was shorter with iFLC than per protocol (2.1 and 3.7 months; P = 0.05). Progression defined using iFLC also correlated well to progression in the protocol (kappa = 0.63). However, the median time to progression (TTP) was more rapid by iFLC than per protocol (13.7 and 18.9 months). We also confirmed that a flare in iFLC in post-rituximab therapy did not correlate with lack of response or shorter TTP. Conclusion: Involved sFLC may be a useful marker of tumor measurement, showing earlier response and progression compared with IgM or M-spike measurements. Clin Cancer Res; 17(9); 3013-8. (C) 2011 AACR. C1 [Leleu, Xavier; Bagshaw, Meghan; Banwait, Ranjit; Leduc, Renee; Roper, Nitin; Ghobrial, Irene M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xie, Wanling; Weller, Edie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Leleu, Xavier] CHRU, Hop Huriez, Serv Malad Sang, Lille, France. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 1B127, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu NR 15 TC 18 Z9 21 U1 1 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 MAY 1 PY 2011 VL 17 IS 9 BP 3013 EP 3018 DI 10.1158/1078-0432.CCR-10-2954 PG 6 WC Oncology SC Oncology GA 757NH UT WOS:000290093600042 PM 21415221 ER PT J AU Haining, WN AF Haining, W. N. TI INTEGRATIVE GENOMIC ANALYSIS OF T CELL IMMUNITY IN HUMANS SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Meeting Abstract C1 [Haining, W. N.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Haining, W. N.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Haining, W. N.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAY PY 2011 VL 49 SU 1 BP S10 EP S10 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 755XR UT WOS:000289974200005 ER PT J AU Januzzi, JL AF Januzzi, James L., Jr. TI NT-PROBNP GUIDED HEART FAILURE THERAPY SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Meeting Abstract C1 [Januzzi, James L., Jr.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Cardiac Intens Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAY PY 2011 VL 49 SU 1 BP S174 EP S174 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 755XR UT WOS:000289974200197 ER PT J AU Melanson, SEF Stevenson, K Kim, H Antin, JH Ho, VT Ritz, J Soiffer, RJ Court, MH Kuo, FC Longtine, JA Jarolim, P AF Melanson, S. E. F. Stevenson, K. Kim, H. Antin, J. H. Ho, V. T. Ritz, J. Soiffer, R. J. Court, M. H. Kuo, F. C. Longtine, J. A. Jarolim, P. TI REDUCED OVERALL SURVIVAL OF CYP2C19*2/*2 HOMOZYGOTES AFTER MYELOABLATIVE HEMATOPOIETIC STEM CELL TRANSPLANTATION SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Meeting Abstract C1 [Melanson, S. E. F.; Kuo, F. C.; Longtine, J. A.; Jarolim, P.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Stevenson, K.; Kim, H.; Antin, J. H.; Ho, V. T.; Ritz, J.; Soiffer, R. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Court, M. H.] Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. EM pjarolim@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAY PY 2011 VL 49 SU 1 BP S667 EP S667 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 755XR UT WOS:000289974201332 ER PT J AU Pratchett, LC Yehuda, R AF Pratchett, Laura C. Yehuda, Rachel TI Foundations of posttraumatic stress disorder: Does early life trauma lead to adult posttraumatic stress disorder? SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID CHILD SEXUAL-ABUSE; CORTICOTROPIN-RELEASING-FACTOR; NATIONAL COMORBIDITY SURVEY; URINARY CORTISOL EXCRETION; INTIMATE PARTNER VIOLENCE; FOLLOW-UP; HOLOCAUST SURVIVORS; MALTREATED CHILDREN; NEGLECTED CHILDREN; PHYSICAL ABUSE AB The effects of childhood abuse are diverse, and although pathology is not the only outcome, psychiatric illness, including posttraumatic stress disorder (PTSD), can develop. However, adult PTSD is less common among those who experienced single-event traumas as children than it is among those who experienced childhood abuse. In addition, PTSD is more common among adults than children who experienced childhood abuse. Such evidence raises doubt about the direct, causal link between childhood trauma and adult PTSD. The experience of childhood trauma, and in particular abuse, has been identified as a risk factor for subsequent development of PTSD following exposure to adult trauma, and a substantial literature identifies revictimization as a factor that plays a pivotal role in this trajectory. The literature on the developmental effects of childhood abuse and pathways to revictimization, when considered in tandem with the biological effects of early stress in animal models, may provide some explanations for this. Specifically, it seems possible that permanent sensitization of the hypothalamic-pituitary-adrenal axis and behavioral outcomes are a consequence of childhood abuse, and these combine with the impact of retraumatization to sustain, perpetuate, and amplify symptomatology of those exposed to maltreatment in childhood. C1 [Pratchett, Laura C.; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Yehuda, Rachel] Mt Sinai Sch Med, New York, NY 10029 USA. RP Pratchett, LC (reprint author), James J Peters Vet Affairs Med Ctr, 526 OOMH,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM laura.pratchett@va.gov FU NIMH NIH HHS [MH088101] NR 206 TC 20 Z9 21 U1 17 U2 37 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD MAY PY 2011 VL 23 IS 2 BP 477 EP 491 DI 10.1017/S0954579411000186 PG 15 WC Psychology, Developmental SC Psychology GA 757OP UT WOS:000290097900009 PM 23786690 ER PT J AU Pasquale, LR Kang, JH AF Pasquale, L. R. Kang, J. H. TI Female reproductive factors and primary open-angle glaucoma in the Nurses' Health Study SO EYE LA English DT Article DE female reproductive factors; age at menarche; parity; oral contraceptives; primary open angle glaucoma ID HORMONE REPLACEMENT THERAPY; DOSE ORAL-CONTRACEPTIVES; INTRAOCULAR-PRESSURE; POSTMENOPAUSAL WOMEN; BREAST-CANCER; PROSPECTIVE COHORT; SEX-HORMONES; RISK-FACTORS; EYE DISEASE; ESTROGEN AB Purpose The purpose of this study was to explore the relation between age at menarche, parity, and oral contraceptive (OC) use, and primary open-angle glaucoma (POAG). Methods We followed 79 440 women in the Nurses' Health Study prospectively from 1980 to 2006 and identified 813 cases of incident POAG. Eligible participants were >= 40 years old, free of POAG at baseline, had information on reproductive history, and reported receiving eye examinations during follow-up. Relevant exposure data and POAG risk factors were updated using biennial questionnaires. We used proportional hazards models to calculate multivariable rate ratios (MVRRs) of POAG and 95% confidence intervals (CI). Results In multivariable analysis, there were no significant linear trends between age at menarche (P for trend=0.65) or reproductive duration defined as time between age at menarche and menopause (P for trend=0.30) and POAG. Although ever using OCs was not associated with POAG risk (MVRR=1.14; 95% CI, 0.98, 1.34), >= 5 years of OC use was associated with a modest 25% increased risk of POAG (MVRR=1.25; 95% CI, 1.02, 1.53; P for linear trend=0.04). Furthermore, among past OC users, a shorter time since stopping OC use was also associated with an increased risk of POAG (P for linear trend=0.02). Parity was not associated with POAG risk. Conclusion The >= 5 years of OC use was associated with a modestly increased risk of POAG. These data add further support for a role of circulating estrogen in the pathogenesis of POAG. Eye (2011) 25, 633-641; doi:10.1038/eye.2011.34; published online 18 February 2011 C1 [Pasquale, L. R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Boston, MA 02114 USA. [Pasquale, L. R.; Kang, J. H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02114 USA. RP Pasquale, LR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Louis_Pasquale@meei.harvard.edu FU National Institutes of Health [CA87969, CA55075, EY09611, HL35464, EY015473]; Research to Prevent Blindness in New York City FX We thank the participants of the Nurses Health Study and Frank Spiezer and Susan Hankinson, the founding and current principal investigators of the Nurses Health Study. Finally, we also thank Rong Chen, Maureen Ireland and Ann Wohlhueter for their contributions to this study. Financial support for this work was provided by grants CA87969, CA55075, EY09611, HL35464, and EY015473 from the National Institutes of Health. A Physician Scientist Award from Research to Prevent Blindness in New York City also supports Dr Pasquale. NR 44 TC 19 Z9 19 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD MAY PY 2011 VL 25 IS 5 BP 633 EP 641 DI 10.1038/eye.2011.34 PG 9 WC Ophthalmology SC Ophthalmology GA 763LE UT WOS:000290557300012 PM 21336255 ER PT J AU Thomas, V Daly, MK Cakiner-Egilmez, T Baker, E AF Thomas, V. Daly, M. K. Cakiner-Egilmez, T. Baker, E. TI Reliability of tonosafe disposable tonometer prisms: clinical implications from the Veterans Affairs Boston Healthcare System Quality Assurance Study SO EYE LA English DT Article DE intraocular pressure; disposable prisms; cross-infection; tonometry ID INTRAOCULAR-PRESSURE MEASUREMENT; EPIDEMIC KERATOCONJUNCTIVITIS; APPLANATION TONOMETRY; GOLDMANN TONOMETERS; DISINFECTION; ACCURACY; OUTBREAK; TIPS AB Purpose Given the Veterans Affairs Boston Healthcare System's recent introduction of single-use Tonosafe disposable tonometer prisms as an alternative to Goldmann applanation tonometers (GATs), this study had two aims: to conduct a large-scale quality assurance trial to assess the reliability of intraocular pressure (IOP) measurements of the Tonosafe disposable tonometer compared with GAT, particularly at extremes of pressure; to evaluate the suitability of Tonosafe disposable tonometer prisms as an acceptable substitute for GATs and for clinic-wide implementation in an academic tertiary referral setting. Methods Ophthalmology resident physicians measured the IOPs of patients in general and specialty eye clinics with the Tonosafe disposable tonometer and GAT. Tonosafe test-retest reliability data were also collected. A retrospective review of patient charts and data analysis were performed to determine the reliability of measurements. Results The IOPs of 652 eyes (326 patients) were measured with both GAT and Tonosafe, with a range of 3-34 mm Hg. Linear regression analysis showed R=0.93, slope=0.91, both of which supported the proposed hypothesis, and the y-intercept=-1.05 was significantly different from the hypothesized value. The Tonosafe test-retest repeatability (40 eyes of 40 patients), r=0.977, was very high, which was further supported by linear regression slope-0.993, y-intercept-0.118, and a Tonosafe repeatability coefficient of 2.06, similar to GAT repeatability. Conclusions The IOP measurements by Tonosafe disposable prisms correlated closely with Goldmann measurements, with similar repeated measurement variability to GAT. This suggests that the Tonosafe is an acceptable substitute for GAT to measure IOP in ophthalmology clinic settings. Eye (2011) 25, 651-656; doi:10.1038/eye.2011.40; published online 1 April 2011 C1 [Thomas, V.; Daly, M. K.; Cakiner-Egilmez, T.; Baker, E.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Thomas, V.; Daly, M. K.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Thomas, V (reprint author), VA Boston Healthcare, Ophthalmol Sect, 150 S Huntington,Off 8C-29, Boston, MA 02130 USA. EM vthomas@bu.edu NR 27 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD MAY PY 2011 VL 25 IS 5 BP 651 EP 656 DI 10.1038/eye.2011.40 PG 6 WC Ophthalmology SC Ophthalmology GA 763LE UT WOS:000290557300014 PM 21455241 ER PT J AU Kellogg, DL Zhao, JL Wu, YB Johnson, JM AF Kellogg, Dean L., Jr. Zhao, Joan L. Wu, Yubo Johnson, John M. TI Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE nitric oxide; guanosine 3 ',5 '-cyclic monophosphate; microdialysis; skin; thermoregulation ID SKIN BLOOD-FLOW; HUMAN CARDIOVASCULAR ADJUSTMENTS; SYNTHASE CONTROL MECHANISMS; NITRIC-OXIDE CONCENTRATION; ACTIVE VASODILATATION; S-NITROSYLATION; IN-VIVO; REACTIVE HYPEREMIA; VASCULAR-RESPONSES; MUNC18-1 BINDING AB Kellogg DL Jr, Zhao JL, Wu Y, Johnson JM. Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans. J Appl Physiol 110: 1406-1413, 2011. First published February 3, 2011; doi: 10.1152/japplphysiol.00702.2010.-We hypothesized that nitric oxide activation of soluble guanylyl cyclase (sGC) participates in cutaneous vasodilation during whole body heat stress and local skin warming. We examined the effects of the sGC inhibitor, 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), on reflex skin blood flow responses to whole body heat stress and on nonreflex responses to increased local skin temperature. Blood flow was monitored by laser-Doppler flowmetry, and blood pressure by Finapres to calculate cutaneous vascular conductance (CVC). Intradermal microdialysis was used to treat one site with 1 mM ODQ in 2% DMSO and Ringer, a second site with 2% DMSO in Ringer, and a third site received Ringer. In protocol 1, after a period of normothermia, whole body heat stress was induced. In protocol 2, local heating units warmed local skin temperature from 34 to 41 C to cause local vasodilation. In protocol 1, in normothermia, CVC did not differ among sites [ ODQ, 15 +/- 3% maximum CVC (CVC(max)); DMSO, 14 +/- 3% CVC(max); Ringer, 17 +/- 6% CVC(max); P > 0.05]. During heat stress, ODQ attenuated CVC increases (ODQ, 54 +/- 4% CVC(max); DMSO, 64 +/- 4% CVC(max); Ringer, 63 +/- 4% CVC(max); P < 0.05, ODQ vs. DMSO or Ringer). In protocol 2, at 34 degrees C local temperature, CVC did not differ among sites (ODQ, 17 +/- 2% CVC(max); DMSO, 18 +/- 4% CVC(max); Ringer, 18 +/- 3% CVC(max); P < 0.05). ODQ attenuated CVC increases at 41 degrees C local temperature (ODQ, 54 +/- 5% CVC(max); DMSO, 86 +/- 4% CVC(max); Ringer, 90 +/- 2% CVCmax; P < 0.05 ODQ vs. DMSO or Ringer). sGC participates in neurogenic active vasodilation during heat stress and in the local response to direct skin warming. C1 [Kellogg, Dean L., Jr.; Zhao, Joan L.; Wu, Yubo] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA. [Kellogg, Dean L., Jr.; Johnson, John M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Kellogg, Dean L., Jr.; Zhao, Joan L.; Wu, Yubo] Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Kellogg, DL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Geriatr Gerontol & Palliat Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kelloggd@uthscsa.edu FU National Heart, Lung, and Blood Institute [HL-065599] FX This work was supported in part by National Heart, Lung, and Blood Institute Grant HL-065599. NR 64 TC 14 Z9 14 U1 0 U2 2 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 MAY PY 2011 VL 110 IS 5 BP 1406 EP 1413 DI 10.1152/japplphysiol.00702.2010 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 762JL UT WOS:000290472400036 PM 21292837 ER PT J AU Winkler, T Venegas, JG AF Winkler, Tilo Venegas, Jose G. TI Self-organized patterns of airway narrowing SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE asthma; bronchoconstriction; airway smooth muscle; emergence; complex behavior ID OBSTRUCTIVE PULMONARY-DISEASE; SYNCHROTRON-RADIATION CT; SMOOTH-MUSCLE; VENTILATION; ASTHMA; BRONCHOCONSTRICTION; METHACHOLINE; RESPONSES; HETEROGENEITY; IMPEDANCE AB Winkler T, Venegas JG. Self-organized patterns of airway narrowing. J Appl Physiol 110: 1482-1486, 2011. First published January 20, 2011; doi: 10.1152/japplphysiol.01163.2010.-The behavior of respiratory diseases such as asthma and COPD may involve complicated interactions among multiple factors. Theoretical and experimental data suggest that interdependence among the airways of the bronchial tree leads to the emergence of self-organized patterns of airway narrowing, ventilation defects, and other phenomena when a tipping point is passed. Additionally, evidence from several studies shows that the behavior of an isolated airway is different from an identical airway embedded in the bronchial tree so that experimental results of isolated elements such as airways, airway smooth muscle, or inflammatory pathways may not explain the whole organ behavior. However, there may be factors in the isolated elements that can dramatically change the complex system's behavior. More effective strategies for prevention or recovery from a disease, such as asthma, will depend on our progress in identifying and understanding the essential parts of the self-organized behavior that is involved. C1 [Winkler, Tilo] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Winkler, T (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM twinkler@vqpet.mgh.harvard.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 32 TC 9 Z9 9 U1 0 U2 2 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 MAY PY 2011 VL 110 IS 5 BP 1482 EP 1486 DI 10.1152/japplphysiol.01163.2010 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 762JL UT WOS:000290472400046 PM 21252219 ER PT J AU Fang, Y Fu, XJ Gu, C Xu, P Wang, Y Yu, WR Sun, Q Sun, XJ Yao, M AF Fang, Yong Fu, Xiu-Jun Gu, Chuan Xu, Peng Wang, Ying Yu, Wei-Rong Sun, Qiang Sun, Xue-Jun Yao, Min TI Hydrogen-Rich Saline Protects Against Acute Lung Injury Induced by Extensive Burn in Rat Model SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID SMOKE-INHALATION INJURY; NF-KAPPA-B; OXIDATIVE STRESS; BACTERIAL TRANSLOCATION; ENDOTHELIAL-CELLS; THERMAL-INJURY; SHEEP; PATHOPHYSIOLOGY; INFLAMMATION; DYSFUNCTION AB Hydrogen has been reported to selectively quench detrimental reactive oxygen species, particularly hydroxyl radical, and to prevent myocardial or hepatic ischemia/reperfusion injury in multiple models. The aim of this study is to investigate whether hydrogen protects against severe burn-induced acute lung injury in rats. Rats were divided into four groups: sham plus normal saline, burn injury plus normal saline, burn injury plus hydrogen-rich saline, and burn injury plus edaravone. Animals were given full-thickness burn wounds (30% TBSA) using boiling water, except the sham group that was treated with room temperature water. The rats in hydrogen group received 5 ml/kg of hydrogen-rich saline, sham and burn controls obtained the same amount of saline, and the edaravone group was treated with 9 mg/kg of edaravone in saline. Lactated Ringer's solution was given at 6 hours postburn. The lungs were harvested 12 hours postburn for laboratory investigations. Severe burns with delayed resuscitation rapidly caused lung edema and impaired oxygenation in rats. These dysfunctions were ameliorated by administration of hydrogen-rich saline or edaravone. When compared with the burn injury plus normal saline group, hydrogen-rich saline or edaravone group significantly attenuated the pulmonary oxidative products, such as malondialdehyde, carbonyl, and 8-hydroxy-2'-deoxyguanosine. Furthermore, administration of hydrogen-rich saline or edaravone dramatically reduced the pulmonary levels of pulmonary inflammation mediators and myeloperoxidase. Intraperitoneal administration of hydrogen-rich saline improves pulmonary function by reducing oxidative stress and inflammatory response in severe burn-induced acute lung injury. (J Burn Care Res 2011;32:e82-e91) C1 [Yao, Min] Shanghai Jiao Tong Univ, Dept Burns & Plast Surg, Peoples Hosp 3, Sch Med,Inst Traumat Med, Shanghai 201900, Peoples R China. [Sun, Qiang; Sun, Xue-Jun] Second Mil Med Univ, Dept Diving Med, Shanghai, Peoples R China. [Yao, Min] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Yao, M (reprint author), Shanghai Jiao Tong Univ, Dept Burns & Plast Surg, Peoples Hosp 3, Sch Med,Inst Traumat Med, 280 Mohe Rd, Shanghai 201900, Peoples R China. RI sun, xuejun/G-5212-2011; sun, xuejun/C-2844-2013; sun, xuejun/A-5561-2010 OI sun, xuejun/0000-0003-2387-5531 FU Foundation of Nature and Science at the School of Medicine, Shanghai Jiao Tong University [2008XZDXK]; National Natural Science Foundation of China [30872682] FX Supported, in part, by a grant from the Foundation of Nature and Science at the School of Medicine, Shanghai Jiao Tong University (2008XZDXK), and the National Natural Science Foundation of China (30872682). NR 40 TC 21 Z9 27 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2011 VL 32 IS 3 BP E82 EP E91 DI 10.1097/BCR.0b013e318217f84f PG 10 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 760EZ UT WOS:000290308500007 PM 21436720 ER PT J AU Zarraga, IGE MacMurdy, KS Raitt, MH AF Zarraga, Ignatius Gerardo E. MacMurdy, Karen S. Raitt, Merritt H. TI Tachycardia With Typical Left Bundle Branch Block Morphology and VA Block: What is the Differential Diagnosis? SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material ID REENTRY; MECHANISM C1 [Zarraga, Ignatius Gerardo E.; MacMurdy, Karen S.; Raitt, Merritt H.] Portland VA Med Ctr, Div Cardiol, Portland, OR 97239 USA. RP Zarraga, IGE (reprint author), Portland VA Med Ctr, Div Cardiol, 3710 SW,US Vet Hos Rd, Portland, OR 97239 USA. EM Ignatius.Zarraga@va.gov OI Raitt, Merritt/0000-0001-5638-7732 NR 6 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAY PY 2011 VL 22 IS 5 BP 601 EP 604 DI 10.1111/j.1540-8167.2010.01965.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 762OT UT WOS:000290490000021 PM 21561505 ER PT J AU Mohr, DC Warren, N Hodgson, MJ Drummond, DJ AF Mohr, David C. Warren, Nicholas Hodgson, Michael J. Drummond, David J. TI Assault Rates and Implementation of a Workplace Violence Prevention Program in the Veterans Health Care Administration SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID EMPLOYERS REPORTS; WORKERS; AGGRESSION; FACILITIES; CALIFORNIA; SETTINGS; INJURIES; BEHAVIOR AB Objective: This study examined the relationship between changes in assault rates over time and the implementation of a workplace violence prevention (WVP) program in 138 Department of Veterans Affairs health care facilities. Methods: Data on WVP implementation were assessed for each facility by a three-person team. We computed three WVP dimension scores: training, workplace practices, and environmental control and security. We obtained 6 years of assault rate data from the national injury system. Using a linear mixed model, we analyzed whether the WVP implementation was associated with lower assault rates controlling for time and organizational characteristics. Results: Training implementation was negatively associated with assault rates. Facilities with smaller bed sizes and without academic affiliates had lower assault rates. Conclusions: Particular attention should be given to these dimensions because they may be associated with lower facility-level assault rates. C1 [Mohr, David C.] Boston Univ, Sch Publ Hlth, Ctr Org Leadership & Management Res, Dept Vet Affairs,VA Boston Healthcare Syst, Boston, MA USA. [Mohr, David C.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Warren, Nicholas] Univ Connecticut, Ctr Hlth, Div Publ Hlth & Populat Sci, Farmington, CT USA. [Hodgson, Michael J.; Drummond, David J.] Dept Vet Affairs, Off Publ Hlth & Environm Hazards, Washington, DC USA. RP Mohr, DC (reprint author), VA Boston Healthcare Syst 152M, 150 S Huntington Ave, Boston, MA 02130 USA. EM david.mohr2@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [IIR 05-221] FX This material is based upon the work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development for IIR 05-221. The authors are also grateful for the advice and support of Dr Charles Welch. NR 37 TC 8 Z9 8 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAY PY 2011 VL 53 IS 5 BP 511 EP 516 DI 10.1097/JOM.0b013e31820d101e PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 761WA UT WOS:000290430500008 PM 21555925 ER PT J AU Ahmed, S Gibson, CM Cannon, CP Murphy, SA Sabatine, MS AF Ahmed, Shaheeda Gibson, C. Michael Cannon, Christopher P. Murphy, Sabina A. Sabatine, Marc S. TI Impact of reduced glomerular filtration rate on outcomes in patients with ST-segment elevation myocardial infarction undergoing fibrinolysis: a CLARITY-TIMI 28 analysis SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE Myocardial infarction; Glomerular filtration rate; Fibrinolysis; Platelet ID ACUTE CORONARY SYNDROMES; CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR OUTCOMES; SUBSEQUENT MORTALITY; REPERFUSION THERAPY; DIABETES-MELLITUS; RENAL DYSFUNCTION; PERFUSION GRADE; ARTERY-DISEASE; ASSOCIATION AB Reduced glomerular filtration rate (GFR) is associated with adverse outcomes in patients with cardiovascular disease. We explored the relationship between GFR and angiographic and clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients receiving pharamacologic reperfusion, with or without clopidogrel. Data were available to estimate GFR in 3,252 STEMI patients undergoing fibrinolysis, randomized to clopidogrel versus placebo in the CLARITY-TIMI 28 trial. Patients with a creatinine > 2.5 mg/dl were excluded from the trial. We compared outcomes between patients with no, mild or moderate reductions in baseline estimated GFR (ml/min/1.73 m(2)) of a parts per thousand yen90, 60-89, and < 60, respectively. Compared to patients with no (n = 841) or mildly reduced GFR (n = 1897), those with moderately reduced GFR (n = 514) were older, more often female, and were more likely to have diabetes and hypertension (P a parts per thousand currency sign 0.001 for all). The risk of the primary endpoint (an occluded infarct-related artery on angiography or death/myocardial infarction by day 8), 30 day cardiovascular events (death, myocardial infarction, or urgent revascularization for recurrent ischemia) and 30 day Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding increased as GFR declined (P for trend 0.003, < 0.0001, and 0.0008 respectively). The adjusted risk of 30 day ischemic complications remained higher in patients with moderately reduced versus normal GFR (OR 1.5, 95% CI 1.0-2.1, P = 0.04). Treatment with clopidogrel tended to yield greater benefit in patients with normal or mildly reduced GFR versus in patients with moderately reduced GFR. In conclusion, STEMI patients with reduced GFR treated with medical reperfusion, including dual antiplatelet therapy, have higher rates of adverse clinical outcome. Further research on optimal STEMI therapy in this high-risk group is warranted. C1 [Ahmed, Shaheeda; Gibson, C. Michael; Cannon, Christopher P.; Murphy, Sabina A.; Sabatine, Marc S.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. [Ahmed, Shaheeda; Gibson, C. Michael; Cannon, Christopher P.; Murphy, Sabina A.; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Dept Med, Cardiovasc Div, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM msabatine@partners.org NR 21 TC 4 Z9 4 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD MAY PY 2011 VL 31 IS 4 BP 493 EP 500 DI 10.1007/s11239-011-0566-9 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 762DA UT WOS:000290451300014 PM 21318582 ER PT J AU Moore, FO Goslar, PW Coimbra, R Velmahos, G Brown, CVR Coopwood, TB Lottenberg, L Phelan, HA Bruns, BR Sherck, JP Norwood, SH Barnes, SL Matthews, MR Hoff, WS de Moya, MA Bansal, V Hu, CKC Karmy-Jones, RC Vinces, F Pembaur, K Notrica, DM Haan, JM AF Moore, Forrest O. Goslar, Pamela W. Coimbra, Raul Velmahos, George Brown, Carlos V. R. Coopwood, Thomas B., Jr. Lottenberg, Lawrence Phelan, Herb A. Bruns, Brandon R. Sherck, John P. Norwood, Scott H. Barnes, Stephen L. Matthews, Marc R. Hoff, William S. de Moya, Marc A. Bansal, Vishal Hu, Charles K. C. Karmy-Jones, Riyad C. Vinces, Fausto Pembaur, Karl Notrica, David M. Haan, James M. TI Blunt Traumatic Occult Pneumothorax: Is Observation Safe?-Results of a Prospective, AAST Multicenter Study SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 69th Annual Meeting of the American-Association-for-the-Surgery-of-Trauma CY SEP 22-25, 2010 CL Boston, MA SP Amer Assoc Surg Trauma DE Occult pneumothorax; Tube thoracostomy; Computed tomography ID TUBE THORACOSTOMY; COMPUTED-TOMOGRAPHY; CRITICAL-CARE; CHEST TRAUMA; MANAGEMENT; CT; COMPLICATIONS; PATIENT AB Background: An occult pneumothorax (OPTX) is found incidentally in 2% to 10% of all blunt trauma patients. Indications for intervention remain controversial. We sought to determine which factors predicted failed observation in blunt trauma patients. Methods: A prospective, observational, multicenter study was undertaken to identify patients with OPTX. Successfully observed patients and patients who failed observation were compared. Multivariate logistic regression was used to identify predictors of failure of observation. OPTX size was calculated by measuring the largest air collection along a line perpendicular from the chest wall to the lung or mediastinum. Results: Sixteen trauma centers identified 588 OPTXs in 569 blunt trauma patients. One hundred twenty-one patients (21%) underwent immediate tube thoracostomy and 448 (79%) were observed. Twenty-seven patients (6%) failed observation and required tube thoracostomy for OPTX progression, respiratory distress, or subsequent hemothorax. Fourteen percent (10 of 73) failed observation during positive pressure ventilation. Hospital and intensive care unit lengths of stay, and ventilator days were longer in the failed observation group. OPTX progression and respiratory distress were significant predictors of failed observation. Most patient deaths were from traumatic brain injury. Fifteen percentage of patients in the failed observation group developed complications. No patient who failed observation developed a tension PTX, or experienced adverse events by delaying tube thoracostomy. Conclusion: Most blunt trauma patients with OPTX can be carefully monitored without tube thoracostomy; however, OPTX progression and respiratory distress are independently associated with observation failure. C1 [Moore, Forrest O.; Goslar, Pamela W.] St Josephs Hosp, Phoenix, AZ 85013 USA. [Moore, Forrest O.; Goslar, Pamela W.] Med Ctr, Phoenix, AZ 85013 USA. [Coimbra, Raul; Bansal, Vishal] UCSD, Med Ctr, San Diego, CA USA. [Velmahos, George; de Moya, Marc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brown, Carlos V. R.; Coopwood, Thomas B., Jr.] Univ Med Ctr Brackenridge, Austin, TX USA. [Lottenberg, Lawrence] Univ Florida, Hlth Sci Ctr, Gainesville, FL USA. [Phelan, Herb A.] UT Southwestern, Med Ctr, Dallas, TX USA. [Bruns, Brandon R.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Sherck, John P.] Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. [Norwood, Scott H.] E Texas Med Ctr, Tyler, TX USA. [Barnes, Stephen L.] Univ Missouri, Columbia, MO USA. [Matthews, Marc R.] Maricopa Cty Gen Hosp, Phoenix, AZ USA. [Hoff, William S.] St Lukes Hosp, Bethlehem, PA USA. [Hoff, William S.] Med Ctr, Bethlehem, PA USA. [Hu, Charles K. C.] Scottsdale Osborne Med Ctr, Scottsdale, AZ USA. [Karmy-Jones, Riyad C.] Southwest Washington Med Ctr, Vancouver, WA USA. [Vinces, Fausto; Pembaur, Karl] Lutheran Med Ctr, Brooklyn, NY USA. [Notrica, David M.] Phoenix Childrens Hosp, Phoenix, AZ USA. [Haan, James M.] Via Christi Reg Med Ctr, Wichita, KS USA. RP Moore, FO (reprint author), St Josephs Hosp, 350 W Thomas Rd, Phoenix, AZ 85013 USA. EM moore677@aol.com NR 21 TC 31 Z9 35 U1 1 U2 2 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 MAY PY 2011 VL 70 IS 5 BP 1019 EP 1023 DI 10.1097/TA.0b013e318213f727 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 762LQ UT WOS:000290480300009 PM 21610419 ER PT J AU Rodriguez, A Lisboa, T Martin-Loeches, I Diaz, E Trefler, S Restrepo, MI Rello, J AF Rodriguez, Alejandro Lisboa, Thiago Martin-Loeches, Ignacio Diaz, Emili Trefler, Sandra Restrepo, Marcos I. Rello, Jordi TI Mortality and Regional Oxygen Saturation Index in Septic Shock Patients: A Pilot Study SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Near-infrared spectroscopy; Sepsis; Microcirculation; Tissue oxygenation; Hypoxia ID NEAR-INFRARED SPECTROSCOPY; MUSCLE-TISSUE OXYGENATION; SEVERE SEPSIS; TRAUMA PATIENTS; BLOOD-FLOW; PERFUSION; RESUSCITATION; CONSUMPTION; DYSFUNCTION; INSTRUMENT AB Background: Peripheral muscle tissue oxygenation determined noninvasively using near-infrared spectroscopy may help to identify tissue hypoperfusion in septic patients. The aim of this study was to investigate regional oxygen saturation index (rSO(2)) in the brachioradialis (forearm) muscle by comparing measurements in healthy subjects and in intensive care unit (ICU) septic shock patients, and determine whether brachioradialis muscle rSO2 is associated with poor outcome in ICU septic shock patients. Methods: We conducted a prospective observational study in healthy volunteers (n = 50) and ICU septic shock patients (n = 19). Brachioradialis (forearm) rSO2 measurements in healthy volunteers at rest and in ICU septic shock patients were compared. Pulmonary artery catheter monitoring was used in ICU patients. Results: Significant differences in rSO(2) were observed between healthy volunteers and ICU septic shock patients at ICU admission (68.7 +/- 4.9 vs. 55.0 +/- 13.0; p < 0.001). When comparing septic shock survivors and nonsurvivors, significant differences were observed in rSO(2) at baseline (64.5 +/- 8.9 vs. 47.5 +/- 10.7; p < 0.01), 12 hours (67.3 +/- 9.6 vs. 45.0 +/- 14.9; p < 0.01), and 24 hours (65.7 +/- 7.0 vs. 50.1 +/- 10.3; p < 0.01). Lactate concentration was lower in survivors than nonsurvivors at 24 hours (12.0 +/- 7.5 mmol/L vs. 23.2 +/- 12.5 mmol/L; p < 0.04). Cardiac index was greater in nonsurvivors than survivors at baseline (4.6 + 1.9 L/min/m(2) vs. 3.0 + 0.9 L/min/m(2); p < 0.05) and 12 h (3.9 + 0.5 L/min/m(2) vs. 3.1 + 0.3 L/min/m(2); p < 0.05). Conclusions: We observed that septic shock patients with forearm skeletal muscle rSO(2) <= 60% throughout first 24 hours after ICU admission had significantly greater mortality rate than patients with forearm skeletal muscle rSO2 >60% throughout this critical time. C1 [Rodriguez, Alejandro; Lisboa, Thiago; Martin-Loeches, Ignacio; Diaz, Emili; Trefler, Sandra] Univ Rovira & Virgili, Crit Care Dept, Joan XXIII Univ Hosp, IISPV,CIBER Enfermedades Resp, Tarragona 43007, Spain. [Lisboa, Thiago] Clin Univ Hosp, Crit Care Dept, Porto Alegre, RS, Brazil. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA. [Rello, Jordi] Vall Hebron Univ Hosp, Crit Care Dept, CIBER Enfermedades Resp, Barcelona, Spain. RP Rodriguez, A (reprint author), Univ Rovira & Virgili, Crit Care Dept, Joan XXIII Univ Hosp, IISPV,CIBER Enfermedades Resp, Carrer Dr Mallafre Guasch 4, Tarragona 43007, Spain. EM ahr1161@yahoo.es RI Martin-Loeches, Ignacio/H-4633-2013; Restrepo, Marcos/H-4442-2014; OI Rodriguez Oviedo, Alejandro/0000-0001-8828-5984; Rello, Jordi/0000-0003-0676-6210 FU Instituto de Salud Carlos III [FIS PI10/01538]; CIBER Enfermedades respiratorias; AGAUR [2009/SGR/1226]; Department of Veterans Affairs, Veterans Integrated Service Network; National Health Institute [KL2 RR025766] FX Supported by FIS PI10/01538 Instituto de Salud Carlos III (FEDER), CIBER Enfermedades respiratorias, and AGAUR (2009/SGR/1226).; Dr. Restrepo is supported by a Department of Veterans Affairs, Veterans Integrated Service Network 17 new faculty grant and National Health Institute Grant KL2 RR025766. NR 52 TC 14 Z9 15 U1 0 U2 1 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 MAY PY 2011 VL 70 IS 5 BP 1145 EP 1152 DI 10.1097/TA.0b013e318216f72c PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 762LQ UT WOS:000290480300035 PM 21610429 ER PT J AU Burns, JA Lopez-Guerra, G Kobler, JB Faquin, W LeClair, M Zeitels, SM AF Burns, James A. Lopez-Guerra, Gerardo Kobler, James B. Faquin, William LeClair, Matthew Zeitels, Steven M. TI Pulsed Potassium-Titanyl-Phosphate Laser Photoangiolytic Treatment of Mucosal Squamous Cell Carcinoma in the Hamster Cheek Pouch SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Combined Section Meeting on Triological-Society CY JAN 27-30, 2011 CL Scottsdale, AZ SP Triolog Soc DE Photoangiolysis; KTP laser; squamous cell carcinoma; hamster cheek pouch ID CHORIOALLANTOIC MEMBRANE; GLOTTAL DYSPLASIA; DYE-LASER; CARCINOGENESIS; PAPILLOMATOSIS; ANGIOGENESIS; ANESTHESIA; MODEL AB Objectives/Hypothesis: Early glottic cancer has been involuted by treatment with the 532 nm pulsed potassium-titanyl-phosphate (KTP) laser in initial clinical studies. Selective photoangiolysis of the sublesional circulation that allows for relative sparing of surrounding tissue is the presumed mechanism. No prior controlled animal-model study has analyzed the ability of selective coagulation of lesional microvasculature coagulation with the KTP laser to involute malignant lesions. This study tests the efficacy of photoangiolysis with the KTP laser in treating squamous cell carcinoma in an established animal model. Study Design: In vivo. Methods: Malignant lesions were induced unilaterally in the cheek pouches of 21 hamsters by applying 9,10-dimethyl-1,2-benzanthrancene. The contralateral cheek pouch served as a control. Weekly lesion photodocumentation and pulsed KTP laser (30 W, 15 msec pulse width, 2 pulses/sec) treatments were done. The endpoint of each treatment was a uniform white-blanching of the lesion. Hamsters were sacrificed 1 week after the last treatment and cheek pouches were analyzed histologically. Results: Carcinoma was confirmed in 19 hamsters, and lesions that were initially < 2 mm were more effectively treated than lesions that were > 2 mm (P = .0004). Every lesion (10/10) that initially measured < 2 mm resolved completely after laser treatment with minimal scarring noted at the treatment site based on histology. Lesions measuring between 2 and 5 mm resolved 33% of the time (2/6), and none (0/3) of the lesions > 5 mm resolved after completion of the treatment period. Conclusions: Pulsed KTP laser photoangiolysis can effectively involute small malignant lesions, but may be less effective at involuting larger (> 2 mm) lesions. C1 [Burns, James A.; Lopez-Guerra, Gerardo; Kobler, James B.; Zeitels, Steven M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, Boston, MA 02114 USA. [Faquin, William] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil,Dept Pathol, Boston, MA 02114 USA. [LeClair, Matthew] Harvard Univ, Cambridge, MA 02138 USA. RP Burns, JA (reprint author), Harvard Univ, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM burns.james@mgh.harvard.edu OI Lopez-Guerra, Gerardo/0000-0003-0305-4680 NR 22 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2011 VL 121 IS 5 BP 942 EP 946 DI 10.1002/lary.21811 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 761JX UT WOS:000290395200009 PM 21495047 ER PT J AU Lee, LN Bhattacharyya, N AF Lee, Linda N. Bhattacharyya, Neil TI Regional and Specialty Variations in the Treatment of Chronic Rhinosinusitis SO LARYNGOSCOPE LA English DT Article DE Chronic rhinosinusitis; treatment; antibiotics; antihistamines; steroids ID CHRONIC SINUSITIS; MEDICAL THERAPY; UNITED-STATES; OUTCOMES; HEALTH; CARE; DIAGNOSIS; CULTURES; IMPACT AB Objectives/Hypothesis: To identify regional and specialty differences in the medical treatment of chronic rhinosinusitis (CRS). Study Design: Cross-sectional analysis of a national database. Methods: Ambulatory visits for CRS were extracted from the National Ambulatory Medical Care Survey (NAMCS) for years 2005 to 2006. Medication utilization associated with CRS (antibiotics, antihistamines, nasal steroids, and oral steroids) was tabulated for medication class and individual drug. Statistical analyses were conducted to determine variations in medication class and specific drug utilization by U.S. geographic region and physician specialty, specifically primary care physicians (PCP) versus otolaryngologists (ORL). Results: Among an estimated 36.2 +/- 0.3 million visits for CRS (mean age, 36.8 +/- 1.4 years; 60.1 +/- 1.9% female), the ratio of PCP to ORL visits was 10:1. The percent of clinician visits with prescriptions for antibiotics (47.3 +/- 3.0% of overall visits), nasal steroids (10.8 +/- 1.4%) and oral steroids (2.8 +/- 0.7%) did not vary significantly by geographic region (P = .79,.66, and.34, respectively). Antihistamines were prescribed significantly more often in the South (15.3 +/- 3.4% of visits vs. 11.3 +/- 1.8% nationally, P = .04). PCPs were significantly more likely to prescribe antibiotics compared to ORLs (53.3 +/- 2.9% vs. 27.4 +/- 4.2%, respectively, P < .001) and less likely to prescribe both nasal steroids (9.7 +/- 1.5% vs. 17.5 +/- 2.8%, P = .01) and oral steroids (2.3 +/- 0.7% vs. 6.6 +/- 2.0%, P = .01). Significant differences existed for specific drugs prescribed according to specialty. Conclusions: There are significant variations in the outpatient medical treatment of CRS according to geography and specialty. This study highlights the need for evidence-based medical treatment protocols for CRS. C1 [Bhattacharyya, Neil] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Otol & Laryngol,Div Otolaryngol, Boston, MA 02115 USA. [Lee, Linda N.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Bhattacharyya, N (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Otol & Laryngol,Div Otolaryngol, 45 Francis St, Boston, MA 02115 USA. EM neiloy@massmed.org NR 25 TC 18 Z9 18 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2011 VL 121 IS 5 BP 1092 EP 1097 DI 10.1002/lary.21550 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 761JX UT WOS:000290395200037 PM 21520129 ER PT J AU Lewis, RF Priesol, AJ Nicoucar, K Lim, K Merfeld, DM AF Lewis, Richard F. Priesol, Adrian J. Nicoucar, Keyvan Lim, Koeun Merfeld, Daniel M. TI Abnormal Motion Perception in Vestibular Migraine SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting on the Association-for-Research-in Otolaryngology CY FEB 06-10, 2010 CL Anaheim, CA SP Assoc Res Otolaryngol DE Vestibular; migraine; vertigo; psychophysics; thresholds C1 [Lewis, Richard F.; Priesol, Adrian J.; Nicoucar, Keyvan; Lim, Koeun; Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Lewis, Richard F.; Priesol, Adrian J.; Nicoucar, Keyvan; Lim, Koeun; Merfeld, Daniel M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lewis, Richard F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Nicoucar, Keyvan] Univ Hosp Geneva, Dept Clin Neurosci, Serv Otorhinolaryngol Head & Neck Surg, Geneva, Switzerland. RP Lewis, RF (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, 243 Charles St, Boston, MA 02114 USA. EM richard_lewis@meei.harvard.edu FU NIDCD NIH HHS [R01 DC004158, DC04158] NR 3 TC 20 Z9 20 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2011 VL 121 IS 5 BP 1124 EP 1125 DI 10.1002/lary.21723 PG 2 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 761JX UT WOS:000290395200043 PM 21520135 ER PT J AU Baer, MR George, SL Sanford, BL Mrozek, K Kolitz, JE Moore, JO Stone, RM Powell, BL Caligiuri, MA Bloomfield, CD Larson, RA AF Baer, M. R. George, S. L. Sanford, B. L. Mrozek, K. Kolitz, J. E. Moore, J. O. Stone, R. M. Powell, B. L. Caligiuri, M. A. Bloomfield, C. D. Larson, R. A. CA Canc Leukemia Group B TI Escalation of daunorubicin and addition of etoposide in the ADE regimen in acute myeloid leukemia patients aged 60 years and older: Cancer and Leukemia Group B Study 9720 SO LEUKEMIA LA English DT Article DE acute myeloid leukemia; age; daunorubicin; dose escalation; etoposide ID RISK MYELODYSPLASTIC SYNDROME; RESISTANCE MODULATOR PSC-833; ACUTE MYELOGENOUS LEUKEMIA; RANDOMIZED PHASE-III; ELDERLY-PATIENTS; MULTIDRUG-RESISTANCE; COMPLETE REMISSION; DOSE CYTARABINE; INDUCTION CHEMOTHERAPY; EUROPEAN ORGANIZATION AB Untreated de novo (n=421) and secondary (n=189) acute myeloid leukemia (AML) patients >= 60 years received intensified chemotherapy, including daunorubicin 60 mg/m(2) and etoposide 100 mg/m(2) during days 1, 2, 3 with cytarabine 100 mg/m(2) during days 1-7, with a second induction if needed and one consolidation course with these drugs and doses for 2, 2 and 5 days, respectively. In all, 287 (47%) achieved complete remission (CR), 136 (22%) died and 187 (31%) were non-responders. CR rates were 27, 44 and 52% for complex karyotypes, rare aberrations and neither (P<0.001), 52 and 37% for de novo and secondary AML (P=0.003), and 53 and 42% for age 60-69 and >= 70 years (P=0.015). In multivariable analysis, CR predictors included non-complex/non-rare karyo-types (P<0.001), de novo AML (P<0.001), better performance status (PS) (P<0.001) and younger age (P=0.001). Disease-free (DFS) and overall (OS) survival medians were 6.8 (95% CI: 6.2, 7.8) and 7.2 (95% CI: 6.4, 8.6) months. In multivariable analysis, DFS was shorter for complex karyotypes (P<0.001) and increasing white blood count (WBC) (P<0.001) and age (P=0.038), and OS for complex karyotypes (P<0.001), increasing WBC (P=0.001) and age (P<0.001), poorer PS (P<0.001) and secondary AML (P=0.010). Outcomes and prognostic factors were similar to those in previous Cancer and Leukemia Group B studies. Leukemia (2011) 25, 800-807; doi: 10.1038/leu.2011.9; published online 15 February 2011 C1 [Baer, M. R.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Baer, M. R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Baer, M. R.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [George, S. L.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. [George, S. L.; Sanford, B. L.] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. [Mrozek, K.; Caligiuri, M. A.; Bloomfield, C. D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Kolitz, J. E.] Hofstra N Shore LIJ Sch Med, Monter Canc Ctr, Div Hematol Oncol, Manhasset, NY USA. [Moore, J. O.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Stone, R. M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Powell, B. L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Larson, R. A.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Baer, MR (reprint author), Univ Maryland, Dept Med, 22 S Greene St, Baltimore, MD 21201 USA. EM mbaer@umm.edu RI Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU National Cancer Institute [CA31946, CA31983, CA02599, CA33601, CA77658, 101140, CA35279, CA47577, CA32291, CA03927, CA41287]; Coleman Leukemia Research Foundation FX The research for CALGB 9720 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman) and to the CALGB Statistical Center (Stephen George, PhD, CA33601), and by grants CA31983 and CA02599 (to MRB), CA33601 (to SLG and BLS), CA77658, 101140 and grants from the Coleman Leukemia Research Foundation (to KM, MAC, CDB), CA35279 (to JEK), CA47577 (to JOM), CA32291 (to RMS), CA03927 (to BLP) and CA41287 (to RAL). The authors thank the many patients, treating physicians, nurses and CALGB clinical research associates who participated in this study, and also thank CALGB Protocol Coordinator Michael Kelly for his assistance. NR 40 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2011 VL 25 IS 5 BP 800 EP 807 DI 10.1038/leu.2011.9 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 762IZ UT WOS:000290471100007 PM 21321569 ER PT J AU Kozora, E Brown, MS Filley, CM Zhang, L Miller, DE West, SG Pelzman, J Arciniegas, DB AF Kozora, E. Brown, M. S. Filley, C. M. Zhang, L. Miller, D. E. West, S. G. Pelzman, J. Arciniegas, D. B. TI Memory impairment associated with neurometabolic abnormalities of the hippocampus in patients with non-neuropsychiatric systemic lupus erythematosus SO LUPUS LA English DT Article DE hippocampal volume; lupus; memory function; neurometabolites ID MAGNETIC-RESONANCE-SPECTROSCOPY; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; NEUROPSYCHOLOGICAL BATTERY; H-1-MR SPECTROSCOPY; LEARNING-ABILITY; GLIAL-CELLS; ANTI-DNA; BRAIN; ATROPHY AB Objective: Memory impairment is common in patients with systemic lupus erythematosus (SLE). This study examined hippocampal volumes and neurometabolic alterations in relation to memory function in SLE patients without a history of neuropsychiatric syndromes (nonNPSLE). Methods: Subjects included 81 nonNPSLE patients and 34 healthy controls. Volumetric magnetic resonance imaging and magnetic resonance spectroscopy of the right and left hippocampal areas (RH, LH) were performed. Verbal and visual memory tests were administered and a Memory Impairment Index (MII) was derived from standardized tests. Results: Higher memory impairment (MII) was correlated with lower RH glutamate + glutamine/creatine (p = 0.009) and lower RH N-acetylaspartic acid/creatine (p = 0.012) in nonNPSLE patients. A trend for a negative correlation between RH and LH volumes and MII was evident for absolute hippocampal volumes. Lower RH glutamate + glutamine/creatine was also correlated with worse performance in a mean visual memory index (p = 0.017). Conclusions: An association between reduced memory and lower N-acetylaspartic acid/creatine in the RH suggests neuronal damage in nonNPSLE patients with very mild and early disease. Alterations in glutamate + glutamine/creatine further indicate early metabolic changes in nonNPSLE are related to memory impairment, a finding that might suggest that memory impairment relates to presynaptic glutamatergic dysfunction in the hippocampus. Lupus (2011) 20, 598-606. C1 [Kozora, E.; Zhang, L.; Pelzman, J.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Kozora, E.; Filley, C. M.; Arciniegas, D. B.] Univ Colorado, Denver Sch Med, Dept Neurol, Denver, CO 80202 USA. [Kozora, E.; Filley, C. M.; Arciniegas, D. B.] Univ Colorado, Denver Sch Med, Dept Psychiat, Denver, CO 80202 USA. [Brown, M. S.; Miller, D. E.] Univ Colorado, Denver Sch Med, Dept Radiol, Denver, CO 80202 USA. [West, S. G.] Univ Colorado, Denver Sch Med, Dept Rheumatol, Denver, CO 80202 USA. [Filley, C. M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kozora, E (reprint author), Natl Jewish Hlth, Dept Med, 1400 Jackson St, Denver, CO 80206 USA. EM kozorae@njhealth.org FU National Institute of Musculoskeletal and Skin Diseases [RO1 AR049152] FX This funding was supported by the National Institute of Musculoskeletal and Skin Diseases (grant number RO1 AR049152). NR 52 TC 16 Z9 18 U1 2 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PD MAY PY 2011 VL 20 IS 6 BP 598 EP 606 DI 10.1177/0961203310392425 PG 9 WC Rheumatology SC Rheumatology GA 761DX UT WOS:000290376600007 PM 21335397 ER PT J AU Filippova, N Yang, XH Wang, YM Gillespie, GY Langford, C King, PH Wheeler, C Nabors, LB AF Filippova, Natalia Yang, Xiuhua Wang, Yimin Gillespie, G. Yancey Langford, Cathy King, Peter H. Wheeler, Crystal Nabors, L. Burt TI The RNA-Binding Protein HuR Promotes Glioma Growth and Treatment Resistance SO MOLECULAR CANCER RESEARCH LA English DT Article ID INCREASED CYCLOOXYGENASE-2 EXPRESSION; TUMOR-NECROSIS-FACTOR; MESSENGER-RNA; POSTTRANSCRIPTIONAL REGULATION; STABILITY FACTOR; XENOGRAFT MODEL; BREAST-CANCER; RICH ELEMENTS; CARCINOMA; CELLS AB Posttranscriptional regulation is a critical control point for the expression of genes that promote or retard tumor growth. We previously found that the mRNA-binding protein, ELAV 1 (HuR), is upregulated in primary brain tumors and stabilizes growth factor mRNAs such as VEGF and IL-8. To better understand the role of HuR in brain tumor growth, we altered levels of HuR in glioma cells by short hairpin RNA or ectopic expression and measured tumor cell phenotype using in vitro and in vivo models. In HuR-silenced cells, we found a significant decrease in anchorage-independent growth and cell proliferation with a concomitant induction of apoptosis. Using an intracranial tumor model with primary glioblastoma cells, HuR silencing produced a significant decrease in tumor volume. In contrast, overexpression of HuR produced in vitro chemoresistance to standard glioma therapies. Because bcl-2 is abundantly expressed in glioma and associated with tumor growth and survival, we determined the impact of HuR on its regulation as a molecular validation to the cellular and animal studies. Using UV cross-linking and RNA immunoprecipitation, we show that HuR bound to the 3'-untranslated region of all bcl-2 family members. Silencing of HuR led to transcript destabilization and reduced protein expression. Polysome profiling indicated loss of HuR from the translational apparatus. In summary, these findings reveal a HuR-dependent mechanism for cancer cell survival and sensitivity to chemotherapeutic drugs suggesting that HuR should be considered as a new therapeutic target. Mol Cancer Res; 9(5); 648-59. (C) 2011 AACR. C1 [Nabors, L. Burt] Univ Alabama, Dept Neurol, Neurooncol Program, Birmingham, AL 35294 USA. [Gillespie, G. Yancey; Langford, Cathy] Univ Alabama, Dept Surg, Div Neurosurg, Birmingham, AL 35294 USA. [Wang, Yimin] So Res Inst, Div Drug Discovery, Birmingham, AL 35255 USA. [King, Peter H.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Nabors, LB (reprint author), Univ Alabama, Dept Neurol, Neurooncol Program, 510 20th St S,FOT 1020, Birmingham, AL 35294 USA. EM bnabors@uab.edu FU NCI [R01 CA112397]; VA Merit Review; UAB Small Animal Imaging Shared Facility [P30CA013148] FX This study was supported by NCI R01 CA112397 (L. B. Nabors), VA Merit Review (P. H. King), and by UAB Small Animal Imaging Shared Facility (P30CA013148). NR 33 TC 43 Z9 45 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAY PY 2011 VL 9 IS 5 BP 648 EP 659 DI 10.1158/1541-7786.MCR-10-0325 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 764EF UT WOS:000290610600012 PM 21498545 ER PT J AU Hawes, MJ Grove, AS Hink, EM AF Hawes, Michael J. Grove, Arthur S., Jr. Hink, Eric M. TI Comparison of Free Tarsoconjunctival Grafts and Hughes Tarsoconjunctival Grafts for Lower Eyelid Reconstruction SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 113th Annual Meeting of the American-Academy-of-Ophthalmology/28th Congress of the Pan-American-Association-of-Ophthalmology CY OCT 24-27, 2009 CL San Francisco, CA SP Amer Acad Ophthalmol, Pan Amer Assoc Ophthalmol ID FLAP; DIVISION; MANAGEMENT; PEDICLE; HEIGHT AB Purpose: To review the use of free autogenous tarsoconjunctival (TC) grafts and Hughes TC flaps in the practice of one of the authors (MJH) and compare complications and outcomes and develop a rationale for the selection of surgical technique. Methods: Retrospective comparative case series of 70 patients who underwent reconstructive surgery for a major full-thickness lower eyelid defect using a free autogenous TC graft or Hughes TC pedicle flap by one of the authors (MJH). Rates of complications, including erythema of the eyelid margin, eyelid position abnormalities, and need for additional surgeries, were reviewed. Results: During a 15-year period, 70 patients with full-thickness lower eyelid defects were treated with autogenous TC grafts and flaps. The average age of the patients receiving a free TC graft was younger than the average age of patients receiving a Hughes TC graft (63 versus 73 years, p < 0.001). Patients with a free TC graft were more likely to have a smaller eyelid defect than the patients receiving a Hughes TC graft (52% versus 72%, p < 0.001). Patients receiving a free TC graft were less likely to require surgery to repair eyelid margin erythema than those in receiving a Hughes TC flap (one patient [2%] versus 5 patients [19%], respectively [odds ratio = 0.10, confidence interval = 0.01 to 0.95]). The average follow up was 22 months. Conclusions: Free TC flaps associated with mycocutaneous advancement flaps are less likely to lead to complications of eyelid margin erythema and subsequent revision surgery than Hughes TC flaps with full-thickness skin grafts. (Ophthal Plast Reconstr Surg 2011;27:219-223) C1 [Grove, Arthur S., Jr.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hink, Eric M.] Univ Colorado, Dept Ophthalmol, Denver, CO 80202 USA. RP Hawes, MJ (reprint author), 850 E Harvard Ave 345, Denver, CO 80210 USA. EM mjhawes1@mac.com NR 35 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAY-JUN PY 2011 VL 27 IS 3 BP 219 EP 223 DI 10.1097/IOP.0b013e318217e194 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 762XH UT WOS:000290515000035 PM 21562393 ER PT J AU Shalaby, A Atwood, CW Selzer, F Suffoletto, M Gorcsan, J Strollo, P AF Shalaby, Alaa Atwood, Charles W. Selzer, Faith Suffoletto, Matthew Gorcsan, John, III Strollo, Patrick TI Cardiac Resynchronization Therapy and Obstructive Sleep-Related Breathing Disorder in Patients with Congestive Heart Failure SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE congestive heart failure; CRT; pacing ID POSITIVE AIRWAY PRESSURE; CHEYNE-STOKES RESPIRATION; RESYNCHRONISATION THERAPY; VENTRICULAR DYSSYNCHRONY; RATE-VARIABILITY; APNEA; TRIAL; DYSFUNCTION; IMPROVEMENT; PREDICTORS AB Introduction: CRT may have a positive influence on SRBD in patients who qualify for the therapy. Data are inconclusive in patients with obstructive SRBD. Methods: Consenting patients eligible for CRT underwent a baseline polysomnography (PSG) 2 weeks after implantation during which pacing was withheld. Patients with an apnea hypopnea index (AHI) >= 15 but < 50 were enrolled and randomized to atrial overdrive pacing (DDD) versus atrial synchronous pacing (VDD) with biventricular pacing in both arms. Patients underwent two further PSGs 12 weeks apart. Results: Nineteen men with New York Heart Association class III congestive heart failure participated in the study (age 67.2 +/- 7.5, Caucasian 78.9%, ischemic 73.7%). The score on Epworth Sleepiness Score was 7.3 +/- 4.0, Pittsburgh Sleep Quality Index 7.4 +/- 3.1, and Minnesota Living with Heart Failure Questionnaire 36.9 +/- 21.9. There were no differences between the groups. At baseline, patients exhibited poor sleep efficiency (65.3 +/- 16.6%) with nadir oxygen saturation of 83.5 +/- 5.3% and moderate to severe SRBD (AHI 21.5 +/- 15.3) that was mainly obstructive (central apnea index 3.3 +/- 6.7/hour). On both follow-up assessments, there was no improvement in indices of SRBD (sleep efficiency [68.3 +/- 17.9%], nadir oxygen saturation of 82.8 +/- 4.6%, and AHI 24.9 +/- 21.9). Conclusion: In a cohort of elderly male CHF patients receiving CRT, CRT had no impact on obstructive SRBD burden with or without atrial overdrive pacing. (PACE 2011; 34:593-603). C1 [Shalaby, Alaa; Atwood, Charles W.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Shalaby, Alaa; Suffoletto, Matthew; Gorcsan, John, III] Univ Pittsburgh, Med Ctr, Div Cardiol, Pittsburgh, PA USA. [Atwood, Charles W.; Strollo, Patrick] Univ Pittsburgh, Grad Sch Publ Hlth, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Selzer, Faith] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. RP Shalaby, A (reprint author), 111C Univ Dr, Pittsburgh, PA 15240 USA. EM Alaa.Shalaby@va.gov FU Boston Scientific, Inc. Cardiac Rhythm Management Division; Boston Scientific FX This study was supported by Boston Scientific, Inc. Cardiac Rhythm Management Division.; Alaa Shalaby: Research support from Boston Scientific. NR 41 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAY PY 2011 VL 34 IS 5 BP 593 EP 603 DI 10.1111/j.1540-8159.2010.03015.x PG 11 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 762CK UT WOS:000290449700014 PM 21609340 ER PT J AU Naeser, MA Saltmarche, A Krengel, MH Hamblin, MR Knight, JA AF Naeser, Margaret A. Saltmarche, Anita Krengel, Maxine H. Hamblin, Michael R. Knight, Jeffrey A. TI Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumatic Brain Injury: Two Case Reports SO PHOTOMEDICINE AND LASER SURGERY LA English DT Article ID LEVEL LASER THERAPY; TERM NEUROLOGICAL DEFICITS; ANTERIOR CINGULATE CORTEX; NEAR-INFRARED LIGHT; SUSTAINED ATTENTION; ISCHEMIC-STROKE; WORKING-MEMORY; UNITED-STATES; RAT-BRAIN; IRRADIATION AB Objective: Two chronic, traumatic brain injury (TBI) cases, where cognition improved following treatment with red and near-infrared light-emitting diodes (LEDs), applied transcranially to forehead and scalp areas, are presented. Background: Significant benefits have been reported following application of transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice with acute TBI. These are the first case reports documenting improved cognitive function in chronic, TBI patients treated with transcranial LED. Methods: Treatments were applied bilaterally and to midline sagittal areas using LED cluster heads [2.1 '' diameter, 61 diodes (9 x 633 nm, 52 x 870 nm); 12-15 mW per diode; total power: 500 mW; 22.2 mW/cm(2); 13.3 J/cm(2) at scalp (estimated 0.4 J/cm(2) to cortex)]. Results: Seven years after closed-head TBI from a motor vehicle accident, Patient 1 began transcranial LED treatments. Pre-LED, her ability for sustained attention (computer work) lasted 20 min. After eight weekly LED treatments, her sustained attention time increased to 3 h. The patient performs nightly home treatments (5 years); if she stops treating for more than 2 weeks, she regresses. Patient 2 had a history of closed-head trauma (sports/military, and recent fall), and magnetic resonance imaging showed frontoparietal atrophy. Pre-LED, she was on medical disability for 5 months. After 4 months of nightly LED treatments at home, medical disability discontinued; she returned to working full-time as an executive consultant with an international technology consulting firm. Neuropsychological testing after 9 months of transcranial LED indicated significant improvement (+1, +2SD) in executive function (inhibition, inhibition accuracy) and memory, as well as reduction in post-traumatic stress disorder. If she stops treating for more than 1 week, she regresses. At the time of this report, both patients are continuing treatment. Conclusions: Transcranial LED may improve cognition, reduce costs in TBI treatment, and be applied at home. Controlled studies are warranted. C1 [Naeser, Margaret A.; Knight, Jeffrey A.] VA Boston Healthcare Syst, Natl Ctr, PTSD Behav Sci Div, Boston, MA 02130 USA. [Naeser, Margaret A.; Krengel, Maxine H.; Knight, Jeffrey A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Saltmarche, Anita] MedX Hlth Inc, Mississauga, ON, Canada. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Naeser, MA (reprint author), VA Boston Healthcare Syst, Natl Ctr, PTSD Behav Sci Div, 12-A,150 So Huntington Ave, Boston, MA 02130 USA. EM mnaeser@bu.edu OI Krengel, Maxine/0000-0001-7632-590X; Hamblin, Michael/0000-0001-6431-4605 FU Department of Veterans Affairs; NIH [RO1AI050875]; US Air Force [FA9550-04-1-0079]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; Congressionally Directed Medical Research Program [W81XWH-09-1-0514] FX The authors thank Charles Foltz for the graphics art in Figure 5; Carole Palumbo, Ph.D. for assistance with MRI analysis; Paula Martin, Anna Kharaz, Michael Ho, Ph.D., and Ethan Treglia, M. S., for manuscript assistance; and Michael and Winter Robinson for photography. M. Naeser was supported by Merit Review Funding, Department of Veterans Affairs. M. Hamblin was supported by the NIH (grant RO1AI050875), US Air Force MFEL program (contract FA9550-04-1-0079), Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), and Congressionally Directed Medical Research Program (W81XWH-09-1-0514). NR 56 TC 57 Z9 59 U1 3 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-5418 J9 PHOTOMED LASER SURG JI Photomed. Laser Surg. PD MAY PY 2011 VL 29 IS 5 BP 351 EP 358 DI 10.1089/pho.2010.2814 PG 8 WC Surgery SC Surgery GA 762JC UT WOS:000290471400009 PM 21182447 ER PT J AU Schlett, CL Hoffmann, U AF Schlett, C. L. Hoffmann, U. TI Identification and quantification of fat compartments with CT and MRI and their importance SO RADIOLOGE LA German DT Article DE Visceral fat; Subcutaneous adipose tissue; Pericardial adipose tissue; Perivascular adipose tissue; Atherosclerosis ID SUBCUTANEOUS ADIPOSE-TISSUE; VISCERAL ABDOMINAL FAT; PERICARDIAL FAT; CORONARY ATHEROSCLEROSIS; COMPUTED-TOMOGRAPHY; RISK-FACTORS; ASSOCIATION; DISEASE; OBESITY; CALCIFICATION AB In addition to being overweight, as defined by the BMI, the distribution, composition and biological activity of adipose tissue are key elements in the cardiovascular risk stratification of patients. Several non-invasive techniques have been developed to quantify local fat depots, whereby computed tomography (CT) and magnetic resonance imaging (MRI) are the most important. In general adipose tissue is subdivided into subcutaneous and visceral compartments and although both are associated with cardiovascular risk factors and disease, visceral fat has on average a stronger association and a clearly higher biological activity independent of traditional risk factors. This maybe explained by the higher endocrine activity and secretion of pro-inflammatory cytokines by visceral fat. Especially pericardial adipose tissue, a local visceral fat depot surrounding the coronary arteries, is associated with the presence, extent and severity of coronary artery disease. However, several other local fat depots have been identified and associations with various diseases have been established. This article gives an overview over the current methods for the identification and quantification of local fat depots and summarizes the hypothesized and known associations. Furthermore, it gives an overview of the potential significance of individual local fat depots for cardiovascular risk stratification. C1 [Schlett, C. L.; Hoffmann, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Schlett, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM cschlett@partners.org NR 29 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-832X EI 1432-2102 J9 RADIOLOGE JI Radiologe PD MAY PY 2011 VL 51 IS 5 BP 372 EP 378 DI 10.1007/s00117-010-2088-4 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 762OX UT WOS:000290490400007 PM 21487800 ER PT J AU Manzano-Fernandez, S Januzzi, JL Garcia, MB Bonaque-Gonzalez, JC Munoz-Esparza, C Albaladejo-Oton, MD Pastor-Perez, FJ Pastor, P Valdes, M Pascual-Figal, DA AF Manzano-Fernandez, Sergio Januzzi, James L. Boronat Garcia, Miguel Bonaque-Gonzalez, Juan C. Munoz-Esparza, Carmen Albaladejo-Oton, Maria D. Pastor-Perez, Francisco J. Pastor, Patricia Valdes, Mariano Pascual-Figal, Domingo A. TI Comparative Prognostic Value of Plasma and Urinary N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Acute Destabilized Heart Failure SO REVISTA ESPANOLA DE CARDIOLOGIA LA English DT Article DE Heart failure; Natriuretic peptide; Prognosis ID DIAGNOSIS; MANAGEMENT; SERUM AB Introduction and objectives: Urinary concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP) may be prognostically meaningful; however, direct comparison to plasma concentrations of this marker have not been performed in patients with acutely decompensated heart failure (ADHF). The aims of this study were to compare the prognostic value of plasma versus urinary NT-proBNP concentration for the risk stratification of patients with ADHF. Methods: Consecutive hospitalized patients with ADHF were prospectively studied. Blood and urine samples were simultaneously collected on hospital arrival to determine NT-proBNP concentrations. Clinical follow-up was obtained, and the occurrence of mortality and heart failure hospitalization was registered. Results: The study included 138 patients (median, 74 years [interquartile range, 67-80]; 54% men). During amedian follow-up period of 387 days [interquartile range, 161-559], 65 patients (47%) suffered adverse clinical events. Plasma NT-proBNP concentration was higher among patients who presented adverse events (4561 pg/mL [2191-8631] vs 2906 pg/mL [1643-5823]; P = .03), whereas urinary NT-proBNP was similar in both groups (P = .62). After multivariable Cox regression analyses, plasma NT-proBNP concentration was associated with a higher risk of adverse events, whether considered continuously (per 100 pg/mL; hazard ratio [HR] = 1.004; 95% confidence interval [CI], 1.001-1.007; P = .003) or categorically (>= 3345 pg/mL; HR = 2.35; 95% CI, 1.41-3.93; P =.001). In contrast, urinary NTproBNP concentration was not associated with adverse outcomes. Conclusions: Plasma NT-proBNP concentration is superior to urinary NT-proBNP concentration for the prediction of adverse clinical outcomes among unselected patients with ADHF. (C) 2010 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S. L. All rights reserved. C1 [Manzano-Fernandez, Sergio; Bonaque-Gonzalez, Juan C.; Munoz-Esparza, Carmen; Pastor-Perez, Francisco J.; Valdes, Mariano; Pascual-Figal, Domingo A.] Hosp Univ Virgen de la Arrixaca, Dept Cardiol, Murcia 30120, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Boronat Garcia, Miguel; Albaladejo-Oton, Maria D.] Hosp Univ Virgen de la Arrixaca, Dept Bioquim, Murcia 30120, Spain. [Pastor, Patricia] Hosp Univ Virgen de la Arrixaca, Dept Cirugia Gen, Murcia 30120, Spain. RP Manzano-Fernandez, S (reprint author), Hosp Univ Virgen de la Arrixaca, Dept Cardiol, Ctra Madrid Cartagena S-N, Murcia 30120, Spain. EM sergiosmf13@hotmail.com RI Pascual Figal, Domingo /B-3794-2008 OI Pascual Figal, Domingo /0000-0002-4993-9540 FU Roche Diagnostics; Siemens; Critical Diagnostics FX Dr. Januzzi reports receiving grant support from Roche Diagnostics, Siemens, and Critical Diagnostics. Dr. Pascual-Figal reports receiving grant support from Roche Diagnostics. No other potential conflicts of interest exist. NR 17 TC 4 Z9 4 U1 0 U2 2 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD MAY PY 2011 VL 64 IS 5 BP 365 EP 372 DI 10.1016/j.rec.2010.10.018 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 763MJ UT WOS:000290561400004 PM 21397374 ER PT J AU Spiegel, BMR Talley, J Shekelle, P Agarwal, N Snyder, B Bolus, R Kurzbard, N Chan, M Ho, A Kaneshiro, M Cordasco, K Cohen, H AF Spiegel, Brennan M. R. Talley, Jennifer Shekelle, Paul Agarwal, Nikhil Snyder, Bradley Bolus, Roger Kurzbard, Nicole Chan, Michael Ho, Andrew Kaneshiro, Marc Cordasco, Kristina Cohen, Hartley TI Development and Validation of a Novel Patient Educational Booklet to Enhance Colonoscopy Preparation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID BOWEL PREPARATION; COLORECTAL-CANCER; PREPARATION QUALITY; IMPACT; ENDOSCOPY; VETERANS; SCALE; COST AB OBJECTIVES: The success of colonoscopy depends on high-quality bowel preparation by patients; yet inadequate preparation is common. We developed and tested an educational booklet to improve bowel preparation quality. METHODS: We conducted patient cognitive interviews to identify knowledge and belief barriers to colonoscopy preparation. We used these interviews to create an educational booklet to enhance preparatory behaviors. We then prospectively randomized patients scheduled for outpatient colonoscopy at a VA Medical Center to receive usual instructions vs. the booklet before colonoscopy. Patients in both groups received standard pharmacy instructions for single-dose bowel preparation; the protocol did not specify which purgatives to prescribe. The primary outcome was preparation quality based on blinded ratings using the validated Ottawa score. We performed bivariate analyses to compare mean scores between groups using a t-test, and logistic regression to measure the booklet effect on preparation quality, adjusting for potential confounders. RESULTS: A total of 436 patients were randomized between arms. In an intention-to-treat analysis of the primary outcome, mean Ottawa scores were superior in patients allocated to booklet vs. controls (P = 0.03). An intention-to-treat analysis of the secondary outcome revealed a "good" preparation in 68 vs. 46% of booklet and control patients, respectively (P = 0.054). In a per-protocol analysis limited to patients who actually received the booklet, preparation was good in 76 vs. 46% patients, respectively (P < 0.00001). Regression analysis revealed that booklet receipt increased the odds of good preparation by 3.7 times (95% confi dence interval = 2.3-5.8). CONCLUSIONS: Provision of a novel educational booklet considerably improves preparation quality in patients receiving single-dose purgatives. The effect of the booklet on split-dose purgatives remains untested and will be evaluated in future research. C1 [Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, UCLA VA Ctr Outcomes Res & Educ CORE,Dept Med, Los Angeles, CA 90073 USA. [Spiegel, Brennan M. R.; Snyder, Bradley; Bolus, Roger; Kurzbard, Nicole; Chan, Michael; Cohen, Hartley] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90073 USA. CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, UCLA VA Ctr Outcomes Res & Educ CORE,Dept Med, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Veteran's Affairs Health Services Research and Development (HSRD) [RCD 03-179-2]; Veterans Affairs [IIR 08-310] FX This research was supported by a Veteran's Affairs Health Services Research and Development (HSR&D) Career Development Transition Award (RCD 03-179-2) and by a Veterans Affairs Merit Award (IIR 08-310) to Dr Spiegel. NR 24 TC 54 Z9 57 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2011 VL 106 IS 5 BP 875 EP 883 DI 10.1038/ajg.2011.75 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 759MP UT WOS:000290250100010 PM 21483463 ER PT J AU Fontana, RJ Sanyal, AJ Ghany, MG Bonkovsky, HL Morgan, TR Litman, HJ Reid, AE Lee, WM Naishadham, D AF Fontana, Robert J. Sanyal, Arun J. Ghany, Marc G. Bonkovsky, Herbert L. Morgan, Timothy R. Litman, Heather J. Reid, Andrea E. Lee, William M. Naishadham, Deepa CA HALT-C Trial Study Grp TI Development and Progression of Portal Hypertensive Gastropathy in Patients With Chronic Hepatitis C SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID VENOUS-PRESSURE GRADIENT; VIRUS-RELATED CIRRHOSIS; NATURAL-HISTORY; ADVANCED FIBROSIS; LIVER-CIRRHOSIS; THERAPY; PREVALENCE; INFECTION; TRIAL AB OBJECTIVES: The objective of this study was to determine the incidence and risk factors associated with new-onset and worsening portal hypertensive gastropathy (PHG) in patients with chronic hepatitis C (CHC). METHODS: A total of 831 CHC patients with bridging fibrosis or cirrhosis at the time of entry were prospectively monitored for clinical and histological liver disease progression while receiving either low-dose peginterferon alpha 2a or no antiviral therapy in the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. Upper endoscopy with grading of PHG was performed at baseline and at year 4 of the study. The presence and severity of PHG were determined using the NIEC (New Italian Endoscopy Conference) criteria, and worsening PHG was defined as a score increase of >= 1 point. RESULTS: During a median follow-up of 3.85 years, 50 % of 514 subjects without PHG developed new-onset PHG, whereas 26% of 317 patients with baseline PHG had worsening PHG. Independent predictors of new-onset PHG included higher alkaline phosphatase and being diabetic, whereas predictors of worsening PHG were Caucasian race, lower albumin, as well as higher serum aspartate transaminase/alanine transaminase ratio and homeostatic model assessment levels. New-onset and worsening PHG were significantly associated with clinical and histological progression. They were also associated with new-onset and worsening gastroesophageal varices. CONCLUSIONS: New-onset and worsening PHG develop at a rate of 12.9% per year and 6.7% per year, respectively, in non-responder CHC patients with advanced fibrosis. If confirmed in other studies, endoscopic surveillance for PHG may need to be tailored to individual patient risk factors. C1 [Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol,Taubman Ctr 3912, Ann Arbor, MI 48109 USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Med Ctr, Dept Internal Med, Div Gastroenterol, Richmond, VA USA. [Ghany, Marc G.] NIDDKD, US Dept HHS, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Dept Internal Med, Charlotte, NC 28203 USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Dept Internal Med, Long Beach, CA USA. [Litman, Heather J.; Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA. [Reid, Andrea E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. RP Fontana, RJ (reprint author), Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol,Taubman Ctr 3912, Ann Arbor, MI 48109 USA. EM rfontana@med.umich.edu FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; New England Research Institutes, Watertown, MA [N01-DK-9-2328]; National Center for Research Resources, National Institutes of Health; University of Massachusetts Medical Center, Worcester, MA [N01-DK-9-2326]; University of Connecticut Health Center, Farmington, CT [M01RR-06192]; Saint Louis University School of Medicine, St Louis, MO [N01-DK-9-2324]; Massachusetts General Hospital, Boston, MA [N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; Harvard Clinical and Translational Science Center; University of Colorado Denver, School of Medicine, Aurora, CO [N01-DK-9-2327, M01RR-00051, 1 UL1 RR 025780-01]; University of California-Irvine, Irvine, CA [N01-DK-9-2320, M01RR-00827]; University of Texas Southwestern Medical Center, Dallas, TX [N01-DK-9-2321, M01RR-00633, 1 UL1 RR024982-01]; North and Central Texas Clinical and Translational Science Initiative); University of Michigan Medical Center, Ann Arbor, MI [RR024986]; Michigan Center for Clinical and Health Research; Virginia Commonwealth University Health System, Richmond, VA [N01-DK-9-2322, M01RR-00065]; Liver Diseases Branch; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD; University of Washington, Seattle, WA [N01-DK-9-2318]; Armed Forces Institute of Pathology, Washington, DC FX This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities, and Minjun Chung Apodaca, BS, ASCP, Rohit Shankar, BC, ASCP, Natalia Antonov, MEd; New England Research Institutes, Watertown, MA (contract N01-DK-9-2328): Kristin K. Snow, MSc, ScD, Anne M. Stoddard, ScD, Linda Massey; Armed Forces Institute of Pathology, Washington, DC: Zachary D. Goodman, MD, PhD, Fanny Monge, Michelle Parks; Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, MD, Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD, Robert P. Perrillo, MD. by the General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). Additional funding to conduct this study was supplied by Hoffmann-La Roche through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. In addition to the authors of this manuscript, the following individuals were instrumental in the planning, conduct, and/or care of patients enrolled in this study at each of the participating institutions as follows: University of Massachusetts Medical Center, Worcester, MA (contract N01-DK-9-2326): Gyongyi Szabo, MD, Barbara F. Banner, MD, Maureen Cormier, RN, Donna Giansiracusa, RN; University of Connecticut Health Center, Farmington, CT (Grant no, M01RR-06192): Gloria Borders, RN, Michelle Kelley, RN, ANP; Saint Louis University School of Medicine, St Louis, MO (contract N01-DK-9-2324): Adrian M. Di Bisceglie, MD, Bruce Bacon, MD, Brent Neuschwander-Tetri, MD, Elizabeth M. Brunt, MD, Debra King, RN; Massachusetts General Hospital, Boston, MA (contract N01-DK-9-2319, Grant no. M01RR-01066; Grant no. 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center): Jules L. Dienstag, MD, Raymond T. Chung, MD, Atul K. Bhan, MD, Wallis A. Molchen, David P. Lundmark; University of Colorado Denver, School of Medicine, Aurora, CO (contract N01-DK-9-2327, Grant no. M01RR-00051, Grant no. 1 UL1 RR 025780-01): Gregory T. Everson, MD, Thomas Trouillot, MD, Marcelo Kugelmas, MD, S. Russell Nash, MD, Jennifer DeSanto, RN, Carol McKinley, RN; University of California-Irvine, Irvine, CA (contract N01-DK-9-2320, Grant no. M01RR-00827): John C. Hoefs, MD, John R. Craig, MD, M. Mazen Jamal, MD, MPH, Muhammad Sheikh, MD, Choon Park, RN; University of Texas Southwestern Medical Center, Dallas, TX (contract N01-DK-9-2321, Grant no. M01RR-00633, Grant no. 1 UL1 RR024982-01, North and Central Texas Clinical and Translational Science Initiative): Thomas E. Rogers, MD, Peter F. Malet, MD, Janel Shelton, Nicole Crowder, LVN, Rivka Elbein, RN, BSN, Nancy Liston, MPH; University of Southern California, Los Angeles, CA (contract N01-DK-9-2325, Grant no. M01RR-00043): Karen L. Lindsay, MD, MMM, Sugantha Govindarajan, MD, Carol B. Jones, RN, Susan L. Milstein, RN; University of Michigan Medical Center, Ann Arbor, MI (contract N01-DK-9-2323, Grant no. M01RR-00042, Grant no. 1 UL1 RR024986, Michigan Center for Clinical and Health Research): Anna S. Lok, MD, Joel K. Greenson, MD, Pamela A. Richtmyer, LPN, CCRC, R. Tess Bonham, BS; Virginia Commonwealth University Health System, Richmond, VA (contract N01-DK-9-2322, Grant no. M01RR-00065): Mitchell L.; Shiffman, MD, RichardK. Sterling, MD, MSc, Melissa J. Contos, MD, A. Scott Mills, MD, Charlotte Hofmann, RN, Paula Smith, RN; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD: T. Jake Liang, MD, David Kleiner, MD, PhD, Yoon Park, RN, Elenita Rivera, RN, Vanessa Haynes-Williams, RN; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD: James E. Everhart, MD, Leonard B. Seeff, MD, Patricia R. Robuck, PhD, Jay H. Hoofnagle, MD, Elizabeth C. Wright, PhD; University of Washington, Seattle, WA (contract N01-DK-9-2318): Chihiro Morishima, MD, David R. Gretch, MD, PhD, Minjun Chung Apodaca, BS, ASCP, Rohit Shankar, BC, ASCP, Natalia Antonov, MEd; New England Research Institutes, Watertown, MA (contract N01-DK-9-2328): Kristin K. Snow, MSc, ScD, Anne M. Stoddard, ScD, Linda Massey; Armed Forces Institute of Pathology, Washington, DC: Zachary D. Goodman, MD, PhD, Fanny Monge, Michelle Parks; Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, MD, Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD, Robert P. Perrillo, MD. NR 27 TC 2 Z9 2 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2011 VL 106 IS 5 BP 884 EP 893 DI 10.1038/ajg.2010.456 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 759MP UT WOS:000290250100011 PM 21139575 ER PT J AU Powe, CE Ecker, J Rana, S Wang, A Ankers, E Ye, J Levine, RJ Karumanchi, A Thadhani, R AF Powe, Camille E. Ecker, Jeffrey Rana, Sarosh Wang, Alice Ankers, Elizabeth Ye, Jun Levine, Richard J. Karumanchi, Ananth Thadhani, Ravi TI Preeclampsia and the risk of large-for-gestational-age infants SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE fetal growth; gestational diabetes; large for gestational age; preeclampsia ID HEALTHY NULLIPAROUS WOMEN; FETAL GROWTH-RETARDATION; GLUCOSE-TOLERANCE; BIRTH-WEIGHT; PREGNANCY; OBESITY; CYTOTROPHOBLASTS; HYPERGLYCEMIA; HYPERTENSION; OUTCOMES AB OBJECTIVE: We sought to compare the risk of giving birth to large-for-gestational-age (LGA) infants in women with and without preeclampsia, after adjustment for obesity and glucose intolerance. STUDY DESIGN: We conducted secondary analysis of a prospective database of pregnant women with and without preeclampsia who delivered infants from 1998 through 2006 at Massachusetts General Hospital (n = 17,465). RESULTS: The risk of LGA was similar in women with and without preeclampsia (odds ratio, 0.81; 95% confidence interval, 0.59-1.14). After adjustment for body mass index, glucose intolerance, and other factors, the risk of LGA was significantly lower in women with preeclampsia compared to those without preeclampsia (odds ratio, 0.69; 95% confidence interval, 0.49-0.96). Stratified analysis in groups with a higher risk of LGA revealed that preeclampsia has a similar effect on the risk of LGA regardless of maternal obesity, glucose intolerance, parity, and race. CONCLUSION: Preeclampsia appears to be characterized by reduced, and not increased, fetal growth. C1 [Powe, Camille E.; Ankers, Elizabeth; Ye, Jun; Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. [Ecker, Jeffrey] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Rana, Sarosh; Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Dept Obstet Gynecol, Boston, MA USA. [Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. [Wang, Alice] Boston Univ, Med Ctr, Dept Pediat, Boston, MA USA. [Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, Dept Med, 55 Fruit St,Bullfinch 127, Boston, MA 02114 USA. EM rthadhani@partners.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Ms Powe is a Howard Hughes Medical Institute Medical Research Training Fellow. Dr Levine receives salary support from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr Karumanchi is an investigator of the Howard Hughes Medical Institute. NR 34 TC 2 Z9 2 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2011 VL 204 IS 5 AR 425.e1 DI 10.1016/j.ajog.2010.12.030 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 758YZ UT WOS:000290206200033 PM 21371687 ER PT J AU Harston, RK McKillop, JC Moschella, PC Van Laer, A Quinones, LS Baicu, CF Balasubramanian, S Zile, MR Kuppuswamy, D AF Harston, Rebecca K. McKillop, John C. Moschella, Phillip C. Van Laer, An Quinones, Lakeya S. Baicu, Catalin F. Balasubramanian, Sundaravadivel Zile, Michael R. Kuppuswamy, Dhandapani TI Rapamycin treatment augments both protein ubiquitination and Akt activation in pressure-overloaded rat myocardium SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE hypertrophy; mammalian target of rapamycin; signal transduction; cell survival ID NF-KAPPA-B; CARDIAC-HYPERTROPHY; IN-VIVO; VENTRICULAR HYPERTROPHY; LIFE-SPAN; MTOR; MICE; PROTEASOME; PATHWAY; GROWTH AB Harston RK, McKillop JC, Moschella PC, Van Laer A, Quinones LS, Baicu CF, Balasubramanian S, Zile MR, Kuppuswamy D. Rapamycin treatment augments both protein ubiquitination and Akt activation in pressure-overloaded rat myocardium. Am J Physiol Heart Circ Physiol 300: H1696-H1706, 2011. First published February 25, 2011; doi:10.1152/ajpheart.00545.2010.-Ubiquitin-mediated protein degradation is necessary for both increased ventricular mass and survival signaling for compensated hypertrophy in pressure-overloaded (PO) myocardium. Another molecular keystone involved in the hypertrophic growth process is the mammalian target of rapamycin (mTOR), which forms two distinct functional complexes: mTORC1 that activates p70S6 kinase-1 to enhance protein synthesis and mTORC2 that activates Akt to promote cell survival. Independent studies in animal models show that rapamycin treatment that alters mTOR complexes also reduces hypertrophic growth and increases lifespan by an unknown mechanism. We tested whether the ubiquitin-mediated regulation of growth and survival in hypertrophic myocardium is linked to the mTOR pathway. For in vivo studies, right ventricle PO in rats was conducted by pulmonary artery banding; the normally loaded left ventricle served as an internal control. Rapamycin (0.75 mg/kg per day) or vehicle alone was administered intraperitoneally for 3 days or 2 wk. Immunoblot and immunofluorescence imaging showed that the level of ubiquitylated proteins in cardiomyocytes that increased following 48 h of PO was enhanced by rapamycin. Rapamycin pretreatment also significantly increased PO-induced Akt phosphorylation at S473, a finding confirmed in cardiomyocytes in vitro to be downstream of mTORC2. Analysis of prosurvival signaling in vivo showed that rapamycin increased PO-induced degradation of phosphorylated inhibitor of kappa B, enhanced expression of cellular inhibitor of apoptosis protein 1, and decreased active caspase-3. Long-term rapamycin treatment in 2-wk PO myocardium blunted hypertrophy, Unproved contractile function, and reduced caspase-3 and calpain activation. These data indicate potential cardioprotective benefits of rapamycin in PO hypertrophy. C1 [Harston, Rebecca K.; McKillop, John C.; Moschella, Phillip C.; Van Laer, An; Quinones, Lakeya S.; Baicu, Catalin F.; Balasubramanian, Sundaravadivel; Zile, Michael R.; Kuppuswamy, Dhandapani] Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, Dept Med, Charleston, SC 29425 USA. [Zile, Michael R.; Kuppuswamy, Dhandapani] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Kuppuswamy, D (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, Dept Med, 114 Doughty St, Charleston, SC 29425 USA. EM kuppusd@musc.edu FU National Institutes of Health [RHL092124A, T32HL07260]; Research Service of the Department of Veterans Affairs; AHA [061546811] FX This study was supported by the National Institutes of Health (RHL092124A to D. Kuppuswamy), and by Merit Award from the Research Service of the Department of Veterans Affairs (to M. Zile), by AHA predoctoral fellowship 061546811 (to R. K. Harston), and by NIH predoctoral fellowship NIH T32HL07260 (to R. K. Harston). NR 42 TC 13 Z9 13 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2011 VL 300 IS 5 BP H1696 EP H1706 DI 10.1152/ajpheart.00545.2010 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 757NA UT WOS:000290092800016 PM 21357504 ER PT J AU Sas, KM Janech, MG Favre, E Arthur, JM Bell, PD AF Sas, Kelli M. Janech, Michael G. Favre, Elizabeth Arthur, John M. Bell, P. Darwin TI Cilia movement regulates expression of the Raf-1 kinase inhibitor protein SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE polycystic kidney disease; renal epithelial cells; renal cysts ID POLYCYSTIC KIDNEY-DISEASE; PROSTATE-CANCER METASTASIS; AUTOSOMAL-DOMINANT; CYST FORMATION; EPITHELIAL-CELLS; COLLECTING DUCT; B-RAF; FLUID; MICE; ACTIVATION AB Sas KM, Janech MG, Favre E, Arthur JM, Bell PD. Cilia movement regulates expression of the Raf-1 kinase inhibitor protein. Am J Physiol Renal Physiol 300: F1163-F1170, 2011. First published February 23, 2011; doi:10.1152/ajprenal.00602.2010.-Renal epithelial cell primary cilia act as mechanosensors in response to changes in luminal fluid flow. To determine the role of cilia bending in the mechanosensory function of cilia, we performed proteomic analysis of collecting duct cell lines with or without cilia that were kept stationary or rotated to stimulate cilia bending. Expression of the Raf-1 kinase inhibitor protein (RKIP), an inhibitor of the MAPK pathway, was significantly elevated in rotated cilia (+) cells. This was compared with RKIP levels in cilia (-) cells that were stationary or rotated as well as in cilia (+) cells that were stationary. This result was confirmed in cilia knockout adult mice that had lower renal RKIP levels compared with adult mice with cilia. Downstream of RKIP, expression of phosphorylated ERK was decreased only in cells that had cilia and were subjected to constant cilia bending. Furthermore, elevated RKIP levels were associated with reduced cell proliferation. Blockade of PKC abrogated ciliary bending-induced increases in RKIP. In summary, we found that ciliary movement may help control the expression of the Raf-1 kinase inhibitor protein and thus maintain cell differentiation. In terms of polycystic kidney disease, loss of cilia and therefore sensitivity to flow may lead to reduced RKIP levels, activation of the MAPK pathway, and contribute to the formation of cysts. C1 [Janech, Michael G.; Arthur, John M.; Bell, P. Darwin] MUSC, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Sas, Kelli M.; Janech, Michael G.; Favre, Elizabeth; Arthur, John M.; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Bell, PD (reprint author), MUSC, Ralph H Johnson Vet Affairs Med Ctr, 173 Ashley Ave,CRI 211, Charleston, SC 29425 USA. EM bellpd@musc.edu OI Janech, Michael/0000-0002-3202-4811 FU Veterans Affairs (VA); National Institutes of Health (NIH) [DK32032, P30 DK074038, T32 DK007752]; Dialysis Clinic, Inc.; Nephcure Foundation; Foundation Young Investigator Award; NIH, National Center for Research Resources [C06 RR015455] FX This work was supported by Veterans Affairs (VA) Merit Awards (P. D. Bell, J. M. Arthur), a VA Career Development Award (M. G. Janech), National Institutes of Health (NIH) Grants DK32032 (P. D. Bell), P30 DK074038 (P. D. Bell; UAB Core Center, Lisa Guay-Woodford, PI) and T32 DK007752 (K. M. Sas; P. D. Bell, PI). Support was also provided by Dialysis Clinic, Inc., and a Nephcure Foundation Young Investigator Award (M. G. Janech). Foundation Young Investigator Award (M. G. Janech). This work was conducted in a facility constructed with support from NIH Grant C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources. NR 54 TC 5 Z9 5 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2011 VL 300 IS 5 BP F1163 EP F1170 DI 10.1152/ajprenal.00602.2010 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 758YY UT WOS:000290206100014 PM 21345975 ER PT J AU Smoller, JW AF Smoller, Jordan W. TI Do Antidepressants Raise the Risk of Stroke? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID CASE-CROSSOVER C1 [Smoller, Jordan W.] Herman Dana Trust, Newton, MA 02459 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu NR 6 TC 4 Z9 4 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2011 VL 168 IS 5 BP 457 EP 459 DI 10.1176/appi.ajp.2011.11020336 PG 3 WC Psychiatry SC Psychiatry GA 757MG UT WOS:000290089000004 PM 21536699 ER PT J AU Dodrill, CL Helmer, DA Kosten, TR AF Dodrill, Carrie L. Helmer, Drew A. Kosten, Thomas R. TI Prescription Pain Medication Dependence SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID CHRONIC NONMALIGNANT PAIN; OPIOID DEPENDENCE; ADDICTION TREATMENT; DRUG-ABUSE; BACK-PAIN; BUPRENORPHINE; METHADONE; THERAPY; DETOXIFICATION; PREVALENCE C1 [Dodrill, Carrie L.] Baylor Coll Med, Dept Psychiat, Michael E Debakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Dodrill, CL (reprint author), Baylor Coll Med, Dept Psychiat, Michael E Debakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,Bldg 110,Rm 223, Houston, TX 77030 USA. EM dodrill@bcm.edu FU NIDA NIH HHS [K05-DA0454] NR 44 TC 16 Z9 16 U1 2 U2 9 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2011 VL 168 IS 5 BP 466 EP 471 DI 10.1176/appi.ajp.2010.10020260 PG 6 WC Psychiatry SC Psychiatry GA 757MG UT WOS:000290089000007 PM 21536702 ER PT J AU Foland-Ross, LC Thompson, PM Sugar, CA Madsen, SK Shen, JK Penfold, C Ahlf, K Rasser, PE Fischer, J Yang, YL Townsend, J Bookheimer, SY Altshuler, LL AF Foland-Ross, Lara C. Thompson, Paul M. Sugar, Catherine A. Madsen, Sarah K. Shen, Jim K. Penfold, Conor Ahlf, Kyle Rasser, Paul E. Fischer, Jeffrey Yang, Yilan Townsend, Jennifer Bookheimer, Susan Y. Altshuler, Lori L. TI Investigation of Cortical Thickness Abnormalities in Lithium-Free Adults With Bipolar I Disorder Using Cortical Pattern Matching SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID VOXEL-BASED MORPHOMETRY; GRAY-MATTER DENSITY; CINGULATE CORTEX VOLUME; PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; RATING-SCALE; GREY-MATTER; HUMAN BRAIN; AMYGDALA; SCHIZOPHRENIA AB Objective: Although several lines of evidence implicate gray matter abnormalities in the prefrontal cortex and anterior cingulate cortex in patients with bipolar disorder, findings have been largely inconsistent across studies. Differences in patients' medication status or mood state or the application of traditional volumetric methods that are insensitive to subtle neuroanatomical differences may have contributed to variations in findings. The authors used MRI in conjunction with cortical pattern matching methods to assess cortical thickness abnormalities in euthymic bipolar patients who were not receiving lithium treatment. Method: Thirty-four lithium-free euthymic patients with bipolar I disorder and 31 healthy comparison subjects under-went MRI scanning. Data were processed to measure cortical gray matter thickness. Thickness maps were spatially normalized using cortical pattern matching and were analyzed to assess illness effects and associations with clinical variables. Results: Relative to healthy comparison subjects, euthymic bipolar patients had significantly thinner gray matter in the left and right prefrontal cortex (Brodmann's areas 11, 10, 8, and 44) and the left anterior cingulate cortex (Brodmann's areas 24/32). Thinning in these regions was more pronounced in patients with a history of psychosis. No areas of thicker cortex were detected in bipolar patients relative to healthy comparison subjects. Conclusions: Using a technique that is highly sensitive to subtle neuroanatomical differences, significant regional cortical thinning was found in lithium-free euthymic patients with bipolar disorder. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab NeuroImaging, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Ahmanson Lovelace Brain Mapping Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Schizophrenia Res Inst, Darlinghurst, NSW, Australia. Univ Newcastle, Prior Ctr Brain & Mental Hlth Res, Callaghan, NSW 2308, Australia. VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. W Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Altshuler, LL (reprint author), 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu FU NIMH [MH078556, MH075944, MH01848]; NARSAD; National Center for Research Resources [AG016570, EB01651, RR019771, RR12169, RR13642, RR00865]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Ahmanson Foundation; William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation; Tamkin Foundation; Jennifer Jones-Simon Foundation; Capital Group Companies Charitable Foundation; Robson Family; Northstar Fund FX Supported by NIMH grants MH078556, MH075944, and MH01848; NARSAD; National Center for Research Resources grants AG016570, EB01651, RR019771, RR12169, RR13642, and RR00865; and the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, the Brain Mapping Medical Research Organization, the Brain Mapping Support Foundation, the Pierson-Lovelace Foundation, the Ahmanson Foundation, the William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, the Tamkin Foundation, the Jennifer Jones-Simon Foundation, the Capital Group Companies Charitable Foundation, the Robson Family, and the Northstar Fund. NR 59 TC 36 Z9 37 U1 0 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2011 VL 168 IS 5 BP 530 EP 539 DI 10.1176/appi.ajp.2010.10060896 PG 10 WC Psychiatry SC Psychiatry GA 757MG UT WOS:000290089000014 PM 21285139 ER PT J AU Didier, JP Villet, R Huggler, E Lew, DP Hooper, DC Kelley, WL Vaudaux, P AF Didier, Jean-Philippe Villet, Regis Huggler, Elzbieta Lew, Daniel P. Hooper, David C. Kelley, William L. Vaudaux, Pierre TI Impact of Ciprofloxacin Exposure on Staphylococcus aureus Genomic Alterations Linked with Emergence of Rifampin Resistance SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID STALLED REPLICATION FORKS; TOPOISOMERASE-IV; RNA-POLYMERASE; MUTATION FREQUENCIES; PRIMARY TARGET; SOS RESPONSE; DNA GYRASE; BACTERIA; REPAIR; MUTANTS AB Intensive use of antimicrobial agents in health care settings not only leads to the selection of multiresistant nosocomial isolates of Staphylococcus aureus but may also promote endogenous, resistance-conferring mutations in bacterial genes that encode drug targets. We evaluated the spectrum of rifampin resistance-conferring mutations in cultures of methicillin-susceptible S. aureus (MSSA) or methicillin-resistant S. aureus (MRSA) strains exposed in vitro to sub-MICs of ciprofloxacin. Growth of ciprofloxacin-susceptible MRSA strain MRGR3 and ciprofloxacin-resistant MSSA strain RA1 (a NCTC 8325 derivative) in the presence of 1/2x or 1/4x MIC of ciprofloxacin led to higher frequencies of rifampin-resistant mutants on agar supplemented with rifampin (0.25 mg/liter) than under ciprofloxacin-free conditions. While rifampin-resistant mutants from ciprofloxacin-free cultures essentially showed single-amino-acid substitutions, a significant proportion of rifampin-resistant mutants from ciprofloxacin-exposed cultures displayed in-frame deletions or insertions in the rpoB gene at several positions of the rifampin resistance cluster I. In-frame deletions or insertions were also recorded in rpoB cluster I of rifampin-resistant mutants from ciprofloxacin-exposed cultures of mutS and mutL DNA repair mutants of ciprofloxacin-resistant S. aureus strain RA1. Frequencies of rifampin-resistant mutants grown under ciprofloxacin-free medium were higher for mutant strains RA1 mutS2 and RA1 mutL, but not RA1 recA, than for their parent RA1. In conclusion, ciprofloxacin-mediated DNA damage in S. aureus, as exemplified by the wide diversity of deletions or insertions in rpoB, suggests the occurrence of major, quinolone-mediated disturbances in DNA fork progression and replication repair. Besides promoting antibiotic resistance, accumulation of unrepaired DNA replication errors, including insertions and deletions, may also contribute to potentially lethal mutations. C1 [Didier, Jean-Philippe; Villet, Regis; Huggler, Elzbieta; Lew, Daniel P.; Kelley, William L.; Vaudaux, Pierre] Univ Hosp Geneva, Infect Dis Serv, CH-1211 Geneva 14, Switzerland. [Hooper, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Vaudaux, P (reprint author), Univ Hosp Geneva, Infect Dis Serv, 4 Rue Gabrielle Perret Gentil, CH-1211 Geneva 14, Switzerland. EM Pierrevaudaux@yahoo.fr FU Swiss National Science Foundation [320000-116518, 31003A-120428, 3200B0-108401]; U.S. Public Health Service, National Institutes of Health [R37-AI023988-20] FX This study was supported by research grants 320000-116518 (to P.V.), 31003A-120428 (to W.K.), and 3200B0-108401 (to D.P.L.) from the Swiss National Science Foundation and by research grant R37-AI023988-20 (to D.C.H.) from the U.S. Public Health Service, National Institutes of Health. NR 45 TC 12 Z9 12 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2011 VL 55 IS 5 BP 1946 EP 1952 DI 10.1128/AAC.01407-10 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 756NM UT WOS:000290019200016 PM 21357297 ER PT J AU Sandweiss, DA Slymen, DJ LeardMann, CA Smith, B White, MR Boyko, EJ Hooper, TI Gackstetter, GD Amoroso, PJ Smith, TC AF Sandweiss, Donald A. Slymen, Donald J. LeardMann, Cynthia A. Smith, Besa White, Martin R. Boyko, Edward J. Hooper, Tomoko I. Gackstetter, Gary D. Amoroso, Paul J. Smith, Tyler C. CA Millennium Cohort Study Team TI Preinjury Psychiatric Status, Injury Severity, and Postdeployment Posttraumatic Stress Disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MOTOR-VEHICLE ACCIDENTS; READJUSTMENT RATING-SCALE; COMBAT TRAUMA REGISTRY; MENTAL-HEALTH PROBLEMS; MILLENNIUM COHORT; PRIMARY-CARE; MILITARY SERVICE; RISK-FACTORS; US MILITARY; PERCEIVED THREAT AB Context: Physical injury has been associated with the development of posttraumatic stress disorder (PTSD). Previous studies have retrospectively examined the relationship of preinjury psychiatric status and postinjury PTSD with conflicting results, but no prospective studies regarding this subject have been conducted, to our knowledge. Objective: To prospectively assess the relationship of predeployment psychiatric status and injury severity with postdeployment PTSD. Design: Prospective, longitudinal study. Setting: United States military personnel deployed in support of the conflicts in Iraq and Afghanistan. Participants: United States service member participants in the Millennium Cohort Study who completed a baseline questionnaire (from July 1, 2001, through June 30, 2003) and at least 1 follow-up questionnaire (from June 1, 2004, through February 14, 2006, and from May 15, 2007, through December 31, 2008) and who were deployed in the intervening period. Self-reported health information was used to prospectively examine the relationship between baseline psychiatric status and follow-up PTSD in injured and uninjured deployed individuals. Main Outcome Measures: A positive screening result using the PTSD Checklist-Civilian Version. Results: Of 22 630 eligible participants, 1840 (8.1%) screened positive for PTSD at follow-up, and 183 (0.8%) sustained a deployment-related physical injury that was documented in the Joint Theater Trauma Registry or the Navy-Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database. The odds of screening positive for PTSD symptoms were 2.52 (95% confidence interval, 2.01-3.16) times greater in those with 1 or more defined baseline mental health disorder and 16.1% (odds ratio, 1.16; 95% confidence interval, 1.01-1.34) greater for every 3-unit increase in the Injury Severity Score. Irrespective of injury severity, self-reported preinjury psychiatric status was significantly associated with PTSD at follow-up. Conclusions: Baseline psychiatric status and deployment-related physical injuries were associated with screening positive for postdeployment PTSD. More vulnerable members of the deployed population might be identified and benefit from interventions targeted to prevent or to ensure early identification and treatment of postdeployment PTSD. C1 [Sandweiss, Donald A.; LeardMann, Cynthia A.; Smith, Besa; White, Martin R.; Smith, Tyler C.] USN, Hlth Res Ctr, Dept Deployment Hlth Res, San Diego, CA 92106 USA. [Slymen, Donald J.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Hooper, Tomoko I.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Gackstetter, Gary D.] Analyt Serv Inc, Arlington, VA USA. [Amoroso, Paul J.] Madigan Army Med Ctr, Dept Clin Invest, Tacoma, WA 98431 USA. RP LeardMann, CA (reprint author), USN, Hlth Res Ctr, Dept Deployment Hlth Res, 140 Sylvester Rd, San Diego, CA 92106 USA. EM cynthia.leardmann@med.navy.mil FU US Department of Defense; Veterans Affairs Puget Sound Health Care System FX This work represents report 10-03, supported by the US Department of Defense, within work unit 60002. The work of Dr Boyko in this project was supported by the Veterans Affairs Puget Sound Health Care System. NR 75 TC 19 Z9 19 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 2011 VL 68 IS 5 BP 496 EP 504 PG 9 WC Psychiatry SC Psychiatry GA 757UY UT WOS:000290114500010 PM 21536979 ER PT J AU Culbertson, CS Bramen, J Cohen, MS London, ED Olmstead, RE Gan, JJ Costello, MR Shulenberger, S Mandelkern, MA Brody, AL AF Culbertson, Christopher S. Bramen, Jennifer Cohen, Mark S. London, Edythe D. Olmstead, Richard E. Gan, Joanna J. Costello, Matthew R. Shulenberger, Stephanie Mandelkern, Mark A. Brody, Arthur L. TI Effect of Bupropion Treatment on Brain Activation Induced by Cigarette-Related Cues in Smokers SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SUSTAINED-RELEASE BUPROPION; ANTERIOR CINGULATE CORTEX; SMOKING-CESSATION; NICOTINE DEPENDENCE; TOBACCO DEPENDENCE; CONTROLLED-TRIAL; RECEPTOR SUBTYPES; RANDOMIZED-TRIAL; DRUG-ADDICTION; FMRI AB Context: Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. Objective: To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Design: Randomized, double-blind, before-after controlled trial. Setting: Academic brain imaging center. Participants: Thirty nicotine-dependent smokers (paid volunteers). Interventions: Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Main Outcome Measures: Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Results: Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Conclusions: Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions. C1 [Culbertson, Christopher S.; Bramen, Jennifer; Cohen, Mark S.; London, Edythe D.; Gan, Joanna J.; Costello, Matthew R.; Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [London, Edythe D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [London, Edythe D.; Brody, Arthur L.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Olmstead, Richard E.; Shulenberger, Stephanie; Mandelkern, Mark A.; Brody, Arthur L.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Nucl Med, Los Angeles, CA USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Brody, AL (reprint author), 300 UCLA Med Plaza,Ste 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU National Institute on Drug Abuse [R01 DA20872, DA245482]; Tobacco-Related Disease Research Program, a Veterans Affairs Type I Merit Review Award [16RT-0098]; Richard Metzner Chair in Clinical Neuropharmacology; Thomas P. and Katherine K. Pike Chair in Addiction Studies; Marjorie M. Greene Trust FX This study was supported by grants R01 DA20872 (Dr Brody) and DA245482 (Mr Culbertson) from the National Institute on Drug Abuse; grant 16RT-0098 from the Tobacco-Related Disease Research Program, a Veterans Affairs Type I Merit Review Award, and endowments from the Richard Metzner Chair in Clinical Neuropharmacology (Dr Brody); and endowments from the Thomas P. and Katherine K. Pike Chair in Addiction Studies and the Marjorie M. Greene Trust (Dr London). NR 92 TC 32 Z9 33 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 2011 VL 68 IS 5 BP 505 EP 515 DI 10.1001/archgenpsychiatry.2010.193 PG 11 WC Psychiatry SC Psychiatry GA 757UY UT WOS:000290114500012 PM 21199957 ER PT J AU Hunt, JL AF Hunt, Jennifer L. TI An Update on Molecular Diagnostics of Squamous and Salivary Gland Tumors of the Head and Neck SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ADENOID CYSTIC CARCINOMA; GROWTH-FACTOR RECEPTOR; IN-SITU HYBRIDIZATION; UPPER AERODIGESTIVE TRACT; LOW-GRADE ADENOCARCINOMA; ETV6-NTRK3 FUSION GENE; CELL LUNG-CANCER; MUCOEPIDERMOID CARCINOMA; HUMAN-PAPILLOMAVIRUS; C-KIT AB Context.-Molecular testing in anatomic pathology is becoming standardized and can contribute valuable diagnostic, therapeutic, and prognostic information for the clinical management of patients. In head and neck pathology, recent advances in molecular testing have provided important targets in several different diagnostic areas, with particular emerging clinical applications in squamous and salivary gland pathology. In squamous mucosal-derived lesions, human papilloma virus has emerged as an important pathogenic etiology in a subset of oropharyngeal squamous cell carcinomas. Within the category of salivary gland tumors, 3 tumors have recently been recognized that contain oncogenic translocations. Objective.-To describe the current state of information about the molecular alterations in squamous lesions and in salivary gland tumors of the head and neck. Data Sources.-Published literature on squamous and salivary gland tumors of the head and neck. Conclusions.-The different approaches to identification of viral-associated tumors include assays using polymerase chain reaction, in situ hybridization, and immunohistochemistry. Most mucoepidermoid carcinomas harbor MECT1-MAML2 gene rearrangement. The MYB-NFIB translocations have recently been identified in adenoid cystic carcinomas. Finally, a newly described tumor of salivary gland, mammary analogue secretory carcinoma, harbors the ETV6-NTRK3 translocation. Although these translocations are just emerging as diagnostic targets, future roles may evolve as potential therapeutic targets. (Arch Pathol Lab Med. 2011;135:602-609) C1 [Hunt, Jennifer L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hunt, Jennifer L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hunt, JL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 202,55 Fruit St, Boston, MA 02114 USA. EM jhunt5@partners.org NR 118 TC 13 Z9 16 U1 0 U2 4 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2011 VL 135 IS 5 BP 602 EP 609 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 759DU UT WOS:000290221700011 PM 21526958 ER PT J AU Mino-Kenudson, M Mark, EJ AF Mino-Kenudson, Mari Mark, Eugene J. TI Reflex Testing for Epidermal Growth Factor Receptor Mutation and Anaplastic Lymphoma Kinase Fluorescence In Situ Hybridization in Non-Small Cell Lung Cancer SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID EML4-ALK FUSION GENE; BRONCHIOLOALVEOLAR PATHOLOGICAL SUBTYPE; EGFR MUTATIONS; TYROSINE KINASE; CLINICAL-TRIALS; ADJUVANT CHEMOTHERAPY; MOLECULAR PREDICTORS; SOMATIC MUTATIONS; GEFITINIB; ADENOCARCINOMA AB Context.-Non-small cell lung cancer (NSCLC) is a poor-prognosis malignancy for which more effective treatments are needed, with accumulating clinical experiences supporting benefits of receptor tyrosine kinase inhibitors for patients with tumors harboring an epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement. Objective.-To review completed and ongoing clinical trials of EGFR tyrosine kinase inhibitors for EGFR mutation-positive NSCLC and an ALK inhibitor for those with ALK rearrangement, while also exploring practical issues surrounding the implementation of molecular testing as a routine component of the diagnostic workup of NSCLC in the United States. Data Sources.-Published biomedical literature, abstracts presented at recent major oncology meetings, and ClinicalTrials.gov. Conclusions.-Continually evolving evidence indicates the possible efficacy of molecularly targeted agents for the treatment of advanced NSCLC, especially adenocarcinoma. To identify patients who will most likely benefit from the targeted therapy, routine determination of the corresponding genetic alterations after histologic diagnosis of NSCLC (reflex molecular testing for EGFR mutations and ALK rearrangement) should be considered. (Arch Pathol Lab Med. 2011;135:655-664) C1 [Mino-Kenudson, Mari; Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 122, Boston, MA 02114 USA. EM mminokenudson@partners.org FU Boehringer Ingelheim Pharmaceuticals, Inc (BIPI; Ridgefield, Connecticut) FX This work is supported by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI; Ridgefield, Connecticut). Editorial assistance is provided by Alyssa Tippens, PhD, of MedErgy (Yardley, Pennsylvania), which is contracted by BIPI for these services. The authors report the payment of $483 by BIPI to the Nature Publishing Company for permission to publish Figure 1, A through F. The authors have received no compensation related to the development of the manuscript. The authors have no relevant financial interest in the products or companies described in this article. NR 74 TC 20 Z9 20 U1 2 U2 5 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2011 VL 135 IS 5 BP 655 EP 664 PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 759DU UT WOS:000290221700017 PM 21526964 ER PT J AU Shon, SM Park, JH Nahrendorf, M Schellingerhout, D Kim, JY Kang, BT Jeong, SW Kim, EJ Ryu, JH Kim, K Kwon, IC Lee, DK Lee, MM Kim, DE AF Shon, Soo-Min Park, Jong-Ho Nahrendorf, Matthias Schellingerhout, Dawid Kim, Jeong-Yeon Kang, Byeong-Teck Jeong, Sang-Wuk Kim, Eo-Jin Ryu, Ju Hee Kim, Kwangmeyung Kwon, Ick Chan Lee, Dong Kun Lee, Myoung Mook Kim, Dong-Eog TI Exercise attenuates matrix metalloproteinase activity in preexisting atherosclerotic plaque SO ATHEROSCLEROSIS LA English DT Article DE Exercise; Atherosclerosis; Matrix metalloproteinase; Preexisting plaque; Molecular imaging ID E-DEFICIENT MICE; LIPID-ACCUMULATION; ENZYME-ACTIVITY; PLASMA-PROTEIN; FOAM CELLS; ADIPONECTIN; EXPRESSION; HEART; ATHEROGENESIS; MACROPHAGES AB Objective: Few studies have investigated if exercise by itself has anti-atherosclerotic effects, without combining interventions with a low-fat diet. We studied the effects of exercise as a stand-alone intervention on preexisting atheromata by measuring not only plaque size but also the levels of plaque-destabilizing matrix-metalloproteinase (MMP) activity in vivo. Methods and results: We used near-infrared fluorescent (NIRF) molecular imaging with an MMP-2/9 activatable NIRF probe to visualize the inflammatory protease activity within preexisting atheromata of 17-week-old ApoE(-/-) mice on: (a) normal chow diet (NCD), (b) Western diet (WD), and (c) WD with treadmill exercise for 10 weeks. We also measured tissue levels of aortic lipid peroxidation (LPO) and plasma levels of glucose/lipid/cytokine profiles. Exercise did not attenuate growth of preexisting atheromatous plaques. However, exercise strongly decreased proteolytic activity in plaques for animals on WD, with levels decreasing almost to NCD levels. Exercise was associated with decreased aortic LPO levels and increased blood adiponectin/leptin levels; however, exercise did not affect WD-consumption/weight-gain or improve blood glucose/lipid profiles. Conclusions: Exercise training reduced aortic MMP activity in mice with preexisting atheromata, even though they remained on a high fat diet and plaque-growth was not attenuated. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Kim, Dong-Eog] Dongguk Univ, Ilsan Hosp, Dept Neurol, Div Stroke Med,Mol Imaging & Neurovasc Res MINER, Goyang, South Korea. [Park, Jong-Ho] Kwandong Univ, Myongji Hosp, Neurovasc Ctr, Goyang, South Korea. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA. [Kim, Eo-Jin] Dongguk Univ, Ilsan Hosp, Dept Pathol, Goyang, South Korea. [Ryu, Ju Hee; Kim, Kwangmeyung; Kwon, Ick Chan] Korea Inst Sci & Technol, Biomed Res Ctr, Seoul, South Korea. [Lee, Myoung Mook] Dongguk Univ, Ilsan Hosp, Div Cardiol, Goyang, South Korea. RP Kim, DE (reprint author), Dongguk Univ, Ilsan Hosp, Dept Neurol, Div Stroke Med,Mol Imaging & Neurovasc Res MINER, 814 Siksa Dong, Goyang, South Korea. EM kdongeog@duih.org FU Translational Stroke Research Center, Ministry of Health & Welfare, Republic of Korea [A08020] FX This work was supported by a grant (A08020, Translational Stroke Research Center Grant to Dr. Dong-Eog Kim) of the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea. NR 23 TC 14 Z9 15 U1 0 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2011 VL 216 IS 1 BP 67 EP 73 DI 10.1016/j.atherosclerosis.2011.01.036 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 758YV UT WOS:000290205800011 PM 21334624 ER PT J AU Sharma, R Prudente, S Andreozzi, F Powers, C Mannino, G Bacci, S Gervino, EV Hauser, TH Succurro, E Mercuri, L Goheen, EH Shah, H Trischitta, V Sesti, G Doria, A AF Sharma, Rajani Prudente, Sabrina Andreozzi, Francesco Powers, Christine Mannino, Gaia Bacci, Simonetta Gervino, Ernest V. Hauser, Thomas H. Succurro, Elena Mercuri, Luana Goheen, Elizabeth H. Shah, Hetal Trischitta, Vincenzo Sesti, Giorgio Doria, Alessandro TI The type 2 diabetes and insulin-resistance locus near IRS1 is a determinant of HDL cholesterol and triglycerides levels among diabetic subjects SO ATHEROSCLEROSIS LA English DT Article DE Coronary artery disease; Polymorphisms; Insulin-resistance; Type 2 diabetes ID CORONARY-ARTERY-DISEASE; HEART-DISEASE; RISK; HERITABILITY; ASSOCIATION; RECEPTOR; EVENTS AB Objective: SNP rs2943641 near the insulin receptor substrate 1 (IRS1) gene has been found to be associated with type 2 diabetes (T2D) and insulin-resistance in genome-wide association studies. We investigated whether this SNP is associated with cardiovascular risk factors and coronary artery disease (CAD) among diabetic individuals. Methods: SNP rs2943641 was typed in 2133 White T2D subjects and tested for association with BMI, serum HDL cholesterol and triglycerides, hypertension history, and CAD risk. Results: HDL cholesterol decreased by 1 mg/dl (p = 0.004) and serum triglycerides increased by 6 mg/dl (p = 0.016) for each copy of the insulin-resistance allele. Despite these effects, no association was found with increased CAD risk (OR = 1.00, 95% CI 0.88-1.13). Conclusions: The insulin-resistance and T2D locus near the IRS1 gene is a determinant of lower HDL cholesterol among T2D subjects. However, this effect is small and does not translate into a detectable increase in CAD risk in this population. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Doria, Alessandro] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Div Res, Boston, MA 02115 USA. [Prudente, Sabrina; Mercuri, Luana; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Mendel Lab, San Giovanni Rotondo, Italy. [Andreozzi, Francesco; Mannino, Gaia; Succurro, Elena; Sesti, Giorgio] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy. [Bacci, Simonetta] IRCCS Casa Sollievo Sofferenza, Unit Endocrinol, San Giovanni Rotondo, Italy. [Gervino, Ernest V.; Hauser, Thomas H.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Gervino, Ernest V.; Hauser, Thomas H.; Shah, Hetal; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy. [Doria, Alessandro] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Doria, A (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Div Res, 1 Joslin Pl, Boston, MA 02115 USA. EM alessandro.doria@joslin.harvard.edu RI Sesti, Giorgio/B-1509-2012; Prudente, Sabrina/H-2886-2016; Mannino, Gaia/K-1580-2016; Trischitta, Vincenzo/K-1487-2016; OI Prudente, Sabrina/0000-0001-9220-8981; Mannino, Gaia/0000-0002-6341-4572; Trischitta, Vincenzo/0000-0003-1174-127X; Andreozzi, Francesco/0000-0001-9375-1513; Sesti, Giorgio/0000-0002-1618-7688; Succurro, Elena/0000-0003-2578-692X FU National Institutes of Health [HL73168, DK36836]; Italian Ministry of Health; Fondazione Roma; European Union [LSHM-CT-2004-512013]; NIDDK [T32 DK007260] FX This research was supported by grants from the National Institutes of Health (HL73168 to A. D. and DK36836 to the Genetics Core of the Diabetes & Endocrinology Research Center at the Joslin Diabetes Center), the Italian Ministry of Health ("Ricerca Corrente 2009 and 2010" to S. P and V. T), the Fondazione Roma ("Sostegno alla ricerca scientifica biomedica 2008" to V. T), and the European Union (FP6 EUGENE2 no LSHM-CT-2004-512013 to G. S.). R. S. was supported by the 2010 NIDDK Medical Student Research Program in Diabetes through grant T32 DK007260 to the Joslin Diabetes Center. The content of the paper is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. We are grateful to Erin Murphy and Alyssa Kanagaki for assistance with the recruitment of study subjects. We acknowledge the invaluable contribution by the individuals who participated in this study. NR 16 TC 12 Z9 12 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2011 VL 216 IS 1 BP 157 EP 160 DI 10.1016/j.atherosclerosis.2011.01.022 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 758YV UT WOS:000290205800025 PM 21353221 ER PT J AU Jegga, AG Schneider, L Ouyang, XS Zhang, J AF Jegga, Anil G. Schneider, Lonnie Ouyang, Xiaosen Zhang, Jianhua TI Systems biology of the autophagy-lysosomal pathway SO AUTOPHAGY LA English DT Article DE systems biology; autophagy; lysosome; transcription factors; microRNA ID CATHEPSIN-D DEFICIENCY; ALZHEIMERS-DISEASE; LIPID-METABOLISM; TRANSCRIPTION FACTORS; MICRORNA EXPRESSION; MUSCLE-CELLS; NEURONS; ACCUMULATION; KINASE; GENES AB The mechanisms of the control and activity of the autophagy-lysosomal protein degradation machinery are emerging as an important theme for neurodevelopment and neurodegeneration. However, the underlying regulatory and functional networks of known genes controlling autophagy and lysosoma I function and their role in disease are relatively unexplored. We performed a systems biology-based integrative computational analysis to study the interactions between molecular components and to develop models for regulation and function of genes involved in autophagy and lysosomal function. Specifically, we analyzed transcriptional and microRNA-based post-transcriptional regulation of these genes and performed functional enrichment analyses to understand their involvement in nervous system-related diseases and phenotypes. Transcriptional regulatory network analysis showed that binding sites for transcription factors, SREBP1, USF, AP-1 and NFE2, are common among autophagy and lysosomal genes. MicroRNA enrichment analysis revealed miR-130, 98, 124, 204 and 142 as the putative post-transcriptional regulators of the autophagy-lysosomal pathway genes. Pathway enrichment analyses revealed that the mTOR and insulin signaling pathways are important in the regulation of genes involved in autophagy. In addition, we found that glycosaminoglycan and glycosphingolipid pathways also make a major contribution to lysosoma I gene regulation. The analysis confirmed the known contribution of the autophagy-lysosomal genes to Alzheimer and Parkinson diseases and also revealed potential involvement in tuberous sclerosis, neuronal ceroid-lipofuscinoses, sepsis and lung, liver and prostatic neoplasms. To further probe the impact of autophagy-lysosomal gene deficits on neurologically-linked phenotypes, we also mined the mouse knockout phenotype data for the autophagy-lysosomal genes and found them to be highly predictive of nervous system dysfunction. Overall this study demonstrates the utility of systems biology-based approaches for understanding the autophagy-lysosomal pathways and gaining additional insights into the potential impact of defects in these complex biological processes. C1 [Schneider, Lonnie; Ouyang, Xiaosen; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Jegga, Anil G.] Cincinnati Childrens Hosp, Med Ctr, Div Biomed Informat, Cincinnati, OH USA. [Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Ouyang, Xiaosen; Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA. RP Zhang, J (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. EM zhanja@uab.edu RI zhang, jianhua/D-3404-2009; Jegga, Anil/H-6140-2011; di Ronza, Alberto/H-7674-2016; OI Jegga, Anil/0000-0002-4881-7752; di Ronza, Alberto/0000-0002-9813-5143; Zhang, Jianhua/0000-0002-2128-9574 FU National Institutes of Health [DK078392]; University of Alabama at Birmingham [NIHR01-NS064090]; VA FX We thank Dr. Victor Darley-Usmar for critical discussions and for editing the manuscript. We acknowledge the help of Ron Bryson, Technical Writer, Division of Biomedical Informatics, CCHMC, OH USA, in editing the article. This work was partially supported by the grants from National Institutes of Health DK078392 (Gene Expression and Sequencing Core and Bioinformatics Core, Digestive Disease Research Core Center in Cincinnati) (A.J.), and University of Alabama at Birmingham start-up support, NIHR01-NS064090 and a VA merit award (J.Z.). NR 71 TC 58 Z9 60 U1 1 U2 17 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD MAY PY 2011 VL 7 IS 5 BP 477 EP 489 DI 10.4161/auto.7.5.14811 PG 13 WC Cell Biology SC Cell Biology GA 757LW UT WOS:000290087600004 PM 21293178 ER PT J AU Huang, J Johnson, AD O'Donnell, CJ AF Huang, Jie Johnson, Andrew D. O'Donnell, Christopher J. TI PRIMe: a method for characterization and evaluation of pleiotropic regions from multiple genome-wide association studies SO BIOINFORMATICS LA English DT Article ID GENERALIZED ESTIMATING EQUATIONS; GENETIC ASSOCIATION; CHARGE CONSORTIUM; LOCI; PHENOTYPES; TRAITS; VARIANTS; TESTS; RISK AB Motivation: The concept of pleiotropy was proposed a century ago, though up to now there have been insufficient efforts to design robust statistics and software aimed at visualizing and evaluating pleiotropy at a regional level. The Pleiotropic Region Identification Method (PRIMe) was developed to evaluate potentially pleiotropic loci based upon data from multiple genome-wide association studies (GWAS). Methods: We first provide a software tool to systematically identify and characterize genomic regions where low association P-values are observed with multiple traits. We use the term Pleiotropy Index to denote the number of traits with low association P-values at a particular genomic region. For GWAS assumed to be uncorrelated, we adopted the binomial distribution to approximate the statistical significance of the Pleiotropy Index. For GWAS conducted on traits with known correlation coefficients, simulations are performed to derive the statistical distribution of the Pleiotropy Index under the null hypothesis of no genotype-phenotype association. For six hematologic and three blood pressure traits where full GWAS results were available from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, we estimated the trait correlations and applied the simulation approach to examine genomic regions with statistical evidence of pleiotropy. We then applied the approximation approach to explore GWAS summarized in the National Human Genome Research Institute (NHGRI) GWAS Catalog. Results: By simulation, we identified pleiotropic regions including SH2B3 and BRAP (12q24.12) for hematologic and blood pressure traits. By approximation, we confirmed the genome-wide significant pleiotropy of these two regions based on the GWAS Catalog data, together with an exploration on other regions which highlights the FTO, GCKR and ABO regions. C1 [Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20824 USA. [O'Donnell, Christopher J.] Harvard Univ, Div Cardiol, Sch Med, Dept Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov RI Johnson, Andrew/G-6520-2013 FU National Heart, Lung and Blood Institute, Division of Intramural Research FX This project is supported by the National Heart, Lung and Blood Institute, Division of Intramural Research. NR 32 TC 33 Z9 36 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 1 PY 2011 VL 27 IS 9 BP 1201 EP 1206 DI 10.1093/bioinformatics/btr116 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 760NS UT WOS:000290331600002 PM 21398673 ER PT J AU Ma, HS Schadt, EE Kaplan, LM Zhao, HY AF Ma, Haisu Schadt, Eric E. Kaplan, Lee M. Zhao, Hongyu TI COSINE: COndition-SpecIfic sub-NEtwork identification using a global optimization method SO BIOINFORMATICS LA English DT Article ID PROTEIN REFERENCE DATABASE; SET ENRICHMENT ANALYSIS; GENE-EXPRESSION; RACIAL-DIFFERENCES; PROSTATE-CANCER; CANDIDATE GENES; DISEASE; PATHWAYS; POPULATIONS; PROFILES AB Motivation: The identification of condition specific sub-networks from gene expression profiles has important biological applications, ranging from the selection of disease-related biomarkers to the discovery of pathway alterations across different phenotypes. Although many methods exist for extracting these sub-networks, very few existing approaches simultaneously consider both the differential expression of individual genes and the differential correlation of gene pairs, losing potentially valuable information in the data. Results: In this article, we propose a new method, COSINE (COndition SpecIfic sub-NEtwork), which employs a scoring function that jointly measures the condition-specific changes of both 'nodes' (individual genes) and 'edges' (gene-gene co-expression). It uses the genetic algorithm to search for the single optimal sub-network which maximizes the scoring function. We applied COSINE to both simulated datasets with various differential expression patterns, and three real datasets, one prostate cancer dataset, a second one from the across-tissue comparison of morbidly obese patients and the other from the across-population comparison of the HapMap samples. Compared with previous methods, COSINE is more powerful in identifying truly significant sub-networks of appropriate size and meaningful biological relevance. C1 [Zhao, Hongyu] Yale Univ, Dept Epidemiol & Publ Hlth, Dept Genet, New Haven, CT 06520 USA. [Ma, Haisu] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06511 USA. [Schadt, Eric E.] Sage Bionetworks, Seattle, WA USA. [Schadt, Eric E.] Pacific Biosci, Menlo Pk, CA 94025 USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. [Kaplan, Lee M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Zhao, HY (reprint author), Yale Univ, Dept Epidemiol & Publ Hlth, Dept Genet, New Haven, CT 06520 USA. EM hongyu.zhao@yale.edu FU National Institutes of Health [GM59507]; Chinese Scholarship Council FX The authors are grateful to funding support from National Institutes of Health (GM59507 to H.Z.) and a graduate student fellowship from the Chinese Scholarship Council to H. M. NR 47 TC 31 Z9 32 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 1 PY 2011 VL 27 IS 9 BP 1290 EP 1298 DI 10.1093/bioinformatics/btr136 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 760NS UT WOS:000290331600014 PM 21414987 ER PT J AU Coen, JJ Feldman, AS Smith, MR Zietman, AL AF Coen, John J. Feldman, Adam S. Smith, Matthew R. Zietman, Anthony L. TI Watchful waiting for localized prostate cancer in the PSA era: what have been the triggers for intervention? SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; watchful waiting; active surveillance; PSA ID ACTIVE SURVEILLANCE; CONSERVATIVE MANAGEMENT; PATIENTS PERCEPTIONS; ANTIGEN ERA; OUTCOMES; LIFE; MEN AB Circulating tumour cells (CTC) have prognostic relevance for patients with different metastatic carcinomas. Detection of CTC using the CellSearch system has also been reported in bladder cancer, but mainly in patients with metastatic disease. This is the largest report demonstrating that detection of CTC in non-metastatic bladder cancer patients is feasible using the CellSearch system. Presence of CTC may be predictive for early systemic disease. OBJECTIVE To prospectively detect and evaluate the biological significance of circulating tumour cells (CTC) in patients with bladder cancer, especially in those patients with non-metastatic, advanced bladder cancer (NMABC). PATIENTS AND METHODS Between July 2007 and January 2009, blood samples of 50 consecutive patients with localized bladder cancer and five patients with metastatic disease scheduled for cystectomy were prospectively investigated for CTC. Peripheral blood (7.5 ml) was drawn before cystectomy. Detection of CTC was performed using the USA Food and Drug Administration-approved CellSearchTM system. Data were compared with the clinical and histopathological findings. RESULTS CTC were detected in 15 of 50 patients (30%) with non-metastatic disease and five of five patients with metastatic disease. The overall mean number of CTC was 33.7 (range: 1-372; median: 2). In non-metastatic patients, the mean number of CTC was 3.1 (range: 1-11; median: 1). Except for a univariate association between CTC with vessel infiltration (P = 0.047), all other common clinical and histopathological parameters did not reveal a significant correlation with CTC detection. A median 1-year follow up was available for 53 patients (96.4%). Ten out of 19 preoperatively CTC-positive patients died as a result of cancer progression. CTC-positive patients showed significantly worse overall (P = 0.001), progression-free (P < 0.001) and cancer specific survival (P < 0.001) compared to preoperatively CTC-negative patients. CONCLUSION This is the largest study demonstrating that detection of CTC in NMABC patients is feasible using the CellSearchTM system. Our findings suggest that the presence of CTC may be predictive for early systemic disease. C1 [Coen, John J.; Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Feldman, Adam S.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Coen, JJ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jcoen@partners.org FU NCI NIH HHS [K24 CA121990, K24 CA121990-05] NR 18 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD MAY PY 2011 VL 107 IS 10 BP 1582 EP 1586 DI 10.1111/j.1464-410X.2010.09652.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 755AN UT WOS:000289899100009 PM 20860650 ER PT J AU Mirman, D Yee, E Blumstein, SE Magnuson, JS AF Mirman, Daniel Yee, Eiling Blumstein, Sheila E. Magnuson, James S. TI Theories of spoken word recognition deficits in Aphasia: Evidence from eye-tracking and computational modeling SO BRAIN AND LANGUAGE LA English DT Article DE Spoken word recognition; Aphasia; Eye-tracking; Computational models; Growth curve analysis ID SHORT-TERM-MEMORY; SPEECH-PERCEPTION; LEXICAL ACCESS; TIME-COURSE; AUDITORY COMPREHENSION; TRACE MODEL; COMPETITION; ACTIVATION; MOVEMENTS; FMRI AB We used eye-tracking to investigate lexical processing in aphasic participants by examining the fixation time course for rhyme (e.g., carrot-parrot) and cohort (e.g., beaker-beetle) competitors. Broca's aphasic participants exhibited larger rhyme competition effects than age-matched controls. A re-analysis of previously reported data (Yee, Blumstein, & Sedivy, 2008) confirmed that Wernicke's aphasic participants exhibited larger cohort competition effects. Individual-level analyses revealed a negative correlation between rhyme and cohort competition effect size across both groups of aphasic participants. Computational model simulations were performed to examine which of several accounts of lexical processing deficits in aphasia might account for the observed effects. Simulation results revealed that slower deactivation of lexical competitors could account for increased cohort competition in Wernicke's aphasic participants; auditory perceptual impairment could account for increased rhyme competition in Broca's aphasic participants; and a perturbation of a parameter controlling selection among competing alternatives could account for both patterns, as well as the correlation between the effects. In light of these simulation results, we discuss theoretical accounts that have the potential to explain the dynamics of spoken word recognition in aphasia and the possible roles of anterior and posterior brain regions in lexical processing and cognitive control. (C) 2011 Elsevier Inc. All rights reserved. C1 [Mirman, Daniel] Moss Rehabil Res Inst, Elkins Pk, PA 19027 USA. [Yee, Eiling] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Blumstein, Sheila E.] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA. [Blumstein, Sheila E.] Res Serv, Dept Vet Affairs Med Ctr, Providence, RI 02908 USA. [Blumstein, Sheila E.] Boston Univ, Harold Goodglass Aphasia Res Ctr, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Blumstein, Sheila E.] Res Serv, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Magnuson, James S.] Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. [Magnuson, James S.] Haskins Labs Inc, New Haven, CT 06511 USA. RP Mirman, D (reprint author), Moss Rehabil Res Inst, 50 Township Line Rd, Elkins Pk, PA 19027 USA. EM mirmand@einstein.edu RI Magnuson, James/E-5046-2011; Mirman, Daniel/A-2113-2012; Yee, Eiling/F-2161-2010 FU Jacob K. Javits Fellowship; NSF [0748684]; National Institutes of Health [DC005765, HD001994, HD40353, DC00314, DC0081]; Moss Rehabilitation Research Institute; [F32HD052364] FX A preliminary report on this work was presented at the 2008 Meeting of the Cognitive Neuroscience Society (April, 2008, San Francisco, CA). This research was supported by F32HD052364 to DM, a Jacob K. Javits Fellowship to EY, NSF CAREER 0748684 to JSM, National Institutes of Health grants DC005765 to JSM, HD001994 and HD40353 to Haskins Labs, DC00314 to Brown University, and DC0081 to the Boston University School of Medicine, and the Moss Rehabilitation Research Institute. This material is the result of work supported with resources and the use of facilities at the Department of Veterans Affairs Medical Centers in Boston, MA and Providence, RI. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the NIH. We thank Kathy Kurowski and Cara Misiurski for assistance with participant testing, James Dixon for helpful suggestions regarding the growth curve analyses, and Ted Strauss for assistance with the simulations. NR 71 TC 27 Z9 28 U1 1 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD MAY PY 2011 VL 117 IS 2 BP 53 EP 68 DI 10.1016/j.bandl.2011.01.004 PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 754OM UT WOS:000289864800001 PM 21371743 ER PT J AU Khalili, H Wolpin, BM Huang, ES Giovannucci, EL Kraft, P Fuchs, CS Chan, AT AF Khalili, Hamed Wolpin, Brian M. Huang, Edward S. Giovannucci, Edward L. Kraft, Peter Fuchs, Charles S. Chan, Andrew T. TI ABO Blood Group and Risk of Colorectal Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PANCREATIC-CANCER AB Background: Recent studies have shown an association between non-O blood group and risk of pancreatic cancer. It is unclear whether this association is observed with other gastrointestinal malignancies, including colorectal cancers. Methods: We examined the relationship between ABO blood group and the risk of incident colorectal cancer in two large prospective cohorts. We calculated HR using Cox proportional hazard modeling while adjusting for known risk factors of colorectal cancer. Results: During 996,779 person-years of follow-up, we documented 1,025 incident cases of colorectal cancers. Compared to individuals with blood group O, the multivariate-adjusted HR were 1.08 (95% CI, 0.94-1.24) for blood group A, 1.20 (95% CI, 1.00-1.45) for blood group B, and 1.08 (95% CI, 0.85-1.36) for blood group AB. Conclusion: In two large prospective cohorts, we did not observe a statistically significant association between ABO blood group and risk of colorectal cancer. Impact: These results do not support an association between ABO blood group and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 20(5); 1017-20. (C) 2011 AACR. C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Div Gastroenterol, Boston, MA 02114 USA. [Giovannucci, Edward L.; Fuchs, Charles S.; Chan, Andrew T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Div Gastroenterol, 55 Fruit St,GRJ-728A, Boston, MA 02114 USA. EM achan@partners.org FU IBD Working Group; [R01 CA137178]; [P01 CA55075]; [P01 CA87969] FX Funded by R01 CA137178, P01 CA55075, P01 CA87969. Dr. Chan is a Damon Runyon Cancer Research Foundation Clinical Investigator. Dr. Khalili is supported by a career development award from the IBD Working Group. NR 12 TC 23 Z9 23 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2011 VL 20 IS 5 BP 1017 EP 1020 DI 10.1158/1055-9965.EPI-10-1250 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 759MU UT WOS:000290251000034 PM 21415359 ER PT J AU Spurdle, AB Marquart, L McGuffog, L Healey, S Sinilnikova, O Wan, F Chen, XQ Beesley, J Singer, CF Dressler, AC Gschwantler-Kaulich, D Blum, JL Tung, N Weitzel, J Lynch, H Garber, J Easton, DF Peock, S Cook, M Oliver, CT Frost, D Conroy, D Evans, DG Lalloo, F Eeles, R Izatt, L Davidson, R Chu, C Eccles, D Selkirk, CG Daly, M Isaacs, C Stoppa-Lyonnet, D Sinilnikova, OM Buecher, B Belotti, M Mazoyer, S Barjhoux, L Verny-Pierre, C Lasset, C Dreyfus, H Pujol, P Collonge-Rame, MA Rookus, MA Verhoef, S Kriege, M Hoogerbrugge, N Ausems, MGEM van Os, TA Wijnen, J Devilee, P Meijers-Heijboer, HEJ Blok, MJ Heikkinen, T Nevanlinna, H Jakubowska, A Lubinski, J Huzarski, T Byrski, T Durocher, F Couch, FJ Lindor, NM Wang, XS Thomassen, M Domchek, S Nathanson, K Caligo, MA Jernstrom, H Liljegren, A Ehrencrona, H For, PK Ganz, PA Olopade, OI Tomlinson, G Neuhausen, S Antoniou, AC Chenevix-Trench, G Rebbeck, TR AF Spurdle, Amanda B. Marquart, Louise McGuffog, Lesley Healey, Sue Sinilnikova, Olga Wan, Fei Chen, Xiaoqing Beesley, Jonathan Singer, Christian F. Dressler, Anne-Catharine Gschwantler-Kaulich, Daphne Blum, Joanne L. Tung, Nadine Weitzel, Jeff Lynch, Henry Garber, Judy Easton, Douglas F. Peock, Susan Cook, Margaret Oliver, Clare T. Frost, Debra Conroy, Don Evans, D. Gareth Lalloo, Fiona Eeles, Ros Izatt, Louise Davidson, Rosemarie Chu, Carol Eccles, Diana Selkirk, Christina G. Daly, Mary Isaacs, Claudine Stoppa-Lyonnet, Dominique Sinilnikova, Olga M. Buecher, Bruno Belotti, Muriel Mazoyer, Sylvie Barjhoux, Laure Verny-Pierre, Carole Lasset, Christine Dreyfus, Helene Pujol, Pascal Collonge-Rame, Marie-Agnes Rookus, Matti A. Verhoef, Senno Kriege, Mieke Hoogerbrugge, Nicoline Ausems, Margreet G. E. M. van Os, Theo A. Wijnen, Juul Devilee, Peter Meijers-Heijboer, Hanne E. J. Blok, Marinus J. Heikkinen, Tuomas Nevanlinna, Heli Jakubowska, Anna Lubinski, Jan Huzarski, Tomasz Byrski, Tomasz Durocher, Francine Couch, Fergus J. Lindor, Noralane M. Wang, Xianshu Thomassen, Mads Domchek, Susan Nathanson, Kate Caligo, M. A. Jernstrom, Helena Liljegren, Annelie Ehrencrona, Hans Karlsson, Per Ganz, Patricia A. Olopade, Olufunmilayo I. Tomlinson, Gail Neuhausen, Susan Antoniou, Antonis C. Chenevix-Trench, Georgia Rebbeck, Timothy R. CA GEMO Study Collaborators SWE-BRCA TI Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNKNOWN CLINICAL-SIGNIFICANCE; DNA-SEQUENCE VARIANTS; OVARIAN-CANCER; HAPLOTYPE FREQUENCIES; CYS557SER ALLELE; SUSCEPTIBILITY; IDENTIFICATION; POPULATION; DISEASE; COHORT AB Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk. Cancer Epidemiol Biomarkers Prev; 20(5); 1032-38. (C) 2011 AACR. C1 [Rebbeck, Timothy R.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Spurdle, Amanda B.; Marquart, Louise; Healey, Sue; Chen, Xiaoqing; Beesley, Jonathan; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [McGuffog, Lesley; Easton, Douglas F.; Peock, Susan; Cook, Margaret; Antoniou, Antonis C.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Oliver, Clare T.; Frost, Debra; Conroy, Don] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England. [Sinilnikova, Olga] IARC, Lyon, France. [Daly, Mary] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Singer, Christian F.; Dressler, Anne-Catharine; Gschwantler-Kaulich, Daphne] Med Univ Vienna, Vienna, Austria. [Blum, Joanne L.] Baylor Sammons Canc Ctr, Hereditary Canc Risk Program, Dallas, TX USA. [Tomlinson, Gail] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Garber, Judy; Neuhausen, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weitzel, Jeff] City Hope Natl Med Ctr, Duarte, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Ganz, Patricia A.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Lynch, Henry] Creighton Univ, Omaha, NE 68178 USA. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, Ros] Inst Canc Res, Oncogenet Team, London SW3 6JB, England. [Eeles, Ros] Royal Marsden NHS Fdn Trust, London, England. [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, London, England. [Davidson, Rosemarie] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Selkirk, Christina G.] Northshore Univ Hlth Syst, Evanston, IL USA. [Olopade, Olufunmilayo I.] Univ Chicago, Chicago, IL 60637 USA. [Isaacs, Claudine] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. [Stoppa-Lyonnet, Dominique; Buecher, Bruno; Belotti, Muriel] Univ Paris 05, INSERM, Inst Curie, Serv Genet Oncol,U509, Paris, France. [Sinilnikova, Olga M.; Barjhoux, Laure; Verny-Pierre, Carole] Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure; Verny-Pierre, Carole] Univ Lyon, CNRS, Ctr Leon Berard, Equipe Labellisee,LIGUE 2008,UMR5201, Lyon, France. [Lasset, Christine] Univ Lyon 1, CNRS, UMR5558, F-69365 Lyon, France. [Lasset, Christine] Ctr Leon Berard, Unite Prevent & Epidemiol Genet, F-69373 Lyon, France. [Dreyfus, Helene] CHU Grenoble, Dept Genet, F-38043 Grenoble, France. [Dreyfus, Helene] Univ Grenoble, Inst Albert Bonniot, Grenoble, France. [Pujol, Pascal] Ctr Hosp Univ Arnaud de Villeneuve, Unite Oncogenet, Montpellier, France. [Pujol, Pascal] CRCM Val dAurelle, INSERM 896, Montpellier, France. CHU Besancon, Serv Genet Histol Biol Dev & Reprod, F-25030 Besancon, France. [GEMO Study Collaborators] Federat Natl Ctr Lutte Canc, GEMO Study Canc Genet Network Grp Genet & Canc, Lyon, France. [Rookus, Matti A.; Verhoef, Senno] Netherlands Canc Inst, Amsterdam, Netherlands. [Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Collonge-Rame, Marie-Agnes; Kriege, Mieke] Erasmus MC, Rotterdam, Netherlands. [Hoogerbrugge, Nicoline] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Ausems, Margreet G. E. M.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [van Os, Theo A.] Amsterdam Med Ctr, Leiden, Netherlands. [Wijnen, Juul; Devilee, Peter] Leiden Univ, Med Ctr, Leiden, Netherlands. [Blok, Marinus J.] Univ Hosp Maastricht, Maastricht, Netherlands. [Heikkinen, Tuomas; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Jakubowska, Anna; Lubinski, Jan; Huzarski, Tomasz; Byrski, Tomasz] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland. [Durocher, Francine] Ctr Hosp Univ Quebec, Quebec City, PQ, Canada. [Durocher, Francine] Univ Laval, Quebec City, PQ, Canada. [Couch, Fergus J.; Lindor, Noralane M.; Wang, Xianshu] Mayo Clin, Rochester, MN USA. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark. [Caligo, M. A.] Univ Hosp Pisa, Pisa, Italy. [Jernstrom, Helena] Univ Lund Hosp, S-22185 Lund, Sweden. [Liljegren, Annelie; SWE-BRCA] Karolinska Inst, Karolinska Univ Hosp, Stockholm, Sweden. [Ehrencrona, Hans] Uppsala Univ, Rudbeck Lab, Uppsala, Sweden. [Karlsson, Per] Sahlgrens Univ Hosp, Gothenburg, Sweden. RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Abramson Canc Ctr, 217 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rebbeck@mail.med.upenn.edu RI Hoogerbrugge, Nicoline/O-1016-2013; BYRSKI, Tomasz/I-2844-2014; Spurdle, Amanda/A-4978-2011; Ehrencrona, Hans/M-5619-2014; Jakubowska, Anna/O-8050-2014; GLADIEFF, Laurence/O-5129-2014 OI Nordling, Margareta/0000-0002-4047-4994; Eeles, Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901; Spurdle, Amanda/0000-0003-1337-7897; Nevanlinna, Heli/0000-0002-0916-2976; Evans, Gareth/0000-0002-8482-5784; Ehrencrona, Hans/0000-0002-5589-3622; GLADIEFF, Laurence/0000-0002-6980-9719 FU Nebraska Department of Health and Human Services; NIH [5UO1 CA86389, R01-CA74415, R01-CA102776, R01-CA083855, CA128978]; MUV Comprensive Cancer Center; Austrian Society for Endocrinological Oncology; Cancer Research, UK [C1287/A10118, C1287/A8874, C8197/A10123, C5047/A8385]; NIHR; Royal Marsden NHS Foundation Trust; Ligue National Contre le Cancer; Association for International Cancer Research [AICR-07-0454]; Association "Le cancer du sein, parlons-en!" Award; Dutch Cancer Society [NKI 1998-1854, NKI 2004-3088, NKI 2007-3756]; Helsinki University Central Hospital; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Canadian Institutes of Health Research (CIHR); Fonds de la Recherche en Sante du Quebec (FRSQ)/Reseau de Medecine Genetique Appliquee (RMGA); CURE Foundation; Canadian Breast Cancer Research Alliance (CBCRA); Fonds de la Recherche en Sante du Quebec (FRSQ); CIHR/R&D Health Research Foundation; NHMRC [145684, 288704, 454508]; National Breast Cancer Foundation; Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria; Cancer Councils of New South Wales, Tasmania; Cancer Councils of New South Wales, South Australia; Cancer Foundation of Western Australia; NCI [CA116201]; breast Cancer Research Foundation; Komen Foundation for the cure; [PBZ_KBN_122/P05/2004]; [HHSN21620074400C] FX MAGIC: The MAGIC Consortium includes the following centers and individuals: Baylor-Charles A. Sammons Cancer Center (J.L. Blum, M. D. Ph.D., Estelle Brothers, RN, Gaby Ethington), Baylor College of Medicine (Claire Noll, Sharon Plon, M. D., Ph.D.), Beth Israel Deaconess Medical Center (N. Tung, M. D.), City of Hope National Medical Center (Veronica Lagos, Jeffery Weitzel, M. D.), Creighton University (Carrie Snyder, B. A., H. T. Lynch, M. D., Patrice Watson, Ph.D.), Dana Farber Cancer Institute (Kathryn Stoeckert, J.E. Garber, M. D., M. P. H.), Duke University (Sydnee Crankshaw, Joellen Schildkraut, Ph.D.), NorthShore University Health-System Center for Medical Genetics (Wendy S. Rubinstein, M. D., Ph.D., C. G. Selkirk, M. S. C. G. C.), Fox Chase Cancer Center (M. B. Daly, M. D., Ph.D., Andrew Godwin, Ph.D.), Queensland Institute of Medical Research (G. Chenevix-Trench), Georgetown University (C. Isaacs, M. D.), Jonsson Comprehensive Cancer Center at the University of California, Los Angeles (Joyce Seldon, M. S. C. G. C., P. A. Ganz, M. D.), Mayo Clinic College of Medicine (Linda Wadum, F.J. Couch, Ph.D.), University of Chicago (Shelly Cummings, O.I. Olopade, M. D.), University of California, Irvine (S. L. Neuhausen, Ph.D., Linda Steele), University of Pennsylvania Health System: (S. Domchek, M. D., K. Nathanson M. D., Tara Friebel, M. P. H., T. R. Rebbeck, Ph.D.), University of Texas, Southwestern (G. Tomlinson, M. D.), University of Vienna (C. F. Singer, M. D.), Women's College Hospital (Steven A. Narod, M. D.). This publication was supported in part by revenue from Nebraska cigarette taxes awarded to Creighton University by the Nebraska Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the State of Nebraska or the Nebraska Department of Health and Human Services. Support was also received from NIH grants 5UO1 CA86389 (to HTL) and R01-CA083855, R01-CA74415 (to SLN) and R01-CA102776 and R01-CA083855 (to T. R. Rebbeck).; Austria MUV: The authors thank Daniela Muhr, Christine Fuerhauser-Rappaport, all the Hereditary Breast and Ovarian Cancer counselling clinics in Austria, and the many families who contributed to this study. This study was supported by the MUV Comprensive Cancer Center (Cluster Genetics and Epigenetics) and by the Austrian Society for Endocrinological Oncology.; EMBRACE: Epidemiologic study of BRCA1 and BRCA2 mutation carriers (EMBRACE): D. F. Easton is the PI of the study. EMBRACE Collaborating Centers are: Coordinating Center, Cambridge: S. Peock, M. Cook, C. T. Oliver, D. Frost. North of Scotland Regional Genetics Service, Aberdeen: Helen Gregory, Zosia Miedzybrodzka. Northern Ireland Regional Genetics Service, Belfast: Patrick Morrison, Lisa Jeffers. West Midlands Regional Clinical Genetics Service, Birmingham: Trevor Cole, Carole McKeown, Kai-Ren Ong, Laura Boyes. South West Regional Genetics Service, Bristol: Alan Donaldson. East Anglian Regional Genetics Service, Cambridge: Joan Paterson. Medical Genetics Services for Wales, Cardiff: Alexandra Murray, Mark T. Rogers, Emma McCann. St James's Hospital, Dublin & National Centre for Medical Genetics, Dublin: M. John Kennedy, David Barton. South East of Scotland Regional Genetics Service, Edinburgh: Mary Porteous. Peninsula Clinical Genetics Service, Exeter: Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman. West of Scotland Regional Genetics Service, Glasgow: R. Davidson, Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt, Sarah Gibson. South East Thames Regional Genetics Service, Guys Hospital London: Louise Izatt, Gabriella Pichert, Chris Jacobs, Caroline Langman. North West Thames Regional Genetics Service, Kennedy-Galton Centre, Harrow: Huw Dorkins. Leicestershire Clinical Genetics Service, Leicester: Julian Barwell. Yorkshire Regional Genetics Service, Leeds: C. Chu, Tim Bishop, Julie Miller. Merseyside & Cheshire Clinical Genetics Service, Liverpool: Ian Ellis, Catherine Houghton. Manchester Regional Genetics Service, Manchester: D. G. Evans, F. Lalloo, Felicity Holt. North East Thames Regional Genetics Service, NE Thames: Alison Male, Lucy Side, Cheryl Berlin. Nottingham Centre for Medical Genetics, Nottingham: Jacqueline Eason, Rebecca Collier. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, Oonagh Claber. Oxford Regional Genetics Service, Oxford: Lisa Walker, Diane McLeod, Dorothy Halliday, Sarah Durrell, Barbara Stayner. The Institute of Cancer Research and Royal Marsden NHS Foundation Trust: R. Eeles, Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Lucia D'Mello, Elizabeth Page, Audrey Ardern-Jones, Kelly Kohut, Jennifer Wiggins. Elena Castro, Anita Mitra, Lisa Robertson. North Trent Clinical Genetics Service, Sheffield: Jackie Cook, Oliver Quarrell, Cathryn Bardsley. South Essex Cancer Research Network, Southend: Anne Robinson. South West Thames Regional Genetics Service, London: Shirley Hodgson, Sheila Goff, Glen Brice, Lizzie Winchester. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton: D. Eccles, Anneke Lucassen, Gillian Crawford, Emma Tyler, Donna McBride. EMBRACE is funded by Cancer Research, UK grants C1287/A10118 and C1287/A8874. D. Conroy is supported by Cancer Research UK grant C8197/A10123. D. G. Evans and F. Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The RoyalMarsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. R. Eeles, Elizabeth Bancroft, and Lucia D'Mello are also supported by Cancer Research UK grant C5047/A8385.; GEMO: The GEMO study (Cancer Genetics Network "Groupe Genetique et Cancer,"Federation Nationale des Centres de Lutte Contre le Cancer, France) is supported by the Ligue National Contre le Cancer; Association for International Cancer Research grant (AICR-07-0454); and the Association "Le cancer du sein, parlons-en!" Award.; HEBON: The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) Collaborating Centers: Coordinating center: Netherlands Cancer Institute, Amsterdam: Frans B. L. Hogervorst, S. Verhoef, Martijn Verheus, Laura J. van't Veer, Flora E. van Leeuwen, M. A. Rookus; Erasmus Medical Center, Rotterdam: Margriet Collee, Ans M. W. van den Ouweland, Agnes Jager, Maartje J. Hooning, Madeleine M. A. Tilanus-Linthorst, Caroline Seynaeve; Leiden University Medical Center, Leiden: Christi J. van Asperen, J. T. Wijnen, Maaike P. Vreeswijk, Rob A. Tollenaar, P. Devilee; Radboud University Nijmegen Medical Center, Nijmegen: Marjolijn J. Ligtenberg, N. Hoogerbrugge; University Medical Center Utrecht, Utrecht: M. G. E. M. Ausems, Rob B. van der Luijt; Amsterdam Medical Center: Cora M. Aalfs, T. A. van Os; VU University Medical Center, Amsterdam: Johan J. P. Gille, Quinten Waisfisz, H. E. J. Meijers-Heijboer; University Hospital Maastricht, Maastricht: Encarna B. Gomez-Garcia, Cees E. van Roozendaal, M. J. Blok; University Medical Center Groningen University: Jan C. Oosterwijk, Annemarie H. van der Hout, Marian J. Mourits; The Netherlands Foundation for the detection of hereditary tumors, Leiden, the Netherlands: Hans F. Vasen. The HEBON study is supported by the Dutch Cancer Society grants NKI 1998-1854, NKI 2004-3088, and NKI 2007-3756.; HEBCS study was supported by Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society and the Sigrid Juselius Foundation. The authors thank Drs. Kristiina Aittomaki, Carl Blomqvist, and Kirsimari Aaltonen for their help with patient data and samples.; IHCC: Support was provided by grant PBZ_KBN_122/P05/2004.; INHERIT: The authors thank Dr. Martine Dumont for sample management, Martine Tranchant for skillful technical assistance, and Dr. Frederic Guenard for genotyping. They also thank Dr. Jacques Simard, Director of the INHERIT BRCAs research program, which is supported by the Canadian Institutes of Health Research (CIHR). This work was also supported by the Fonds de la Recherche en Sante du Quebec (FRSQ)/Reseau de Medecine Genetique Appliquee (RMGA), the CURE Foundation, and the Canadian Breast Cancer Research Alliance (CBCRA). F. Durocher is a recipient of a chercheur-boursier from the Fonds de la Recherche en Sante du Quebec (FRSQ) and a Research Career Award in the Health Sciences from CIHR/R&D Health Research Foundation.; kConFab: The authors thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded by NHMRC grants 145684, 288704, and 454508) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. A. B. Spurdle and G. Chenevix-Trench are supported by a NHMRC Senior Research and Principal Research Fellowships, respectively.; Mayo: This research was supported by NIH grant CA128978, and NCI breast cancer specialized program of research excellence (SPORE) CA116201, and grants from the breast Cancer Research Foundation and the Komen Foundation for the cure. The authors thank Zachary Fredericksen, Robert Tarrell, and Vernon S. Pankratz for their assistance.; Penn: This work was supported by HHSN21620074400C (to SMD), the Breast Cancer Research Foundation (to KLN), and R01-CA102776 and R01-CA083855 (to T. R. Rebbeck). NR 21 TC 4 Z9 5 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2011 VL 20 IS 5 BP 1032 EP 1038 DI 10.1158/1055-9965.EPI-10-0909 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 759MU UT WOS:000290251000037 PM 21393566 ER PT J AU Chan, AT AF Chan, Andrew T. TI Aspirin and Familial Adenomatous Polyposis: Coming Full Circle SO CANCER PREVENTION RESEARCH LA English DT Article ID SPORADIC COLORECTAL ADENOMAS; DIFLUOROMETHYLORNITHINE PLUS SULINDAC; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SPONTANEOUS INTESTINAL ADENOMAS; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND TRIAL; LOW-DOSE ASPIRIN; MIN MOUSE MODEL; CARDIOVASCULAR RISK; SODIUM-SALICYLATE AB This perspective discusses the clinical trial reported by Burn and colleagues in this issue of the journal (beginning on page 655), which assessed aspirin and resistant starch for the prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP). The findings are examined in the context of previous clinical trials of aspirin in patients with sporadic adenomas and of sulindac or celecoxib in patients with FAP. This newly reported work raises important considerations of a role for aspirin in the clinical management of FAP patients and adds to considerations of a role for aspirin in the chemoprevention of colorectal cancer among broader populations. Cancer Prev Res; 4(5); 623-7. (c) 2011 AACR. C1 [Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dep Med, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02114 USA. RP Chan, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dep Med, 55 Fruit St, Boston, MA 02114 USA. EM achan@partners.org FU NCI NIH HHS [R01 CA137178-03, R01 CA137178] NR 59 TC 5 Z9 5 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAY PY 2011 VL 4 IS 5 BP 623 EP 627 DI 10.1158/1940-6207.CAPR-11-0157 PG 5 WC Oncology SC Oncology GA 758XP UT WOS:000290201100001 PM 21543340 ER PT J AU Pomerantz, MM Werner, L Xie, WL Regan, MM Lee, GSM Sun, T Evan, C Petrozziello, G Nakabayashi, M Oh, WK Kantoff, PW Freedman, ML AF Pomerantz, Mark M. Werner, Lillian Xie, Wanling Regan, Meredith M. Lee, Gwo-Shu Mary Sun, Tong Evan, Carolyn Petrozziello, Gillian Nakabayashi, Mari Oh, William K. Kantoff, Philip W. Freedman, Matthew L. TI Association of Prostate Cancer Risk Loci with Disease Aggressiveness and Prostate Cancer-Specific Mortality SO CANCER PREVENTION RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; RADICAL PROSTATECTOMY; SUSCEPTIBILITY LOCI; CHROMOSOME 8Q24; MULTIPLE LOCI; VARIANTS; ANTIGEN; IDENTIFICATION; POLYMORPHISMS; PROMOTER AB Genome-wide association studies have detected more than 30 inherited prostate cancer risk variants. While clearly associated with risk, their relationship with clinical outcome, particularly prostate cancer-specific mortality, is less well known. We investigated whether the risk variants are associated with various measures of disease aggressiveness and prostate cancer-specific mortality. In a cohort of 3,945 men of European ancestry with prostate cancer, we genotyped 36 single nucleotide polymorphisms (SNP): 35 known prostate cancer risk variants and one SNP (rs4054823) that was recently reported to be associated with prostate cancer aggressiveness. The majority of subjects had a diagnosis of prostate cancer between 1995 and 2004, and the cohort included a total of 580 prostate cancer-specific deaths. We evaluated associations between the 36 polymorphisms and prostate cancer survival, as well as other clinical parameters including age at diagnosis, prostate-specific antigen (PSA) at diagnosis, and Gleason score. Two SNPs, rs2735839 at chromosome 19(413 and rs7679673 at 4q24, were associated with prostate cancer-specific survival (P = 7 x 10(-4) and 0,014, respectively). A total of 12 SNPs were associated with other variables (P < 0.05): age at diagnosis, PSA at diagnosis, Gleason score, and/or disease aggressiveness based on D'Amico criteria, Genotype status at rs4054823 was not associated with aggressiveness or outcome. Our results identify two common polymorphisms associated with prostate cancer-specific mortality. Cancer Prey Res; 4(5); 719-28. (c) 2011 AACR. C1 [Pomerantz, Mark M.; Lee, Gwo-Shu Mary; Sun, Tong; Evan, Carolyn; Petrozziello, Gillian; Nakabayashi, Mari; Kantoff, Philip W.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Werner, Lillian; Xie, Wanling; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Werner, Lillian; Xie, Wanling; Regan, Meredith M.] Harvard Univ, Sch Med, Boston, MA USA. [Oh, William K.] Mt Sinai Sch Med, Dept Med Oncol, New York, NY USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana Bldg Rm 710A,44 Binney St, Boston, MA 02115 USA. EM freedman@broadinstitute.org RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU William L. Edwards Prostate Cancer Foundation; Howard Hughes Medical Institute Physician Scientist Early Career Awardee; Doris Duke Clinical Scientist Development Award; NIH [R01 CA129435]; Mayer Foundation; H.L. Snyder Medical Foundation; Emerald Foundation, Inc.; Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (National Cancer Institute) [5P50CA90381] FX M. Pomerantz is the recipient of the William L. Edwards Prostate Cancer Foundation Young Investigator Award. M.L. Freedman is a Howard Hughes Medical Institute Physician Scientist Early Career Awardee and is a recipient of a 2006 Doris Duke Clinical Scientist Development Award. This is was supported by grants from the NIH (R01 CA129435 to M.L. Freedman), the Mayer Foundation (to M.L. Freedman), the H.L. Snyder Medical Foundation (to M.L. Freedman), the Emerald Foundation, Inc. (to M.L. Freedman), and the Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (National Cancer Institute Grant 5P50CA90381). NR 40 TC 22 Z9 24 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAY PY 2011 VL 4 IS 5 BP 719 EP 728 DI 10.1158/1940-6207.CAPR-10-0292 PG 10 WC Oncology SC Oncology GA 758XP UT WOS:000290201100012 PM 21367958 ER PT J AU Lee, JE Li, HJ Chan, AT Hollis, BW Lee, IM Stampfer, MJ Wu, K Giovannucci, E Ma, J AF Lee, Jung Eun Li, Haojie Chan, Andrew T. Hollis, Bruce W. Lee, I-Min Stampfer, Meir J. Wu, Kana Giovannucci, Edward Ma, Jing TI Circulating Levels of Vitamin D and Colon and Rectal Cancer: The Physicians' Health Study and a Meta-analysis of Prospective Studies SO CANCER PREVENTION RESEARCH LA English DT Article ID COLORECTAL-CANCER; SUBSEQUENT RISK; VDR GENOTYPES; CALCIUM; PLASMA; 25-HYDROXYVITAMIN-D; CARCINOGENESIS; INHIBITION; PROSTATE; D-3 AB It remains unknown whether increased risk with low levels of vitamin D is present for colon and/or rectal cancer. To investigate the association between circulating vitamin D levels and colon and rectal cancer, we examined the associations between plasma levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and colon and rectal cancer in the Physicians' Health Study and then conducted a meta-analysis of eight prospective studies of circulating levels of 25(OH)D and colon and rectal cancers, including the Physicians' Health Study. Study-specific ORs and 95% CIs were pooled by using a random-effects model. A total of 1,822 colon and 868 rectal cancers were included in the meta-analysis. We observed a significant inverse association for colorectal cancer (OR = 0.66; 95% Cl, 0.54-0.81), comparing top versus bottom quantiles of circulating 25(OH)D levels. The inverse association stronger for rectal cancer (OR = 0.50 for top versus bottom quantiles; 95% CI, 0.28-0.88) than colon cancer (OR = 0.77; 95% CI, 0.56-1.07; P value for difference between colon and rectal cancer = 0.20). These data suggest an inverse association between circulating 25(OH)D levels and colorectal cancer, with a stronger association for rectal cancer. Cancer Pier Res; 4(5); 735-43. (c) 2011 AACR. C1 [Ma, Jing] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Lee, I-Min] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA. [Chan, Andrew T.; Lee, I-Min] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Stampfer, Meir J.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Li, Haojie] GlaxoSmithKline R&D, Worldwide Epidemiol, Collegeville, PA USA. [Hollis, Bruce W.] Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, Charleston, SC 29425 USA. RP Ma, J (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. EM jing.ma@channing.harvard.edu OI Lee, Jung Eun/0000-0003-1141-878X FU National Cancer Institute [CA42182, CA90598, CA58684, CA34944, CA40360, CA137178, CA097193]; National Heart, Lung, and Blood Institute [HL26490, HL34595]; Damon Runyon clinical investigator award; National Cancer Institute of Canada [019894]; Prevent Cancer Foundation FX This study was supported by grant CA42182, CA90598, CA58684, CA34944, CA40360, CA137178, and CA097193 from the National Cancer Institute; by grant HL26490 and HL34595 from the National Heart, Lung, and Blood Institute; by Damon Runyon clinical investigator award (ATC); by the National Cancer Institute of Canada (019894) and by Prevent Cancer Foundation fellowship grant (JEL) A.T. Chan is a Damon Runs on Clinical Investigator. NR 33 TC 88 Z9 91 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAY PY 2011 VL 4 IS 5 BP 735 EP 743 DI 10.1158/1940-6207.CAPR-10-0289 PG 9 WC Oncology SC Oncology GA 758XP UT WOS:000290201100014 PM 21430073 ER PT J AU Alam, MM Riyadh, MA Fatema, K Rahman, MA Akhtar, N Ahmed, T Chowdhury, MI Chowdhury, F Calderwood, SB Harris, JB Ryan, ET Qadri, F AF Alam, Mohammad Murshid Riyadh, M. Asrafuzzaman Fatema, Kaniz Rahman, Mohammad Arif Akhtar, Nayeema Ahmed, Tanvir Chowdhury, Mohiul Islam Chowdhury, Fahima Calderwood, Stephen B. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi TI Antigen-Specific Memory B-Cell Responses in Bangladeshi Adults after One- or Two-Dose Oral Killed Cholera Vaccination and Comparison with Responses in Patients with Naturally Acquired Cholera SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID IMMUNOLOGICAL MEMORY; SWEDISH VOLUNTEERS; IMMUNE-RESPONSES; TOXIN ADJUVANT; FIELD TRIAL; IMMUNIZATION; VACCINES; INFECTION; O1; LIPOPOLYSACCHARIDE AB The mediators of protective immunity against cholera are currently unknown, but memory B-cell responses may play a central role in facilitating long-term and anamnestic responses against Vibrio cholerae, the cause of cholera. We compared memory B-cell responses in adults with natural cholera in Bangladesh (n = 70) to responses in Bangladeshi adults after one-dose (n = 30) or two-dose (n = 30) administration of an oral killed cholera vaccine, WC-rBS (Dukoral; Crucell), assessing the responses at the acute stage of disease or prevaccination and then on days 3, 30, 90, 180, 270, and 360. Individuals with natural cholera developed prominent vibriocidal and plasma anti-cholera toxin B subunit (CtxB) and lipopolysaccharide (LPS) IgG and IgA responses, but these responses returned to baseline by 1 year of follow-up. Vaccinees developed plasma anti-CtxB and anti-LPS IgG and IgA responses that were generally comparable to those in individuals recovering from natural disease, but vibriocidal responses were lower in vaccinees than in infected patients. Individuals recovering from natural disease developed memory B-cell IgG and IgA anti-CtxB and anti-LPS responses by day 30, and these responses were detectable through at least days 180 to 360. In contrast, we detected no IgA or IgG memory B-cell responses to LPS in vaccinees; anti-CtxB IgA responses were only detectable on day 30, and anti-CtxB IgG responses were detectable until days 90 to 180, compared to days 270 to 360 in patients. These findings may explain in part the relatively short-term protection afforded by oral cholera vaccination compared to natural disease. C1 [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Immunol Unit, Dhaka 1212, Bangladesh. [Calderwood, Stephen B.; Harris, Jason B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Qadri, F (reprint author), Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Immunol Unit, 68 Shaheed Tajuddin Ahmed Sarani, Dhaka 1212, Bangladesh. EM fqadri@icddrb.org FU ICDDR,B; National Institutes of Health, including the National Institute of Allergy and Infectious Diseases [AI058935, AI077883]; Fogarty International Center [TW05572, K01]; Swedish Sida FX This study was supported by the ICDDR,B and by grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (AI058935 [S.B.C., E.T.R., and F.Q.] and AI077883 [E.T.R. and F.Q.]), a training grant in vaccine development from the Fogarty International Center (TW05572 [M.M.A. and F.Q.], and a career development award (K01) from the Fogarty International Center (TW007409 [J.B.H.]). This study was also supported by the Swedish Sida (F.Q.). NR 42 TC 36 Z9 36 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2011 VL 18 IS 5 BP 844 EP 850 DI 10.1128/CVI.00562-10 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 758IB UT WOS:000290156600021 PM 21346055 ER PT J AU Porwancher, RB Hagerty, CG Fan, JQ Landsberg, L Johnson, BJB Kopnitsky, M Steere, AC Kulas, K Wong, SJ AF Porwancher, Richard B. Hagerty, C. Greg Fan, Jianqing Landsberg, Lisa Johnson, Barbara J. B. Kopnitsky, Mark Steere, Allen C. Kulas, Karen Wong, Susan J. TI Multiplex Immunoassay for Lyme Disease Using VlsE1-IgG and pepC10-IgM Antibodies: Improving Test Performance through Bioinformatics SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; BORRELIA-BURGDORFERI; SERODIAGNOSIS; CLASSIFICATION; DIAGNOSIS; PEPTIDE; VLSE; REGRESSION; ACCURACY; CRITERIA AB The Centers for Disease Control and Prevention currently recommends a 2-tier serologic approach to Lyme disease laboratory diagnosis, comprised of an initial serum enzyme immunoassay (EIA) for antibody to Borrelia burgdorferi followed by supplementary IgG and IgM Western blotting of EIA-positive or -equivocal samples. Western blot accuracy is limited by subjective interpretation of weakly positive bands, false-positive IgM immunoblots, and low sensitivity for detection of early disease. We developed an objective alternative second-tier immunoassay using a multiplex microsphere system that measures VlsE1-IgG and pepC10-IgM antibodies simultaneously in the same sample. Our study population comprised 79 patients with early acute Lyme disease, 82 patients with early-convalescent-phase disease, 47 patients with stage II and III disease, 34 patients post-antibiotic treatment, and 794 controls. A bioinformatic technique called partial receiver-operator characteristic (ROC) regression was used to combine individual antibody levels into a single diagnostic score with a single cutoff; this technique enhances test performance when a high specificity is required (e. g., >= 95%). Compared to Western blotting, the multiplex assay was equally specific (95.6%) but 20.7% more sensitive for early-convalescent-phase disease (89.0% versus 68.3%, respectively; 95% confidence interval [95% CI] for difference, 12.1% to 30.9%) and 12.5% more sensitive overall (75.0% versus 62.5%, respectively; 95% CI for difference, 8.1% to 17.1%). As a second-tier test, a multiplex assay for VlsE1-IgG and pepC10-IgM antibodies performed as well as or better than Western blotting for Lyme disease diagnosis. Prospective validation studies appear to be warranted. C1 [Porwancher, Richard B.; Landsberg, Lisa] Infect Dis Consultants PC, Mercerville, NJ 08619 USA. [Porwancher, Richard B.; Hagerty, C. Greg] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Piscataway, NJ 08854 USA. [Fan, Jianqing] Princeton Univ, Dept Operat Res & Financial Engn, Princeton, NJ 08544 USA. [Johnson, Barbara J. B.] Ctr Dis Control & Prevent, Div Vector Borne Dis, Ft Collins, CO USA. [Kopnitsky, Mark] Zeus Sci Inc, Branchburg, NJ USA. [Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Kulas, Karen; Wong, Susan J.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. RP Porwancher, RB (reprint author), Infect Dis Consultants PC, 1245 Whitehorse Mercerville Rd,Suite 411, Mercerville, NJ 08619 USA. EM porwancher@aol.com FU SBIR-AT-NIAID [1R43AI069564-01, -01S1]; National Institute of Allergy and Infectious Diseases, National Institutes of Health; Zeus Scientific, Inc., to Health Research, Inc., Menands, NY FX Financial support was provided by SBIR-AT-NIAID grants 1R43AI069564-01 and -01S1 to Infectious Disease Consultants, PC, from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by a grant from Zeus Scientific, Inc., to Health Research, Inc., Menands, NY, a nonprofit organization which supported the work performed by S.J.W. and K.K. at the NYSDOH, Albany, NY, for this study. NR 41 TC 18 Z9 19 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2011 VL 18 IS 5 BP 851 EP 859 DI 10.1128/CVI.00409-10 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 758IB UT WOS:000290156600022 PM 21367982 ER PT J AU Chawla, A Sterns, RH Nigwekar, SU Cappuccio, JD AF Chawla, Arun Sterns, Richard H. Nigwekar, Sagar U. Cappuccio, Joseph D. TI Mortality and Serum Sodium: Do Patients Die from or with Hyponatremia? SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SEVERE SYMPTOMATIC HYPONATREMIA; CENTRAL PONTINE MYELINOLYSIS; CHARLSON COMORBIDITY INDEX; IN-HOSPITAL MORTALITY; RISK-FACTOR; POPULATION; MANAGEMENT; OSTEOPOROSIS; MORBIDITY; FRACTURE AB Background and objectives Severe hyponatremia (<120 mEq/L) in hospitalized patients has a high mortality rate. We hypothesized that underlying diseases causing hyponatremia attribute to mortality rather than hyponatremia itself. Design, setting, participants, & measurements The relationship between mortality and serum sodium (sNa) was examined in 45,693 patients admitted to a single community teaching hospital between January 1996 and December 2007. We conducted a comprehensive retrospective review of the medical records of 53 patients who died after developing sNa <120 mEq/L before or after admission and of 32 patients who survived after developing sNa <110 mEq/L. Results Mortality rates tended to increase as the sNa fell from 134 to 120 mEq/L, rising above 10% for patients with sNa of 120 to 124 mEq/L. However, below sNa of 120 mEq/L, the trend reversed, such that the mortality rate progressively decreased as sNa fell. More than two thirds of patients who died after sNa <120mEq/L had at least two additional acute severe progressive illnesses, most commonly sepsis and multiorgan failure. Three deaths (5.6%) in 12 years could plausibly be related to adverse consequences of hyponatremia, and one (1.8% of the fatal cases and 0.15% of all patients with sNa <120 mEq/L) was from cerebral edema. Most patients who survived with sNa <110 mEq/L had medication-induced hyponatremia. Severe underlying illnesses were uncommon in this group. Conclusions The nature of underlying illness rather than the severity of hyponatremia best explains mortality associated with hyponatremia. Neurologic complications from hyponatremia are uncommon among patients who die with hyponatremia. C1 [Sterns, Richard H.; Nigwekar, Sagar U.; Cappuccio, Joseph D.] Univ Rochester, Rochester Gen Hosp, Sch Med, Rochester, NY 14621 USA. [Chawla, Arun] Hofstra N Shore LIJ Sch Med, Div Nephrol & Hypertens, Great Neck, NY USA. [Nigwekar, Sagar U.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Nigwekar, Sagar U.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. RP Sterns, RH (reprint author), Univ Rochester, Rochester Gen Hosp, Sch Med, Rochester, NY 14621 USA. EM richard.sterns@rochestergeneral.org NR 27 TC 76 Z9 78 U1 0 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2011 VL 6 IS 5 BP 960 EP 965 DI 10.2215/CJN.10101110 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 761CK UT WOS:000290372600004 PM 21441132 ER PT J AU Lachin, JM Viberti, G Zinman, B Haffner, SM Aftring, RP Paul, G Kravitz, BG Herman, WH Holman, RR Kahn, SE AF Lachin, John M. Viberti, Giancarlo Zinman, Bernard Haffner, Steven M. Aftring, R. Paul Paul, Gitanjali Kravitz, Barbara G. Herman, William H. Holman, Rury R. Kahn, Steven E. CA ADOPT Study Grp TI Renal Function in Type 2 Diabetes with Rosiglitazone, Metformin, and Glyburide Monotherapy SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID AMBULATORY BLOOD-PRESSURE; GLUCOSE CONTROL; FOLLOW-UP; MICROALBUMINURIA; NEPHROPATHY; COMPLICATIONS; MELLITUS; METAANALYSIS; PROGRESSION; PREVENTION AB Background and objectives In ADOPT (A Diabetes Outcomes Prevention Trial), initial monotherapy with rosiglitazone provided more durable glycemic control than metformin or glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine differences in albumin excretion, renal function (estimated GFR), and BP over 5 years between treatment groups. Design, setting, participants, & measurements A total of 4351 recently diagnosed, drug-naive patients with type 2 diabetes were treated and followed for up to 5 years with rosiglitazone, metformin, or glyburide and were examined with periodic assessments of albumin/creatinine ratio (ACR), modification of diet in renal disease (MDRD)-estimated GFR, and BP. Results The ACR rose slowly with metformin. It fell with rosiglitazone and less so with glyburide over the first 2 years, and then rose slowly over time. Estimated GFR (eGFR) with all therapies rose into the high normal range over the first 3 to 4 years, more so with rosiglitazone, and then declined, more so with glyburide. Systolic BP was stable over time, values with rosiglitazone being lower, and diastolic BP declined over time, more so with rosiglitazone than with metformin or glyburide. There was no difference among groups in the incidence of emergent albuminuria (ACR >= 30 mg/g), hypertension, or impaired eGFR (<60 ml/min per 1.73 m(2)). Conclusions Over a 5-year period, initial monotherapy with rosiglitazone retards the rise of ACR compared with metformin, preserves eGFR compared with glyburide, and lowers BP relative to both comparators. Clin J Ant Sac Nephrol 6: 1032-1040, 2011. doi: 10.2215/CJN.09291010 C1 [Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Viberti, Giancarlo] Kings Coll London, Kings Coll London Sch Med, London WC2R 2LS, England. [Zinman, Bernard] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Zinman, Bernard] Univ Toronto, Toronto, ON, Canada. [Aftring, R. Paul; Paul, Gitanjali; Kravitz, Barbara G.] GlaxoSmithKline, King Of Prussia, PA USA. [Herman, William H.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Herman, William H.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Holman, Rury R.] Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. RP Lachin, JM (reprint author), George Washington Univ, Ctr Biostat, 6110 Execut Blvd, Rockville, MD 20852 USA. EM jml@bsc.gwu.edu RI Zinman, Bernard/E-7266-2013; OI Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002 NR 34 TC 20 Z9 22 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2011 VL 6 IS 5 BP 1032 EP 1040 DI 10.2215/CJN.09291010 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 761CK UT WOS:000290372600013 PM 21454723 ER PT J AU Delucchi, KL Katerberg, H Stewart, SE Denys, DAJP Lochner, C Stack, DE den Boer, JA van Balkom, AJLM Jenike, MA Stein, DJ Cath, DC Mathews, CA AF Delucchi, Kevin L. Katerberg, Hilga Stewart, S. Evelyn Denys, Damiaan A. J. P. Lochner, Christine Stack, Denise E. den Boer, Johan A. van Balkom, Anton J. L. M. Jenike, Michael A. Stein, Dan J. Cath, Danielle C. Mathews, Carol A. TI Latent class analysis of the Yale-Brown Obsessive-Compulsive Scale symptoms in obsessive-compulsive disorder SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; COMPLEX SEGREGATION ANALYSIS; FACTOR-ANALYZED SYMPTOM; DSM-IV ADHD; SPECTRUM DISORDERS; DIMENSIONS; SUBTYPES; ADOLESCENTS; HETEROGENEITY; POLYMORPHISM AB Objective: Obsessive-compulsive disorder (OCD) is phenomenologically heterogeneous, and findings of underlying structure classification based on symptom grouping have been ambiguous to date. Variable-centered approaches, primarily factor analysis, have been used to identify homogeneous groups of symptoms; but person-centered latent methods have seen little use. This study was designed to uncover sets of homogeneous groupings within 1611 individuals with OCD based on symptoms. Method: Latent class analysis models using 61 obsessive-compulsive symptoms collected from the Yale-Brown Obsessive-Compulsive Scale were fit. Relationships between latent class membership and treatment response, sex, symptom severity, and comorbid tic disorders were tested for relationship to class membership. Results: Latent class analysis models of best fit yielded 3 classes. Classes differed only in frequency of symptom endorsement. Classes with higher symptom endorsement were associated with earlier age of onset, being male, higher Yale-Brown Obsessive-Compulsive Scale symptom severity scores, and comorbid tic disorders. There were no differences in treatment response between classes. Conclusions: These results provide support for the validity of a single underlying latent OCD construct, in addition to the distinct symptom factors identified previously via factor analyses. (C) 2011 Elsevier Inc. All rights reserved. C1 [Delucchi, Kevin L.; Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Katerberg, Hilga; den Boer, Johan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Stewart, S. Evelyn; Jenike, Michael A.] Massachusetts Gen Hosp, Obsess Compuls Disorder Clin Adult & Pediat, Boston, MA 02114 USA. [Stewart, S. Evelyn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit, Boston, MA USA. [Stewart, S. Evelyn; Stack, Denise E.; Jenike, Michael A.] McLean Hosp, Obsess Compuls Disorder Inst, Belmont, MA 02178 USA. [Denys, Damiaan A. J. P.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. [Denys, Damiaan A. J. P.] Netherlands Inst Neurosci, Amsterdam, Netherlands. [Katerberg, Hilga; Lochner, Christine; Stein, Dan J.] Univ Stellenbosch, Dept Psychiat, MRC Unit Anxiety & Stress Disorders, ZA-7600 Stellenbosch, South Africa. [Cath, Danielle C.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, GGZ Buitenamstel, Amsterdam, Netherlands. [Stein, Dan J.] Univ Cape Town, Dept Psychiat, ZA-7700 Rondebosch, South Africa. [van Balkom, Anton J. L. M.; Cath, Danielle C.] Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands. [van Balkom, Anton J. L. M.; Cath, Danielle C.] Altrecht Anxiety Outpatient Program, Utrecht, Netherlands. RP Delucchi, KL (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 0984-TRC, San Francisco, CA 94143 USA. EM kdelucchi@lppi.ucsf.edu RI Stewart, Evelyn/K-6961-2014; Stein, Dan/A-1752-2008; OI Stein, Dan/0000-0001-7218-7810; Stewart, S. Evelyn/0000-0002-0994-6383 FU NARSAD; Obsessive Compulsive Foundation; Harvard Scholar in Medicine Program; Canadian Institutes of Health Research FX The authors are grateful to the families with OCD in all of the participating centers who generously agreed to be part of this study. This work was partially supported by funds from NARSAD (CAM), the Obsessive Compulsive Foundation (CAM, SES), the Harvard Scholar in Medicine Program (SES), and the Canadian Institutes of Health Research (SES). NR 63 TC 6 Z9 6 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAY-JUN PY 2011 VL 52 IS 3 BP 334 EP 341 DI 10.1016/j.comppsych.2010.06.007 PG 8 WC Psychiatry SC Psychiatry GA 754TS UT WOS:000289880900015 PM 21145539 ER PT J AU Kahn, SE Lachin, JM Zinman, B Haffner, SM Aftring, RP Pau, G Kravitz, BG Herman, WH Viberti, G Holman, RR AF Kahn, Steven E. Lachin, John M. Zinman, Bernard Haffner, Steven M. Aftring, R. Paul Pau, Gitanjali Kravitz, Barbara G. Herman, William H. Viberti, Giancarlo Holman, Rury R. CA ADOPT Study Grp TI Effects of Rosiglitazone, Glyburide, and Meiformin on beta-Cell Function and Insulin Sensitivity in ADOPT SO DIABETES LA English DT Article ID HUMAN PANCREATIC-ISLETS; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; RESISTANCE; SECRETION; METFORMIN; DYSFUNCTION; THERAPY; INDEX AB OBJECTIVE-ADOPT (A Diabetes Outcome Progression Trial) demonstrated that initial monotherapy with rosiglitazone provided superior durability of glycemic control compared with metformin and glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine measures of beta-cell function and insulin sensitivity from an oral glucose tolerance test (OGTT) over a 4-year period among the three treatments. RESEARCH DESIGN AND METHODS-Recently diagnosed, drug-naive patients with type 2 diabetes (4,360 total) were treated for a median of 4.0 years with rosiglitazone, metformin, or glyburide and were examined with periodic metabolic testing using an OGTT. RESULTS-Measures of beta-cell function and insulin sensitivity from an OGTT showed more favorable changes over time with rosiglitazone versus metformin or glyburide. Persistent improvements were seen in those who completed 4 years of monotherapy and marked deterioration of beta-cell function in those who failed to maintain adequate glucose control with initial monotherapy. CONCLUSIONS-The favorable combined changes in beta-cell function and insulin sensitivity over time with rosiglitazone appear to be responsible for its superior glycemic durability over metformin and glyburide as initial monotherapy in type 2 diabetes. Diabetes 60:1552-1560, 2011 C1 [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Zinman, Bernard] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Zinman, Bernard] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Aftring, R. Paul; Pau, Gitanjali; Kravitz, Barbara G.] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Herman, William H.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Herman, William H.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Viberti, Giancarlo] Kings Coll London, Kings Coll London Sch Med, London WC2R 2LS, England. [Holman, Rury R.] Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. EM skahn@u.washington.edu RI Zinman, Bernard/E-7266-2013; OI Kahn, Steven/0000-0001-7307-9002 FU GlaxoSmithKline FX The study was supported by GlaxoSmithKline. Academic members of the ADOPT Steering Committee have received honoraria, consulting fees, and/or grant/research support from GlaxoSmithKline. R.P.A., G.P., and B.G.K are employees of the company. No other potential conflicts of interest relevant to this article were reported. NR 21 TC 60 Z9 62 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2011 VL 60 IS 5 BP 1552 EP 1560 DI 10.2337/db10-1392 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 760UP UT WOS:000290349700023 PM 21415383 ER PT J AU Clermont, A Chilcote, TJ Kita, T Liu, J Riva, P Sinha, S Feener, EP AF Clermont, Allen Chilcote, Tamie J. Kita, Takeshi Liu, Jia Riva, Priscilla Sinha, Sukanto Feener, Edward P. TI Plasma Kallikrein Mediates Retinal Vascular Dysfunction and Induces Retinal Thickening in Diabetic Rats SO DIABETES LA English DT Article ID B-1 RECEPTOR ANTAGONIST; MACULAR EDEMA; KININ SYSTEM; BLOOD-FLOW; FACTOR-XII; DEFICIENT MICE; IN-VIVO; RETINOPATHY; BRADYKININ; PERMEABILITY AB OBJECTIVE Plasma kallikrein (PK) has been identified in vitreous fluid obtained from individuals with diabetic retinopathy and has been implicated in contributing to retinal vascular dysfunction. In this report, we examined the effects of PK on retinal vascular functions and thickness in diabetic rats. RESEARCH DESIGN AND METHODS We investigated the effects of a selective PK inhibitor, ASP-440, and Cl inhibitor (C1-INH), the primary physiological inhibitor of PK, on retinal vascular permeability (RVP) and hemodynamics in rats with streptozotocin-induced diabetes. The effect of intravitreal PK injection on retinal thickness was examined by spectral domain optical coherence tomography. RESULTS Systemic continuous administration of ASP-440 for 4 weeks initiated at the time of diabetes onset inhibited RVP by 42% (P = 0.013) and 83% (P < 0.001) at doses of 0.25 and 0.6 mg/kg per day, respectively. Administration of ASP-440 initiated 2 weeks after the onset of diabetes ameliorated both RVP and retinal blood flow abnormalities in diabetic rats measured at 4 weeks' diabetes duration. Intravitreal injection of C1-INH similarly decreased impaired RVP in rats with 2 weeks' diabetes duration. Intravitreal injection of PK increased both acute RVP and sustained focal RVP (24 h postinjection) to a greater extent in diabetic rats compared with nondiabetic control rats. Intravitreal injection of PK increased retinal thickness compared with baseline to a greater extent (P = 0.017) in diabetic rats (from 193 +/- 10 mu m to 223 +/- 13 mu m) compared with nondiabetic rats (from 182 +/- 8 mu m to 193 +/- 9 mu m). CONCLUSIONS These results show that PK contributes to retinal vascular dysfunctions in diabetic rats and that the combination of diabetes and intravitreal injection of PK in rats induces retinal thickening. Diabetes 60:1590-1598, 2011 C1 [Clermont, Allen; Kita, Takeshi; Liu, Jia; Riva, Priscilla; Feener, Edward P.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Clermont, Allen; Kita, Takeshi; Liu, Jia; Feener, Edward P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Chilcote, Tamie J.; Sinha, Sukanto] ActiveSite Pharmaceut, Berkeley, CA USA. RP Feener, EP (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM edward.feener@joslin.harvard.edu FU Juvenile Diabetes Foundation International; National Institutes of Health [EY-19029, DK-36836, HL-090132] FX This work was supported in part by the Juvenile Diabetes Foundation International and the National Institutes of Health (grants EY-19029, DK-36836, and HL-090132). NR 39 TC 30 Z9 30 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2011 VL 60 IS 5 BP 1590 EP 1598 DI 10.2337/db10-1260 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 760UP UT WOS:000290349700028 PM 21444925 ER PT J AU Cooper, JD Smyth, DJ Walker, NM Stevens, H Burren, OS Wallace, C Greissl, C Ramos-Lopez, E Hypponen, E Dunger, DB Spector, TD Ouwehand, WH Wang, TJ Badenhoop, K Todd, JA AF Cooper, Jason D. Smyth, Deborah J. Walker, Neil M. Stevens, Helen Burren, Oliver S. Wallace, Chris Greissl, Christopher Ramos-Lopez, Elizabeth Hyppoenen, Elina Dunger, David B. Spector, Timothy D. Ouwehand, Willem H. Wang, Thomas J. Badenhoop, Klaus Todd, John A. TI Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; MULTIPLE-SCLEROSIS; D DEFICIENCY; 25-HYDROXYVITAMIN-D LEVELS; RHEUMATOID-ARTHRITIS; YOUNG-ADULTS; RISK; CHILDHOOD; CYP27B1; SERUM AB OBJECTIVE Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) is commonly reported in both children and adults worldwide, and growing evidence indicates that vitamin D deficiency is associated with many extraskeletal chronic disorders, including the autoimmune diseases type 1 diabetes and multiple sclerosis. RESEARCH DESIGN AND METHODS We measured 25(OH)D concentrations in 720 case and 2,610 control plasma samples and genotyped single nucleotide polymorphisms from seven vitamin D metabolism genes in 8,517 case, 10,438 control, and 1,933 family samples. We tested genetic variants influencing 25(OH)D metabolism for an association with both circulating 25(OH)D concentrations and disease status. RESULTS Type 1 diabetic patients have lower circulating levels of 25(OH)D than similarly aged subjects from the British population. Only 4.3 and 18.6% of type 1 diabetic patients reached optimal levels (>= 75 nmol/L) of 25(OH)D for bone health in the winter and summer, respectively. We replicated the associations of four vitamin D metabolism genes (GC, DHCR7, CYP2R1, and CYP24A1) with 25(OH)D in control subjects. In addition to the previously reported association between type 1 diabetes and CYP27B1 (P = 1.4 x 10(-4)), we obtained consistent evidence of type 1 diabetes being associated with DHCR7 (P = 1.2 x 10(-3)) and CYP2R1 (P = 3.0 x 10(-3)). CONCLUSIONS Circulating levels of 25(OH)D in children and adolescents with type 1 diabetes vary seasonally and are under the same genetic control as in the general population but are much lower. Three key 25(OH)D metabolism genes show consistent evidence of association with type 1 diabetes risk, indicating a genetic etiological role for vitamin D deficiency in type 1 diabetes. Diabetes 60:1624-1631, 2011 C1 [Cooper, Jason D.; Smyth, Deborah J.; Walker, Neil M.; Stevens, Helen; Burren, Oliver S.; Wallace, Chris; Todd, John A.] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res,Dept Med Genet, Juvenile Diabet Res Fdn,Wellcome Trust Diabet & I, Cambridge CB2 2QQ, England. [Greissl, Christopher; Ramos-Lopez, Elizabeth; Badenhoop, Klaus] Univ Hosp Frankfurt, Div Endocrinol Diabet & Metab, Dept Internal Med 1, Frankfurt, Germany. [Hyppoenen, Elina] UCL, Inst Child Hlth, Ctr Epidemiol Child Hlth, MRC, London, England. [Hyppoenen, Elina] UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. [Dunger, David B.] Univ Cambridge, Addenbrookes Hosp, Dept Paediat, Cambridge CB2 2QQ, England. [Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England. [Ouwehand, Willem H.] Wellcome Trust Sanger Inst, Hinxton, England. [Ouwehand, Willem H.] Natl Hlth Serv Blood & Transplant, Cambridge, England. [Wang, Thomas J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Wang, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP Todd, JA (reprint author), Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res,Dept Med Genet, Juvenile Diabet Res Fdn,Wellcome Trust Diabet & I, Cambridge CB2 2QQ, England. EM john.todd@cimr.cam.ac.uk RI Hypponen, Elina/B-2596-2014; OI Hypponen, Elina/0000-0003-3670-9399; Walker, Neil/0000-0001-9796-7688; Burren, Oliver/0000-0002-3388-5760; smyth, deborah/0000-0002-6330-2669; Dunger, Professor David/0000-0002-2566-9304; Wallace, Chris/0000-0001-9755-1703; Ouwehand, Willem/0000-0002-7744-1790 FU U.K. Medical Research Council (MRC) [G0000934]; Wellcome Trust [068545/Z/02, 076113/C/04/Z, 076113, 079895]; Wellcome Trust/Juvenile Diabetes Research Foundation [061858]; National Institutes of Health Research of England; Department of Health's National Institute for Health Research (Biomedical Research Centre); Medical Research Council [G0601653]; Food Standards Agency; Department of Health [4243]; Juvenile Diabetes Research Foundation International; National Institute for Health Research Cambridge Biomedical Centre; European Union [241447, 201167]; American Heart Association FX The authors thank the U.K. Medical Research Council (MRC) (grant no. G0000934) and the Wellcome Trust (grant no. 068545/Z/02) for funding the collection of DNA for the British 1958 Birth Cohort. The authors acknowledge use of DNA from the UKBS-CC, funded by the Wellcome Trust (grant 076113/C/04/Z), the Wellcome Trust/Juvenile Diabetes Research Foundation (grant 061858), and the National Institutes of Health Research of England. The collection was established as part of the Wellcome Trust Case-Control Consortium. The authors acknowledge use of DNA from the Human Biological Data Interchange and Diabetes U.K. for the U.S. and U.K. multiplex families, respectively; the Norwegian Study Group for Childhood Diabetes (D. Undlien, University of Oslo, and K. Ronningen, Norwegian Institute of Public Health, Norway) for the Norwegian families; D. Savage of the Belfast Health and Social Care Trust; C. Patterson and D. Carson of Queen's University Belfast; P. Maxwell of Belfast City Hospital for the Northern Irish families; and C. Guja and C. Ionescu-Tirgoviste of the Institute of Diabetes "N Paulescu", Romania, for the Romanian families. Funding for the project was provided by the Wellcome Trust (award no. 076113). The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (079895). The Great Ormond Street Hospital/University College London, Institute of Child Health receives a proportion of funding from the Department of Health's National Institute for Health Research (Biomedical Research Centre Funding). The Medical Research Council provides funds for the MRC Centre of Epidemiology for Child Health and for the vitamin D genetics project (G0601653). The National Diet and Nutrition Survey was funded by the Food Standards Agency and Department of Health and was accessed through the U.K. Data Archive (study no. 4243). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. J.D.C. was funded by the Juvenile Diabetes Research Foundation International and the Wellcome Trust, the National Institute for Health Research Cambridge Biomedical Centre, and the European Union (FP7-NAIMIT; grant agreement no. 241447). D.J.S., N.M.W., H.S., and J.A.T. were funded by the Juvenile Diabetes Research Foundation International, the Wellcome Trust, and the National Institute for Health Research Cambridge Biomedical Centre. J.A.T. is a Senior Investigator of the National Institute for Health Research. K.B. is funded by the European Union (FP7-NAIMIT and FP7-EURADRENAL; grant agreement no. 241447 and 201167) and T.J.W. by the American Heart Association. E.H. is funded by the Department of Health (U.K.) Public Health Career Scientist Award. NR 50 TC 113 Z9 114 U1 0 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2011 VL 60 IS 5 BP 1624 EP 1631 DI 10.2337/db10-1656 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 760UP UT WOS:000290349700032 PM 21441443 ER PT J AU Beverly, EA Hultgren, BA Brooks, KM Ritholz, MD Abrahamson, MJ Weinger, K AF Beverly, Elizabeth A. Hultgren, Brittney A. Brooks, Kelly M. Ritholz, Marilyn D. Abrahamson, Martin J. Weinger, Katie TI Understanding Physicians' Challenges When Treating Type 2 Diabetic Patients' Social and Emotional Difficulties A qualitative study SO DIABETES CARE LA English DT Article ID GLYCEMIC CONTROL; NEEDS DAWN; DEPRESSION; CARE; METAANALYSIS; PREVALENCE; ATTITUDES; ADHERENCE; SYMPTOMS; BURNOUT AB OBJECTIVE-To explore physicians' awareness of and responses to type 2 diabetic patients' social and emotional difficulties. RESEARCH DESIGN AND METHODS-We conducted semistructured interviews with 19 physicians. Interviews were transcribed, coded, and analyzed using thematic analysis. RESULTS-Three themes emerged: 1) physicians' awareness of patients' social and emotional difficulties: physicians recognized the frequency and seriousness of patients' social and emotional difficulties; 2) physicians' responses to patients' social and emotional difficulties: many reported that intervening with these difficulties was challenging with few treatment options beyond making referrals, individualizing care, and recommending more frequent follow-up visits; and 3) the impact of patients' social and emotional difficulties on physicians: few available patient treatment options, time constraints, and a perceived lack of psychological expertise contributed to physicians' feeling frustrated, inadequate, and overwhelmed. CONCLUSIONS-Recognition and understanding of physicians' challenges when treating diabetes patients' social and emotional difficulties are important for developing programmatic interventions. C1 [Beverly, Elizabeth A.; Hultgren, Brittney A.; Brooks, Kelly M.; Ritholz, Marilyn D.; Abrahamson, Martin J.; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Beverly, Elizabeth A.; Ritholz, Marilyn D.; Abrahamson, Martin J.; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA USA. [Ritholz, Marilyn D.] Childrens Hosp, Boston, MA 02115 USA. RP Weinger, K (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM katie.weinger@joslin.harvard.edu FU The Kathleen P. Welsh Fund; Pfizer FX The Kathleen P. Welsh Fund supported this study. M.J.A. has received research funding from Pfizer and has provided consulting services to Novo Nordisk, sanofi-aventis, Halozyme, and Merck. No other potential conflicts of interest relevant to this article were reported. NR 15 TC 17 Z9 17 U1 3 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2011 VL 34 IS 5 BP 1086 EP 1088 DI 10.2337/dc10-2298 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761RV UT WOS:000290419200004 PM 21411508 ER PT J AU Becker, JR Deo, RC Werdich, AA Panakova, D Coy, S MacRae, CA AF Becker, Jason R. Deo, Rahul C. Werdich, Andreas A. Panakova, Daniela Coy, Shannon MacRae, Calum A. TI Human cardiomyopathy mutations induce myocyte hyperplasia and activate hypertrophic pathways during cardiogenesis in zebrafish SO DISEASE MODELS & MECHANISMS LA English DT Article ID CARDIAC TROPONIN-T; VENTRICULAR-TACHYCARDIA; GENE-EXPRESSION; MOUSE MODEL; HEART; GROWTH; MICE; MECHANISMS; PHENOTYPES; ARRHYTHMIA AB To assess the effects during cardiac development of mutations that cause human cardiomyopathy, we modeled a sarcomeric gene mutation in the embryonic zebrafish. We designed morpholino antisense oligonucleotides targeting the exon 13 splice donor site in the zebrafish cardiac troponin T (tnnt2) gene, in order to precisely recapitulate a human TNNT2 mutation that causes hypertrophic cardiomyopathy (HCM). HCM is a disease characterized by myocardial hypertrophy, myocyte and myofibrillar disarray, as well as an increased risk of sudden death. Similar to humans with HCM, the morphant zebrafish embryos displayed sarcomere disarray and there was a robust induction of myocardial hypertrophic pathways. Microarray analysis uncovered a number of shared transcriptional responses between this zebrafish model and a well-characterized mouse model of HCM. However, in contrast to adult hearts, these embryonic hearts developed cardiomyocyte hyperplasia in response to this genetic perturbation. The re-creation of a human disease-causing TNNT2 splice variant demonstrates that sarcomeric mutations can alter cardiomyocyte biology at the earliest stages of heart development with distinct effects from those observed in adult hearts despite shared transcriptional responses. C1 [Becker, Jason R.; Deo, Rahul C.; Werdich, Andreas A.; Panakova, Daniela; Coy, Shannon; MacRae, Calum A.] Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Becker, Jason R.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. [Panakova, Daniela; MacRae, Calum A.] Harvard Univ, Sch Med, Div Cardiol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Becker, JR (reprint author), Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA 02129 USA. EM jason.r.becker@vanderbilt.edu FU Hypertrophic Cardiomyopathy Center at Massachusetts General Hospital; [T32HL007208] FX We would like to thank Mary McKee for the electron microscopy technical assistance and Jennifer Love for the microarray technical assistance. We would also like to thank Michael Fifer and Barry London for their advice and encouragement. This work was supported by an institutional grant from the Hypertrophic Cardiomyopathy Center at Massachusetts General Hospital (C.A.M.) and T32HL007208 (J.R.B., R.C.D.). NR 36 TC 23 Z9 23 U1 0 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD MAY PY 2011 VL 4 IS 3 BP 400 EP 410 DI 10.1242/dmm.006148 PG 11 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 761EG UT WOS:000290377900016 PM 21245263 ER PT J AU Choma, MA Suter, MJ Vakoc, BJ Bouma, BE Tearney, GJ AF Choma, Michael A. Suter, Melissa J. Vakoc, Benjamin J. Bouma, Brett E. Tearney, Guillermo J. TI Physiological homology between Drosophila melanogaster and vertebrate cardiovascular systems SO DISEASE MODELS & MECHANISMS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; CARDIAC-OUTPUT; DORSAL VESSEL; HEART; ZEBRAFISH; QUANTIFICATION; IDENTIFICATION; PERFORMANCE; DISEASE; MODEL AB The physiology of the Drosophila melanogaster cardiovascular system remains poorly characterized compared with its vertebrate counterparts. Basic measures of physiological performance remain unknown. It also is unclear whether subtle physiological defects observed in the human cardiovascular system can be reproduced in D. melanogaster. Here we characterize the cardiovascular physiology of D. melanogaster in its pre-pupal stage by using high-speed dye angiography and optical coherence tomography. The heart has vigorous pulsatile contractions that drive intracardiac, aortic and extracellular-extravascular hemolymph flow. Several physiological measures, including weight-adjusted cardiac output, body-length-adjusted aortic velocities and intracardiac shear forces, are similar to those in the closed vertebrate cardiovascular systems, including that of humans. Extracellular-extravascular flow in the pre-pupal D. melanogaster circulation drives convection-limited fluid transport. To demonstrate homology in heart dysfunction, we showed that, at the pre-pupal stage, a troponin I mutant, held-up2 (hdp2), has impaired systolic and diastolic heart wall velocities. Impaired heart wall velocities occur in the context of a non-dilated phenotype with a mildly depressed fractional shortening. We additionally derive receiver operating characteristic curves showing that heart wall velocity is a potentially powerful discriminator of systolic heart dysfunction. Our results demonstrate physiological homology and support the use of D. melanogaster as an animal model of complex cardiovascular disease. C1 [Choma, Michael A.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06520 USA. [Choma, Michael A.] Childrens Hosp Boston, Boston, MA 02115 USA. [Choma, Michael A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Suter, Melissa J.; Vakoc, Benjamin J.; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Suter, Melissa J.; Vakoc, Benjamin J.; Bouma, Brett E.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Vakoc, Benjamin J.; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Choma, MA (reprint author), Yale Univ, Sch Med, Dept Diagnost Radiol, 333 Cedar St, New Haven, CT 06520 USA. EM michael.choma@yale.edu FU NIH [R01HL076398, R01CA103769]; Department of Defense Air Force Office of Scientific Research [FA9550-04-1-0079] FX This work was generously supported by the Frederick H. Lovejoy Fund, Children's Hospital Boston (M. A. C.) and by an American Medical Association Foundation Seed Grant (M. A. C.). We additionally acknowledge funding support from NIH R01HL076398 and NIH R01CA103769 (development of the imaging system) and from the Department of Defense Air Force Office of Scientific Research, Medical Free Electron Laser Program FA9550-04-1-0079. We thank Thorlabs their loan of an OCT system. We thank James Vigoreaux for supplying hdp2 D. melanogaster. NR 46 TC 19 Z9 19 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD MAY PY 2011 VL 4 IS 3 BP 411 EP 420 DI 10.1242/dmm.005231 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 761EG UT WOS:000290377900017 PM 21183476 ER PT J AU Obstein, KL Estepar, RSJ Jayender, J Patil, VD Spofford, IS Ryan, MB Lengyel, BI Shams, R Vosburgh, KG Thompson, CC AF Obstein, K. L. Estepar, R. S. J. Jayender, J. Patil, V. D. Spofford, I. S. Ryan, M. B. Lengyel, B. I. Shams, R. Vosburgh, K. G. Thompson, C. C. TI Image Registered Gastroscopic Ultrasound (IRGUS) in human subjects: a pilot study to assess feasibility SO ENDOSCOPY LA English DT Article ID NEEDLE ASPIRATION; PANCREATIC MASSES; MENTAL WORKLOAD; COLONOSCOPY; ULTRASONOGRAPHY; NAVIGATION; EFFICIENCY; THERAPY; IMPACT; TASK AB Background and study aims: Endoscopic ultrasound (EUS) is a complex procedure due to the subtleties of ultrasound interpretation, the small field of observation, and the uncertainty of probe position and orientation. Animal studies demonstrated that Image Registered Gastroscopic Ultrasound (IRGUS) is feasible and may be superior to conventional EUS in efficiency and image interpretation. This study explores whether these attributes of IRGUS will be evident in human subjects, with the aim of assessing the feasibility, effectiveness, and efficiency of IRGUS in patients with suspected pancreatic lesions. Patients and methods: This was a prospective feasibility study at a tertiary care academic medical center in human patients with pancreatic lesions on computed tomography (CT) scan. Patients who were scheduled to undergo conventional EUS were randomly chosen to undergo their procedure with IRGUS. Main outcome measures included feasibility, ease of use, system function, validated task load (TLX) assessment instrument, and IRGUS experience questionnaire. Results: Five patients underwent IRGUS without complication. Localization of pancreatic lesions was accomplished efficiently and accurately (TLX temporal demand 3.7 %; TLX effort 8.6 %). Image synchronization and registration was accomplished in real time without procedure delay. The mean assessment score for endoscopist experience with IRGUS was positive (66.6 +/- 29.4). Real-time display of CT images in the EUS plane and echoendoscope orientation were the most beneficial characteristics. Conclusions: IRGUS appears feasible and safe in human subjects, and efficient and accurate at identification of probe position and image interpretation. IRGUS has the potential to broaden the adoption of EUS techniques and shorten EUS learning curves. Clinical studies comparing IRGUS with conventional EUS are ongoing. C1 [Ryan, M. B.; Thompson, C. C.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Obstein, K. L.] Vanderbilt Univ, Med Ctr, Div Gastroenterol, Nashville, TN USA. [Estepar, R. S. J.; Lengyel, B. I.; Vosburgh, K. G.] Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA. [Jayender, J.; Patil, V. D.; Vosburgh, K. G.] Massachusetts Gen Hosp, Ctr Integrat Med, Boston, MA 02114 USA. [Jayender, J.; Patil, V. D.; Vosburgh, K. G.] Massachusetts Gen Hosp, Innovat Technol Image Guidance Lab, Boston, MA 02114 USA. [Spofford, I. S.] Massachusetts Gen Hosp, Div Pediat Gastroenterol, Boston, MA 02114 USA. [Shams, R.] Australian Natl Univ, Coll Engn & Comp Sci, Canberra, ACT, Australia. RP Thompson, CC (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. EM ccthompson@partners.org FU NCI NIH HHS [R42 CA115112, R25 CA089017]; NCRR NIH HHS [U41 RR019703, P41 RR019703]; NIBIB NIH HHS [P41 EB015898] NR 29 TC 4 Z9 4 U1 2 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD MAY PY 2011 VL 43 IS 5 BP 394 EP 399 DI 10.1055/s-0030-1256241 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 759MM UT WOS:000290249700003 PM 21425041 ER PT J AU Jeffries, MA Dozmorov, M Tang, YH Merrill, JT Wren, JD Sawalha, AH AF Jeffries, Matlock A. Dozmorov, Mikhail Tang, Yuhong Merrill, Joan T. Wren, Jonathan D. Sawalha, Amr H. TI Genome-wide DNA methylation patterns in CD4(+) T cells from patients with systemic lupus erythematosus SO EPIGENETICS LA English DT Article DE lupus; T cells; CD4(+) T cells; methylation; methylome ID MATRIX METALLOPROTEINASES; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; GENE-EXPRESSION; IN-VITRO; OVEREXPRESSION; DEMETHYLATION; LYMPHOCYTES; INFECTION; CD11A AB Systemic lupus erythematosus is a chronic-relapsing autoimmune disease of incompletely understood etiology. Recent evidence strongly supports an epigenetic contribution to the pathogenesis of lupus. To understand the extent and nature of dysregulated DNA methylation in lupus T cells, we performed a genome-wide DNA methylation study in CD4(+) T cells in lupus patients compared to normal healthy controls. Cytosine methylation was quantified in 27,578 CG sites located within the promoter regions of 14,495 genes. We identified 236 hypomethylated and 105 hypermethylated CG sites in lupus CD4(+) T cells compared to normal controls, consistent with widespread DNA methylation changes in lupus T cells. Of interest, hypomethylated genes in lupus T cells include CD9, which is known to provide potent T-cell co-stimulation signals. Other genes with known involvement in autoimmunity such as MMP9 and PDGFRA were also hypomethylated. The BST2 gene, an interferon-inducible membrane-bound protein that helps restrict the release of retroviral particles was also hypomethylated in lupus patients. Genes involved in folate biosynthesis, which plays a role in DNA methylation, were overrepresented among hypermethylated genes. In addition, the transcription factor RUNX3 was hypermethylated in patients, suggesting an impact on T-cell maturation. Protein-protein interaction maps identified a transcription factor, HNF4a, as a regulatory hub affecting a number of differentially methylated genes. Apoptosis was also an overrepresented ontology in these interaction maps. Further, our data suggest that the methylation status of RAB22A, STX1B2, LGALS3BP, DNASE1L1 and PREX1 correlates with disease activity in lupus patients. C1 [Jeffries, Matlock A.; Sawalha, Amr H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Jeffries, Matlock A.; Dozmorov, Mikhail; Wren, Jonathan D.; Sawalha, Amr H.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Tang, Yuhong] Samuel Roberts Noble Fdn Inc, Oklahoma City, OK USA. [Merrill, Joan T.] Oklahoma Med Res Fdn, Clin Pharmacol Program, Oklahoma City, OK 73104 USA. [Sawalha, Amr H.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Sawalha, AH (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. EM amr-sawalha@omrf.ouhsc.edu RI Wren, Jonathan/E-5611-2011; Dozmorov, Mikhail/B-1374-2009; OI Wren, Jonathan/0000-0003-2776-3545; Dozmorov, Mikhail/0000-0002-0086-8358; Jeffries, Matlock/0000-0001-9516-4312 FU NIH from the National Institute of Allergy and Infectious Diseases [R03AI076729]; NIH [P20RR020143, P30AR053483]; Lupus Research Institute FX This work was made possible by NIH Grant Number R03AI076729 from the National Institute of Allergy and Infectious Diseases and NIH Grants Number P20RR020143 and P30AR053483 and the Lupus Research Institute. We are thankful to the genotyping core at OMRF and in particular to Adam Adler and Kenneth Kaufman, Ph.D., for their help with this study. NR 53 TC 81 Z9 81 U1 0 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD MAY PY 2011 VL 6 IS 5 BP 593 EP 601 DI 10.4161/epi.6.5.15374 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 758YH UT WOS:000290203600009 PM 21436623 ER PT J AU Fifer, MA Sigwart, U AF Fifer, Michael A. Sigwart, Ulrich TI Controversies in cardiovascular medicine Hypertrophic obstructive cardiomyopathy: alcohol septal ablation SO EUROPEAN HEART JOURNAL LA English DT Review DE Alcohol septal ablation; Hypertrophic cardiomyopathy; Hypertrophic obstructive cardiomyopathy ID MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; VENTRICULAR OUTFLOW TRACT; COMPLETE HEART-BLOCK; REDUCTION THERAPY; TRANSCORONARY ABLATION; FOLLOW-UP; DIASTOLIC FUNCTION; TIME-COURSE; MYECTOMY; EXPERIENCE AB Alcohol septal ablation (ASA) was introduced in 1994 as an alternative to septal myectomy for patients with hypertrophic obstructive cardiomyopathy and symptoms refractory to medical therapy. This procedure alleviates symptoms by producing a targeted, limited infarction of the upper interventricular septum, resulting in an increase in left ventricular outflow tract (LVOT) diameter, a decrease in LVOT gradient, and regression of the component of LV hypertrophy that is due to pressure overload. Clinical success, with improvement in symptoms and reduction in gradient, is achieved in the great majority of patients with either resting or provocable LVOT obstruction. The principal morbidity of the procedure is complete heart block, resulting in some patients in the requirement for a permanent pacemaker. The introduction of myocardial contrast echocardiography as a component of the ASA procedure has contributed to the induction of smaller myocardial infarctions with lower dosages of alcohol and, in turn, fewer complications. Non-randomized comparisons of septal ablation and septal myectomy have shown similar mortality rates and post-procedure New York Heart Association class for the two procedures. C1 [Sigwart, Ulrich] Univ Geneva, Ctr Cardiol, Geneva, Switzerland. [Fifer, Michael A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Fifer, Michael A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sigwart, U (reprint author), Univ Geneva, Ctr Cardiol, Geneva, Switzerland. EM ulrich.sigwart@unige.ch NR 88 TC 26 Z9 27 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2011 VL 32 IS 9 BP 1059 EP U44 DI 10.1093/eurheartj/ehr013 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 760HR UT WOS:000290315900010 PM 21447511 ER PT J AU Cooley, J Sontag, MK Accurso, FJ Remold-O'Donnell, E AF Cooley, J. Sontag, M. K. Accurso, F. J. Remold-O'Donnell, E. TI SerpinB1 in cystic fibrosis airway fluids: quantity, molecular form and mechanism of elastase inhibition SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Cystic fibrosis; elastase; neutrophil serine proteases; protease inhibitors; Serpin ID NEUTROPHIL ELASTASE; LUNG-DISEASE; SERINE PROTEASES; ACTIVE-SITE; PROTEINS; MNEI; PSEUDOMONAS; SPUTUM; EXPRESSION; INFECTION AB Neutrophil serine proteases (NSPs), especially elastase, are major agents of lung destruction in cystic fibrosis (CF) patients. This study investigated SerpinB1, a highly efficient inhibitor of NSPs, in CF lung disease. Bronchoalveolar lavage fluid (BALF) from 31 children with CF and 24 control children was examined for amount and molecular species of SerpinB1, and its mechanism of action was studied. CF BALF had more SerpinB1 than control BALF (geometric mean 3.9 (95% CI 2.60-5.62) versus 1.37 (1.20-1.55) mu g.mL(-1); p < 0.001). BALF levels of SerpinB1 were higher for infected versus uninfected CF subjects (5.5 versus 2.7 mu g.mL(-1); p < 0.04) and substantially higher for elastase-positive versus -negative CF subjects (8.41 versus 1.89 mu g.mL(-1); p < 0.001). Most SerpinB1 in CF BALF had been cleaved. Adding recombinant SerpinB1 to CF BALF stoichiometrically inhibited endogenous elastase, indicating that the inhibitor functions in the CF microenvironment. In vitro simulations comparing SerpinB1 and alpha(1)-antitrypsin (SerpinA1) showed that both rapidly form irreversible inhibitory covalent complexes with elastase and that these differed in survival time. The SerpinB1-elastase complex survived only briefly due to fragmentation of bound elastase, releasing cleaved SerpinB1, the molecular form in CF BALF. The findings define an innate role for SerpinB1 in CF airways. C1 [Cooley, J.; Remold-O'Donnell, E.] Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. [Cooley, J.; Remold-O'Donnell, E.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. [Remold-O'Donnell, E.] Harvard Univ, Sch Med, Dept Paediat, Boston, MA USA. [Sontag, M. K.] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Accurso, F. J.] Childrens Hosp, Dept Paediat, Aurora, CO USA. [Accurso, F. J.] Univ Colorado Denver, Sch Med, Aurora, CO USA. RP Remold-O'Donnell, E (reprint author), Childrens Hosp Boston, Immune Dis Inst, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. EM remold@idi.harvard.edu FU National Institutes of Health [HL066548, HL41579, HL081335, RR0069]; Cystic Fibrosis Foundation FX The study was supported by National Institutes of Health (grants HL066548, HL41579, HL081335 and RR0069) and the Cystic Fibrosis Foundation. NR 33 TC 11 Z9 11 U1 0 U2 3 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD MAY PY 2011 VL 37 IS 5 BP 1083 EP 1090 DI 10.1183/09031936.00073710 PG 8 WC Respiratory System SC Respiratory System GA 757MI UT WOS:000290089200016 PM 20817705 ER PT J AU Kwon, JY Myerson, MS AF Kwon, John Y. Myerson, Mark S. TI Talar Neck Fracture After Tibiotalar Arthrodesis: Case Report SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE Tatar Neck Fracture; Tibiotalar Arthrodesis ID TALUS FRACTURES; ANKLE ARTHRODESIS; INTRAMEDULLARY NAIL; FOLLOW-UP; FIXATION; HINDFOOT C1 [Kwon, John Y.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Kwon, JY (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM jkwon@partners.org NR 27 TC 0 Z9 0 U1 0 U2 0 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD MAY PY 2011 VL 32 IS 5 BP 560 EP 563 DI 10.3113/FAI.2011.0560 PG 4 WC Orthopedics SC Orthopedics GA 758DC UT WOS:000290139700016 ER PT J AU Nguyen, DM El-Serag, HB Shub, M Integlia, M Henderson, L Richardson, P Fairly, K Gager, MA AF Nguyen, Dang M. El-Serag, Hashem B. Shub, Mitchell Integlia, Mark Henderson, Louise Richardson, Peter Fairly, Kenneth Gager, Mark A. TI Barrett's esophagus in children and adolescents without neurodevelopmental or tracheoesophageal abnormalities: a prospective study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; NATURAL-HISTORY; PREVALENCE; CHILDHOOD; SYMPTOMS; POPULATION; DEFINITION; METAPLASIA; VALIDATION; GERD AB Background: Barrett's esophagus (BE) in children has been examined in retrospective studies, consisting of case series and cross-sectional studies. Objective: To evaluate the prevalence and determinants of BE in children who are free from neurodevelopmental disorders and tracheoesophageal abnormalities. Design: A prospective, cross-sectional study. Setting: Three pediatric GI Centers in Houston, Texas; Phoenix, Arizona; and Portland, Maine between February 2006 and December 2007. Patients: This study involved children and adolescents consecutively presenting for elective upper endoscopy. Patients with neurodevelopmental and tracheoesophageal disorders were excluded. Intervention: Endoscopic pictures of all cases with suspected BE were independently reviewed and verified by two experienced investigators. Esophageal biopsy specimens were obtained in all patients, and targeted biopsy specimens also were obtained from suspected BE. Main Outcome Measurements: Endoscopically suspected BE and histologically confirmed BE. Results: A total of 840 patients (mean age 9.5 years) were enrolled and had complete questionnaire and endoscopic data. Twelve patients were suspected of having BE (prevalence of 1.43%; 95% confidence interval [CI], 0.73-2.45), and only 1 patient had intestinal metaplasia, for a prevalence of 0.12% (95% Cl, 0-0.65), whereas the rest had gastric oxyntic glands (n = 6) or squamous esophageal epithelium (n = 5). Patients with suspected BE had a higher mean body mass index (23.0 vs 19.1, P =.05) and more chest pain (50% vs 13%, P < .01.) than patients without BE or reflux esophagitis. There was a trend toward a higher frequency of dysphagia, heartburn, and regurgitation in patients with suspected BE. Limitations: The accuracy of BE prevalence estimates is limited by the small number of cases. Conclusion: BE is rare in children without neurodevelopmental delay or tracheoesophageal anomalies presenting for elective upper endoscopy. (Gastrointest Enclose 201:1;73:875-80.) C1 [El-Serag, Hashem B.; Richardson, Peter] Michael E DeBakey Vet Affairs Med Ctr 152, Houston, TX 77030 USA. [Nguyen, Dang M.; El-Serag, Hashem B.; Richardson, Peter; Fairly, Kenneth; Gager, Mark A.] Baylor Coll Med, Houston, TX 77030 USA. [Fairly, Kenneth; Gager, Mark A.] Texas Childrens Hosp, Houston, TX 77030 USA. [Integlia, Mark] Barbara Bush Childrens Hosp, Portland, ME USA. [Shub, Mitchell] Phoenix Childrens Hosp, Phoenix, AZ USA. [Henderson, Louise] Univ N Carolina, Chapel Hill, NC USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIH [1-R03-DK068148-01]; Texas Gulf Coast Digestive Diseases Center [NIH P50 DK56338]; Houston Veterans Affairs HSR&D center of Excellence [HFP90-020] FX M. Gilger and H. El-Serag are supported by grants R03 (NIH 1-R03-DK068148-01). H. El-Serag also is supported in part by grants from the Texas Gulf Coast Digestive Diseases Center (NIH P50 DK56338) and the Houston Veterans Affairs HSR&D center of Excellence (HFP90-020). No other financial relationships relevant to this publication were disclosed. NR 22 TC 7 Z9 7 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2011 VL 73 IS 5 BP 875 EP 880 DI 10.1016/j.gie.2011.01.017 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 760AK UT WOS:000290292800004 PM 21354565 ER PT J AU Koh, H Hayashi, T Sato, KK Harita, N Maeda, I Nishizawa, Y Endo, G Fujimoto, WY Boyko, EJ Hikita, Y AF Koh, Hideo Hayashi, Tomoshige Sato, Kyoko Kogawa Harita, Nobuko Maeda, Isseki Nishizawa, Yoshiki Endo, Ginji Fujimoto, Wilfred Y. Boyko, Edward J. Hikita, Yonezo TI Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men: the Ohtori study SO HYPERTENSION RESEARCH LA English DT Article DE computed tomography; epidemiology; high normal blood pressure; visceral adiposity ID CORONARY-HEART-DISEASE; BODY-FAT; RISK-FACTORS; FOLLOW-UP; WAIST CIRCUMFERENCE; INSULIN-RESISTANCE; METABOLIC SYNDROME; DIABETES-MELLITUS; VASCULAR-DISEASE; HYPERTENSION AB Visceral adiposity is considered to have a key role in cardiometabolic diseases. The purpose of this study is to investigate cross-sectionally the association between intra-abdominal fat area (IAFA) measured by computed tomography (CT) and high blood pressure independent of abdominal subcutaneous fat area (ASFA) and insulin resistance. Study participants included 624 Japanese men not taking oral hypoglycemic medications or insulin. Abdominal, thoracic and thigh fat areas were measured by CT. Total fat area (TFA) was calculated as the sum of abdominal, thoracic and thigh fat area. Total subcutaneous fat area (TSFA) was defined as TFA minus IAFA. Hypertension and high normal blood pressure were defined using the 1999 criteria of the World Health Organization. Multiple-adjusted odds ratios of hypertension for tertiles of IAFA were 2.64 (95% confidence interval, 1.35-5.16) for tertile 2, and 5.08 (2.48-10.39) for tertile 3, compared with tertile 1 after adjusting for age, fasting immunoreactive insulin, diabetes status, ASFA, alcohol consumption, regular physical exercise and smoking habit. IAFA remained significantly associated with hypertension even after adjustment for ASFA, TSFA, TFA, body mass index or waist circumference, and no other measure of regional or total adiposity was associated with the odds of hypertension in models, which included IAFA. Similar results were obtained for the association between IAFA and the prevalence of high normal blood pressure or hypertension. In conclusion, greater visceral adiposity was associated with a higher odds of high blood pressure in Japanese men. Hypertension Research (2011) 34, 565-572; doi:10.1038/hr.2010.271; published online 13 January 2011 C1 [Hayashi, Tomoshige] Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Abeno Ku, Osaka 5458585, Japan. [Hayashi, Tomoshige; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Nishizawa, Yoshiki] Osaka City Univ, Grad Sch Med, Dept Metab Endocrinol & Mol Med, Osaka 5458585, Japan. [Fujimoto, Wilfred Y.; Boyko, Edward J.] Univ Washington, Dept Med, Seattle, WA USA. [Hikita, Yonezo] Ohtori Hlth Promot Ctr, Sakai, Osaka, Japan. RP Hayashi, T (reprint author), Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Abeno Ku, 1-4-3 Asahi Machi, Osaka 5458585, Japan. EM thayashi@med.osaka-cu.ac.jp RI Hayashi, Tomoshige/N-8508-2015 FU Ministry of Education, Culture, Sports, Science and Technology [17390177, 20390187] FX This work was supported by a Grant-in-Aid for Scientific Research (17390177, 20390187) from the Ministry of Education, Culture, Sports, Science and Technology, as well as by the facilities and services provided by the Ohtori Health Promotion Center. The funding sources had no role in the decision to submit the paper for publication. We thank the participants in the Ohtori Study for their dedication. NR 43 TC 10 Z9 11 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0916-9636 J9 HYPERTENS RES JI Hypertens. Res. PD MAY PY 2011 VL 34 IS 5 BP 565 EP 572 DI 10.1038/hr.2010.271 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 759MQ UT WOS:000290250200006 PM 21228782 ER PT J AU Bhan, I Camargo, CA Wenger, J Ricciardi, C Ye, J Borregaard, N Thadhani, R AF Bhan, Ishir Camargo, Carlos A., Jr. Wenger, Julia Ricciardi, Catherine Ye, Jun Borregaard, Niels Thadhani, Ravi TI Circulating levels of 25-hydroxyvitamin D and human cathelicidin in healthy adults SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID VITAMIN-D; ANTIMICROBIAL PEPTIDE; PLASMA; HCAP18 C1 [Bhan, Ishir; Ye, Jun; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Ricciardi, Catherine] MIT, Clin Res Ctr, Cambridge, MA 02139 USA. [Borregaard, Niels] Univ Copenhagen, Dept Hematol, Rigshosp, DK-1168 Copenhagen, Denmark. RP Bhan, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA 02115 USA. EM ibhan@partners.org FU NIDDK NIH HHS [K23 1K23DK081677, K23 DK081677, K23 DK081677-02] NR 9 TC 39 Z9 42 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2011 VL 127 IS 5 BP 1302 EP 1304 DI 10.1016/j.jaci.2010.12.1097 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 756NG UT WOS:000290018600030 PM 21310475 ER PT J AU Klingman, KM Marsh, EE Klerman, EB Anderson, EJ Hall, JE AF Klingman, Kara M. Marsh, Erica E. Klerman, Elizabeth B. Anderson, Ellen J. Hall, Janet E. TI Absence of Circadian Rhythms of Gonadotropin Secretion in Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LUTEINIZING-HORMONE SECRETION; FREE ALPHA-SUBUNIT; FOLLICLE-STIMULATING-HORMONE; POSTMENOPAUSAL WOMEN; INHIBIN-B; PULSE FREQUENCY; MENSTRUAL-CYCLE; SLEEP; PHASE; MEN AB Context: Diurnal rhythms of LH and FSH have been reported in normal women, but it is unclear whether these reflect underlying circadian control from the suprachiasmatic nucleus and/or external influences. Objective: The aim of this study was to determine whether endogenous circadian rhythms of LH, FSH, and the glycoprotein free alpha-subunit (FAS) are present in reproductive-aged women. Design and Setting: Subjects were studied in the early follicular phase using a constant routine protocol in a Clinical Research Center at an academic medical center. Subjects: Subjects were healthy, normal-cycling women aged 23-29 yr (n = 11). Main Outcome Measures: Temperature data were collected, and blood samples were assayed for LH, FSH, FAS, and TSH. Results: Core body temperature and TSH were best fit by a sinusoid model, indicating that known circadian rhythms were present in this population. However, the patterns of FSH, LH, and FAS over 24 h were best fit by a linear model. Furthermore, there were no differences in LH and FAS interpulse intervals or pulse amplitudes between evening, night, and morning. Conclusions: Under conditions that control for sleep/wake, light/dark, activity, position, and nutritional cues, there is no circadian rhythm of LH, FSH, or FAS in women during the early follicular phase despite the presence of endogenous rhythms of TSH and core body temperature. These studies indicate that endogenous circadian control does not contribute to previously reported diurnal rhythms in reproductive-aged women and emphasizes the importance of environmental cues in controlling normal reproductive function. (J Clin Endocrinol Metab 96: 1456-1461, 2011) C1 [Klingman, Kara M.; Marsh, Erica E.; Hall, Janet E.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Marsh, Erica E.] Northwestern Univ, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Feinberg Sch Med, Chicago, IL 60611 USA. [Klerman, Elizabeth B.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Anderson, Ellen J.] Massachusetts Gen Hosp, Mallinkrodt Clin Res Ctr, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX-5,55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org FU National Institutes of Health (NIH) [R01-AG-13241, M01 RR 01066, NIH P01-AG009975, NIH K02-HD045459, NIH R01-HD40291] FX This work was supported by National Institutes of Health (NIH) Grant R01-AG-13241, M01 RR 01066, and NIH P01-AG009975, NIH K02-HD045459, and NIH R01-HD40291 (to E.B.K.). NR 44 TC 10 Z9 10 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2011 VL 96 IS 5 BP 1456 EP 1461 DI 10.1210/jc.2010-2739 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 759AE UT WOS:000290210600050 PM 21346063 ER PT J AU Tritos, NA Greenspan, SL King, D Hamrahian, A Cook, DM Jonsson, PJ Wajnrajch, MP Koltowska-Haggstrom, M Biller, BMK AF Tritos, Nicholas A. Greenspan, Susan L. King, Donna Hamrahian, Amir Cook, David M. Jonsson, Peter J. Wajnrajch, Michael P. Koltowska-Haggstrom, Maria Biller, Beverly M. K. TI Unreplaced Sex Steroid Deficiency, Corticotropin Deficiency, and Lower IGF-I Are Associated with Lower Bone Mineral Density in Adults with Growth Hormone Deficiency: A KIMS Database Analysis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RADIOLOGICAL SPINAL DEFORMITIES; GH REPLACEMENT THERAPY; HYPOPITUITARISM; STANDARDIZATION; PROLIFERATION; MULTICENTER; CHILDHOOD; ONSET; MICE; MASS AB Context: GH deficiency (GHD) is associated with low bone mineral density (BMD). Risk factors for lower BMD in this GHD population have not been fully elucidated. In particular, there are limited published data in GH-naive subjects. Objective: The objective of the study was to identify endocrine correlates of low BMD in treatment naive adult GHD subjects. Design: This was a retrospective analysis of data extracted from the (Pfizer International Metabolic Study) KIMS database. Setting: The study was an international epidemiological survey of more than 15,000 adult GHD patients from 31 countries. Patients: A total of 1218 subjects with stringently defined GHD of adult onset (641 women and 577 men) who were GH naive and had BMD measured in the posterior anterior lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Main Outcome Measures: Variables associated with standardized BMD(sBMD) in adult-onset GHD were examined. Results: In the LS, body mass index (r = 0.13, P < 0.01), unreplaced sex steroid deficiency (r = -0.17, P < 0.0001), and corticotropin deficiency (r = -0.11, P < 0.01) were independently associated with sBMD. In the FN, age (r = -0.19, P < 0.0001), female gender (r = -0.18, P < 0.0001), body mass index (r = 0.21, P < 0.0001), and decreased IGF-I SD scores (r = 0.10, P < 0.001) were independently associated with sBMD. Conclusions: Hormone variables associated with lower sBMD in patients with adult-onset GHD include unreplaced sex steroid deficiency and corticotropin deficiency in the LS and lower IGF-I SDS in the FN. (J Clin Endocrinol Metab 96: 1516-1523, 2011) C1 [Tritos, Nicholas A.; Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Greenspan, Susan L.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Hamrahian, Amir] Cleveland Clin, Dept Endocrinol Diabet & Metab, Cleveland, OH 44195 USA. [Cook, David M.] Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97239 USA. [Jonsson, Peter J.; Koltowska-Haggstrom, Maria] Pfizer Endocrine Care, KIMS Med Outcomes, S-19190 Sollentuna, Sweden. [King, Donna; Wajnrajch, Michael P.] Pfizer Inc, New York, NY 10017 USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl,Suite 112, Boston, MA 02114 USA. EM ntritos@partners.org OI Wajnrajch, Michael/0000-0002-8211-9237 FU Pfizer Inc.; Eli Lilly; Warner Chilcott; Tarsa; Serono; Indevus; Novo Nordisk FX KIMS is sponsored by Pfizer Inc. D. K. and M. P. W. are full-time employees of Pfizer Inc. P.J.J. and M. K.-H. are employed by Pfizer Health AB. N.A.T., S. L. G., A. H., D. M. C., and B. M. K. B. were not compensated for their contributions to this manuscript.; N.A.T., A. H., D. M. C., and B. M. K. B. are KIMS Investigators. N.A.T. has been a recipient of lecture fees from Pfizer Inc., and his spouse is an employee of Pfizer Inc. S. L. G. has been a recipient of research funding from Eli Lilly, Warner Chilcott, and Tarsa and has consulted and served on an advisory board for Amgen and Merck. A. H. has been a recipient of lecture fees from Pfizer Inc. and has consulted for Novo Nordisk. D. M. C. has received lecture fees from Pfizer, has received research funding from Serono, Eli Lilly, and Indevus, and served on an advisory board for Novo Nordisk. D. K. and M. P. W. are full-time employees of Pfizer Inc. P.J.J. and M. K.-H. are employed by Pfizer Health AB. B. M. K. B. has been a recipient of research funding from Eli Lilly and Novo Nordisk and has served on an advisory board and received consulting fees from Pfizer and Novo Nordisk. NR 28 TC 12 Z9 12 U1 0 U2 0 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 MAY PY 2011 VL 96 IS 5 BP 1516 EP 1523 DI 10.1210/jc.2010-2662 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 759AE UT WOS:000290210600058 PM 21367928 ER PT J AU Elmariah, SB Kundu, RV AF Elmariah, Sarina B. Kundu, Roopal V. TI Progressive Macular Hypomelanosis SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Article ID BAND ULTRAVIOLET-B; UVB AB Progressive macular hypomelanosis is an under-recognized disorder characterized by the presence of numerous ill-defined hypopigmented macules and patches on the trunk of young adults. Although common, particularly in Fitzpatrick skin types IV-VI, this condition is frequently misdiagnosed and treated inadequately with antifungals or topical steroids resulting in patient frustration. The exact pathogenesis of progressive macular hypomelanosis is unknown; however, recent studies suggest hypopigmentation results from decreased melanin formation and altered melanosome distribution in response to Proprionibacterium. While there are no well-established or consistently effective therapies for progressive macular hypomelanosis, our growing understanding of its pathogenesis urges consideration of alternative treatment strategies. Here, we report five patients with progressive macular hypomelanosis who benefitted from topical and systemic antimicrobial therapy and summarize the current clinical, pathological and treatment paradigms of this disorder. C1 [Kundu, Roopal V.] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA. [Elmariah, Sarina B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kundu, RV (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Dermatol, 676 N St Clair St,Suite 1600, Chicago, IL 60611 USA. EM rkundu@nmff.org NR 21 TC 3 Z9 3 U1 0 U2 0 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD MAY PY 2011 VL 10 IS 5 BP 502 EP 506 PG 5 WC Dermatology SC Dermatology GA 760YR UT WOS:000290361700007 PM 21533296 ER PT J AU Davis, LL Gilliss, CL Deshefy-Longhi, T Chestnutt, DH Molloy, M AF Davis, Linda Lindsey Gilliss, Catherine L. Deshefy-Longhi, Tess Chestnutt, Deborah H. Molloy, Margory TI The Nature and Scope of Stressful Spousal Caregiving Relationships SO JOURNAL OF FAMILY NURSING LA English DT Article DE spousal caregivers; spousal relationships; relationship quality; relational stress; caregiving burden; Alzheimer's disease; Parkinson's disease ID PARKINSONS-DISEASE; DEPRESSIVE SYMPTOMS; FAMILY CAREGIVERS; PHYSICAL HEALTH; DEMENTIA; BURDEN; MUTUALITY; GENDER; INTERVENTION; METAANALYSIS AB The caregiving literature provides compelling evidence that caregiving burden and depressive symptoms are linked with stressful care relationships, however, relational difficulties around caregiving are seldom described in the literature. This article presents findings from content analysis of baseline interviews with 40 Alzheimer's disease (AD) and Parkinson's disease (PD) spousal caregivers enrolled in a home care skill-training trial who identified their care relationship as a source of care burden. Disappointment and sadness about the loss of the relationship; tension within the relationship; and care decision conflicts within the relationship were recurrent themes of relational stress in caregiving. These spousal caregivers had relationship quality scores below the mean and burden and depressive symptom scores above the means of other caregivers in the study. These findings provide support for developing dyadic interventions that help spouses manage relational losses, care-related tensions, and care decision-making conflicts. C1 [Davis, Linda Lindsey; Molloy, Margory] Duke Univ, Sch Nursing, Ctr Nursing Discovery, Durham, NC 27710 USA. [Deshefy-Longhi, Tess] Fairfield Univ, Sch Nursing, Fairfield, CT 06430 USA. [Chestnutt, Deborah H.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Davis, LL (reprint author), Duke Univ, Sch Nursing, Ctr Nursing Discovery, 307 Trent Dr,DUMC 3322, Durham, NC 27710 USA. EM davis317@mc.duke.edu FU National Institute for Nursing Research [RO1 NR008285]; Duke University Center for the Study of Aging and Human Development [AG00029] FX Project ASSIST for Chronic Illness Caregivers was funded by the National Institute for Nursing Research: Grant number: RO1 NR008285. (L. Davis, Principal Investigator). Dr. Deshefy-Longhi's work with the ASSIST study was supported by the Duke University Center for the Study of Aging and Human Development, where she completed postdoctoral training under T-32 Grant number: AG00029. NR 40 TC 20 Z9 21 U1 4 U2 20 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-8407 J9 J FAM NURS JI J. Fam. Nurs. PD MAY PY 2011 VL 17 IS 2 BP 224 EP 240 DI 10.1177/1074840711405666 PG 17 WC Family Studies; Nursing SC Family Studies; Nursing GA 756PS UT WOS:000290027300006 PM 21531858 ER PT J AU Brouwer, KM Jupiter, JB Ring, D AF Brouwer, Kim M. Jupiter, Jesse B. Ring, David TI Nonunion of Operatively Treated Capitellum and Trochlear Fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Osteonecrosis; open reduction internal fixation; capitellum; trochlea; fracture ID INTERNAL-FIXATION; OPEN REDUCTION; HUMERUS AB Purpose To test the hypothesis that comminuted fractures of the capitellum and trochlea with posterior comminution (Dubberley type 3B) have a greater risk of nonunion than other types of capitellum and trochlea fractures. Methods We observed 30 patients with operatively treated fractures of the capitellum and trochlea for an average of 34 months (range, 12-75 mo). We compared 18 fractures with comminution of the capitellum and trochlea and posterior comminution (type 3B according to Dubberley and colleagues) with 12 fractures consisting of single large anterior fracture fragments with (6 patients; Dubberley type 2B) or without (6 patients; Dubberley type 2A) posterior comminution. Results Of 18 patients, 8 with type 3B fractures were noted to have nonunion. No patients with type 2 fractures had a nonunion. Conclusions Fractures of the capitellum and trochlea are prone to nonunion when they create multiple articular fragments and there is posterior comminution (Dubberley type 3B). (J Hand Surg 2011;36A:804-807. Copyright (C) 2011 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Yawkey Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Wright Medical FX D.R. receives royalities from and is a consultant with Wright Medical, and he is a consultant with Acumed and Tomier. NR 9 TC 3 Z9 4 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 2011 VL 36A IS 5 BP 804 EP 807 DI 10.1016/j.jhsa.2011.01.022 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 758SC UT WOS:000290185700006 PM 21435800 ER PT J AU Peterson, SL Rayan, GM AF Peterson, Steven L. Rayan, Ghazi M. TI Shoulder and Upper Arm Muscle Architecture SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Muscle architecture; musculotendinous transfer; shoulder muscles ID TENDON TRANSFER; POTENTIAL EXCURSION; RELATIVE TENSION; HAND; TRANSFERS; RELEVANCE; FOREARM AB Purpose To examine the architecture of the shoulder and upper arm muscles and generate data that could serve as a guide for comparison, compatibility, and relative performance among these muscles for use in transfer. Method Eleven shoulder and arm muscles were dissected bilaterally in 5 fresh cadavers. Of these 110 potentially available muscles, 107 were suitable for evaluation and were grouped according to similarities in architecture. Resting muscle length, required excursion, muscle fiber length, pennation angle, and mass were determined. Physiologic cross-sectional area (PCSA) was then calculated from these parameters using a standard formula. Results Based on the gross appearance of muscle fiber orientation, the 11 muscles were subdivided into 3 groups. Required excursion was found to be less than fiber length in all muscles except for the teres major and middle deltoid with abduction. The middle deltoid muscle was found to have a short fiber length, complex multipennate structure, and high PCSA. Comparison showed the biceps and posterior deltoid to have fiber lengths greater than any portion of the triceps; however, neither demonstrated architectural features that would generate the force (represented by PCSA) determined for the combined triceps. Conclusions Data presented in this study offer the opportunity for direct comparison of architectural features of select shoulder and arm musculature. Clinical relevance This information might help in the evaluation of compatibility of various musculotendinous transfers around the shoulder and elbow. (J Hand Surg 2011;36A:881-889. Copyright (C) 2011 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Rayan, Ghazi M.] Univ Oklahoma, Hlth Sci Ctr, Dept Orthoped & Rehabil, Oklahoma City, OK 73112 USA. [Rayan, Ghazi M.] Integris Baptist Hosp, Dept Orthoped & Rehabil, Oklahoma City, OK 73112 USA. Portland VA Med Ctr, Hand & Plast Surg Sect, Operat Care Div, Portland, OR USA. RP Rayan, GM (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Orthoped & Rehabil, 3366 NW Expressway,Bldg D 700, Oklahoma City, OK 73112 USA. EM ouhsgmr@aol.com NR 26 TC 7 Z9 7 U1 0 U2 9 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 MAY PY 2011 VL 36A IS 5 BP 881 EP 889 DI 10.1016/j.jhsa.2011.01.008 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 758SC UT WOS:000290185700019 PM 21527142 ER PT J AU Ulvila, J Vanha-aho, LM Kleino, A Vaha-Makila, M Vuoksio, M Eskelinen, S Hultmark, D Kocks, C Hallman, M Parikka, M Ramet, M AF Ulvila, Johanna Vanha-aho, Leena-Maija Kleino, Anni Vaha-Makila, Mari Vuoksio, Milka Eskelinen, Sinikka Hultmark, Dan Kocks, Christine Hallman, Mikko Parikka, Mataleena Ramet, Mika TI Cofilin regulator 14-3-3 zeta is an evolutionarily conserved protein required for phagocytosis and microbial resistance SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE Drosophila; zebrafish; plasmatocyte; macrophage; immunity ID DROSOPHILA IMD PATHWAY; SCAVENGER RECEPTOR; RNAI SCREEN; BACTERIAL-INFECTION; IMMUNE-RESPONSE; ACTIN DYNAMICS; S2 CELLS; REVEALS; EXPRESSION; ZEBRAFISH AB Phagocytosis is an ancient cellular process that plays an important role in host defense. In Drosophila melanogaster phagocytic, macrophage-like hemocytes recognize and ingest microbes. We performed an RNAi-based in vitro screen in the Drosophila hemocyte cell line S2 and identified Abi, cpa, cofilin regulator 14-3-3 zeta, tlk, CG2765, and CG15609 as mediators of bacterial phagocytosis. Of these identified genes, 14-3-3 zeta had an evolutionarily conserved role in phagocytosis: bacterial phagocytosis was compromised when 14-3-3 zeta was targeted with RNAi in primary Drosophila hemocytes and when the orthologous genes Ywhab and Ywhaz were silenced in zebrafish and mouse RAW 264.7 cells, respectively. In Drosophila and zebrafish infection models, 14-3-3 zeta was required for resistance against Staphylococcus aureus. We conclude that 14-3-3 zeta is essential for phagocytosis and microbial resistance in insects and vertebrates. J. Leukoc. Biol. 89: 649-659; 2011. C1 [Ulvila, Johanna; Vaha-Makila, Mari; Hallman, Mikko] Univ Oulu, Bioctr Oulu, Dept Pediat, Oulu, Finland. [Eskelinen, Sinikka] Univ Oulu, Bioctr Oulu, Dept Pathol, Oulu, Finland. [Vanha-aho, Leena-Maija; Kleino, Anni; Vuoksio, Milka; Hultmark, Dan; Parikka, Mataleena; Ramet, Mika] Univ Tampere, Inst Biomed Technol, Tampere 33014, Finland. [Ramet, Mika] Univ Tampere, Dept Pediat, Tampere 33014, Finland. [Kleino, Anni; Hultmark, Dan] Umea Univ, Dept Mol Biol, Umea, Sweden. [Kocks, Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kocks, Christine] Harvard Univ, Sch Med, Boston, MA USA. RP Ramet, M (reprint author), Univ Tampere, Inst Med Technol, Tampere 33014, Finland. EM mika.ramet@uta.fi RI Parikka, Mataleena/D-4364-2014; Hultmark, Dan/C-5058-2013; Hammaren, Milka/C-6990-2016; OI Hultmark, Dan/0000-0002-6506-5855; Hammaren, Milka/0000-0001-9076-8782; Parikka, Mataleena/0000-0001-5555-3815 FU Sigrid Juselius Foundation; Academy of Finland; Foundation for Pediatric Research; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Swedish Research Council; Swedish Cancer Society; Pirkanmaa Hospital District; Biocenter Finland FX This work was supported by grants from the Sigrid Juselius Foundation (M. H. and M. R.), the Academy of Finland (M. R., D. H., and M. P.), the Foundation for Pediatric Research (M. R.), Tampere Tuberculosis Foundation (M. R.), the Emil Aaltonen Foundation (M. R.), the Swedish Research Council and the Swedish Cancer Society (D. H.), and Competitive Research Funding of the Pirkanmaa Hospital District (M. R. and M. P.). The zebrafish work was done at University of Tampere Zebrafish Core Facility, funded by Biocenter Finland. The fly work was done at University of Tampere Drosophila Core Facility, funded by Biocenter Finland. We thank Heidi Enwald, Tapio Kotipelto, Mirkka Ovaska, and Dr. Samuli Rounioja for technical assistance and members of the M. H. and M. R. labs for stimulating discussions. In addition, we thank NIG-Fly and VDRC for RNAi fly lines. NR 54 TC 22 Z9 23 U1 1 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY PY 2011 VL 89 IS 5 BP 649 EP 659 DI 10.1189/jlb.0410195 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 757PL UT WOS:000290100100003 PM 21208897 ER PT J AU Goodman, D AF Goodman, Daisy TI Buprenorphine for the Treatment of Perinatal Opioid Dependence: Pharmacology and Implications for Antepartum, Intrapartum, and Postpartum Care SO JOURNAL OF MIDWIFERY & WOMENS HEALTH LA English DT Review DE buprenorphine; neonatal abstinence; perinatal opioid dependence; pregnancy ID NEONATAL ABSTINENCE SYNDROME; SUBSTANCE USE DISORDERS; ACUTE PAIN MANAGEMENT; PREGNANT-WOMEN; PSYCHOSOCIAL CHARACTERISTICS; METHADONE; MAINTENANCE; METABOLISM; EXPOSURE; OUTCOMES AB Opioid dependence during pregnancy is associated with significant health risks for both the mother and her fetus. Opioid maintenance therapy with methadone (Dolophine) is the current standard of care, reduces medical and social risks associated with illicit drug use, and decreases rates of prematurity and low birth weight. However, treatment with methadone is frequently associated with neonatal abstinence syndrome. Buprenorphine is an alternative to methadone that preliminary data indicates is equivalent in safety and efficacy to methadone and significantly increases access to treatment. The pharmacology of buprenorphine and its implications for the care of pregnant women with opioid dependence are described. C1 [Goodman, Daisy] Franklin Mem Hosp, Farmington, ME USA. [Goodman, Daisy] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Goodman, D (reprint author), 111 Franklin Hlth Commons, Farmington, ME 04938 USA. EM dgood-man@fchn.org NR 51 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-9523 J9 J MIDWIFERY WOM HEAL JI J. Midwifery Women Health PD MAY-JUN PY 2011 VL 56 IS 3 BP 240 EP 247 DI 10.1111/j.1542-2011.2011.00049.x PG 8 WC Nursing SC Nursing GA 756DR UT WOS:000289992400007 PM 21535372 ER PT J AU Horky, LL Hsiao, EM Weiss, SE Drappatz, J Gerbaudo, VH AF Horky, Laura L. Hsiao, Edward M. Weiss, Stephanie E. Drappatz, Jan Gerbaudo, Victor H. TI Dual phase FDG-PET imaging of brain metastases provides superior assessment of recurrence versus post-treatment necrosis SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Brain; Metastasis; Tumor; Recurrence; Necrosis; Radiation; FDG; PET; PET/CT; FDG-PET; Dual phase imaging; Dual time point ID POSITRON-EMISSION-TOMOGRAPHY; RADIATION NECROSIS; F-18 FLUORODEOXYGLUCOSE; TUMOR; TISSUE; TIME; DIFFERENTIATION; METABOLISM; INDEX AB To study the ability of dual phase FDG-PET/CT imaging to accurately distinguish tumor versus necrosis in patients treated for brain metastases. 32 (22 female, 10 male) consecutive patients with treated brain metastases, lesion size greater than 0.5 cm(3) and suspected recurrence on MRI underwent dual-phase FDG-PET/CT. Clinical outcome was assessed by biopsy or by MRI. SUVmax and SUVmean values of the lesion (L) and gray matter (GM) at the level of the thalamus were measured on early (1) and delayed (2) imaging. L1/GM1 and L2/GM2 and the change of L/GM ratios as a function of time were calculated [(L2/GM2 - L1/GM1)/(L1/GM1)]. Cut-off values were obtained by ROC analysis. P < 0.05 defined statistical significance. Seven patients were excluded due to indeterminate outcomes. 25 patients (16 female, 9 male; 27 lesions; 28 scan sessions) had clear outcomes, proven by either biopsy (n = 16 patients) or serial follow-up MRI (n = 9 patients). Primary subtypes included breast (n = 9), lung (n = 7), melanoma (n = 3), squamous cell cancer of the head and neck (n = 2) and other (n = 4). Twenty-two patients underwent prior radiation (2-113 months) and three received only prior chemotherapy (5 months to 3 years). A change > 0.19 of L/GM ratios as a function of time was 95% sensitive, 100% specific, and 96.4% accurate (P = 0.0001; AUC = 0.97) for distinguishing tumor versus radiation necrosis. The ratio of the change of the lesion to WM ratios over time was the second best indicator of outcome when compared to all indices used (ROC cut-off = 0.25, sensitivity 89.5% and specificity 90.9%, and accuracy 89.2%; P = 0.0001; AUC = 0.95), Early or late SUVs of the lesion alone did not differentiate between tumor and necrosis. Regardless of histological type, differentiation of necrosis from metastatic brain lesions was improved by using the change of lesion to gray matter SUVmax ratios as a function of time. C1 [Horky, Laura L.; Hsiao, Edward M.; Gerbaudo, Victor H.] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging,Med Sch, Boston, MA 02115 USA. [Weiss, Stephanie E.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02115 USA. [Drappatz, Jan] Harvard Univ, Dana Farber Canc Inst, Sch Med, Ctr Neurooncol, Boston, MA 02115 USA. [Drappatz, Jan] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. RP Horky, LL (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging,Med Sch, 75 Francis St, Boston, MA 02115 USA. EM lhorky@partners.org NR 26 TC 30 Z9 30 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2011 VL 103 IS 1 BP 137 EP 146 DI 10.1007/s11060-010-0365-8 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 760KL UT WOS:000290323100012 PM 20838854 ER PT J AU Kelly, PJ Dinkin, MJ Drappatz, J O'Regan, KN Weiss, SE AF Kelly, Paul J. Dinkin, Marc J. Drappatz, Jan O'Regan, Kevin N. Weiss, Stephanie E. TI Unexpected late radiation neurotoxicity following bevacizumab use: a case series SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Optic neuropathy; Bevacizumab; Radiation; Neurotoxicity; Glioblastoma ID ENDOTHELIAL GROWTH-FACTOR; OPTIC NEUROPATHY; TUMOR-GROWTH; SPINAL-CORD; ANGIOGENESIS AB The purpose of this case series is to report the unexpected occurrence of four cases of late radiation-induced neurotoxicity with bevacizumab use following radiotherapy to the CNS. We retrospectively reviewed the case records of four patients, three with glioblastoma and one with bone metastases secondary to metastatic breast cancer, who were treated with radiotherapy and developed late radiation-induced neurotoxicity following bevacizumab use. Three cases of optic neuropathy in glioblastoma patients and a single case of Brown-S,quard syndrome in the thoracic spine of a patient with metastatic breast cancer are reported. We hypothesize that bevacizumab use following radiotherapy to the CNS may inhibit vascular endothelial growth factor-dependent repair of normal neural tissue, and thus may increase the risk of late radiation neurotoxicity. Phase III data on the safety and efficacy of bevacizumab use with radiation in the setting of glioblastoma is awaited. C1 [Kelly, Paul J.; Weiss, Stephanie E.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [Dinkin, Marc J.] New York Presbyterian Hosp, Dept Ophthalmol, Weill Cornell Med Coll, New York, NY USA. [Drappatz, Jan] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Ctr Neurooncol,Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [O'Regan, Kevin N.] Harvard Univ, Dana Farber Canc Inst, Dept Radiol, Sch Med, Boston, MA 02115 USA. RP Kelly, PJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Med Sch, 75 Francis St ASB1,L2, Boston, MA 02115 USA. EM pkelly@lroc.harvard.edu NR 17 TC 6 Z9 7 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2011 VL 102 IS 3 BP 485 EP 490 DI 10.1007/s11060-010-0336-0 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 760KE UT WOS:000290322400016 PM 20680396 ER PT J AU Adams, JM AF Adams, Jeffrey M. TI The Development of Nurse Executive Leadership An Interview With Marjorie Beyers SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, 275 Cambridge St,POB 4, Boston, MA 02114 USA. EM jadams9@partners.org NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAY PY 2011 VL 41 IS 5 BP 194 EP 196 DI 10.1097/NNA.0b013e3182171b5e PG 3 WC Nursing SC Nursing GA 754WD UT WOS:000289887500002 ER PT J AU Bienstock, DA Dodson, TB Perrott, DH Chuang, SK AF Bienstock, Daniel A. Dodson, Thomas B. Perrott, David H. Chuang, Sung-Kiang TI Prognostic Factors Affecting the Duration of Disability After Third Molar Removal SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID QUALITY-OF-LIFE; ALVEOLAR OSTEITIS; 3RD-MOLAR SURGERY; RISK-FACTORS; RECOVERY; COMPLICATIONS; CHLORHEXIDINE; OUTCOMES; AGE AB Purpose: The purposes of this investigation were 1) to estimate the duration of disability after third molar removal and 2) to identify factors associated with prolonged recovery. Materials and Methods: This was a prospective cohort study composed of subjects enrolled in the American Association of Oral and Maxillofacial Surgeons Age-Related Third Molar Study. The predictor variables were grouped as follows: demographic, health status, anatomic, pathologic, medications, and complications. The outcome variable was the duration of postoperative disability measured as the number of days the subject reported inability to perform normal daily activities after third molar removal. Bivariate and multiple linear regression analyses were used. The level of statistical significance was P < .05. Results: The study sample included 4,004 subjects who had 8,748 third molars removed. The mean duration of postoperative disability was 1.4 +/- 1.8 days (range, 0-26; median, 1 day). In the multiple linear regression model, age, female gender, number of third molars removed, mandibular third molar removal, full-bony impaction, sum of antibiotics or pain medications, and complications were associated with prolonged recovery (P < .05). Erupted third molars, periodontal disease or other preoperative pathology, and use of chlorhexidine were associated with earlier return to normal daily activities (P < .05). Conclusion: The study results suggest that third molar removal is associated with a mean delay in returning to normal activities of less than 2 days. Several factors were statistically associated with time to return to normal activities. (C) 2011 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 69:1272-1277, 2011 C1 [Dodson, Thomas B.; Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Dodson, Thomas B.; Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Perrott, David H.] Salinas Valley Mem Healthcare Syst, Salinas, CA USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Boston, MA 02114 USA. RP Chuang, SK (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM sungkiangchuang@gmail.com FU Oral and Maxillofacial Surgery Foundation; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery's Center; Harvard Medical School Office; Massachusetts General Physicians Organization FX This investigation was supported by 1) the Student Research Training Award from the Oral and Maxillofacial Surgery Foundation, 2) Massachusetts General Hospital Department of Oral and Maxillofacial Surgery's Center for Applied Clinical Investigation and Education and Research Fund, 3) Harvard Medical School Office of Enrichment Programs Student Research Fund, and 4) Massachusetts General Physicians Organization. NR 12 TC 11 Z9 11 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 MAY PY 2011 VL 69 IS 5 BP 1272 EP 1277 DI 10.1016/j.joms.2010.06.211 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 759KS UT WOS:000290242300013 PM 21256646 ER PT J AU Marcus, SC Durkin, M AF Marcus, Steven C. Durkin, Michael TI Stimulant Adherence and Academic Performance in Urban Youth With Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE stimulant; adherence; academic performance; school; ADHD ID DEFICIT HYPERACTIVITY DISORDER; TERM SCHOOL OUTCOMES; AFRICAN-AMERICAN; CHILDREN; ADHD; METHYLPHENIDATE; MEDICATION; ADOLESCENTS; ACHIEVEMENT; CHILDHOOD AB Objective: This analysis assessed whether stimulant adherence was associated with improvement in academic grade point average (GPA) among children diagnosed with and treated for attention-deficit/hyperactivity disorder (ADHD). Method: Medicaid claims were merged with academic records from Philadelphia public schools of Medicaid-eligible children in first through eighth grades who were diagnosed with ADHD and who had filled one or more stimulant prescription. Students diagnosed with mental retardation, autism, or speech, hearing, visual, or language impairments were excluded. Marking periods were scored for GPA (range: 0-4.0) based on English, mathematics, social studies, and science grades and for stimulant adherence (medication possession ratio >= 0.70). Random and fixed-effects models estimated the effects of stimulant adherence on GPA, between all adherent and nonadherent marking periods in aggregate and within individual student's marking periods, respectively. Results: A total of 3,543 students contributed 29,992 marking periods, of which 18.6% were adherent. Mean GPA was significantly higher during stimulant-adherent (2.18) than stimulant-nonadherent (1.99) marking periods in aggregate (p < .0001). The regression coefficient representing within-student association between stimulant adherence and GPA over time was 0.108 (p < .0001), indicating that adherence was associated with a 0.108 increase in GPA. In stratified analyses, analogous coefficients were 0.106 for boys, 0.111 for girls, 0.078 for elementary students, and 0.118 for middle school students (all p < .0001). The association was stronger among students with (0.139) than without (0.088) comorbid disruptive behavior disorders (both p < .0001). Conclusions: Stimulant adherence, although found to be low among urban elementary and middle school students diagnosed with ADHD, was associated with a marginal improvement in GPA. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(5):480-489. C1 [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19103 USA. [Marcus, Steven C.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Durkin, Michael] Ortho McNeil Janssen Sci Affairs LLC, Titusville, NJ USA. RP Marcus, SC (reprint author), Univ Penn, Sch Social Policy & Practice, 3701 Locust Walk, Philadelphia, PA 19103 USA. EM marcuss@sp2.upenn.edu FU Ortho-McNeil Janssen Scientific Affairs, LLC; Eli Lilly and Co., Bristol-Myers Squibb; Johnson and Johnson FX This project was funded by Ortho-McNeil Janssen Scientific Affairs, LLC.; Dr. Marcus has received grant support from Ortho-McNeil Janssen, and has served as a consultant to Eli Lilly and Co., Bristol-Myers Squibb, and AstraZeneca. Mr. Durkin holds stock in Johnson and Johnson. NR 35 TC 18 Z9 18 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2011 VL 50 IS 5 BP 480 EP 489 DI 10.1016/j.jaac.2011.02.007 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 757GH UT WOS:000290073000009 PM 21515197 ER PT J AU Rao, SR DesRoches, CM Donelan, K Campbe, EG Miralles, PD Jha, AK AF Rao, Sowmya R. DesRoches, Catherine M. Donelan, Karen Campbe, Eric G. Miralles, Paola D. Jha, Ashish K. TI Electronic health records in small physician practices: availability, use, and perceived benefits SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID ADOPTION; CARE AB Objective To examine variation in the adoption of electronic health record (EHR) functionalities and their use patterns, barriers to adoption, and perceived benefits by physician practice size. Design Mailed survey of a nationally representative random sample of practicing physicians identified from the Physician Masterfile of the American Medical Association. Measurements We measured, stratified by practice size: (1) availability of EHR functionalities, (2) functionality use, (3) barriers to the adoption and use of EHR, and (4) impact of the EHR on the practice and quality of patient care. Results With a response rate of 62%, we found that <2% of physicians in solo or two-physician (small) practices reported a fully functional EHR and 5% reported a basic EHR compared with 13% of physicians from 11+ group (largest group) practices with a fully functional system and 26% with a basic system. Between groups, a 21-46% difference in specific functionalities available was reported. Among adopters there were moderate to large differences in the use of the EHR systems. Financial barriers were more likely to be reported by smaller practices, along with concerns about future obsolescence. These differences were sizable (13-16%) and statistically significant (p<0.001). All adopters reported similar benefits. Limitations Although we have adjusted for response bias, influences may still exist. Conclusion Our study found that physicians in small practices have lower levels of EHR adoption and that these providers were less likely to use these systems. Ensuring that unique barriers are addressed will be critical to the widespread meaningful use of EHR systems among small practices. C1 [Jha, Ashish K.] Harvard Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA 02115 USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Ctr Biostat, Boston, MA 02114 USA. RP Jha, AK (reprint author), Harvard Univ, Dept Hlth Policy & Management, Vet Affairs Boston Healthcare Syst, Brigham & Womens Hosp,Div Gen Med,Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu FU Office of the National Coordinator for Health Information Technology; Robert Wood Johnson Foundation; GE Corporation Healthcare; UpToDate FX This study was supported by the Office of the National Coordinator for Health Information Technology and a grant from the Robert Wood Johnson Foundation. Drs Rao and Donelan report receiving grant support from GE Corporation Healthcare, and Dr Jha reports receiving consulting fees from UpToDate. NR 12 TC 46 Z9 46 U1 7 U2 15 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY PY 2011 VL 18 IS 3 BP 271 EP 275 DI 10.1136/amiajnl-2010-000010 PG 5 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 755TT UT WOS:000289960600010 PM 21486885 ER PT J AU Schnipper, JL Liang, CL Hamann, C Karson, AS Palchuk, MB McCarthy, PC Sherlock, M Turchin, A Bates', DW AF Schnipper, Jeffrey L. Liang, Catherine L. Hamann, Claus Karson, Andrew S. Palchuk, Matvey B. McCarthy, Patricia C. Sherlock, Melanie Turchin, Alexander Bates', David W. TI Development of a tool within the electronic medical record to facilitate medication reconciliation after hospital discharge SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB Serious medication errors occur commonly in the period after hospital discharge. Medication reconciliation in the postdischarge ambulatory setting may be one way to reduce the frequency of these errors. The authors describe the design and implementation of a novel tool built into an ambulatory electronic medical record ([MA) to facilitate postdischarge medication reconciliation. The tool compares the preadmission medication list within the ambulatory EMR to the hospital discharge medication list, highlights all changes, and allows the EMR medication list to be easily updated. As might be expected for a novel tool intended for use in a minority of visits, use of the tool was low at first: 20% of applicable patient visits within 30 days of discharge. Clinician outreach, education, and a pop-up reminder succeeded in increasing use to 41% of applicable visits. Review of feedback identified several usability issues that will inform subsequent versions of the tool and provide generalizable lessons for how best to design medication reconciliation tools for this setting. C1 [Schnipper, Jeffrey L.] Brigham & Womens Hosp, Div Gen Med, Brigham & Womens Hosp Hospitalist Serv, Boston, MA 02120 USA. [Schnipper, Jeffrey L.; Liang, Catherine L.; Bates', David W.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02120 USA. [Hamann, Claus; Karson, Andrew S.; McCarthy, Patricia C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hamann, Claus] Massachusetts Gen Hosp, Geriatr Med Unit, Boston, MA 02114 USA. [Karson, Andrew S.; McCarthy, Patricia C.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Palchuk, Matvey B.; Sherlock, Melanie; Turchin, Alexander] Partners Informat Syst Clin Informat Res & Dev, Wellesley, MA USA. [Turchin, Alexander] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02120 USA. [Bates', David W.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Schnipper, JL (reprint author), Brigham & Womens Hosp, Div Gen Med, Brigham & Womens Hosp Hospitalist Serv, 1620 Tremont St,BC3-2Y, Boston, MA 02120 USA. EM jschnipper@partners.org FU Agency for Healthcare Research and Quality [1 U18 HS016970-01]; National Heart Lung and Blood Institute [1 K08 HL072806-01] FX This study was supported by a grant from the Agency for Healthcare Research and Quality (1 U18 HS016970-01). JLS was supported by a mentored career development award from the National Heart Lung and Blood Institute (1 K08 HL072806-01). NR 11 TC 30 Z9 30 U1 0 U2 7 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY PY 2011 VL 18 IS 3 BP 309 EP 313 DI 10.1136/amiajnl-2010-000040 PG 5 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 755TT UT WOS:000289960600016 PM 21486889 ER PT J AU Kozora, E Filley, CM AF Kozora, Elizabeth Filley, Christopher M. TI Cognitive Dysfunction and White Matter Abnormalities in Systemic Lupus Erythematosus SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Review DE Lupus; Neuropsychology; Magnetic resonance imaging; Magnetic resonance spectroscopy; Mechanisms; Methodology ID MAGNETIC-RESONANCE SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; PROTON MR SPECTROSCOPY; BRAIN-LESIONS; ACUTE ONSET; DEFICITS; INJURY; SLE; MANIFESTATIONS; IMPAIRMENT AB Brain abnormalities have been documented by neuropsychological assessment as well as a variety of neuroimaging techniques in patients with systemic lupus erythematosus (SLE). Conventional neuroimaging in patients with neuropsychiatric disease (NPSLE) typically discloses periventricular white matter (WM) hyperintensities, infarcts, hemorrhages, and cerebral atrophy. In SLE patients with none of these findings, sophisticated neuroimaging techniques have recently supported associations between microstructural WM abnormalities and abnormal attention, executive function, and processing speed. This mild cognitive dysfunction in SLE (MCD-SLE), which may result from early myelinopathy, precedes the more severe cognitive dysfunction of NPSLE, related to more obvious WM and neuronal damage. (JINS, 2011, 17, 385-392) C1 [Kozora, Elizabeth] Natl Jewish Hlth, Denver, CO 80206 USA. [Kozora, Elizabeth; Filley, Christopher M.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO USA. [Kozora, Elizabeth; Filley, Christopher M.] Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kozora, E (reprint author), Natl Jewish Hlth, 1400 Jackson St, Denver, CO 80206 USA. EM kozorae@njhealth.org RI Burleson, Andrew/B-5609-2016 OI Burleson, Andrew/0000-0002-4857-3583 FU National Institute of Musculoskeletal and Skin Diseases [RO1 AR049152] FX The authors report no conflicts of interest. This manuscript has not been published previously either electronically or in print. Supported in part by the National Institute of Musculoskeletal and Skin Diseases, (Grant RO1 AR049152). NR 40 TC 20 Z9 20 U1 1 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2011 VL 17 IS 3 BP 385 EP 392 DI 10.1017/S1355617711000191 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 757QU UT WOS:000290103600001 PM 21338548 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Texting the Doctor SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Burstein, Harold J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2011 VL 9 IS 5 BP 459 EP 459 PG 1 WC Oncology SC Oncology GA 760AG UT WOS:000290292400002 PM 21550965 ER PT J AU Zelenetz, AD Abramson, JS Advani, RH Andreadis, CB Bartlett, N Bellam, N Byrd, JC Czuczman, MS Fayad, LE Glenn, MJ Gockerman, JP Gordon, LI Harris, NL Hoppe, RT Horwitz, SM Kelsey, CR Kim, YH LaCasce, AS Nademanee, A Porcu, P Press, O Pro, B Reddy, N Sokol, L Swinnen, LJ Tsien, C Vose, JM Wierda, WG Yahalom, J Zafar, N AF Zelenetz, Andrew D. Abramson, Jeremy S. Advani, Ranjana H. Andreadis, C. Babis Bartlett, Nancy Bellam, Naresh Byrd, John C. Czuczman, Myron S. Fayad, Luis E. Glenn, Martha J. Gockerman, Jon P. Gordon, Leo I. Harris, Nancy Lee Hoppe, Richard T. Horwitz, Steven M. Kelsey, Christopher R. Kim, Youn H. LaCasce, Ann S. Nademanee, Auayporn Porcu, Pierluigi Press, Oliver Pro, Barbara Reddy, Nashitha Sokol, Lubomir Swinnen, Lode J. Tsien, Christina Vose, Julie M. Wierda, William G. Yahalom, Joachim Zafar, Nadeem TI Non-Hodgkin's Lymphomas SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; chronic lymphocytic leukemia; follicular lymphoma; diffuse large B-cell lymphoma; mantle cell lymphoma; peripheral T-cell lymphoma; cutaneous T-cell lymphoma; mycosis fungoides; Sezary syndrome; marginal zone lymphoma; mucosaassociated lymphoid tissue lymphoma; diagnosis; treatment; hematopathology; immunohistochemistry; treatment guidelines; staging evaluation; lymphoma pathology; lymphoma therapy ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL LYMPHOMA; TERM-FOLLOW-UP; RANDOMIZED CONTROLLED-TRIAL; PHASE-II TRIAL; ANTI-CD20 MONOCLONAL-ANTIBODY; PREVIOUSLY UNTREATED PATIENTS; POSITRON-EMISSION-TOMOGRAPHY; INVOLVED-FIELD RADIOTHERAPY; PROGRESSION-FREE SURVIVAL C1 [Zelenetz, Andrew D.; Horwitz, Steven M.; Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Abramson, Jeremy S.; Harris, Nancy Lee] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Advani, Ranjana H.; Hoppe, Richard T.; Kim, Youn H.] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Andreadis, C. Babis] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Bartlett, Nancy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Bartlett, Nancy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Bellam, Naresh] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Byrd, John C.; Porcu, Pierluigi] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY USA. [Fayad, Luis E.; Wierda, William G.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Glenn, Martha J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Gordon, Leo I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [LaCasce, Ann S.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Nademanee, Auayporn] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Press, Oliver] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Pro, Barbara] Fox Chase Canc Ctr, Philadelphia, PA USA. [Sokol, Lubomir] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Swinnen, Lode J.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Tsien, Christina] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Vose, Julie M.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Zafar, Nadeem] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. RP Zelenetz, AD (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [P30 CA016672] NR 387 TC 33 Z9 37 U1 0 U2 11 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2011 VL 9 IS 5 BP 484 EP 560 PG 77 WC Oncology SC Oncology GA 760AG UT WOS:000290292400005 PM 21550968 ER PT J AU Arellano, RS Gervais, DA Mueller, PR AF Arellano, Ronald S. Gervais, Debra A. Mueller, Peter R. TI Computed Tomography-guided Drainage of Mediastinal Abscesses: Clinical Experience with 23 Patients SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID DESCENDING NECROTIZING MEDIASTINITIS; ESOPHAGOGASTRIC ANASTOMOTIC LEAK; PERCUTANEOUS DRAINAGE; ESOPHAGECTOMY; MANAGEMENT; CANCER AB Purpose: To evaluate the technical and clinical success rates of computed tomography (CT) guided percutaneous drainage of mediastinal abscesses. Materials and Methods: An interventional radiology database was used to identify patients who underwent CT-guided percutaneous drainage of mediastinal abscesses. Medical records were reviewed to evaluate abscess etiology, drainage technique, clinical outcome, and complications. Results: Over a 10-year period, 23 patients (20 men; average age, 54 y; range, 34-77 y) with 24 mediastinal abscesses underwent 25 CT-guided drainage procedures. Abscess etiologies included esophageal leak after esophagectomy (n = 6), perforated esophageal cancer (n = 4), Nissen fundoplication (n = 3), emetogenic esophageal rupture (n = 3), infectious (n = 2), cardiac surgery (n = 1), iatrogenic (n = 1), gastric strangulation (n = 1), Whipple procedure (n = 1), and thoracotomy for lung cancer (n = I). Drainages were performed with tandem trocar (n = 14) or Seldinger (n = 11) technique. A total of 25 catheters were used: 8.5 F (n = 9), 10 (n = 8), 12 F (n = 6), 14 F (n = 1), and 16 F (n = 1). The mean time of catheter drainage was 13.6 days. Technical success was achieved in all 25 attempts (100%). Twenty-two of the 23 patients had complete resolution of the abscess without the need for surgical debridement, for a clinical success rate of 95.6%. One patient underwent technically and clinically successful abscess drainage but required surgical exploration for repair of an anastomotic leak after esophagogastrectomy. There was one complication. One patient had inadvertent placement of a catheter within a pulmonary vein. The catheter was removed after 24 hours without hemodynamic consequences. Conclusions: Percutaneous CT-guided drainage of mediastinal abscesses is an uncommon procedure, but the results of this study suggest that it is associated with high technical and clinical success rates. C1 [Arellano, Ronald S.; Gervais, Debra A.; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Arellano, RS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM rarellano@partners.org NR 23 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAY PY 2011 VL 22 IS 5 BP 673 EP 677 DI 10.1016/j.jvir.2011.01.427 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 760XT UT WOS:000290358700013 PM 21439848 ER PT J AU Levenson, RB Pearson, KM Saokar, A Lee, SI Mueller, PR Hahn, PF AF Levenson, Robin B. Pearson, Kara M. Saokar, Anuradha Lee, Susanna I. Mueller, Peter R. Hahn, Peter F. TI Image-guided Drainage of Tuboovarian Abscesses of Gastrointestinal or Genitourinary Origin: A Retrospective Analysis SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID TRANSVAGINAL DRAINAGE; PERCUTANEOUS DRAINAGE; FLUID COLLECTIONS; ASPIRATION AB Purpose: To analyze the authors' success with image-guided drainage of tuboovarian abscesses (TOAs). Materials and Methods: Retrospective analysis of patients with image-guided TOA drainage from 1999 to 2008 was performed. Patient recovery without salpingo-oophorectomy was considered clinical success. A total of 57 TOAs were drained in 49 female patients (mean age, 43; range, 12 to > 89). Results: Thirty-three (58%) TOAs were drained percutaneously using computed tomography guidance and 24 were ultrasound guided (21 transvaginally, three transabdominally). Fifty-three TOAs were drained with catheter placement, and four were drained with aspiration alone. Abscess etiologies include pelvic inflammatory disease (n = 21, 37%), gastrointestinal conditions related (n = 21, 37%), gynecologic surgery (n = 8, 14%), and other (12%). Image-guided drainage resolved TOAs without salpingo-oophorectomy in 74% of cases overall (42 of 57) and 88% (29 of 33) of gynecologic-related cases, including 95% (20 of 21) of pelvic inflammatory disease cases. Salpingo-oophorectomy was performed more often in gastrointestinal-related cases (10 of 21, 48%) than for all other causes (five of 36, 14%; P < .001), with concurrent bowel surgery performed in the majority of the gastrointestinal-related cases. Mean follow-up after image-guided drainage was 48 months (range, 1-113) in patients who did not have related surgery. In patients who underwent salpingo-oophorectomy, it was performed on average 2.2 months (range, 0.5-5) after initial drainage. Two minor complications occurred; both involved catheter transgression of the urinary bladder in patients with transvaginal ultrasound-guided drainages. The patients were successfully treated conservatively with Foley catheter bladder decompression, without prolonged hospitalization. Conclusions: TOAs, especially of gynecologic origin, can often be managed successfully with image-guided drainage. After image-guided drainage, patients with gynecologic-related TOA were less likely to undergo salpingo-oophorectomy than patients with gastrointestinal-related TOAs. C1 [Levenson, Robin B.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Levenson, Robin B.; Pearson, Kara M.; Saokar, Anuradha; Lee, Susanna I.; Mueller, Peter R.; Hahn, Peter F.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. RP Levenson, RB (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 1 Deaconess Rd, Boston, MA 02215 USA. EM rlevenso@bidmc.harvard.edu NR 20 TC 5 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 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAY PY 2011 VL 22 IS 5 BP 678 EP 686 DI 10.1016/j.jvir.2010.10.032 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 760XT UT WOS:000290358700014 PM 21419651 ER PT J AU Gloviczki, P Comerota, AJ Dalsing, MC Eklof, BG Gillespie, DL Gloviczki, ML Lohr, JM McLafferty, RB Meissner, MH Murad, MH Padberg, FT Pappas, PJ Passman, MA Raffetto, JD Vasquez, MA Wakefield, TW AF Gloviczki, Peter Comerota, Anthony J. Dalsing, Michael C. Eklof, Bo G. Gillespie, David L. Gloviczki, Monika L. Lohr, Joann M. McLafferty, Robert B. Meissner, Mark H. Murad, M. Hassan Padberg, Frank T. Pappas, Peter J. Passman, Marc A. Raffetto, Joseph D. Vasquez, Michael A. Wakefield, Thomas W. TI The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID GREAT SAPHENOUS-VEIN; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; ENDOVENOUS LASER-ABLATION; TRANSILLUMINATED POWERED PHLEBECTOMY; GUIDED FOAM SCLEROTHERAPY; ENDOSCOPIC PERFORATOR SURGERY; RADIOFREQUENCY OBLITERATION CLOSURE; TELANGIECTATIC LEG VEINS; PLACEBO-CONTROLLED TRIAL AB The Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) have developed clinical practice guidelines for the care of patients with varicose veins of the lower limbs and pelvis. The document also includes recommendations on the management of superficial and perforating vein incompetence in patients with associated, more advanced chronic venous diseases (CVDs), including edema, skin changes, or venous ulcers. Recommendations of the Venous Guideline Committee are based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system as strong (GRADE I) if the benefits clearly outweigh the risks, burden, and costs. The suggestions are weak (GRADE 2) if the benefits are closely balanced with risks and burden. The level of available evidence to support the evaluation or treatment can be of high (A), medium (B), or low or very low (C) quality. The key recommendations of these guidelines are: We recommend that in patients with varicose veins or more severe CVD, a complete history and detailed physical examination are complemented by duplex ultrasound scanning of the deep and superficial veins (GRADE 1A). We recommend that the CEAP classification is used for patients with CVD (GRADE 1A) and that the revised Venous Clinical Severity Score is used to assess treatment outcome (GRADE 1B). We suggest compression therapy for patients with symptomatic varicose veins (GRADE 2C) but recommend against compression therapy as the primary treatment if the patient is a candidate for saphenous vein ablation (GRADE 1B). We recommend compression therapy as the primary treatment to aid healing of venous ulceration (GRADE 1B). To decrease the recurrence of venous ulcers, we recommend ablation of the incompetent superficial veins in addition to compression therapy (GRADE 1A). For treatment of the incompetent great saphenous vein (GSV), we recommend endovenous thermal ablation (radiofrequency or laser) rather than high ligation and inversion stripping of the saphenous vein to the level of the knee (GRADE 1B). We recommend phlebectomy or sclerotherapy to treat varicose tributaries (GRADE 1B) and suggest foam sclerotherapy as an option for the treatment of the incompetent saphenous vein (GRADE 2C). We recommend against selective treatment of perforating vein incompetence in patients with simple varicose veins (CEAP class C-2; GRADE 1B), but we suggest treatment of pathologic perforating veins (outward flow duration >= 500 ms, vein diameter >= 3.5 mm) located underneath healed or active ulcers (CEAP class C-5-C-6; GRADE 2B). We suggest treatment of pelvic congestion syndrome and pelvic varices with coil embolization, plugs, or transcatheter sclerotherapy, used alone or together (GRADE 2B). ( J Vase Surg 2011;53:2S-48S.) C1 [Gloviczki, Peter] Mayo Clin, Div Vasc & Endovasc Surg, Rochester, MN 55905 USA. [Gloviczki, Monika L.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA. [Murad, M. Hassan] Mayo Clin, Div Prevent Occupat & Aerosp Med, Rochester, MN 55905 USA. [Comerota, Anthony J.] Jobst Vasc Ctr, Toledo, OH USA. [Dalsing, Michael C.] Indiana Univ Sch Med, Indianapolis, IN USA. [Eklof, Bo G.] Lund Univ, Helsingborg, Sweden. [Gillespie, David L.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Lohr, Joann M.] Lohr Surg Specialists, Cincinnati, OH USA. [McLafferty, Robert B.] So Illinois Univ, Springfield, IL USA. [Meissner, Mark H.] Univ Washington, Sch Med, Seattle, WA USA. [Padberg, Frank T.; Pappas, Peter J.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Passman, Marc A.] Univ Alabama Birmingham, Birmingham, AL USA. [Raffetto, Joseph D.] VA Boston Healthcare Syst, W Roxbury, MA USA. [Vasquez, Michael A.] Venous Inst Buffalo, N Tonawanda, NY USA. [Wakefield, Thomas W.] Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Gloviczki, P (reprint author), Mayo Clin, Div Vasc & Endovasc Surg, 200 1st St SW, Rochester, MN 55905 USA. EM gloviczki.peter@mayo.edu OI Gillespie, David/0000-0002-4378-9465; Murad, Mohammad Hassan/0000-0001-5502-5975 NR 374 TC 206 Z9 231 U1 5 U2 30 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2011 VL 53 SU S BP 2S EP 48S DI 10.1016/j.jvs.2011.01.079 PG 47 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 760YZ UT WOS:000290362600002 PM 21536172 ER PT J AU Conrad, MF Ergul, EA Patel, VI Cambria, MR LaMuraglia, GM Simon, M Cambria, RP AF Conrad, Mark F. Ergul, Emel A. Patel, Virendra I. Cambria, Matthew R. LaMuraglia, Glenn M. Simon, Mirela Cambria, Richard P. TI Evolution of operative strategies in open thoracoabdominal aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Vascular Annual Meeting/Society-for-Vascular Surgery CY JUN 10-13, 2010 CL Boston, MA SP Soc Vasc Surg ID HYPOTHERMIC CARDIOPULMONARY BYPASS; INTERCOSTAL ARTERY REATTACHMENT; MOTOR-EVOKED POTENTIALS; AORTIC-ANEURYSM; SPINAL-CORD; CIRCULATORY ARREST; NEUROLOGIC DEFICIT; FLUID DRAINAGE; SURGERY; RISK AB Objective: During a 24-year interval, we managed >90% of thoracoabdominal aortic aneurysm (TAA) repairs with a clamp-and-sew (clamp/sew) approach supplemented with protective adjuncts, including renal hypothermia and epidural cooling with aggressive intercostal reconstruction for spinal cord protection. A finite paraplegia rate led to operative modifications using distal aortic perfusion (DAP) through atriofemoral bypass to support cord collateral circulation and selective intercostal reconstruction based on motor evoked potential (MEP) monitoring. This study evaluated the effect of DAP/MEP on perioperative outcomes. Methods: Consecutive patients undergoing repair of nonruptured Crawford extent I-III TAA using DAP/MEP were compared with propensity-matched patients treated with the clamp/sew technique. Outcomes included 30-day mortality and paraplegia. Results: There were 52 patients in the DAP cohort vs 127 undergoing clamp/sew. The DAP and clamp/sew cohorts differed in age (62.6 vs 69.5 years, P = .0003), presence of Marfan disease (10% vs 2%, P = .01), and chronic dissection (37% vs 8%, P = .001). Operative mortality was low (DAP, 2%; clamp/sew, 5%; P = .38). Postoperative renal insufficiency, although doubled in clamp/sew (17%) vs DAP (8%; P = .10), was not significant. DAP patients had a significantly lower incidence of intercostal reconstruction than the clamp/sew group (1.0% vs 34%, P < .0001), yet there was no paraplegia in the DAP cohort vs 5% in clamp/sew (P = .11). The composite death/paraplegia rate was decreased with DAP at 1 of 52 (2%) vs clamp/sew at 11 of 127 (9%; P = .01). Paraparesis with complete recovery occurred in 5 of 52 (10%) of the DAP group. Conclusions: Elective TAA repair was accomplished with a low mortality in the DAP and clamp/sew cohorts. The use of MEP in the DAP cohort (despite a higher spinal cord ischemic risk due to the number of chronic dissection patients) decreased the need for intercostal reconstruction, with no paraplegia to date. DAP with MEP is the preferred operative strategy for extent I to III TAA repair. (J Vasc Surg 2011;53:1195-201.) C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Conrad, MF (reprint author), 15 Parkman St,WAC 440, Boston, MA 02114 USA. EM mconrad@partners.org NR 45 TC 29 Z9 34 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2011 VL 53 IS 5 BP 1195 EP 1201 DI 10.1016/j.jvs.2010.11.055 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 760YU UT WOS:000290362100006 PM 21315544 ER PT J AU Zhao, GF Shaik, RS Zhao, H Beagle, J Kuo, S Hales, CA AF Zhao, Gaofeng Shaik, Rahamthulla S. Zhao, Hang Beagle, John Kuo, Shuennwen Hales, Charles A. TI Low molecular weight (LMW) heparin inhibits injury-induced femoral artery remodeling in mouse via upregulating CD44 expression SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID SMOOTH-MUSCLE-CELLS; PULMONARY-HYPERTENSION; NEOINTIMAL HYPERPLASIA; HYALURONAN RECEPTOR; PROLIFERATION; MECHANISMS; MODEL; ATHEROSCLEROSIS; RESTENOSIS; APOPTOSIS AB Objective: The mechanism of postangioplasty restenosis remains poorly understood. Low molecular weight (LMW) heparin has been shown to inhibit the proliferation of vascular smooth muscle cells (VSMCs), which is the principal characteristic of restenosis. Studies have shown that LMW heparin could bind to CD44. We hypothesized that LMW heparin might modulate CD44 expression thereby decreasing vascular remodeling. Methods: Vascular remodeling was induced in CD44(+/+) and CD44(-/-) mice and treated with LMW heparin. The arteries were harvested for histologic assessment and determination of CD44 expression. Bone marrow transplantation was introduced to further explore the role and functional sites of CD44. Effects of LMW heparin on growth capacity, CD44 expression were further studied using the cultured mouse VSMCs. Results: Transluminal injury induced remarkable remodeling in mouse femoral artery (sham wall thickness percentage [WT%]: 3.4 +/- 1.2% vs injury WT%: 31.8 +/- 4.7%; P < .001). LMW heparin reduced the remodeling significantly (WT%: 17.8 +/- 3.5%, P < .005). CD44(-/-) mice demonstrated considerably thicker arterial wall remodeling (WT%: 46.2 +/- 7.6%, P = .0035), and CD44-chimeric mice exhibited equal contributions of the local and circulating CD44 signal to the neointima formation. LMW heparin markedly upregulated CD44 expression in the injured femoral arteries. In vitro, LMW heparin decreased mouse VSMC growth capacity and upregulated its CD44 expression simultaneously in a dose-dependent and time-dependent manner, which could be partially blocked by CD44 inhibitor. Conclusions: LMW heparin inhibits injury-induced femoral artery remodeling, at least partially, by upregulating CD44 expression. (J Vase Surg 2011;53:1359-67.) C1 [Zhao, Gaofeng; Shaik, Rahamthulla S.; Zhao, Hang; Beagle, John; Kuo, Shuennwen; Hales, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit,Dept Med, Boston, MA 02114 USA. [Zhao, Gaofeng] Zhengzhou Univ, Affiliated Hosp 1, Dept Surg, Zhengzhou, Peoples R China. [Kuo, Shuennwen] Natl Taiwan Univ, Dept Surg & Traumatol, Taipei 10764, Taiwan. RP Hales, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit,Dept Med, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM chales@partners.org OI KUO, SHUENN-WEN/0000-0001-5026-5582 FU National Institutes of Health (NIH) [HL039150] FX Supported by National Institutes of Health (NIH) grant HL039150 (C.A.H) NR 28 TC 3 Z9 3 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2011 VL 53 IS 5 BP 1359 EP 1367 DI 10.1016/j.jvs.2010.11.048 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 760YU UT WOS:000290362100027 PM 21276692 ER PT J AU Ye, Q Yan, Z Liao, XD Li, Y Yang, J Sun, JN Kawano, T Wang, XJ Cao, Z Wang, ZG Huang, L AF Ye, Qing Yan, Zheng Liao, Xiaodong Li, Yuan Yang, Jie Sun, Jiening Kawano, Takeshi Wang, Xiaojin Cao, Ziang Wang, Zhugang Huang, Lei TI MUC1 induces metastasis in esophageal squamous cell carcinoma by upregulating matrix metalloproteinase 13 SO LABORATORY INVESTIGATION LA English DT Article DE ESCC; metastasis; MMP13; MUC1; transcription ID INHIBITS TUMOR INVASION; GENE-TRANSCRIPTION; IN-VITRO; EXPRESSION; PROGNOSIS; CANCER; STRESS; RNA AB Esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances because of its high frequency of metastasis. Given the associations of MUC1 with ESCC and tumor metastasis, we explored a potential role of MUC1 in ESCC metastasis. Among 40 ESCC and 20 paired normal tissue specimens examined, we found a significant increase of MUC1 expression in ESCC and more importantly, that expression of MUC1 and MMP13 are strongly correlated in patients who had lymph node metastasis. Studies with cell models indicated that overexpression of MUC1 upregulates the expression of MMP13, leading to increased cell migration. In support of a mode of transcriptional regulation, promoter analysis revealed that MUC1 stimulates MMP13 expression through the Runx-2-binding site. The link of MUC1 to cell motility was further confirmed by the finding that depletion of MUC1 resulted in reduced expression of MMP13 and cell migration, invasion and adhesion. Moreover, the loss of cell metastatic potential was rescued by overexpression of MMP13 completely. Collectively, our findings indicate that MUC1 contributes to ESCC metastasis by stimulating MMP13 expression, suggesting MUC1 as a novel diagnostic biomarker and therapeutic target in ESCC. Laboratory Investigation (2011) 91, 778-787; doi:10.1038/labinvest.2011.12; published online 21 February 2011 C1 [Yan, Zheng; Liao, Xiaodong; Li, Yuan; Yang, Jie; Sun, Jiening; Wang, Zhugang; Huang, Lei] Shanghai Jiao Tong Univ, Dept Med Genet, Sch Med, Shanghai Univ,E Inst, Shanghai 200025, Peoples R China. [Ye, Qing; Cao, Ziang] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Cardiothorac Surg, Shanghai 200025, Peoples R China. [Wang, Xiaojin] Shanghai Jiao Tong Univ, Dept Biostat, Sch Med, Shanghai 200025, Peoples R China. [Kawano, Takeshi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Huang, L (reprint author), Shanghai Jiao Tong Univ, Dept Med Genet, Sch Med, Shanghai Univ,E Inst, 280 S Chongqing Rd, Shanghai 200025, Peoples R China. EM zhugangw@shsmu.edu.cn; leihuang@shsmu.edu.cn FU NNSF of China [30871363, 81071666]; State Education Ministry; Science and Technology Commission of Shanghai Municipality [07pj14065, 06ZR14067]; Shanghai Municipal Education Commission [E03003, J50201]; [NCET-08-0349] FX This work was supported by program 30871363, 81071666 by NNSF of China, program NCET-08-0349 and the SRF for ROCS by State Education Ministry, the program 07pj14065 and 06ZR14067 by Science and Technology Commission of Shanghai Municipality and program E03003 and J50201 by the Shanghai Municipal Education Commission. The authors are very grateful to Dr Donald Kufe (Dana-Farber Cancer Institute, Harvard Medical School) for expert advice and to Dr Zhimin Yuan (UT Health Science Center) for critical comments on the manuscript. NR 25 TC 22 Z9 22 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 2011 VL 91 IS 5 BP 778 EP 787 DI 10.1038/labinvest.2011.12 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 755WT UT WOS:000289971200013 PM 21339746 ER PT J AU Zinman, L Cudkowicz, M AF Zinman, Lorne Cudkowicz, Merit TI Emerging targets and treatments in amyotrophic lateral sclerosis SO LANCET NEUROLOGY LA English DT Review ID STEM-CELL TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; FRONTOTEMPORAL LOBAR DEGENERATION; RANDOMIZED SEQUENTIAL TRIAL; GROWTH-FACTOR-I; MOUSE MODEL; WILD-TYPE; SUPEROXIDE-DISMUTASE; CLINICAL-TRIAL; SKELETAL-MUSCLE AB Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that is currently untreatable. Many compounds have been tested in laboratory-based models and in patients with ALS, but so far only one drug, riluzole, has shown efficacy, yet it only slightly slows disease progression. Several new insights into the causes of motor neuron death have led to the identification of some important novel targets for intervention. At no time have studies involved such a wide range of innovations and such advanced technologies. Many promising studies are underway to test potential targets that will hopefully translate into meaningful therapeutics for patients with ALS. C1 [Zinman, Lorne] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA USA. RP Zinman, L (reprint author), Sunnybrook Hlth Sci Ctr, 2075 Bayview Ave,UG-26, Toronto, ON M4N 3M5, Canada. EM lorne.zinman@sunnybrook.ca FU Neuralstem; ISIS; Knopp Neuroscience FX MC has received research grants from Neuralstem, ISIS, and Knopp Neuroscience, and has consulted for Trophos and Synapse, serving as chairperson of the data and safety monitoring board. LZ declares that he has no conflicts of interest. NR 106 TC 46 Z9 50 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD MAY PY 2011 VL 10 IS 5 BP 481 EP 490 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 761TV UT WOS:000290424800017 PM 21511200 ER PT J AU Askenazi, M Webber, JT Marto, JA AF Askenazi, Manor Webber, James T. Marto, Jarrod A. TI mzServer: Web-based Programmatic Access for Mass Spectrometry Data Analysis SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID PROTEOMIC MS REPOSITORIES; PIPELINES; WORLD AB Continued progress toward systematic generation of large-scale and comprehensive proteomics data in the context of biomedical research will create project-level data sets of unprecedented size and ultimately overwhelm current practices for results validation that are based on distribution of native or surrogate mass spectrometry files. Moreover, the majority of proteomics studies leverage discovery-mode MS/MS analyses, rendering associated data-reduction efforts incomplete at best, and essentially ensuring future demand for re-analysis of data as new biological and technical information become available. Based on these observations, we propose to move beyond the sharing of interpreted spectra, or even the distribution of data at the individual file or project level, to a system much like that used in high-energy physics and astronomy, whereby raw data are made programmatically accessible at the site of acquisition. Toward this end we have developed a web-based server (mzServer), which exposes our common API (mzAPI) through very intuitive (RESTful) uniform resource locators (URL) and provides remote data access and analysis capabilities to the research community. Our prototype mzServer provides a model for lab-based and community-wide data access and analysis. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.003988, 1-7, 2011. C1 [Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, IL-91904 Jerusalem, Israel. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1158A, Boston, MA 02115 USA. EM jarrod_marto@dfci.harvard.edu OI Webber, James/0000-0001-8594-9888 FU Dana-Farber Cancer Institute; National Institutes of Health, NHGRI [P50HG004233]; National Institutes of Health, NINDS [P01NS047572] FX Generous support for this work was provided by the Dana-Farber Cancer Institute and the National Institutes of Health, NHGRI (P50HG004233), and NINDS (P01NS047572). NR 15 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAY PY 2011 VL 10 IS 5 SI SI DI 10.1074/mcp.M110.003988 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 759CC UT WOS:000290216700008 ER PT J AU Webber, JT Askenazi, M Marto, JA AF Webber, James T. Askenazi, Manor Marto, Jarrod A. TI mzResults: An Interactive Viewer for Interrogation and Distribution of Proteomics Results SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID MASS-SPECTROMETRY; MS REPOSITORIES; PROTEIN; GUIDELINES; MS/MS; QUANTITATION; PIPELINES; STRATEGY; TANDEM; TOOLS AB The growing use of mass spectrometry in the context of biomedical research has been accompanied by an increased demand for distribution of results in a format that facilitates rapid and efficient validation of claims by reviewers and other interested parties. However, the continued evolution of mass spectrometry hardware, sample preparation methods, and peptide identification algorithms complicates standardization and creates hurdles related to compliance with journal submission requirements. Moreover, the recently announced Philadelphia Guidelines (1, 2) suggest that authors provide native mass spectrometry data files in support of their peer-reviewed research articles. These trends highlight the need for data viewers and other tools that work independently of manufacturers' proprietary data systems and seamlessly connect proteomics results with original data files to support user-driven data validation and review. Based upon our recently described API1-based framework for mass spectrometry data analysis (3, 4), we created an interactive viewer (mzResults) that is built on established database standards and enables efficient distribution and interrogation of results associated with proteomics experiments, while also providing a convenient mechanism for authors to comply with data submission standards as described in the Philadelphia Guidelines. In addition, the architecture of mzResults supports in-depth queries of the native mass spectrometry files through our multiplierz software environment. We use phosphoproteomics data to illustrate the features and capabilities of mzResults. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.003970, 1-7, 2011. C1 [Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Askenazi, Manor; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Askenazi, Manor] Hebrew Univ Jerusalem, Dept Biol Chem, IL-91905 Jerusalem, Israel. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1158A, Boston, MA 02115 USA. EM jarrod_marto@dfci.harvard.edu OI Webber, James/0000-0001-8594-9888 FU Dana-Farber Cancer Institute; National Institutes of Health, NHGRI [P50HG004233]; National Institutes of Health, NINDS [P01NS047572] FX Generous support for this work was provided by the Dana-Farber Cancer Institute and the National Institutes of Health, NHGRI (P50HG004233), and NINDS (P01NS047572). NR 28 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAY PY 2011 VL 10 IS 5 SI SI DI 10.1074/mcp.M110.003970 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 759CC UT WOS:000290216700007 ER PT J AU Kure, M Pezzolesi, MG Poznik, GD Katavetin, P Skupien, J Dunn, JS Mychaleckyj, JC Warram, JH Krolewski, AS AF Kure, Masahiko Pezzolesi, Marcus G. Poznik, G. David Katavetin, Pisut Skupien, Jan Dunn, Jonathon S. Mychaleckyj, Josyf C. Warram, James H. Krolewski, Andrzej S. TI Genetic variation in the matrix metalloproteinase genes and diabetic nephropathy in type 1 diabetes SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Diabetic nephropathy; Type 1 diabetes; End-stage renal disease; Matrix metalloproteinase; Genetic association ID ALLELE-SPECIFIC REGULATION; ARTERY LUMINAL DIMENSIONS; GENOME-WIDE ASSOCIATION; PROMOTER ACTIVITY; SUSCEPTIBILITY; DISEASE; EXPRESSION; MELLITUS; GLOMERULOSCLEROSIS; ATHEROSCLEROSIS AB Genetic data support the notion that polymorphisms in members of the matrix metalloproteinase (MMP) family of genes play an important role in extracellular matrix remodeling and contribute to the pathogenesis of vascular disease. To identify novel genetic markers for diabetic nephropathy (DN), we examined the relationship between MMP gene polymorphisms and DN in the Genetics of Kidneys in Diabetes (GoKinD) population. Genotypic data from the Genetic Association Information Network (GAIN) type 1 DN project were analyzed for associations across 21 MMP genes in 1705 individual with type 1 diabetes, including 885 normoalbuminuric control subjects and 820 advanced DN case subjects. In total, we investigated the role of 1283 SNPs (198 genotyped SNPs and 1085 imputed SNPs) mapping to the MMP genes. We identified associations at several correlated SNPs across a 29.2 kb interval on chromosome 11q at the MMP-3/MMP-12 locus. The strongest associations occurred at 2 highly-correlated SNPs, rs610950 (OR=0.50, P=1.6x10(-5)) and rs1277718 (OR = 0.50, P = 2.1 x 10(-5)). Further examination of this locus identified 17 SNPs (2 genotyped SNPs and 15 imputed SNPs) in complete linkage disequilibrium associated with ON (P-values < 2.5 x 10(-4)), including a non-synonymous SNP (rs652438, Asn357Ser) located in exon 8 of MMP-12 that significantly reduced the risk of DN among carriers of the serine substitution relative to homozygous carriers of asparagine (OR = 0.51; 95% CI = 0.37-0.71, P=62 x 10(-5)). Taken together, our study suggests that genetic variations within the MMP-3/MMP-12 locus influence susceptibility of ON in type 1 diabetes. (C) 2011 Elsevier Inc. All rights reserved. C1 [Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Kure, Masahiko; Pezzolesi, Marcus G.; Poznik, G. David; Katavetin, Pisut; Skupien, Jan; Dunn, Jonathon S.; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mychaleckyj, Josyf C.] Univ Virginia, Sch Med, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. [Katavetin, Pisut] Chulalongkorn Univ, Fac Med, Dept Med, Div Nephrol, Bangkok 10330, Thailand. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM Andrzej.Krolewski@joslin.harvard.edu FU Juvenile Diabetes Research Foundation (JDRF) [3-2009-397]; Centers for Disease Control (CDC) [PL 105-33, 106-554, 107-360]; National Institutes of Health (NIH) [DK58549, DK77532, DK36836]; Joslin Diabetes Center's NIH [DK007260-31] FX Funding support for the GAIN Search for Susceptibility Genes for Diabetic Nephropathy in Type 1 Diabetes (GoKinD study participants) study was provided by the Juvenile Diabetes Research Foundation (JDRF), and the Centers for Disease Control (CDC) (PL 105-33, 106-554, and 107-360 administered by the National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK) and the genotyping of samples was provided through the Genetic Association Information Network (GAIN). The dataset(s) used for the analyses described in this manuscript were obtained from the database of Genotype and Phenotype (dbGaP) found at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000018.v1.p1.; We acknowledge grant support from the National Institutes of Health (NIH) (DK58549 and DK77532 to ASK and DK36836 to the Genetics Core of the Diabetes and Endocrinology Research Center at the Joslin Diabetes Center). We also acknowledge the Joslin Diabetes Center's NIH T32 Training Grant (DK007260-31 to MGP) and support from the Juvenile Diabetes Research Foundation (JDRF) (3-2009-397 to JS). NR 36 TC 3 Z9 3 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2011 VL 103 IS 1 BP 60 EP 65 DI 10.1016/j.ymgme.2011.01.001 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 758WW UT WOS:000290199100009 PM 21277817 ER PT J AU Nathwani, AC Rosales, C McIntosh, J Rastegarlari, G Nathwani, D Raj, D Nawathe, S Waddington, SN Bronson, R Jackson, S Donahue, RE High, KA Mingozzi, F Ng, CYC Zhou, JF Spence, Y McCarville, MB Valentine, M Allay, J Coleman, J Sleep, S Gray, JT Nienhuis, AW Davidoff, AM AF Nathwani, Amit C. Rosales, Cecilia McIntosh, Jenny Rastegarlari, Ghasem Nathwani, Devhrut Raj, Deepak Nawathe, Sushmita Waddington, Simon N. Bronson, Roderick Jackson, Scott Donahue, Robert E. High, Katherine A. Mingozzi, Federico Ng, Catherine Y. C. Zhou, Junfang Spence, Yunyu McCarville, M. Beth Valentine, Marc Allay, James Coleman, John Sleep, Susan Gray, John T. Nienhuis, Arthur W. Davidoff, Andrew M. TI Long-term Safety and Efficacy Following Systemic Administration of a Self-complementary AAV Vector Encoding Human FIX Pseudotyped With Serotype 5 and 8 Capsid Proteins SO MOLECULAR THERAPY LA English DT Article ID ADENOASSOCIATED VIRAL VECTORS; HUMAN-FACTOR-IX; NONHUMAN PRIMATE MODEL; HEMOPHILIA-B; GENE-THERAPY; EFFICIENT TRANSDUCTION; LIVER TRANSDUCTION; SKELETAL-MUSCLE; VIRUS VECTORS; LARGE-SCALE AB Adeno-associated virus vectors (AAV) show promise for liver-targeted gene therapy. In this study, we examined the long-term consequences of a single intravenous administration of a self-complementary AAV vector (scAAV2/8-LP1-hFIXco) encoding a codon optimized human factor IX (hFIX) gene in 24 nonhuman primates (NHPs). A dose-response relationship between vector titer and transgene expression was observed. Peak hFIX expression following the highest dose of vector (2 x 10(12) pcr-vector genomes (vg)/kg) was 21 +/- 3 mu g/ml (similar to 420% of normal). Fluorescent in-situ hybridization demonstrated scAAV provirus in almost 100% of hepatocytes at that dose. No perturbations of clinical or laboratory parameters were noted and vector genomes were cleared from bodily fluids by 10 days. Macaques transduced with 2 x 10(11) pcr-vg/kg were followed for the longest period (similar to 5 years), during which time expression of hFIX remained > 10% of normal level, despite a gradual decline in transgene copy number and the proportion of transduced hepatocytes. All macaques developed serotype-specific antibodies but no capsid-specific cytotoxic T lymphocytes were detected. The liver was preferentially transduced with 300-fold more proviral copies than extrahepatic tissues. Long-term biochemical, ultrasound imaging, and histologic follow-up of this large cohort of NHP revealed no toxicity. These data support further evaluation of this vector in hemophilia B patients. C1 [Nathwani, Amit C.; Rosales, Cecilia; McIntosh, Jenny; Rastegarlari, Ghasem; Nathwani, Devhrut; Raj, Deepak; Nawathe, Sushmita] UCL, UCL Canc Inst, Dept Hematol, London WC1E 6BT, England. [Nathwani, Amit C.] NHS Blood & Transplant, London, England. [Waddington, Simon N.] UCL, Inst Womens Hlth, London WC1E 6BT, England. [Bronson, Roderick; Davidoff, Andrew M.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Jackson, Scott] Univ Tennessee, Hlth Sci Ctr, Dept Comparat Med, Memphis, TN USA. [Donahue, Robert E.] NHLBI, Hematol Branch, Washington, DC USA. [High, Katherine A.; Mingozzi, Federico] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA. [High, Katherine A.] Childrens Hosp Philadelphia, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. [Ng, Catherine Y. C.; Zhou, Junfang; Spence, Yunyu] St Jude Childrens Hosp, Dept Surg, Memphis, TN 38105 USA. [McCarville, M. Beth] St Jude Childrens Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. [Valentine, Marc] St Jude Childrens Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA. [Allay, James; Coleman, John; Sleep, Susan] St Jude Childrens Hosp, Childrens GMP, Memphis, TN 38105 USA. [Gray, John T.; Nienhuis, Arthur W.] St Jude Childrens Hosp, Div Expt Hematol, Memphis, TN 38105 USA. RP Nathwani, AC (reprint author), UCL, UCL Canc Inst, Dept Hematol, Paul OGorman Bldg,72 Huntley St, London WC1E 6BT, England. EM a.nathwani@ucl.ac.uk RI Waddington, Simon/G-3778-2011; mingozzi, federico/I-2332-2013 OI Waddington, Simon/0000-0003-4970-4730; FU Katharine Dormandy Trust, U.K., Medical Research Council, UK, Department of Health's NIHR Biomedical Research Centers; National Heart, Lung, and Blood Institute [HL073838]; National Cancer Institute Cancer Center [CA027165] FX This work was supported by The Katharine Dormandy Trust, U.K., Medical Research Council, UK, Department of Health's NIHR Biomedical Research Centers funding award to UCLH/UCL, UK, The ASSISI Foundation of Memphis, the American Lebanese Syrian Associated Charities (ALSAC), the National Heart, Lung, and Blood Institute grant HL073838 and the National Cancer Institute Cancer Center Support Grant CA027165. This report/article presents independent research commissioned by the National Institute for Health Research (NIHR), UK under its Programme Grants for Applied Research scheme (RP-PG-0310-1001). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. The authors declared no conflict of interest. NR 45 TC 107 Z9 109 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2011 VL 19 IS 5 BP 876 EP 885 DI 10.1038/mt.2010.274 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 758FE UT WOS:000290146200012 PM 21245849 ER PT J AU Kostic, AD Ojesina, AI Pedamallu, CS Jung, J Verhaak, RGW Getz, G Meyerson, M AF Kostic, Aleksandar D. Ojesina, Akinyemi I. Pedamallu, Chandra Sekhar Jung, Joonil Verhaak, Roel G. W. Getz, Gad Meyerson, Matthew TI PathSeq: software to identify or discover microbes by deep sequencing of human tissue SO NATURE BIOTECHNOLOGY LA English DT Letter ID HUMAN GENOME; SUBTRACTION; CARCINOMA; SEARCH C1 [Kostic, Aleksandar D.; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Jung, Joonil; Verhaak, Roel G. W.; Getz, Gad; Meyerson, Matthew] Massachusetts Inst Technol & Harvard, Broad Inst, Cambridge, MA USA. [Kostic, Aleksandar D.; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Jung, Joonil; Verhaak, Roel G. W.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Jung, Joonil; Verhaak, Roel G. W.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kostic, AD (reprint author), Massachusetts Inst Technol & Harvard, Broad Inst, Cambridge, MA USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI Ojesina, Akinyemi/0000-0003-0755-3639; Kostic, Aleksandar/0000-0002-0837-4360 FU NCI NIH HHS [RC2 CA148317, RC2CA148317] NR 15 TC 108 Z9 113 U1 0 U2 14 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 MAY PY 2011 VL 29 IS 5 BP 393 EP 396 DI 10.1038/nbt.1868 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 760CX UT WOS:000290301700013 PM 21552235 ER PT J AU Lupberger, J Zeisel, MB Xiao, F Thumann, C Fofana, I Zona, L Davis, C Mee, CJ Turek, M Gorke, S Royer, C Fischer, B Zahid, MN Lavillette, D Fresquet, J Cosset, FL Rothenberg, SM Pietschmann, T Patel, AH Pessaux, P Doffoel, M Raffelsberger, W Poch, O McKeating, JA Brino, L Baumert, TF AF Lupberger, Joachim Zeisel, Mirjam B. Xiao, Fei Thumann, Christine Fofana, Isabel Zona, Laetitia Davis, Christopher Mee, Christopher J. Turek, Marine Gorke, Sebastian Royer, Cathy Fischer, Benoit Zahid, Muhammad N. Lavillette, Dimitri Fresquet, Judith Cosset, Francois-Loic Rothenberg, S. Michael Pietschmann, Thomas Patel, Arvind H. Pessaux, Patrick Doffoel, Michel Raffelsberger, Wolfgang Poch, Olivier McKeating, Jane A. Brino, Laurent Baumert, Thomas F. TI EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy SO NATURE MEDICINE LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; B TYPE-I; FACTOR RECEPTOR; NEUTRALIZING ANTIBODIES; HEPATOMA-CELLS; TRANSFORMING-GROWTH; HUMAN LIVER; INFECTION; CD81 AB Hepatitis C virus (HCV) is a major cause of liver disease, but therapeutic options are limited and there are no prevention strategies. Viral entry is the first step of infection and requires the cooperative interaction of several host cell factors. Using a functional RNAi kinase screen, we identified epidermal growth factor receptor and ephrin receptor A2 as host cofactors for HCV entry. Blocking receptor kinase activity by approved inhibitors broadly impaired infection by all major HCV genotypes and viral escape variants in cell culture and in a human liver chimeric mouse model in vivo. The identified receptor tyrosine kinases (RTKs) mediate HCV entry by regulating CD81-claudin-1 co-receptor associations and viral glycoprotein-dependent membrane fusion. These results identify RTKs as previously unknown HCV entry cofactors and show that tyrosine kinase inhibitors have substantial antiviral activity. Inhibition of RTK function may constitute a new approach for prevention and treatment of HCV infection. C1 [Lupberger, Joachim; Zeisel, Mirjam B.; Xiao, Fei; Thumann, Christine; Fofana, Isabel; Zona, Laetitia; Turek, Marine; Royer, Cathy; Zahid, Muhammad N.; Baumert, Thomas F.] INSERM, U748, Strasbourg, France. [Lupberger, Joachim; Zeisel, Mirjam B.; Xiao, Fei; Thumann, Christine; Fofana, Isabel; Zona, Laetitia; Turek, Marine; Royer, Cathy; Zahid, Muhammad N.; Baumert, Thomas F.] Univ Strasbourg, Strasbourg, France. [Davis, Christopher; Mee, Christopher J.; McKeating, Jane A.] Univ Birmingham, Div Immun & Infect, Hepatitis C Res Grp, Birmingham, W Midlands, England. [Gorke, Sebastian] Univ Freiburg, Dept Med 2, Freiburg, Germany. [Fischer, Benoit; Raffelsberger, Wolfgang; Poch, Olivier; Brino, Laurent; Baumert, Thomas F.] Univ Strasbourg, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire,U964,UMR1704, Illkirch Graffenstaden, France. [Lavillette, Dimitri; Fresquet, Judith; Cosset, Francois-Loic] Univ Lyon 1, INSERM, Ecole Normale Super, Inst Fed Rech 128,U758, F-69365 Lyon, France. [Rothenberg, S. Michael] Massachusetts Gen Hosp, Ctr Canc, Howard Hughes Med Inst, Charlestown, MA USA. [Rothenberg, S. Michael] Harvard Univ, Sch Med, Charlestown, MA USA. [Pietschmann, Thomas] Ctr Expt & Clin Infect Res, TWINCORE, Div Expt Virol, Hannover, Germany. [Patel, Arvind H.] Univ Glasgow, MRC, Ctr Virus Res, Glasgow, Lanark, Scotland. [Pessaux, Patrick; Doffoel, Michel; Baumert, Thomas F.] Hop Univ Strasbourg, Strasbourg, France. RP Baumert, TF (reprint author), INSERM, U748, Strasbourg, France. EM thomas.baumert@unistra.fr RI Xiao, Fei/E-7133-2013; zahid, Muhammad Nauman/F-8793-2013; Pietschmann, Thomas/E-9241-2015; Zeisel, Mirjam/E-9205-2016; OI Xiao, Fei/0000-0001-7353-2700; Pietschmann, Thomas/0000-0001-5138-6239; Zeisel, Mirjam/0000-0003-1606-0131; Mee, Christopher/0000-0002-6359-2694; McKeating, Jane/0000-0002-7229-5886 FU European Research Council [ERC-2008-AdG-233130-HEPCENT]; INTERREG-IV-Rhin Superieur-FEDER-Hepato-Regio-Net; Agence Nationale de la Recherche [ANR-05-CEXC-008]; Agence Nationale de Recherche sur le Sida [2008/354]; Region Alsace; Institut National du Cancer; Institut de Genetique et de Biologie Moleculaire et Cellulaire; Institut National de la Sante et de la Recherche Medicale; Centre National de la Recherche Scientifique; Universite de Strasbourg; US National Insititutes of Health [1K08DE020139-01A1]; UK Medical Research Council; Wellcome Trust FX This work was supported by the European Research Council (ERC-2008-AdG-233130-HEPCENT), INTERREG-IV-Rhin Superieur-FEDER-Hepato-Regio-Net 2009, Agence Nationale de la Recherche (ANR-05-CEXC-008), Agence Nationale de Recherche sur le Sida 2008/354, Region Alsace, Institut National du Cancer, the Institut de Genetique et de Biologie Moleculaire et Cellulaire, Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique, Universite de Strasbourg, the US National Insititutes of Health (1K08DE020139-01A1), the UK Medical Research Council and the Wellcome Trust. We acknowledge A.-L. Morand, L. Froidevaux, A. Weiss, L. Poidevin, S. Durand and E. Soulier for excellent technical work. We thank R. Bartenschlager (University of Heidelberg) for providing Jc1 and Luc-Jc1 expression vectors, J. Ball (University of Nottingham) for UKN2A.2.4, UKN3A1.28 and UKN4.21.16 expression vectors, T. Wakita (National Institute of Infectious Diseases, Japan) for JFH1 constructs, C. M. Rice (The Rockefeller University) for Huh7.5 cells, F. V. Chisari (The Scripps Research Institute) for Huh7.5.1 cells, E. Harlow (Harvard University) for CDC2 expression plasmids and M. Tanaka (Hamamatsu University) for EphA2 expression plasmids. NR 55 TC 318 Z9 328 U1 4 U2 52 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2011 VL 17 IS 5 BP 589 EP U109 DI 10.1038/nm.2341 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 759MR UT WOS:000290250400035 PM 21516087 ER PT J AU Vemula, PK Anderson, RR Karp, JM AF Vemula, Praveen Kumar Anderson, R. Rox Karp, Jeffrey M. TI Nanoparticles reduce nickel allergy by capturing metal ions SO NATURE NANOTECHNOLOGY LA English DT Article ID CONTACT-DERMATITIS; ACETIC ACID; SOFT ACIDS; IN-VIVO; RELEASE; DISULFIRAM; CHELATION; BASES; HARD; EDTA AB Approximately 10% of the population in the USA(1,2) suffer from nickel allergy(3-5), and many are unable to wear jewellery or handle coins and other objects that contain nickel(6-10). Many agents have been developed to reduce the penetration of nickel through skin(11,12), but few formulations are safe and effective(13-15). Here, we show that applying a thin layer of glycerine emollient containing nanoparticles of either calcium carbonate or calcium phosphate on an isolated piece of pig skin (in vitro) and on the skin of mice (in vivo) prevents the penetration of nickel ions into the skin. The nanoparticles capture nickel ions by cation exchange, and remain on the surface of the skin, allowing them to be removed by simple washing with water. Approximately 11-fold fewer nanoparticles by mass are required to achieve the same efficacy as the chelating agent ethylenediamine tetraacetic acid. Using nanoparticles with diameters smaller than 500 nm in topical creams may be an effective way to limit the exposure to metal ions that can cause skin irritation. C1 [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Univ, Sch Med, Ctr Regenerat Therapeut, Boston, MA 02115 USA. [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Anderson, R. Rox] Harvard Univ, Sch Med, Laser & Cosmet Dermatol Ctr, Boston, MA 02114 USA. [Anderson, R. Rox] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Vemula, PK (reprint author), Harvard Univ, Sch Med, Ctr Regenerat Therapeut, Boston, MA 02115 USA. EM jkarp@rics.bwh.harvard.edu FU Brigham and Women's Hospital; Ewing Marion Kauffman Foundation FX The authors thank A. Kimball from the Massachusetts General Hospital for helpful discussions. This work was funded by start-up funds from the Brigham and Women's Hospital (J.M.K.). P.K.V. acknowledges the Ewing Marion Kauffman Foundation for an entrepreneur postdoctoral fellowship. The authors also thank D. Blankschtein and B. Polat for the generous gift of pigskin, as well as the MIT Center for Material Science Engineering Imaging facility and P. Boisvert for assistance, and S. Sonis for valuable discussions. NR 30 TC 14 Z9 14 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD MAY PY 2011 VL 6 IS 5 BP 291 EP 295 DI 10.1038/NNANO.2011.37 PG 5 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 760CV UT WOS:000290301300009 PM 21460828 ER PT J AU Laubach, J Richardson, PG Anderson, K AF Laubach, Jacob Richardson, Paul G. Anderson, Kenneth TI HEMATOLOGY Setting the standard for newly diagnosed multiple myeloma SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; THALIDOMIDE PLUS DEXAMETHASONE; BORTEZOMIB; THERAPY; TRIAL C1 [Laubach, Jacob; Richardson, Paul G.; Anderson, Kenneth] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Laubach, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jacobp_laubach@dfci.harvard.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAY PY 2011 VL 8 IS 5 BP 255 EP 256 DI 10.1038/nrclinonc.2011.43 PG 2 WC Oncology SC Oncology GA 758GG UT WOS:000290150100001 PM 21423257 ER PT J AU Zhu, AX Duda, DG Sahani, DV Jain, RK AF Zhu, Andrew X. Duda, Dan G. Sahani, Dushyant V. Jain, Rakesh K. TI HCC and angiogenesis: possible targets and future directions SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID ENDOTHELIAL-GROWTH-FACTOR; ADVANCED HEPATOCELLULAR-CARCINOMA; TYROSINE KINASE INHIBITOR; TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; MESSENGER-RNA EXPRESSION; PHASE-II TRIAL; CANCER-RELATED INFLAMMATION; FACTOR-RECEPTOR; PROGNOSTIC-SIGNIFICANCE; VASCULAR NORMALIZATION AB Hepatocellular carcinoma (HCC), the most common primary liver tumor, is notoriously resistant to systemic therapies, and often recurs even after aggressive local therapies. HCCs rely on the formation of new blood vessels for growth, and VEGF is critical in this process. A hallmark of new vessel formation in tumors is their structural and functional abnormality. This leads to an abnormal tumor microenvironment characterized by low oxygen tension. The liver is perfused by both arterial and venous blood and the resulting abnormal microenvironment selects for more-aggressive malignancies. Anti-VEGF therapy with sorafenib was the first systemic therapy to demonstrate improved survival in patients with advanced-stage HCC. This important development in the treatment of HCC raises hope as well as critical questions on the future development of targeted agents including other antiangiogenic agents, which hold promise to further increase survival in this aggressive disease. C1 [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Duda, Dan G.; Jain, Rakesh K.] Harvard Univ, Steele Lab Tumor Biol, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Sahani, Dushyant V.] Harvard Univ, Dept Radiol, Sch Med, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org FU National Institutes of Health [P01CA80124, R01CA115767, R21CA139168, M01RR01066]; Department of Defense [W81XWH-10-1-0016]; American Cancer Society [RSG-11-073-01-TBG] FX The authors acknowledge support by the National Institutes of Health (P01CA80124, R01CA115767, R21CA139168, M01RR01066, Federal Share/NCI Proton Beam Program Income Grants); by a Department of Defense Breast Cancer Research Innovator award (W81XWH-10-1-0016) and by an American Cancer Society Research Grant (RSG-11-073-01-TBG). NR 147 TC 156 Z9 166 U1 0 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAY PY 2011 VL 8 IS 5 BP 292 EP 301 DI 10.1038/nrclinonc.2011.30 PG 10 WC Oncology SC Oncology GA 758GG UT WOS:000290150100007 PM 21386818 ER PT J AU Tercyak, KP Alford, SH Emmons, KM Lipkus, IM Wilfond, BS McBride, CM AF Tercyak, Kenneth P. Alford, Sharon Hensley Emmons, Karen M. Lipkus, Isaac M. Wilfond, Benjamin S. McBride, Colleen M. TI Parents' Attitudes Toward Pediatric Genetic Testing for Common Disease Risk SO PEDIATRICS LA English DT Article DE genetic testing; chronic disease; risks and benefits; children; parents ID PERSONALIZED MEDICINE; PSYCHOLOGICAL-ASPECTS; CONFOUNDER-SELECTION; GENOMICS; CHILDREN; HEALTH; CANCER; BEHAVIORS; WILL; OPPORTUNITIES AB OBJECTIVE: To describe parents' attitudes toward pediatric genetic testing for common, adult-onset health conditions and to identify factors underlying these attitudes. PARTICIPANTS AND METHODS: Parents (n = 219) enrolled in a large, group-practice health plan were offered a "multiplex" genetic test for susceptibility to 8 common, adult-onset health conditions and completed an online survey assessing attitudes and beliefs about the risks and benefits of the test for their child, their willingness to consider having their child tested, and other psychosocial variables. RESULTS: Parents viewed the benefits of pediatric testing to outweigh its risks (positive decisional balance) and were moderately interested in pediatric testing. Variables associated with positive decisional balance included greater interest in knowing about gene-health associations in their child, anticipation of less difficulty understanding their child's genetic health risks, and more positive emotional reactions to learning about their child's decreased health risks (adjusted R-2 = 0.33, P < .0001). Similarly, variables associated with greater parental willingness to test were being a mother (versus being a father), greater perceived risk of diseases in their child, greater interest in knowing about gene-health relationships in their child, anticipating less difficulty learning about their child's genetic health risks, anticipating more positive emotional reactions to learning about their child's decreased health risks, and positive decisional balance (adjusted R-2 = 0.57, P < .0001). CONCLUSIONS: As genetic susceptibility testing for common, adult-onset health conditions proliferates, pediatricians should anticipate parents' interest in testing children and be prepared to facilitate informed decision making about such testing. Pediatrics 2011;127:e1288-e1295 C1 [Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Div Hlth Outcomes & Hlth Behav,Dept Oncol, Washington, DC 20007 USA. [Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. [Alford, Sharon Hensley] Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI USA. [Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lipkus, Isaac M.] Duke Univ, Sch Nursing, Durham, NC USA. [Wilfond, Benjamin S.] Univ Washington, Sch Med, Seattle Childrens Hosp, Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA. [Wilfond, Benjamin S.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Tercyak, KP (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Div Hlth Outcomes & Hlth Behav,Dept Oncol, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA. EM tercyakk@georgetown.edu FU National Institutes of Health (NIH) [HHSN268200782096C]; National Human Genome Research Institute at the National Institutes of Health; National Institutes of Health/National Cancer Institute [U19CA079689]; Group Health Research Institute; Henry Ford Hospital; Center for Inherited Disease Research; National Human Genome Research Institute [R01HG002686]; National Cancer Institute [R01CA137625] FX Funded by the National Institutes of Health (NIH).; This work was supported by the Intramural Research Program of the National Human Genome Research Institute at the National Institutes of Health. The research also was made possible by collaboration with the health management organization Cancer Research Network (CRN) funded by the National Institutes of Health/National Cancer Institute (U19CA079689). The overall goal of the CRN is to use a consortium of delivery systems to conduct cancer research. Additional resources were provided by the Group Health Research Institute and the Henry Ford Hospital. Genotyping services were provided by the Center for Inherited Disease Research, an entity fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (HHSN268200782096C). Manuscript preparation was supported by grants from the Ethical, Legal, and Social Implication Research Program of the National Human Genome Research Institute (R01HG002686) and from the National Cancer Institute (R01CA137625 to Kenneth P. Tercyak). NR 35 TC 28 Z9 28 U1 1 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAY PY 2011 VL 127 IS 5 BP E1288 EP E1295 DI 10.1542/peds.2010-0938 PG 8 WC Pediatrics SC Pediatrics GA 757OO UT WOS:000290097800024 PM 21502235 ER PT J AU Liu, AS Kao, HK Reish, RG Hergrueter, CA May, JW Guo, LF AF Liu, Allen S. Kao, Huang-Kai Reish, Richard G. Hergrueter, Charles A. May, James W., Jr. Guo, Lifei TI Postoperative Complications in Prosthesis-Based Breast Reconstruction Using Acellular Dermal Matrix SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID EXPANDER/IMPLANT RECONSTRUCTION; CAPSULE FORMATION; ALLODERM; IMPLANT; ALLOGRAFT; RADIATION AB Background: Acellular dermal matrix has become a common adjunct in prosthesis-based breast reconstruction. The authors' aim was to determine whether acellular dermal matrix use in immediate prosthesis-based breast reconstruction is associated with higher rate of complications. Methods: Over a 5 1/2-year period at the Brigham and Women's Hospital, 470 postmastectomy defects were reconstructed immediately using tissue expanders or implants. These were divided into two groups: reconstructions with or without acellular dermal matrix. Data were collected on patient comorbidities, radiation, intraoperative tumescent solution use, prosthesis size, initial fill volume, and complications. Results: The risk for major infections that required prosthesis removal was elevated in the acellular dermal matrix group (4.9 versus 2.5 percent), but this increase did not reach statistical significance (p = 0.172). There was a statistically significant increase in overall wound infection rate in the acellular dermal matrix group (6.8 versus 2.5 percent, p = 0.031), but in a multivariate analysis, the use of acellular dermal matrix did not materialize as a significant risk factor for overall wound infection. Overall surgical complication rate was significantly higher in the acellular dermal matrix group at 19.5 percent, compared with the non-acellular dermal matrix group at 12.3 percent (p = 0.001). Other significant risk factors for overall surgical complication included smoking, higher body mass index, higher initial volume, and larger implant size. Conclusions: Patient selection for prosthesis reconstruction involving acellular dermal matrix should be judicious, especially among smokers and patients with elevated body mass index. Even though the use of acellular dermal matrix allows higher initial volumes and reduced number of expansions, one should be careful about putting in too high of an initial volume. (Plast. Reconstr. Surg. 127: 1755, 2011.) C1 [Guo, Lifei] Brigham & Womens Hosp, Dept Surg, Div Plast Surg, Boston, MA 02115 USA. Chang Gung Mem Hosp, Dept Plast & Reconstruct Surg, Kaohsiung, Taiwan. Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP Guo, LF (reprint author), Brigham & Womens Hosp, Dept Surg, Div Plast Surg, 75 Francis St, Boston, MA 02115 USA. EM lguo@partners.org NR 23 TC 102 Z9 107 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2011 VL 127 IS 5 BP 1755 EP 1762 DI 10.1097/PRS.0b013e31820cf233 PG 8 WC Surgery SC Surgery GA 758FT UT WOS:000290148100002 PM 21228744 ER PT J AU Yaremchuk, MJ Doumit, G Thomas, MA AF Yaremchuk, Michael J. Doumit, Gabe Thomas, Matthew A. TI Alloplastic Augmentation of the Facial Skeleton: An Occasional Adjunct or Alternative to Orthognathic Surgery SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID IMPLANTS AB Background: Alloplastic implants can be adjunctive to orthognathic surgery by correcting contour irregularities or disharmonies after skeletal movements. Implant augmentation can also simulate the visual effect of osteotomies in patients with skeletal deficiencies whose occlusion is normal or has been corrected. Although sometimes it is an adjunct or an alternative to facial skeletal rearrangements, facial skeleton augmentation is not a substitute for orthognathic surgery. Methods: Alloplastic implants designed specifically to augment the infraorbital rim can correct the residual upper midface deficiency remaining after Le Fort I maxillary advancement. When used with paranasal and malar implants, they can simulate the visual effect of the Le Fort III osteotomy with advancement. Paranasal implants can simulate the appearance after Le Fort I advancement. Mandible and extended chin implants can correct skeletal irregularities and deficiencies after sagittal and horizontal osteotomies. They can also simulate the visual effect of these osteotomies. Results: The application of these concepts has been effective, with low morbidity, in 294 patients. No implants extruded or migrated. Eight patients (3 percent) had early postoperative infections. There were no late infections. Ten of 108 patients (9 percent) with midface implants had implant visibility with time. Conclusion: Alloplastic augmentation of the facial skeleton can be a useful adjunct or an alternative to orthognathic surgical procedures in situations when the occlusion is normal or has been corrected. (Plast. Reconstr. Surg. 127: 2021, 2011.) C1 [Yaremchuk, Michael J.; Doumit, Gabe; Thomas, Matthew A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM myaremchuk@partners.org NR 19 TC 11 Z9 11 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2011 VL 127 IS 5 BP 2021 EP 2030 DI 10.1097/PRS.0b013e31820e9263 PG 10 WC Surgery SC Surgery GA 758FT UT WOS:000290148100034 PM 21532429 ER PT J AU Decanini-Mancera, A Lessell, S Lee, MS Subramanian, PS AF Decanini-Mancera, Alejandra Lessell, Simmons Lee, Michael S. Subramanian, Prem S. TI Syphilis and the Monk SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE aritifungal therapy; Aspergillus infection; corticosteroids; primary orbital Aspergillosis ID ORBITAL APEX SYNDROME; ASPERGILLUS-FUMIGATUS; OPTIC NEUROPATHY; SINUS ASPERGILLOSIS; INFECTION; NEURITIS; NERVE AB Primary orbital aspergillus infection may occur in immunocompetent individuals. It frequently represents a diagnostic challenge for clinicians due to nonspecific clinical presentations and neuroimaging signs. We present a 47-year-old otherwise healthy man with an isolated unilateral optic neuropathy secondary to primary orbital aspergillosis. He had a remote history of tuberculosis and positive syphilis serologies. After he worsened despite intravenous penicillin therapy, a biopsy showed chronic inflammation. Corticosteroids treatment was followed by further deterioration of his clinical condition. Finally, a repeat biopsy revealed the aspergillus infection. Despite antifungal therapy, the outcome was unfavorable. A high index of suspicion should result in aggressive diagnostic testing and prompt institution of antifungal therapy in patients with primary orbital aspergillosis. (Surv Ophthalmol 56:267-273, 2011. (C) 2011 Elsevier Inc. All rights reserved.) C1 [Decanini-Mancera, Alejandra; Lee, Michael S.] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. [Lessell, Simmons] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Subramanian, Prem S.] Wilmer Eye Inst, Baltimore, MD 21287 USA. RP Lee, MS (reprint author), Univ Minnesota, Dept Ophthalmol, MMC 493,420 Delaware St SE, Minneapolis, MN 55455 USA. OI Subramanian, Prem/0000-0001-5824-8322 FU Research to Prevent Blindness, New York, NY; Lions Club of Minnesota FX The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. Publication of this article was supported by unrestricted grants from Research to Prevent Blindness, New York, NY, and the Lions Club of Minnesota. NR 23 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAY-JUN PY 2011 VL 56 IS 3 BP 267 EP 273 DI 10.1016/j.survophthal.2010.08.004 PG 7 WC Ophthalmology SC Ophthalmology GA 758SU UT WOS:000290187600006 PM 21056446 ER PT J AU Ackerly, DC Sangvai, DG Udayakumar, K Shah, BR Kalman, NS Cho, AH Schulman, KA Fulkerson, WJ Dzau, VJ AF Ackerly, D. Clay Sangvai, Devdutta G. Udayakumar, Krishna Shah, Bimal R. Kalman, Noah S. Cho, Alex H. Schulman, Kevin A. Fulkerson, William J., Jr. Dzau, Victor J. TI Training the Next Generation of Physician-Executives: An Innovative Residency Pathway in Management and Leadership SO ACADEMIC MEDICINE LA English DT Article ID DUAL-DEGREE; MD-MBA; BUSINESS; MEDICINE AB The rapidly changing field of medicine demands that future physician-leaders excel not only in clinical medicine but also in the management of complex health care enterprises. However, many physicians have become leaders "by accident," and the active cultivation of future leaders is required. Addressing this need will require multiple approaches, targeting trainees at various stages of their careers, such as degree-granting programs, residency and fellowship training, and career and leadership development programs. Here, the authors describe a first-of-its-kind graduate medical education pathway at Duke Medicine, the Management and Leadership Pathway for Residents (MLPR). This program was developed for residents with both a medical degree and management training. Created in 2009, with its first cohort enrolled in the summer of 2010, the MLPR is intended to help catalyze the emergence of a new generation of physician-leaders. The program will provide physiciansin-training with rigorous clinical exposure along with mentorship and rotational opportunities in management to accelerate the development of critical leadership and management skills in all facets of medicine, including care delivery, research, and education. To achieve this, the MLPR includes 15 to 18 months of project-based rotations under the guidance of senior leaders in many disciplines including finance, patient safety, health system operations, strategy, and others. Developing both clinical and management skill sets during graduate medical education holds the promise of engaging future leaders of health care at an early career stage, keeping more MD-MBA graduates within health care, and creating a bench of talented future physician-executives. C1 [Dzau, Victor J.] Duke Univ, Off Chancellor, Durham, NC 27710 USA. [Fulkerson, William J., Jr.; Dzau, Victor J.] Duke Univ Hlth Syst, Durham, NC USA. [Ackerly, D. Clay; Schulman, Kevin A.] Duke Univ, Duke Clin Res Inst, Durham, NC 27710 USA. [Udayakumar, Krishna] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. [Ackerly, D. Clay] Harvard Univ, Sch Med, Boston, MA USA. [Ackerly, D. Clay] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dzau, VJ (reprint author), Duke Univ, Off Chancellor, Box 3701 Med Ctr, Durham, NC 27710 USA. EM victor.dzau@duke.edu FU Duke's Graduate Medical Education Endowment Innovation Fund FX The MLPR relies on a shared investment model, reflecting the broad support for the program across the institution. Funding support is provided by Duke's Graduate Medical Education Endowment Innovation Fund, participating clinical departments, the administrative units through which trainees will rotate, and the office of the chancellor for health affairs. Trainees will receive their regular salary stipend during their enrollment in the MLPR. The program will seek to obtain additional funding to enable future expansion and sustainability from multiple other sources such as grants, private-public partnerships, and philanthropy. NR 12 TC 30 Z9 31 U1 0 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAY PY 2011 VL 86 IS 5 BP 575 EP 579 DI 10.1097/ACM.0b013e318212e51b PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 755WU UT WOS:000289971300016 PM 21436663 ER PT J AU Herrle, SR Corbett, EC Fagan, MJ Moore, CG Elnicki, DM AF Herrle, Scott R. Corbett, Eugene C., Jr. Fagan, Mark J. Moore, Charity G. Elnicki, D. Michael TI Bayes' Theorem and the Physical Examination: Probability Assessment and Diagnostic Decision Making SO ACADEMIC MEDICINE LA English DT Article ID CLINICAL EXAMINATION; INTERNAL-MEDICINE; AUSCULTATORY SKILLS; FAMILY-PRACTICE; PATIENT; CARE; HEURISTICS; JUDGMENT; HISTORY; ERRORS AB Purpose To determine how examination findings influence the probability assessment and diagnostic decision making of third-and fourth-year medical students, internal medicine residents, and academic general internists. Method In a 2008 cross-sectional, Web-based survey, participants from three medical schools were asked questions about their training and eight examination scenarios representing four conditions. Participants were given literature-derived preexamination probabilities for each condition and were asked to (1) estimate postexamination probabilities (post-EPs) and (2) select a diagnostic choice (report that condition is present, order more tests, or report that condition is absent). Participants' inverse transformed logit (ITL) mean post-EPs were compared with corresponding literature-derived post-EPs. Results Of 906 individuals invited to participate, 684 (75%) submitted a completed survey. In two of four scenarios with positive findings, the participants' ITL mean post-EPs were significantly less than corresponding literature-derived post-EP point estimates (P < .001 for each). In three of four scenarios with negative findings, ITL mean post-EPs were significantly greater than corresponding literature-derived post-EP point estimates (P < .001 for each). In the four scenarios with positive findings, 17% to 38% of participants ordered more diagnostic tests when the literature indicated a > 85% probability that the condition was present. In the four scenarios with largely negative findings, 70% to 85% chose to order diagnostic tests to further reduce diagnostic uncertainty. Conclusions All three groups tended to similarly underestimate the impact of examination findings on condition probability assessment, especially negative findings, and often ordered more tests when probabilities indicated that additional testing was unnecessary. C1 [Herrle, Scott R.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Gen Internal Med, Dept Med,Sect Gen Internal Med, Pittsburgh, PA 15240 USA. [Corbett, Eugene C., Jr.] Univ Virginia, Dept Med, Div Gen Med Geriatr & Palliat Care, Charlottesville, VA USA. [Fagan, Mark J.] Brown Univ, Dept Med, Alpert Med Sch, Providence, RI 02912 USA. [Moore, Charity G.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Ctr Res Hlth Care Data Ctr, Pittsburgh, PA 15240 USA. RP Herrle, SR (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Gen Internal Med, Dept Med,Sect Gen Internal Med, 130-U,Univ Dr C, Pittsburgh, PA 15240 USA. EM herrles@pitt.edu RI liu, jing/D-9482-2012; OI Moore, Charity/0000-0002-0060-0124 FU National Center for Research Resources (NCRR), National Institutes of Health (NIH) [UL1 RR024153]; NIH Roadmap for Medical Research FX This study was made possible by Grant Number UL1 RR024153 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Additional funding for this study was provided by the Shadyside Hospital Foundation. The Shadyside Hospital Foundation had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 41 TC 10 Z9 10 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAY PY 2011 VL 86 IS 5 BP 618 EP 627 DI 10.1097/ACM.0b013e318212eb00 PG 10 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 755WU UT WOS:000289971300025 PM 21436660 ER PT J AU Geithner, CA Scharpf, JA Delistraty, J AF Geithner, Christina A. Scharpf, Jean Ann Delistraty, Jema TI EXPERIENTIAL LEARNING AND COMMUNITY SERVICE ENHANCE PROFESSIONAL DEVELOPMENT A 2-and 4-Year Approach SO ACSMS HEALTH & FITNESS JOURNAL LA English DT Article DE Academic training programs; Exercise testing and prescription; Experiential learning; Client-based projects; Community service ID REVEALS FITNESS TRENDS; WORLDWIDE SURVEY C1 [Geithner, Christina A.] Gonzaga Univ, Dept Human Physiol, Spokane, WA 99258 USA. [Scharpf, Jean Ann] Suffolk CCC, Dept Phys Educ, New York, NY USA. [Scharpf, Jean Ann] Fitness Specialist Program, San Diego, CA USA. [Delistraty, Jema] Deaconess Med Ctr, Prevent Cardiol Dept, Boston, MA USA. RP Geithner, CA (reprint author), Gonzaga Univ, Dept Human Physiol, Spokane, WA 99258 USA. NR 11 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1091-5397 J9 ACSMS HEALTH FIT J JI ACSMS Health Fit. J. PD MAY-JUN PY 2011 VL 15 IS 3 BP 19 EP 28 DI 10.1249/FIT.0b013e3182160f67 PG 10 WC Sport Sciences SC Sport Sciences GA 755WR UT WOS:000289970900005 ER PT J AU Rodriguez, FJ Scheithauer, BW George, D Midha, R MacCollin, M Stemmer-Rachamimov, AO AF Rodriguez, Fausto J. Scheithauer, Bernd W. George, David Midha, Rajiv MacCollin, Mia Stemmer-Rachamimov, Anat O. TI Superficial neurofibromas in the setting of schwannomatosis: nosologic implications SO ACTA NEUROPATHOLOGICA LA English DT Article DE Schwannoma; Neurofibroma; Schwannomatosis; Neurofibromatosis; Peripheral nerve ID FAMILIAL SCHWANNOMATOSIS; DIAGNOSTIC-CRITERIA; NF2 LOCUS; TYPE-2; SMARCB1; TUMOR AB First described in the past decade, schwannomatosis is a syndrome distinct from neurofibromatosis 2 (NF2). It is characterized by the development of multiple schwannomas, sparing the vestibular division of cranial nerve VIII, and may also predispose to develop meningiomas. We report two female patients, a 27 and a 44 years old who developed multiple peripheral schwannomas, but without involvement of the vestibular nerves, satisfying clinical criteria for schwannomatosis. Lack of vestibular nerve involvement was confirmed with MRI using an internal auditory canal protocol with 3 mm thick slices in both patients after age 30. Both patients developed a small neurofibroma in axillary subcutaneous tissues and a diffuse cutaneous neurofibroma of the left buttock, respectively. This report highlights that superficial neurofibromas may arise in the setting of schwannomatosis, which may have implications for the diagnostic criteria of this unique syndrome. In particular, the presence of a cutaneous neurofibroma in a patient with multiple schwannomas should not lead to a diagnosis of NF2. C1 [Rodriguez, Fausto J.] Johns Hopkins Univ, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA. [Rodriguez, Fausto J.; Scheithauer, Bernd W.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [George, David] Foothills Prov Gen Hosp, Dept Pathol & Neurosurg, Calgary, AB T2N 2T9, Canada. [Midha, Rajiv] Univ Calgary, Fac Med, Dept Clin Neurosci, Calgary, AB, Canada. [MacCollin, Mia] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rodriguez, FJ (reprint author), Johns Hopkins Univ, Dept Pathol, Div Neuropathol, 720 Rutland Ave,Ross Bldg 512B, Baltimore, MD 21205 USA. EM frodrig4@jhmi.edu FU NCI NIH HHS [P30 CA006973] NR 16 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAY PY 2011 VL 121 IS 5 BP 663 EP 668 DI 10.1007/s00401-010-0793-8 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 756RS UT WOS:000290033000010 PM 21191601 ER PT J AU Pisculli, ML Reichmann, WM Losina, E Donnell-Fink, LA Arbelaez, C Katz, JN Walensky, RP AF Pisculli, Mary L. Reichmann, William M. Losina, Elena Donnell-Fink, Laurel A. Arbelaez, Christian Katz, Jeffrey N. Walensky, Rochelle P. TI Factors Associated with Refusal of Rapid HIV Testing in an Emergency Department SO AIDS AND BEHAVIOR LA English DT Article DE Rapid HIV testing; HIV test refusal; HIV test acceptance; Routine HIV testing; Emergency department; Human immunodeficiency virus ID TRANSMITTED DISEASE CLINICS; UNITED-STATES; MISSED OPPORTUNITIES; ETHNIC DISPARITIES; INFECTION; ROUTINE; RISK; PERSPECTIVE; PERCEPTIONS; ACCEPTANCE AB HIV screening studies in the emergency department (ED) have demonstrated rates of HIV test refusal ranging from 40-67%. This study aimed to determine the factors associated with refusal to undergo routine rapid HIV testing in an academic ED in Boston. HIV counselors offered routine testing to 1,959 patients; almost one-third of patients (29%) refused. Data from a self-administered survey were used to determine independent correlates of HIV testing refusal. In multivariate analysis, women and patients with annual household incomes of $50,000 or more were more likely to refuse testing, as were those who reported not engaging in HIV risk behaviors, those previously HIV tested and those who did not perceive a need for testing. Enrollment during morning hours was also associated with an increased risk of refusal. Increased educational efforts to convey the rationale and benefits of universal screening may improve testing uptake among these groups. C1 [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Pisculli, Mary L.; Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Reichmann, William M.; Losina, Elena; Donnell-Fink, Laurel A.; Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Reichmann, William M.; Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Arbelaez, Christian] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [T32 AI007433]; NIMH NIH HHS [R01 MH065869, R01 MH073445, R01 MH65869] NR 38 TC 18 Z9 18 U1 2 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD MAY PY 2011 VL 15 IS 4 BP 734 EP 742 DI 10.1007/s10461-010-9837-2 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 754YS UT WOS:000289894400007 PM 20978834 ER PT J AU Wanyenze, RK Hahn, JA Liechty, CA Ragland, K Ronald, A Mayanja-Kizza, H Coates, T Kamya, MR Bangsberg, DR AF Wanyenze, Rhoda K. Hahn, Judith A. Liechty, Cheryl A. Ragland, Kathie Ronald, Allan Mayanja-Kizza, Harriet Coates, Thomas Kamya, Moses R. Bangsberg, David R. TI Linkage to HIV Care and Survival Following Inpatient HIV Counseling and Testing SO AIDS AND BEHAVIOR LA English DT Article DE Provider Initiated HIV Testing and Counseling (PITC); Inpatient; Access to care; Survival; Africa ID ANTIRETROVIRAL THERAPY; INCOME COUNTRIES; UGANDA; PROGRAMS; COUPLES; SEROCONVERSION; POPULATION; PREVALENCE; SEROSTATUS; EXPERIENCE AB Linkage to HIV care and survival in sub-Saharan Africa is not well documented. In 2004 we conducted a randomized trial among medical inpatients in Mulago Hospital to assess the impact of HIV counseling and testing (HCT) on linkage to care and survival. Participants were randomized to inpatient HCT (intervention) or outpatient HCT 1 week post-discharge (control); inpatient HCT was not available at Mulago during the study. Among 590 eligible patients, 85% (500) agreed to participate; 98.8% (248) in the intervention arm received HCT compared to 68.7% (171) in the control arm. Within 6 months, 62.2% (92) of surviving HIV-infected participants received HIV care; 15.0% (20) received antiretroviral medications (ARVs). Overall mortality among HIV-infected participants was 34.6% (72). HCT had significant impact on linkage to care among surviving participants. Referral for HCT was a missed opportunity for diagnosis. There is need for earlier diagnosis and linkage to HIV care among inpatients. C1 [Wanyenze, Rhoda K.] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Hahn, Judith A.; Ragland, Kathie] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Liechty, Cheryl A.] Glen Cove Internal Med, Rockport, ME USA. [Ronald, Allan] Infect Dis Inst, Kampala, Uganda. [Mayanja-Kizza, Harriet; Kamya, Moses R.] Makerere Univ, Sch Med, Kampala, Uganda. [Coates, Thomas] Univ Calif Los Angeles, Los Angeles, CA USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth, Boston, MA USA. RP Wanyenze, RK (reprint author), Makerere Univ, Sch Publ Hlth, POB 7072, Kampala, Uganda. EM rwanyenze@hotmail.com OI Mayanja-Kizza, Harriet/0000-0002-9297-6208; Ronald, Allan/0000-0002-5746-3490 FU NIMH NIH HHS [K24-MH087227, R01 MH077512, R01 MH077512-01A1, R01 MH077512-02, R01 MH077512-03, K24 MH087227, R01 MH077512-04, R01 MH077512-05, R01 MH054907] NR 28 TC 27 Z9 28 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD MAY PY 2011 VL 15 IS 4 BP 751 EP 760 DI 10.1007/s10461-010-9704-1 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 754YS UT WOS:000289894400009 PM 20431933 ER PT J AU Korthuis, PT Saha, S Chander, G McCarty, D Moore, RD Cohn, JA Sharp, VL Beach, MC AF Korthuis, P. Todd Saha, Somnath Chander, Geetanjali McCarty, Dennis Moore, Richard D. Cohn, Jonathan A. Sharp, Victoria L. Beach, Mary Catherine TI Substance Use and the Quality of Patient-Provider Communication in HIV Clinics SO AIDS AND BEHAVIOR LA English DT Article DE Alcoholism; Substance-related disorders; Communication; HIV; Quality of health care; Patient satisfaction ID ADDICTION SEVERITY INDEX; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; ABUSE TREATMENT; UNITED-STATES; DRUG-USERS; SERVICES UTILIZATION; MEDICAL INTERACTIONS; RELAPSE PREVENTION; INFECTED ADULTS AB The objective of this study was to estimate the influence of substance use on the quality of patient-provider communication during HIV clinic encounters. Patients were surveyed about unhealthy alcohol and illicit drug use and rated provider communication quality. Audio-recorded encounters were coded for specific communication behaviors. Patients with vs. without unhealthy alcohol use rated the quality of their provider's communication lower; illicit drug user ratings were comparable to non-users. Visit length was shorter, with fewer activating/engaging and psychosocial counseling statements for those with vs. without unhealthy alcohol use. Providers and patients exhibited favorable communication behaviors in encounters with illicit drug users vs. non-users, demonstrating greater evidence of patient-provider engagement. The quality of patient-provider communication was worse for HIV-infected patients with unhealthy alcohol use but similar or better for illicit drug users compared with non-users. Interventions should be developed that encourage providers to actively engage patients with unhealthy alcohol use. C1 [Korthuis, P. Todd; Saha, Somnath] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97239 USA. [Korthuis, P. Todd; Saha, Somnath; McCarty, Dennis] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR USA. [Chander, Geetanjali; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. [Cohn, Jonathan A.] Wayne State Univ, Sch Med, Dept Med, Div Infect Dis, Detroit, MI 48201 USA. [Sharp, Victoria L.] Columbia Univ, St Lukes Roosevelt Hosp Ctr, Ctr Comprehens Care, New York, NY USA. RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA. EM korthuis@ohsu.edu FU AHRQ HHS [K08 HS013903-05, K08 HS013903]; NIAAA NIH HHS [K23 AA015313, K23AA015313, R01 AA016893, R01 AA016893-01A2, R01 AA16893]; NIAID NIH HHS [U01 AI069918, U01 AI069918-05]; NIDA NIH HHS [K23 DA019809, K23DA019809, K24 DA000432, K24 DA000432-10, R01 DA011602, R01 DA011602-13, R01 DA11602]; NIMH NIH HHS [R34 MH089279, R34 MH089279-01A1, R34 MH089279-02]; PHS HHS [AHRQ 290-01-0012] NR 51 TC 16 Z9 17 U1 3 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD MAY PY 2011 VL 15 IS 4 BP 832 EP 841 DI 10.1007/s10461-010-9779-8 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 754YS UT WOS:000289894400017 PM 20703792 ER PT J AU Oslin, D AF Oslin, David TI Personalized Addiction Treatment: How Close Are We? SO ALCOHOL AND ALCOHOLISM LA English DT Editorial Material ID OPIOID RECEPTOR GENE; NALTREXONE RESPONSE; ALCOHOL DEPENDENCE; OPRM1; CUES C1 [Oslin, David] Univ Penn, Philadelphia, PA 19104 USA. [Oslin, David] Philadelphia VA Med Ctr, Treatment Res Ctr, Philadelphia, PA 19104 USA. RP Oslin, D (reprint author), Univ Penn, 3600 Chestnut St, Philadelphia, PA 19104 USA. EM oslin@upenn.edu NR 10 TC 3 Z9 4 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD MAY-JUN PY 2011 VL 46 IS 3 BP 231 EP 232 DI 10.1093/alcalc/agr030 PG 2 WC Substance Abuse SC Substance Abuse GA 754ET UT WOS:000289837300003 PM 21508195 ER PT J AU Pandol, SJ Lugea, A Mareninova, OA Smoot, D Gorelick, FS Gukovskaya, AS Gukovsky, I AF Pandol, Stephen J. Lugea, Aurelia Mareninova, Olga A. Smoot, Duane Gorelick, Fred S. Gukovskaya, Anna S. Gukovsky, Ilya TI Investigating the Pathobiology of Alcoholic Pancreatitis SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcoholic Pancreatitis; Inflammation; Autophagy; Mitochondrial Permeabilization; Endoplasmic Reticulum Stress; Pancreatic Stellate Cell ID CERULEIN-INDUCED PANCREATITIS; ENDOPLASMIC-RETICULUM STRESS; PERMEABILITY TRANSITION PORE; KEY PATHOLOGICAL RESPONSES; UNFOLDED PROTEIN RESPONSE; KAPPA-B ACTIVATION; STELLATE CELLS; ACINAR-CELLS; ZYMOGEN ACTIVATION; BASOLATERAL EXOCYTOSIS AB Alcohol abuse is one of the most common causes of pancreatitis. The risk of developing alcohol-induced pancreatitis is related to the amount and duration of drinking. However, only a small portion of heavy drinkers develop disease, indicating that other factors (genetic, environmental, or dietary) contribute to disease initiation. Epidemiologic studies suggest roles for cigarette smoking and dietary factors in the development of alcoholic pancreatitis. The mechanisms underlying alcoholic pancreatitis are starting to be understood. Studies from animal models reveal that alcohol sensitizes the pancreas to key pathobiologic processes that are involved in pancreatitis. Current studies are focussed on the mechanisms responsible for the sensitizing effect of alcohol; recent findings reveal disordering of key cellular organelles including endoplasmic reticulum, mitochondria, and lysosomes. As our understanding of alcohol's effects continue to advance to the level of molecular mechanisms, insights into potential therapeutic strategies will emerge providing opportunities for clinical benefit. C1 [Pandol, Stephen J.; Lugea, Aurelia; Mareninova, Olga A.; Gukovskaya, Anna S.; Gukovsky, Ilya] Univ Calif Los Angeles, Pancreat Res Grp, Dept Vet Affairs Greater Los Angeles, Los Angeles, CA USA. So Calif Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. [Smoot, Duane] Howard Univ, Washington, DC 20059 USA. [Gorelick, Fred S.] Yale Univ, New Haven, CT USA. RP Pandol, SJ (reprint author), UCLA VA Greater Los Angeles, Pancreat Res Grp, W Los Angeles VA Healthcare Ctr, 11301 Wilshire Blvd,Blg 258,Rm 340, Los Angeles, CA 90073 USA. EM stephen.pandol@va.gov; igukovsk@ucla.edu FU AGA Foundation FX Southern California Research Center for Alcoholic Liver and Pancreatic Diseases (P50AA11999); UCLA Center for Excellence in Pancreatic Diseases (P01AT003960); NIH/NIAAA (U56 AA0114643, R21AA016010, R21AA015781, R21AA017276); NIH/NCI (R01CA119025); NIH/NIDDK (R01DK059936, R01DK54021); and the AGA Foundation Designated Research Scholar Award in Pancreatitis. NR 88 TC 20 Z9 21 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2011 VL 35 IS 5 BP 830 EP 837 DI 10.1111/j.1530-0277.2010.01408.x PG 8 WC Substance Abuse SC Substance Abuse GA 754ZK UT WOS:000289896200013 PM 21284675 ER PT J AU Arnedt, JT Rohsenow, DJ Almeida, AB Hunt, SK Gokhale, M Gottlieb, DJ Howland, J AF Arnedt, J. Todd Rohsenow, Damaris J. Almeida, Alissa B. Hunt, Sarah K. Gokhale, Manjusha Gottlieb, Daniel J. Howland, Jonathan TI Sleep Following Alcohol Intoxication in Healthy, Young Adults: Effects of Sex and Family History of Alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol; Sleep; Polysomnography; Sex; Family History ID GENDER-DIFFERENCES; MENSTRUAL-CYCLE; PERFORMANCE; DRINKING; ETHANOL; EEG; HANGOVER; ELECTROENCEPHALOGRAM; DEPENDENCE; LEVEL AB Background: This study evaluated sex and family history of alcoholism as moderators of subjective ratings of sleepiness/sleep quality and polysomnography (PSG) following alcohol intoxication in healthy, young adults. Methods: Ninety-three healthy adults [mean age 24.4 +/- 2.7 years, 59 women, 29 subjects with a positive family history of alcoholism (FH+)] were recruited. After screening PSG, participants consumed alcohol (sex/weight adjusted dosing) to intoxication [peak breath alcohol concentration (BrAC) of 0.11 +/- 0.01 g% for men and women] or matching placebo between 20:30 and 22:00 hours. Sleep was monitored using PSG between 23:00 and 07:00 hours. Participants completed the Stanford Sleepiness Scale and Karolinska Sleepiness Scale at bedtime and on awakening and a validated post-sleep questionnaire. Results: Following alcohol, total sleep time, sleep efficiency, nighttime awakenings, and wake after sleep onset were more disrupted in women than men, with no differences by family history status. Alcohol reduced sleep onset latency, sleep efficiency, and rapid eye movement sleep while increasing wakefulness and slow wave sleep across the entire night compared with placebo. Alcohol also generally increased sleep consolidation in the first half of the night, but decreased it during the second half. Sleepiness ratings were higher following alcohol, particularly in women at bedtime. Morning sleep quality ratings were lower following alcohol than placebo. Conclusions: Alcohol intoxication increases subjective sleepiness and disrupts sleep objectively more in healthy women than in men, with no differences evident by family history of alcoholism status. Evaluating moderators of alcohol effects on sleep may provide insight into the role of sleep in problem drinking. C1 [Arnedt, J. Todd] Univ Michigan, Dept Psychiat, Sleep & Chronophysiol Lab, Ann Arbor, MI 48109 USA. [Rohsenow, Damaris J.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Almeida, Alissa B.; Hunt, Sarah K.] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA. [Howland, Jonathan] Boston Univ, Dept Emergency Med, Boston, MA 02215 USA. [Gokhale, Manjusha] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02215 USA. [Gottlieb, Daniel J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Gottlieb, Daniel J.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA. RP Arnedt, JT (reprint author), Univ Michigan, Dept Psychiat, Sleep & Chronophysiol Lab, 4250 Plymouth Rd, Ann Arbor, MI 48109 USA. EM tarnedt@med.umich.edu OI Howland, Jonathan/0000-0001-8079-1188 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01 AA12087]; National Center for Research Resources, General Clinical Research Center [M01 RR00533] FX This research was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Grant #R01 AA12087 to the Boston University School of Public Health and the National Center for Research Resources, General Clinical Research Center grant M01 RR00533. NR 47 TC 13 Z9 13 U1 2 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2011 VL 35 IS 5 BP 870 EP 878 DI 10.1111/j.1530-0277.2010.01417.x PG 9 WC Substance Abuse SC Substance Abuse GA 754ZK UT WOS:000289896200022 PM 21323679 ER PT J AU Reinke, LF Griffith, RG Wolpin, S Donesky-Cuenco, D Carrieri-Kohlman, V Nguyen, HQ AF Reinke, Lynn F. Griffith, Randall G. Wolpin, Seth Donesky-Cuenco, DorAnne Carrieri-Kohlman, Virginia Nguyen, Huong Q. TI Feasibility of a Webinar for Coaching Patients With Chronic Obstructive Pulmonary Disease on End-of-Life Communication SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE webinar; end-of-life communication; chronic obstructive pulmonary disease; patient education; advanced care planning; technology ID ADVANCE DIRECTIVE EDUCATION; CARE; REHABILITATION; BARRIERS; OUTCOMES; SUPPORT; CANCER; COPD AB Rationale: Previous research has shown that patients with chronic obstructive pulmonary disease (COPD) desire conversations about end-of-life wishes. However, most clinicians do not initiate these discussions. We explored whether educating patients via Web conferencing (webinar) would equip them with knowledge and skills to engage in conversations about end-of-life care. Results: Prewebinar, 6 of the 7 patients had completed advanced care planning forms but only half had shared these with their clinicians. Most patients felt confident about discussing end-of-life preferences. At 3 months, all participants had taken further action on end-of-life planning. Five felt the webinar was an acceptable option if unable to participate in person. All patients voiced that adding a video stream would have promoted interaction in the context of these sensitive conversations. Conclusions: This pilot project demonstrated that a webinar to educate patients on end-of-life communication was acceptable for the majority of patients. Improvements in audio and video bandwidth may facilitate more interaction among virtual participants. This may be particularly useful for patient education on sensitive topics. C1 [Reinke, Lynn F.] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA 98101 USA. [Donesky-Cuenco, DorAnne; Carrieri-Kohlman, Virginia] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Reinke, LF (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Vet Affairs, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM reinkl@u.washington.edu FU [R01 NR008938]; [1KL2RR025015-01]; [TPP-61-021] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article:; R01 NR008938 (Carrieri-Kohlman); 1KL2RR025015-01 (Nguyen); TPP-61-021 (Reinke). NR 18 TC 7 Z9 7 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD MAY PY 2011 VL 28 IS 3 BP 147 EP 152 DI 10.1177/1049909110376807 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 756FQ UT WOS:000289997500002 PM 20834035 ER PT J AU Huang, ES Strate, LL Ho, WW Lee, SS Chan, AT AF Huang, Edward S. Strate, Lisa L. Ho, Wendy W. Lee, Salina S. Chan, Andrew T. TI Long-Term Use of Aspirin and the Risk of Gastrointestinal Bleeding SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Aspirin; Dose; Duration; Gastrointestinal bleeding; Long-term ID LOW-DOSE ASPIRIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIALS; PRIMARY PREVENTION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; AMERICAN-COLLEGE; UNSTABLE ANGINA AB BACKGROUND: In short-term trials, aspirin is associated with gastrointestinal bleeding. However, the effect of dose and duration of aspirin use on risk remains unclear. METHODS: We conducted a prospective study of 87,680 women enrolled in the Nurses' Health Study in 1990 who provided biennial data on aspirin use. We examined the relative risk (RR) of major gastrointestinal bleeding requiring hospitalization or blood transfusion. RESULTS: During a 24-year follow-up, 1537 women reported a major gastrointestinal bleeding. Among women who used aspirin regularly (>= 2 standard [325 mg] tablets/week), the multivariate RR of gastrointestinal bleeding was 1.43 (95% confidence interval [CI], 1.29-1.59) when compared with nonregular users. Compared with women who denied any aspirin use, the multivariate RRs of gastrointestinal bleeding were 1.03 (95% CI, 0.85-1.24) for women who used 0.5 to 1.5 standard aspirin tablets/week, 1.30 (95% CI, 1.07-1.58) for women who used 2 to 5 tablets/week, 1.77 (95% CI, 1.44-2.18) for women who used 6 to 14 tablets/week, and 2.24 (95% CI, 1.66-3.03) for women who used more than 14 tablets/week (P(trend)<.001). Similar dose-response relationships were observed among short-term users (<= 5 years; P(trend)<.001) and long-term users (>5 years; P(trend)<.001). In contrast, after adjustments were made for dose, increasing duration of use did not confer a greater risk of bleeding (P(trend) = .28). CONCLUSION: Regular aspirin use is associated with gastrointestinal bleeding. Risk seems more strongly related to dose than duration of aspirin use. Efforts to minimize adverse effects of aspirin therapy should emphasize using the lowest effective dose among both short-and long-term users. (C) 2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, 426-433 C1 [Huang, Edward S.; Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Huang, Edward S.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Strate, Lisa L.] Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA USA. [Ho, Wendy W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Dept Med, Los Angeles, CA 90095 USA. [Lee, Salina S.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM achan@partners.org FU National Cancer Institute, National Institutes of Health [CA 87969, CA 55075, CA 107412, CA 137178]; American Gastroenterological Association; American Gastroenterological Association/Foundation for Digestive Health and Nutrition FX Supported by grants (CA 87969, CA 55075, CA 107412, CA 137178) from the National Cancer Institute, National Institutes of Health. Dr. Chan was a recipient of the American Gastroenterological Association/Foundation for Digestive Health and Nutrition Pilot Research Award for this work. Dr. Chan is a Damon Runyon Clinical Investigator. Dr. Huang is supported by American Gastroenterological Association Fellow to Faculty Transition Award. No pharmaceutical industry funds were received for preparation of this manuscript. The National Cancer Institute, the National Institutes of Health, the American Gastroenterological Association, the Foundation for Digestive Health and Nutrition, and the Damon Runyon Cancer Research Foundation had no role in the collection, management, analysis, or interpretation of the data, and had no role in the preparation, review, or approval of the manuscript. NR 45 TC 53 Z9 59 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2011 VL 124 IS 5 BP 426 EP 433 DI 10.1016/j.amjmed.2010.12.022 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 756NB UT WOS:000290017900014 PM 21531232 ER PT J AU Moss, M Au, DH AF Moss, Marc Au, David H. TI ATS International Conference Preview Where Today's Science Will Meet Tomorrow's Care SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 [Moss, Marc] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, ATS Int Conf Comm 2010 2011, Aurora, CO USA. [Au, David H.] Univ Washington, VA Puget Sound Hlth Care Syst, ATS Int Conf Comm 2010 2011, Seattle, WA USA. RP Moss, M (reprint author), Univ Colorado Denver, Div Pulm Sci & Crit Care Med, ATS Int Conf Comm 2010 2011, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2011 VL 183 IS 9 BP 1117 EP 1118 DI 10.1164/rccm.201103-0386ED PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 756IO UT WOS:000290005100001 PM 21531948 ER PT J AU Bellani, G Guerra, L Musch, G Zanella, A Patroniti, N Mauri, T Messa, C Pesenti, A AF Bellani, Giacomo Guerra, Luca Musch, Guido Zanella, Alberto Patroniti, Nicolo Mauri, Tommaso Messa, Cristina Pesenti, Antonio TI Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; respiration; artificial; tomography; X-ray computed; positron emission tomography ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; POSITRON-EMISSION-TOMOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; MECHANICAL VENTILATION; PULMONARY INFLAMMATION; BURST ACTIVITY; RECRUITMENT; ACTIVATION; STRATEGY AB Rationale: During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment-derecruitment. As an estimate of the intensity of inflammation, metabolic activity can be measured by positron emission tomography imaging of [(18)F]fluoro-2-deoxy-D-glucose. Objectives: To assess the relationship between gas volume changes induced by tidal ventilation and pulmonary metabolic activity in patients with ALI. Methods: In 13 mechanically ventilated patients with ALI and relatively high positive end-expiratory pressure, we performed a positron emission tomography scan of the chest and three computed tomography scans: at mean airway pressure, end-expiration, and end-inspiration. Metabolic activity was measured from the [(18)F]fluoro-2-deoxy-D-glucose uptake rate. The computed tomography scans were used to classify lung regions as derecruited throughout the respiratory cycle, undergoing recruitment-derecruitment, and normally aerated. Measurements and Main Results: Metabolic activity of normally aerated lung was positively correlated both with plateau pressure, showing a pronounced increase above 26 to 27 cm H(2)O, and with regional V(T) normalized by end-expiratory lung gas volume. This relationship did not appear to be caused by a higher underlying parenchymal metabolic activity in patients with higher plateau pressure. Regions undergoing cyclic recruitment-derecruitment did not have higher metabolic activity than those collapsed throughout the respiratory cycle. Conclusions: In patients with ALI managed with relatively high end-expiratory pressure, metabolic activity of aerated regions was associated with both plateau pressure and regional VT normalized by end-expiratory lung gas volume, whereas no association was found between cyclic recruitment-derecruitment and increased metabolic activity. C1 [Bellani, Giacomo; Zanella, Alberto; Patroniti, Nicolo; Mauri, Tommaso; Pesenti, Antonio] Univ Milano Bicocca, Dept Expt Med, Monza, MI, Italy. [Bellani, Giacomo; Zanella, Alberto; Patroniti, Nicolo; Mauri, Tommaso; Pesenti, Antonio] San Gerardo Hosp, Dept Perioperat Med & Intens Care, Monza, MI, Italy. [Guerra, Luca; Messa, Cristina] San Gerardo Hosp, Nucl Med Unit, Monza, MI, Italy. [Guerra, Luca; Messa, Cristina] Univ Milano Bicocca, Ctr Bioimmagini Mol, I-20052 Monza, MB, Italy. [Musch, Guido] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Messa, Cristina] Natl Res Council CNR, Inst Mol Bioimaging & Physiol IBFM, Milan, Italy. RP Pesenti, A (reprint author), Univ Milano Bicocca, Dept Expt Med DIMS, Via Cadore 48, I-20052 Monza, MB, Italy. EM antonio.pesenti@unimib.it RI Bellani, Giacomo/D-2379-2010; Pesenti, Antonio/H-7483-2012; Patroniti, Nicolo/K-6347-2016; OI Bellani, Giacomo/0000-0002-3089-205X; Patroniti, Nicolo/0000-0003-3600-193X; zanella, Alberto/0000-0002-2967-2527 FU European Society of Intensive Care Medicine; National Institutes of Health [R01HL094639] FX Supported in part by a grant from the European Society of Intensive Care Medicine (ECCRN Young Investigator Award 2006), by departmental funding, and by National Institutes of Health grant R01HL094639 (G.M.). NR 50 TC 68 Z9 70 U1 0 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2011 VL 183 IS 9 BP 1193 EP 1199 DI 10.1164/rccm.201008-1318OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 756IO UT WOS:000290005100014 PM 21257791 ER PT J AU Kuna, ST Gurubhagavatula, I Maislin, G Hin, S Hartwig, KC McCloskey, S Hachadoorian, R Hurley, S Gupta, R Staley, B Atwood, CW AF Kuna, Samuel T. Gurubhagavatula, Indira Maislin, Greg Hin, Sakhena Hartwig, Kathryn C. McCloskey, Sue Hachadoorian, Robert Hurley, Sharon Gupta, Rajesh Staley, Bethany Atwood, Charles W. TI Noninferiority of Functional Outcome in Ambulatory Management of Obstructive Sleep Apnea SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE polysomnogram; portable monitor testing; obstructive sleep apnea; continuous positive airway pressure ID POSITIVE AIRWAY PRESSURE; PRACTICE PARAMETERS; POLYSOMNOGRAPHY; DISORDERS; DIAGNOSIS AB Rationale: Home portable monitor testing is increasingly being used to diagnose patients with obstructive sleep apnea (OSA) and to initiate them on continuous positive airway pressure (CPAP) treatment. Objectives: To compare functional outcome and treatment adherence in patients who receive ambulatory versus in-laboratory testing for OSA. Methods: Veterans with suspected OSA were randomized to either home testing or standard in-laboratory testing. Home testing consisted of a type 3 portable monitor recording followed by at least three nights using an automatically adjusting positive airway pressure apparatus. Participants diagnosed with OSA were treated with (PAP for 3 months. Measurements and Main Results: We measured the change in Functional Outcomes of Sleep Questionnaire score, with an a priori noninferiority delta of -1, and the mean daily hours of objectively measured CPAP adherence, with an a priori noninferiority delta of -0.75 hour/day. Of the 296 subjects enrolled, 260 (88%) were diagnosed with OSA, and 213 (75%) were initiated on CPAP. Mean +/- SD functional outcome score improved 1.74 +/- 2.81 in the home group (P < 0.001) and 1.85 +/- 2.46 in the in-laboratory group (P < 0.0001). The lower bound of the one-sided 95% noninferiority confidence interval was -0.54. Mean +/- SD hours of daily (PAP adherence were 3.5 +/- 2.5 hours/day in the home group and 2.9 +/- 2.3 hours/day in the in-laboratory group (P = 0.08). The lower bound of the one-sided 95% noninferiority confidence interval was 0.03. Conclusions: Functional outcome and treatment adherence in patients evaluated according to a home testing algorithm is not clinically inferior to that in patients receiving standard in-laboratory polysomnography. C1 [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, VISN Eastern Reg Sleep Ctr 111P 4, Dept Med, Philadelphia, PA 19104 USA. [Kuna, Samuel T.; Gurubhagavatula, Indira; Staley, Bethany] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Maislin, Greg; Hachadoorian, Robert; Hurley, Sharon] Biomed Stat Consulting, Wynnewood, PA USA. [Hartwig, Kathryn C.; Atwood, Charles W.] Vet Affairs Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. [Atwood, Charles W.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Kuna, ST (reprint author), Philadelphia Vet Affairs Med Ctr, VISN Eastern Reg Sleep Ctr 111P 4, Dept Med, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Samuel.Kuna@va.gov FU Veterans Health Administration, Health Services Research and Development [IIR-04-021-2]; Center for Health Equity Research and Promotion at the Philadelphia VA Medical Center; Philips; Embla, Inc.; Philips-Respironics; NIH; Resmed; Vapotherm; Boston Scientific FX Supported by Veterans Health Administration, Health Services Research and Development grant IIR-04-021-2; the Center for Health Equity Research and Promotion at the Philadelphia VA Medical Center; Philips; and Embla, Inc.; S.T.K. received grant support from Philips-Respironics. I.G. received loaned portable monitoring equipment for use in an NIH-funded clinical research study from Embla Corp. G.M., S.H., K.C.H., S.M., R.H., S.H., R.G., and B.S. do not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. C.W.A. was on the Board or Advisory Board for Cephalon and received lecture fees from Embla. He received grant support from Philips-Respironics, Resmed, Vapotherm, Boston Scientific, and the VA HSR&D. NR 23 TC 83 Z9 87 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2011 VL 183 IS 9 BP 1238 EP 1244 DI 10.1164/rccm.201011-1770OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 756IO UT WOS:000290005100020 PM 21471093 ER PT J AU Zhang, Y Ren, YP Jiao, JJ Li, D Zhang, Y AF Zhang, Yu Ren, Yiping Jiao, Jingjing Li, Dong Zhang, Ying TI Ultra High-Performance Liquid Chromatography-Tandem Mass Spectrometry for the Simultaneous Analysis of Asparagine, Sugars, and Acrylamide in Maillard Reactions SO ANALYTICAL CHEMISTRY LA English DT Article ID ATMOSPHERIC AEROSOLS; FOOD; GLUCOSE; MS/MS; GENOTOXICITY; ATTACHMENT; STRATEGIES; REDUCTION; KNOWLEDGE; PRODUCTS AB We developed an automated microwave digestion labstation (MDL) combined with ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method under the control of positive-negative ion switching as a robust kinetic study tool for rapid and simultaneous quantification of asparagine, glucose, fructose, and acrylamide in Maillard reaction products. Maillard reactions were conducted in a potato model via MDL. The two-step simple pretreatment procedures included the addition of isotope internal standards (15)N(2)-asparagine, (13)C(6)-glucose, and D(3)-acrylamide, followed by appropriate dilution with the mobile phase and filtration. Analytes were separated on a Hypercarb column and monitored by MS/MS. Study of matrix effects indicated Maillard reaction products induce an ionization suppression of both positive and negative precursor ions, but quantitative results are corrected through the use of isotopically labeled internal standards. Using this method, the limit of detection (LOD) and limit of quantification (LOQ) ranges of all analytes were calculated as 0.04-0.6 and 0.1-1.1 mu M, respectively. Excellent repeatability (RSD < 9.6%) and acceptable within-laboratory reproducibility (RSD < 9.2%) substantially supported the use of this method for sample analysis. The present kinetic tools, with 10-50 min mimic of Maillard reactions and short instrumental run time (5.5 min per sample), were successfully validated and applied to simultaneous determination of acrylamide and its pre-cursors and intermediates during Maillard reactions and kinetic elucidation. Furthermore, current tools of MDL combined with simple sample treatment procedures and UHPLC-MS/MS analysis reduce sample analysis time and labor in the kinetic study. C1 [Zhang, Yu; Jiao, Jingjing; Li, Dong; Zhang, Ying] Zhejiang Univ, Sch Biosyst Engn & Food Sci, Dept Food Sci & Nutr, Hangzhou 310058, Zhejiang, Peoples R China. [Ren, Yiping] Zhejiang Prov Ctr Dis Control & Prevent, Hangzhou 310051, Zhejiang, Peoples R China. [Zhang, Yu; Jiao, Jingjing] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Zhang, Yu; Jiao, Jingjing] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Zhang, Y (reprint author), Zhejiang Univ, Sch Biosyst Engn & Food Sci, Dept Food Sci & Nutr, Hangzhou 310058, Zhejiang, Peoples R China. EM y_zhang@zju.edu.cn; y_zhang@zju.edu.cn FU National Natural Science Foundation of China [30972486]; Eleventh Five-Year National Key Technology R&D Program of China [2009BADB9B07-2a] FX This study was financially supported by the National Natural Science Foundation of China (Grant No. 30972486) and the Eleventh Five-Year National Key Technology R&D Program of China (Grant No. 2009BADB9B07-2a). NR 25 TC 31 Z9 33 U1 7 U2 65 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAY 1 PY 2011 VL 83 IS 9 BP 3297 EP 3304 DI 10.1021/ac1029538 PG 8 WC Chemistry, Analytical SC Chemistry GA 755SN UT WOS:000289956800014 PM 21462916 ER PT J AU Alfille, PH AF Alfille, Paul H. TI Using Recruitment Maneuvers to Decrease Tidal Volumes during One-lung Ventilation SO ANESTHESIOLOGY LA English DT Editorial Material ID END-EXPIRATORY PRESSURE; INJURY C1 [Alfille, Paul H.] Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA. [Alfille, Paul H.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Management, Boston, MA 02114 USA. RP Alfille, PH (reprint author), Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA. EM palfille@partners.org NR 9 TC 1 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2011 VL 114 IS 5 BP 1009 EP 1010 DI 10.1097/ALN.0b013e318216469f PG 2 WC Anesthesiology SC Anesthesiology GA 755ZG UT WOS:000289980200001 PM 21521963 ER PT J AU Ng, JB Bittner, EA AF Ng, Joshua B. Bittner, Edward A. TI Tracheobronchomegaly A Rare Cause of Endotracheal Tube Cuff Leak SO ANESTHESIOLOGY LA English DT Editorial Material ID MOUNIER-KUHN-SYNDROME C1 [Ng, Joshua B.; Bittner, Edward A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Ng, JB (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM jbng@partners.org NR 3 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2011 VL 114 IS 5 BP 1211 EP 1211 DI 10.1097/ALN.0b013e318206ff9a PG 1 WC Anesthesiology SC Anesthesiology GA 755ZG UT WOS:000289980200026 PM 21270631 ER PT J AU Posner, MR Lorch, JH Goloubeva, O Tan, M Schumaker, LM Sarlis, NJ Haddad, RI Cullen, KJ AF Posner, M. R. Lorch, J. H. Goloubeva, O. Tan, M. Schumaker, L. M. Sarlis, N. J. Haddad, R. I. Cullen, K. J. TI Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial SO ANNALS OF ONCOLOGY LA English DT Article DE chemoradiotherapy; chemotherapy; head and neck cancer; human papillomavirus; oropharynx cancer; randomized trials ID SQUAMOUS-CELL CARCINOMA; RANDOMIZED-TRIAL; NECK-CANCER; RADIATION-THERAPY; ORGAN PRESERVATION; TONSILLAR CANCER; HEAD; CHEMOTHERAPY; RADIOTHERAPY; LARYNX AB Background: The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. Methods: Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. Results: Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local-regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV- patients (P < 0.0001). Conclusions: HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment. C1 [Posner, M. R.] Mt Sinai Sch Med, Tisch Canc Inst, Head & Neck Oncol Ctr, New York, NY 10029 USA. [Lorch, J. H.; Haddad, R. I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goloubeva, O.; Tan, M.; Schumaker, L. M.; Cullen, K. J.] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Sarlis, N. J.] Sanofi Aventis US, Bridgewater, MA USA. RP Posner, MR (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, Head & Neck Oncol Ctr, 1 Gustave L Levy Pl,Box 1128, New York, NY 10029 USA. EM marshall.posner@mssm.edu OI Schumaker, Lisa/0000-0002-8454-9660 FU Sanofi-Aventis; Steven Tendrich Fund FX Sanofi-Aventis; Steven Tendrich Fund to M.R.P. These Funds were used for HPV testing of tissues and the statistical analysis of the data. NR 27 TC 160 Z9 163 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 IS 5 BP 1071 EP 1077 DI 10.1093/annonc/mdr006 PG 7 WC Oncology SC Oncology GA 756YB UT WOS:000290049600011 PM 21317223 ER PT J AU Arriaga, AF Elbardissi, AW Regenbogen, SE Greenberg, CC Berry, WR Lipsitz, S Moorman, D Kasser, J Warshaw, AL Zinner, MJ Gawande, AA AF Arriaga, Alexander F. Elbardissi, Andrew W. Regenbogen, Scott E. Greenberg, Caprice C. Berry, William R. Lipsitz, Stuart Moorman, Donald Kasser, James Warshaw, Andrew L. Zinner, Michael J. Gawande, Atul A. TI A Policy-based Intervention for the Reduction of Communication Breakdowns in Inpatient Surgical Care Results From a Harvard Surgical Safety Collaborative SO ANNALS OF SURGERY LA English DT Article ID CLOSED MALPRACTICE CLAIMS; TEACHING HOSPITALS; PATIENT-CARE; ERRORS; MORTALITY; SURGERY; INSURERS; TEAMWORK AB Objective: To develop and evaluate an intervention to reduce breakdowns in communication during inpatient surgical care. Background: Communication breakdowns are the second most common cause of avoidable surgical adverse events after technical errors. Methods: In a pre- and postintervention study, a random selection of patients on the surgical services of 4 teaching hospitals were observed according to 3 measures: (1) resident-attending communication of critical patient events (eg, transfer into the intensive care unit, unplanned intubation, cardiac arrest); (2) resident-attending notification regarding routine weekend patient status; and (3) frequency of weekend patient visits by an attending. All departments then developed and adopted a set of policy and education initiatives designed to increase prompt and consistent resident-attending communication (especially in critical events) and to improve regular attending visits with surgical patients. Specific reinforcement of the policies included a pocket information card for residents, as well as periodic reminders. Repeat audits of the surgical services were then conducted. Results: We reviewed information for 211 critical events and 1360 patients for the nature of resident and attending communication practices. After the intervention, the proportion of critical events not conveyed to an attending decreased from 33% (26/80) to 2% (1/47), and gaps in the frequency of attending notification of patient status on weekends were virtually eliminated (P < 0.0001); the proportion of weekend patients not visited by an attending for greater than 24 hours decreased by half (from 61% to 33%; P = 0.0002). Contact resulted in attending-led changes in patient management in one-third of cases. Conclusions: An intervention to improve surgical communication practices at 4 teaching hospitals led to significant reductions in potentially harmful communication breakdowns during inpatient care; significant alterations in patient management were noted in one-third of cases in which there was an adherence to recommended communication practices. C1 [Arriaga, Alexander F.; Elbardissi, Andrew W.; Regenbogen, Scott E.; Greenberg, Caprice C.; Berry, William R.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Arriaga, Alexander F.; Elbardissi, Andrew W.; Greenberg, Caprice C.; Lipsitz, Stuart; Zinner, Michael J.; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Regenbogen, Scott E.; Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Moorman, Donald] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Kasser, James] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Arriaga, AF (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM aarriaga@partners.org OI Gawande, Atul/0000-0002-1824-9176 FU Harvard Risk Management Foundation (CRICO/RMF) FX Supported by a grant from the Harvard Risk Management Foundation (CRICO/RMF). NR 27 TC 19 Z9 19 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2011 VL 253 IS 5 BP 849 EP 854 DI 10.1097/SLA.0b013e3181f4dfc8 PG 6 WC Surgery SC Surgery GA 749ZD UT WOS:000289510600001 PM 21173696 ER PT J AU Livhits, M Ko, CY Leonardi, MJ Zingmond, DS Gibbons, MM de Virgilio, C AF Livhits, Masha Ko, Clifford Y. Leonardi, Michael J. Zingmond, David S. Gibbons, Melinda Maggard de Virgilio, Christian TI Risk of Surgery Following Recent Myocardial Infarction SO ANNALS OF SURGERY LA English DT Article ID MAJOR NONCARDIAC SURGERY; RANDOMIZED CONTROLLED-TRIAL; BETA-BLOCKER THERAPY; VASCULAR-SURGERY; CARDIAC RISK; CARDIOVASCULAR EVENTS; ADMINISTRATIVE DATA; MORTALITY; ATORVASTATIN; ANESTHESIA AB Objective: We aimed to assess the impact of recentmyocardial infarction (MI) on outcomes after subsequent surgery in the contemporary clinical setting. Background: Prior work shows that a history of a recent MI is a risk factor for complications following noncardiac surgery. However, this data does not reflect current advances in clinical management. Methods: Using the California Patient Discharge Database, we retrospectively analyzed patients undergoing hip surgery, cholecystectomy, colectomy, elective abdominal aortic aneurysm repair, and lower extremity amputation from 1999 to 2004 (n = 563,842). Postoperative 30-day MI rate, 30-day mortality, and 1-year mortality were compared for patients with and without a recent MI using univariate analyses and multivariate logistic regression. Relative risks (RR) with 95% confidence intervals were estimated using bootstrapping with 1000 repetitions. Results: Postoperative MI rate for the recent MI cohort decreased substantially as the length of time from MI to operation increased (0-30 days = 32.8%, 31-60 days = 18.7%, 61-90 days = 8.4%, and 91-180 days = 5.9%), as did 30-day mortality (0-30 days = 14.2%, 31-60 days = 11.5%, 61-90 days = 10.5%, and 91-180 days = 9.9%). MI within 30 days of an operation was associated with a higher risk of postoperative MI (RR range = 9.98-44.29 for the 5 procedures), 30-day mortality (RR range, 1.83-3.84), and 1-year mortality (RR range, 1.56-3.14). Conclusions: A recent MI remains a significant risk factor for postoperative MI and mortality following surgery. Strategies such as delaying elective operations for at least 8 weeks and medical optimization should be considered. C1 [de Virgilio, Christian] Harbor UCLA Med Ctr, Dept Surg, Torrance, CA 90509 USA. [de Virgilio, Christian] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Livhits, Masha; Ko, Clifford Y.; Leonardi, Michael J.; Gibbons, Melinda Maggard] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Livhits, Masha; Ko, Clifford Y.; Gibbons, Melinda Maggard] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Zingmond, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Gibbons, Melinda Maggard] Olive View UCLA, Dept Surg, Sylmar, CA USA. RP de Virgilio, C (reprint author), Harbor UCLA Med Ctr, Dept Surg, 1000 W Carson St, Torrance, CA 90509 USA. EM cdevirgilio@labiomed.org FU VA Department of Surgery; Robert Wood Johnson Physician Faculty FX Supported by VA Department of Surgery and Robert Wood Johnson Physician Faculty Scholars program. NR 31 TC 21 Z9 21 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2011 VL 253 IS 5 BP 857 EP 864 DI 10.1097/SLA.0b013e3182125196 PG 8 WC Surgery SC Surgery GA 749ZD UT WOS:000289510600003 PM 21372685 ER PT J AU Funk, LM Gawande, AA Semel, ME Lipsitz, SR Berry, WR Zinner, MJ Jha, AK AF Funk, Luke M. Gawande, Atul A. Semel, Marcus E. Lipsitz, Stuart R. Berry, William R. Zinner, Michael J. Jha, Ashish K. TI Esophagectomy Outcomes at Low-Volume Hospitals The Association Between Systems Characteristics and Mortality SO ANNALS OF SURGERY LA English DT Article ID CANCER-SURGERY; UNITED-STATES; OPERATIVE MORTALITY; SURGICAL VOLUME; RESECTION; CENTERS; PATTERNS; IMPACT AB Objective: To evaluate the association between systems characteristics and esophagectomy mortality at low-volume hospitals Background: High-volume hospitals have lower esophagectomy mortality rates, but receiving care at such centers is not always feasible. We examined low-volume hospitals and sought to identify characteristics of those with better outcomes. Methods: Using national data from Medicare and the American Hospital Association, we studied 4498 elderly patients who underwent an esophagectomy from 2004 to 2007. We divided hospitals into terciles based on esophagectomy volume and examined characteristics of patients and hospitals (size, nurse ratios, and presence of advanced medical, surgical, and radiological services). Our primary outcome was mortality. We identified 5 potentially beneficial systems characteristics in our data set and used multi-variable logistic regression to determine whether these characteristics were associated with lower mortality rates at low-volume hospitals. Results: Of the 874 hospitals that performed esophagectomies, 83% (723) were low-volume hospitals whereas only 3% (25) were high-volume. Low-volume hospitals performed a median of 1 esophagectomy during the 4-year study period and cared for patients that were older, more likely to be minority, and more likely to have multiple comorbidities compared with high-volume centers. Low-volume hospitals that had at least 3 of 5 characteristics (high nurse ratios, lung transplantation services, complex medical oncology services, bariatric surgery services, and positron emission tomography scanners) had markedly lower mortality rates compared with low-volume hospitals with none of these characteristics (12.5% vs. 5.0%; P value = 0.042). Conclusions: Low-volume hospitals with certain systems characteristics seem to achieve better esophagectomy outcomes. A more comprehensive study of the beneficial characteristics of low-volume hospitals is warranted because high-volume hospitals are difficult to access for many patients. C1 [Funk, Luke M.; Gawande, Atul A.; Semel, Marcus E.; Berry, William R.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Funk, Luke M.; Gawande, Atul A.; Semel, Marcus E.; Lipsitz, Stuart R.; Berry, William R.; Zinner, Michael J.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Funk, LM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave,Kresge Bldg,Off 440, Boston, MA 02115 USA. EM lfunk@partners.org OI Gawande, Atul/0000-0002-1824-9176 FU NIH [T32DK007754-11]; Robert Wood Johnson Physician Faculty; Department of Surgery, Brigham and Women's Hospital FX Dr. Funk is supported by the Department of Surgery, Brigham and Women's Hospital. Dr. Semel is supported by an NIH research training grant in digestive diseases and surgery (T32DK007754-11). Dr. Jha is funded by the Robert Wood Johnson Physician Faculty Scholar Program. NR 40 TC 25 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2011 VL 253 IS 5 BP 912 EP 917 DI 10.1097/SLA.0b013e318213862f PG 6 WC Surgery SC Surgery GA 749ZD UT WOS:000289510600011 PM 21422913 ER PT J AU Lan, JG Heneghan, AF Sano, Y Jonker, MA Omata, J Xu, WT Pierre, JF Kudsk, KA AF Lan, Jinggang Heneghan, Aaron F. Sano, Yoshifumi Jonker, Mark A. Omata, Jiro Xu, Wentong Pierre, Joseph F. Kudsk, Kenneth A. TI Parenteral Nutrition Impairs Lymphotoxin beta Receptor Signaling via NF-kappa B SO ANNALS OF SURGERY LA English DT Article ID GUT ISCHEMIC INSULT; LYMPHOID-TISSUE; ENTERAL NUTRITION; MUCOSAL IMMUNITY; INTEGRIN EXPRESSION; MICE; HOMEOSTASIS; INTESTINE; BLOCKADE; SELECTIN AB Objective: To determine effects of (1) parenteral nutrition (PN), (2) exogenous Lymphotoxin beta receptor (LT beta R) stimulation in PN animals, and (3) exogenous LT beta R blockade in chow animals on NF-kappa B activation pathways and products: MAdCAM-1, chemokine (C-C motif) Ligand (CCL) 19, CCL20, CCL25, interleukin (IL)-4, and IL-10. Background: LT stimulates LT beta R in Peyer's patches (PP) to activate NF-kappa B via the noncanonical pathway. The p100/RelB precursor yields p52/RelB producingMAdCAM-1, cytokines, and chemokines important in cell trafficking. TNF alpha, IL-1 beta, and bacterial products stimulate the inflammatory canonical NF-kappa B pathway producing p65/p50 and c-Rel/p50. PN decreases LT beta R, MAdCAM-1, and chemokines in PP and lowers small intestinal IgA compared with chow. Methods: Canonical (p50 and p65) and noncanonical (p52 and Rel B) NF-kappa B proteins in PP were analyzed by TransAM NF-kappa B kit after 5 days of chow or PN, 2 days of LT beta R stimulation or 3 days of LT beta R blockade. MAdCAM-1, chemokines, and cytokines in PP were measured by ELISA after LT beta R stimulation or blockade. Results: PN significantly reduced all NF-kappa B proteins in PP compared with chow. Exogenous LT beta R stimulation during PN increased p50, p52, Rel B, MAdCAM-1, IL-4, and IL-10 in PP, but not p65, CCL19, CCL20, or CCL25 compared with PN. LT beta R blockade reduced noncanonical products (p52 and Rel B), MAdCAM-1, CCL19, CCL20, CCL25, IL-4, and IL-10 but had no effect on the inflammatory pathway (p50 and p65) compared with chow. Conclusion: Lack of enteral stimulation during PN decreases both canonical and noncanonical NF-kappa B pathways in PP. LT beta R stimulation during PN feeding completely restores PP noncanonical NF-kappa B activity, MAdCAM-1, IL-4, IL-10, and partly the canonical pathway. LT beta R blockade decreases the noncanonical NF-kappa B activity, MAdCAM-1, chemokines, and cytokines without effect on the canonical LT beta R activity in PP. C1 [Lan, Jinggang; Heneghan, Aaron F.; Sano, Yoshifumi; Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Surg Serv, Madison, WI USA. [Lan, Jinggang; Heneghan, Aaron F.; Sano, Yoshifumi; Jonker, Mark A.; Omata, Jiro; Xu, Wentong; Pierre, Joseph F.; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. RP Kudsk, KA (reprint author), 600 Highland Ave,G5-341 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU National Institute of Health (NIH) [R01 GM53439]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service FX Supported by the National Institute of Health (NIH) grant R01 GM53439. This material is also based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 34 TC 8 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2011 VL 253 IS 5 BP 996 EP 1003 DI 10.1097/SLA.0b013e31821224eb PG 8 WC Surgery SC Surgery GA 749ZD UT WOS:000289510600024 PM 21368655 ER PT J AU Zhou, JH Bashey, A Zhong, RK Corringham, S Messer, K Pu, MY Ma, WX Chut, T Soiffer, R Mitrovich, RC Lowy, I Ball, ED AF Zhou, Jiehua Bashey, Asad Zhong, Ruikun Corringham, Sue Messer, Karen Pu, Minya Ma, Wenxue Chut, Theresa Soiffer, Robert Mitrovich, Rachel C. Lowy, Israel Ball, Edward D. TI CTLA-4 Blockade following Relapse of Malignancy after Allogeneic Stem Cell Transplantation Is Associated with T Cell Activation But Not with Increased Levels of T Regulatory Cells SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Ipilimumab; T lymphocytes ID VERSUS-HOST-DISEASE; METASTATIC MELANOMA; PERIPHERAL-BLOOD; LYMPHOCYTE ANTIGEN-4; MONOCLONAL-ANTIBODY; BONE-MARROW; PHASE I/II; CANCER; IPILIMUMAB; EXPRESSION AB Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) is a key negative regulator of T cell activation and proliferation. Ipilimumab is a human monoclonal antibody that specifically blocks the binding of CTLA-4 to its ligand. To test the hypothesis that blockade of CTLA-4 by ipilimumab could augment graft-versus-malignancy (GVM) effects without a significant impact on graft-versus-host disease (GVHD), we conducted a phase I clinical trial of ipilimumab infusion in patients with relapsed malignancy following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we report the analysis of peripheral blood T lymphocyte reconstitution, T regulatory cell (Treg) expression, and T cell activation markers after a single dose of ipilimumab in 29 patients. Peripheral blood samples were collected from all patients before and after ipilimumab infusion. Lymphocyte immunophenotyes, including levels of CD4(+)CD25(high) cells and T cell activation markers, were analyzed in all cases. Levels of CD4(+) CD25(high)Foxp3(+) cells and intracellular CTLA-4 in CD4(+) T cells also were evaluated in the last II cases. We found lower baseline levels of CD4(+) and CD45RO(+) T cells in patients compared with normal controls. More than 50% of the patients had abnormally low lymphocyte counts (CD4 or/and CD8 T cells), and some had no circulating B lymphocytes. The percentages of both CD4(+)CD25(high) and CD4(+)CD25(high)Foxp3(+) T cells were significantly higher in patients before ipilimumab infusion than in healthy donors. Twenty of 29 patients exhibited an elevated level of CD4(+)CD25(low) activated T cells at baseline, compared with only 3 of 26 healthy donors. Both CD4(+) and CD8(+) T lymphocyte counts were significantly increased after ipilimumab infusion. There was no consistent change in absolute lymphocyte count or in the number of T cells expressing the activation marker CD69. However, increases in CD4(+)CD25(low) T cells were seen in 20 of 29 patients and increases in CD4(+)HLA-DR(+) T cells were seen in the last 10 patients in the first 60 days after ipilimumab infusion. Although the percentages of both CD4(+)CD25(high) and CD4(+)CD25(high)Foxp3(+) T cells decreased significantly during the observation period, the absolute cell counts did not change. Intracellular CTLA-4 expression in CD4(+)CD25(lo/-) T cells increased significantly after ipilimumab infusion. We conclude that CTLA-4 blockade by a single infusion of ipilimumab increased CD4(+) and CD4(+)HLA-DR(+) T lymphocyte counts and intracellular CTLA-4 expression at the highest dose level. There was no significant change in Treg cell numbers after ipilimumab infusion. These data demonstrate that significant changes in T cell populations occur on exposure to a single dose of ipilimumab. Further studies with multiple doses are needed to explore this phenomenon further and to correlate changes in lymphocyte subpopulations with clinical events. Biol Blood Marrow Transplant 17: 682-692 (2011) 2011 (C) American Society for Blood and Marrow Transplantation C1 [Zhou, Jiehua; Zhong, Ruikun; Corringham, Sue; Messer, Karen; Pu, Minya; Ma, Wenxue; Chut, Theresa; Ball, Edward D.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Bashey, Asad] Northside Hosp, Blood & Marrow Transplant Leukemia Program, Atlanta, GA USA. [Soiffer, Robert; Mitrovich, Rachel C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lowy, Israel] Medarex Inc, Princeton, NJ USA. RP Ball, ED (reprint author), Univ Calif San Diego, Moores Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA. EM tball@ucsd.edu FU NCI NIH HHS [R01 CA093891-04, R01 CA093891] NR 42 TC 19 Z9 19 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2011 VL 17 IS 5 BP 682 EP 692 DI 10.1016/j.bbmt.2010.08.005 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 757CK UT WOS:000290061500011 PM 20713164 ER PT J AU Barker, CC Agovi, MA Logan, B Lazarus, HM Ballen, KK Gupta, V Hale, GA Frangoul, H Ho, V Rizzo, JD Pasquini, MC AF Barker, Collin C. Agovi, Manza-A. Logan, Brent Lazarus, Hillard M. Ballen, Karen K. Gupta, Vikas Hale, Gregory A. Frangoul, Haydar Ho, Vincent Rizzo, J. Douglas Pasquini, Marcelo C. CA Ctr Int Blood Marrow Transplant TI Childhood Obesity and Outcomes after Bone Marrow Transplantation for Patients with Severe Aplastic Anemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Transplant; Pediatrics; Aplastic anemia ID BODY-MASS INDEX; HEMATOPOIETIC-CELL TRANSPLANTATION; UNRELATED DONOR TRANSPLANTATION; HOST-DISEASE; CHILDREN; ADOLESCENTS; OVERWEIGHT; LEUKEMIA; MORTALITY; LYMPHOMA AB The prevalence of obesity in the pediatric population has increased in the last 2 decades and represents a serious health concern, with potential impact on outcomes of hematopoietic cell transplantation (HCT). We studied the effect of weight by age-adjusted body mass index (BMI) percentile in 1,281 pediatric patients (age 2-19 years) with severe aplastic anemia who underwent HCT between 1990 and 2005. The study population was divided into 5 weight groups-underweight risk of underweight, normal BMI range, risk of overweight, and overweight-according to age-adjusted BMI percentiles. Cox proportional hazards regression models for survival and acute graft-versus-host disease (aGVHD), performed using weight groups as the main effect and the normal BMI range (26th-75th percentile) as the baseline comparison, found higher mortality among overweight children (>95th percentile adjusted for age). Weight at transplantation did not increase the adjusted risk of grade III-IV aGVHD. The 1-year and 2-year overall survival rates were 60% and 59% for overweight children, compared with >70% in children with lower BMI at both time points (P<.001). Other significant factors associated with survival included race and region, donor type, conditioning regimens in related donor transplants, performance score, and year of transplantation. In conclusion, overweight children with aplastic anemia have worse outcomes after HCT. The impact of obesity on survival outcomes in children should be discussed during pretransplantation counseling. Biol Blood Marrow Transplant 17: 737-744 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [Agovi, Manza-A.; Logan, Brent; Rizzo, J. Douglas; Pasquini, Marcelo C.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53005 USA. [Barker, Collin C.] British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada. [Lazarus, Hillard M.] Univ Hosp Case Western Med Ctr, Cleveland, OH USA. [Ballen, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Frangoul, Haydar] Vanderbilt Univ, Nashville, TN USA. [Ho, Vincent] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pasquini, MC (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,CCC5500, Milwaukee, WI 53005 USA. EM mpasquin@mcw.edu FU NCI NIH HHS [U24 CA076518-12, U24 CA076518, U24 CA076518-12S1] NR 22 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2011 VL 17 IS 5 BP 737 EP 744 DI 10.1016/j.bbmt.2010.08.019 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 757CK UT WOS:000290061500018 PM 20817111 ER PT J AU Duncan, CN Vrooman, L Apfelbaum, EM Whitley, K Bechard, L Lehmann, LE AF Duncan, Christine N. Vrooman, Lynda Apfelbaum, Erin M. Whitley, Katherine Bechard, Lori Lehmann, Leslie E. TI 25-Hydroxy Vitamin D Deficiency Following Pediatric Hematopoietic Stem Cell Transplant SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Pediatric; Vitamin D; Children; HSCT; BMT ID BONE-MINERAL DENSITY; VERSUS-HOST DISEASE; D INSUFFICIENCY; COLORECTAL-CANCER; HYPOVITAMINOSIS-D; D INADEQUACY; CHILDREN; PREVALENCE; RISK; RICKETS AB Children may be at increased risk for vitamin D deficiency following HSCT because of lack of sun exposure, the recommended use of sunscreen, dietary insufficiency, malabsorption, and the use of certain medications. We prospectively assessed the prevalence of and risk factors for 25-hydroxy (25-OH) vitamin D deficiency in 67 patients transplanted at our institution. 25-OH vitamin D levels were checked during 3 separate 4-week periods in the spring, autumn, and winter. Subjects were <2 years following transplant and/or being treated for chronic graft-versus-host disease (cGVHD). Levels less than 20 ng/mL were considered deficient, and those less than 30 ng/mL were considered insufficient. The mean 25-OH vitamin D level was 22.8 ng/mL (range: 7-46.2). A total of 80.6% (confidence interval [CI] 69.1%-89.3%) of patients had a level less than the lower limit of the institutional normal range. The deficiency rate was 37.3% (CI 25.8%-50%). The mean parathyroid hormone (PTH) level was 77.5 (SD = 80.5). There was no correlation between 25-OH vitamin D and PTH levels. We evaluated potential risk factors for 25-OH vitamin D deficiency including age, season of testing, sun exposure, sunscreen use, use of steroid or calcineurin inhibitor, race, and dairy intake. In multivariate logistic regression, only older age was found to be a risk factor for deficiency (P = .004). Patients with deficient levels were treated with 50,000 IU of ergocalciferol once weekly for 6 weeks. A postrepletion 25-OH level was available for 22 patients. The majority of repleted patients had a normal posttreatment level (63.6%). The postsupplementation level corrected into the insufficient range for 31.8% of patients and 4.6% remained deficient. Vitamin D insufficiency and deficiency are common following HSCT. Further investigation into potential risk factors and the appropriate supplementation for these patients is warranted. Biol Blood Marrow Transplant 17: 749-753 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [Duncan, Christine N.; Vrooman, Lynda; Apfelbaum, Erin M.; Whitley, Katherine; Bechard, Lori; Lehmann, Leslie E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Duncan, CN (reprint author), Dana Farber Canc Inst, 44 Binney St,SW-330, Boston, MA 02115 USA. EM christine_Juncan@dfci.harvard.edu NR 51 TC 9 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2011 VL 17 IS 5 BP 749 EP 753 DI 10.1016/j.bbmt.2010.10.009 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 757CK UT WOS:000290061500020 PM 20951818 ER PT J AU Tallaj, JA Singla, I Bourge, RC AF Tallaj, Jose A. Singla, Ish Bourge, Robert C. TI Implantable Hemodynamic Monitors SO CARDIOLOGY CLINICS LA English DT Article DE Congestive heart failure; Diastolic heart failure; BNP; Implantable monitors; Hypervolemia; Chronicle IHM; CardioMEMS ID ADVANCED HEART-FAILURE; PULMONARY-ARTERY PRESSURE; RIGHT-VENTRICULAR PRESSURE; NATRIURETIC PEPTIDE; INITIAL-EXPERIENCE; SENSOR; MULTICENTER; MANAGEMENT; DIAGNOSIS; THERAPY AB The evaluation and management of volume status in patients with heart failure is a challenge for most clinicians. In addition, such an evaluation is possible only during a personal clinician patient interface. The ability to acquire hemodynamic data continuously with the help of implanted devices with remote monitoring capability can provide early warning of heart failure decompensation and thus may aid in preventing hospitalizations for heart failure. The data obtained also may improve the understanding of the disease process. It is important for the clinician treating patients who have heart failure to become acquainted with this type of technology and learn to interpret and use these data appropriately. This article reviews the implantable hemodynamics monitors currently available. C1 [Bourge, Robert C.] Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Tallaj, Jose A.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Bourge, RC (reprint author), Univ Alabama, Dept Med, Div Cardiovasc Dis, 1900 Univ Blvd, Birmingham, AL 35294 USA. EM bbourge@uab.edu NR 29 TC 4 Z9 4 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2011 VL 29 IS 2 BP 289 EP + DI 10.1016/j.ccl.2011.03.002 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 756IZ UT WOS:000290006200013 PM 21459250 ER PT J AU Klein, AJ Garcia, JA Hudson, PA Kim, MS Messenger, JC Casserly, IP Wink, O Hattler, B Tsai, TT Chen, SYJ Hansgen, A Carroll, JD AF Klein, Andrew J. Garcia, Joel A. Hudson, Paul A. Kim, Michael S. Messenger, John C. Casserly, Ivan P. Wink, Onno Hattler, Brack Tsai, Thomas T. Chen, S. Y. James Hansgen, Adam Carroll, John D. TI Safety and Efficacy of Dual-Axis Rotational Coronary Angiography Vs. Standard Coronary Angiography SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE coronary angiography; rotational coronary angiography; dual-axis angiography ID INTRAVASCULAR ULTRASOUND; ARTERY-DISEASE; CLINICAL UTILITY; INTERVENTION AB Objective: To determine the safety and efficacy of dual-axis rotational coronary angiography (DARCA) by directly comparing it to standard coronary angiography (SA). Background: Standard coronary angiography (SA) requires numerous fixed static images of the coronary tree and has multiple well-documented limitations. Dual-axis rotational coronary angiography (DARCA) is a new rotational acquisition technique that entails simultaneous LAO/RAO and cranial/caudal gantry movement. This technological advancement obtains numerous unique images of the left or right coronary tree with a single coronary injection. We sought to assess the safety and efficacy of DARCA as well as determine DARCA's adequacy for CAD screening and assessment. Methods: Thirty patients underwent SA following by DARCA. Contrast volume, radiation dose (DAP) and procedural time were recorded for each method to assess safety. For DARCA acquisitions, blood pressure (BP), heart rate (HR), symptoms and any arrhythmias were recorded. All angiograms were reviewed for CAD screening adequacy by two independent invasive cardiologists. Results: Compared to SA, use of DARCA was associated with a 51% reduction in contrast, 35% less radiation exposure, and 18% shorter procedural time. Both independent reviewers noted DARCA to be at least equivalent to SA with respect to the ability to screen for CAD. Conclusion: DARCA represents a new angiographic technique which is equivalent in terms of image quality and is associated with less contrast use, radiation exposure, and procedural time than SA. (C) 2011 Wiley-Liss, Inc. C1 [Klein, Andrew J.; Garcia, Joel A.; Hudson, Paul A.; Kim, Michael S.; Messenger, John C.; Casserly, Ivan P.; Chen, S. Y. James; Hansgen, Adam; Carroll, John D.] Univ Colorado Denver, Div Cardiol, Aurora, CO 80045 USA. [Wink, Onno] Philips Healthcare, Clin Res, Aurora, CO USA. [Hattler, Brack; Tsai, Thomas T.] Denver VA Med Ctr, Div Cardiol, Denver, CO USA. RP Carroll, JD (reprint author), Univ Colorado Denver, Div Cardiol, Campus Box 132,12401 E 17th Ave, Aurora, CO 80045 USA. EM John.Carroll@ucdenver.edu NR 21 TC 15 Z9 20 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAY 1 PY 2011 VL 77 IS 6 BP 820 EP 827 DI 10.1002/ccd.22804 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 757DD UT WOS:000290063700011 PM 20853352 ER PT J AU Cannon, CP AF Cannon, Christopher P. TI Clopidogrel: To Test or Not to Test? That Is the Question-Still SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 Harvard Univ, Div Cardiovasc, TIMI Study Grp, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Harvard Univ, Div Cardiovasc, TIMI Study Grp, Brigham & Womens Hosp,Med Sch, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 6 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 2011 VL 57 IS 5 BP 659 EP 661 DI 10.1373/clinchem.2010.158709 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 756AY UT WOS:000289985100001 PM 21402801 ER PT J AU Wang, L Manson, JE Gaziano, JM Liu, SM Cochrane, B Cook, NR Ridker, PM Rifai, N Sesso, HD AF Wang, Lu Manson, JoAnn E. Gaziano, J. Michael Liu, Simin Cochrane, Barbara Cook, Nancy R. Ridker, Paul M. Rifai, Nader Sesso, Howard D. TI Circulating Inflammatory and Endothelial Markers and Risk of Hypertension in White and Black Postmenopausal Women SO CLINICAL CHEMISTRY LA English DT Article ID C-REACTIVE PROTEIN; APPARENTLY HEALTHY-MEN; ADHESION MOLECULES; BLOOD-PRESSURE; INCIDENT HYPERTENSION; OXIDATIVE STRESS; INTERLEUKIN-6; CELLS; ATHEROSCLEROSIS; ATHEROGENESIS AB BACKGROUND: Systemic inflammation and endothelial activation are implicated in the development of hypertension. However, epidemiologic studies have yet to compare multiple corresponding biomarkers in relation to risk of hypertension, particularly in multiethnic populations. METHODS: We identified 800 individuals with incident hypertension and 800 matched controls, each group with equal numbers of white and black women, in a nested case-control study within the Women's Health Initiative Observational Study. We measured markers of inflammation [high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-1 beta, tumor necrosis factor receptor 2 (TNF-r2)] and endothelial activation [soluble intercellular adhesion molecule-1 (sICAM-1)] in baseline blood samples. RESULTS: Before adjustment for measures of adiposity, higher hsCRP and IL-6 concentrations were associated with increased risk of hypertension in both white and black women, higher TNF-r2 was associated with increased risk of hypertension in black women only, and IL-1 beta and sICAM-1 were not associated with risk of hypertension. All the positive associations were attenuated after adjustment for body mass index. The resulting multivariable-adjusted relative risks (95% CI) of hypertension comparing the highest vs lowest quartile were 1.52 (0.94-2.48) and 1.23 (0.76-1.97) for hsCRP and IL-6 in white women and 1.30 (0.81-2.07), 1.58 (0.96-2.59), and 1.49 (0.94-2.36) for hsCRP, IL-6, and TNF-r2 in black women. The results after adjustment for waist circumference were similar. CONCLUSIONS: After adjustment for measures of adiposity, there was no significant association of hsCRP, IL-6, IL-1 beta, TNF-r2, or sICAM-1 with incident hypertension in either white or black women. The interrelationships between inflammation and adiposity in development of hypertension need further investigation. (C) 2011 American Association for Clinical Chemistry C1 [Wang, Lu; Manson, JoAnn E.; Gaziano, J. Michael; Cook, Nancy R.; Ridker, Paul M.; Sesso, Howard D.] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02215 USA. [Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02215 USA. [Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, Boston, MA 02215 USA. [Manson, JoAnn E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Jamaica Plain, MA USA. [Liu, Simin] Univ Calif Los Angeles, Dept Epidemiol, Ctr Metab Dis Prevent, Los Angeles, CA USA. [Liu, Simin] Univ Calif Los Angeles, Dept Med, Ctr Metab Dis Prevent, Los Angeles, CA 90024 USA. [Cochrane, Barbara] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Rifai, Nader] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. RP Wang, L (reprint author), Brigham & Womens Hosp, Div Prevent Med, Dept Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM luwang@rics.bwh.harvard.edu RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU National Heart, Lung, and Blood Institute (NHLBI) [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; Novartis; AstraZeneca; National Cancer Institute; NIH [HL-075455] FX B. Cochrane, National Heart, Lung, and Blood Institute (NHLBI). P.M Ridker, Novartis, AstraZeneca, NHLBI, National Cancer Institute. H. D. Sesso, research grant HL-075455 from the NIH. The WHI program is funded by the NHLBI through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. These grants provided funding for study conduct and data collection. NR 40 TC 10 Z9 12 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 2011 VL 57 IS 5 BP 729 EP 736 DI 10.1373/clinchem.2010.156794 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 756AY UT WOS:000289985100013 PM 21398601 ER PT J AU Shlipak, MG Weekley, CC Li, YM Hansson, LO Larsson, A Whooley, M AF Shlipak, Michael G. Weekley, Cristin C. Li, Yongmei Hansson, Lars-Olof Larsson, Anders Whooley, Mary TI Comparison of Cardiovascular Prognosis by 3 Serum Cystatin C Methods in the Heart and Soul Study SO CLINICAL CHEMISTRY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; BODY-COMPOSITION; RISK; CREATININE; MORTALITY; DISEASE; MARKER; HEALTH; ASSOCIATION; FAILURE AB BACKGROUND: Cystatin C is a promising new biomarker to determine the estimated glomerular filtration. However, the Siemens' cystatin C assay (Siemens), used in many longitudinal studies, has had limited clinical applicability because it requires a specific, dedicated instrument. Other companies, including Gentian and Roche, have developed cystatin C assays that can be used with most routine clinical chemistry analyzers. METHODS: We compared the agreement of Gentian and Roche with Siemens assays in 948 participants at the baseline visit of the Heart and Soul Study, a cohort of participants with established coronary artery disease who were followed for an average of 8 years. We then compared associations of all 3 cystatin C measures and eGFR-Modification of Diet in Renal Disease (MDRD) with clinical outcomes. RESULTS: The Gentian assay had higher correlation with Siemens (r = 0.96) than did Roche (r = 0.93, P < 0.001). After cross-tabulating quartiles of each cystatin Cmeasure, agreements (kappa statistic) were higher for Siemens and Gentian (0.73, 95% CI 0.72-0.75) than for Roche and Siemens (0.64, 0.63-0.66) or for Roche and Gentian (0.69, 0.65-0.71). These differences in agreement had minimal impact on associations with clinical outcomes; the hazard ratios (HRs) for mortality comparing the high vs low quartiles were 3.2 (95% CI 2.1-4.8) for Siemens, 3.1 (CI 2.1-4.7) for Gentian, 3.1 (CI 2.1-4.7) for Roche, and 1.6 (CI 1.1-2.3) for eGFR-MDRD, after multivariate adjustment. CONCLUSIONS: In summary, agreement with the Siemens' assay was modestly higher for the Gentian compared with the Roche assay, although all 3 methods for cystatin C measurement had similar utility as predictors of clinical outcomes. (C) 2011 American Association for Clinical Chemistry C1 [Shlipak, Michael G.; Weekley, Cristin C.; Li, Yongmei; Whooley, Mary] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Shlipak, Michael G.; Weekley, Cristin C.; Whooley, Mary] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hansson, Lars-Olof; Larsson, Anders] Uppsala Univ, Uppsala, Sweden. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, Box 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU NIH [R01 DK066488-01]; American Heart Association; Siemens; Gentian; Roche FX M.G. Shlipak, NIH (R01 DK066488-01) and the American Heart Association Established Investigator Award. Siemens cystatin C measures were supported by a grant by Siemens (Dade-Behring) to the Heart and Soul Study. The Gentian and Roche measures were funded by a grant from Gentian and Roche, respectively, to the Heart and Soul Study. These funding sources had no involvement in the design or execution of this study. NR 18 TC 14 Z9 14 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 2011 VL 57 IS 5 BP 737 EP 745 DI 10.1373/clinchem.2010.158915 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 756AY UT WOS:000289985100014 PM 21310869 ER PT J AU Li, J Janne, PA Makrigiorgos, GM AF Li, Jin Jaenne, Pasi A. Makrigiorgos, G. Mike TI Biotinylated Probe Isolation of Targeted Gene Region Improves Detection of T790M Epidermal Growth Factor Receptor Mutation via Peptide Nucleic Acid-Enriched Real-Time PCR SO CLINICAL CHEMISTRY LA English DT Article ID CELL LUNG-CANCER; EGFR T790M; RESISTANCE; GEFITINIB C1 [Li, Jin; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Jaenne, Pasi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Level L2,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU NIH [CA-138280, CA-135257, CA-090578] FX G.M. Makrigiorgos, NIH grant CA-138280; P.A. Janne, NIH grants CA-135257 and CA-090578. NR 21 TC 7 Z9 7 U1 0 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 2011 VL 57 IS 5 BP 770 EP 773 DI 10.1373/clinchem.2010.157784 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 756AY UT WOS:000289985100018 PM 21325655 ER PT J AU Larsson, A Hansson, LO Flodin, M Katz, R Shlipak, MG AF Larsson, Anders Hansson, Lars-Olof Flodin, Mats Katz, Ronit Shlipak, Michael G. TI Calibration of the Siemens Cystatin C Immunoassay Has Changed over Time SO CLINICAL CHEMISTRY LA English DT Letter ID KIDNEY-FUNCTION; CREATININE; VALUES; MG/L C1 [Larsson, Anders; Hansson, Lars-Olof; Flodin, Mats] Uppsala Univ, Uppsala, Sweden. [Katz, Ronit] Univ Washington, Seattle, WA 98195 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Larsson, A (reprint author), Univ Hosp, Dept Med Sci, S-75185 Uppsala, Sweden. EM anders.larsson@akademiska.se NR 5 TC 29 Z9 30 U1 1 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 2011 VL 57 IS 5 BP 777 EP 778 DI 10.1373/clinchem.2010.159848 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 756AY UT WOS:000289985100021 PM 21364028 ER PT J AU Tierney, EP Hanke, CW Kimball, AB AF Tierney, Emily P. Hanke, C. William Kimball, Alexa Boer TI Practice Models and Roles of Physician Extenders in Dermatologic Surgery SO DERMATOLOGIC SURGERY LA English DT Article AB BACKGROUND The prevalence of physician extenders (PEs) has increased significantly in dermatologic surgery over the last decade. METHODS An analysis was performed of the staff in dermatologic surgery practices, roles of PEs, and level of supervision. RESULTS Mohs fellowship-trained (MMSFT) dermatologic surgeons were more likely to employ registered nurses (n=85, 73.9%) than non-fellowship-trained (NMMSFT) surgeons (n=65, 50.0%, p <.05) (dermatologists who reported performing Mohs without having completed a Mohs College fellowship). NMMSFT surgeons (n=46, 35.4%) were 33% more likely to employ physician assistants than MMSFT surgeons (n=30, 26.1%, p=.05). Both surgeon types reported that their physician assistants and nurse practitioners spent the majority of their time treating medical dermatology patients, but NMMSFT surgeons were twice as likely as MMSFT surgeons to have their PEs involved in performing or assisting with cosmetic procedures. MMSFT surgeons (38.5%) were twice as likely to have direct supervision of their PEs as NMMSFT surgeons (16.1%, p=.01). CONCLUSIONS PEs are highly prevalent in dermatologic surgery practices and are playing direct roles in the delivery of dermatologic care. Promoting patient safety through appropriate extender supervision and reporting of patient outcomes are highly needed as this sector of the dermatologic surgery workforce continues to expand. The authors have indicated no significant interest with commercial supporters. C1 [Tierney, Emily P.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02111 USA. [Hanke, C. William] Laser & Skin Surg Ctr Indiana, Carmel, IN USA. [Kimball, Alexa Boer] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kimball, Alexa Boer] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Tierney, EP (reprint author), Boston Univ, Sch Med, Dept Dermatol, 609 Albany St, Boston, MA 02111 USA. EM etierney29@gmail.com NR 7 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAY PY 2011 VL 37 IS 5 BP 677 EP 683 DI 10.1111/j.1524-4725.2011.01984.x PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 755BZ UT WOS:000289902900017 PM 21492314 ER PT J AU Laby, DM Kirschen, DG Goldstein, M AF Laby, Daniel M. Kirschen, David G. Goldstein, Michael TI Guest Editorial-Eye & Contact Lens Sports Vision Special Issue SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Editorial Material C1 [Laby, Daniel M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Kirschen, David G.] Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, David Geffen Sch Med, Los Angeles, CA 90024 USA. Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. [Goldstein, Michael] Tufts Univ, Sch Med, New England Eye Ctr, Boston, MA 02111 USA. RP Laby, DM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD MAY PY 2011 VL 37 IS 3 BP 114 EP 115 DI 10.1097/ICL.0b013e3182134a2a PG 2 WC Ophthalmology SC Ophthalmology GA 755XO UT WOS:000289973900002 PM 21471816 ER PT J AU Laby, DM Kirschen, DG Pantall, P AF Laby, Daniel M. Kirschen, David G. Pantall, Paige TI The Visual Function of Olympic-Level Athletes-An Initial Report SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Article DE Vision; sport; Olympic games; Archery; Boxing; Fencing; Soccer; Softball; Skating; Track-and-field; Volleyball; Acuity; Stereo; Contrast AB Objective: To describe the visual functions of Olympic-level athletes and begin to describe any differences between sports. Methods: A commercially available testing system was used to evaluate 157 Olympic-level athletes. These sports vision evaluations were therefore performed under standardized conditions. Visual functions, tested at a distance, consisted of monocular visual acuity, contour and random dot stereoacuity, and contrast sensitivity. Results: Boxers and track-and-field athletes demonstrated mean logMAR visual acuities between 0.078 and 0.060. All others demonstrated results better than -0.121. There were statistically significant differences and suggestive trends in the visual acuity in the right and left eyes between the track-and-field and archery and track-and-field and softball, and between softball and boxing (range P-0.0005-0.0243). Mean distance contour stereoacuity of the archers was 62 arcsec, worse than the soccer, softball, and speed skaters. All athletes demonstrated similar contrast sensitivity results at low spatial frequencies, whereas at higher spatial frequencies, softball players performed better than did the speed skaters, track-and-field, and volleyball athletes. Conclusions and Application to Clinical Practice: There seems to be a unique set of visual skills that are common to athletes in certain sports. In addition, visual performance measures vary between sports at the Olympic level. The ability to identify the visual needs for an athlete who wishes to participate in a given sport, and to correct any deficits an athlete may have, could lead to more success, at the elite and amateur levels. C1 [Laby, Daniel M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Kirschen, David G.] Univ Calif Los Angeles, Div Pediat Ophthalmol & Strabismus, Dept Ophthalmol, Jules Stein Eye Inst,David Geffen Sch Med, Los Angeles, CA 90024 USA. So Calif Coll Optometry, Dept Vis Sci & Optometry, Fullerton, CA USA. [Pantall, Paige] LLC, Vis Care Inst, Jacksonville, FL USA. RP Laby, DM (reprint author), Suite 592,95Washington St, Canton, MA 02021 USA. EM drlaby@eyecareforkidsllc.com FU M & S Professional Sports Vision Testing System; Vision Care Institute, LLC, a Johnson & Johnson Company FX D.M.L. and D.G.K. have a financial interest in the M & S Professional Sports Vision Testing System.; Supported by The Vision Care Institute, LLC, a Johnson & Johnson Company. NR 7 TC 4 Z9 4 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD MAY PY 2011 VL 37 IS 3 BP 116 EP 122 DI 10.1097/ICL.0b013e31820c5002 PG 7 WC Ophthalmology SC Ophthalmology GA 755XO UT WOS:000289973900003 PM 21378577 ER PT J AU Kirschen, DG Laby, DL AF Kirschen, David G. Laby, Daniel L. TI The Role of Sports Vision in Eye Care Today SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Review DE Sports vision; Eye care ID PLAYERS; GAZE AB Sports vision as an academic discipline is in its infancy. This review traces its history on many different fronts: early work, research, organizations, literature, cultural environment, sports injuries, and a view of the future. This article was presented as the opening remarks to the first-ever academic sports vision meeting held at Fenway Park in Boston, Massachusetts, in January 2010. C1 [Kirschen, David G.] Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Kirschen, David G.] So Calif Coll Optometry, Dept Vis Sci & Optometry, Fullerton, CA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Kirschen, DG (reprint author), 428 S Brea Blvd, Brea, CA 92821 USA. EM davidkirschen@mac.com NR 19 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD MAY PY 2011 VL 37 IS 3 BP 127 EP 130 DI 10.1097/ICL.0b013e3182126a08 PG 4 WC Ophthalmology SC Ophthalmology GA 755XO UT WOS:000289973900005 PM 21451416 ER PT J AU Laby, DM Kirschen, DG AF Laby, Daniel M. Kirschen, David G. TI Thoughts on Ocular Dominance-Is It Actually a Preference? SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Review DE Ocular dominance; Eye dominance ID EYE DOMINANCE; BASEBALL PLAYERS; VISUAL-SYSTEM; PERFORMANCE AB Background: Ocular dominance has been studied for many years, and there have been many attempts to correlate eye dominance with athletic performance. Although many reports have failed to show a correlation, some reports have shown a relationship between sports performance and eye dominance. Methods: This report reviews some of those studies and the tests of eye dominance used in the reports. Additionally, we review the physical basis of eye dominance and the role of the binocular visual system in its determination. Lastly, a review of common facts and fallacies relating to ocular dominance is provided. Results/Conclusion: It is suggested that the visual system is designed as a binocular system, and only tests that allow for maintenance of binocular vision during the determination of ocular preference should be used if an accurate evaluation is to be made. C1 [Laby, Daniel M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Kirschen, David G.] Univ Calif Los Angeles, Dept Ophthalmol, Jules Stein Eye Inst, David Geffen Sch Med, Los Angeles, CA 90024 USA. So Calif Coll Optometry, Fullerton, CA USA. RP Laby, DM (reprint author), Suite 592,95 Washington St, Canton, MA 02021 USA. EM drlaby@drlaby.com NR 18 TC 2 Z9 2 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD MAY PY 2011 VL 37 IS 3 BP 140 EP 144 DI 10.1097/ICL.0b013e31820e0bdf PG 5 WC Ophthalmology SC Ophthalmology GA 755XO UT WOS:000289973900007 PM 21455079 ER PT J AU Strate, LL Liu, YL Huang, ES Giovannucci, EL Chan, AT AF Strate, Lisa L. Liu, Yan L. Huang, Edward S. Giovannucci, Edward L. Chan, Andrew T. TI Use of Aspirin or Nonsteroidal Anti-inflammatory Drugs Increases Risk for Diverticulitis and Diverticular Bleeding SO GASTROENTEROLOGY LA English DT Article DE Side Effects; Toxicity; Colon Medication; Diverticular Disease ID MALE HEALTH-PROFESSIONALS; COLORECTAL-CANCER; DISEASE; MEN; COMPLICATIONS; HEMORRHAGE; EVENTS; REPRODUCIBILITY; ACETAMINOPHEN; QUESTIONNAIRE AB BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been implicated in diverticular complications. We examined the influence of aspirin and NSAID use on risk of diverticulitis and diverticular bleeding in a large prospective cohort. METHODS: We studied 47,210 US men in the Health Professionals Follow-up Study cohort who were 40-75 years old at baseline in 1986. We assessed use of aspirin, nonaspirin NSAIDs, and other risk factors biennially. We identified men with diverticulitis or diverticular bleeding based on responses to biennial and supplementary questionnaires. RESULTS: We documented 939 cases of diverticulitis and 256 cases of diverticular bleeding during a 22-year period of follow-up evaluation. After adjustment for risk factors, men who used aspirin regularly (>= 2 times/wk) had a multivariable hazard ratio (HR) of 1.25 (95% confidence interval [CI], 1.05-1.47) for diverticulitis and a HR of 1.70 (95% CI, 1.21-2.39) for diverticular bleeding, compared with nonusers of aspirin and NSAIDs. Use of aspirin at intermediate doses (2-5.9 standard, 325-mg tablets/wk) and frequency (4-6 days/wk) were associated with the highest risk of bleeding (multivariable HR, 2.32; 95% CI, 1.34-4.02, and multivariable HR, 3.13; 95% CI, 1.82-5.38, respectively). Regular users of nonaspirin NSAIDs also had an increased risk of diverticulitis (multivariable HR, 1.72; 95% CI, 1.40-2.11) and diverticular bleeding (multivariable HR, 1.74; 95% CI, 1.15-2.64), compared with men who denied use of these medications. CONCLUSIONS: Regular use of aspirin or NSAIDs is associated with an increased risk of diverticulitis and diverticular bleeding. Patients at risk of diverticular complications should carefully consider the potential risks and benefits of using these medications. C1 [Strate, Lisa L.] Univ Washington, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA. [Strate, Lisa L.] Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Huang, Edward S.; Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Giovannucci, Edward L.; Chan, Andrew T.] Harvard Univ, Sch Med, Channing Lab, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [Liu, Yan L.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Strate, LL (reprint author), Univ Washington, Harborview Med Ctr, Sch Med, 325 9th Ave,Box 359773, Seattle, WA 98104 USA. EM lstrate@u.washington.edu FU National Institutes of Health [CA55075]; American Gastroenterological Association FX This project was funded by a grant from the National Institutes of Health (CA55075); Dr Chan is a Damon Runyon Cancer Research Foundation Clinical Investigator; and Dr Huang is supported by an American Gastroenterological Association Fellow to Faculty Transition Award. NR 38 TC 71 Z9 72 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2011 VL 140 IS 5 BP 1427 EP 1433 DI 10.1053/j.gastro.2011.02.004 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 756QA UT WOS:000290028200023 PM 21320500 ER PT J AU Goldsby, R Chen, Y Raber, S Li, LD Diefenbach, K Shnorhavorian, M Kadan-Lottick, N Kastrinos, F Yasui, Y Stovall, M Oeffinger, K Sklar, C Armstrong, GT Robison, LL Diller, L AF Goldsby, Robert Chen, Yan Raber, Shannon Li, Linda Diefenbach, Karen Shnorhavorian, Margarett Kadan-Lottick, Nina Kastrinos, Fay Yasui, Yutaka Stovall, Marilyn Oeffinger, Kevin Sklar, Charles Armstrong, Gregory T. Robison, Leslie L. Diller, Lisa TI Survivors of Childhood Cancer Have Increased Risk of Gastrointestinal Complications Later in Life SO GASTROENTEROLOGY LA English DT Article DE Tumor; Chemotherapy; Side Effect; Pediatric ID PELVIC RADIOTHERAPY; THERAPY; IRRADIATION; TOXICITY; OUTCOMES AB BACKGROUND & AIMS: Children who receive cancer therapy experience numerous acute gastrointestinal (GI) toxicities. However, the long-term GI consequences have not been extensively studied. We evaluated the incidence of long-term GI outcomes and identified treatment-related risk factors. METHODS: Upper GI, hepatic, and lower GI adverse outcomes were assessed in cases from participants in the Childhood Cancer Survivor Study, a study of 14,358 survivors of childhood cancer who were diagnosed between 1970 and 1986; data were compared with those from randomly selected siblings. The median age at cancer diagnosis was 6.8 years (range, 0-21.0 years), and the median age at outcome assessment was 23.2 years (5.6-48.9 years) for survivors and 26.6 years (1.8-56.2 years) for siblings. Rates of self-reported late GI complications (occurred 5 or more years after cancer diagnosis) were determined and associated with patient characteristics and cancer treatments, adjusting for age, sex, and race. RESULTS: Compared with siblings, survivors had increased risk of late-onset complications of the upper GI tract (rate ratio [RR], 1.8; 95% confidence interval [CI], 1.6-2.0), liver (RR, 2.1; 95% CI, 1.8-2.5), and lower GI tract (RR, 1.9; 95% CI, 1.7-2.2). The RRs for requiring colostomy/ileostomy, liver biopsy, or developing cirrhosis were 5.6 (95% CI, 2.4-13.1), 24.1 (95% CI, 7.5-77.8), and 8.9 (95% CI, 2.0-40.0), respectively. Older age at diagnosis, intensified therapy, abdominal radiation, and abdominal surgery increased the risk of certain GI complications. CONCLUSIONS: Individuals who received therapy for cancer during childhood have an increased risk of developing GI complications later in life. C1 [Goldsby, Robert; Raber, Shannon; Li, Linda] UCSF Benioff Childrens Hosp, San Francisco, CA USA. [Chen, Yan; Yasui, Yutaka] Univ Alberta, Edmonton, AB, Canada. [Diefenbach, Karen; Kadan-Lottick, Nina] Yale Univ, Sch Med, New Haven, CT USA. [Shnorhavorian, Margarett] Seattle Childrens Hosp, Seattle, WA USA. [Kastrinos, Fay] Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Oeffinger, Kevin; Sklar, Charles] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Armstrong, Gregory T.; Robison, Leslie L.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Diller, Lisa] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Goldsby, R (reprint author), Univ Calif San Francisco, Childrens Hosp, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM goldsbyr@peds.ucsf.edu RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU National Cancer Institute [U24 CA55727]; Campini Foundation; Mount Zion Foundation; Swim Across America FX The Childhood Cancer Survivor Study is supported by a grant from the National Cancer Institute (U24 CA55727, L.L. Robison, principal investigator) and the American Lebanese Syrian Associated Charities (St. Jude Children's Research Hospital) in in part by funds from the Campini Foundation, Mount Zion Foundation, and Swim Across America. NR 28 TC 14 Z9 14 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2011 VL 140 IS 5 BP 1464 EP U142 DI 10.1053/j.gastro.2011.01.049 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 756QA UT WOS:000290028200027 PM 21315721 ER PT J AU Villanueva, A Hoshida, Y Battiston, C Tovar, V Sia, D Alsinet, C Cornella, H Liberzon, A Kobayashi, M Kumada, H Thung, SN Bruix, J Newell, P April, C Fan, JB Roayaie, S Mazzaferro, V Schwartz, ME Llovet, JM AF Villanueva, Augusto Hoshida, Yujin Battiston, Carlo Tovar, Victoria Sia, Daniela Alsinet, Clara Cornella, Helena Liberzon, Arthur Kobayashi, Masahiro Kumada, Hiromitsu Thung, Swan N. Bruix, Jordi Newell, Philippa April, Craig Fan, Jian-Bing Roayaie, Sasan Mazzaferro, Vincenzo Schwartz, Myron E. Llovet, Josep M. TI Combining Clinical, Pathology, and Gene Expression Data to Predict Recurrence of Hepatocellular Carcinoma SO GASTROENTEROLOGY LA English DT Article DE Liver Cancer; Relapse; Prognosis; Microarray ID INTRAHEPATIC RECURRENCE; CANCER; SIGNATURE; CLASSIFICATION; PROGNOSIS; RESECTION; PROFILES; PHENOTYPE; SURVIVAL; DEFINES AB BACKGROUND & AIMS: In approximately 70% of patients with hepatocellular carcinoma (HCC) treated by resection or ablation, disease recurs within 5 years. Although gene expression signatures have been associated with outcome, there is no method to predict recurrence based on combined clinical, pathology, and genomic data (from tumor and cirrhotic tissue). We evaluated gene expression signatures associated with outcome in a large cohort of patients with early stage (Barcelona-Clinic Liver Cancer 0/A), single-nodule HCC and heterogeneity of signatures within tumor tissues. METHODS: We assessed 287 HCC patients undergoing resection and tested genome-wide expression platforms using tumor (n = 287) and adjacent nontumor, cirrhotic tissue (n = 226). We evaluated gene expression signatures with reported prognostic ability generated from tumor or cirrhotic tissue in 18 and 4 reports, respectively. In 15 additional patients, we profiled samples from the center and periphery of the tumor, to determine stability of signatures. Data analysis included Cox modeling and random survival forests to identify independent predictors of tumor recurrence. RESULTS: Gene expression signatures that were associated with aggressive HCC were clustered, as well as those associated with tumors of progenitor cell origin and those from nontumor, adjacent, cirrhotic tissues. On multivariate analysis, the tumor-associated signature G3-proliferation (hazard ratio [HR], 1.75; P = .003) and an adjacent poor-survival signature (HR, 1.74; P = .004) were independent predictors of HCC recurrence, along with satellites (HR, 1.66; P = .04). Samples from different sites in the same tumor nodule were reproducibly classified. CONCLUSIONS: We developed a composite prognostic model for HCC recurrence, based on gene expression patterns in tumor and adjacent tissues. These signatures predict early and overall recurrence in patients with HCC, and complement findings from clinical and pathology analyses. C1 [Villanueva, Augusto; Tovar, Victoria; Sia, Daniela; Alsinet, Clara; Cornella, Helena; Bruix, Jordi; Llovet, Josep M.] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Liver Unit, Barcelona Clin Liver Canc Grp,HCC Translat Res La, E-08036 Barcelona, Spain. [Villanueva, Augusto; Tovar, Victoria; Sia, Daniela; Alsinet, Clara; Cornella, Helena; Bruix, Jordi; Llovet, Josep M.] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain. [Hoshida, Yujin; Liberzon, Arthur] Broad Inst, Canc Program, Cambridge, MA USA. [Hoshida, Yujin; Llovet, Josep M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Battiston, Carlo; Sia, Daniela; Mazzaferro, Vincenzo] Natl Canc Inst, Gastrointestinal Surg & Liver Transplantat Unit, I-20133 Milan, Italy. [Kobayashi, Masahiro; Kumada, Hiromitsu] Toranomon Gen Hosp, Tokyo, Japan. [Thung, Swan N.; Roayaie, Sasan; Schwartz, Myron E.; Llovet, Josep M.] Mt Sinai Sch Med, Div Liver Dis, Mt Sinai Liver Canc Program, New York, NY USA. [Thung, Swan N.; Roayaie, Sasan; Schwartz, Myron E.; Llovet, Josep M.] Mt Sinai Sch Med, Div Pathol, Mt Sinai Liver Canc Program, New York, NY USA. [Thung, Swan N.; Roayaie, Sasan; Schwartz, Myron E.; Llovet, Josep M.] Mt Sinai Sch Med, Div Surg Oncol, Mt Sinai Liver Canc Program, New York, NY USA. [Newell, Philippa] Providence Portland Med Ctr, Oregon Clin PC, Hepatobiliary Surg Sect, Portland, OR USA. [April, Craig; Fan, Jian-Bing] Illumina Inc, San Diego, CA USA. Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain. RP Llovet, JM (reprint author), Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Liver Unit, Barcelona Clin Liver Canc Grp,HCC Translat Res La, Villarroel 170, E-08036 Barcelona, Spain. EM jmllovet@clinic.ub.es RI Augusto, Villanueva/F-9378-2012; Llovet, Josep M /D-4340-2014; Mazzaferro, Vincenzo/C-2726-2017; Battiston, Carlo/E-8771-2017; OI Augusto, Villanueva/0000-0003-3585-3727; Llovet, Josep M /0000-0003-0547-2667; Mazzaferro, Vincenzo/0000-0002-4013-8085; Battiston, Carlo/0000-0001-6826-7893; Bruix, Jordi/0000-0002-9826-0753 FU Augusto Villanueva is a recipient of a Sheila Sherlock fellowship; Instituto de Salud Carlos III [ISCIII/FIS FI09/00605, ISCIII/FIS PI 05-0150]; Spanish National Health Institute [SAF-2007-61898, SAF-2010-16055]; US National Institutes of Health [5R01CA121941]; US National Institutes of Diabetes and Digestive and Kidney Diseases [1R01DK076986-01]; European Commission [259744]; Samuel Waxman Cancer Research Foundation; Landon Foundation-American Association for Cancer Research FX Augusto Villanueva is a recipient of a Sheila Sherlock fellowship (European Association for the Study of the Liver); Clara Alsinet is supported by a grant from the Instituto de Salud Carlos III (ISCIII/FIS FI09/00605); Helena Cornella is supported by a grant from the Spanish National Health Institute (SAF-2007-61898); Arthur Liberzon is supported by a grant from the US National Institutes of Health (5R01CA121941); Jordi Bruix is supported by a grant from the Instituto de Salud Carlos III (ISCIII/FIS PI 05-0150); and Josep Llovet is supported by grants from the US National Institutes of Diabetes and Digestive and Kidney Diseases (1R01DK076986-01), European Commission-FP7 Framework (HEPTROMIC, proposal no: 259744), the Samuel Waxman Cancer Research Foundation and the Spanish National Health Institute (SAF-2007-61898 and SAF-2010-16055). The study was supported by the Landon Foundation-American Association for Cancer Research Innovator Award for International Collaboration in Cancer Research. NR 42 TC 120 Z9 122 U1 1 U2 14 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 MAY PY 2011 VL 140 IS 5 BP 1501 EP U188 DI 10.1053/j.gastro.2011.02.006 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 756QA UT WOS:000290028200031 PM 21320499 ER PT J AU Gourcerol, G Wu, SV Yuan, PQ Pham, H Miampamba, M Larauche, M Sanders, P Amano, T Mulak, A Im, E Pothoulakis, C Rivier, J Tache, Y Million, M AF Gourcerol, Guillaume Wu, S. Vincent Yuan, Pu-Qing Hung Pham Miampamba, Marcel Larauche, Muriel Sanders, Paul Amano, Tomofumi Mulak, Agata Im, Eunok Pothoulakis, Charalabos Rivier, Jean Tache, Yvette Million, Mulugeta TI Activation of Corticotropin-Releasing Factor Receptor 2 Mediates the Colonic Motor Coping Response to Acute Stress in Rodents SO GASTROENTEROLOGY LA English DT Article DE Colonic Contraction; Myenteric Neurons; nNOS; Stress Response ID GIANT MIGRATING CONTRACTIONS; INFLAMMATORY-BOWEL-DISEASE; ENTERIC NERVOUS-SYSTEM; C-FOS EXPRESSION; MYENTERIC NEURONS; CRF RECEPTORS; PHARMACOLOGICAL CHARACTERIZATION; NITRERGIC REGULATION; TRANSGENIC MICE; CONSCIOUS RATS AB BACKGROUND & AIMS: Corticotropin-releasing factor receptor-1 (CRF1) mediates the stress-induced colonic motor activity. Less is known about the role of CRF(2) in the colonic response to stress. METHODS: We studied colonic contractile activity in rats and CRF(2)-/-, CRF-overexpressing, and wild-type mice using still manometry; we analyzed defecation induced by acute partial-restraint stress (PRS), and/or intraperitoneal injection of CRF ligands. In rats, we monitored activation of the colonic longitudinal muscle myenteric plexus (LMMP) neurons and localization of CRF(1) and CRF(2) using immunohistochemical and immunoblot analyses. We measured phosphorylation of extracellular signal-regulated kinase 1/2 by CRF ligands in primary cultures of LMMP neurons (PC-LMMPn) and cyclic adenosine monophosphate (cAMP) production in human embryonic kidney-293 cells transfected with CRF(1) and/or CRF(2). RESULTS: In rats, a selective agonist of CRF(2) (urocortin 2) reduced CRF-induced defecation (> 50%), colonic contractile activity, and Fos expression in the colonic LMMP. A selective antagonist of CRF(2) (astressin(2)-B) increased these responses. Urocortin 2 reduced PRS-induced colonic contractile activity in wild-type and CRF-overexpressing mice, whereas disruption of CRF(2) increased PRS-induced colonic contractile activity and CRF-induced defecation. CRF(2) colocalized with CRF(1) and neuronal nitric oxide synthase in the rat colon, LMMP, and PC-LMMPn. CRF-induced phosphorylation of extracellular signal-regulated kinase in PC-LMMPn; this was inhibited or increased by a selective antagonist of CRF(1) (NBI35965) or astressin(2)-B, respectively. The half maximal effective concentration, EC(50), for the CRF-induced cAMP response was 8.6 nmol/L in human embryonic kidney-293 cells that express only CRF(1); this response was suppressed 10-fold in cells that express CRF(1) and CRF(2). CONCLUSIONS: In colon tissues of rodents, CRF(2) activation inhibits CRF(1) signaling in myenteric neurons and the stress-induced colonic motor responses. Disruption of CRF(2) function impairs colonic coping responses to stress. C1 [Million, Mulugeta] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. [Gourcerol, Guillaume; Wu, S. Vincent; Yuan, Pu-Qing; Hung Pham; Miampamba, Marcel; Larauche, Muriel; Sanders, Paul; Amano, Tomofumi; Mulak, Agata; Im, Eunok; Pothoulakis, Charalabos; Tache, Yvette; Million, Mulugeta] Univ Calif Los Angeles, Dept Med, Div Digest Dis, Ctr Neurobiol Stress, Los Angeles, CA 90073 USA. [Gourcerol, Guillaume] Univ Rouen, Rouen Univ Hosp, Dept Physiol & Appareil Digestif Environm Nutr AD, Equipe Accueil 4311,IFRMP23, F-76821 Mont St Aignan, France. [Rivier, Jean] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. RP Million, M (reprint author), Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Digest Dis Res Ctr, CURE, CURE Bldg 115,Room 118B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM millionmulugeta@mednet.ucla.edu OI Larauche, Muriel/0000-0003-3320-3675; Sanders, Paul/0000-0002-2915-5714 FU National Institute for Diabetes and Digestive and Kidney Diseases [R21 DK-068155, RO1 DK078676, DK-57238, DK-41301]; VA Career Scientist Award; French Foreign Office; French Society of Gastroenterology; NIH [DK PO1-26741, P01 DK 33506, KO1 DK083336] FX This work was supported by National Institute for Diabetes and Digestive and Kidney Diseases grants R21 DK-068155 and RO1 DK078676 (M.M.), DK-57238 (Y.T.), and DK-41301 (Center Grant, Animal core, Y.T.); a VA Career Scientist Award (Y.T.); the French Foreign Office (Egide program); the French Society of Gastroenterology (G.G.); NIH DK PO1-26741 (J.R.); NIH P01 DK 33506 (C.P.); NIH KO1 DK083336 (E.I.). NR 55 TC 27 Z9 27 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2011 VL 140 IS 5 BP 1586 EP U313 DI 10.1053/j.gastro.2011.01.039 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 756QA UT WOS:000290028200039 PM 21277852 ER PT J AU Popov, Y Sverdlov, DY Sharma, AK Bhaskar, KR Li, SY Freitag, TL Lee, J Dieterich, W Melino, G Schuppan, D AF Popov, Yury Sverdlov, Deanna Y. Sharma, Anisha K. Bhaskar, K. Ramakrishnan Li, Shaoyong Freitag, Tobias L. Lee, James Dieterich, Walburga Melino, Gerry Schuppan, Detlef TI Tissue Transglutaminase Does Not Affect Fibrotic Matrix Stability or Regression of Liver Fibrosis in Mice SO GASTROENTEROLOGY LA English DT Article DE Cirrhosis; Liver Disease; Mouse Model; Fibrosis Gene Expression ID HEPATIC STELLATE CELLS; CROSS-LINKING; ANTIFIBROTIC THERAPIES; EXTRACELLULAR-MATRIX; BILIARY FIBROSIS; CELIAC-DISEASE; COLLAGEN; CIRRHOSIS; GROWTH; PHAGOCYTOSIS AB BACKGROUND & AIMS: The ubiquitous cross-linking enzyme tissue transglutaminase (TG2) has been implicated in irreversible collagen stabilization in liver fibrosis, although functional evidence is lacking. We studied the contribution of TG2 to hepatic fibrotic matrix stability, as well as liver fibrosis progression and regression in TG2-deficient mice. METHODS: Advanced liver fibrosis was induced by carbon tetrachloride or thioacetamide in TG2(-/-) mice and their wild-type littermates to study fibrosis progression and its spontaneous regression for up to 36 weeks. Pattern and extent of fibrosis were analyzed by histology and hepatic hydroxyproline quantification. Dynamic changes in hepatic matrix cross-linking were assessed by stepwise collagen extraction. Expression of 7 TGs and fibrosis-related genes was determined by quantitative reverse-transcription polymerase chain reaction. RESULTS: Transglutaminase activity was increased in fibrosis, and the level of TG2 messenger RNA correlated with the expression of fibrosis-related genes. Biochemical analysis revealed progressive collagen stabilization, with an up to 6-fold increase in the highly crosslinked, pepsin-insoluble fraction (26%). In TG2(-/-) mice, hepatic TG activity was significantly decreased, but chronic administration of carbon tetrachloride or thioacetamide led to a comparable extent and pattern of liver fibrosis, as in wild-type mice. In TG2(-/-) mice, the composition of hepatic collagen fractions and levels of fibrosis-related transcripts were unchanged, and fibrosis reversal was not facilitated. CONCLUSIONS: TG2 and TG activity are up-regulated during hepatic fibrosis progression, but do not contribute to fibrogenesis or stabilization of the collagen matrix. TG2 deletion does not promote regression of liver fibrosis. TG2-independent collagen cross-linking is a remarkable feature of progressing hepatic fibrosis and represents an important therapeutic target for liver fibrosis. C1 [Popov, Yury; Sverdlov, Deanna Y.; Sharma, Anisha K.; Bhaskar, K. Ramakrishnan; Li, Shaoyong; Freitag, Tobias L.; Schuppan, Detlef] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol & Hepatol, Boston, MA 02215 USA. [Lee, James] Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA. [Dieterich, Walburga] Univ Erlangen Nurnberg, Dept Med 1, Erlangen, Germany. [Melino, Gerry] Univ Roma Tor Vergata, Rome, Italy. RP Schuppan, D (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol & Hepatol, Dana 501,330 Brookline Ave, Boston, MA 02215 USA. EM dschuppa@bidmc.harvard.edu RI LI, Shaoyong/D-1052-2013; OI Popov, Yury V./0000-0001-7973-942X FU Beth Israel Deaconess Medical Center; National Institutes of Health [1 R21 DK076873-01A1, 1 R21 DK075857-01A2]; European Association FX This work was supported by an appointment grant by the Beth Israel Deaconess Medical Center, and the National Institutes of Health (grants NIH 1 R21 DK076873-01A1 and 1 R21 DK075857-01A2) to D.S. Y.P. was the recipient of a Sheila Sherlock fellowship of the European Association for the Study of the Liver. NR 37 TC 46 Z9 46 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2011 VL 140 IS 5 BP 1642 EP 1652 DI 10.1053/j.gastro.2011.01.040 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 756QA UT WOS:000290028200044 PM 21277850 ER PT J AU Villablanca, EJ Cassani, B von Andrian, UH Mora, JR AF Villablanca, Eduardo J. Cassani, Barbara von Andrian, Ulrich H. Mora, J. Rodrigo TI Blocking Lymphocyte Localization to the Gastrointestinal Mucosa as a Therapeutic Strategy for Inflammatory Bowel Diseases SO GASTROENTEROLOGY LA English DT Article DE CCR9; alpha 4 beta 7; IBD; Ulcerative Colitis; Crohn's Disease ID ACTIVE CROHNS-DISEASE; REGULATORY T-CELLS; REFRACTORY ULCERATIVE-COLITIS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; THYMUS-EXPRESSED CHEMOKINE; PLACEBO-CONTROLLED TRIAL; INTERCELLULAR-ADHESION MOLECULE-1; ANTIINTERFERON-GAMMA ANTIBODY; PLASMACYTOID DENDRITIC CELLS; ANTI-CD4 MONOCLONAL-ANTIBODY AB Lymphocyte migration (homing) to specific tissues has an important role during protective and pathological immune responses, including inflammatory bowel diseases. Lymphocytes use integrin alpha 4 beta 7 and the chemokine receptor CCR9 to localize to the gastrointestinal mucosa; their respective ligands, mucosal addressin cell adhesion molecule-1 and CCL25, are displayed on endothelial cells in intestinal postcapillary venules. Although gastrointestinal-homing receptors are required for lymphocyte migration to the intestine in the noninflamed steady state, their role during inflammation is a matter of debate. Reagents designed to block interactions between these receptors and their ligands have had variable degrees of success in animal models of inflammatory bowel diseases and patients. We discuss the mechanisms involved in lymphocyte localization to the intestinal mucosa and how they can be applied to therapy for inflammatory bowel diseases. C1 [Villablanca, Eduardo J.; Cassani, Barbara; Mora, J. Rodrigo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA USA. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. EM uva@hms.harvard.edu; j_rodrigo_mora@hms.harvard.edu RI von Andrian, Ulrich/A-5775-2008; Villablanca, Eduardo/E-1380-2016; Cassani, Barbara/K-3871-2016 OI Villablanca, Eduardo/0000-0001-9522-9729; Cassani, Barbara/0000-0002-4115-8109 FU Crohn's & Colitis Foundation of America (CCFA); EMBO postdoctoral fellowship; National Institutes of Health (NIH) [DP2 2009A054301]; Cancer Research Institute (CRI); Howard H. Goodman (MGH); Massachusetts Life Science Center (MLSC) FX EJV was supported by a postdoctoral fellowship from Crohn's & Colitis Foundation of America (CCFA). BC was supported by an EMBO postdoctoral fellowship. UHvA was supported by grants from National Institutes of Health (NIH). JRM was supported by grants from CCFA, Cancer Research Institute (CRI), Howard H. Goodman (MGH), Massachusetts Life Science Center (MLSC), and NIH DP2 2009A054301. NR 122 TC 33 Z9 34 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2011 VL 140 IS 6 BP 1776 EP U104 DI 10.1053/j.gastro.2011.02.015 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 756MT UT WOS:000290016700010 PM 21530744 ER PT J AU Cuker, A Arepally, G Crowther, MA Rice, L Datko, F Hook, K Kuter, DJ Ortel, TL Konkle, BA Cines, DB AF Cuker, Adam Arepally, Gowthami Crowther, Mark A. Rice, Lawrence Datko, Farrah Hook, Karen Kuter, David J. Ortel, Thomas L. Konkle, Barbara A. Cines, Douglas B. TI Construction and validation of a clinical scoring model for heparin-induced thrombocytopenia (HIT) SO HAEMOPHILIA LA English DT Meeting Abstract C1 [Cuker, Adam; Datko, Farrah; Hook, Karen; Cines, Douglas B.] Univ Penn, Philadelphia, PA 19104 USA. [Arepally, Gowthami; Ortel, Thomas L.] Duke Univ, Durham, NC USA. [Crowther, Mark A.] McMaster Univ, Hamilton, ON, Canada. [Rice, Lawrence] Weill Cornell Med Coll, Houston, TX USA. [Kuter, David J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Konkle, Barbara A.] Puget Sound Blood Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD MAY PY 2011 VL 17 IS 3 BP 558 EP 559 PG 2 WC Hematology SC Hematology GA 754YQ UT WOS:000289894200046 ER PT J AU Grabowski, EF Cheung, M Biliouris, EE Kushak, RI Van Cott, E AF Grabowski, Eric F. Cheung, Ming Biliouris, Emily E. Kushak, Rafail I. Van Cott, Elizabeth TI Reduced area/platelet aggregate in platelet aggregation imaged using epifluorescence digital videomicroscopy in a high shear rate blood flow allows for the sensitive and specific diagnosis of vWD SO HAEMOPHILIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD MAY PY 2011 VL 17 IS 3 BP 559 EP 559 PG 1 WC Hematology SC Hematology GA 754YQ UT WOS:000289894200048 ER PT J AU Grabowski, EF Skaria, A Cheung, M Kushak, RI Van Cott, E AF Grabowski, Eric F. Skaria, Amy Cheung, Ming Kushak, Rafail I. Van Cott, Elizabeth TI Reduced platelet adhesion/aggregation under high shear rate blood flow supports a definitive diagnosis of Type 1 von Willebrand disease SO HAEMOPHILIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD MAY PY 2011 VL 17 IS 3 BP 565 EP 565 PG 1 WC Hematology SC Hematology GA 754YQ UT WOS:000289894200077 ER PT J AU Wolk, DA Dunfee, KL Dickerson, BC Aizenstein, HJ DeKosky, ST AF Wolk, David A. Dunfee, Kathryn L. Dickerson, Bradford C. Aizenstein, Howard J. DeKosky, Steven T. TI A Medial Temporal Lobe Division of Labor: Insights From Memory in Aging and Early Alzheimer Disease SO HIPPOCAMPUS LA English DT Article DE memory; recollection; familiarity; Alzheimer's disease; medial temporal lobe ID MILD COGNITIVE IMPAIRMENT; RECOGNITION MEMORY; MR-IMAGES; FAMILIARITY; RECOLLECTION; HIPPOCAMPUS; BRAIN; SEGMENTATION; DAMAGE; SINGLE AB Dual process theories of recognition memory posit that recollection and familiarity represent dissociable processes. Animal studies and human functional imaging experiments support an anatomic dissociation of these processes in the medial temporal lobes (MTL). By this hypothesis, recollection may be dependent on the hippocampus, while familiarity appears to rely on extrahippocampal MTL (ehMTL) structures, particularly perirhinal and lateral entorhinal cortices. Despite these findings, the dual process model and these anatomic mappings remain controversial, in part because the study of patients with lesions to the MTL has been limited and has revealed predominantly single dissociations. We examined measures of recollection and familiarity in three groups (normal older adults, amnesic-mild cognitive impairment, Alzheimer's disease) in which these memory measures and the relative integrity of MTL structures are variable, thus enhancing our power to detect MTL-memory relationships. Recollection and familiarity and volumes of hippocampus and ehMTL, defined as a region including entorhinal/perirhinal cortices and parahippocampus, were measured. Regression analyses revealed a stronger relationship of recollection with the hippocampus compared to ehMTL, while familiarity was more highly related to ehMTL compared to hippocampus. These results are consistent with a division of labor in the MTL and the dual process model. (C) 2010 Wiley-Liss, Inc. C1 [Wolk, David A.] Univ Penn, Penn Memory Ctr, Philadelphia, PA 19104 USA. [Wolk, David A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Wolk, David A.] Univ Penn, Alzheimer Dis Ctr, Philadelphia, PA 19104 USA. [Dunfee, Kathryn L.; Aizenstein, Howard J.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Frontotemporal Dementia Unit, Boston, MA 02114 USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Aizenstein, Howard J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. RP Wolk, DA (reprint author), Univ Penn, Penn Memory Ctr, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM david.wolk@uphs.upenn.edu FU National Institute of Aging [AG028018, AG05133, AG29411, AG29840]; Alzheimer's Association FX Grant sponsor: National Institute of Aging; Grant numbers: AG028018, AG05133, AG29411, AG29840; Grant sponsor: the Alzheimer's Association. NR 32 TC 26 Z9 26 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PD MAY PY 2011 VL 21 IS 5 BP 461 EP 466 DI 10.1002/hipo.20779 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 755SJ UT WOS:000289956400001 PM 20232383 ER PT J AU Fuchsluger, TA Jurkunas, U Kazlauskas, A Dana, R AF Fuchsluger, Thomas A. Jurkunas, Ula Kazlauskas, Andrius Dana, Reza TI Corneal Endothelial Cells Are Protected from Apoptosis by Gene Therapy SO HUMAN GENE THERAPY LA English DT Article ID ORGAN-CULTURED CORNEAS; GRAFT-REJECTION; FOLLOW-UP; IN-VIVO; DEATH; TRANSPLANTATION; STORAGE; KERATOPLASTY; TRANSDUCTION; RECOGNITION AB Corneal grafting is the most prevalent form of transplantation. Corneal endothelial cells (ECs), which form a monolayer of the cornea with minimal proliferative potential, are pivotal for maintenance of corneal clarity. Loss of EC viability and apoptosis leads to graft failure posttransplantation and reduces the quality of donor corneas in storage, such that up to 30% do not meet selection criteria and must be discarded. The current study investigates antiapoptotic effects of transduced mammalian Bcl-x(L) and baculoviral p35 on human ECs. Multiple apoptotic cell features are observed while inducing apoptosis either via the extrinsic (death receptor) or intrinsic (mitochondrial) apoptotic pathway. Human ECs were studied under three experimental conditions: (1) as an immortalized cell line, (2) as primary cells, and (3) in an intact cornea. Interestingly, in primary EC suspensions, Bcl-xL was protective against apoptosis mediated via both pathways. However, p35 was significantly more protective against apoptosis mediated via the intrinsic pathway compared with Bcl-xL. Our results provide critical insight into the role of apoptotic pathways in the maintenance of EC viability and the efficacy with which these protective proteins exert their effect. These observations could form the basis for future applications of antiapoptotic gene therapy to corneal preservation aiming to reduce both graft failure after transplantation as well as donor corneal damage during storage. C1 [Fuchsluger, Thomas A.; Jurkunas, Ula; Kazlauskas, Andrius; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. [Fuchsluger, Thomas A.] Univ Duisburg Essen, Essen Univ Hosp, Ctr Ophthalmol, D-45122 Essen, Germany. [Jurkunas, Ula; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU NIH [R01EY012963, K24EY019098]; Lew R. Wasserman Merit Award; German Research Foundation [DFG/FU 726/1-1]; Eye Bank Association of America FX This work was supported by NIH R01EY012963 (R.D.), K24EY019098 (R.D.), Research to Prevent Blindness, a Lew R. Wasserman Merit Award (R.D.), the German Research Foundation (DFG/FU 726/1-1; T.F.), and the Eye Bank Association of America (T.F.). The authors thank Tissue Banks International and the Lions Eye Institute for Transplant and Research (Tampa, FL) for providing corneas for research purposes. The authors thank Kim Fechtel for the critical review of the manuscript. NR 44 TC 15 Z9 15 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY PY 2011 VL 22 IS 5 BP 549 EP 558 DI 10.1089/hum.2010.079 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 754VY UT WOS:000289887000005 PM 21158568 ER PT J AU Ullman-Cullere, MH Mathew, JP AF Ullman-Cullere, Mollie H. Mathew, Jomol P. TI Emerging Landscape of Genomics in the Electronic Health Record for Personalized Medicine SO HUMAN MUTATION LA English DT Article DE electronic health record; personalized medicine; clinical genomics; genetics; healthcare informatics; biomedical informatics; cancer genetics ID INFORMATION-TECHNOLOGY; MOLECULAR PATHOLOGY; CANCER; CARE; GUIDELINES; DATABASES; TOOLS AB The Information Technology (IT) roadmap for personalized medicine requires Electronic Health Records (EHRs), extension of Healthcare IT (HIT) standards, and understanding of how genetics/genomics should be integrated into the clinical applications. For reduced overall costs and development times, these three initiatives should run in parallel. EHRs must contain structured data and infrastructure that enables quality analysis, Clinical Decision Support (CDS) and messaging within the healthcare information network. Fortunately, as a result of sustained financial commitment to nongenetic-based healthcare, the industry has HIT data standards and understanding of EHR functionality that improves patient safety and outcomes while reducing overall healthcare costs. However, the HIT standards and EHR functional requirements, needed for personalized medicine, are only beginning to support simple genetic tests and need significant extension. In addition, our understanding of the clinical implications of genomic data is evolving and translation of new discovery into clinical care remains a challenge. Therefore, priority areas include CDS, educational resources, and knowledgebases for the EHR, clinical and research data warehouses, messaging frameworks, and continued review of healthcare policies and regulations supporting personalized medicine. Where core infrastructure remains to be developed and implemented, funding is needed for pilot projects, data standards, policy, and stakeholder collaboration. Hum Mutat 32:512-516, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Ullman-Cullere, Mollie H.; Mathew, Jomol P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ullman-Cullere, MH (reprint author), Dana Farber Canc Inst, 44 Binney St,OS 358, Boston, MA 02115 USA. EM Mollie_Ullman-Cullere@DFCI.Harvard.edu NR 46 TC 19 Z9 21 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD MAY PY 2011 VL 32 IS 5 SI SI BP 512 EP 516 DI 10.1002/humu.21456 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 756AP UT WOS:000289984100004 PM 21309042 ER PT J AU Kahle, KT Staley, KJ AF Kahle, Kristopher T. Staley, Kevin J. TI Response to "A Claim for Caution in the Use of Promising Bumetanide to Treat Neonatal Seizures" SO JOURNAL OF CHILD NEUROLOGY LA English DT Letter ID DEVELOPING BRAIN; NKCC1; GABA; PHARMACOKINETICS; INTELLIGENCE; INHIBITOR; INFANTS; NEURONS; MODEL C1 [Kahle, Kristopher T.; Staley, Kevin J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kahle, Kristopher T.; Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA. RP Kahle, KT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 22 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 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD MAY PY 2011 VL 26 IS 5 BP 658 EP 659 DI 10.1177/0883073811401400 PG 2 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 756YX UT WOS:000290051800024 ER PT J AU McGrath, LM Pennington, BF Shanahan, MA Santerre-Lemmon, LE Barnard, HD Willcutt, EG DeFries, JC Olson, RK AF McGrath, Lauren M. Pennington, Bruce F. Shanahan, Michelle A. Santerre-Lemmon, Laura E. Barnard, Holly D. Willcutt, Erik G. DeFries, John C. Olson, Richard K. TI A multiple deficit model of reading disability and attention-deficit/hyperactivity disorder: searching for shared cognitive deficits SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Reading disability; attention-deficit; hyperactivity disorder; processing speed; comorbidity; multiple deficit model ID HYPERACTIVITY DISORDER; ENVIRONMENTAL-INFLUENCES; INHIBITORY CONTROL; PROCESSING SPEED; ENERGETIC MODEL; CHILDREN; ADHD; ADOLESCENTS; COMORBIDITY; DYSLEXIA AB Background: This study tests a multiple cognitive deficit model of reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), and their comorbidity. Methods: A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique predictor of RD and response inhibition as a unique predictor of ADHD. Processing speed, naming speed, and verbal working memory were modeled as potential shared cognitive deficits. Results: Model fit indices from the SEM indicated satisfactory fit. Closer inspection of the path weights revealed that processing speed was the only cognitive variable with significant unique relationships to RD and ADHD dimensions, particularly inattention. Moreover, the significant correlation between reading and inattention was reduced to non-significance when processing speed was included in the model, suggesting that processing speed primarily accounted for the phenotypic correlation (or comorbidity) between reading and inattention. Conclusions: This study illustrates the power of a multiple deficit approach to complex developmental disorders and psychopathologies, particularly for exploring comorbidities. The theoretical role of processing speed in the developmental pathways of RD and ADHD and directions for future research are discussed. C1 [McGrath, Lauren M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [McGrath, Lauren M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Pennington, Bruce F.; Santerre-Lemmon, Laura E.] Univ Denver, Denver, CO 80208 USA. [Shanahan, Michelle A.; Barnard, Holly D.] Univ Illinois, Chicago, IL USA. [Willcutt, Erik G.; DeFries, John C.; Olson, Richard K.] Univ Colorado, Boulder, CO 80309 USA. RP McGrath, LM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 6th Floor,185 Cambridge St, Boston, MA 02114 USA. EM mcgrath@pngu.mgh.harvard.edu OI McGrath, Lauren/0000-0001-6928-9656 FU NIH [HD 27802]; [HD 47264]; [DC 87262]; [MH 62120]; [MH 63941] FX This work was supported by NIH grant HD 27802. The authors were also supported by HD 47264, DC 87262, MH 62120, and MH 63941 during the preparation of this report. Thanks to Micaela Christopher and Angela Friend for consultation regarding SEM approaches. The valuable contributions of the children, their families, and the staff members of the many school districts who participated in this study are gratefully acknowledged. NR 48 TC 76 Z9 79 U1 2 U2 47 PU WILEY-BLACKWELL 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 MAY PY 2011 VL 52 IS 5 BP 547 EP 557 DI 10.1111/j.1469-7610.2010.02346.x PG 11 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 751PZ UT WOS:000289631400006 PM 21126246 ER PT J AU Ramalingam, SS Lee, JW Belani, CP Aisner, SC Kolesar, J Howe, C Velasco, MR Schiller, JH AF Ramalingam, Suresh S. Lee, Ju-Whei Belani, Chandra P. Aisner, Seena C. Kolesar, Jill Howe, Craig Velasco, Mario R. Schiller, Joan H. TI Cetuximab for the Treatment of Advanced Bronchioloalveolar Carcinoma (BAC): An Eastern Cooperative Oncology Group Phase II Study (ECOG 1504) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; CONSENSUS CONFERENCE; TRIAL; GEFITINIB; ADENOCARCINOMA; MUTATIONS; THERAPY; EPIDEMIOLOGY; FEATURES; FLEX AB Purpose Inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase have demonstrated modest anticancer activity in advanced bronchioloalveolar carcinoma (BAC). We conducted a phase II study to evaluate cetuximab for the treatment of advanced BAC. Patients and Methods Patients with advanced-stage pure BAC or adenocarcinoma with BAC features, fewer than two prior chemotherapy regimens, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 were eligible. Those with prior EGFR inhibitor therapy were excluded. Cetuximab was given as a weekly intravenous infusion at 250 mg/m(2) after an initial loading dose of 400 mg/m(2) in week 1. The primary end point was determination of response rate. EGFR and KRAS mutations were evaluated by pyrosequencing. Results Seventy-two patients were enrolled and 68 met eligibility requirements. Characteristics of patients included median age, 71 years; sex, 57% females; PS 0 or 1, 88% of patients; and smoking status, 19% never-smokers. Central pathology review confirmed the diagnosis in 45 of 49 available specimens. Approximately 50% of patients received more than two cycles of therapy (> 8 weeks). Skin rash was the most common toxicity (grade 3, 15%). The confirmed response rate was 7%, and stable disease was observed in 35%. The median survival and progression-free survival were 13 and 3.3 months, respectively. Only one of the six patients with an EGFR mutation and one of the seven patients with a KRAS mutation had a partial response. Conclusion Cetuximab was associated with modest efficacy in patients with advanced BAC, despite a low response rate. EGFR and KRAS mutations were not predictive of response to cetuximab. C1 Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Penn State Canc Inst, Hershey, PA USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Wisconsin, Madison, WI USA. United Hosp, St Paul, MN USA. Decatur Mem Hosp, Decatur, IL USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Ramalingam, SS (reprint author), 1365 Clifton Rd NE,Rm C-3090, Atlanta, GA 30322 USA. EM suresh.ramalingam@emory.edu OI Belani, Chandra/0000-0001-5049-5329 FU National Cancer Institute [CA23318, CA66636, CA21115, CA21076]; National Institutes of Health; Department of Health and Human Services, Public Health Service FX Supported in part by Grants No. CA23318, CA66636, CA21115, and CA21076 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Public Health Service. NR 23 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 MAY 1 PY 2011 VL 29 IS 13 BP 1709 EP 1714 DI 10.1200/JCO.2010.33.4094 PG 6 WC Oncology SC Oncology GA 757MN UT WOS:000290090400026 PM 21422434 ER PT J AU D'Amico, AV Chen, MH AF D'Amico, Anthony V. Chen, Ming-Hui TI Do the Data Support the Comorbidity Hypothesis for the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Results? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID MORTALITY C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Storrs, CT USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 1 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 MAY 1 PY 2011 VL 29 IS 13 BP E388 EP E389 DI 10.1200/JCO.2011.35.0249 PG 2 WC Oncology SC Oncology GA 757MN UT WOS:000290090400012 ER PT J AU Maduekwe, UN Yoon, SS AF Maduekwe, Ugwuji N. Yoon, Sam S. TI An Evidence-Based Review of the Surgical Treatment of Gastric Adenocarcinoma SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Review DE Gastric cancer; Surgery; Gastrectomy; Lymphadenectomy ID RANDOMIZED CONTROLLED-TRIAL; LYMPH-NODE DISSECTION; ASSISTED DISTAL GASTRECTOMY; ROUX-EN-Y; MARUYAMA COMPUTER-PROGRAM; OPEN SUBTOTAL GASTRECTOMY; BILLROTH-I GASTRECTOMY; CANCER SURGERY; NEOADJUVANT CHEMOTHERAPY; LAPAROSCOPIC GASTRECTOMY AB The management of gastric adenocarcinoma continues to evolve. Chemotherapy is being increasingly used in both the neoadjuvant and adjuvant setting. Surgical resection of the stomach and regional lymph nodes remains the mainstay of potentially curative therapy, but significant regional differences persist in the surgical management. This review provides an update on the current literature regarding the preoperative evaluation and staging, extent of gastric resection, extent of lymph node resection, and adjuvant therapy for patients with gastric adenocarcinoma. C1 [Maduekwe, Ugwuji N.; Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Maduekwe, Ugwuji N.; Yoon, Sam S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yoon, Sam S.] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. RP Yoon, SS (reprint author), Massachusetts Gen Hosp, Dept Surg, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA. EM syoon@partners.org NR 95 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY PY 2011 VL 15 IS 5 BP 730 EP 741 DI 10.1007/s11605-011-1477-y PG 12 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 753TX UT WOS:000289803700004 PM 21399886 ER PT J AU Ebrahimi, F Malo, MS Alam, SN Moss, AK Yammine, H Ramasamy, S Biswas, B Chen, KT Muhammad, N Mostafa, G Warren, HS Hohmann, EL Hodin, RA AF Ebrahimi, Farzad Malo, Madhu S. Alam, Sayeda Nasrin Moss, Angela K. Yammine, Halim Ramasamy, Sundaram Biswas, Brishti Chen, Kathryn T. Muhammad, Nur Mostafa, Golam Warren, H. Shaw Hohmann, Elizabeth L. Hodin, Richard A. TI Local Peritoneal Irrigation with Intestinal Alkaline Phosphatase Is Protective Against Peritonitis in Mice SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Sepsis; Cecal ligation and puncture; Intestinal alkaline phosphatase; Peritonitis ID TUMOR-NECROSIS-FACTOR; SECONDARY PERITONITIS; CECAL LIGATION; BACTERIAL-DNA; SEVERE SEPSIS; SEPTIC SHOCK; LUNG INJURY; IN-VIVO; SURVIVAL; INFLAMMATION AB The brush-border enzyme intestinal alkaline phosphatase (IAP) functions as a gut mucosal defense factor and detoxifies different toll-like receptor ligands. This study aimed to determine the therapeutic effects of locally administered calf IAP (cIAP) in a cecal ligation and puncture (CLP) model of polymicrobial sepsis. C57BL/6 mice underwent CLP followed by intraperitoneal injection of cIAP or normal saline. Blood leukocyte counts, levels of cytokines and liver enzymes, and lung myeloperoxidase activity were determined. Peritoneal lavage fluid (PLF) was assayed for neutrophil infiltration and both aerobic and anaerobic bacterial counts. After intraperitoneal injection, cIAP activity in PLF decreased 50% within 15 min with minimal activity evident at 4 h. Compared with irrigation with normal saline, cIAP irrigation increased the 7-day survival rate in mice undergoing CLP, with maximal effects seen at 25 units of cIAP (0% vs. 46% survival rate, respectively; p < 0.001). cIAP treatment reduced lung inflammation, liver damage and levels of tumor necrosis factor alpha and interleukin-6. Peritoneal irrigation with cIAP significantly enhances survival in a mouse model of peritonitis, likely through reduction of local inflammation and remote organ damage. We suggest that intraperitoneal cIAP irrigation could be a novel therapy for intra-abdominal sepsis. C1 [Ebrahimi, Farzad; Malo, Madhu S.; Alam, Sayeda Nasrin; Moss, Angela K.; Yammine, Halim; Ramasamy, Sundaram; Biswas, Brishti; Chen, Kathryn T.; Muhammad, Nur; Mostafa, Golam; Hodin, Richard A.] Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Warren, H. Shaw] Harvard Univ, Infect Dis Unit, Massachusetts Gen Hosp, Dept Pediat,Sch Med, Boston, MA 02114 USA. [Warren, H. Shaw] Harvard Univ, Dept Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Hohmann, Elizabeth L.] Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Dept Med,Sch Med, Boston, MA 02114 USA. RP Malo, MS (reprint author), Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, Jackson 812,55 Fruit St, Boston, MA 02114 USA. EM mmalo@partners.org OI Kuhnen, Angela/0000-0003-4944-9143 FU NIH [R01DK050623, R01DK047186]; MGH Department of Surgery; Bill and Melinda Gates Foundation FX This work was supported by NIH grants R01DK050623 and R01DK047186 to RAH, and a Junior Faculty Award from the MGH Department of Surgery and a Grand Challenge Exploration Grant from the Bill and Melinda Gates Foundation to MSM. NR 41 TC 9 Z9 10 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY PY 2011 VL 15 IS 5 BP 860 EP 869 DI 10.1007/s11605-010-1405-6 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 753TX UT WOS:000289803700023 PM 21360208 ER PT J AU Cohen-Adad, J Descoteaux, M Wald, LL AF Cohen-Adad, Julien Descoteaux, Maxime Wald, Lawrence L. TI Quality Assessment of High Angular Resolution Diffusion Imaging Data Using Bootstrap on Q-Ball Reconstruction SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE HARDI; Q-Ball imaging; bootstrap; reproducibility; SNR; orientation distribution function ID WILD BOOTSTRAP; FIBER ORIENTATION; MEASUREMENT UNCERTAINTIES; SPHERICAL DECONVOLUTION; PHASED-ARRAY; HUMAN BRAIN; TENSOR MRI; DTI DATA; PARAMETERS; OPTIMIZATION AB Purpose: To develop a bootstrap method to assess the quality of High Angular Resolution Diffusion Imaging (HARDI) data using Q-Ball imaging (QBI) reconstruction. Materials and Methods: HARDI data were re-shuffled using regular bootstrap with jackknife sampling. For each bootstrap dataset, the diffusion orientation distribution function (ODF) was estimated voxel-wise using QBI reconstruction based on spherical harmonics functions. The reproducibility of the ODF was assessed using the Jensen-Shannon divergence (JSD) and the angular confidence interval was derived for the first and the second ODF maxima. The sensitivity of the bootstrap method was evaluated on a human subject by adding synthetic noise to the data, by acquiring a map of image signal-to-noise ratio (SNR) and by varying the echo time and the b-value. Results: The JSD was directly linked to the image SNR. The impact of echo times and b-values was reflected by both the JSD and the angular confidence interval, proving the usefulness of the bootstrap method to evaluate specific features of HARDI data. Conclusion: The bootstrap method can effectively assess the quality of HARDI data and can be used to evaluate new hardware and pulse sequences, perform multifiber probabilistic tractography, and provide reliability metrics to support clinical studies. C1 [Cohen-Adad, Julien; Wald, Lawrence L.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Cohen-Adad, Julien; Wald, Lawrence L.] Harvard Univ, Sch Med, Boston, MA USA. [Descoteaux, Maxime] Univ Sherbrooke, MOIVRE Ctr, Dept Comp Sci, Sherbrooke, PQ J1K 2R1, Canada. [Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Cohen-Adad, J (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, 149 13 St, Charlestown, MA 02129 USA. EM jcohen@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009 FU National Institute of Health [P41RR14075, U0IMH093765]; Association pour la Recherche sur la Sclerose en Plaques (ARSEP) FX Contract grant sponsor: National Institute of Health: Contract grant numbers: P41RR14075. U0IMH093765: Contract grant sponsor: Association pour la Recherche sur la Sclerose en Plaques (ARSEP). NR 48 TC 14 Z9 14 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAY PY 2011 VL 33 IS 5 BP 1194 EP 1208 DI 10.1002/jmri.22535 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 756GM UT WOS:000289999700024 PM 21509879 ER PT J AU Zada, G Agarwalla, PK Mukundan, S Dunn, I Golby, AJ Laws, ER AF Zada, Gabriel Agarwalla, Pankaj K. Mukundan, Srinivasan, Jr. Dunn, Ian Golby, Alexandra J. Laws, Edward R., Jr. TI The neurosurgical anatomy of the sphenoid sinus and sellar floor in endoscopic transsphenoidal surgery SO JOURNAL OF NEUROSURGERY LA English DT Article DE sphenoid sinus; sella turcica; tuberculum sellae; clivus; transsphenoidal approach; pituitary gland ID MICROSURGICAL ANATOMY; REGION AB Object. A considerable degree of variability exists in the anatomy of the sphenoid sinus, sella turcica, and surrounding skull base structures. The authors aimed to characterize neuroimaging and intraoperative variations in the sagittal and coronal surgical anatomy of healthy controls and patients with sellar lesions. Methods. Magnetic resonance imaging studies obtained in 100 healthy adults and 78 patients with sellar lesions were reviewed. The following measurements were made on midline sagittal images: sellar face, sellar prominence, sellar angle, tuberculum sellae angle, sellar-clival angle, length of planum sphenoidale, and length of clivus. The septal configuration of the sphenoid sinus was classified as either simple or complex, according to the number of septa, their symmetry, and their morphological features. The following measurements were made on coronal images: maximum width of the sphenoid sinus and sellar face, and the distance between the parasellar and midclivus internal carotid arteries. Neuroimaging results were correlated with intraoperative findings during encloscopic transsphenoidal surgery. Results. Three sellar floor morphologies were defined in normal adults: prominent (sellar angle of < 90 degrees) in 25%, curved (sellar angle 90-150 degrees) in 63%, flat (sellar angle > 150 degrees) in 11%, and no floor (conchal sphenoid) in 1%. In healthy adults, the following mean measurements were obtained: sellar face, 13.4 mm; sellar prominence, 3.0 mm; sellar angle, 112 degrees; angle of tuberculum sellae, 112 degrees; and sellar-clival angle, 117 degrees. Compared with healthy adults, patients with sellar lesions were more likely to have prominent sellar types (43% vs 25%, p = 0.01), a more acute sellar angle (102 degrees vs 112 degrees, p = 0.03), a more prominent sellar floor (3.8 vs 3.0 mm, p < 0.005), and more acute tuberculum (105 degrees vs 112 degrees, p < 0.01) and sellar-clival (105 degrees vs 117 degrees, p < 0.003) angles. A flat sellar floor was more difficult to identify intraoperatively and more likely to require the use of a chisel or drill to expose (75% vs 25%, p = 0.01). A simple sphenoid sinus configuration (no septa, 1 vertical septum, or 2 symmetric vertical septa) was noted in 71% of studies, and the other 29% showed a complex configuration (2 or more asymmetrical septa, 3 or more septa of any kind, or the presence of a horizontal septum). Intraoperative correlation was more challenging in cases with complex sinus anatomy; the most reliable intraoperative midline markers were the vomer, superior sphenoid rostrum, and bilateral parasellar and clival carotid protuberances. Conclusions. Preoperative assessment of neuroimaging studies is critical for characterizing the morphological characteristics of the sphenoid sinus, sellar floor, tuberculum sellae, and clivus. The flat sellar type identified in 11% of people) or a complex sphenoid sinus configuration (in 29% of people) may make intraoperative correlation substantially more challenging. An understanding of the regional anatomy and its variability can improve the safety and accuracy of transsphenoidal and extended encloscopic skull base approaches. (DOI: 10.3171/2010.11.JNS10768) C1 [Zada, Gabriel] Univ So Calif, Dept Neurosurg, Keck Sch Med, Los Angeles, CA 90089 USA. [Agarwalla, Pankaj K.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Sch Med, Cambridge, MA 02138 USA. [Mukundan, Srinivasan, Jr.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Neuroradiol, Boston, MA 02115 USA. [Dunn, Ian; Golby, Alexandra J.; Laws, Edward R., Jr.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. RP Zada, G (reprint author), Univ So Calif, Dept Neurosurg, Keck Sch Med, 1200 N State St,Suite 5046, Los Angeles, CA 90089 USA. EM gzada@usc.edu FU NIBIB NIH HHS [P41 EB015898] NR 17 TC 38 Z9 43 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 2011 VL 114 IS 5 BP 1319 EP 1330 DI 10.3171/2010.11.JNS10768 PG 12 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 755FW UT WOS:000289913900019 PM 21235317 ER PT J AU Wilkinson, HA AF Wilkinson, Harold A. TI Low-back pain and L-2 ganglion SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wilkinson, HA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD MAY PY 2011 VL 14 IS 5 BP 685 EP 685 DI 10.3171/2010.3.SPINE10204 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 755FY UT WOS:000289914100021 PM 21332282 ER PT J AU Surti, S Scheuermann, J El Fakhri, G Daube-Witherspoon, ME Lim, R Abi-Hatem, N Moussallem, E Benard, F Mankoff, D Karp, JS AF Surti, Suleman Scheuermann, Joshua El Fakhri, Georges Daube-Witherspoon, Margaret E. Lim, Ruth Abi-Hatem, Nathalie Moussallem, Elie Benard, Francois Mankoff, David Karp, Joel S. TI Impact of Time-of-Flight PET on Whole-Body Oncologic Studies: A Human Observer Lesion Detection and Localization Study SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE lesion detection; human observers; LROC; time-of-flight PET ID PERFORMANCE; SCANNER; BENEFIT AB Phantom studies have shown improved lesion detection performance with time-of-flight (TOF) PET. In this study, we evaluate the benefit of fully 3-dimensional, TOF PET in clinical whole-body oncology using human observers to localize and detect lesions in realistic patient anatomic backgrounds. Our hypothesis is that with TOF imaging we achieve improved lesion detection and localization for clinically challenging tasks, with a bigger impact in large patients. Methods: One hundred patient studies with normal (18)F-FDG uptake were chosen. Spheres (diameter, 10 mm) were imaged in air at variable locations in the scanner field of view corresponding to lung and liver locations within each patient. Sphere data were corrected for attenuation and merged with patient data to produce fused list-mode data files with lesions added to normal-uptake scans. All list files were reconstructed with full corrections and with or without the TOF kernel using a list-mode iterative algorithm. The images were presented to readers to localize and report the presence or absence of a lesion and their confidence level. The interpretation results were then analyzed to calculate the probability of correct localization and detection, and the area under the localized receiver operating characteristic (LROC) curve. The results were analyzed as a function of scan time per bed position, patient body mass index (BMI < 26 and BMI >= 26), and type of imaging (TOF and non-TOF). Results: Our results showed that longer scan times led to an improved area under the LROC curve for all patient sizes. With TOF imaging, there was a bigger increase in the area under the LROC curve for larger patients (BMI > 26). Finally, we saw smaller differences in the area under the LROC curve for large and small patients when longer scan times were combined with TOF imaging. Conclusion: A combination of longer scan time (3 min in this study) and TOF imaging provides the best performance for imaging large patients or a low-uptake lesion in small or large patients. This imaging protocol also provides similar performance for all patient sizes for lesions in the same organ type with similar relative uptake, indicating an ability to provide a uniform clinical diagnosis in most oncologic lesion detection tasks. C1 [Surti, Suleman; Scheuermann, Joshua; Daube-Witherspoon, Margaret E.; Karp, Joel S.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [El Fakhri, Georges; Lim, Ruth; Abi-Hatem, Nathalie; Moussallem, Elie] Harvard Univ, Sch Med, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. [El Fakhri, Georges; Lim, Ruth; Abi-Hatem, Nathalie; Moussallem, Elie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Benard, Francois] BC Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada. [Mankoff, David] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. RP Surti, S (reprint author), Univ Penn, Dept Radiol, 110 Donner Bldg HUP,3400 Spruce St, Philadelphia, PA 19104 USA. EM surti@mail.med.upenn.edu RI Benard, Francois/M-7720-2015 OI Benard, Francois/0000-0001-7995-3581 FU National Institutes of Health [R01-CA113941, R01-EB009056] FX We thank Matthew Werner (Radiology, University of Pennsylvania, Philadelphia) for help with generating the images. This work was supported by the National Institutes of Health grants R01-CA113941 and R01-EB009056. NR 19 TC 40 Z9 42 U1 0 U2 9 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 MAY PY 2011 VL 52 IS 5 BP 712 EP 719 DI 10.2967/jnumed.110.086678 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 757ME UT WOS:000290088600012 PM 21498523 ER PT J AU Cai, XX Zhang, Y Yang, XM Grottkau, BE Lin, YF AF Cai, Xiaoxiao Zhang, Yi Yang, Xingmei Grottkau, Brian E. Lin, Yunfeng TI Uniaxial cyclic tensile stretch inhibits osteogenic and odontogenic differentiation of human dental pulp stem cells SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE LA English DT Article DE human dental pulp stem cells; uniaxial cyclic tensile stretch; mechanical stress; odontogenesis; osteogenesis ID SEQUENCE DETERMINATION; TOOTH MORPHOGENESIS; IN-VITRO; EXPRESSION; TISSUE; DENTINOGENESIS; PHOSPHOPROTEIN; GENE; MSCS; VIVO AB As the most important organs of occlusion, teeth are subjected to a variety of mechanical stresses. These stresses are transmitted into the dental pulp tissue and affect the dental pulp stem cells. In this study, human dental pulp stem cells were isolated from human impacted third molars and their multilineage differentiation abilities were tested. Human dental pulp stem cells were then exposed to cyclic tensile stretch. The results showed that the cyclic tensile stretch inhibited the expression of osteogenic marker genes and proteins such as BMP-2, OCN and ALP. Simultaneously, odontogenic marker genes and proteins such as DSPP, DSP and BSP were also inhibited by the mechanical stress. It was concluded that cyclic tensile stretch inhibits the osteogenic and odontogenic differentiation of dental pulp stem cells. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Grottkau, Brian E.; Lin, Yunfeng] MassGen Hosp Children, Dept Orthopaed Surg, Boston, MA USA. [Cai, Xiaoxiao; Yang, Xingmei; Lin, Yunfeng] Sichuan Univ, W China Coll Stomatol, State Key Lab Oral Dis, Chengdu 610064, Peoples R China. [Zhang, Yi] Chongqing Med Univ, Coll Stomatol, Dept Orthodont, Chongqing, Peoples R China. [Grottkau, Brian E.; Lin, Yunfeng] Harvard Univ, Sch Med, Pediat Orthopaed Lab Tissue Engn & Regenerat Med, Boston, MA USA. RP Grottkau, BE (reprint author), MassGen Hosp Children, Dept Orthopaed Surg, Boston, MA USA. EM bgrottkau@partners.org; yunfenglin@scu.edu.cn RI Lin, Yunfeng/M-5438-2013; Lin, Yunfeng/H-3393-2011; OI Lin, Yunfeng/0000-0003-1224-6561; Lin, Yunfeng/0000-0003-1224-6561; Cai, Xiaoxiao/0000-0002-5654-7414 FU Constance and Anthony A Franchi Sr Fund; Peabody Foundation Inc.; National Natural Science Foundation of China [30801304]; Program for New Century Excellent Talents in University [NCET-08-0373]; Foundation for the Author of National Excellent Doctoral Dissertation of the People's Republic of China [FANEDD200977] FX This work was funded by the Constance and Anthony A Franchi Sr Fund for the Pediatric Orthopaedic and Spine Service at the MassGeneral Hospital for Children, the Peabody Foundation Inc., the National Natural Science Foundation of China (Grant No. 30801304), the Program for New Century Excellent Talents in University (Grant No. NCET-08-0373) and the Foundation for the Author of National Excellent Doctoral Dissertation of the People's Republic of China (Grant No. FANEDD200977). NR 31 TC 6 Z9 6 U1 0 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1932-6254 J9 J TISSUE ENG REGEN M JI J. Tissue Eng. Regen. Med. PD MAY PY 2011 VL 5 IS 5 BP 347 EP 353 DI 10.1002/term.319 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical SC Cell Biology; Biotechnology & Applied Microbiology; Engineering GA 756GG UT WOS:000289999100002 PM 20827678 ER PT J AU Rathi, Y Kubicki, M Bouix, S Westin, CF Goldstein, J Seidman, L Mesholam-Gately, R McCarley, RW Shenton, ME AF Rathi, Yogesh Kubicki, Marek Bouix, Sylvain Westin, Carl-Fredrik Goldstein, Jill Seidman, Larry Mesholam-Gately, Raquelle McCarley, Robert W. Shenton, Martha E. TI Statistical analysis of fiber bundles using multi-tensor tractography: application to first-episode schizophrenia SO MAGNETIC RESONANCE IMAGING LA English DT Article DE Two-tensor tractography; Kernel methods; First-episode schizophrenia ID WHITE-MATTER AB This work proposes a new method to detect abnormalities in fiber bundles of first-episode (FE) schizophrenia patients. Existing methods have either examined a particular region of interest or used voxel-based morphometry or used tracts generated using the single tensor model for locating statistically different fiber bundles. Further, a two-sample t test, which assumes a Gaussian distribution for each population, is the most widely used statistical hypothesis testing algorithm. In this study, we use the unscented Kalman filter based two-tensor tractography algorithm for tracing neural fiber bundles of the brain that connect 105 different cortical and subcortical regions. Next, fiber bundles with significant connectivity across the entire population were determined. Several diffusion measures derived from the two-tensor model were computed and used as features in the subsequent analysis. For each fiber bundle, an affine-invariant descriptor was computed, thus obviating the need for precise registration of patients to an atlas. A kernel-based statistical hypothesis testing algorithm, which makes no assumption regarding the distribution of the underlying population, was then used to determine the abnormal diffusion properties of all fiber bundles for 20 FE patients and 20 age-matched healthy controls. Of the 1254 fiber bundles with significant connectivity, 740 fiber bundles were found to be significantly different in at least one diffusion measure after correcting for multiple comparisons. Thus, the changes affecting first-episode patients seem to be global in nature (spread throughout the brain). (c) 2011 Elsevier Inc. All rights reserved. C1 [Rathi, Yogesh; Kubicki, Marek; Bouix, Sylvain; Goldstein, Jill; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Rathi, Yogesh] Georgia Inst Technol, Dept Elect & Comp Engn, Atlanta, GA 30332 USA. [Westin, Carl-Fredrik] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Rathi, Yogesh; McCarley, Robert W.; Shenton, Martha E.] VA Clin Neurosci Div, Brockton, MA USA. [Seidman, Larry; Mesholam-Gately, Raquelle] Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Goldstein, Jill] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Rathi, Y (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM yogesh@bwh.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Bouix, Sylvain/0000-0003-1326-6054 FU Department of Veteran Affairs; VA Schizophrenia Center; NIH [1P50MH080272-01, P41 RR13218, R01 MH 52807, R01 MH 50740, R01MH074794]; NA-MIC (NIH) [U54 GM072977-01] FX This work was supported in part by a Department of Veteran Affairs Merit Award (Dr. M. Shenton, Dr. R. McCarley), the VA Schizophrenia Center Grant (RM, MS) and NIH grants: 1P50MH080272-01 (MS, RM), P41 RR13218 (MS), R01 MH 52807 (RM), R01 MH 50740 (MS), R01MH074794 (Dr. C.-F. Westin) and NA-MIC (NIH) grant U54 GM072977-01 (Dr. R. Kikinis). NR 21 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD MAY PY 2011 VL 29 IS 4 BP 507 EP 515 DI 10.1016/j.mri.2010.10.005 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 756GS UT WOS:000290000300005 PM 21277725 ER PT J AU Stanton, RC King, GL AF Stanton, Robert C. King, George L. TI A complex interplay of factors causes diabetic nephropathy SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID OXIDATIVE STRESS; KIDNEY-DISEASE; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; INHIBITION; APOPTOSIS; PODOCYTE C1 [Stanton, Robert C.] Joslin Diabet Ctr, Vasc Biol Sect, Boston, MA 02215 USA. Joslin Diabet Ctr, Renal Sect, Boston, MA 02215 USA. RP Stanton, RC (reprint author), Joslin Diabet Ctr, Vasc Biol Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM robert.stanton@joslin.harvard.edu NR 22 TC 4 Z9 4 U1 0 U2 13 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 MAY PY 2011 VL 60 IS 5 BP 591 EP 593 DI 10.1016/j.metabol.2010.10.004 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 756GV UT WOS:000290000600001 PM 21109270 ER PT J AU Johnson, PV Blair, BM Zeller, S Kotton, CN Hohmann, EL AF Johnson, Paul V. Blair, Barbra M. Zeller, Skye Kotton, Camille N. Hohmann, Elizabeth L. TI Attenuated Listeria monocytogenes vaccine vectors expressing Influenza A nucleoprotein: preclinical evaluation and oral inoculation of volunteers SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE attenuated vaccine vector; ELISpot; human study; Listeria monocytogenes ID HELICOBACTER-PYLORI UREASE; CELL-MEDIATED-IMMUNITY; ADULT VOLUNTEERS; T-CELLS; VIRUS; INDUCTION; GROWTH; MICE; IMMUNOGENICITY; LYMPHOCYTES AB Listeria monocytogenes vectors have shown promise for delivery of viral and tumor antigens in animals. We used two mutant vector strains deleted for actA/plcB (BMB72) and actA/inlB (BMB54), and engineered both strains to secrete a heterologous nucleoprotein antigen from the Influenza A virus. Strains were evaluated in vitro and in mice. Twenty-two healthy volunteers received single oral doses of either strain in a physiological study of safety, shedding, and immunogenicity. Volunteers were observed in the hospital for seven days and had daily blood cultures, routine safety blood tests (complete blood count with differential; hepatic and renal function), and fecal cultures; none had fever, positive blood cultures, prolonged shedding, or serious or unexpected events. Four of 12 volunteers who received the actA/plcB-deleted strain had minor, transient, asymptomatic serum transaminase elevations (maximum increase 1.4x upper normal). Six of six volunteers who received >= 4 x 109 colony forming units had detectable mucosal immune responses to listerial antigens, but not to the vectored influenza antigen. Approximately half the volunteers had modest interferon-gamma ELISpot responses to a complex listerial antigen, but none had increases over their baseline responses to the influenza antigen. Comparison with prior work suggests that foreign antigen expression, and perhaps also freezing, may adversely affect the organisms' immunogenicity. C1 [Johnson, Paul V.; Blair, Barbra M.; Zeller, Skye; Kotton, Camille N.; Hohmann, Elizabeth L.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Infect Dis, Boston, MA 02114 USA. RP Hohmann, EL (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM ehohmann@partners.org FU NIH/NIAID-NERCE/BEID [5 U54 A1057159-03]; NIH/NIAID [R01 AI51206]; National Center for Research Resources [M01-RR-01066, UL1 RR025758-01] FX This work was supported in part by NIH/NIAID-NERCE/BEID Career Development Fellowship 5 U54 A1057159-03 (BMB), NIH/NIAID R01 AI51206 (ELH) and grants M01-RR-01066 (Massachusetts General Hospital GCRC) and UL1 RR025758-01 (Harvard Clinical and Translational Science Center) from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. We acknowledge the generosity of the Cerus Corporation, Concord, CA, USA, for providing us with the L. monocytogenes Delta actA/inlB strain as well as the LLO peptide pool. We especially thank our volunteers, and the inpatient clinical research center nursing staff and clinical microbiology laboratory at Massachusetts General Hospital. NR 41 TC 11 Z9 12 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0385-5600 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PD MAY PY 2011 VL 55 IS 5 BP 304 EP 317 DI 10.1111/j.1348-0421.2011.00322.x PG 14 WC Immunology; Microbiology SC Immunology; Microbiology GA 754XM UT WOS:000289891100002 PM 21338384 ER PT J AU Bernjak, A Deitrick, GA Bauman, WA Stefanovska, A Tuckman, J AF Bernjak, A. Deitrick, G. A. Bauman, W. A. Stefanovska, A. Tuckman, J. TI Basal sympathetic activity to the microcirculation in tetraplegic man revealed by wavelet transform of laser Doppler flowmetry SO MICROVASCULAR RESEARCH LA English DT Article DE Blood flow; Autonomic; Sympathetic; Wave, wavelet transform; Laser Doppler flowmetry ID SPINAL-CORD-INJURY; BLOOD-FLOW OSCILLATIONS; HUMAN SKIN; CIRCULATION; RESPONSES; CLONIDINE; OUTFLOW; LESIONS; HUMANS; MUSCLE AB Background: The 1984/86 published neurogram results showing only rare sympathetic nerve activity (SNA) to the muscles and skin in tetraplegia are still accepted. The present study by a different method attempted to confirm or deny those findings. Methods and results: The effect of basal SNA to the microcirculation of the feet and calf in 10 complete (AIS A) traumatic tetraplegic and 10 healthy age matched subjects were evaluated by wavelet transform of laser Doppler flowmetry (LDF) recordings. The results clearly indicated there is significant basal SNA from the decentralized spinal cord in tetraplegia. In addition, wavelet analysis allowed a study of other influences on the microcirculation besides SNA. Collectively, in tetraplegia compared with controls, the powers of the low frequency oscillations in blood flow were reduced; in that the endothelium caused less vasodilatation while the SNA and intrinsic vascular smooth muscles induced smaller degrees of vasoconstriction. However, the high frequency and especially the cardiac powers were greater. The latter presenting an obvious important factor for the preservation of blood flow in the microcirculation. Conclusions: It is suggested that basal SNA to the cutaneous microcirculation occurs in complete tetraplegia, and the significant levels of circulating noradrenaline reported by others indicate this is also true in other parts of the body. This may explain the usual absence of severe, incapacitating, autonomic deficiency in this condition. Published by Elsevier Inc. C1 [Deitrick, G. A.] James J Peters VA Med Ctr, Dept Surg, Bronx, NY 10461 USA. [Deitrick, G. A.] Mt Sinai Med Ctr, Dept Surg, New York, NY 10029 USA. [Deitrick, G. A.] Mt Sinai Sch Med, SCI Patient Care Unit, New York, NY 10029 USA. [Bauman, W. A.; Tuckman, J.] Mt Sinai Sch Med, Spinal Cord Damage Res Ctr, New York, NY 10029 USA. [Bauman, W. A.; Tuckman, J.] Mt Sinai Sch Med, VA RR&D Ctr Excellence Med Consequences Spinal Co, New York, NY 10029 USA. [Bauman, W. A.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Bernjak, A.; Stefanovska, A.] Univ Lancaster, Dept Phys, Lancaster LA1 4YB, England. [Stefanovska, A.] Univ Ljubljana, Fac Elect Engn, Ljubljana, Slovenia. RP Deitrick, GA (reprint author), James J Peters VA Med Ctr, Dept Surg, 130 W Kingsbridge Rd, Bronx, NY 10461 USA. EM george.deitrick@va.gov FU VA RR&D Center of Excellence for the Medical Consequences of Spinal Cord Injury [B4162C]; Wellcome Trust; UK; Slovenia Research Agency, ARRS, Slovenia; ESRC, UK FX 1) VA RR&D Center of Excellence for the Medical Consequences of Spinal Cord Injury, #B4162C; 2) Wellcome Trust; UK; 3) Slovenia Research Agency, ARRS, Slovenia; 4) ESRC - New Dynamics of Ageing Research Programme, UK NR 28 TC 6 Z9 6 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAY PY 2011 VL 81 IS 3 BP 313 EP 318 DI 10.1016/j.mvr.2011.01.005 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 756GY UT WOS:000290000900011 PM 21262239 ER PT J AU Chen, JH Faquin, WC Lloyd, RV Nose, V AF Chen, Jey-Hsin Faquin, William C. Lloyd, Ricardo V. Nose, Vania TI Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma SO MODERN PATHOLOGY LA English DT Article DE BRAF (BRAF(V600E)); beta-catenin; columnar cell variant; cyclin D1; papillary thyroid carcinoma ID OF-THE-LITERATURE; BRAF MUTATION ANALYSIS; CYCLIN D1; BETA-CATENIN; TALL-CELL; HIGH PREVALENCE; IMMUNOHISTOCHEMICAL ANALYSIS; DIFFERENTIATED CARCINOMAS; GENETIC ALTERATIONS; ESTROGEN-RECEPTORS AB The majority of papillary thyroid carcinoma is indolent and associated with long-term survival. The columnar cell variant, however, is a rare subtype that is variable in biological behavior; some are clinically aggressive, whereas others are more clinically indolent. Tumor size, tumor circumscription, and encapsulation may influence the behavior of columnar cell carcinomas. Other variables including genetic changes and putative biomarkers associated with malignant growth have not been thoroughly examined in these neoplasms. In this study, nine cases of columnar cell variant of papillary thyroid carcinoma from three institutions were classified as clinically indolent or aggressive based on pathological features, clinical history, and outcome. Indolent tumors were typically small, circumscribed or encapsulated, and from younger female patients, whereas aggressive tumors were large, locally aggressive, associated with regional and distant metastasis, and from older male patients. The missense mutation, V600E in the BRAF oncogene (BRAF(V600E)), was detected in three of nine of cases, of which two were clinically aggressive. Immunohistochemical evaluation of neoplasia-associated markers showed increased nuclear cyclin D1 expression, elevated Ki-67 proliferation indices, and predominantly weak nuclear p53 staining in both indolent and aggressive tumors. Expression of beta-catenin was largely restricted to a membranous pattern in both tumor types. Cytoplasmic expression of bcl-2 was overall mildly reduced in indolent neoplasms. Nuclear expression of estrogen and progesterone receptors was increased in both indolent and aggressive neoplasms, but was without sex-or age-related differences; however, whereas progesterone receptor expression was diffuse and strong in clinically indolent carcinomas, its expression was diminished in aggressive neoplasms. Recognition of the clinicopathological characteristics and the molecular and immunophenotypic features of the columnar cell variant of papillary thyroid carcinoma may aid in characterizing neoplasms that behave indolently or aggressively. Modern Pathology (2011) 24, 739-749; doi:10.1038/modpathol.2011.2; published online 25 February 2011 C1 [Chen, Jey-Hsin; Nose, Vania] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chen, Jey-Hsin] Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA. [Faquin, William C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Lloyd, Ricardo V.] Mayo Clin Rochester, Dept Lab Med & Pathol, Rochester, MN USA. [Lloyd, Ricardo V.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA. [Nose, Vania] Univ Miami, Leonard M Miller Sch Med, Dept Pathol, Miami, FL 33136 USA. RP Nose, V (reprint author), Univ Miami, Miller Sch Med, Dept Pathol R 5, 1120 NW 14th Ave,Room 1411, Miami, FL 33136 USA. EM vnose@med.miami.edu NR 81 TC 16 Z9 22 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 MAY PY 2011 VL 24 IS 5 BP 739 EP 749 DI 10.1038/modpathol.2011.2 PG 11 WC Pathology SC Pathology GA 757MV UT WOS:000290091900014 PM 21358618 ER PT J AU Ginjala, V Nacerddine, K Kulkarni, A Oza, J Hill, SJ Yao, M Citterio, E van Lohuizen, M Ganesan, S AF Ginjala, Vasudeva Nacerddine, Karim Kulkarni, Atul Oza, Jay Hill, Sarah J. Yao, Ming Citterio, Elisabetta van Lohuizen, Maarten Ganesan, Shridar TI BMI1 Is Recruited to DNA Breaks and Contributes to DNA Damage-Induced H2A Ubiquitination and Repair SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; HISTONE H2A; POLYUBIQUITINATED PROTEINS; MONOCLONAL-ANTIBODIES; IN-VITRO; POLYCOMB; SITES; COMPLEX; 53BP1; UBIQUITYLATION AB DNA damage activates signaling pathways that lead to modification of local chromatin and recruitment of DNA repair proteins. Multiple DNA repair proteins having ubiquitin ligase activity are recruited to sites of DNA damage, where they ubiquitinate histones and other substrates. This DNA damage-induced histone ubiquitination is thought to play a critical role in mediating the DNA damage response. We now report that the polycomb protein BMI1 is rapidly recruited to sites of DNA damage, where it persists for more than 8 h. The sustained localization of BMI1 to damage sites is dependent on intact ATM and ATR and requires H2AX phosphorylation and recruitment of RNF8. BMI1 is required for DNA damage-induced ubiquitination of histone H2A at lysine 119. Loss of BMI1 leads to impaired repair of DNA double-strand breaks by homologous recombination and the accumulation of cells in G(2)/M. These data support a crucial role for BMI1 in the cellular response to DNA damage. C1 [Ginjala, Vasudeva; Kulkarni, Atul; Oza, Jay; Yao, Ming; Ganesan, Shridar] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Nacerddine, Karim; Citterio, Elisabetta; van Lohuizen, Maarten] Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands. [Nacerddine, Karim; Citterio, Elisabetta; van Lohuizen, Maarten] Netherlands Canc Inst, Ctr Biomed Genet, NL-1066 CX Amsterdam, Netherlands. [Hill, Sarah J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ganesan, S (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, 195 Little Albany St, New Brunswick, NJ 08903 USA. EM ganesash@umdnj.edu FU NIH; NJCCR; CINJ Foundation; DOD FX S.G. was supported by the NIH, the NJCCR, and the CINJ Foundation. J.O. was supported by a predoctoral grant from the NJCCR and the DOD. NR 62 TC 101 Z9 104 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2011 VL 31 IS 10 BP 1972 EP 1982 DI 10.1128/MCB.00981-10 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 755MQ UT WOS:000289936600005 PM 21383063 ER PT J AU Verzi, MP Shin, HJ Ho, LL Liu, XS Shivdasani, RA AF Verzi, Michael P. Shin, Hyunjin Ho, Li-Lun Liu, X. Shirley Shivdasani, Ramesh A. TI Essential and Redundant Functions of Caudal Family Proteins in Activating Adult Intestinal Genes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSGENIC MICE; CDX2 EXPRESSION; HOMEOBOX GENE; EPITHELIUM; DIFFERENTIATION; METAPLASIA; CELLS; MOUSE; ELONGATION; REPRESSION AB Transcription factors that potently induce cell fate often remain expressed in the induced organ throughout life, but their requirements in adults are uncertain and varied. Mechanistically, it is unclear if they activate only tissue-specific genes or also directly repress heterologous genes. We conditionally inactivated mouse Cdx2, a dominant regulator of intestinal development, and mapped its genome occupancy in adult intestinal villi. Although homeotic transformation, observed in Cdx2-null embryos, was absent in mutant adults, gene expression and cell morphology were vitally compromised. Lethality was significantly accelerated in mice lacking both Cdx2 and its homolog Cdx1, with particular exaggeration of defects in villus enterocyte differentiation. Importantly, Cdx2 occupancy correlated with hundreds of transcripts that fell but not with equal numbers that rose with Cdx loss, indicating a predominantly activating role at intestinal cis-regulatory regions. Integrated consideration of a transcription factor's mutant phenotype and cistrome hence reveals the continued and distinct requirement in adults of a critical developmental regulator that activates tissue-specific genes. C1 [Verzi, Michael P.; Ho, Li-Lun; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Shin, Hyunjin; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Shin, Hyunjin; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Verzi, Michael P.; Ho, Li-Lun; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Verzi, Michael P.; Ho, Li-Lun; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu RI cheng, yong/I-4270-2012 FU National Institutes of Health [R01DK082889, R01HG4069, 1K01DK088868-01]; Crohn's and Colitis Foundation [1987]; aegis of center [P50CA127003] FX This work was supported by National Institutes of Health grants R01DK082889 (R.A.S.), R01HG4069 (X.S.L.), and 1K01DK088868-01 (M.P.V.), a fellowship from the Crohn's and Colitis Foundation (grant 1987 to M.P.V.), and core resources provided under the aegis of center grant P50CA127003. NR 44 TC 43 Z9 43 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2011 VL 31 IS 10 BP 2026 EP 2039 DI 10.1128/MCB.01250-10 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 755MQ UT WOS:000289936600009 PM 21402776 ER PT J AU de Zoeten, EF Wang, LQ Butler, K Beier, UH Akimova, T Sai, H Bradner, JE Mazitschek, R Kozikowski, AP Matthias, P Hancock, WW AF de Zoeten, Edwin F. Wang, Liqing Butler, Kyle Beier, Ulf H. Akimova, Tatiana Sai, Hong Bradner, James E. Mazitschek, Ralph Kozikowski, Alan P. Matthias, Patrick Hancock, Wayne W. TI Histone Deacetylase 6 and Heat Shock Protein 90 Control the Functions of Foxp3(+) T-Regulatory Cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; INFLAMMATORY-BOWEL-DISEASE; ALLOGRAFT TOLERANCE; CHAPERONE FUNCTION; INHIBITORS; HDAC6; ACETYLATION; COLITIS; MICE; POTENT AB Foxp3(+) T-regulatory cells (Tregs) are key to immune homeostasis such that their diminished numbers or function can cause autoimmunity and allograft rejection. Foxp3(+) Tregs express multiple histone/protein deacetylases (HDACs) that regulate chromatin remodeling, gene expression, and protein function. Pan-HDAC inhibitors developed for oncologic applications enhance Treg production and Treg suppression function but have limited nononcologic utility given their broad actions and various side effects. We show, using HDAC6-deficient mice and wild-type (WT) mice treated with HDAC6-specific inhibitors, that HDAC6 inhibition promotes Treg suppressive activity in models of inflammation and autoimmunity, including multiple forms of experimental colitis and fully major histocompatibility complex (MHC)-incompatible cardiac allograft rejection. Many of the beneficial effects of HDAC6 targeting are also achieved by inhibition of the HDAC6-regulated protein heat shock protein 90 (HSP90). Hence, selective targeting of a single HDAC isoform, HDAC6, or its downstream target, HSP90, can promote Treg-dependent suppression of autoimmunity and transplant rejection. C1 [de Zoeten, Edwin F.; Sai, Hong] Childrens Hosp Philadelphia, Dept Pediat, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA. [Wang, Liqing; Akimova, Tatiana] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Div Transplant Immunol, Philadelphia, PA 19104 USA. [Akimova, Tatiana; Hancock, Wayne W.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Biesecker Ctr Studies Pediat Liver Dis, Philadelphia, PA 19104 USA. [Beier, Ulf H.] Childrens Hosp Philadelphia, Dept Pediat, Div Nephrol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Butler, Kyle; Kozikowski, Alan P.] Univ Illinois, Dept Med Chem & Pharmacognosy, Drug Discovery Program, Chicago, IL 60612 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Mazitschek, Ralph] Broad Inst Harvard Univ & Massachusetts Inst Tech, Chem Biol Program, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Matthias, Patrick] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland. RP Hancock, WW (reprint author), Childrens Hosp Philadelphia, Abramson Res Ctr 916B, Div Transplant Immunol Pathol & Lab Med, 3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM whancock@mail.med.upenn.edu RI Akimova, Tatiana/I-7200-2012; Mazitschek, Ralph/E-3741-2013; OI Mazitschek, Ralph/0000-0002-1105-689X; de Zoeten, Edwin/0000-0002-0946-9759 FU National Institutes of Health [K08DK080189, P01AI073489]; CDHNF/CCFA [2712] FX This work was supported by research grants from the National Institutes of Health (K08DK080189 to E.F.D. and P01AI073489 to W.W.H.) and CDHNF/CCFA (2712) grants to E.F.D. NR 61 TC 86 Z9 87 U1 0 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2011 VL 31 IS 10 BP 2066 EP 2078 DI 10.1128/MCB.05155-11 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 755MQ UT WOS:000289936600012 PM 21444725 ER PT J AU Storchova, Z Becker, JS Talarek, N Kogelsberger, S Pellman, D AF Storchova, Zuzana Becker, Justin S. Talarek, Nicolas Koegelsberger, Sandra Pellman, David TI Bub1, Sgo1, and Mps1 mediate a distinct pathway for chromosome biorientation in budding yeast SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SPINDLE CHECKPOINT; PROTEIN-KINASE; BI-ORIENTATION; MEIOSIS-I; MITOTIC CHROMOSOMES; INNER CENTROMERE; SHUGOSHIN; TENSION; KINETOCHORES AB The conserved mitotic kinase Bub1 performs multiple functions that are only partially characterized. Besides its role in the spindle assembly checkpoint and chromosome alignment, Bub1 is crucial for the kinetochore recruitment of multiple proteins, among them Sgo1. Both Bub1 and Sgo1 are dispensable for growth of haploid and diploid budding yeast, but they become essential in cells with higher ploidy. We find that overexpression of SGO1 partially corrects the chromosome segregation defect of bub1 Delta haploid cells and restores viability to bub1 Delta tetraploid cells. Using an unbiased high-copy suppressor screen, we identified two members of the chromosomal passenger complex (CPC), BIR1 (survivin) and SLI15 (INCENP, inner centromere protein), as suppressors of the growth defect of both bub1 Delta and sgo1 Delta tetraploids, suggesting that these mutants die due to defects in chromosome biorientation. Overexpression of BIR1 or SLI15 also complements the benomyl sensitivity of haploid bub1 Delta and sgo1 Delta cells. Mutants lacking SGO1 fail to biorient sister chromatids attached to the same spindle pole (syntelic attachment) after nocodazole treatment. Moreover, the sgo1 Delta cells accumulate syntelic attachments in unperturbed mitoses, a defect that is partially corrected by BIR1 or SLI15 overexpression. We show that in budding yeast neither Bub1 nor Sgo1 is required for CPC localization or affects Aurora B activity. Instead we identify Sgo1 as a possible partner of Mps1, a mitotic kinase suggested to have an Aurora B-independent function in establishment of biorientation. We found that Sgo1 overexpression rescues defects caused by metaphase inactivation of Mps1 and that Mps1 is required for Sgo1 localization to the kinetochore. We propose that Bub1, Sgo1, and Mps1 facilitate chromosome biorientation independently of the Aurora B-mediated pathway at the budding yeast kinetochore and that both pathways are required for the efficient turnover of syntelic attachments. C1 [Storchova, Zuzana; Becker, Justin S.; Talarek, Nicolas; Pellman, David] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Storchova, Zuzana; Becker, Justin S.; Talarek, Nicolas; Pellman, David] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Storchova, Zuzana; Koegelsberger, Sandra] Max Planck Inst Biochem, Grp Maintenance Genome Stabil, D-82152 Martinsried, Germany. [Pellman, David] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Storchova, Z (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM storchov@biochem.mpg.de; david_pellman@dfci.harvard.edu NR 54 TC 20 Z9 20 U1 0 U2 5 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY 1 PY 2011 VL 22 IS 9 BP 1473 EP 1485 DI 10.1091/mbc.E10-08-0673 PG 13 WC Cell Biology SC Cell Biology GA 756OT UT WOS:000290023700006 PM 21389114 ER PT J AU Naj, AC Jun, G Beecham, GW Wang, LS Vardarajan, BN Buros, J Gallins, PJ Buxbaum, JD Jarvik, GP Crane, PK Larson, EB Bird, TD Boeve, BF Graff-Radford, NR De Jager, PL Evans, D Schneider, JA Carrasquillo, MM Ertekin-Taner, N Younkin, SG Cruchaga, C Kauwe, JSK Nowotny, P Kramer, P Hardy, J Huentelman, MJ Myers, AJ Barmada, MM Demirci, FY Baldwin, CT Green, RC Rogaeva, E St George-Hyslop, P Arnold, SE Barber, R Beach, T Bigio, EH Bowen, JD Boxer, A Burke, JR Cairns, NJ Carlson, CS Carney, RM Carroll, SL Chui, HC Clark, DG Corneveaux, J Cotman, CW Cummings, JL DeCarli, C DeKosky, ST Diaz-Arrastia, R Dick, M Dickson, DW Ellis, WG Faber, KM Fallon, KB Farlow, MR Ferris, S Frosch, MP Galasko, DR Ganguli, M Gearing, M Geschwind, DH Ghetti, B Gilbert, JR Gilman, S Giordani, B Glass, JD Growdon, JH Hamilton, RL Harrell, LE Head, E Honig, LS Hulette, CM Hyman, BT Jicha, GA Jin, LW Johnson, N Karlawish, J Karydas, A Kaye, JA Kim, R Koo, EH Kowall, NW Lah, JJ Levey, AI Lieberman, AP Lopez, OL Mack, WJ Marson, DC Martiniuk, F Mash, DC Masliah, E McCormick, WC McCurry, SM McDavid, AN Mckee, AC Mesulam, M Miller, BL Miller, CA Miller, JW Parisi, JE Perl, DP Peskind, E Petersen, RC Poon, WW Quinn, JF Rajbhandary, RA Raskind, M Reisberg, B Ringman, JM Roberson, ED Rosenberg, RN Sano, M Schneider, LS Seeley, W Shelanski, ML Slifer, MA Smith, CD Sonnen, JA Spina, S Stern, RA Tanzi, RE Trojanowski, JQ Troncoso, JC Van Deerlin, VM Vinters, HV Vonsattel, JP Weintraub, S Welsh-Bohmer, KA Williamson, J Woltjer, RL Cantwell, LB Dombroski, BA Beekly, D Lunetta, KL Martin, ER Kamboh, MI Saykin, AJ Reiman, EM Bennett, DA Morris, JC Montine, TJ Goate, AM Blacker, D Tsuang, DW Hakonarson, H Kukull, WA Foroud, TM Haines, JL Mayeux, R Pericak-Vance, MA Farrer, LA Schellenberg, GD AF Naj, Adam C. Jun, Gyungah Beecham, Gary W. Wang, Li-San Vardarajan, Badri Narayan Buros, Jacqueline Gallins, Paul J. Buxbaum, Joseph D. Jarvik, Gail P. Crane, Paul K. Larson, Eric B. Bird, Thomas D. Boeve, Bradley F. Graff-Radford, Neill R. De Jager, Philip L. Evans, Denis Schneider, Julie A. Carrasquillo, Minerva M. Ertekin-Taner, Nilufer Younkin, Steven G. Cruchaga, Carlos Kauwe, John S. K. Nowotny, Petra Kramer, Patricia Hardy, John Huentelman, Matthew J. Myers, Amanda J. Barmada, Michael M. Demirci, F. Yesim Baldwin, Clinton T. Green, Robert C. Rogaeva, Ekaterina St George-Hyslop, Peter Arnold, Steven E. Barber, Robert Beach, Thomas Bigio, Eileen H. Bowen, James D. Boxer, Adam Burke, James R. Cairns, Nigel J. Carlson, Chris S. Carney, Regina M. Carroll, Steven L. Chui, Helena C. Clark, David G. Corneveaux, Jason Cotman, Carl W. Cummings, Jeffrey L. DeCarli, Charles DeKosky, Steven T. Diaz-Arrastia, Ramon Dick, Malcolm Dickson, Dennis W. Ellis, William G. Faber, Kelley M. Fallon, Kenneth B. Farlow, Martin R. Ferris, Steven Frosch, Matthew P. Galasko, Douglas R. Ganguli, Mary Gearing, Marla Geschwind, Daniel H. Ghetti, Bernardino Gilbert, John R. Gilman, Sid Giordani, Bruno Glass, Jonathan D. Growdon, John H. Hamilton, Ronald L. Harrell, Lindy E. Head, Elizabeth Honig, Lawrence S. Hulette, Christine M. Hyman, Bradley T. Jicha, Gregory A. Jin, Lee-Way Johnson, Nancy Karlawish, Jason Karydas, Anna Kaye, Jeffrey A. Kim, Ronald Koo, Edward H. Kowall, Neil W. Lah, James J. Levey, Allan I. Lieberman, Andrew P. Lopez, Oscar L. Mack, Wendy J. Marson, Daniel C. Martiniuk, Frank Mash, Deborah C. Masliah, Eliezer McCormick, Wayne C. McCurry, Susan M. McDavid, Andrew N. Mckee, Ann C. Mesulam, Marsel Miller, Bruce L. Miller, Carol A. Miller, Joshua W. Parisi, Joseph E. Perl, Daniel P. Peskind, Elaine Petersen, Ronald C. Poon, Wayne W. Quinn, Joseph F. Rajbhandary, Ruchita A. Raskind, Murray Reisberg, Barry Ringman, John M. Roberson, Erik D. Rosenberg, Roger N. Sano, Mary Schneider, Lon S. Seeley, William Shelanski, Michael L. Slifer, Michael A. Smith, Charles D. Sonnen, Joshua A. Spina, Salvatore Stern, Robert A. Tanzi, Rudolph E. Trojanowski, John Q. Troncoso, Juan C. Van Deerlin, Vivianna M. Vinters, Harry V. Vonsattel, Jean Paul Weintraub, Sandra Welsh-Bohmer, Kathleen A. Williamson, Jennifer Woltjer, Randall L. Cantwell, Laura B. Dombroski, Beth A. Beekly, Duane Lunetta, Kathryn L. Martin, Eden R. Kamboh, M. Ilyas Saykin, Andrew J. Reiman, Eric M. Bennett, David A. Morris, John C. Montine, Thomas J. Goate, Alison M. Blacker, Deborah Tsuang, Debby W. Hakonarson, Hakon Kukull, Walter A. Foroud, Tatiana M. Haines, Jonathan L. Mayeux, Richard Pericak-Vance, Margaret A. Farrer, Lindsay A. Schellenberg, Gerard D. TI Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; IDENTIFIES VARIANTS; MISSENSE MUTATIONS; APOLIPOPROTEIN-E; GENE; METAANALYSIS; POPULATION; APOE; RISK; LOCI AB The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P-M) = 1.7 x 10(-9), joint analysis P (P-J) = 1.7 x 10(-9); stages 1, 2 and 3, P-M = 8.2 x 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P-M = 8.6 x 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P-M = 6.0 x 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P-M = 1.6 x 10(-9)). We also replicated previous associations at CR1 (rs6701713; P-M = 4.6 x 10(-10), P-J = 5.2 x 10(-11)), CLU (rs1532278; P-M = 8.3 x 10(-8), P-J = 1.9 x 10(-8)), BIN1 (rs7561528; P-M = 4.0 x 10(-14), P-J = 5.2 x 10(-14)) and PICALM (rs561655; P-M = 7.0 x 10(-11), P-J = 1.0 x 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility(1-3). C1 [Wang, Li-San; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Cantwell, Laura B.; Dombroski, Beth A.; Schellenberg, Gerard D.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Naj, Adam C.; Beecham, Gary W.; Gallins, Paul J.; Gilbert, John R.; Rajbhandary, Ruchita A.; Slifer, Michael A.; Martin, Eden R.; Pericak-Vance, Margaret A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA. [Jun, Gyungah; Lunetta, Kathryn L.; Farrer, Lindsay A.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Jun, Gyungah; Vardarajan, Badri Narayan; Buros, Jacqueline; Baldwin, Clinton T.; Green, Robert C.; Farrer, Lindsay A.] Boston Univ, Dept Med, Genet Program, Boston, MA 02215 USA. [Jun, Gyungah; Farrer, Lindsay A.] Boston Univ, Dept Ophthalmol, Boston, MA 02215 USA. [Gilbert, John R.; Martin, Eden R.; Pericak-Vance, Margaret A.] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Buxbaum, Joseph D.; Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, Sch Med, New York, NY USA. [Jarvik, Gail P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Jarvik, Gail P.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA. [Crane, Paul K.; McCormick, Wayne C.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Larson, Eric B.] Res Inst, Grp Hlth, Seattle, WA USA. [Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Boeve, Bradley F.; Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Graff-Radford, Neill R.; Carrasquillo, Minerva M.; Ertekin-Taner, Nilufer; Younkin, Steven G.; Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Graff-Radford, Neill R.; Ertekin-Taner, Nilufer] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Dept Neurol, Boston, MA 02115 USA. [De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Evans, Denis] Rush Univ, Med Ctr, Rush Inst Healthy Aging, Dept Internal Med, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Dept Pathol Neuropathol, Chicago, IL 60612 USA. [Schneider, Julie A.; Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Cruchaga, Carlos; Nowotny, Petra; Goate, Alison M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Cruchaga, Carlos; Nowotny, Petra; Goate, Alison M.] Washington Univ, Sch Med, Hope Ctr Program Prot Aggregat & Neurodegenerat, St Louis, MO 63110 USA. [Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA. [Kramer, Patricia] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Kramer, Patricia; Kaye, Jeffrey A.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Hardy, John] UCL, Dept Neurol, London, England. [Huentelman, Matthew J.; Corneveaux, Jason; Reiman, Eric M.] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA. [Myers, Amanda J.] Univ Miami, Dept Psychiat & Behav Sci, Miami, FL USA. [Barmada, Michael M.; Demirci, F. Yesim; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Green, Robert C.; Kowall, Neil W.; Mckee, Ann C.; Stern, Robert A.; Farrer, Lindsay A.] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Green, Robert C.; Farrer, Lindsay A.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Rogaeva, Ekaterina; St George-Hyslop, Peter] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. [St George-Hyslop, Peter] Univ Cambridge, Dept Clin Neurosci, Cambridge, Massachusetts, England. [Arnold, Steven E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Barber, Robert] Univ Texas SW, Dept Pharmacol & Neurosci, Ft Worth, TX USA. [Beach, Thomas] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Phoenix, AZ USA. [Bigio, Eileen H.] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA. [Bowen, James D.] Swedish Med Ctr, Seattle, WA USA. [Boxer, Adam; Karydas, Anna; Miller, Bruce L.; Seeley, William] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Burke, James R.; Welsh-Bohmer, Kathleen A.] Duke Univ, Dept Med, Durham, NC USA. [Cairns, Nigel J.; Morris, John C.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA. [Carlson, Chris S.; McDavid, Andrew N.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Carney, Regina M.] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. [Carroll, Steven L.; Fallon, Kenneth B.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Chui, Helena C.; Schneider, Lon S.] Univ So Calif, Dept Neurol, Los Angeles, CA USA. [Clark, David G.; Harrell, Lindy E.; Marson, Daniel C.; Roberson, Erik D.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Cotman, Carl W.; Dick, Malcolm; Poon, Wayne W.] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Irvine, CA USA. [Cummings, Jeffrey L.; Ringman, John M.; Vinters, Harry V.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Diaz-Arrastia, Ramon; Rosenberg, Roger N.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Ellis, William G.; Jin, Lee-Way; Miller, Joshua W.] Univ Calif Davis, Dept Pathol & Lab Med, Sacramento, CA 95817 USA. [Faber, Kelley M.; Saykin, Andrew J.; Foroud, Tatiana M.] Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN 46204 USA. [Farlow, Martin R.] Indiana Univ, Dept Neurol, Indianapolis, IN 46204 USA. [Ferris, Steven; Reisberg, Barry] NYU, Dept Psychiat, New York, NY 10016 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Charlestown, MA USA. [Galasko, Douglas R.; Koo, Edward H.; Masliah, Eliezer] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Ganguli, Mary] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Gearing, Marla] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Gearing, Marla] Emory Univ, Emory Alzheimers Dis Ctr, Atlanta, GA 30322 USA. [Geschwind, Daniel H.] Univ Calif Los Angeles, Neurogenet Program, Los Angeles, CA USA. [Ghetti, Bernardino; Spina, Salvatore] Indiana Univ, Dept Pathol & Lab Med, Indianapolis, IN 46204 USA. [Gilman, Sid] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Giordani, Bruno] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Glass, Jonathan D.; Lah, James J.; Levey, Allan I.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Growdon, John H.; Hyman, Bradley T.; Tanzi, Rudolph E.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hamilton, Ronald L.] Univ Pittsburgh, Dept Pathol Neuropathol, Pittsburgh, PA USA. [Head, Elizabeth] Univ Calif Irvine, Dept Mol & Biomed Pharmacol, Irvine, CA USA. [Honig, Lawrence S.; Williamson, Jennifer; Mayeux, Richard] Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA. [Hulette, Christine M.] Duke Univ, Dept Pathol, Durham, NC 27706 USA. [Jicha, Gregory A.; Smith, Charles D.] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. [Johnson, Nancy] Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Karlawish, Jason] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97201 USA. [Kim, Ronald] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA. [Kowall, Neil W.; Mckee, Ann C.] Boston Univ, Dept Pathol, Boston, MA 02215 USA. [Lieberman, Andrew P.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Lopez, Oscar L.; Kamboh, M. Ilyas] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA USA. [Mack, Wendy J.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Martiniuk, Frank] NYU, Dept Med Pulm, New York, NY USA. [Mash, Deborah C.] Univ Miami, Dept Neurol, Miami, FL USA. [Masliah, Eliezer] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [McCurry, Susan M.] Univ Washington, Sch Nursing, NW Res Grp Aging, Seattle, WA 98195 USA. [Mesulam, Marsel; Weintraub, Sandra] Northwestern Univ, Alzheimers Dis Ctr, Chicago, IL 60611 USA. [Miller, Carol A.] Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. [Parisi, Joseph E.] Mayo Clin, Dept Anat Pathol, Rochester, MN USA. [Parisi, Joseph E.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Perl, Daniel P.] Mt Sinai Sch Med, Dept Pathol, New York, NY USA. [Peskind, Elaine; Raskind, Murray; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Reisberg, Barry] NYU, Alzheimers Dis Ctr, New York, NY USA. [Schneider, Lon S.] Univ So Calif, Dept Psychiat, Los Angeles, CA USA. [Shelanski, Michael L.] Columbia Univ, Dept Pathol, New York, NY USA. [Sonnen, Joshua A.; Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Troncoso, Juan C.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Vinters, Harry V.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. [Vonsattel, Jean Paul] Columbia Univ, Dept Pathol, Taub Inst, New York, NY USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Woltjer, Randall L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Beekly, Duane] Univ Washington, Natl Alzheimers Coordinating Ctr, Seattle, WA 98195 USA. [Saykin, Andrew J.] Indiana Univ, Dept Radiol & Imaging Sci, Indianapolis, IN 46204 USA. [Reiman, Eric M.] Univ Arizona, Dept Psychiat, Phoenix, AZ USA. [Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ USA. [Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Morris, John C.] Washington Univ, Dept Neurol, St Louis, MO USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Kukull, Walter A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Haines, Jonathan L.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Haines, Jonathan L.] Vanderbilt Univ, Vanderbilit Ctr Human Genet Res, Nashville, TN 37232 USA. [Mayeux, Richard] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. [St George-Hyslop, Peter] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. RP Schellenberg, GD (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. EM gerardsc@mail.med.upenn.edu RI Jarvik, Gail/N-6476-2014; Burke, James/E-4245-2016; Roberson, Erik/A-5718-2009; Myers, Amanda/B-1796-2010; Kauwe, John/B-2034-2009; Morris, John/A-1686-2012; Haines, Jonathan/C-3374-2012; Hardy, John/C-2451-2009; Kowall, Neil/G-6364-2012; Arnold, Steven/J-7546-2012; Ganguli, Mary/A-3638-2013; Saykin, Andrew/A-1318-2007; Crane, Paul/C-8623-2014; Sonnen, 37382016/H-3738-2016; Tsuang, Debby/L-7234-2016; OI Jarvik, Gail/0000-0002-6710-8708; Burke, James/0000-0002-3408-7787; Roberson, Erik/0000-0002-1810-9763; Myers, Amanda/0000-0002-3100-9396; Kauwe, John/0000-0001-8641-2468; Kowall, Neil/0000-0002-6624-0213; Saykin, Andrew/0000-0002-1376-8532; Sonnen, 37382016/0000-0001-9267-8705; Tsuang, Debby/0000-0002-4716-1894; Jun, Gyungah/0000-0002-3230-8697; Lunetta, Kathryn/0000-0002-9268-810X; Stern, Robert/0000-0002-5008-077X; Farrer, Lindsay/0000-0001-5533-4225; Reisberg, Barry/0000-0002-9104-7423; Carroll, Steven/0000-0001-6714-4373; Demirci, F. Yesim/0000-0001-6907-9843; Dickson, Dennis W/0000-0001-7189-7917; Kaye, Jeffrey/0000-0002-9971-3478; Kukull, Walter/0000-0001-8761-9014; Kamboh, M. Ilyas/0000-0002-3453-1438; Barmada, M Michael/0000-0002-3604-6460; Crane, Paul/0000-0003-4278-7465; Cruchaga, Carlos/0000-0002-0276-2899; Buros, Jacqueline/0000-0001-9588-4889; Ferris, Steven/0000-0001-8641-6223; Buxbaum, Joseph/0000-0001-8898-8313 FU National Institutes of Health, National Institute on Aging (NIH-NIA) [U01 AG032984, RC2 AG036528, U24 AG021886, U24 AG026395, U24 AG026390, P30 AG013846, R01 HG02213, K24 AG027841, U01 AG10483, R01 CA129769]; Northern California Institute for Research and Education; Abbott; AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; GlaxoSmithKline; Innogenetics; Johnson and Johnson; Eli Lilly and Co.; Medpace, Inc.; Merck and Co., Inc.; Novartis AG; Pfizer Inc.; F. Hoffman-La Roche; Schering-Plough; Synarc, Inc.; Alzheimer's Association [IIRG-08-89720, IIRG-05-14147]; Alzheimer's Drug Discovery Foundation; Dana Foundation; National Institute of Biomedical Imaging and Bioengineering and NIA [U01 AG024904, RC2 AG036535, K01 AG030514]; Veterans Affairs Administration; Wellcome Trust; Howard Hughes Medical Institute; Canadian Institute of Health Research; [U01 AG016976]; [R01 MH080295]; [R01 AG009029]; [R01 AG017173]; [R01 AG025259]; [P50 AG008702]; [R37 AG015473]; [P30 AG028377]; [AG025688]; [P30 AG10133]; [P50 AG005146]; [R01 AG020688]; [P50 AG005134]; [P50 AG016574]; [P50 AG005138]; [P01 AG002219]; [P30 AG08051]; [MO1RR00096]; [UL1 RR029893]; [P30 AG013854]; [P30 AG008017]; [R01 AG026916]; [P30 AG010161]; [R01 AG019085]; [R01 AG15819]; [R01 AG17917]; [R01 AG30146]; [P50 AG016582]; [UL1RR02777]; [P30 AG019610]; [R01 AG031581]; [R01 NS059873]; [P30 AG010129]; [P50 AG016573]; [P50]; [P50 AG016575]; [P50 AG016576]; [P50 AG016577]; [P50 AG016570]; [P50 AG005131]; [P50 AG023501]; [P01 AG019724]; [P30 AG028383]; [P50 AG008671]; [P30 AG010124]; [P50 AG005133]; [AG030653]; [P50 AG005142]; [P30 AG012300]; [R01 AG027944]; [AG010491]; [AG027944]; [AG021547]; [AG019757]; [P50 AG005136]; [UO1 AG06781]; [UO1 AG004610]; [P50 AG005681]; [P01 AG03991] FX The National Institutes of Health, National Institute on Aging (NIH-NIA) supported this work through the following grants: ADGC, U01 AG032984, RC2 AG036528; NACC, U01 AG016976; NCRAD, U24 AG021886; NIA LOAD, U24 AG026395, U24 AG026390; Boston University, P30 AG013846, R01 HG02213, K24 AG027841, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG009029, R01 AG017173, R01 AG025259; Columbia University, P50 AG008702, R37 AG015473; Duke University, P30 AG028377; Emory University, AG025688; Indiana University, P30 AG10133; Johns Hopkins University, P50 AG005146, R01 AG020688; Massachusetts General Hospital, P50 AG005134; Mayo Clinic, P50 AG016574; Mount Sinai School of Medicine, P50 AG005138, P01 AG002219; New York University, P30 AG08051, MO1RR00096, and UL1 RR029893; Northwestern University, P30 AG013854; Oregon Health & Science University, P30 AG008017, R01 AG026916; Rush University, P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146; University of Alabama at Birmingham, P50 AG016582, UL1RR02777; University of Arizona/TGEN, P30 AG019610, R01 AG031581, R01 NS059873; University of California, Davis, P30 AG010129; University of California, Irvine, P50 AG016573, P50, P50 AG016575, P50 AG016576, P50 AG016577; University of California, Los Angeles, P50 AG016570; University of California, San Diego, P50 AG005131; University of California, San Francisco, P50 AG023501, P01 AG019724; University of Kentucky, P30 AG028383; University of Michigan, P50 AG008671; University of Pennsylvania, P30 AG010124; University of Pittsburgh, P50 AG005133, AG030653; University of Southern California, P50 AG005142; University of Texas Southwestern, P30 AG012300; University of Miami, R01 AG027944, AG010491, AG027944, AG021547, AG019757; University of Washington, P50 AG005136, UO1 AG06781, UO1 HG004610; Vanderbilt University, R01 AG019085; and Washington University, P50 AG005681, P01 AG03991. ADNI Funding for ADNI is through the Northern California Institute for Research and Education by grants from Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc., F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., Alzheimer's Association, Alzheimer's Drug Discovery Foundation, the Dana Foundation, and by the National Institute of Biomedical Imaging and Bioengineering and NIA grants U01 AG024904, RC2 AG036535, K01 AG030514. We thank C. Phelps, M. Morrison-Bogorad and M. Miller from NIA who are ex-officio ADGC members. Support was also from the Alzheimer's Association (LAF, IIRG-08-89720; MP-V, IIRG-05-14147) and the Veterans Affairs Administration. P.S.-H. is supported by Wellcome Trust, Howard Hughes Medical Institute, and the Canadian Institute of Health Research. NR 42 TC 702 Z9 716 U1 12 U2 85 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 MAY PY 2011 VL 43 IS 5 BP 436 EP + DI 10.1038/ng.801 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 755XF UT WOS:000289972600012 PM 21460841 ER PT J AU DePristo, MA Banks, E Poplin, R Garimella, KV Maguire, JR Hartl, C Philippakis, AA del Angel, G Rivas, MA Hanna, M McKenna, A Fennell, TJ Kernytsky, AM Sivachenko, AY Cibulskis, K Gabriel, SB Altshuler, D Daly, MJ AF DePristo, Mark A. Banks, Eric Poplin, Ryan Garimella, Kiran V. Maguire, Jared R. Hartl, Christopher Philippakis, Anthony A. del Angel, Guillermo Rivas, Manuel A. Hanna, Matt McKenna, Aaron Fennell, Tim J. Kernytsky, Andrew M. Sivachenko, Andrey Y. Cibulskis, Kristian Gabriel, Stacey B. Altshuler, David Daly, Mark J. TI A framework for variation discovery and genotyping using next-generation DNA sequencing data SO NATURE GENETICS LA English DT Article ID SHORT READ ALIGNMENT; RESEQUENCING DATA; POPULATION-SCALE; QUALITY SCORES; SNP DISCOVERY; HUMAN EXOMES; GENOME; ACCURACY AB Recent advances in sequencing technology make it possible to comprehensively catalog genetic variation in population samples, creating a foundation for understanding human disease, ancestry and evolution. The amounts of raw data produced are prodigious, and many computational steps are required to translate this output into high-quality variant calls. We present a unified analytic framework to discover and genotype variation among multiple samples simultaneously that achieves sensitive and specific results across five sequencing technologies and three distinct, canonical experimental designs. Our process includes (i) initial read mapping; (ii) local realignment around indels; (iii) base quality score recalibration; (iv) SNP discovery and genotyping to find all potential variants; and (v) machine learning to separate true segregating variation from machine artifacts common to next-generation sequencing technologies. We here discuss the application of these tools, instantiated in the Genome Analysis Toolkit, to deep whole-genome, whole-exome capture and multi-sample low-pass (similar to 4x) 1000 Genomes Project datasets. C1 [DePristo, Mark A.; Banks, Eric; Poplin, Ryan; Garimella, Kiran V.; Maguire, Jared R.; Hartl, Christopher; Philippakis, Anthony A.; del Angel, Guillermo; Rivas, Manuel A.; Hanna, Matt; McKenna, Aaron; Fennell, Tim J.; Kernytsky, Andrew M.; Sivachenko, Andrey Y.; Cibulskis, Kristian; Gabriel, Stacey B.; Altshuler, David; Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Philippakis, Anthony A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Philippakis, Anthony A.; Altshuler, David; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. [Rivas, Manuel A.; Altshuler, David; Daly, Mark J.] Massachusetts Gen Hosp, Richard B Simches Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. RP DePristo, MA (reprint author), Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. EM depristo@broadinstitute.org RI Sincan, Murat /A-3794-2010; Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU National Human Genome Research Institute [54 HG003067, U01 HG005208] FX Many thanks to our colleagues in Medical and Population Genetics and Cancer Informatics and the 1000 Genomes Project who encouraged and supported us during the development of the Genome Analysis Toolkit and associated tools. This work was supported by grants from the National Human Genome Research Institute, including the Large Scale Sequencing and Analysis of Genomes grant (54 HG003067) and the Joint SNP and CNV calling in 1000 Genomes sequence data grant (U01 HG005208). We would also like to thank our excellent anonymous reviewers for their thoughtful comments. NR 38 TC 2492 Z9 2517 U1 69 U2 477 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 MAY PY 2011 VL 43 IS 5 BP 491 EP + DI 10.1038/ng.806 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 755XF UT WOS:000289972600023 PM 21478889 ER PT J AU Ni, JQ Zhou, R Czech, B Liu, LP Holderbaum, L Yang-Zhou, DH Shim, HS Tao, R Handler, D Karpowicz, P Binari, R Booker, M Brennecke, J Perkins, LA Hannon, GJ Perrimon, N AF Ni, Jian-Quan Zhou, Rui Czech, Benjamin Liu, Lu-Ping Holderbaum, Laura Yang-Zhou, Donghui Shim, Hye-Seok Tao, Rong Handler, Dominik Karpowicz, Phillip Binari, Richard Booker, Matthew Brennecke, Julius Perkins, Lizabeth A. Hannon, Gregory J. Perrimon, Norbert TI A genome-scale shRNA resource for transgenic RNAi in Drosophila SO NATURE METHODS LA English DT Article ID GENE-EXPRESSION; MELANOGASTER; PATHWAY; GERMLINE AB Existing transgenic RNAi resources in Drosophila melanogaster based on long double-stranded hairpin RNAs are powerful tools for functional studies, but they are ineffective in gene knockdown during oogenesis, an important model system for the study of many biological questions. We show that shRNAs, modeled on an endogenous microRNA, are extremely effective at silencing gene expression during oogenesis. We also describe our progress toward building a genome-wide shRNA resource. C1 [Ni, Jian-Quan; Zhou, Rui; Liu, Lu-Ping; Holderbaum, Laura; Yang-Zhou, Donghui; Shim, Hye-Seok; Tao, Rong; Karpowicz, Phillip; Binari, Richard; Booker, Matthew; Perrimon, Norbert] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. [Czech, Benjamin; Hannon, Gregory J.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA. [Perkins, Lizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA USA. [Handler, Dominik; Brennecke, Julius] Inst Mol Biotechnol, Vienna, Austria. RP Perrimon, N (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. EM perrimon@receptor.med.harvard.edu RI Brennecke, Julius/C-1626-2015; Karpowicz, Phillip/C-3334-2016; OI Brennecke, Julius/0000-0002-5141-0814; Czech, Benjamin/0000-0001-8471-0007; Handler, Dominik/0000-0002-1059-4960; Booker, Matthew/0000-0002-6902-1032 FU Janelia Farm Visitor Program; Leukemia and Lymphoma Society; Boehringer Ingelheim Fonds; US National Institute of General Medical Sciences [GM067761, GM084947]; EU FP7 European Research Council FX The design and construction of the first shRNAs were supported in part by the Janelia Farm Visitor Program. We thank G. Rubin, C. Zuker and T. Laverty for their interest and support; R. Hardy and C. Zuker for the data presented in Supplementary Table 2; B. Haley for helpful discussion on shRNAs; L. Cooley (Yale University) for the gift of the MTD-Gal4 line; and Z. Xuan for help with library design. S. Zusman and M. Tworoger of Genetic Services, Inc. generated the transgenic lines. R.Z. is supported by the Leukemia and Lymphoma Society. B.C. is supported by a PhD fellowship from the Boehringer Ingelheim Fonds. This work was supported by two US National Institute of General Medical Sciences R01 grants (GM067761 and GM084947) to N.P., an EU FP7 European Research Council starting grant to J.B. and contributions from the US National Institute of Neurological Disorders and Stroke. NR 26 TC 269 Z9 270 U1 8 U2 46 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD MAY PY 2011 VL 8 IS 5 BP 405 EP U46 DI 10.1038/NMETH.1592 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 756BQ UT WOS:000289987100017 PM 21460824 ER PT J AU Ganguly, K Dimitrov, DF Wallis, JD Carmena, JM AF Ganguly, Karunesh Dimitrov, Dragan F. Wallis, Jonathan D. Carmena, Jose M. TI Reversible large-scale modification of cortical networks during neuroprosthetic control SO NATURE NEUROSCIENCE LA English DT Article ID BRAIN-COMPUTER INTERFACE; MOTOR CORTEX; REACHING MOVEMENTS; MACHINE INTERFACE; ARM MOVEMENTS; UNIT-ACTIVITY; FORCE-FIELD; PERFORMANCE; NEURONS; ADAPTATION AB Brain-machine interfaces (BMIs) provide a framework for studying cortical dynamics and the neural correlates of learning. Neuroprosthetic control has been associated with tuning changes in specific neurons directly projecting to the BMI (hereafter referred to as direct neurons). However, little is known about the larger network dynamics. By monitoring ensembles of neurons that were either causally linked to BMI control or indirectly involved, we found that proficient neuroprosthetic control is associated with large-scale modifications to the cortical network in macaque monkeys. Specifically, there were changes in the preferred direction of both direct and indirect neurons. Notably, with learning, there was a relative decrease in the net modulation of indirect neural activity in comparison with direct activity. These widespread differential changes in the direct and indirect population activity were markedly stable from one day to the next and readily coexisted with the long-standing cortical network for upper limb control. Thus, the process of learning BMI control is associated with differential modification of neural populations based on their specific relation to movement control. C1 [Ganguly, Karunesh; Wallis, Jonathan D.; Carmena, Jose M.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Ganguly, Karunesh] San Francisco VA Med Ctr, Dept Neurol & Rehabil, San Francisco, CA USA. [Ganguly, Karunesh; Carmena, Jose M.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. [Ganguly, Karunesh] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Dimitrov, Dragan F.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Wallis, Jonathan D.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Carmena, Jose M.] Univ Calif Berkeley, Program Cognit Sci, Berkeley, CA 94720 USA. [Carmena, Jose M.] Univ Calif San Francisco, Joint Grad Grp Bioengn, San Francisco, CA 94143 USA. RP Carmena, JM (reprint author), Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. EM carmena@eecs.berkeley.edu OI Wallis, Joni/0000-0001-7262-7417 FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development; American Heart Association/American Stroke Association; National Institute of Neurological Disorders and Stroke [NS21135]; Alfred P. Sloan Foundation; Christopher and Dana Reeve Foundation; National Science Foundation [0954243]; Defense Advanced Research Projects Agency [N66001-10-C-2008] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development, and the American Heart Association/American Stroke Association (to K. G.), the National Institute of Neurological Disorders and Stroke grant number NS21135 (to J.D.W.), the Alfred P. Sloan Foundation, the Christopher and Dana Reeve Foundation, the National Science Foundation CAREER Award #0954243 and the Defense Advanced Research Projects Agency contract N66001-10-C-2008 (to J.M.C.). NR 45 TC 84 Z9 84 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2011 VL 14 IS 5 BP 662 EP U164 DI 10.1038/nn.2797 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 754VU UT WOS:000289886600024 PM 21499255 ER PT J AU Delmonico, FL AF Delmonico, Francis L. TI Transplant tourism-an update regarding the realities SO NATURE REVIEWS NEPHROLOGY LA English DT News Item ID KIDNEY DONORS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Delmonico, FL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM francis_delmonico@neob.org NR 10 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD MAY PY 2011 VL 7 IS 5 BP 248 EP 250 DI 10.1038/nrneph.2011.40 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 755YK UT WOS:000289977200002 PM 21522193 ER PT J AU Biffi, A Devan, WJ Anderson, CD Ayres, AM Schwab, K Cortellini, L Viswanathan, A Rost, NS Smith, EE Goldstein, JN Greenberg, SM Rosand, J AF Biffi, A. Devan, W. J. Anderson, C. D. Ayres, A. M. Schwab, K. Cortellini, L. Viswanathan, A. Rost, N. S. Smith, E. E. Goldstein, J. N. Greenberg, S. M. Rosand, J. TI Statin use and outcome after intracerebral hemorrhage Case-control study and meta-analysis SO NEUROLOGY LA English DT Article ID COA REDUCTASE INHIBITOR; NITRIC-OXIDE SYNTHASE; ATORVASTATIN; MORTALITY; STROKE; NEUROGENESIS; ANGIOGENESIS; ACTIVATION AB Objectives: Intracerebral hemorrhage (ICH) is a highly lethal disease of the elderly. Use of statins is increasingly widespread among the elderly, and therefore common in patients who develop ICH. Accumulating data suggests that statins have neuroprotective effects, but their association with ICH outcome has been inconsistent. We therefore performed a meta-analysis of all available evidence, including unpublished data from our own institution, to determine whether statin exposure is protective for patients who develop ICH. Methods: In our prospectively ascertained cohort, we compared 90-day functional outcome in 238 pre-ICH statin cases and 461 statin-free ICH cases. We then meta-analyzed results from our cohort along with previously published studies using a random effects model, for a total of 698 ICH statin cases and 1,823 non-statin-exposed subjects. Results: Data from our center demonstrated an association between statin use before ICH and increased probability of favorable outcome (odds ratio [OR] = 2.08, 95% confidence interval [CI] 1.37-3.17) and reduced mortality (OR = 0.47, 95% CI 0.32-0.70) at 90 days. No compound-specific statin effect was identified. Meta-analysis of all published evidence confirmed the effect of statin use on good outcome (OR = 1.91, 95% CI 1.38-2.65) and mortality (OR = 0.55, 95% CI 0.42-0.72) after ICH. Conclusion: Antecedent use of statins prior to ICH is associated with favorable outcome and reduced mortality after ICH. This phenomenon appears to be a class effect of statins. Further studies are required to clarify the biological mechanisms underlying these observations. Neurology (R) 2011;76:1581-1588 C1 [Biffi, A.; Devan, W. J.; Anderson, C. D.; Cortellini, L.; Rost, N. S.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Biffi, A.; Devan, W. J.; Anderson, C. D.; Ayres, A. M.; Schwab, K.; Cortellini, L.; Viswanathan, A.; Rost, N. S.; Goldstein, J. N.; Greenberg, S. M.; Rosand, J.] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Biffi, A.; Devan, W. J.; Anderson, C. D.; Cortellini, L.; Rost, N. S.; Goldstein, J. N.; Rosand, J.] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Dept Neurol, Boston, MA 02114 USA. [Goldstein, J. N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Smith, E. E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM jrosand@partners.org RI Goldstein, Joshua/H-8953-2016; OI Smith, Eric/0000-0003-3956-1668 FU Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; NIH/NINDS; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research; American Heart Association/Bugher Foundation; NIH (NINDS, NIA); NIH/NIA; National Stroke Association; NIH; CIHR; Canadian Stroke Network; Alberta Heritage Fund; Hotchkiss Brain Institute; Heart and Stroke Foundation of Canada; CSL Behring; Alzheimer's Association; NIH (NINDS, NHLBI); MGH Deane Institute for Integrative Research in Atrial Fibrillation and Stroke FX Supported by the Deane Institute for Integrative Study of Atrial Fibrillation and Stroke, the NIH/NINDS, and the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research. The funding entities had no involvement in study design, data collection, analysis, or interpretation, writing of the report, or in the decision to submit the paper for publication.; Dr. Biffi receives research support from the American Heart Association/Bugher Foundation. W.J. Devan reports no disclosures. Dr. Anderson has received research support from the American Heart Association/Bugher Foundation. A. M. Ayres reports no disclosures. K. Schwab receives research support from the NIH (NINDS, NIA). L. Cortellini reports no disclosures. Dr. Viswanathan has served as consultant for Athena Diagnostics, Inc. and receives research support from the NIH/NIA. Dr. Rost serves as an Associate Editor for Frontiers in Hospitalist Neurology and an Assistant Editor for Stroke and has received research support from the NIH/NINDS, the National Stroke Association, and the American Stroke Association/Bugher Foundation. Dr. Smith serves as an Assistant Editor for Stroke; has received speaker honoraria from the Canadian Consortium on Dementia; serves on speakers' bureaus for QuantiaMD and BMJ Best Practice; and receives research support from the NIH, the CIHR, the Canadian Stroke Network, Alberta Innovates-Health Solutions (funded by the Alberta Heritage Fund for Medical Research), Hotchkiss Brain Institute, and the Heart and Stroke Foundation of Canada. Dr. Goldstein serves on a scientific advisory board for and received funding for travel and consulting honoraria from CSL Behring; serves on the editorial board of the International Journal of Emergency Medicine; and receives research support from CSL Behring and the NIH/NINDS. Dr. Greenberg serves on a data safety monitoring board for the NIH/NINDS; has received speaker honoraria from Esteve, Medtronics, Inc., and Pfizer Inc; serves on the editorial boards of Neurology (R), Stroke, Cerebrovascular Disease, and the Journal of Alzheimer's Disease and Other Dementias; has served as a consultant for Roche, Janssen Alzheimer Immunotherapy, and Bristol-Myers Squibb; and has received/receives research support from the NIH and the Alzheimer's Association. Dr. Rosand receives research support from the NIH (NINDS, NHLBI), the American Heart Association/Bugher Foundation, and the MGH Deane Institute for Integrative Research in Atrial Fibrillation and Stroke. NR 30 TC 33 Z9 36 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2011 VL 76 IS 18 BP 1581 EP 1588 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 758GK UT WOS:000290150800011 PM 21451150 ER PT J AU Gallagher, A Kovach, A Stemmer-Rachamimov, A Rosenberg, AE Eskandar, E Thiele, EA AF Gallagher, A. Kovach, A. Stemmer-Rachamimov, A. Rosenberg, A. E. Eskandar, E. Thiele, E. A. TI METAPLASTIC BONE IN A CORTICAL TUBER OF A YOUNG PATIENT WITH TUBEROUS SCLEROSIS COMPLEX SO NEUROLOGY LA English DT Editorial Material ID EPILEPSY C1 [Gallagher, A.; Thiele, E. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, Boston, MA 02114 USA. [Kovach, A.; Rosenberg, A. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stemmer-Rachamimov, A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Stemmer-Rachamimov, A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Eskandar, E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU NINDS NIH HHS [NINDS1P01NS24279] NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2011 VL 76 IS 18 BP 1602 EP 1604 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 758GK UT WOS:000290150800015 PM 21536642 ER PT J AU Taylor, CE Camargo, CA AF Taylor, Christopher E. Camargo, Carlos A., Jr. TI Impact of micronutrients on respiratory infections SO NUTRITION REVIEWS LA English DT Review DE immune response; micronutrients; respiratory infection ID PLACEBO-CONTROLLED TRIAL; A VIRUS-INFECTION; VITAMIN-D LEVELS; MYCOBACTERIUM-TUBERCULOSIS; TRACT INFECTION; INFLUENZA-A; FOLIC-ACID; 25-HYDROXYVITAMIN-D LEVELS; DIETARY REQUIREMENT; DOUBLE-BLIND AB Several studies have documented the impact of vitamin D and other micronutrients on host responses to upper and lower respiratory tract infections, such as influenza and tuberculosis. These studies include observational as well as micronutrient intervention studies. Other studies have been conducted to understand the mechanisms by which micronutrients alter immune responses. However, critical information gaps and challenges remain. An immediate need exists for randomized controlled trials of vitamin D supplementation in high-risk populations, such as infants, children, and patients with immunocompromised health. Other important areas of research include vitamin D genetics, the impact of other micronutrient deficiencies on innate and adaptive immunity, the 25(OH)D threshold for insufficiency, the need for valuable reliable markers, standardization of assays to detect 25(OH)D, novel functional markers beyond serum 25(OH)D, and further development of in vitro and animal models that could be useful for preclinical studies. Lastly, a new systems biology approach is needed to address the complexity of micronutrient effects and regulation. C1 [Taylor, Christopher E.] NIAID, Resp Dis Branch, Div Microbiol & Infect Dis, Bethesda, MD 20852 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Taylor, CE (reprint author), NIAID, Resp Dis Branch, Div Microbiol & Infect Dis, 6610 Rockledge Dr,Room 5045, Bethesda, MD 20852 USA. EM ctaylor@niaid.nih.gov RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 NR 71 TC 20 Z9 20 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 2011 VL 69 IS 5 BP 259 EP 269 DI 10.1111/j.1753-4887.2011.00386.x PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 754XV UT WOS:000289892100002 PM 21521228 ER PT J AU Bredella, MA Torriani, M Ghomi, RH Thomas, BJ Brick, DJ Gerweck, AV Harrington, LM Miller, KK AF Bredella, Miriam A. Torriani, Martin Ghomi, Reza H. Thomas, Bijoy J. Brick, Danielle J. Gerweck, Anu V. Harrington, Lindsey M. Miller, Karen K. TI Adiponectin Is Inversely Associated With Intramyocellular and Intrahepatic Lipids in Obese Premenopausal Women SO OBESITY LA English DT Article ID MOLECULAR-WEIGHT ADIPONECTIN; HEPATIC INSULIN-RESISTANCE; NONALCOHOLIC FATTY LIVER; NECROSIS-FACTOR-ALPHA; ADIPOSE-TISSUE; RESONANCE SPECTROSCOPY; PLASMA ADIPONECTIN; METABOLIC SYNDROME; HYPOADIPONECTINEMIA; SENSITIVITY AB Adiponectin, an adipokine secreted by adipocytes, exerts beneficial effects on glucose and lipid metabolism and has been found to improve insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. Adiponectin is found in several isoforms and the high-molecular weight (HMW) form has been linked most strongly to the insulin-sensitizing effects. Fat content in skeletal muscle (intramyocellular lipids, IMCL) and liver (intrahepatic lipids, IHL) can be quantified noninvasively using proton magnetic resonance spectroscopy ((1)H-MRS). The purpose of our study was to assess the relationship between HMW adiponectin and measures of glucose homeostasis, IMCL and IHL, and to determine predictors of adiponectin levels. We studied 66 premenopausal women (mean BMI 31.0 +/- 6.6 kg/m(2)) who underwent 1H-MRS of calf muscles and liver for IMCL and IHL, computed tomography (CT) of the abdomen for abdominal fat depots, dual-energy X-ray absorptiometry (DXA) for fat and lean mass assessments, HMW and total adiponectin, fasting lipid profile and an oral glucose tolerance test (homeostasis model assessment of insulin resistance (HOMA(IR)), glucose and insulin area under the curve). There were strong inverse associations between HMW adiponectin and measures of insulin resistance, IMCL and IHL, independent of visceral adipose tissue (VAT) and total body fat. IHL was the strongest predictor of adiponectin and adiponectin was a predictor of HOMA(IR). Our study showed that in premenopausal obese women HMW adiponectin is inversely associated with IMCL and IHL content. This suggests that adiponectin exerts positive effects on insulin sensitivity in obesity by decreasing intracellular triglyceride content in skeletal muscle and liver; it is also possible that our results reflect effects of insulin on adiponectin. C1 [Bredella, Miriam A.; Torriani, Martin; Ghomi, Reza H.; Thomas, Bijoy J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Brick, Danielle J.; Gerweck, Anu V.; Harrington, Lindsey M.; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM mbredella@partners.org OI Hosseini Ghomi, Reza/0000-0003-4369-8237 FU National Institutes of Health [RO1 HL-077674, UL1 RR025758, K23 RR-23090] FX This work was supported in part by National Institutes of Health Grants RO1 HL-077674, UL1 RR025758, and K23 RR-23090. NR 37 TC 11 Z9 11 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD MAY PY 2011 VL 19 IS 5 BP 911 EP 916 DI 10.1038/oby.2010.296 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 755LS UT WOS:000289933300006 PM 21151017 ER PT J AU Keay, LJ Gower, EW Iovieno, A Oechsler, RA Alfonso, EC Matoba, A Colby, K Tuli, SS Hammersmith, K Cavanagh, D Lee, SM Irvine, J Stulting, RD Mauger, TF Schein, OD AF Keay, Lisa J. Gower, Emily W. Iovieno, Alfonso Oechsler, Rafael A. Alfonso, Eduardo C. Matoba, Alice Colby, Kathryn Tuli, Sonal S. Hammersmith, Kristin Cavanagh, Dwight Lee, Salena M. Irvine, John Stulting, R. Doyle Mauger, Thomas F. Schein, Oliver D. TI Clinical and Microbiological Characteristics of Fungal Keratitis in the United States, 2001-2007: A Multicenter Study SO OPHTHALMOLOGY LA English DT Article ID INFECTIOUS CORNEAL ULCERS; CONTACT-LENS WEAR; MICROBIAL KERATITIS; SOUTH-INDIA; EPIDEMIOLOGIC CHARACTERISTICS; ETIOLOGIC DIAGNOSIS; RISK-FACTORS; SPECTRUM; FUSARIUM; EYE AB Objective: To study the epidemiology, clinical observations, and microbiologic characteristics of fungal keratitis at tertiary eye care centers in the United States. Design: Retrospective multicenter case series. Participants: Fungal keratitis cases presenting to participating tertiary eye care centers. Methods: Charts were reviewed for all fungal keratitis cases confirmed by culture, histology, or confocal microscopy between January 1, 2001, and December 31, 2007, at 11 tertiary clinical sites in the United States. Main Outcome Measures: Frequency of potential predisposing factors and associations between these factors and fungal species. Results: A total of 733 cases of fungal keratitis were identified. Most cases were confirmed by culture from corneal scraping (n = 693) or biopsies (n = 19); 16 cases were diagnosed by microscopic examination of corneal scraping alone; and 5 cases were diagnosed by confocal microscopy alone. Some 268 of 733 cases (37%) were associated with refractive contact lens wear, 180 of 733 cases (25%) were associated with ocular trauma, and 209 of 733 cases (29%) were associated with ocular surface disease. No predisposing factor was identified in 76 cases (10%). Filamentous fungi were identified in 141 of 180 ocular trauma cases (78%) and in 231 of 268 refractive contact lens-associated cases (86%). Yeast was the causative organism in 111 of 209 cases (53%) associated with ocular surface disease. Yeast accounted for few cases of fungal keratitis associated with refractive contact-lens wear (20 cases), therapeutic contact-lens wear (11 cases), or ocular trauma (21 cases). Surgical intervention was undertaken in 26% of cases and was most frequently performed for fungal keratitis associated with ocular surface disease (44%). Surgical intervention was more likely in cases associated with filamentous fungi (P = 0.03). Among contact lens wearers, delay in diagnosis of 2 or more weeks increased the likelihood of surgery (age-adjusted odds ratio = 2.2; 95% confidence interval, 1.2-4.2). Conclusions: Trauma, contact lens wear, and ocular surface disease predispose patients to developing fungal keratitis. Filamentous fungi are most frequently the causative organism for fungal keratitis associated with trauma or contact lens wear, whereas yeast is most frequently the causative organism in patients with ocular surface disease. Delay in diagnosis increases the likelihood of surgical intervention for contact lens-associated fungal keratitis. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011;118:920-926 (C) 2011 by the American Academy of Ophthalmology. C1 [Keay, Lisa J.] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Gower, Emily W.; Schein, Oliver D.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. [Iovieno, Alfonso] CIR Lab Ophthalmol, Rome, Italy. [Oechsler, Rafael A.; Alfonso, Eduardo C.] Univ Miami, Bascom Palmer Eye Inst, Miami, FL USA. [Matoba, Alice] Baylor Coll Med, Cullen Eye Inst, Dept Ophthalmol, Houston, TX 77030 USA. [Colby, Kathryn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Ophthalmol, Boston, MA USA. [Tuli, Sonal S.] Univ Florida, Dept Ophthalmol, Gainesville, FL USA. [Hammersmith, Kristin] Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Hosp, Philadelphia, PA 19107 USA. [Cavanagh, Dwight] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX USA. [Lee, Salena M.] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. [Irvine, John] Univ So Calif, Doheny Eye Inst, Los Angeles, CA USA. [Stulting, R. Doyle] Woolfson Eye Inst, Stulting Res Ctr, Atlanta, GA USA. [Mauger, Thomas F.] Ohio State Univ, Havener Eye Inst, Columbus, OH 43210 USA. [Iovieno, Alfonso] GB Bietti Eye Fdn, Rome, Italy. RP Gower, EW (reprint author), Johns Hopkins Sch Med, 600 N Wolfe St,116 Wilmer Bldg, Baltimore, MD 21287 USA. EM egower1@jhmi.edu RI Iovieno, Alfonso /B-2939-2011 FU Alcon Laboratories Inc. Emily Gower; Bausch Lomb, Inc.; Research to Prevent Blindness FX The author(s) have made the following disclosures: Eduardo Alfonso, Consultant, Bausch & Lomb, Inc. Oliver Schein, Consultant, Bausch & Lomb, Inc. R. Doyle Stulting, Consultant, Allergan Inc. and Alcon Laboratories Inc. Emily Gower, Grant Support, Bausch & Lomb, Inc. This project was funded by an unrestricted grant from Bausch & Lomb, Inc. Bausch & Lomb, Inc. did not provide input into the content of this manuscript.; An unrestricted grant from Bausch & Lomb Inc. Bausch & Lomb, Inc., did not have input on the content of the manuscript or the analyses. Dr. Gower is a recipient of the Research to Prevent Blindness Althouse Special Scholars Award. NR 32 TC 44 Z9 51 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2011 VL 118 IS 5 BP 920 EP 926 DI 10.1016/j.ophtha.2010.09.011 PG 7 WC Ophthalmology SC Ophthalmology GA 757MM UT WOS:000290090300020 PM 21295857 ER PT J AU Jampel, HD Singh, K Lin, SC Chen, TC Francis, BA Hodapp, E Samples, JR Smith, SD Collins, N AF Jampel, Henry D. Singh, Kuldev Lin, Shan C. Chen, Teresa C. Francis, Brian A. Hodapp, Elizabeth Samples, John R. Smith, Scott D. Collins, Nancy TI Assessment of Visual Function in Glaucoma A Report by the American Academy of Ophthalmology SO OPHTHALMOLOGY LA English DT Article ID FREQUENCY-DOUBLING TECHNOLOGY; WAVELENGTH AUTOMATED PERIMETRY; MACHINE LEARNING CLASSIFIERS; INTERACTIVE THRESHOLD ALGORITHM; STANDARD ACHROMATIC PERIMETRY; PASS RESOLUTION PERIMETRY; FIELD PROGRESSION; OCULAR HYPERTENSION; MATRIX PERIMETRY; FULL-THRESHOLD AB Objective: To review the published literature to summarize and evaluate the effectiveness of visual function tests in diagnosing glaucoma and in monitoring progression. Methods: Literature searches of the PubMed and Cochrane Library databases were conducted last on May 7, 2010, and were restricted to citations published on or after January 1, 1994. The search yielded 1063 unique citations. The first author reviewed the titles and abstracts of these articles and selected 185 of possible clinical relevance for further review. The panel members reviewed the full text of these articles and determined that 85 met inclusion criteria. They conducted data abstraction of the 85 studies, and the panel methodologist assigned a level of evidence to each of the selected articles. One study was rated as level I evidence. The remaining articles were classified broadly as providing level II evidence. Studies deemed to provide level III evidence were not included in the assessment. Results: Standard white-on-white automated perimetry remains the most commonly performed test for assessing the visual field, with the Swedish interactive threshold algorithm (SITA) largely replacing full-threshold testing strategies. Frequency-doubling technology and its refinement into Matrix perimetry, as well as short-wavelength automated perimetry, now available with SITA, have been evaluated extensively. Machine learning classifiers seem to be ready for incorporation into software to help distinguish glaucomatous from nonglauco-matous fields. Other technologies, such as multifocal visual-evoked potential and electroretinography, which were designed as objective measures of visual function, provide testing free of patient input, but issues prevent their adoption for glaucoma management. Conclusions: Advances in technology and analytic tools over the past decade have provided us with more rapid and varied ways of assessing visual function in glaucoma, but they have yet to produce definitive guidance on the diagnosis of glaucoma or its progression over time. Further research on an objective measure of visual function is needed. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011; 118: 986-1002 (C) 2011 by the American Academy of Ophthalmology. C1 [Jampel, Henry D.] Johns Hopkins Univ, Wilmer Eye Inst, Glaucoma Div, Baltimore, MD 21218 USA. [Singh, Kuldev] Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA. [Lin, Shan C.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Chen, Teresa C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv, Boston, MA USA. [Francis, Brian A.] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA. [Hodapp, Elizabeth] Bascom Palmer Eye Inst, Miami, FL 33136 USA. [Samples, John R.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Samples, John R.] Rocky Vista Univ, Dept Surg, Parker, CO USA. [Smith, Scott D.] Columbia Univ, Edward S Harkness Eye Inst, New York, NY USA. RP Collins, N (reprint author), Amer Acad Ophthalmol, POB 7424, San Francisco, CA 94120 USA. EM ncollins@aao.org FU American Academy of Ophthalmology FX Funded without commercial support by the American Academy of Ophthalmology. NR 81 TC 28 Z9 30 U1 0 U2 9 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 MAY PY 2011 VL 118 IS 5 BP 986 EP 1002 DI 10.1016/j.ophtha.2011.03.019 PG 17 WC Ophthalmology SC Ophthalmology GA 757MM UT WOS:000290090300030 PM 21539982 ER PT J AU Alonzo, CA Yun, SH AF Alonzo, Carlo Amadeo Yun, Seok H. TI Harmonic mode locking in a sliding-frequency fiber laser SO OPTICS LETTERS LA English DT Article ID SHIFTED FEEDBACK; REPETITION RATE; PULSES AB We demonstrate a sliding-frequency mode-locked (SFM) erbium fiber laser generating 20 ps pulses with center wavelengths rapidly sweeping across a spectral range of 50nm. Excess optical nonlinearity in the laser cavity leads to multipulsing, with a tendency to tight pulse bunching (<3 ns) at the fundamental cavity frequency of 25 MHz. The addition of a parallel optical delay line, with a path difference equal to a rational fraction of the cavity length, distributes the pulses uniformly across the entire cavity and achieves a harmonic SFM up to 1 GHz. The result establishes cavity nonlinearity as a critical design parameter for picosecond wavelength-swept lasers. (C) 2011 Optical Society of America C1 [Yun, Seok H.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 40 Blossom St,BAR8, Boston, MA 02114 USA. EM syun@hms.harvard.edu FU National Science Foundation (NSF) [ECCS-0801412] FX This work was supported by the National Science Foundation (NSF) (ECCS-0801412). NR 13 TC 1 Z9 1 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAY 1 PY 2011 VL 36 IS 9 BP 1590 EP 1592 PG 3 WC Optics SC Optics GA 756TJ UT WOS:000290037300022 PM 21540937 ER PT J AU Greenbaum, CJ McCulloch-Olson, M Chiu, HK Palmer, JP Brooks-Worrell, B AF Greenbaum, Carla J. McCulloch-Olson, Marli Chiu, Harvey K. Palmer, Jerry P. Brooks-Worrell, Barbara TI Parenteral insulin suppresses T cell proliferation to islet antigens SO PEDIATRIC DIABETES LA English DT Article DE diabetes prevention trial; T cell; type 1 diabetes ID BLOOD MONONUCLEAR-CELLS; TYPE-1 AB The diabetes prevention trial-type 1 (DPT-1) tested whether a combination of SQ and IV insulin therapy would delay the onset of disease in individuals at high risk of progression. We investigated whether this regimen altered T cell responses to human islet proteins using cellular immunoblotting. Among the 10 treated and 7 control subjects studied, we found that there was a significant effect of treatment on cellular immunoblotting responses. We conclude that parenteral insulin may suppress proliferation to islet antigens in individuals at risk for diabetes, but this effect may be transient. Further study is needed to determine whether a therapy that results in sustained suppression of T cell proliferation could yield a measurable clinical benefit. C1 [Greenbaum, Carla J.] Benaroya Res Inst, Seattle, WA 98101 USA. [McCulloch-Olson, Marli] Seattle Childrens Hosp, Seattle, WA USA. [Palmer, Jerry P.; Brooks-Worrell, Barbara] Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Greenbaum, CJ (reprint author), Benaroya Res Inst, 1201 9th Ave, Seattle, WA 98101 USA. EM cjgreen@benaroyaresearch.org FU Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development; National Center for Research Resources; American Diabetes Association; Juvenile Diabetes Research Foundation; Medical Research Services of the Department of Veterans Affairs; NIH/NIDDK [P30 DK17047, U01 DK46601]; NCRR [M01-RR-00037]; Benaroya Research Institute FX The DPT-1 study was supported by cooperative agreements with the Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute of Allergy and Infectious Diseases; the National Institute of Child Health and Human Development; the National Center for Research Resources; the American Diabetes Association; and the Juvenile Diabetes Research Foundation. Supplies were provided by Eli Lilly, Bayer, Becton Dickinson, International Technidyne, LifeScan, the Mead Johnson Nutritionals Division of Bristol-Myers Squibb, the Medisense Division of Abbott Laboratories, MiniMed, and Roche Diagnostics. Harvey Chiu was an Endocrinology fellow supported (in part) by the Medical Research Services of the Department of Veterans Affairs. This research was also supported in part by NIH/NIDDK grants P30 DK17047, U01 DK46601 and a Clinical Research grant from the American Diabetes Association. DPT-1 subjects in this ancillary study and those in the pilot study for individuals with type 1 diabetes were observed at the GCRC of the University of Washington. This study is currently funded under NCRR Grant M01-RR-00037. Additional support is provided in part by the Buse Diabetes Research Fund at the Benaroya Research Institute. NR 16 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD MAY PY 2011 VL 12 IS 3 BP 150 EP 155 DI 10.1111/j.1399-5448.2010.00674.x PN 1 PG 6 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 754XW UT WOS:000289892200003 PM 20522167 ER PT J AU Whitford, TJ Mathalon, DH Shenton, ME Roach, BJ Bammer, R Adcock, RA Bouix, S Kubicki, M De Siebenthal, J Rausch, AC Schneiderman, JS Ford, JM AF Whitford, T. J. Mathalon, D. H. Shenton, M. E. Roach, B. J. Bammer, R. Adcock, R. A. Bouix, S. Kubicki, M. De Siebenthal, J. Rausch, A. C. Schneiderman, J. S. Ford, J. M. TI Electrophysiological and diffusion tensor imaging evidence of delayed corollary discharges in patients with schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Arcuate fasciculus; conduction delays; efference copy; forward model; white matter ID HUMAN AUDITORY-CORTEX; NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; OPTIC NEURITIS; HUMAN BRAIN; OLIGODENDROCYTE; DYSFUNCTION; PATHWAYS; HALLUCINATIONS; RESPONSIVENESS AB Background. Patients with schizophrenia (SZ) characteristically exhibit supranormal levels of cortical activity to self-induced sensory stimuli, ostensibly because of abnormalities in the neural signals (corollary discharges, CDs) normatively involved in suppressing the sensory consequences of self-generated actions. The nature of these abnormalities is unknown. This study investigated whether SZ patients experience CDs that are abnormally delayed in their arrival at the sensory cortex. Method. Twenty-one patients with SZ and 25 matched control participants underwent electroencephalography (EEG). Participants' level of cortical suppression was calculated as the amplitude of the N1 component evoked by a button press-elicited auditory stimulus, subtracted from the N1 amplitude evoked by the same stimulus presented passively. In the three experimental conditions, the auditory stimulus was delivered 0, 50 or 100 ms subsequent to the button-press. Fifteen SZ patients and 17 healthy controls (HCs) also underwent diffusion tensor imaging (DTI), and the fractional anisotropy (FA) of participants' arcuate fasciculus was used to predict their level of cortical suppression in the three conditions. Results. While the SZ patients exhibited subnormal N1 suppression to undelayed, self-generated auditory stimuli, these deficits were eliminated by imposing a 50-ms, but not a 100-ms, delay between the button-press and the evoked stimulus. Furthermore, the extent to which the 50-ms delay normalized a patient's level of N1 suppression was linearly related to the FA of their arcuate fasciculus. Conclusions. These data suggest that SZ patients experience temporally delayed CDs to self-generated auditory stimuli, putatively because of structural damage to the white-matter (WM) fasciculus connecting the sites of discharge initiation and destination. C1 [Whitford, T. J.; Shenton, M. E.; Bouix, S.; Kubicki, M.; De Siebenthal, J.; Rausch, A. C.; Schneiderman, J. S.] Harvard Univ, Sch Med, Psychiat Neuroimaging Lab, Dept Psychiat,Brigham & Womens Hosp, Boston, MA 02215 USA. [Whitford, T. J.] Univ Melbourne & Melbourne Hlth, Melbourne Neuropsychiat Ctr, Dept Psychiat, Melbourne, Vic, Australia. [Mathalon, D. H.; Roach, B. J.; Ford, J. M.] Univ Calif San Francisco, Dept Psychiat, Brain Imaging & EEG Lab, San Francisco, CA 94143 USA. [Mathalon, D. H.; Roach, B. J.; Ford, J. M.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA USA. [Shenton, M. E.; Kubicki, M.] Harvard Univ, Clin Neurosci Div, Neurosci Lab,Brockton Div,Med Sch, Dept Psychiat,Boston Vet Affairs Healthcare Syst, Brockton, MA 02401 USA. [Bammer, R.] Stanford Univ, Radiol Sci Lab, Stanford, CA 94305 USA. [Adcock, R. A.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. RP Whitford, TJ (reprint author), Harvard Univ, Sch Med, Psychiat Neuroimaging Lab, Dept Psychiat,Brigham & Womens Hosp, 1249 Boylston St, Boston, MA 02215 USA. EM whitford@bwh.harvard.edu RI Schneiderman, Jason/E-1528-2013; OI Schneiderman, Jason/0000-0002-9313-0415; Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974; Rausch, Andrew/0000-0002-7246-4563 FU National Health and Medical Research Council of Australia [NHMRC 520627]; National institutes of Health (NIH) [R03 MH068464-0, R01 MH 50747, T32 MH 016259, K05 MH 070047, R01 MH 082918, R01 DA 027802, R01 MH076989, R01 MH058262, K02 MH067967]; Harvard Medical School; National Alliance for Research on Schizophrenia and Depression; Department of Veterans Affairs; Boston Center for Intervention Development and Applied Research (CIDAR) [P50 MH 080272]; Center for Integration of Medicine and Innovative Technology; Sloan Foundation; Esther A. & Joseph Klingenstein Fund; Dana Foundation FX T.J.W. is supported by an Overseas-Based Biomedical Training Fellowship from the National Health and Medical Research Council of Australia (NHMRC 520627), administered through the University of Melbourne. M.K. is supported by grants from the National institutes of Health (NIH) (R03 MH068464-0; R01 MH 50747 to MES), the Harvard Medical School (Milton Award), and the National Alliance for Research on Schizophrenia and Depression. J.S.S. is supported by a fellowship from the NIH (T32 MH 016259). M.E.S. is supported by grants from the NIH (K05 MH 070047 and R01 MH 50747), the Department of Veterans Affairs (VA Merit Award, VA Research Enhancement Award Program and VA Schizophrenia Research Center Grant), and the Boston Center for Intervention Development and Applied Research (CIDAR) funded through a center grant mechanism (P50 MH 080272). S.B. is supported by grants from the NIH (R01 MH 082918) and the Center for Integration of Medicine and Innovative Technology Soldier in Medicine Award. R.A.A. is supported by grants from the NIH (R01 DA 027802), Sloan Foundation, Esther A. & Joseph Klingenstein Fund, Dana Foundation, and the National Alliance for Research on Schizophrenia and Depression. D.H.M. is supported by the Department of Veterans Affairs and the NIH (R01 MH076989). J.M.F is supported by the Department of Veterans Affairs and the NIH (R01 MH058262, K02 MH067967). NR 52 TC 33 Z9 35 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD MAY PY 2011 VL 41 IS 5 BP 959 EP 969 DI 10.1017/S0033291710001376 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 753GK UT WOS:000289760100006 PM 20663254 ER PT J AU Giani, A Esmaili, DD Luiselli, C Cigada, M Salvetti, P Miller, JW Staurenghi, G AF Giani, Andrea Esmaili, Daniel D. Luiselli, Cristiano Cigada, Mario Salvetti, Paola Miller, Joan W. Staurenghi, Giovanni TI DISPLAYED REFLECTIVITY OF CHOROIDAL NEOVASCULAR MEMBRANES BY OPTICAL COHERENCE TOMOGRAPHY CORRELATES WITH PRESENCE OF LEAKAGE BY FLUORESCEIN ANGIOGRAPHY SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE age-related macular degeneration; choroidal neovascularization; fluorescein angiography; optical coherence tomography; optical reflectivity ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; PHOTODYNAMIC THERAPY; BRUCHS MEMBRANE; VERTEPORFIN; RISK; TAP; EYE AB Purpose: To evaluate and correlate the displayed optical reflectivity of choroidal neovascularization (CNV) subretinal material on spectral-domain optical coherence tomography with the presence of dye leakage on fluorescein angiography (FA). Methods: Thirty-nine eyes of 39 patients with a diagnosis of predominantly classic CNV from age-related macular degeneration underwent simultaneous spectral-domain optical coherence tomography and FA imaging. Eight patients had a newly diagnosed untreated CNV. Thirty-one patients had already been treated with anti-vascular endothelial growth factor agents. In 18 of these eyes, CNV lesions showed persistent leakage on FA. In 13 eyes, CNV lesions did not show leakage by FA. Subretinal CNV material boundaries visualized on spectral-domain optical coherence tomography B-scans were manually traced, and optical reflectivity was calculated using the mean grayscale value. To account for variable image brightness, the retinal pigment epithelial reflectivity was measured. The absolute difference between CNV material and retinal pigment epithelial reflectivity (Delta REF) from the three groups (newly diagnosed CNV, previously treated CNV showing FA leakage, and previously treated CNV not showing FA leakage) was compared. Results: In untreated lesions, Delta REF was significantly higher compared with previously treated, but still leaky CNV (P < 0.0001). Lesions showing FA leakage had significantly higher Delta REF compared with those that did not display leakage (P < 0.0001). Conclusion: The displayed reflectivity of subretinal CNV material in spectral-domain optical coherence tomography appears to be an important parameter that can provide information regarding the FA leakage status. RETINA 31:942-948, 2011 C1 [Giani, Andrea; Esmaili, Daniel D.; Miller, Joan W.] Harvard Univ, Retina Serv, Dept Ophthalmol, Sch Med,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Giani, Andrea; Luiselli, Cristiano; Cigada, Mario; Salvetti, Paola; Staurenghi, Giovanni] Univ Milan, Eye Clin, Dept Clin Sci Luigi Sacco, Sacco Hosp, Milan, Italy. RP Giani, A (reprint author), Harvard Univ, Retina Serv, Dept Ophthalmol, Sch Med,Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM andrea_giani@meei.harvard.edu FU Heidelberg Engineering, Heidelberg, Germany; Zeiss Meditec, Dublin, CA FX A. Giani received travel fees for attending a meeting from Heidelberg Engineering, Heidelberg, Germany. C. Luiselli received travel fees for attending a meeting from Heidelberg Engineering, Heidelberg, Germany, and Zeiss Meditec, Dublin, CA. G. Staurenghi received fees for advisory board from Heidelberg Engineering, Heidelberg, Germany, and received fees for attending a meeting from Zeiss Meditec, Dublin, CA. NR 23 TC 13 Z9 17 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD MAY PY 2011 VL 31 IS 5 BP 942 EP 948 DI 10.1097/IAE.0b013e31820a68cc PG 7 WC Ophthalmology SC Ophthalmology GA 755LV UT WOS:000289933600018 PM 21358457 ER PT J AU Hurford, IM Marder, SR Keefe, RSE Reise, SP Bilder, RM AF Hurford, Irene M. Marder, Stephen R. Keefe, Richard S. E. Reise, Steven P. Bilder, Robert M. TI A Brief Cognitive Assessment Tool for Schizophrenia: Construction of a Tool for Clinicians SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; cognition; cognitive assessment; neurocognitive battery; clinical assessment ID III DIGIT SYMBOL; NEUROCOGNITIVE DEFICITS; NEUROPSYCHOLOGICAL STATUS; FUNCTIONAL-CAPACITY; REPEATABLE BATTERY; CATEGORY FLUENCY; HEALTHY CONTROLS; CODING SUBTEST; SCREENING-TEST; MEMORY AB Cognitive impairment in schizophrenia is often severe, enduring, and contributes significantly to chronic disability. But clinicians have difficulty in assessing cognition due to a lack of brief instruments. We evaluated whether a brief battery of cognitive tests derived from larger batteries could generate a summary score representing global cognitive function. Using data from 3 previously published trials, we calculated the corrected item-total correlations (CITCs) or the correlation of each test with the battery total score. We computed the proportion of variance that each test shares with the global score excluding that test (Rt2=CITC(2)) and the variance explained per minute of administration time for each test (Rt2/min). The 3 tests with the highest Rt2/min were selected for the brief battery. The composite score from the trail making test B, category fluency, and digit symbol correlated .86 with the global score of the larger battery in 2 of the studies and correlated between .73 and .82 with the total battery scores excluding these 3 tests. A Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) using the above 3 tests can be administered in 10-11 min. The full batteries of the larger studies have administration times ranging from 90 to 210 min. Given prior research suggesting that a single factor of global cognition best explains the pattern of cognitive deficit in schizophrenia, an instrument like B-CATS can provide clinicians with meaningful data regarding their patients' cognitive function. It can also serve researchers who want an estimate of global cognitive function without requiring a full neuropsychological battery. C1 [Hurford, Irene M.] Philadelphia VA Med Ctr, Dept Behav Hlth, Philadelphia, PA 19104 USA. [Hurford, Irene M.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Marder, Stephen R.; Bilder, Robert M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Marder, Stephen R.] VA Greater Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Keefe, Richard S. E.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Reise, Steven P.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Hurford, IM (reprint author), Philadelphia VA Med Ctr, Dept Behav Hlth, Rm 7A-113,Mail Code 116, Philadelphia, PA 19104 USA. EM ihurford@upenn.edu RI Bilder, Robert/A-8894-2008 OI Bilder, Robert/0000-0001-5085-7852 FU National Alliance for Research on Schizophrenia and Depression [20062767] FX National Alliance for Research on Schizophrenia and Depression Young Investigator grant (20062767 to I.M.H.). NR 36 TC 25 Z9 26 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2011 VL 37 IS 3 BP 538 EP 545 DI 10.1093/schbul/sbp095 PG 8 WC Psychiatry SC Psychiatry GA 753UF UT WOS:000289804500016 PM 19776205 ER PT J AU Itani, KMF Hoballah, J Kaafarani, H Crisostomo, AC Michelassi, F AF Itani, Kamal M. F. Hoballah, Jamal Kaafarani, Haytham Crisostomo, Armando C. Michelassi, Fabrizio TI Could international medical graduates offer a solution to the surgical workforce crisis? Balancing national interest and global responsibility SO SURGERY LA English DT Editorial Material C1 [Itani, Kamal M. F.] Boston Univ, Dept Surg, VA Boston Hlth Care Syst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. [Hoballah, Jamal] Amer Univ Beirut, Dept Surg, Beirut, Lebanon. [Kaafarani, Haytham] Tufts Med Ctr, Dept Surg, Boston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. [Crisostomo, Armando C.] Univ Philippines, Coll Med, Dept Surg, Manila, Philippines. Philippine Gen Hosp, Manila, Philippines. [Michelassi, Fabrizio] Weill Cornell Med Coll, Dept Surg, New York, NY USA. RP Itani, KMF (reprint author), Boston Univ, VA Boston Hlth Care Syst 112A, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM kitani@va.gov NR 8 TC 5 Z9 5 U1 0 U2 2 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 MAY PY 2011 VL 149 IS 5 BP 597 EP 600 DI 10.1016/j.surg.2010.12.011 PG 4 WC Surgery SC Surgery GA 755KV UT WOS:000289930700001 PM 21429545 ER PT J AU Shen, CA Fagan, S Fischman, AJ Carter, EE Chai, JK Lu, XM Yu, YM Tompkins, RG AF Shen, Chuan-an Fagan, Shawn Fischman, Alan J. Carter, Edward E. Chai, Jia-Ke Lu, Xiao-Ming Yu, Yong-Ming Tompkins, Ronald G. TI Effects of glucagon-like peptide 1 on glycemia control and its metabolic consequence after severe thermal injury-studies in an animal model SO SURGERY LA English DT Article ID INTENSIVE-CARE-UNIT; ACUTE MYOCARDIAL-INFARCTION; PANCREATIC BETA-CELLS; INSULIN THERAPY; GLUCOSE VARIABILITY; DIABETES-MELLITUS; BURNED PATIENTS; APOPTOSIS; GLP-1; MORTALITY AB Background. Hyperglycemia with insulin resistance is commonly seen in, severely burned patients and tight glycemia control with insulin may be beneficial in this condition. The most potent insulinotropic hormone, gucagon-like peptide 1 (GLP-1), stimulates insulin secretion in a glucose-dependent manner. Because infusion of GLP-1 never reduces glucose levels to below similar to 70 mg/dL, the risk of hypoglycemia by using insulin is reduced. In this study we investigated the metabolic effects of GLP-1 infusion after burn injury in an animal model. Methods. Male CD rats were divided in. 3 groups: burn injury with saline, burn injury with GLP-1 treatment, and sham burn (SB). Burn injury was full thickness 40% total body surface area. The burn. injury with GLP-1 treatment group received GLP-1 infusion via osmotic pump. Fasting blood glucose, plasma insulin, and plasma GLP-1 levels were measured during intraperitoneal glucose tolerance tests. Expressions of caspase 3 and bcl-2 were evaluated in pancreatic islets. In a subset of animals, protein metabolism and total energy expenditure were measured. Results. Fasting GLP-1 was reduced in burn injury with saline compared to SB or burn injury with GLP-1 treatment. Burn injury with GLP-1 treatment showed reduced fasting blood glucose, improved intraperitoneal glucose tolerance test results, with increased plasma insulin and GLP-1 responses to glucose. GLP-1 reduced protein breakdown and total energy expenditure in burn injury with GLP-1 treatment versus burn injury with saline, with improved protein balance. Increased expression of caspase 3 and decreased expression of bcl-2 in islet cells by burn injury were ameliorated by GLP-1. Conclusion. Burn injury reduced plasma GLP-1 in association with insulin resistance. GLP-1 infusion improved glucose tolerance and showed anabolic effects on protein metabolism and reduced total energy expenditure riper burn injury, possibly via insulinotropic and non insulinotropic mechanisms. (Surgery 2011;149:635-44.) C1 [Shen, Chuan-an; Fagan, Shawn; Fischman, Alan J.; Carter, Edward E.; Lu, Xiao-Ming; Yu, Yong-Ming; Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA USA. [Shen, Chuan-an; Chai, Jia-Ke] Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, PLA Burn Ctr, Beijing, Peoples R China. RP Yu, YM (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM yyu@partners.org FU National Institutes of Health [2P50 GM 021700 GM 07035]; Shriners Hospitals for Children [8470] FX Supported by the National Institutes of Health (2P50 GM 021700 GM 07035) and Shriners Hospitals for Children (Grant 8470). NR 50 TC 8 Z9 11 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 MAY PY 2011 VL 149 IS 5 BP 635 EP 644 DI 10.1016/j.surg.2010.11.017 PG 10 WC Surgery SC Surgery GA 755KV UT WOS:000289930700006 PM 21295809 ER PT J AU Deol, RC MacRae, CA AF Deol, Rahul C. MacRae, Calum A. TI The zebrafish: scalable in vivo modeling for systems biology SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE LA English DT Article ID RIGHT-VENTRICULAR CARDIOMYOPATHY; GENOME-WIDE ASSOCIATION; CIS-REGULATORY FUNCTION; C-ELEGANS; HUMAN-DISEASE; SACCHAROMYCES-CEREVISIAE; INTERACTOME NETWORK; ATRIAL-FIBRILLATION; PHENOME PROJECT; GENE-EXPRESSION AB The zebrafish offers a scalable vertebrate model for many areas of biologic investigation. There is substantial conservation of genetic and genomic features and, at a higher order, conservation of intermolecular networks, as well as physiologic systems and phenotypes. We highlight recent work demonstrating the extent of this homology, and efforts to develop high-throughput phenotyping strategies suited to genetic or chemical screening on a scale compatible with in vivo validation for systems biology. We discuss the implications of these approaches for functional annotation of the genome, elucidation of multicellular processes in vivo, and mechanistic exploration of hypotheses generated by a broad range of 'unbiased' omic technologies such as expression profiling and genome-wide association. Finally, we outline potential strategies for the application of the zebrafish to the systematic study of phenotypic architecture, disease heterogeneity and drug responses. (C) 2010 John Wiley & Sons, Inc. WIREs Syst Biol Med 2011 3 335-346 DOI: 10.1002/wsbm.117 C1 [MacRae, Calum A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Deol, Rahul C.; MacRae, Calum A.] Harvard Univ, Sch Med, Boston, MA USA. [Deol, Rahul C.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP MacRae, CA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM camacrae@bics.bwh.harvard.edu NR 89 TC 0 Z9 0 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5094 EI 1939-005X J9 WIRES SYST BIOL MED JI Wiley Interdiscip. Rev.-Syst. Biol PD MAY-JUN PY 2011 VL 3 IS 3 BP 335 EP 346 DI 10.1002/wsbm.117 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 757YN UT WOS:000290125100008 ER PT J AU Loftis, JM Huckans, M AF Loftis, Jennifer M. Huckans, Marilyn TI COGNITIVE ENHANCEMENT IN COMBINATION WITH 'BRAIN REPAIR' MAY BE OPTIMAL FOR THE TREATMENT OF STIMULANT ADDICTION SO ADDICTION LA English DT Letter DE Cognition; depression; methamphetamine; pharmacotherapy; relapse ID METHAMPHETAMINE-DEPENDENT INDIVIDUALS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; ABNORMALITIES; ACTIVATION; MODAFINIL; ABUSERS C1 [Loftis, Jennifer M.; Huckans, Marilyn] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Res & Dev Serv, Portland, OR 97239 USA. [Loftis, Jennifer M.; Huckans, Marilyn] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Loftis, JM (reprint author), Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Res & Dev Serv, Portland, OR 97239 USA. EM loftisj@ohsu.edu FU NIDA NIH HHS [RC1 DA028537, R41 DA029345, P50 DA018165, RC1DA028537] NR 19 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD MAY PY 2011 VL 106 IS 5 BP 1021 EP 1022 DI 10.1111/j.1360-0443.2010.03354.x PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 747CC UT WOS:000289296900039 PM 21382112 ER PT J AU Lewandrowski, EL Van Cott, EM Gregory, K Jang, IK Lewandrowski, KB AF Lewandrowski, Elizabeth Lee Van Cott, Elizabeth M. Gregory, Kimberly Jang, Ik-Kyung Lewandrowski, Kent B. TI Clinical Evaluation of the i-STAT Kaolin Activated Clotting Time (ACT) Test in Different Clinical Settings in a Large Academic Urban Medical Center Comparison With the Medtronic ACT Plus SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Activated clotting time; ACT; Kaolin; Method comparison ID HEMOCHRON AB Historically, it has been difficult for hospitals to change methods for activated clotting time (ACT) testing because of differences in ACT values obtained with different instruments, wide differences in target ranges used in different procedures, and the difficulty of performing crossover studies at the bedside in critical care situations. There are limited published data comparing the i-STAT (Abbott Point of Care, Princeton, NJ) kaolin ACT with the Medtronic ACT Plus (Medtronic, Minneapolis, MN). The i-STAT system can perform ACT testing in addition to testing of a number of critical care analytes and may offer potential advantages over other ACT analyzers. Comparison of ACT values on 121 simultaneous split-sample tests yielded an R(2) of 0.88 with i-STAT = 0.79 Medtronic + 72.0. The Pearson correlation was R = 0.94, indicating statistically significant correlation between the 2 methods. Based on this comparison, we were able to implement the i-STAT ACT throughout our institution without changing target ranges for any individual procedure. C1 [Lewandrowski, Elizabeth Lee; Van Cott, Elizabeth M.; Gregory, Kimberly; Jang, Ik-Kyung; Lewandrowski, Kent B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lewandrowski, Elizabeth Lee; Van Cott, Elizabeth M.; Gregory, Kimberly; Lewandrowski, Kent B.] Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gray 5 Chem, Boston, MA 02114 USA. FU Abbott Point of Care FX Supported in part by Abbott Point of Care. NR 10 TC 4 Z9 5 U1 0 U2 3 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 2011 VL 135 IS 5 BP 741 EP 748 DI 10.1309/AJCPSF8ASGONNQM6 PG 8 WC Pathology SC Pathology GA 753CV UT WOS:000289743400011 PM 21502428 ER PT J AU Flavin, RJ Cook, J Fiorentino, M Bailey, D Brown, M Loda, MF AF Flavin, Richard J. Cook, Jennifer Fiorentino, Michelangelo Bailey, Dyane Brown, Myles Loda, Massimo F. TI beta-Catenin Is a Useful Adjunct Immunohistochemical Marker for the Diagnosis of Pulmonary Lymphangioleiomyomatosis SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Lymphangioleiomyomatosis; beta-Catenin; Angiomyolipoma; Immunohistochemistry ID TUBEROUS SCLEROSIS; STEROID-RECEPTORS; LYMPHANGIOMYOMATOSIS; ANGIOMYOLIPOMA; MANAGEMENT; HMB-45; HMB45; TUMOR; LUNG AB Lymphangioleiomyomatosis (LAM) is a rare multisystem disease leading to cystic destruction of the lung parenchyma and is associated with abnormal smooth muscle proliferation affecting airways, lymphatics, and blood vessels. LAM occurs sporadically or in association with the tuberous sclerosis complex (TSC). Recent evidence demonstrates the role of aberrant beta-catenin signaling in TSC. To further understand the pathogenesis of LAM and to examine the diagnostic usefulness of beta-catenin, we examined protein expression in 28 pulmonary LAM cases and 10 cases of renal angiomyolipoma resected from patients with sporadic LAM Immunohistochemical analysis was performed for established markers of LAM cells (HMB45, estrogen receptor [ER]-alpha, and progesterone receptor [PR]) and beta-catenin. All LAM cases were positive for beta-catenin and demonstrated high specificity with overall immunoreactivity superior to HMB45, ER-alpha, and PR. Similar expression was demonstrated in renal angiomyolipoma. Our results indicate that beta-catenin is a useful marker of LAM and may be clinically useful in the diagnostic setting. C1 [Flavin, Richard J.; Fiorentino, Michelangelo; Bailey, Dyane; Loda, Massimo F.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Cook, Jennifer; Brown, Myles; Loda, Massimo F.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Flavin, Richard J.] Natl Univ Ireland, Dept Pathol, Galway, Ireland. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Addarii Inst, Mol Pathol Lab, Bologna, Italy. [Loda, Massimo F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Loda, MF (reprint author), Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. OI Brown, Myles/0000-0002-8213-1658 FU National Institutes of Health, Bethesda, MD [1 RCI HL100655-01]; LAM Treatment Alliance Postdoctoral Fellowship, Cambridge, MA FX Supported in part by LAM Challenge grant 1 RCI HL100655-01, National Institutes of Health, Bethesda, MD (Dr Flavin); and LAM Treatment Alliance Postdoctoral Fellowship, Cambridge, MA (Dr Cook). NR 22 TC 13 Z9 16 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 2011 VL 135 IS 5 BP 776 EP 782 DI 10.1309/AJCPPC9EX1ZHMRMA PG 7 WC Pathology SC Pathology GA 753CV UT WOS:000289743400017 PM 21502434 ER PT J AU Viswanath, K AF Viswanath, Kasisomayajula TI Cyberinfrastructure An Extraordinary Opportunity to Bridge Health and Communication Inequalities? SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID CONSUMER HEALTH; MEANINGFUL USE; INFORMATION-TECHNOLOGY; ETHNIC DISPARITIES; PALLIATIVE CARE; RECORDS; DETERMINANTS; HOSPITALS; HOSPICE; TRENDS C1 [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst LW 630, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Viswanath, K (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst LW 630, Dept Soc Human Dev & Hlth, 44 Binney St, Boston, MA 02115 USA. EM vish_viswanath@dfci.harvard.edu FU National Institutes of Health FX Publication of this article was supported by the National Institutes of Health. NR 37 TC 10 Z9 10 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2011 VL 40 IS 5 SU 2 BP S245 EP S248 DI 10.1016/j.amepre.2011.02.005 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 754DR UT WOS:000289833200023 PM 21521602 ER PT J AU Hoo, GWS Wu, CC Vazirani, S Li, ZP Barack, BM AF Hoo, Guy W. Soo Wu, Carol C. Vazirani, Sondra Li, Zhaoping Barack, Bruce M. TI Does a Clinical Decision Rule Using D-Dimer Level Improve the Yield of Pulmonary CT Angiography? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE clinical decision rule; D-dimer assay; pulmonary CT angiography; pulmonary embolism; Wells score ID DEEP-VEIN THROMBOSIS; COMPUTED-TOMOGRAPHY; VENOUS THROMBOEMBOLISM; EMERGENCY-DEPARTMENT; GUIDELINE IMPLEMENTATION; UTILIZATION PATTERNS; EMBOLISM; MANAGEMENT; DIAGNOSIS; PROBABILITY AB OBJECTIVE. The objective of our study was to evaluate the impact of incorporating a mandatory clinical decision rule and selective D-dimer use on the yield of pulmonary CT angiography (CTA). MATERIALS AND METHODS. Guidelines incorporating a clinical decision rule (Wells score: range, 0-12.5) and a highly sensitive D-dimer assay as decision points were placed into a computerized order entry menu. From December 2006 through November 2008, 261 pulmonary CTA examinations of 238 men and 14 women (mean age +/- SD, 65 +/- 12 years; range, 31-92 years) were performed. Eight patients underwent more than one pulmonary CTA examination. Charts were reviewed. The results of pulmonary CTA, the clinical decision rule, and D-dimer level (if obtained) were analyzed with the Student t test, chi-square test, or other comparisons using statistical software (MedCalc, version 11.0). RESULTS. Of the pulmonary CTA examinations, 16.5% (43/261) were positive for pulmonary embolism (PE) compared with 3.1% (6/196) during the previous 2 years. The mean clinical decision rule score and mean d-dimer level were 5.5 +/- 2.4 (SD) and 4956 +/- 2892 ng/mL, respectively, for those with PE compared with 4.5 +/- 2.1 and 2398 +/- 2100 ng/mL for those without PE (both, p < 0.01). The negative predictive value of a clinical decision rule score of 4 or less and d-dimer level of less than 1000 ng/mL was 1.0. A clinical decision rule of greater than 4 and a higher d-dimer level were better predictors for PE, especially a d-dimer level of greater than 3000 ng/mL (odds ratio = 6.69; 95% CI = 2.72-16.43). CONCLUSION. Guidelines combining a clinical decision rule with d-dimer level significantly improved the utilization of pulmonary CTA and positive yield for PE. C1 [Hoo, Guy W. Soo] W Los Angeles Med Ctr, Pulm & Crit Care Sect, Los Angeles, CA 90073 USA. [Hoo, Guy W. Soo; Vazirani, Sondra; Li, Zhaoping] VA Greater Angeles Healthcare Syst, Dept Med, W Los Angeles Med Ctr, Los Angeles, CA USA. [Wu, Carol C.; Barack, Bruce M.] VA Greater Angeles Healthcare Syst, Dept Imaging, W Los Angeles Med Ctr, Los Angeles, CA USA. RP Hoo, GWS (reprint author), W Los Angeles Med Ctr, Pulm & Crit Care Sect, 11301 Wilshire Blvd,111Q, Los Angeles, CA 90073 USA. EM Guy.Soohoo@va.gov NR 31 TC 6 Z9 7 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2011 VL 196 IS 5 BP 1059 EP 1064 DI 10.2214/AJR.10.4200 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 753JS UT WOS:000289769000037 PM 21512071 ER PT J AU Cronin, CG Gervais, DA Hahn, PF Arellano, R Guimaraes, AR Mueller, PR AF Cronin, Carmel G. Gervais, Debra A. Hahn, Peter F. Arellano, Ronald Guimaraes, Alexander R. Mueller, Peter R. TI Treatment of Deep Intramuscular and Musculoskeletal Abscess: Experience With 99 CT-Guided Percutaneous Catheter Drainage Procedures SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE abdominal drainage; muscle abscess; musculoskeletal collection ID SPINAL EPIDURAL ABSCESS; PELVIC ABSCESSES; OSTEOMYELITIS; MANAGEMENT; UROKINASE AB OBJECTIVE. The purpose of this article is to describe our experience draining deep muscular and musculoskeletal abscess collections with CT guidance, emphasizing clinicopathologic factors associated with drain failure, and to further analyze patient outcomes according to whether the process involves muscle alone or also involves adjacent bone or joint (skeletal involvement). MATERIALS AND METHODS. The details of percutaneous catheter drainage were retrospectively recorded for all drainages performed over a 9-year period. The technical and clinical successes of percutaneous catheter drainage were determined. Multifactor logistic regression analysis was used to identify predictors of drain failure (malignancy, age, chemotherapy, surgery, infection, complexity, size, days in situ, and skeletal involvement). These parameters were assessed in all patients, those with muscle involvement alone and those with musculoskeletal collections. RESULTS. Eighty-nine of 94 patients underwent one percutaneous drainage procedure and 5 of 94 patients underwent two drainages for a total of 99 drainages in 94 patients (one drainage [n = 89] and two drainages [n = 5]). There were 62 men and 32 women with a mean age of 58.5 years (age range [+/- SD], 22.3-88.0 +/- 16 years). The abscess diameters ranged from 1.8 to 13 cm (mean, 5.3 +/- 2.5 cm), volume aspirated ranged from 0 to 200 mL (mean, 45 +/- 44 mL), and mean duration of drainage was 16.2 days (range, 2-110 +/- 18.7 days). The iliopsoas muscle was the most common site of drainage, accounting for 87.8% of the total. Catheter insertion was possible in all patients, with the muscular component successfully drained in 82% (81/99) overall: 85% (46/54) of those with muscle involvement alone and 77% (35/45) of those with musculoskeletal collections. Catheter drainage and antibiotic administration resulted in 65.6% (65/99) not requiring any surgical intervention and resolution of abnormal white cell count or fevers in 98.8% (79/80) of those with abnormal parameters before treatment. Skeletal infection was associated with increased risk of drainage failure (p = 0.0001). CONCLUSION. Percutaneous imaging-guided musculoskeletal drainage is clinically useful, safe, and effective for draining complex musculoskeletal collections. It is highly effective for draining collections involving muscle alone; however, skeletal infection is associated with a higher risk of drain failure. C1 [Cronin, Carmel G.; Gervais, Debra A.; Hahn, Peter F.; Arellano, Ronald; Guimaraes, Alexander R.; Mueller, Peter R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02214 USA. RP Cronin, CG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02214 USA. EM cgcronin@partners.org NR 16 TC 3 Z9 3 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2011 VL 196 IS 5 BP 1182 EP 1188 DI 10.2214/AJR.09.4082 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 753JS UT WOS:000289769000056 PM 21512090 ER PT J AU Wu, CC Maher, MM Shepard, JAO AF Wu, Carol C. Maher, Michael M. Shepard, Jo-Anne O. TI CT-Guided Percutaneous Needle Biopsy of the Chest: Preprocedural Evaluation and Technique SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE biopsy; CT-guided biopsy; lung biopsy; lung cancer diagnosis; thorax ID PULMONARY-LESIONS; DIAGNOSTIC YIELD; COMPUTED TOMOGRAPHY; LUNG-BIOPSY; ASPIRATION; MUTATIONS C1 [Wu, Carol C.; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Imaging, Thorac Div, Boston, MA 02114 USA. [Wu, Carol C.; Shepard, Jo-Anne O.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Maher, Michael M.] Cork Univ Hosp, Dept Radiol, Cork, Ireland. [Maher, Michael M.] Mercy Univ Hosp, Cork, Ireland. [Maher, Michael M.] Univ Coll Cork, Cork, Ireland. RP Wu, CC (reprint author), Massachusetts Gen Hosp, Dept Imaging, Thorac Div, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM cwu8@partners.org NR 13 TC 11 Z9 15 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2011 VL 196 IS 5 BP W511 EP W514 DI 10.2214/AJR.10.4657 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 753JS UT WOS:000289769000002 PM 21512038 ER PT J AU Martinez, EA Thompson, DA Errett, NA Kim, GR Bauer, L Lubomski, LH Gurses, AP Marsteller, JA Mohit, B Goeschel, CA Pronovost, PJ AF Martinez, Elizabeth A. Thompson, David A. Errett, Nicole A. Kim, George R. Bauer, Laura Lubomski, Lisa H. Gurses, Ayse P. Marsteller, Jill A. Mohit, Babak Goeschel, Christine A. Pronovost, Peter J. TI High Stakes and High Risk: A Focused Qualitative Review of Hazards During Cardiac Surgery SO ANESTHESIA AND ANALGESIA LA English DT Review ID ARTERY-BYPASS-SURGERY; HARVARD MEDICAL-PRACTICE; CARBON-DIOXIDE EMBOLISM; INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHY; RIGHT-VENTRICULAR PERFORATION; DRUG ADMINISTRATION SYSTEM; PATIENT SAFETY; SURGICAL-PATIENTS; PULMONARY-ARTERY; ADVERSE EVENTS AB Cardiac surgery is a high-risk procedure performed by a multidisciplinary team using complex tools and technologies. Efforts to improve cardiac surgery safety have been ongoing for more than a decade, yet the literature provides little guidance regarding best practices for identifying errors and improving patient safety. This focused review of the literature was undertaken as part of the FOCUS initiative (Flawless Operative Cardiovascular Unified Systems), a multifaceted effort supported by the Society of Cardiovascular Anesthesiologists Foundation to identify hazards and develop evidence-based protocols to improve cardiac surgery safety. Hazards were defined as anything that posed a potential or real risk to the patient, including errors, near misses, and adverse events. Of the 1438 articles identified for title review, 390 underwent full abstract screening, and 69 underwent full article review, which in turn yielded 55 meeting the inclusion criteria for this review. Two key themes emerged. First, studies were predominantly reactive (responding to an event or report) instead of proactive (using prospective designs such as self-assessments and external reviewers, etc.) and very few tested interventions. Second, minor events were predictive of major problems: multiple, often minor, deviations from normal procedures caused a cascade effect, resulting in major distractions that ultimately led to major events. This review fills an important gap in the literature on cardiac surgery safety, that of systematically identifying and categorizing known hazards according to their primary systemic contributor (or contributors). We conclude with recommendations for improving patient outcomes by building a culture of safety, promoting transparency, standardizing training, increasing teamwork, and monitoring performance. Finally, there is an urgent need for studies that evaluate interventions to mitigate the inherent risks of cardiac surgery. (Anesth Analg 2011;112:1061-74) C1 [Martinez, Elizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Cambridge, MA 02138 USA. [Thompson, David A.; Bauer, Laura; Lubomski, Lisa H.; Gurses, Ayse P.; Goeschel, Christine A.; Pronovost, Peter J.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Errett, Nicole A.; Gurses, Ayse P.; Marsteller, Jill A.; Mohit, Babak; Goeschel, Christine A.; Pronovost, Peter J.] Johns Hopkins Univ, Dept Hlth Policy & Management, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. RP Martinez, EA (reprint author), Dept Anesthesia Crit Care & Pain Med, GRB 444,55 Fruit St, Boston, MA 02114 USA. EM emartinez10@partners.org FU Agency for Healthcare Research and Quality [HS013904-02, HS018762]; Society of Cardiovascular Anesthesia (SCA) Foundation FX This work was completed as part of the FOCUS initiative. The FOCUS Initiative is a collaborative project of the Society of Cardiovascular Anesthesiologists (SCA), the SCA Foundation, and the Johns Hopkins University Quality and Safety Research group. FOCUS is funded exclusively by the SCA Foundation. Elizabeth A. Martinez, MD, MHS, was supported by the Agency for Healthcare Research and Quality K08 grant #HS013904-02. Ayse P. Gurses, PhD, was partially supported by the Agency for Healthcare Research and Quality K01 grant #HS018762.; This author received research funding from Society of Cardiovascular Anesthesia (SCA) Foundation. Attestation: This author approved the final manuscript. NR 83 TC 15 Z9 15 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2011 VL 112 IS 5 BP 1061 EP 1074 DI 10.1213/ANE.0b013e31820bfe8e PG 14 WC Anesthesiology SC Anesthesiology GA 753NI UT WOS:000289785100011 PM 21372272 ER PT J AU Rudolph, JL Marcantonio, ER AF Rudolph, James L. Marcantonio, Edward R. TI Postoperative Delirium: Acute Change with Long-Term Implications SO ANESTHESIA AND ANALGESIA LA English DT Article ID CONFUSION ASSESSMENT METHOD; INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED PATIENTS; PATIENT-CONTROLLED ANALGESIA; POSTACUTE FACILITY PATIENTS; RANDOMIZED CONTROLLED-TRIAL; HOSPITALIZED OLDER PATIENTS; PLACEBO-CONTROLLED TRIAL; MAJOR ABDOMINAL-SURGERY; CRITICALLY-ILL PATIENTS AB Delirium is an acute change in cognition and attention, which may include alterations in consciousness and disorganized thinking. Although delirium may affect any age group, it is most common in older patients, especially those with preexisting cognitive impairment. Patients with delirium after surgery recover more slowly than those without delirium and, as a result, have increased length of stay and hospital costs. The measured incidence of postoperative delirium varies with the type of surgery, the urgency of surgery, and the type and sensitivity of the delirium assessment. Although generally considered a short-term condition, delirium can persist for months and is associated with poor cognitive and functional outcomes beyond the immediate postoperative period. In this article, we provide a guide to assess delirium risk preoperatively and to prevent, diagnose, and treat this common and morbid condition. Care improvements such as identifying delirium risk preoperatively; training surgeons, anesthesiologists, and nurses to screen for delirium; implementing delirium prevention programs; and developing standardized delirium treatment protocols may reduce the risk of delirium and its associated morbidity. (Anesth Analg 2011; 112: 1202-11) C1 [Rudolph, James L.] VA Boston Healthcare Syst, GRECC, Boston, MA 02130 USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care & Gerontol, Boston, MA 02215 USA. [Rudolph, James L.; Marcantonio, Edward R.] Harvard Univ, Sch Med, Boston, MA USA. RP Rudolph, JL (reprint author), VA Boston Healthcare Syst, GRECC, 150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org FU National Institute on Aging [K24 AG035075] FX Dr. Rudolph is the recipient of a VA Rehabilitation Research Career Development Award and Dr. Marcantonio is a recipient of a Mid-Career Investigator Award in patient-oriented research from the National Institute on Aging (K24 AG035075). NR 105 TC 94 Z9 106 U1 5 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2011 VL 112 IS 5 BP 1202 EP 1211 DI 10.1213/ANE.0b013e3182147f6d PG 10 WC Anesthesiology SC Anesthesiology GA 753NI UT WOS:000289785100031 PM 21474660 ER PT J AU Peterfreund, RA Driscoll, WD Walsh, JL Subramanian, A Anupama, S Weaver, M Morris, T Arnholz, S Zheng, H Pierce, ET Spring, SF AF Peterfreund, Robert A. Driscoll, William D. Walsh, John L. Subramanian, Aparna Anupama, Shaji Weaver, Melissa Morris, Theresa Arnholz, Sarah Zheng, Hui Pierce, Eric T. Spring, Stephen F. TI Evaluation of a Mandatory Quality Assurance Data Capture in Anesthesia: A Secure Electronic System to Capture Quality Assurance Information Linked to an Automated Anesthesia Record SO ANESTHESIA AND ANALGESIA LA English DT Article ID INCIDENT REPORTING SYSTEM; PATIENT SAFETY; EVENTS; PROGRAM AB BACKGROUND: Efforts to assure high-quality, safe, clinical care depend upon capturing information about near-miss and adverse outcome events. Inconsistent or unreliable information capture, especially for infrequent events, compromises attempts to analyze events in quantitative terms, understand their implications, and assess corrective efforts. To enhance reporting, we developed a secure, electronic, mandatory system for reporting quality assurance data linked to our electronic anesthesia record. METHODS: We used the capabilities of our anesthesia information management system (AIMS) in conjunction with internally developed, secure, intranet-based, Web application software. The application is implemented with a backend allowing robust data storage, retrieval, data analysis, and reporting capabilities. We customized a feature within the AIMS software to create a hard stop in the documentation workflow before the end of anesthesia care time stamp for every case. The software forces the anesthesia provider to access the separate quality assurance data collection program, which provides a checklist for targeted clinical events and a free text option. After completing the event collection program, the software automatically returns the clinician to the AIMS to finalize the anesthesia record. RESULTS: The number of events captured by the departmental quality assurance office increased by 92% (95% confidence interval [CI] 60.4%-130%) after system implementation. The major contributor to this increase was the new electronic system. This increase has been sustained over the initial 12 full months after implementation. Under our reporting criteria, the overall rate of clinical events reported by any method was 471 events out of 55,382 cases or 0.85% (95% CI 0.78% to 0.93%). The new system collected 67% of these events (95% confidence interval 63%-71%). CONCLUSION: We demonstrate the implementation in an academic anesthesia department of a secure clinical event reporting system linked to an AIMS. The system enforces entry of quality assurance information (either no clinical event or notification of a clinical event). System implementation resulted in capturing nearly twice the number of events at a relatively steady case load. (Anesth Analg 2011; 112:1218-25) C1 [Peterfreund, Robert A.; Driscoll, William D.; Walsh, John L.; Subramanian, Aparna; Anupama, Shaji; Weaver, Melissa; Morris, Theresa; Arnholz, Sarah; Zheng, Hui; Pierce, Eric T.; Spring, Stephen F.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Peterfreund, RA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Jackson 439,55 Fruit St, Boston, MA 02114 USA. EM RPeterfreund@Partners.org FU Massachusetts General Hospital FX Supported by institutional and departmental funds from Massachusetts General Hospital. NR 17 TC 16 Z9 16 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2011 VL 112 IS 5 BP 1218 EP 1225 DI 10.1213/ANE.0b013e31821207f0 PG 8 WC Anesthesiology SC Anesthesiology GA 753NI UT WOS:000289785100033 PM 21415434 ER PT J AU Pickerodt, PA Pickerodt, VW Boemke, W Swenson, ER AF Pickerodt, Philipp A. Pickerodt, Volker W. Boemke, Willehad Swenson, Erik R. TI Management of Severe Acute Anemia: Who Needs Blood? SO ANESTHESIA AND ANALGESIA LA English DT Letter C1 [Pickerodt, Philipp A.; Pickerodt, Volker W.; Boemke, Willehad] Charite, Dept Anesthesiol & Intens Care Med, Campus Virchow Klinikum, D-13353 Berlin, Germany. [Pickerodt, Philipp A.; Pickerodt, Volker W.; Boemke, Willehad] Charite, Dept Anesthesiol & Intens Care Med, Campus Charite Mitte, D-13353 Berlin, Germany. [Swenson, Erik R.] Univ Washington, Dept Med, Seattle, WA USA. [Swenson, Erik R.] VA Puget Sound Hlth Care Syst, Sect Pulm & Crit Care Med, Seattle, WA USA. RP Pickerodt, PA (reprint author), Charite, Dept Anesthesiol & Intens Care Med, Campus Virchow Klinikum, D-13353 Berlin, Germany. EM Philipp.pickerodt@charite.de NR 9 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2011 VL 112 IS 5 BP 1251 EP 1252 DI 10.1213/ANE.0b013e31821245a6 PG 3 WC Anesthesiology SC Anesthesiology GA 753NI UT WOS:000289785100049 PM 21515657 ER PT J AU Donelan, K Rogers, RS Eisenhauer, A Mort, E Agnihotri, AK AF Donelan, Karen Rogers, Robert S. Eisenhauer, Andy Mort, Elizabeth Agnihotri, Arvind K. TI Consumer Comprehension of Surgeon Performance Data for Coronary Bypass Procedures SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 25-27, 2010 CL Ft Lauderdale, FL SP Soc Thorac Surg ID NEW-YORK-STATE; CARDIAC-SURGERY; QUALITY; OUTCOMES AB Background. Public and private organizations have called for increased transparency in reporting of outcomes data for hospitals and surgeons, including risk-adjusted coronary artery bypass graft surgery (CABG) mortality data. Limited information is available about how the public actually interprets these data. Methods. Four different graphical and tabular displays of CABG outcomes for surgeons, three of which were modeled on current state public reports, were shown to 337 adults. Each display contained data for 3 to 5 hypothetical surgeons. For each format, respondents were asked to choose which surgeon they would be most and least likely to choose based on the data. Additionally, they were asked questions about public reporting. Results. Accurate identification of best surgeon performance varied by display format, with a high of 66% on one display and a low of 16% on another. Only 6.4% identified the surgeon with the lowest risk mortality across all four displays. Respondents with at least some college education were significantly more likely to identify the surgeon with the lowest risk-adjusted mortality, compared with respondents having no college education (21% to 72% vs. 9% to 59%; p < 0.01). In one display, the surgeon with the lowest risk-adjusted mortality was effectively penalized for taking on higher-risk patients; respondents tended to select the surgeon with the lowest-risk population but the highest risk-adjusted mortality. Overall, 82% of respondents said that access to these types of data would be "absolutely essential" or "very important" in choosing a surgeon. Conclusions. Comprehension by the public of risk-adjusted CABG outcomes is limited and varies by display format. Poorly constructed displays may have led to misinterpretation, with potential unintended adverse consequences such as risk aversion. Further work is needed to design displays that maximize accurate interpretation by the public and more clearly define the risk and benefit of public reporting of surgeon performance. (Ann Thorac Surg 2011; 91: 1400-6) (C) 2011 by The Society of Thoracic Surgeons C1 [Agnihotri, Arvind K.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Ctr Heart, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Qual & Safety, Boston, MA 02114 USA. RP Agnihotri, AK (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Ctr Heart, COX 642,55 Fruit St, Boston, MA 02114 USA. EM aagnihotri@partners.org NR 13 TC 12 Z9 12 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2011 VL 91 IS 5 BP 1400 EP 1405 DI 10.1016/j.athoracsur.2011.01.019 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 754EE UT WOS:000289835000028 PM 21524448 ER PT J AU Bu, DX Tarrio, M Maganto-Garcia, E Stavrakis, G Tajima, G Lederer, J Jarolim, P Freeman, GJ Sharpe, AH Lichtman, AH AF Bu, De-xiu Tarrio, Margarite Maganto-Garcia, Elena Stavrakis, George Tajima, Goro Lederer, James Jarolim, Petr Freeman, Gordon J. Sharpe, Arlene H. Lichtman, Andrew H. TI Impairment of the Programmed Cell Death-1 Pathway Increases Atherosclerotic Lesion Development and Inflammation SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; cytokines; immune system; T cells; costimulation ID RECEPTOR-DEFICIENT MICE; COSTIMULATORY MOLECULE; POSITIVE SELECTION; T-CELLS; PD-1; RESPONSES; INFECTION; RECRUITMENT; IMMUNITY; LIGANDS AB Objective-Programmed cell death-1 (PD-1) is a member of the CD28 superfamily that delivers negative signals on interaction with its 2 ligands, PD-L1 and PD-L2. We studied the contribution of the PD-1 pathway to regulation of T cells that promote atherosclerotic lesion formation and inflammation. Methods and Results-We show that compared with Ldlr(-/-) control mice, Pd1(-/-)Ldlr(-/-) mice developed larger lesions with more abundant CD4(+) and CD8(+) T cells and macrophages, accompanied by higher levels of serum tumor necrosis factor-alpha. Iliac lymph node T cells from Pd1(-/-)Ldlr(-/-) mice proliferated more to alpha CD3 or oxidized low-density lipoprotein stimulation compared with controls. CD8(+) T cells from Pd1(-/-)Ldlr(-/-) mice displayed more cytotoxic activity compared with controls in vivo and in vitro. Administration of a blocking anti-PD-1 antibody increased lesional inflammation in hypercholesterolemic Ldlr(-/-) mice with more lesional T cells and more activated T cells in paraaortic lymph nodes. The changes in lesional T-cell content when PD-1 was absent or blocked were also observed in bone marrow chimeric Ldlr(-/-) mice lacking PD-L1 and PD-L2 on hematopoietic cells. Conclusion-PD-1 has an important role in downregulating proatherogenic T-cell responses, and blockade of this molecule for treatment of viral infections or cancer may increase risk of cardiovascular complications. (Arterioscler Thromb Vasc Biol. 2011;31:1100-1107.) C1 [Bu, De-xiu; Tarrio, Margarite; Maganto-Garcia, Elena; Stavrakis, George; Jarolim, Petr; Sharpe, Arlene H.; Lichtman, Andrew H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Tajima, Goro; Lederer, James] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, 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 Lichtman, AH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, NRB Rm 752N,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM alichtman@rics.bwh.harvard.edu FU National Institutes of Health [HL087282, R01-AI46414, P01-AI56299, R01-AI056299] FX This work was supported by National Institutes of Health Grants HL087282 (to A.H.L.), R01-AI46414 and P01-AI56299 (to A.H.S.), and R01-AI056299 (to G.J.F.). NR 26 TC 34 Z9 36 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2011 VL 31 IS 5 BP 1100 EP U411 DI 10.1161/ATVBAHA.111.224709 PG 27 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 752UR UT WOS:000289720800024 PM 21393583 ER PT J AU Reid, PR Bridges, TM Sheffler, DJ Cho, HP Lewis, LM Days, E Daniels, JS Jones, CK Niswender, CM Weaver, CD Conn, PJ Lindsley, CW Wood, MR AF Reid, Paul R. Bridges, Thomas M. Sheffler, Douglas J. Cho, Hyekyung P. Lewis, L. Michelle Days, Emily Daniels, J. Scott Jones, Carrie K. Niswender, Colleen M. Weaver, C. David Conn, P. Jeffrey Lindsley, Craig W. Wood, Michael R. TI Discovery and optimization of a novel, selective and brain penetrant M-1 positive allosteric modulator (PAM): The development of ML169, an MLPCN probe SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Muscarinic; Acetylcholine; Positive allosteric modulator (PAM); ML169; BQCA; Alzheimer's disease; MLPCN ID ACETYLCHOLINE-RECEPTOR GENES; MUSCARINIC RECEPTORS; CNS DISORDERS; GPCRS AB This Letter describes a chemical lead optimization campaign directed at VU0108370, a weak M-1 PAM hit with a novel chemical scaffold from a functional HTS screen within the MLPCN. An iterative parallel synthesis approach rapidly established SAR for this series and afforded VU0405652 (ML169), a potent, selective and brain penetrant M-1 PAM with an in vitro profile comparable to the prototypical M-1 PAM, BQCA, but with an improved brain to plasma ratio. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Bridges, Thomas M.; Sheffler, Douglas J.; Cho, Hyekyung P.; Daniels, J. Scott; Jones, Carrie K.; Niswender, Colleen M.; Weaver, C. David; Conn, P. Jeffrey; Lindsley, Craig W.; Wood, Michael R.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Lindsley, Craig W.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [Sheffler, Douglas J.; Daniels, J. Scott; Jones, Carrie K.; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Wood, Michael R.] Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA. [Bridges, Thomas M.; Cho, Hyekyung P.; Daniels, J. Scott; Jones, Carrie K.; Niswender, Colleen M.; Weaver, C. David; Conn, P. Jeffrey; Lindsley, Craig W.; Wood, Michael R.] Vanderbilt Specialized Chem Ctr MLPCN, Nashville, TN 37232 USA. [Reid, Paul R.; Lewis, L. Michelle; Days, Emily; Weaver, C. David; Lindsley, Craig W.] Vanderbilt Inst Chem Biol Chem Synth Core, Nashville, TN 37232 USA. [Jones, Carrie K.] Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37232 USA. RP Wood, MR (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. EM michael.r.wood@vanderbilt.edu RI Conn, Peter/D-7848-2012 FU MLPCN [1U54 MH084659]; NIMH [1RO1 MH082867]; NIH; Alzheimer's Association [IIRG-07-57131] FX The authors thank the MLPCN (1U54 MH084659), NIMH (1RO1 MH082867), NIH and the Alzheimer's Association (IIRG-07-57131) for support of our Program in the development of subtype selective allosteric ligands of mAChRs. NR 21 TC 41 Z9 42 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 1 PY 2011 VL 21 IS 9 BP 2697 EP 2701 DI 10.1016/j.bmcl.2010.12.015 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 753KW UT WOS:000289773300025 PM 21194936 ER PT J AU Lesselroth, BJ Yang, J McConnachie, J Brenk, T Winterbottom, L AF Lesselroth, Blake J. Yang, Jianji McConnachie, Judy Brenk, Thomas Winterbottom, Lisa TI Addressing the sociotechnical drivers of quality improvement: a case study of post-operative DVT prophylaxis computerised decision support SO BMJ QUALITY & SAFETY LA English DT Article ID HOSPITALIZED MEDICAL PATIENTS; VENOUS THROMBOEMBOLISM; HEALTH-CARE; ANTICOAGULANT PROPHYLAXIS; INFORMATION-TECHNOLOGY; PATIENT SAFETY; FRAMEWORK; SYSTEMS; MODEL; METAANALYSIS AB Background: Quality improvement (QI) initiatives characterised by iterative cycles of quantitative data analysis do not readily explain the organisational determinants of change. However, the integration of sociotechnical theory can inform more effective strategies. Our specific aims were to (1) describe a computerised decision support intervention intended to improve adherence with deep venous thrombosis (DVT) prophylaxis recommendations; and (2) show how sociotechnical theory expressed in 'Fit between Individuals, Task and Technology' framework (FITT) can identify and clarify the facilitators and barriers to QI work. Methods: A multidisciplinary team developed and implemented electronic menus with DVT prophylaxis recommendations. Stakeholders were interviewed and human factors were analysed to optimise integration. Menu exposure, order placement and clinical performance were measured. Vista tool extraction and chart review were used. Performance compliance pre-implementation was 77%. Results: There were 80-110 eligible cases per month. Initial menu use rate was 20%. After barriers were classified and addressed using the FITT framework, use improved 50% to 90%. Tasks, users and technology issues in the FITT model and their interfaces were identified and addressed. Workflow styles, concerns about validity of guidelines, cycle times and perceived ambiguity of risk were issues identified. Conclusions: DVT prophylaxis in a surgical setting is fraught with socio-political agendas, cognitive dissonance and misaligned expectations. These must be sought and articulated if organisations are to respond to internal resistance to change. This case study demonstrates that QI teams using information technology must understand the clinical context, even in mature electronic health record environments, in order to implement sustainable systems. C1 [Lesselroth, Blake J.; Yang, Jianji; Winterbottom, Lisa] Oregon Hlth & Sci Univ, Portland Oregon VA Med Ctr, Portland, OR 97201 USA. RP Lesselroth, BJ (reprint author), Portland VA Med Ctr, Portland Ctr Evaluat Clin Serv, P3 MED,3710 SW US Vet Hosp Dr, Portland, OR USA. EM blake.lesselroth@va.gov RI Johnson, Marilyn/E-7209-2011 FU Portland VA Informatics Center FX The authors wish to thank Dr. Jennifer Logan, Dr. Devan Kansagara, and Dr. Ana Quinones for their insightful comments during manuscript preparation. The authors also wish to thank Dr. David Douglas and the Portland VA Informatics Center for project support. NR 35 TC 12 Z9 12 U1 6 U2 15 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD MAY PY 2011 VL 20 IS 5 BP 381 EP 389 DI 10.1136/bmjqs.2010.042689 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 753JT UT WOS:000289769100001 PM 21209144 ER PT J AU Foy, R Ovretveit, J Shekelle, PG Pronovost, PJ Taylor, SL Dy, S Hempel, S McDonald, KM Rubenstein, LV Wachter, RM AF Foy, Robbie Ovretveit, John Shekelle, Paul G. Pronovost, Peter J. Taylor, Stephanie L. Dy, Sydney Hempel, Susanne McDonald, Kathryn M. Rubenstein, Lisa V. Wachter, Robert M. TI The role of theory in research to develop and evaluate the implementation of patient safety practices SO BMJ QUALITY & SAFETY LA English DT Article ID HEALTH-CARE; COMPLEX INTERVENTIONS; PSYCHOLOGICAL THEORY; QUALITY IMPROVEMENT; CLINICAL-PRACTICE; FEEDBACK; BEHAVIOR; STRATEGIES; KNOWLEDGE; DESIGN AB Theories provide a way of understanding and predicting the effects of patient safety practices (PSPs), interventions intended to prevent or mitigate harm caused by healthcare or risks of such harm. Yet most published evaluations make little or no explicit reference to theory, thereby hindering efforts to generalise findings from one context to another. Theories from a wide range of disciplines are potentially relevant to research on PSPs. Theory can be used in research to explain clinical and organisational behaviour, to guide the development and selection of PSPs, and in evaluating their implementation and mechanisms of action. One key recommendation from an expert consensus process is that researchers should describe the theoretical basis for chosen intervention components or provide an explicit logic model for 'why this PSP should work.' Future theory-driven evaluations would enhance generalisability and help build a cumulative understanding of the nature of change. C1 [Foy, Robbie] Univ Leeds, Leeds Inst Hlth Sci, Leeds LS2 9LJ, W Yorkshire, England. [Ovretveit, John] Karolinska Inst, Med Management Ctr, Stockholm, Sweden. [Shekelle, Paul G.; Taylor, Stephanie L.; Hempel, Susanne; Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. [Shekelle, Paul G.; Taylor, Stephanie L.; Rubenstein, Lisa V.] VA Greater Los Angeles, Los Angeles, CA USA. [Pronovost, Peter J.; Dy, Sydney] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [McDonald, Kathryn M.] Stanford Univ, Stanford, CA 94305 USA. [Wachter, Robert M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Foy, R (reprint author), Univ Leeds, Leeds Inst Hlth Sci, 101 Clarendon Rd, Leeds LS2 9LJ, W Yorkshire, England. EM r.foy@leeds.ac.uk FU AHRQ FX Funding AHRQ. NR 48 TC 39 Z9 39 U1 4 U2 21 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD MAY PY 2011 VL 20 IS 5 BP 453 EP 459 DI 10.1136/bmjqs.2010.047993 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 753JT UT WOS:000289769100012 PM 21317181 ER PT J AU Bhavsar, KV Subramanian, ML AF Bhavsar, Kavita V. Subramanian, Manju L. TI Risk factors for progression of subclinical diabetic macular oedema SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; RETINAL THICKNESS ANALYZER; QUANTITATIVE ASSESSMENT; RETINOPATHY; EYES; HEALTHY; NO AB Backgroud/aims The purpose of this study was to determine the incidence of, and risk factors dictating, progression of subclinical macular oedema (SCME) to clinically significant macular oedema (CSME) in patients with diabetes. Methods This was a retrospective, observational case-controlled study at the Veterans Administration (VA) Boston Healthcare System. The study group included subjects with central subfield macular thickness (CSMT) of 200-300 mu m, measured by optical coherence tomography, compared with a control group with foveal thickness of < 200 mu m, matched for age, sex and duration of diabetes. Main outcomes measured were progression to CSME by clinical examination. Results A total 124 eyes of 73 diabetic patients from the greater Boston area were included in this retrospective study. The study group comprised 52 eyes of 37 diabetic patients with SCME in one or both eyes. The control group included 72 eyes of 36 patients without macular oedema. Sixteen eyes of 13 subjects (35%) progressed to CSME in the study group, compared with six eyes of four subjects (11%) in the control group. Stepwise logistic regression analysis confirmed that prior history of CSME increased the risk of progression (OR 3.69, CI 1.10 to 12.31, p=0.03). Logistic regression analysis also depicted a 15% increase in odds of progression with each 10 mu m increase in CSMT (OR 1.15, CI 1.03 to 1.28, p=0.01). Conclusions The results and statistical analyses of this retrospective study suggest that a significant number of patients with SCME ultimately progress to CSME compared with controls. A significant association with prior history of CSME, advancing age and graded increases in CSMT was found. C1 [Bhavsar, Kavita V.; Subramanian, Manju L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhavsar, Kavita V.; Subramanian, Manju L.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. RP Subramanian, ML (reprint author), 85 E Concord St, Boston, MA 02118 USA. EM manju.subramanian@bmc.org NR 23 TC 6 Z9 6 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAY PY 2011 VL 95 IS 5 BP 671 EP 674 DI 10.1136/bjo.2010.182337 PG 4 WC Ophthalmology SC Ophthalmology GA 752TN UT WOS:000289717300018 PM 21071757 ER PT J AU Sandberg, MA Rosner, B Weigel-DiFranco, C Berson, EL AF Sandberg, Michael A. Rosner, Bernard Weigel-DiFranco, Carol Berson, Eliot L. TI Lack of scientific rationale for use of valproic acid for retinitis pigmentosa SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Letter C1 [Sandberg, Michael A.; Rosner, Bernard; Weigel-DiFranco, Carol; Berson, Eliot L.] Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Sandberg, MA (reprint author), Harvard Univ, Sch Med, Berman Gund Lab, 243 Charles St, Boston, MA 02114 USA. EM michael_sandberg@meei.harvard.edu NR 2 TC 12 Z9 12 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAY PY 2011 VL 95 IS 5 BP 744 EP 744 DI 10.1136/bjo.2010.198176 PG 1 WC Ophthalmology SC Ophthalmology GA 752TN UT WOS:000289717300036 PM 21131379 ER PT J AU Merry, AF Cooper, JB Soyannwo, O Wilson, IH Eichhorn, JH AF Merry, Alan F. Cooper, Jeffrey B. Soyannwo, Olaitan Wilson, Iain H. Eichhorn, John H. TI A call for standards on perioperative CO2 regulation Reply SO CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Letter ID INTERNATIONAL STANDARDS; ANESTHESIA 2010; SAFE PRACTICE C1 [Merry, Alan F.] Univ Auckland, Auckland 1, New Zealand. [Cooper, Jeffrey B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Soyannwo, Olaitan] Univ Ibadan, Coll Med, Univ Coll Hosp, Ibadan, Nigeria. [Wilson, Iain H.] Exeter NHS Fdn Trust, Exeter, Devon, England. [Eichhorn, John H.] Univ Kentucky, Coll Med, Lexington, KY USA. [Eichhorn, John H.] Univ Kentucky, Med Ctr, Lexington, KY USA. RP Merry, AF (reprint author), Univ Auckland, Auckland 1, New Zealand. OI Merry, Alan/0000-0001-7100-009X NR 2 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0832-610X J9 CAN J ANESTH JI Can. J. Anesth. PD MAY PY 2011 VL 58 IS 5 BP 474 EP 475 PG 2 WC Anesthesiology SC Anesthesiology GA 752II UT WOS:000289684400013 ER PT J AU Hatziapostolou, M Iliopoulos, D AF Hatziapostolou, Maria Iliopoulos, Dimitrios TI Epigenetic aberrations during oncogenesis SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Epigenetics; Networks; Methylation; Histones; MicroRNAs; Oncogenic transformation ID HUMAN CANCER-CELLS; HUMAN BREAST-CANCER; HISTONE DEACETYLASE INHIBITORS; DEMETHYLASE JMJD3 CONTRIBUTES; ACUTE LYMPHOBLASTIC-LEUKEMIA; CPG ISLAND HYPERMETHYLATION; GLOBAL DNA HYPOMETHYLATION; PUTATIVE TUMOR-SUPPRESSOR; ACUTE MYELOID-LEUKEMIA; BINDING PROTEIN MECP2 AB The aberrant epigenetic landscape of a cancer cell is characterized by global genomic hypomethylation, CpG island promoter hypermethylation of tumor suppressor genes, and changes in histone modification patterns, as well as altered expression profiles of chromatin-modifying enzymes. Recent advances in the field of epigenetics have revealed that microRNAs' expression is also under epigenetic regulation and that certain microRNAs control elements of the epigenetic machinery. The reversibility of epigenetic marks catalyzed the development of epigenetic-altering drugs. However, a better understanding of the intertwined relationship between genetics, epigenetics and microRNAs is necessary in order to resolve how gene expression aberrations that contribute to tumorigenesis can be therapeutically corrected. C1 [Hatziapostolou, Maria; Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Hatziapostolou, Maria; Iliopoulos, Dimitrios] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Iliopoulos, D (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM dimitrios_iliopoulos@dfci.harvard.edu RI Hatziapostolou, Maria/N-1820-2015 OI Hatziapostolou, Maria/0000-0003-2493-7028 NR 226 TC 75 Z9 79 U1 2 U2 16 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAY PY 2011 VL 68 IS 10 BP 1681 EP 1702 DI 10.1007/s00018-010-0624-z PG 22 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 750TE UT WOS:000289570100004 PM 21249513 ER PT J AU Teitelman, AM Ratcliffe, SJ McDonald, CC Brawner, BM Sullivan, CM AF Teitelman, Anne M. Ratcliffe, Sarah J. McDonald, Catherine C. Brawner, Bridgette M. Sullivan, Cris M. TI Relationships Between Physical and Non-Physical Forms of Intimate Partner Violence and Depression among Urban Minority Adolescent Females SO CHILD AND ADOLESCENT MENTAL HEALTH LA English DT Article DE Violence; depression; adolescence ID AFRICAN-AMERICAN ADOLESCENTS; DATING VIOLENCE; RISK-FACTORS; SEXUAL RISK; CAUCASIAN ADOLESCENTS; YOUNG ADOLESCENTS; HEALTH OUTCOMES; MENTAL-HEALTH; UNITED-STATES; SYMPTOMS AB Background: Little is known about intimate partner violence (IPV) and depression among low income, urban African American and Hispanic adolescent females. Method: Interviews with 102 urban African American and Hispanic adolescent females examined physical abuse, emotional/verbal abuse, and threats, and their unique and combined associations with depression. Results: One-quarter of the sample experienced all three types of abuse. Non-physical forms of IPV were significantly associated with depression. Conclusions: Some urban adolescent females from lower income households experience high rates of IPV. Physical and non-physical forms of IPV are important in understanding and responding to depression in this population. Key Practitioner Message: Among urban adolescent females, it is important to assess for non-physical as well as physical forms of IPV, and if detected, to also screen for depression Adolescent females reporting higher levels of IPV may have higher levels of depression, and thus may need more extensive treatment, support, and require greater follow-up Adolescent females who present with depression should be screened for IPV It is important to assess for protective factors, such as social support, and make referrals accordingly. Early detection and intervention for both IPV and depression can reduce future vulnerabilities C1 [Teitelman, Anne M.; McDonald, Catherine C.; Brawner, Bridgette M.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Ratcliffe, Sarah J.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Sullivan, Cris M.] Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. RP Teitelman, AM (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Fagin Hall,2L Rm-244,418 Curie Blvd, Philadelphia, PA 19104 USA. EM teitelm@nursing.upenn.edu FU Michigan Department of Community Health and Michigan State University; National Institute of Nursing Research [F31NR011107] FX This research was supported by funds from Michigan Department of Community Health and Michigan State University. This research was also supported by Award Number F31NR011107 (PI: Catherine C. McDonald) from the National Institute of Nursing Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. Drs. Teitelman and Ratcliffe had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 61 TC 3 Z9 3 U1 3 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1475-357X J9 CHILD ADOL MENT H-UK JI Child Adolesc. Ment. Health PD MAY PY 2011 VL 16 IS 2 BP 92 EP 100 DI 10.1111/j.1475-3588.2010.00572.x PG 9 WC Psychology, Clinical; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 749MS UT WOS:000289472500005 PM 21617762 ER PT J AU Valdez, C Locke, C Sloan, N AF Valdez, Christine Locke, Christy Sloan, Nancy TI Healing Touch (HT) as an Innovative Method of Care for Patients SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Valdez, Christine; Locke, Christy; Sloan, Nancy] US Dept Vet Affairs, Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAY-JUN PY 2011 VL 25 IS 3 BP 145 EP 145 PG 1 WC Nursing SC Nursing GA 748QH UT WOS:000289405000025 ER PT J AU Saeed, M Villarroel, M Reisner, AT Clifford, G Lehman, LW Moody, G Heldt, T Kyaw, TH Moody, B Mark, RG AF Saeed, Mohammed Villarroel, Mauricio Reisner, Andrew T. Clifford, Gari Lehman, Li-Wei Moody, George Heldt, Thomas Kyaw, Tin H. Moody, Benjamin Mark, Roger G. TI Multiparameter Intelligent Monitoring in Intensive Care II: A public-access intensive care unit database SO CRITICAL CARE MEDICINE LA English DT Article DE databases; clinical decision support; hemodynamic instability; information technology; patient monitoring ID OUTCOME PREDICTION; SEPTIC SHOCK; VENTILATION; MODELS AB Objective: We sought to develop an intensive care unit research database applying automated techniques to aggregate high-resolution diagnostic and therapeutic data from a large, diverse population of adult intensive care unit patients. This freely available database is intended to support epidemiologic research in critical care medicine and serve as a resource to evaluate new clinical decision support and monitoring algorithms. Design: Data collection and retrospective analysis. Setting: All adult intensive care units (medical intensive care unit, surgical intensive care unit, cardiac care unit, cardiac surgery recovery unit) at a tertiary care hospital. Patients: Adult patients admitted to intensive care units between 2001 and 2007. Interventions: None. Measurements and Main Results: The Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) database consists of 25,328 intensive care unit stays. The investigators collected detailed information about intensive care unit patient stays, including laboratory data, therapeutic intervention profiles such as vasoactive medication drip rates and ventilator settings, nursing progress notes, discharge summaries, radiology reports, provider order entry data, International Classification of Diseases, 9th Revision codes, and, for a subset of patients, high-resolution vital sign trends and waveforms. Data were automatically deidentified to comply with Health Insurance Portability and Accountability Act standards and integrated with relational database software to create electronic intensive care unit records for each patient stay. The data were made freely available in February 2010 through the Internet along with a detailed user's guide and an assortment of data processing tools. The overall hospital mortality rate was 11.7%, which varied by critical care unit. The median intensive care unit length of stay was 2.2 days (interquartile range, 1.1-4.4 days). According to the primary International Classification of Diseases, 9th Revision codes, the following disease categories each comprised at least 5% of the case records: diseases of the circulatory system (39.1%); trauma (10.2%); diseases of the digestive system (9.7%); pulmonary diseases (9.0%); infectious diseases (7.0%); and neoplasms (6.8%). Conclusions: MIMIC-II documents a diverse and very large population of intensive care unit patient stays and contains comprehensive and detailed clinical data, including physiological waveforms and minute-by-minute trends for a subset of records. It establishes a new public-access resource for critical care research, supporting a diverse range of analytic studies spanning epidemiology, clinical decision-rule development, and electronic tool development. (Crit Care Med 2011; 39: 952-960) C1 [Saeed, Mohammed; Villarroel, Mauricio; Reisner, Andrew T.; Clifford, Gari; Lehman, Li-Wei; Moody, George; Heldt, Thomas; Moody, Benjamin; Mark, Roger G.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Mark, Roger G.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Saeed, Mohammed] Univ Michigan Hosp, Ann Arbor, MI 48109 USA. [Villarroel, Mauricio] Philips Healthcare, Andover, MA USA. [Clifford, Gari] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Clifford, Gari] Univ Oxford, Dept Engn Sci, Inst Biomed Engn, Oxford OX1 3PJ, England. [Kyaw, Tin H.] AdMob Inc, San Mateo, CA USA. RP Mark, RG (reprint author), MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM rgmark@mit.edu FU National Institute of Biomedical Imaging and Bioengineering [R01 EB001659]; Philips Healthcare; National Institutes of Health (NIH) FX This research was supported by grant R01 EB001659 from the National Institute of Biomedical Imaging and Bioengineering and by support from Philips Healthcare.; Dr. Saeed is employed by Philips Healthcare. Dr. Villarroel, Dr. Lehman, Mr. Moody, Dr. Heldt, and Dr. Mark received funding from the National Institutes of Health (NIH). Dr. Reisner consulted with General Electric Healthcare and received funding from the NIH. The remaining authors have not disclosed any potential conflicts of interest. NR 30 TC 223 Z9 229 U1 6 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2011 VL 39 IS 5 BP 952 EP 960 DI 10.1097/CCM.0b013e31820a92c6 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 752CX UT WOS:000289667000004 PM 21283005 ER PT J AU Hug, CW Clifford, GD Reisner, AT AF Hug, Caleb W. Clifford, Gari D. Reisner, Andrew T. TI Clinician blood pressure documentation of stable intensive care patients: An intelligent archiving agent has a higher association with future hypotension SO CRITICAL CARE MEDICINE LA English DT Article DE hypotension; intensive care; physiologic monitoring; electronic medical record; digital signal processing; automatic data processing ID RESPIRATORY RATE; VITAL SIGN; NURSES AB Objective: To compare invasive blood pressure measurements recorded using an automated archiving method against clinician-documented values from the same invasive monitor and determine which method of recording blood pressure is more highly associated with the subsequent onset of hypotension. Design: Retrospective comparative analysis. Setting: Intensive care patients in a university hospital. Patients: Mixed medical/surgical patients. Interventions: None. Measurements and Main Results: Using intervals of hemodynamic stability from 2,320 patient records, we retrospectively compared paired sources of invasive blood pressure data: 1) measurements documented by the nursing staff and 2) measurements generated by an automated archiving method that intelligently excludes unreliable (e. g., noisy or excessively damped) blood pressure values. The primary outcome was the occurrence of subsequent "consensus" hypotension, i.e., hypotension documented jointly by the nursing staff and the automated archive. The automated method could be adjusted to alter its operating characteristics (sensitivity and specificity). At a matched level of specificity (96%), blood pressures from the automated archiving method were more sensitive (28%) for subsequent consensus hypotension vs. the nurse-documented values (21%). Likewise, at a matched level of sensitivity (21%), the values from the automated method were more specific (99%) vs. the nurse-documented values (96%). These significant findings (p < .001) were consistent in a set of sensitivity analyses that employed alternative criteria for patient selection and the clinical outcome definition. Conclusions: During periods of hemodynamic stability in an intensive care unit patient population, clinician-documented blood pressure values were inferior to values from an intelligent automated archiving method as early indicators of hemodynamic instability. Human oversight may not be necessary for creating a valid archive of vital sign data within an electronic medical record. Furthermore, if clinicians do have a tendency to disregard early indications of instability, then an automated archive may be a preferable source of data for so-called early warning systems that identify patients at risk of decompensation. (Crit Care Med 2011; 39:1006-1014) C1 [Hug, Caleb W.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Clifford, Gari D.; Reisner, Andrew T.] MIT, Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. [Clifford, Gari D.] Univ Oxford, Inst Biomed Engn, Oxford, England. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Hug, CW (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. EM chug@csail.mit.edu FU National Library of Medicine (Bethesda, MD) [LM 07092]; U.S. National Institute of Biomedical Imaging and Bioengineering (Bethesda, MD); National Institutes of Health (Bethesda, MD) [R01 EB001659]; Philips Healthcare (An-dover, MA); Information and Communication University (Daejeon, Korea); National Institutes of Health (Bethesda, MD); National Institutes of Health FX Supported, in part, by the National Library of Medicine (Bethesda, MD) Medical Informatics Traineeship (grant LM 07092), the U.S. National Institute of Biomedical Imaging and Bioengineering (Bethesda, MD) and the National Institutes of Health (Bethesda, MD) under grant R01 EB001659, Philips Healthcare (An-dover, MA), and theInformation and Communication University (Daejeon, Korea). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Library of Medicine, the U. S. National Institute of Biomedical Imaging and Bioengineering, the National Institutes of Health, Philips Healthcare, or Information and Communication University.; Dr. Hug and Dr. Clifford received funding from the National Institutes of Health (Bethesda, MD). Dr. Reisner received funding from the National Institutes of Health and consulted for General Electric (Fairfield, CT). NR 22 TC 14 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2011 VL 39 IS 5 BP 1006 EP 1014 DI 10.1097/CCM.0b013e31820eab8e PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 752CX UT WOS:000289667000011 PM 21336136 ER PT J AU Akeju, O Alston, TA AF Akeju, Oluwaseun Alston, Theodore A. TI Stemming electrical outage in myocardial infarction SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE arrhythmia; cell therapy; induced pluripotent stem cell; stem cell; ventricular fibrillation ID HUMAN FIBROBLASTS; CELLS; CARDIOMYOCYTES; PLURIPOTENCY; INDUCTION; MOUSE C1 [Akeju, Oluwaseun; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. RP Akeju, O (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. NR 15 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2011 VL 39 IS 5 BP 1222 EP 1223 DI 10.1097/CCM.0b013e31820a838a PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 752CX UT WOS:000289667000053 PM 21610588 ER PT J AU Norris, PR Cobb, JP AF Norris, Patrick R. Cobb, J. Perren TI Ten years later, still "gene in a haystack?" SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE genetic polymorphisms; candidate gene association; surfactant protein B; surfactant; pneumonia; pediatrics; mechanical ventilation ID PREDISPOSITION; ASSOCIATION; OUTCOMES C1 [Norris, Patrick R.] Vanderbilt Univ, Med Ctr, Div Trauma & Surg Crit Care, Nashville, TN 37235 USA. [Cobb, J. Perren] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Crit Care Ctr, Dept Surg, Boston, MA 02114 USA. RP Norris, PR (reprint author), Vanderbilt Univ, Med Ctr, Div Trauma & Surg Crit Care, Nashville, TN 37235 USA. NR 14 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2011 VL 39 IS 5 BP 1231 EP 1232 DI 10.1097/CCM.0b013e318211f8f7 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 752CX UT WOS:000289667000059 PM 21610594 ER PT J AU Christov, M Koren, S Yuan, Q Baron, R Lanske, B AF Christov, Marta Koren, Shany Yuan, Quan Baron, Roland Lanske, Beate TI Genetic Ablation of Sfrp4 in Mice Does Not Affect Serum Phosphate Homeostasis SO ENDOCRINOLOGY LA English DT Article ID FRIZZLED-RELATED PROTEIN-4; CHRONIC KIDNEY-DISEASE; VITAMIN-D METABOLISM; NULL MICE; EXPRESSION; MORTALITY; TUMORS; FGF23; 1,25-DIHYDROXYVITAMIN-D; HYPERPHOSPHATEMIA AB Serum phosphate levels are regulated by PTH and the fibroblast growth factor 23 (Fgf23)/Klotho endocrine system, which both affect expression of Npt2a and thus the apical reabsorption of phosphate in the proximal renal tubules. In addition to Fgf23, secreted frizzled-related protein 4 (Sfrp4) has recently been implicated as an additional phosphate regulator in vivo and in vitro. Here we demonstrate that ablation of the Sfrp4 gene in mice does not lead to altered serum or urine phosphate levels. Furthermore, Sfrp4 is unable to compensate for the absence of Fgf23 or Klotho because double knockouts have a similar biochemical profile and phenotype as animals with ablation of Fgf23 or Klotho alone. Taken together, our data suggest that Sfrp4 does not contribute to the long-term regulation of serum phosphate levels in mice. (Endocrinology 152: 2031-2036, 2011) C1 [Christov, Marta; Koren, Shany; Yuan, Quan; Lanske, Beate] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Christov, Marta] Beth Israel Deaconess Med Ctr, Div Nephrol, Dept Med, Renal Unit Farr8, Boston, MA 02215 USA. [Baron, Roland] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Endocrine Unit, Boston, MA 02114 USA. RP Lanske, B (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, Res & Educ Bldg,Room 303,188 Longwood Ave, Boston, MA 02115 USA. EM mchrist3@bidmc.harvard.edu; beate_lanske@hsdm.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK007199-33, DK073944] FX M.C. is supported by National Institute of Diabetes and Digestive and Kidney Diseases T32 Training Grant DK007199-33, and BL and QY are supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK073944. NR 29 TC 10 Z9 10 U1 0 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2011 VL 152 IS 5 BP 2031 EP 2036 DI 10.1210/en.2010-1351 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 753OJ UT WOS:000289788500034 PM 21427221 ER PT J AU McQuillin, A Bass, N Anjorin, A Lawrence, J Kandaswamy, R Lydall, G Moran, J Sklar, P Purcell, S Gurling, H AF McQuillin, Andrew Bass, Nicholas Anjorin, Adebayo Lawrence, Jacob Kandaswamy, Radhika Lydall, Greg Moran, Jennifer Sklar, Pamela Purcell, Shaun Gurling, Hugh TI Analysis of genetic deletions and duplications in the University College London bipolar disorder case control sample SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE bipolar disorder; genetic susceptibility; deletions; duplications; structural variation; schizophrenia ID GENOME-WIDE ASSOCIATION; COPY NUMBER VARIATION; IDIOPATHIC GENERALIZED EPILEPSY; ALZHEIMERS-DISEASE; MENTAL-RETARDATION; INCREASE RISK; RECURRENT MICRODELETIONS; 15Q13.3 MICRODELETIONS; STRUCTURAL VARIATION; 16P13.11 PREDISPOSE AB Genetic deletions and duplications known as copy number variants have been strongly implicated in genetic susceptibility to schizophrenia, autism, attention deficit hyperactivity disorder and epilepsy. The overall rate of copy number variants in the University College London (UCL) bipolar disorder sample was found to be slightly lower than the rate in controls. This finding confirms the results from other studies that have also shown no increased rate of copy number variants in bipolar disorder. However, some rare duplications and deletions were observed only in bipolar disorder cases and not in controls, these included some that had previously been detected only in rare cases of bipolar disorder. We conclude that copy-number variant analysis shows no obvious sharing of the same genetic susceptibility between schizophrenia and bipolar disorder. Copy number variants do not seem to have an important role in susceptibility to bipolar disorder, they may, however, still represent a rare cause of the disease, although the evidence for this is far from clear. European Journal of Human Genetics (2011) 19, 588-592; doi:10.1038/ejhg.2010.221; published online 5 January 2011 C1 [McQuillin, Andrew; Bass, Nicholas; Anjorin, Adebayo; Lawrence, Jacob; Kandaswamy, Radhika; Lydall, Greg; Gurling, Hugh] UCL, Res Dept Mental Hlth Sci, Windeyer Inst Med Sci, Mol Psychiat Lab, London, England. [Moran, Jennifer; Sklar, Pamela; Purcell, Shaun] MIT, Cambridge, MA 02139 USA. [Moran, Jennifer; Sklar, Pamela; Purcell, Shaun] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Sklar, Pamela; Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sklar, Pamela; Purcell, Shaun] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sklar, Pamela; Purcell, Shaun] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Sklar, Pamela; Purcell, Shaun] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Sklar, Pamela; Purcell, Shaun] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP McQuillin, A (reprint author), Royal Free & Univ Coll London Med Sch, Res Dept Mental Hlth Sci, Mol Psychiat Lab, London W1T 4JF, England. EM a.mcquillin@ucl.ac.uk RI Gurling, Hugh/A-5029-2010; McQuillin, Andrew/C-1623-2008; OI McQuillin, Andrew/0000-0003-1567-2240; Moran, Jennifer/0000-0002-5664-4716 FU Medical Research Council [G1000708] NR 63 TC 29 Z9 29 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2011 VL 19 IS 5 BP 588 EP 592 DI 10.1038/ejhg.2010.221 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 753OR UT WOS:000289789500020 PM 21206513 ER PT J AU Janssens, ACJW Ioannidis, JPA Bedrosian, S Boffetta, P Dolan, SM Dowling, N Fortier, I Freedman, AN Grimshaw, JM Gulcher, J Gwinn, M Hlatky, MA Janes, H Kraft, P Melillo, S O'Donnell, CJ Pencina, MJ Ransohoff, D Schully, SD Seminara, D Winn, DM Wright, CF van Duijn, CM Little, J Khoury, MJ AF Janssens, A. Cecile J. W. Ioannidis, John P. A. Bedrosian, Sara Boffetta, Paolo Dolan, Siobhan M. Dowling, Nicole Fortier, Isabel Freedman, Andrew N. Grimshaw, Jeremy M. Gulcher, Jeffrey Gwinn, Marta Hlatky, Mark A. Janes, Holly Kraft, Peter Melillo, Stephanie O'Donnell, Christopher J. Pencina, Michael J. Ransohoff, David Schully, Sheri D. Seminara, Daniela Winn, Deborah M. Wright, Caroline F. van Duijn, Cornelia M. Little, Julian Khoury, Muin J. TI Strengthening the reporting of genetic risk prediction studies (GRIPS): explanation and elaboration SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; HEART-DISEASE RISK; OPERATING CHARACTERISTIC CURVE; TYPE-2 DIABETES RISK; RECLASSIFICATION MEASURES; MACULAR DEGENERATION; DIAGNOSTIC-ACCURACY; CARDIOVASCULAR RISK; CONTROLLED-TRIALS; PROSTATE-CANCER AB The rapid and continuing progress in gene discovery for complex diseases is fueling interest in the potential application of genetic risk models for clinical and public health practice. The number of studies assessing the predictive ability is steadily increasing, but they vary widely in completeness of reporting and apparent quality. Transparent reporting of the strengths and weaknesses of these studies is important to facilitate the accumulation of evidence on genetic risk prediction. A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by previous reporting guidelines. These recommendations aim to enhance the transparency, quality and completeness of study reporting, and thereby to improve the synthesis and application of information from multiple studies that might differ in design, conduct or analysis. European Journal of Human Genetics (2011) 19; doi:10.1038/ejhg.2011.27; published online 16 March 2011 C1 [Janssens, A. Cecile J. W.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Fdn Res & Technol, Biomed Res Inst, Ioannina, Greece. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Ioannidis, John P. A.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Tufts CTSI, Boston, MA USA. [Ioannidis, John P. A.] Ctr Genet Epidemiol & Modeling, Boston, MA USA. [Ioannidis, John P. A.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. [Ioannidis, John P. A.; Bedrosian, Sara; Dowling, Nicole; Gwinn, Marta; Melillo, Stephanie; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Dolan, Siobhan M.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA. [Fortier, Isabel] Publ Populat Project Genom P3G, Montreal, PQ, Canada. [Freedman, Andrew N.; Schully, Sheri D.; Seminara, Daniela; Winn, Deborah M.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Grimshaw, Jeremy M.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Grimshaw, Jeremy M.] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Gulcher, Jeffrey] deCODE Genet, Reykjavik, Iceland. [Hlatky, Mark A.] Stanford Univ, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. [Janes, Holly] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA. [Janes, Holly] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [O'Donnell, Christopher J.] NHLBIs Framingham Heart Study, Framingham, MA USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Pencina, Michael J.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Pencina, Michael J.] Harvard Clin Res Inst, Boston, MA USA. [Ransohoff, David] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Wright, Caroline F.] PHG Fdn, Cambridge, England. [Little, Julian] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Janssens, ACJW (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM a.janssens@erasmusmc.nl RI Ioannidis, John/G-9836-2011; janssens, cecile/L-1075-2015; OI Janssens, A Cecile/0000-0002-6153-4976; Wright, Caroline/0000-0003-2958-5076 FU National Heart, Lung and Blood Institute; National Cancer Institute, National Institutes of Health; Donald W. Reynolds Foundation; Leducq Foundation FX Examples: 'This study was supported by grants from the National Heart, Lung and Blood Institute and National Cancer Institute, National Institutes of Health; the Donald W. Reynolds Foundation; and the Leducq Foundation. Additional support for DNA extraction, reagents and data analysis was provided by Roche Diagnostics and Amgen. Genotyping of the 9p21.3 variant was performed by Celera. The funding sources had no role in the design, conduct, or reporting of this study or the decision to submit the manuscript for publication'.56 NR 93 TC 2 Z9 2 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2011 VL 19 IS 5 DI 10.1038/ejhg.2011.27 PG 18 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 753OR UT WOS:000289789500001 ER PT J AU Gavin, MC Newton-Cheh, C Gaziano, JM Cook, NR VanDenburgh, M Albert, CM AF Gavin, Michael C. Newton-Cheh, Christopher Gaziano, John Michael Cook, Nancy R. VanDenburgh, Martin Albert, Christine M. TI A common variant in the beta(2)-adrenergic receptor and risk of sudden cardiac death SO HEART RHYTHM LA English DT Article DE Beta(2)-adrenergic receptor; Genetic epidemiology; Sudden cardiac death; Sympathetic nervous system ID UNITED-STATES; VENTRICULAR-FIBRILLATION; NERVOUS-SYSTEM; CORONARY DEATH; IN-VIVO; POLYMORPHISMS; AGONIST; WOMEN AB BACKGROUND Homozygosity for a common nonsynonymous single nucleotide polymorphism (Gln27Glu) in the beta(2)-adrenergic receptor gene (ADRB2) has been inconsistently associated with sudden cardiac death (SCD) in individual studies of small sample size. OBJECTIVE The purpose of this study was to examine the association between the Gln27Glu polymorphism and SCD in a large combined sample of SCD cases. METHODS Nested case-control analysis was performed for individuals of Caucasian ancestry enrolled in six prospective cohort studies. Genotypes for the Gln27Glu variant were determined for 492 cases of SCD and 1,388 controls matched for age, sex, cohort, follow-up time, and history of cardiovascular disease (CVD) and at the time of the blood draw. Individual studies were combined with conditional logistic regression with fixed effects meta-analysis assuming a recessive model. RESULTS Homozygosity for the Gln27 allele conferred a nonsignificant elevation of the age-adjusted odds ratio (OR 1.22, 95% confidence interval [CI] 0.98-1.53, P = .08) for SCD, which became marginally significant after controlling for multiple cardiac risk factors (OR 1.30, 95% CI 1.01-1.67, P = .046). In secondary analyses using controls additionally matched for the development of nonfatal CVD after the blood draw, results were attenuated (OR 1.19, 95% CI 0.92-1.52, P = .19). When the results of the primary analysis were combined in meta-analysis with published reports, a significant association between ADRB2 genotype and SCD emerged (OR 1.35, 95% CI 1.15-1.60, P = .0003). CONCLUSION These data from a large prospective case-control series, when combined with published studies, provide further evidence for an association between ADRB2 genotype and SCD. The mechanism is unknown but appears to be partly mediated by development of CVD. C1 [Albert, Christine M.] Harvard Univ, Ctr Arrhythmia Prevent, Div Prevent Med, Brigham & Womens Hosp,Cardiovasc Div,Med Sch, Boston, MA 02115 USA. [Gavin, Michael C.] Harvard Univ, Div Cardiovasc, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA. [Newton-Cheh, Christopher] Harvard & MIT, Broad Inst, Cambridge, MA USA. [Gaziano, John Michael] Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Gaziano, John Michael] Boston VA Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Gaziano, John Michael] Harvard Univ, Div Aging, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Cook, Nancy R.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Albert, CM (reprint author), Harvard Univ, Ctr Arrhythmia Prevent, Div Prevent Med, Brigham & Womens Hosp,Cardiovasc Div,Med Sch, 900 Commonwealth Ave E, Boston, MA 02115 USA. EM calbert@partners.org FU National Heart, Lung, and Blood Institute [HL-68070, HL-26490, HL-34595, HL-34594, HL-35464, HL-43851, HL-46959, HL-80467]; Doris Duke Charitable Foundation; National Cancer Institute [CA-34944, CA 40360, CA-47988, CA55075, CA-87969, CA 97193]; Lerner Young Investigator Award FX Supported by Grant HL-68070 from the National Heart, Lung, and Blood Institute and a Lerner Young Investigator Award to Dr. Albert and a Doris Duke Charitable Foundation Clinical Scientist Development Award to Dr. Newton-Cheh. The cohort studies were supported by Grants HL-26490, HL-34595, HL-34594, HL-35464, HL-43851, HL-46959, and HL-80467 from the National Heart, Lung, and Blood Institute and Grants CA-34944, CA 40360, CA-47988, CA55075, CA-87969, and CA 97193 from the National Cancer Institute. NR 27 TC 13 Z9 14 U1 0 U2 5 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 MAY PY 2011 VL 8 IS 5 BP 704 EP 710 DI 10.1016/j.hrthm.2011.01.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 753MW UT WOS:000289782600014 PM 21215823 ER PT J AU Chiang, S Oliva, E AF Chiang, Sarah Oliva, Esther TI Cytogenetic and molecular aberrations in endometrial stromal tumors SO HUMAN PATHOLOGY LA English DT Article DE Endometrial stromal tumor; JJAZ1; Translocation; Molecular pathogenesis; Cytogenetics; Uterine mesenchymal tumor ID SMOOTH-MUSCLE DIFFERENTIATION; JAZF1-JJAZ1 GENE FUSION; IN-SITU HYBRIDIZATION; SARCOMA-CELL-LINE; SEX-CORD TUMORS; HIGH-GRADE SARCOMAS; OF-THE-LITERATURE; MESENCHYMAL TUMORS; BETA-CATENIN; GLANDULAR DIFFERENTIATION AB Endometrial stromal tumors (ESTs) are rare uterine mesenchymal tumors, comprising <10% of all uterine mesenchymal neoplasms. The latest World Health Organization classification divides endometrial stromal tumors into 3 categories based on morphologic features: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma, and undifferentiated endometrial sarcoma. Specific cytogenetic aberrations and molecular genetic alterations have recently been identified in endometrial stromal tumors, providing insights into their molecular biology, potential diagnostic markers, and possible therapeutic targets. Currently, recurrent chromosomal rearrangements resulting in gene fusion play a substantive role in the pathogenesis of endometrial stromal nodules, endometrial stromal sarcomas, and a small subset of undifferentiated endometrial sarcomas. Loss of heterozygosity of tumor suppressor genes and deregulation of the Wnt signaling pathway have also been implicated in EST tumorigenesis. In this review, we summarize the recent advances in the molecular pathology of endometrial stromal tumors. (C) 2011 Elsevier Inc. All rights reserved. C1 [Chiang, Sarah] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 2, Boston, MA 02114 USA. EM eoliva@partners.org NR 88 TC 28 Z9 31 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 MAY PY 2011 VL 42 IS 5 BP 609 EP 617 DI 10.1016/j.humpath.2010.12.005 PG 9 WC Pathology SC Pathology GA 753VU UT WOS:000289808900001 PM 21420714 ER PT J AU Lin, JR Wang, H Collins, AB Stone, JR AF Lin, James R. Wang, He Collins, A. Bernard Stone, James R. TI Tongue necrosis and systemic vascular amyloidosis SO HUMAN PATHOLOGY LA English DT Article DE Tongue necrosis; Amyloidosis; Macroglossia; Giant cell arteritis ID POSTMORTEM; ARTERITIS AB Tongue necrosis is a rare but dramatic clinical finding, which is most often related to infection, trauma, malignancy, or vasculitis. We describe an extremely unusual case in which systemic amyloid deposition in small arteries caused by senile systemic amyloidosis was associated with necrosis of the tongue as well as necrosis of portions of the bowel. To our knowledge, this is the first report of ischemic tongue necrosis resulting from vascular amyloidosis. (C) 2011 Elsevier Inc. All rights reserved. C1 [Lin, James R.; Wang, He; Collins, A. Bernard; Stone, James R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Stone, James R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Stone, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. EM jrstone@partners.org NR 14 TC 1 Z9 1 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2011 VL 42 IS 5 BP 734 EP 737 DI 10.1016/j.humpath.2010.08.011 PG 4 WC Pathology SC Pathology GA 753VU UT WOS:000289808900014 PM 21236468 ER PT J AU Johnson, AD Newton-Cheh, C Chasman, DI Ehret, GB Johnson, T Rose, L Rice, K Verwoert, GC Launer, LJ Gudnason, V Larson, MG Chakravarti, A Psaty, BM Caulfield, M van Duijn, CM Ridker, PM Munroe, PB Levy, D AF Johnson, Andrew D. Newton-Cheh, Christopher Chasman, Daniel I. Ehret, Georg B. Johnson, Toby Rose, Lynda Rice, Kenneth Verwoert, Germaine C. Launer, Lenore J. Gudnason, Vilmundur Larson, Martin G. Chakravarti, Aravinda Psaty, Bruce M. Caulfield, Mark van Duijn, Cornelia M. Ridker, Paul M. Munroe, Patricia B. Levy, Daniel CA Cohorts Heart Aging Res Genom Global BPgen Consortium Women's Genome Hlth Study TI Association of Hypertension Drug Target Genes With Blood Pressure and Hypertension in 86 588 Individuals SO HYPERTENSION LA English DT Article DE drug target; genome-wide; SNP; hypertension; blood pressure ID GENOME-WIDE ASSOCIATION; BETA(1)-ADRENERGIC RECEPTOR POLYMORPHISMS; CALCIUM-CHANNEL BLOCKERS; ANGIOTENSINOGEN GENE; ADRENERGIC-RECEPTOR; WHITE SUBJECTS; SUBUNIT GENES; HEART-RATE; RISK; POPULATION AB We previously conducted genome-wide association meta-analysis of systolic blood pressure, diastolic blood pressure, and hypertension in 29 136 people from 6 cohort studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Here we examine associations of these traits with 30 gene regions encoding known antihypertensive drug targets. We find nominal evidence of association of ADRB1, ADRB2, AGT, CACNA1A, CACNA1C, and SLC12A3 polymorphisms with 1 or more BP traits in the Cohorts for Heart and Aging Research in Genomic Epidemiology genome-wide association meta-analysis. We attempted replication of the top meta-analysis single nucleotide polymorphisms for these genes in the Global BPgen Consortium (n = 34 433) and the Women's Genome Health Study (n = 23 019) and found significant results for rs1801253 in ADRB1 (Arg389Gly), with the Gly allele associated with a lower mean systolic blood pressure (beta : 0.57 mm Hg; SE: 0.09 mm Hg; meta-analysis: P = 4.7 x 10(-10)), diastolic blood pressure (beta : 0.36 mm Hg; SE: 0.06 mm Hg; meta-analysis: P = 9.5 x 10(-10)), and prevalence of hypertension (beta : 0.06 mm Hg; SE: 0.02 mm Hg; meta-analysis: P = 3.3 x 10(-4)). Variation in AGT (rs2004776) was associated with systolic blood pressure (beta : 0.42 mm Hg; SE: 0.09 mm Hg; meta-analysis: P = 3.8 x 10(-6)), as well as diastolic blood pressure (P = 5.0 x 10(-8)) and hypertension (P = 3.7 x 10(-7)). A polymorphism in ACE (rs4305) showed modest replication of association with increased hypertension (beta : 0.06 mm Hg; SE: 0.01 mm Hg; meta-analysis: P = 3.0 x 10(-5)). Two loci, ADRB1 and AGT, contain single nucleotide polymorphisms that reached a genome-wide significance threshold in meta-analysis for the first time. Our findings suggest that these genes warrant further studies of their genetic effects on blood pressure, including pharmacogenetic interactions. (Hypertension. 2011;57:903-910.) . Online Data Supplement C1 [Johnson, Andrew D.; Larson, Martin G.; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Johnson, Andrew D.; Levy, Daniel] NHLBI, Ctr Populat Studies, Framingham, MA 01702 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. [Chasman, Daniel I.; Rose, Lynda; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Chasman, Daniel I.; Rose, Lynda; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA. [Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA. [Ehret, Georg B.] CHU Vaudois, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland. [Ehret, Georg B.] Univ Lausanne, Lausanne, Switzerland. [Ehret, Georg B.] Univ Hosp Geneva, Dept Med, Ctr Cardiol, Geneva, Switzerland. [Johnson, Toby; Caulfield, Mark; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol & Genome Ctr, London, England. [Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Verwoert, Germaine C.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Verwoert, Germaine C.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Verwoert, Germaine C.] Leiden Univ, Med Ctr, Netherlands Ctr Healthy Aging, Dept Mol Epidemiol, Leiden, Netherlands. [Launer, Lenore J.] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA. [Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [van Duijn, Cornelia M.] Erasmus MC, Ctr Med Syst Biol, Rotterdam, Netherlands. [Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM levyd@nhlbi.nih.gov RI EHRET, Georg/A-9532-2009; Rice, Kenneth/A-4150-2013; Johnson, Andrew/G-6520-2013; Gudnason, Vilmundur/K-6885-2015; OI EHRET, Georg/0000-0002-5730-0675; Rice, Kenneth/0000-0001-5779-4495; Gudnason, Vilmundur/0000-0001-5696-0084; Larson, Martin/0000-0002-9631-1254; Johnson, Toby/0000-0002-5998-3270 FU National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL087652]; National Institute of Neurological Disorders and Stroke; National Center for Research Resources [M01-RR00425]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Boston University School of Medicine Department of Medicine; Boston Medical Center; Erasmus Medical Center and Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly; Netherlands Heart Foundation; Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; Netherlands Organization for Scientific Research (NWO Groot) [175.010.2005.011, 911.03.012]; Research Institute for Diseases in the Elderly [014.93.015, RIDE2]; Netherlands Genomics Initiative/Netherlands Organization for Scientific Research [050-060-810]; National Genomics Initiative Centre for Medical Systems Biology; Netherlands Centre for Healthy Aging; Doris Duke Charitable Foundation; Burroughs Wellcome Fund; National Institutes of Health [N01-AG-12100, HHSN268200625226C]; National Institute on Aging Intramural Research, Hjartavernd; National Human Genome Research Institute [U01HG004402]; National Institute for Health Research Biomedical Research Unit; National Heart, Lung, and Blood Institute. [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC55021, N01-HC-55022, R01HL087641, R01HL59367, R37HL051021, R01HL086694, U10HL054512]; [UL1RR025005] FX The Cardiovascular Health Study research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, and R01 HL087652 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. DNA handling and genotyping were supported in part by National Center for Research Resources grant M01-RR00425 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center.; The National Heart, Lung, and Blood Institute's Framingham Heart Study is a joint project of the National Institutes of Health and Boston University School of Medicine and was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01-HC-25195) and its contract with Affymetrix, Inc, for genotyping services (contract No. N02-HL-6-4278). A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Boston University School of Medicine Department of Medicine and Boston Medical Center.; The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Netherlands Heart Foundation; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission; and the Municipality of Rotterdam. Support for genotyping was provided by the Netherlands Organization for Scientific Research (NWO Groot 175.010.2005.011 and 911.03.012) and Research Institute for Diseases in the Elderly (014.93.015; RIDE2). This study was supported by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research project 050-060-810 and the National Genomics Initiative Centre for Medical Systems Biology and Netherlands Centre for Healthy Aging.; C. N.-C. is supported by the Doris Duke Charitable Foundation, the Burroughs Wellcome Fund, and the National Institutes of Health. The Age, Gene/Environment Susceptibility Reykjavik Study is funded by National Institutes of Health contract N01-AG-12100, the National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC55021, and N01-HC-55022, and grants R01HL087641, R01HL59367, R37HL051021, R01HL086694, and U10HL054512; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by grant UL1RR025005, a component of the National Institutes of Health and National Institutes of Health Roadmap for Medical Research.; M. C. and P. M. are funded by the National Institute for Health Research Biomedical Research Unit. NR 54 TC 83 Z9 86 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2011 VL 57 IS 5 BP 903 EP U99 DI 10.1161/HYPERTENSIONAHA.110.158667 PG 24 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 752YA UT WOS:000289730200016 PM 21444836 ER PT J AU Delinsky, SS Thomas, JJ Germain, SAS Craigen, KE Weigel, TJ Levendusky, PG Becker, AE AF Delinsky, Sherrie S. Thomas, Jennifer J. Germain, Sarah A. St. Craigen, Katherine Ellison Weigel, Thomas J. Levendusky, Philip G. Becker, Anne E. TI Motivation to Change Among Residential Treatment Patients with an Eating Disorder: Assessment of the Multidimensionality of Motivation and Its Relation to Treatment Outcome SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE motivation; ambivalence; eating disorders; adolescence ID COGNITIVE-BEHAVIORAL THERAPY; ADOLESCENT ANOREXIA-NERVOSA; BULIMIA-NERVOSA; DECISIONAL BALANCE; DOUBLE-BLIND; QUESTIONNAIRE; MAINTENANCE; PREDICTORS; INTERVIEW; WEIGHT AB Objective: To examine the multidimensional nature of motivation to change in an adolescent sample in residential eating disorder (ED) treatment and relate it to outcome. Method: To determine whether different dimensions of motivation (benefits, burdens, and functional avoidance) are differentially associated with symptom severity and outcome, we assessed eating pathology and motivation to change in consecutively admitted female patients (n = 67) with AN, BN, and EDNOS in a residential ED program with the Eating Disorder Examination Questionnaire (EDE-Q) and the Decisional Balance Scale (DB). Results: Pretreatment DB benefits and functional avoidance subscales were correlated with ED and comorbid psychopathology. Admission to discharge change in DB benefits-but not other measured dimensions of motivation was significantly associated with post-treatment EDE-Q global scores. Discussion: Our findings support that motivation to change is a multidimensional construct among ED patients. A reduction in perceived benefits of illness is associated with less severe post-treatment eating pathology. (C) 2010 by Wiley Periodicals, Inc. C1 [Delinsky, Sherrie S.; Thomas, Jennifer J.; Germain, Sarah A. St.; Craigen, Katherine Ellison; Weigel, Thomas J.; Levendusky, Philip G.] McLean Hosp, Klarman Eating Disorders Ctr, Belmont, MA 02178 USA. [Delinsky, Sherrie S.; Thomas, Jennifer J.; Becker, Anne E.] Massachusetts Gen Hosp, Dept Psychiat, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Delinsky, Sherrie S.; Thomas, Jennifer J.; Weigel, Thomas J.; Levendusky, Philip G.; Becker, Anne E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Germain, Sarah A. St.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Craigen, Katherine Ellison] Fairleigh Dickinson Univ, Dept Psychol, Teaneck, NJ USA. [Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. RP Delinsky, SS (reprint author), McLean Hosp, Klarman Eating Disorders Ctr, 115 Mill St, Belmont, MA 02178 USA. EM sdelinsky@gmail.com NR 39 TC 1 Z9 1 U1 3 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2011 VL 44 IS 4 BP 340 EP 348 DI 10.1002/eat.20809 PG 9 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 748EX UT WOS:000289373900008 PM 21472753 ER PT J AU Lafleur, DL Petty, C Mancuso, E McCarthy, K Biederman, J Faro, A Levy, HC Geller, DA AF Lafleur, Daniel L. Petty, Carter Mancuso, Elizabeth McCarthy, Katherine Biederman, Joseph Faro, Alyssa Levy, Hannah C. Geller, Daniel A. TI Traumatic events and obsessive compulsive disorder in children and adolescents: Is there a link? SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Trauma; OCD; PTSD; Child; Adolescent ID POSTTRAUMATIC-STRESS-DISORDER; DEFICIT HYPERACTIVITY DISORDER; NATIONAL COMORBIDITY SURVEY; ANXIETY DISORDERS; EMISSION-TOMOGRAPHY; GENERAL-POPULATION; CHILDHOOD TRAUMA; MENTAL-DISORDERS; PANIC DISORDER; LIFE EVENTS AB Background: The extant literature supports an association between psychological trauma and development of OCD in adults, and this link is a plausible mediator for environment-gene interactions leading to phenotypic expression of OCD. Objective: To explore the relationship between OCD and traumatic life events in children and adolescents. Methods: We examined the prevalence of traumatic life events and PTSD in a large sample of systematically assessed children with OCD. OCD symptoms and severity were assessed using the Children's Yale Brown Obsessive Compulsive Scale (CY-BOCS) in those with and without concurrent PTSD. Results: Rate of PTSD and trauma exposure was higher in children with OCD than in a comparable control group of non-OCD youth matched for age, gender and SES. Children with concurrent PTSD had more intrusive fears and distress and less control over their rituals than children with OCD but without PTSD. Total CY-BOCS scores were higher in those with concurrent PTSD. Specific type of OCD symptoms was not altered by a PTSD diagnosis. Conclusions: A history of psychologically traumatic events may be over-represented in children with OCD. Given the need to search for non-genetic factors that may lead to onset of OCD, better and more systematic methods to obtain and quantify psychologically traumatic life events are needed in clinical populations. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Lafleur, Daniel L.] British Columbia Childrens Hosp, Child & Youth Mental Hlth Program, Vancouver, BC V6H 3V4, Canada. [Lafleur, Daniel L.] Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada. [Petty, Carter; Mancuso, Elizabeth; McCarthy, Katherine; Biederman, Joseph; Faro, Alyssa; Geller, Daniel A.] Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Biederman, Joseph; Geller, Daniel A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Levy, Hannah C.] Concordia Univ, Dept Psychol, Montreal, PQ H3G 1M8, Canada. RP Geller, DA (reprint author), Suite 2000,185 Alewife Brook Pkwy, Cambridge, MA 02318 USA. EM dageller@partners.org FU NIMH NIH HHS [K08 MH001481, K08 MH001481-01A2, K08 MH001481-02, K08 MH001481-03, K08 MH001481-04, K08 MH001481-05, K08 MH0148] NR 47 TC 13 Z9 14 U1 5 U2 24 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 MAY PY 2011 VL 25 IS 4 BP 513 EP 519 DI 10.1016/j.janxdis.2010.12.005 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 750ZV UT WOS:000289588000007 PM 21295942 ER PT J AU Hoge, EA Marques, L Wechsler, RS Lasky, AK Delong, HR Jacoby, RJ Worthington, JJ Pollack, MH Simon, NM AF Hoge, E. A. Marques, L. Wechsler, R. S. Lasky, A. K. Delong, H. R. Jacoby, R. J. Worthington, J. J. Pollack, M. H. Simon, N. M. TI The role of anxiety sensitivity in sleep disturbance in panic disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Panic disorder; Sleep disturbance; Insomnia; Anxiety sensitivity ID NONDEPRESSED PATIENTS; INSOMNIA; QUALITY; SYSTEM AB Previous research has demonstrated that individuals with panic disorder (PD) report significant sleep disturbances, although the mechanism of this disturbance is not clear. Patients with PD tend to report abnormally high levels of anxiety sensitivity (AS). Because higher AS involves increases in attention and fearfulness about anxiety and associated physical sensations, which in turn may cause excessive psychological and physiologic arousal, we hypothesized that amongst individuals with PD, higher AS would be associated with sleep disruption, particularly in the form of increased sleep latency. As expected, PD was associated with poorer sleep as measured by the Global Pittsburgh Sleep Quality Index (PSQI) compared to controls and AS was significantly associated with longer sleep latency. Our data suggest that sleep disturbance, and in particular sleep latency, in PD may be partly due to high levels of AS, which can be targeted with cognitive-behavioral therapeutic strategies. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Hoge, E. A.; Marques, L.; Wechsler, R. S.; Lasky, A. K.; Delong, H. R.; Jacoby, R. J.; Worthington, J. J.; Pollack, M. H.; Simon, N. M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Hoge, EA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM ehoge@partners.org RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 NR 23 TC 17 Z9 18 U1 1 U2 5 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 MAY PY 2011 VL 25 IS 4 BP 536 EP 538 DI 10.1016/j.janxdis.2010.12.008 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 750ZV UT WOS:000289588000010 PM 21277737 ER PT J AU Maguen, S Luxton, DD Skopp, NA Gahm, GA Reger, MA Metzler, TJ Marmar, CR AF Maguen, Shira Luxton, David D. Skopp, Nancy A. Gahm, Gregory A. Reger, Mark A. Metzler, Thomas J. Marmar, Charles R. TI Killing in combat, mental health symptoms, and suicidal ideation in Iraq war veterans SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Posttraumatic stress disorder; Suicide; OEF/OIF; Military ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; RISK; MILITARY; PTSD; MEDIATION AB This study examined combat and mental health as risk factors of suicidal ideation among 2854 U.S. soldiers returning from deployment in support of Operation Iraqi Freedom. Data were collected as part of a postdeployment screening program at a large Army medical facility. Overall, 2.8% of soldiers reported suicidal ideation. Postdeployment depression symptoms were associated with suicidal thoughts, while postdeployment PTSD symptoms were associated with current desire for self harm. Postdeployment depression and PTSD symptoms mediated the association between killing in combat and suicidal thinking, while postdeployment PTSD symptoms mediated the association between killing in combat and desire for self harm. These results provide preliminary evidence that suicidal thinking and the desire for self-harm are associated with different mental health predictors, and that the impact of killing on suicidal ideation may be important to consider in the evaluation and care of our newly returning veterans. Published by Elsevier Ltd. C1 [Maguen, Shira] San Francisco VA Med Ctr, PTSD Program 116 P, San Francisco, CA 94121 USA. [Maguen, Shira] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Luxton, David D.; Skopp, Nancy A.; Gahm, Gregory A.; Reger, Mark A.] Natl Ctr Telehlth & Technol, Def Ctr Excellence Psychol Hlth, OMAMC, Joint Base Lewis McChord, Tacoma, WA 98431 USA. [Marmar, Charles R.] NYU, Langone Med Ctr, Dept Psychiat, New York, NY 10016 USA. [Luxton, David D.; Skopp, Nancy A.; Gahm, Gregory A.; Reger, Mark A.] Natl Ctr Telehlth & Technol, Def Ctr Traumat Brain Injury, OMAMC, Joint Base Lewis McChord, Tacoma, WA 98431 USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, PTSD Program 116 P, 4150 Clement St, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov; David.Luxton@us.army.mil; Nancy.Skopp@us.army.mil; Gregory.Gahm@us.army.mil; Mark.Reger@us.army.mil; Thomas.Metzler@va.gov; Charles.Marmar@nyumc.org RI Schueter, nicos/A-3625-2014 NR 25 TC 38 Z9 41 U1 2 U2 19 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 MAY PY 2011 VL 25 IS 4 BP 563 EP 567 DI 10.1016/j.janxdis.2011.01.003 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 750ZV UT WOS:000289588000014 PM 21333486 ER PT J AU Lyall, K Pauls, DL Santangelo, S Spiegelman, D Ascherio, A AF Lyall, Kristen Pauls, David L. Santangelo, Susan Spiegelman, Donna Ascherio, Alberto TI Maternal Early Life Factors Associated with Hormone Levels and the Risk of Having a Child with an Autism Spectrum Disorder in the Nurses Health Study II SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorders; Reproductive risk factors; Hormonal factors ID ORAL-CONTRACEPTIVE USE; BREAST-CANCER; PREMENOPAUSAL WOMEN; PROSPECTIVE COHORT; SEX-HORMONES; BIRTH-WEIGHT; PREGNANCY; COMPLICATIONS; RECALL; AGE AB It is not known whether reproductive factors early in the mother's life influence risk of autism spectrum disorders (ASD). We assessed maternal age at menarche, menstrual cycle characteristics during adolescence, oral contraceptive use prior to first birth, body shape, and body mass index (BMI) in association with ASD using binomial regression in a cohort study of 61,596 women, including 743 cases. Overall, early life factors were not associated with ASD, though early age at menarche (RR for age 10 or less = 1.54, 95% CI 1.18, 2.02, p = 0.0002) and BMI at age 18 of a parts per thousand yen30 (RR 2.03, 95% CI 1.34, 3.08, p = 0.0008) were significantly associated with increased risk of ASD. Further work should investigate the potential influence of these factors. C1 [Lyall, Kristen; Pauls, David L.; Santangelo, Susan; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Pauls, David L.; Santangelo, Susan] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Pauls, David L.; Santangelo, Susan] Massachusetts Gen Hosp, Ctr Human Genet Res, Neurodev Genet Unit, Boston, MA 02114 USA. [Spiegelman, Donna] Dept Epidemiol, San Francisco, CA USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Spiegelman, Donna] Dept Biostat, San Francisco, CA USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 665 Huntington Ave,Bldg 2,3rd Floor, Boston, MA 02115 USA. EM klyall@hsph.harvard.edu FU Autism Speaks [AS1788, AS2210]; NCI NIH HHS [CA50385, R01 CA050385] NR 44 TC 18 Z9 18 U1 2 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2011 VL 41 IS 5 BP 618 EP 627 DI 10.1007/s10803-010-1079-7 PG 10 WC Psychology, Developmental SC Psychology GA 750FR UT WOS:000289531500009 PM 20700638 ER PT J AU Katz, JN Wright, EA Baron, JA Corbett, KL Nti, AA Malchau, H Wright, J Losina, E AF Katz, Jeffrey N. Wright, Elizabeth A. Baron, John A. Corbett, Kelly L. Nti, Akosua A. Malchau, Henrik Wright, John Losina, Elena TI Predictive value of Medicare claims data for identifying revision of index hip replacement was modest SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Total hip replacement; Revision; Administrative data; Medicare claims; Misclassification; Accuracy ID SURGEON PROCEDURE VOLUME; UNITED-STATES; RHEUMATOLOGIC DIAGNOSES; KNEE ARTHROPLASTY; ACCURACY; ASSOCIATION; POPULATION; OUTCOMES AB Objective: To determine the positive predictive value of Medicare claims for identifying revision of total hip replacement (THR), a frequent marker of THR quality and outcome. Study Design and Setting: We obtained Medicare Part A (Hospital) claims from seven states on patients that had primary THR from July 1995 through June 1996. We searched claims to determine whether these THR recipients had a subsequent revision THR through December 2006. We selected a sample of subjects with codes indicating both index primary and subsequent revision THR. We obtained medical records for both procedures to establish whether the revision occurred on the same side as index primary THR. Results: Three hundred seventy-four subjects had codes indicating primary THR in 1995-96 and subsequent revision. Seventy-one percent (95% confidence interval: 66, 76) of the revisions were performed on the index joint and would be correctly attributed as revisions of the index THR, using Medicare claims data. Conclusion: Claims data on revision THR that do not contain information on the side that was operated on are ambiguous with respect to whether the revision was performed on the index or contralateral side. Claims-based analyses of revisions after an index THR should acknowledge and adjust for this source of potential misclassification. (C) 2011 Elsevier Inc. All rights reserved. C1 [Katz, Jeffrey N.; Wright, Elizabeth A.; Corbett, Kelly L.; Nti, Akosua A.; Wright, John; Losina, Elena] Harvard Univ, Orthoped & Arthrit Ctr Outcomes Res, Brigham & Womens Hosp, Dept Orthoped Surg,Med Sch, Boston, MA 02115 USA. [Katz, Jeffrey N.; Wright, Elizabeth A.; Losina, Elena] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Malchau, Henrik] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Baron, John A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Family Med,Div Biostat & Epidemiol, Hanover, NH 03756 USA. RP Katz, JN (reprint author), Harvard Univ, Orthoped & Arthrit Ctr Outcomes Res, Brigham & Womens Hosp, Dept Orthoped Surg,Med Sch, 75 Francis St,OBC 4, Boston, MA 02115 USA. EM jnkatz@partners.org FU National Institutes of Health [P60 AR 47782, K24 AR 057827] FX Supported by National Institutes of Health grant nos. P60 AR 47782 and K24 AR 057827. NR 18 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 2011 VL 64 IS 5 BP 543 EP 546 DI 10.1016/j.jclinepi.2010.05.005 PG 4 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 749GA UT WOS:000289450800013 PM 20800448 ER PT J AU Bogaev, RC Pamboukian, SV Moore, SA Chen, L John, R Boyle, AJ Sundareswaran, KS Farrar, DJ Frazier, OH AF Bogaev, Roberta C. Pamboukian, Salpy V. Moore, Stephanie A. Chen, Leway John, Ranjit Boyle, Andrew J. Sundareswaran, Kartik S. Farrar, David J. Frazier, O. H. CA HeartMate II Clinical Investigator TI Comparison of outcomes in women versus men using a continuous-flow left ventricular assist device as a bridge to transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE heart failure; heart-assist devices; women ID ADVANCED HEART-FAILURE; MECHANICAL CIRCULATORY SUPPORT; INTRACEREBRAL HEMORRHAGE; RISK-FACTORS; MANAGEMENT; ADULT; NEED AB BACKGROUND: The use of large, pulsatile left ventricular assist devices (LVADs) has been limited in women because of their small body size. METHODS: We compared the survival outcomes, quality of life, and adverse events in 465 patients (104 women, 361 men) with advanced systolic heart failure in their first 18 months of support with the HeartMate II (Thoratec Corp, Pleasanton, CA) continuous-flow LVAD for bridge to transplantation. RESULTS: During the first 18 months, there were no differences in survival between women and men while on LVAD support (73% +/- 3% vs 73% +/- 5%, p = 0.855) but fewer women (40%) underwent heart transplantation than did men (55%; p = 0.001). More women continued on support after 18 months (p = 0.007). Median duration of support was 238 days for women and 184 days for men (p = 0.003). Mortality was 20% for women and 19% for men (p = 0.89). Adverse events were similar, with the exception of hemorrhagic stroke, which occurred more frequently in women (0.10 vs 0.04 events/patient-year, p = 0.02), and device-related infections, which occurred less frequently in women (0.23 vs 0.44, p = 0.006). Functional capacity and quality of life at 6 months improved significantly in women and men. CONCLUSIONS: Continuous-flow left ventricular assistance as a bridge to transplantation is associated with similar survival rates in women and men. Differences observed in higher stroke rates and fewer infections among women require further study. J Heart Lung Transplant 2011;30:515-22 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Bogaev, Roberta C.; Frazier, O. H.] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX 77225 USA. [Bogaev, Roberta C.] St Lukes Episcopal Hosp, Baylor Coll Med, Houston, TX 77225 USA. [Pamboukian, Salpy V.] Univ Alabama, Birmingham, AL USA. [Moore, Stephanie A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chen, Leway] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [John, Ranjit] Univ Minnesota, Minneapolis, MN USA. [Boyle, Andrew J.] Aurora St Lukes Med Ctr, Milwaukee, WI USA. [Sundareswaran, Kartik S.; Farrar, David J.] Thoratec Corp, Pleasanton, CA USA. RP Bogaev, RC (reprint author), St Lukes Episcopal Hosp, Texas Heart Inst, POB 20345,MC 2-114A, Houston, TX 77225 USA. EM rbogaev@heart.thi.tmc.edu FU Thoratec Corporation, Pleasanton, Calif; Thoratec FX The HeartMate II bridge-to-transplantation trial was sponsored by Thoratec Corporation, Pleasanton, Calif.; Dr Bogaev is a consultant to Thoratec. Dr Pamboukian has recieved honoraria from Thoratec. Dr John has received research support from Thoratec. Dr Moore served on the Clinical Events Committee of the HeartMate II clinical trial while the trial was in progress. Drs Farrar and Sundareswaran are employees and stockholders of Thoratec. The remaining authors report no financial relationships with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose. NR 24 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD MAY PY 2011 VL 30 IS 5 BP 515 EP 522 DI 10.1016/j.healun.2010.12.009 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 753EN UT WOS:000289748800005 PM 21257321 ER PT J AU Dustin, ML Rothlein, R Bhan, AK Dinarello, CA Springer, TA AF Dustin, Michael L. Rothlein, Robert Bhan, Atul K. Dinarello, Charles A. Springer, Timothy A. TI INDUCTION BY IL 1 AND INTERFERON-gamma: TISSUE DISTRIBUTION BIOCHEMISTRY, AND FUNCTION OF A NATURAL ADHERENCE MOLECULE (ICAM-1) SO JOURNAL OF IMMUNOLOGY LA English DT Reprint ID FUNCTION-ASSOCIATED ANTIGEN-1; T-CELL FUNCTION; LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; FIBROBLAST PROLIFERATION; POLYACRYLAMIDE-GELS; LFA-1; INTERLEUKIN-1; STIMULATION; EXPRESSION AB ICAM-1 is a cell surface glycoprotein originally defined by a monoclonal antibody (MAb) that inhibits phorbol ester-stimulated leukocyte aggregation. Staining of frozen sections and immunofluorescence flow cytometry showed intercellular adhesion molecule-1 (ICAM-1) is expressed on non-hematopoietic cells such as vascular endothelial cells, thymic epithelial cells, certain other epithelial cells, and firboblasts, and on hematopoietic cells such as tissue macrophages, mitogen-stimulated T lymphocyte blasts, and germinal center dendritic cells intonsils, lymph nodes, and Peyer's patches. ICAM-1 staining on vascular endothelial cells is most intense in T cell areas in lymph nodes and tonsils showing reactive hyperplasia. ICAM-1 is expressed in low amounts on peripheral blood leukocytes. Phorbol ester-stimulated differentiation of myelomonocytic cell lines greatly increases ICAM-1 expression. ICAM-1 expression on dermal fibroblasts is increased threefold to fivefold by either interleukin 1 (IL 1) or interferon-gamma at 10 U/mol over a period of 4 or 10 hr, respectively. The induction is dependent on protein and mRNa synthesis and is reversible. ICAM-1 displays M(r) of 97,000 on fibroblasts, 114,000 on the myelomonocytic cell line U937, and 90,000 on the B lymphoblastoid cell JY. ICAM-1 biosynthesis involves a M(r) similar to 73,000 intracellular percursor. The non-N-glycosylated form resulting from tynicamycin treatment has a M(r) of 55,000. ICAM-1 isolated from phorbol myristic acetate (PMA) stimulated U937 and from fibroblasts yields an identical major product of M(r) = 60,000 after chemical deglycosylation. ICAM-1 MAb interferes with the adhesion of phytohemaglutinin blasts, and the adhesion of the cell line SKW3 to human dermal fibroblast cell layers. Pretreatment of fibroblasts but not lymphocytes with ICAM-1 MAb, and of lymphocytes but not fibroblasts with lymphocyte function-associated antigen 1 MAb inhibits adhesion. Intercellular adhesion is increased by prior exposure of fibroblasts to IL 1, and correlates with induction of ICAM-1. C1 [Dustin, Michael L.; Rothlein, Robert; Dinarello, Charles A.; Springer, Timothy A.] Dana Farber Canc Inst, Lab Membrane Immunochem, Boston, MA 02115 USA. [Dustin, Michael L.; Springer, Timothy A.] Comm Cell Dev Biol, Boston, MA USA. [Bhan, Atul K.; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Bhan, Atul K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dinarello, Charles A.] Tufts Univ, Sch Med, Div Expt Med, Boston, MA 02111 USA. RP Dustin, ML (reprint author), Dana Farber Canc Inst, Lab Membrane Immunochem, Boston, MA 02115 USA. NR 50 TC 9 Z9 9 U1 1 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2011 VL 186 IS 9 BP 5024 EP 5033 PG 10 WC Immunology SC Immunology GA 752GN UT WOS:000289679600004 PM 21505214 ER PT J AU Rothlein, R Dustin, ML Marlin, SD Springer, TA AF Rothlein, Robert Dustin, Michael L. Marlin, Steven D. Springer, Timothy A. TI A HUMAN INTERCELLULAR ADHESION MOLECULE (ICAM-1) DISTINCT FROM LFA-1 SO JOURNAL OF IMMUNOLOGY LA English DT Reprint ID CELL-SURFACE ANTIGENS; DIFFERENTIATION; ANTIBODIES; FAMILY AB Homotypic adhesion by phorbol ester-stimulated lymphocytes requries LFA-1 and Mg(+2) and does not involve like-like interactions between LFA-1 molecules on adjacent cells. The latter finding suggested that a second molecule, distinct from LFA-1, also participates in LFA-1-dependent adhesion. The identification of such a molecule was the object of this investigation. After immunization with LFA-1-deficient EBV-transformed lymphoblastoid cells, a MAb was obtained that inhibits phorbol ester-stimulated aggregation of LFA-1(+) EBV lines. This MAb defines a novel cell surface molecule, which is designated intercellular adhesion molecule 1 (ICAM-1). ICAM-1 is distinct from LFA-1 in both cell distribution and structure. In SDS-PAGE, ICAM-1 isolated from JY cells is a single chain of M(r) = 90,000. As shown by MAb inhibition. ICAM-1 participates in phorbol ester-stimulated adhesion reactions of B lymphocyte and myeloid cell lines and T lymphocyte blasts. However, aggregation of one T lymphocyte cell line (SKW-3) was inhibited by LFA-1 but not ICAM-1 MAb. It is proposed that ICAM-1 may be a ligand in many, but not all, LFA-1-dependent adhesion reactions. C1 [Rothlein, Robert] Dana Farber Canc Inst, Lab Membrane Immunochem, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rothlein, R (reprint author), Dana Farber Canc Inst, Lab Membrane Immunochem, Boston, MA 02115 USA. NR 21 TC 1 Z9 1 U1 1 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 MAY 1 PY 2011 VL 186 IS 9 BP 5034 EP 5038 PG 5 WC Immunology SC Immunology GA 752GN UT WOS:000289679600005 PM 21505215 ER PT J AU DaRocha-Souto, B Scotton, TC Coma, M Serrano-Pozo, A Hashimoto, T Sereno, L Rodriguez, M Sanchez, B Hyman, BT Gomez-Isla, T AF DaRocha-Souto, Bibiana Scotton, Thomas C. Coma, Mireia Serrano-Pozo, Alberto Hashimoto, Tadafumi Sereno, Lidia Rodriguez, Marta Sanchez, Belen Hyman, Bradley T. Gomez-Isla, Teresa TI Brain Oligomeric beta-Amyloid but Not Total Amyloid Plaque Burden Correlates With Neuronal Loss and Astrocyte Inflammatory Response in Amyloid Precursor Protein/Tau Transgenic Mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; Amyloid plaques; Astrocytes; Neuronal cell death; Oligomeric A beta; Transgenic mice ID IMPAIR SYNAPTIC PLASTICITY; TG2576 MOUSE MODEL; ALZHEIMERS-DISEASE; A-BETA; SPINE LOSS; IN-VIVO; MEMORY; ABNORMALITIES; PATHOLOGY; ACCUMULATION AB It has long been assumed that beta-amyloid (A beta) had to assemble into fibrillar amyloid plaques to exert its neurotoxic effects in Alzheimer disease. An alternative hypothesis is that soluble oligomers of A beta play a much larger role in neuronal damage than the insoluble component. We have tested these competing hypotheses in vivo by studying the clinicopathologic correlates of oligomeric A beta species and classic fibrillar amyloid plaques in the brains of double-transgenic APP(sw)-tau(vlw) mice up to 17 months of age. Biochemical and immunohistochemical measures of brain oligomeric A beta exponentially increased with age. Oligomeric A beta load correlated with morphological markers of fibrillar A beta deposition. In contrast to total amyloid plaque burden, the amount of oligomeric A beta deposits labeled by the conformational epitope-specific antibody Nab61 closely correlated with neuronal loss and numbers of astrocytes in the entorhinal cortex and the CA1 hippocampal subfield. However, like other morphological A beta measurements, brain oligomeric A beta burden did not correlate well with memory deficits in these mice. The number of glial fibrillary acidic protein-positive astrocytes in entorhinal cortex and CA1 most tightly correlated with memory impairment and neuronal cell loss. Based on these findings, we hypothesize that the astrocyte response, which is likely triggered by brain oligomeric A beta accumulation, adversely affects cognition and might also contribute to neuronal cell death in this model. C1 [DaRocha-Souto, Bibiana; Scotton, Thomas C.; Coma, Mireia; Serrano-Pozo, Alberto; Hashimoto, Tadafumi; Hyman, Bradley T.; Gomez-Isla, Teresa] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sereno, Lidia; Rodriguez, Marta; Sanchez, Belen; Gomez-Isla, Teresa] Univ Autonoma Barcelona, Dept Neurol, Hosp Santa Creu & Sant Pau, E-08193 Barcelona, Spain. RP Gomez-Isla, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, WACC Suite 715,15th Parkman St, Boston, MA 02114 USA. EM tgomezisla@partners.org RI Hashimoto, Tadafumi/A-7723-2013; SERRANO-POZO, ALBERTO/F-5119-2013 FU FIS [PI041887]; CIBERNED FX This project was funded in part by FIS PI041887 and CIBERNED. NR 54 TC 35 Z9 36 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2011 VL 70 IS 5 BP 360 EP 376 DI 10.1097/NEN.0b013e318217a118 PG 17 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 753JX UT WOS:000289769600004 PM 21487307 ER PT J AU Klein, R Moghadam-Kia, S Taylor, L Coley, C Okawa, J LoMonico, J Chren, MM Werth, VP AF Klein, Rachel Moghadam-Kia, Siamak Taylor, Lynne Coley, Christopher Okawa, Joyce LoMonico, Jonathan Chren, Mary-Margaret Werth, Victoria P. TI Quality of life in cutaneous lupus erythematosus SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE cutaneous lupus erythematosus; Cutaneous Lupus Erythematosus Disease Area and Severity Index; psychiatric comorbidity; quality of life; Short Form-36 (SF-36); Skindex-29 ID HEALTH SURVEY SF-36; PSYCHIATRIC MORBIDITY; DERMATOLOGICAL OUTPATIENTS; PSYCHOLOGICAL DISTRESS; OUTCOME INSTRUMENT; ATOPIC-DERMATITIS; SUICIDAL IDEATION; SEVERITY INDEX; SKIN DISEASES; PSORIASIS AB Background: Little is known about quality of life in patients with cutaneous lupus erythematosus. Objective: We sought to determine how cutaneous lupus affects quality of life and which independent variables are associated with poor quality of life. Methods: A total of 157 patients with cutaneous lupus completed surveys related to quality of life, including the Skindex-29 and the Short Form-36. Results: Quality of life in cutaneous lupus is severely impaired, particularly with respect to emotional wellbeing. Patients with cutaneous lupus have worse quality of life than those with other common dermatologic conditions, such as acne, nonmelanoma skin cancer, and alopecia. With respect to mental health status, patients with cutaneous lupus have similar or worse scores than patients with hypertension, type 2 diabetes mellitus, recent myocardial infarction, and congestive heart failure. Factors related to poor quality of life include female gender, generalized disease, severe disease, distribution of lesions, and younger age. Limitations: The study was done at a single referral-only center. Conclusion: Patients with cutaneous lupus have very impaired quality of life, particularly from an emotional perspective. (J Am Acad Dermatol 201164:849-58.) C1 [Werth, Victoria P.] Univ Penn, Sch Med, Dept Dermatol, Perelman Ctr Adv Med, Philadelphia, PA 19104 USA. [Klein, Rachel; Moghadam-Kia, Siamak; Okawa, Joyce; LoMonico, Jonathan; Werth, Victoria P.] Philadelphia Dept Vet Affairs Med Ctr, Philadelphia, PA USA. [Taylor, Lynne; Coley, Christopher] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. RP Werth, VP (reprint author), Univ Penn, Sch Med, Dept Dermatol, Perelman Ctr Adv Med, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU National Institutes of Health [NIH K24-AR 02207, NIH K24 AR052667, NIH T32-AR007465-25]; Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX This material is based on work supported by the National Institutes of Health, including NIH K24-AR 02207 (Dr Werth), NIH K24 AR052667 (Dr Chren), and training grant NIH T32-AR007465-25 (Ms Klein). This work was also partially supported by a Merit Review Grant from the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. NR 39 TC 35 Z9 35 U1 0 U2 2 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 MAY PY 2011 VL 64 IS 5 BP 849 EP 858 DI 10.1016/j.jaad.2010.02.008 PG 10 WC Dermatology SC Dermatology GA 754PW UT WOS:000289869800006 PM 21397983 ER PT J AU Nagueh, SF Bierig, SM Budoff, MJ Desai, M Dilsizian, V Eidem, B Goldstein, SA Hung, J Maron, MS Ommen, SR Woo, A AF Nagueh, Sherif F. Bierig, S. Michelle Budoff, Matthew J. Desai, Milind Dilsizian, Vasken Eidem, Benjamin Goldstein, Steven A. Hung, Judy Maron, Martin S. Ommen, Steve R. Woo, Anna CA ASE Amer Soc Nuclear Cardiology Soc Cardiovasc Magnetic Resonance Soc Cardiovasc Computed Tomography TI American Society of Echocardiography Clinical Recommendations for Multimodality Cardiovascular Imaging of Patients with Hypertrophic Cardiomyopathy Endorsed by the American Society of Nuclear Cardiology, Society for Cardiovascular Magnetic Resonance, and Society of Cardiovascular Computed Tomography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Hypertrophic cardiomyopathy; Echocardiography; Nuclear imaging; Cardiovascular magnetic resonance; Cardiac computed tomography ID VENTRICULAR OUTFLOW TRACT; SEPTAL REDUCTION THERAPY; LEFT ATRIAL VOLUME; MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; PAPILLARY-MUSCLE MORPHOLOGY; OBSTRUCTIVE CARDIOMYOPATHY; DIASTOLIC FUNCTION; PERFUSION ABNORMALITIES; FILLING PRESSURES; PROGNOSTIC-SIGNIFICANCE C1 [Nagueh, Sherif F.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [Bierig, S. Michelle] St Anthonys Med Ctr, St Louis, MO USA. [Budoff, Matthew J.] Los Angeles Biomed Res Inst, Torrance, CA USA. [Desai, Milind] Cleveland Clin, Cleveland, OH 44106 USA. [Dilsizian, Vasken] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Eidem, Benjamin; Ommen, Steve R.] Mayo Clin, Rochester, MN USA. [Goldstein, Steven A.] Washington Hosp Ctr, Washington, DC 20010 USA. [Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Maron, Martin S.] Tufts Med Ctr, Boston, MA USA. [Woo, Anna] Univ Toronto, Toronto Gen Hosp, Toronto, ON M5G 1L7, Canada. RP Nagueh, SF (reprint author), Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. NR 127 TC 81 Z9 84 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAY PY 2011 VL 24 IS 5 BP 473 EP 498 DI 10.1016/j.echo.2011.03.006 PG 26 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 753ML UT WOS:000289779500003 PM 21514501 ER PT J AU Amrein, PC AF Amrein, Philip C. TI The potential for dasatinib in treating chronic lymphocytic leukemia, acute myeloid leukemia, and myeloproliferative neoplasms SO LEUKEMIA & LYMPHOMA LA English DT Review ID STEM-CELL FACTOR; CHRONIC EOSINOPHILIC LEUKEMIA; KINASE INHIBITOR DASATINIB; LYN TYROSINE KINASE; SRC-FAMILY KINASES; HUMAN MAST-CELLS; C-KIT; B-CELLS; SYSTEMIC MASTOCYTOSIS; IMATINIB-RESISTANT AB Dasatinib is a kinase inhibitor that inhibits BCR--ABL, Src family kinases, c-Kit, and platelet-derived growth factor receptor kinase. It is licensed for the first- and second-line treatment of chronic myeloid leukemia and second-line treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia on the basis of BCR--ABL inhibition, but the activity of dasatinib against additional molecular targets may enable treatment of other hematologic disorders. Potential targets for dasatinib in chronic lymphocytic leukemia (CLL) include Lyn (a Src family kinase), ABL, and the associated CD40 pathway. Although dasatinib monotherapy has modest clinical activity in CLL, ongoing studies are evaluating combination treatment. In acute myeloid leukemia (AML), FLT3, Lyn, c-Kit, and BCR--ABL are expressed in a subpopulation of patients. To date, clinical responses to dasatinib in patients with unselected AML have been mixed and larger studies are needed, particularly correlating clinical response to molecular markers. Imatinib has been used successfully to treat patients with chronic eosinophilic disorders with the FIP1L1--PDGFRA fusion kinase; limited clinical data indicate that dasatinib could be active in imatinib-resistant disease. Ongoing clinical studies should further define the value of dasatinib in these disorders.The production of Secretory Aspartyl Proteases (Sap) is an important virulence factor of Candida albicans. Many studies have shown that a challenge with sub-inhibitory concentrations of antifungals lead species of Candida to the secretion of higher concentrations of Sap. Nevertheless, published studies only reported the secretion of such enzymes by cells growing in planktonic phase, with few mention of biofilms. The present study evaluated the alterations in the secretion of Sap by C. albicans grown in biofilms and exposed to sub-inhibitory concentrations of fluconazole. The MICs for fluconazole of seven clinical strains were determined for planktonic cells. Biofilm and planktonic cells were grown in the presence of 1/2 MIC, 1/4 MIC, and no medication (control). The relative metabolic activity, indirectly related to cell loads, were estimated by the absorbance of reduced XTT and the Sap activity was evaluated by bovine albumin test. It was observed that 72 h-old biofilms under the influence of 1/2 MIC had fewer cells than 1/4 MIC and control. The production of Sap was inversely proportional to the cell content, with higher secretion in 1/2 MIC, followed by 1/4 MIC and control. Biofilms of C. albicans challenged by sub-MICs of fluconazole tend to secrete higher quantities of Sap. C1 [Mores, Alinne Ulbrich; Souza, Roberta Djavana; Cavalca, Laura; de Paula e Carvalho, Alessandra; Gursky, Lauren Christine; Rosa, Rosimeire Takaki; Ribeiro Rosa, Edvaldo Antonio] Pontif Catholic Univ Parana, Lab Stomatol, Curitiba, PR, Brazil. [Gursky, Lauren Christine] Forsyth Inst, Dept Periodontol, Boston, MA USA. [Samaranayake, Lakshman Perera; Ribeiro Rosa, Edvaldo Antonio] Univ Hong Kong, Prince Philip Dent Hosp, Fac Dent, Hong Kong, Hong Kong, Peoples R China. RP Rosa, EAR (reprint author), Pontificia Univ Catolica Parana, Curso Odontol, Rua Imaculada Conceicao 1155, BR-80215901 Curitiba, PR, Brazil. EM edvaldo.rosa@pucpr.br RI Samaranayake, Lakshman/B-2171-2009; Rosa, Edvaldo/B-1228-2008; OI Rosa, Edvaldo/0000-0001-6087-4365; /0000-0002-9122-336X FU Pontifical Catholic University of Parana (PUCPR); National Council of Technological and Scientific Development (CNPq); Coordination for Improvement of Higher Scholar Degree Personnel (Capes) FX This study was conducted using intramural funds from the Pontifical Catholic University of Parana (PUCPR) and was part of the Scientific Initiation Program of A.U.M. that was granted by the National Council of Technological and Scientific Development (CNPq). A.P.C and L.C.G. are doctorate candidates supported by the Coordination for Improvement of Higher Scholar Degree Personnel (Capes). R.D.S. and L.C. are research fellows supported by the Scientific Initiation Program of PUCPR. NR 40 TC 8 Z9 10 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0933-7407 J9 MYCOSES JI Mycoses PD MAY PY 2011 VL 54 IS 3 BP 195 EP 201 DI 10.1111/j.1439-0507.2009.01793.x PG 7 WC Dermatology; Mycology SC Dermatology; Mycology GA 749KY UT WOS:000289466500003 PM 19878458 ER PT J AU Irvine, DJ AF Irvine, Darrell J. TI DRUG DELIVERY One nanoparticle, one kill SO NATURE MATERIALS LA English DT News Item ID LIPOSOMES C1 [Irvine, Darrell J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Irvine, Darrell J.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Irvine, Darrell J.] Ragon Inst Massachusetts Gen Hosp MIT & Harvard U, Boston, MA 02129 USA. [Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Irvine, DJ (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM djirvine@MIT.EDU FU Howard Hughes Medical Institute NR 8 TC 73 Z9 73 U1 5 U2 58 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1476-1122 J9 NAT MATER JI Nat. Mater. PD MAY PY 2011 VL 10 IS 5 BP 342 EP 343 DI 10.1038/nmat3014 PG 2 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Materials Science; Physics GA 752UJ UT WOS:000289720000009 PM 21499312 ER PT J AU de Gelder, B Tamietto, M AF de Gelder, Beatrice Tamietto, Marco TI A unified science of the non-conscious mind? SO NATURE REVIEWS NEUROSCIENCE LA English DT Letter ID SIGNALS; MODE C1 [de Gelder, Beatrice; Tamietto, Marco] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. [de Gelder, Beatrice] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP de Gelder, B (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. EM degelder@uvt.nl OI Tamietto, Marco/0000-0002-8815-8499 NR 10 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD MAY PY 2011 VL 12 IS 5 DI 10.1038/nrn2889-c2 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 752VS UT WOS:000289724200013 ER PT J AU Sheth, KN Gilson, AJ Chang, YC Kumar, MA Rahman, RM Rost, NS Schwab, K Cortellini, L Goldstein, JN Smith, EE Greenberg, SM Rosand, J AF Sheth, Kevin N. Gilson, Aaron J. Chang, Yuchiao Kumar, Mona A. Rahman, Rosanna M. Rost, Natalia S. Schwab, Kristin Cortellini, Lynelle Goldstein, Joshua N. Smith, Eric E. Greenberg, Steven M. Rosand, Jonathan TI Packed Red Blood Cell Transfusion and Decreased Mortality in Intracerebral Hemorrhage SO NEUROSURGERY LA English DT Article DE Anemia; Cerebral Hemorrhage; Intensive care unit; Stroke; Transfusion ID CEREBRAL OXYGENATION; SUBARACHNOID HEMORRHAGE; HEMOGLOBIN; OUTCOMES; ASSOCIATION; WARFARIN; VOLUME; SCORE; CARE AB BACKGROUND: Accumulating data suggest that anemia worsens outcomes in critically ill patients, including those with subarachnoid and intracerebral hemorrhage (ICH). Although packed red blood cell (PRBC) transfusion appears to increase brain tissue oxygen, it is unknown whether such transfusions, which are commonly administered in patients with intracranial hemorrhage, alter outcome. OBJECTIVE: Following up on our observation that anemia is associated with poor outcome in patients with ICH, we investigated whether PRBC transfusion was associated with any benefit. METHODS: Five hundred forty-six consecutive subjects were identified from an ongoing single-center, prospective cohort study of nontraumatic ICH over a 6-year period. Clinical and radiographic characteristics, laboratory values including admission and daily mean hemoglobin values, and all instances of PRBC transfusion were recorded. Aggressiveness of care was assessed by whether the patient had a "do not resuscitate'' order activated during hospitalization. The primary endpoint was 30-day survival. RESULTS: Anemia was present in 144 of 546 patients (26%) on admission and developed subsequently in an additional 250, leaving just 152 of 546 patients (28%) who never developed anemia. PRBC transfusion was administered to 100 patients (18%) during their hospital stay, 98% of whom were anemic. In multivariable analysis, PRBC transfusion was associated with improved survival at 30 days (odds ratio: 2.76; 95% confidence interval: 1.45-5.26; P = .002). CONCLUSION: Anemia develops in the majority of patients with ICH at some point during their hospitalization. PRBC transfusion was associated with improved outcome in these patients. C1 [Sheth, Kevin N.] Univ Maryland, Med Ctr, Dept Neurol, Div Stroke & Neurocrit Care, Baltimore, MD 21201 USA. [Gilson, Aaron J.; Rahman, Rosanna M.; Schwab, Kristin; Cortellini, Lynelle; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rost, Natalia S.; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Kumar, Mona A.] Thomas Jefferson Univ Hosp, Dept Neurol, Stroke & Neurocrit Care Div, Philadelphia, PA 19107 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Calgary, AB, Canada. RP Sheth, KN (reprint author), Univ Maryland, Med Ctr, Dept Neurol, Div Stroke & Neurocrit Care, 110 S Paca St,3rd Floor, Baltimore, MD 21201 USA. EM ksheth@som.umaryland.edu RI Smith, Eric/C-5443-2012; Goldstein, Joshua/H-8953-2016 OI Smith, Eric/0000-0003-3956-1668; FU National Institute of Neurological Disorders and Stroke [R01 NS059727]; American Heart Association [0755984T, 11CRP5480009]; Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, American Academy of Neurology FX Funding provided by the National Institute of Neurological Disorders and Stroke (R01 NS059727), American Heart Association Grant-in-Aid (0755984T), Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, American Academy of Neurology. Support provided by the American Heart Association Clinical Research Award 11CRP5480009. The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. NR 24 TC 23 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 2011 VL 68 IS 5 BP 1286 EP 1292 DI 10.1227/NEU.0b013e31820cccb2 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 746GE UT WOS:000289230300050 PM 21307801 ER PT J AU Shields, DC Flaherty, AW Eskandar, EN Williams, ZM AF Shields, Donald C. Flaherty, Alice W. Eskandar, Emad N. Williams, Ziv M. TI Ventral Intermediate Thalamic Stimulation for Monoclonal Gammopathy-Associated Tremor: Case Report SO NEUROSURGERY LA English DT Article DE Action tremor; Deep brain stimulation; Microelectrode recording; Monoclonal gammopathy; Polyneuropathy; Thalamus ID DEMYELINATING NEUROPATHY AB BACKGROUND AND IMPORTANCE: Peripheral and central sensory loss are often associated with significant tremor or sensory ataxia, which can be highly refractory to medical therapy. CLINICAL PRESENTATION: We present the case of a 67-year-old man with progressive and debilitating intention tremor from monoclonal gammopathy-associated peripheral neuropathy. The patient was implanted with bilateral thalamic deep brain stimulator electrodes under microelectrode guidance. Following optimization of stimulation parameters, the patient's appendicular tremor and gait improved, as did his general activities of daily living. CONCLUSION: These initial findings suggest that deep brain stimulation may benefit not only tremor presumed to originate from central nervous system dysfunction, but also tremor originating peripherally from neuropathy-related sensory loss. C1 [Shields, Donald C.; Eskandar, Emad N.; Williams, Ziv M.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Shields, Donald C.; Flaherty, Alice W.; Eskandar, Emad N.; Williams, Ziv M.] Harvard Univ, Sch Med, Boston, MA USA. [Flaherty, Alice W.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Williams, ZM (reprint author), Wang Ambulatory Care Ctr, 15 Parkman St,745K, Boston, MA 02114 USA. EM zwilliams@partners.org NR 9 TC 1 Z9 1 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 MAY PY 2011 VL 68 IS 5 BP E1464 EP E1467 DI 10.1227/NEU.0b013e3182124633 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 746GE UT WOS:000289230300001 PM 21311371 ER PT J AU Burwick, RM Schulkin, J Cooley, SW Janakiraman, V Norwitz, ER Robinson, JN AF Burwick, Richard M. Schulkin, Jay Cooley, Sarah W. Janakiraman, Vanitha Norwitz, Errol R. Robinson, Julian N. TI Recent Trends in Continuing Medical Education Among Obstetrician-Gynecologists SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SIMULATION AB OBJECTIVE: To estimate current trends in continuing medical education among obstetrician-gynecologists in relation to the Maintenance of Certification program. METHODS: A validated questionnaire was mailed to 1,030 randomly selected physicians of the American College of Obstetricians and Gynecologists in the United States, Puerto Rico, and Canada. Participants were asked about current practices and opinions regarding continuing medical education activities. Responses were compared between members mandated for Maintenance of Certification (board certification 1986 or later; time-limited certificate) or not (board certification before 1986; non-time-limited certificate). RESULTS: Five hundred twenty (50.4%) surveys were completed. Respondents were more often male (57.1%), generalists (87.3%), in community-based (73.8%) group practices (77.2%) with mean (+/- standard deviation) age 52.4 +/- 9.9 years. College physicians mandated to participate in the Maintenance of Certification program were more likely to rely on Annual Board Certification articles as a major source of continuing medical education credits compared with those not requiring Maintenance of Certification (79.9% compared with 44.6%, P<.001). This finding remained significant after multivariable adjustment for age, gender, years in practice, and practice type (odds ratio [OR] 9.09, 95% confidence interval [CI] 4.03-20.5). Conversely, Maintenance of Certification requirement led to decreased use of the national or international meetings (OR 0.31, 95% CI 0.14-0.67) and self-selected continuing medical education materials (OR 0.29, 95% CI 0.14-0.60) as sources of continuing medical education credits. Despite these differences, physicians in both groups equally valued the relevance of Annual Board Certification articles (92.6% compared with 96.4%, P=.23), the importance of content at academic meetings (98.3% compared with 99.3%, P=.33), the usefulness of simulation drills (97.8% compared with 94.3%, P=.35), and the general ability of continuing medical education activities to improve skills as a physician (90.9% compared with 86.4%, P=.20). CONCLUSION: Requirement of the Maintenance of Certification program has led to significant changes in continuing medical education choices by obstetrician-gynecologists. The changes in continuing medical education appear related to mandated obligations rather than personal preference. (Obstet Gynecol 2011; 117: 1060-4) DOI: 10.1097/AOG.0b013e318214e561 C1 [Burwick, Richard M.] Harvard Univ, Brigham & Womens Hosp, Div Maternal Fetal Med, Sch Med, Boston, MA 02115 USA. Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA. Newton Wellesley Hosp, Newton, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA. RP Burwick, RM (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Maternal Fetal Med, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM rburwick@partners.org FU Maternal and Child Health Bureau, Health Resources and Services Administration, Department of Health and Human Services [R60 MC 05674] FX Supported by grant R60 MC 05674 from the Maternal and Child Health Bureau (Title V, Social Security Act), Health Resources and Services Administration, Department of Health and Human Services. NR 11 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2011 VL 117 IS 5 BP 1060 EP 1064 DI 10.1097/AOG.0b013e318214e561 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 753KF UT WOS:000289771000005 PM 21508743 ER PT J AU Ecker, J Minkoff, H AF Ecker, Jeffrey Minkoff, Howard TI Home Birth What Are Physicians' Ethical Obligations When Patient Choices May Carry Increased Risk? SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PLANNED HOME AB Patient choices and plans may sometimes carry increased risk or include alternatives that individual physicians feel uncomfortable supporting or recommending. We consider in this commentary how the ethical principles of respect for autonomy and nonmaleficence can be balanced using, among other examples, the choice by some for a home birth. We discuss how absolute rather than relative risk should guide individuals' evaluation of patient choices, and how in some circumstances the value and safety added by a physician's participation may outweigh a potentially small increment in absolute risk that a particular patient choice carries. (Obstet Gynecol 2011; 117: 1179-82) DOI: 10.1097/AOG.0b013e3182167413 C1 [Ecker, Jeffrey] Harvard Univ, Sch Med, Dept Obstet & Gynecol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Maimonides Hosp, Dept Obstet & Gynecol, New York, NY USA. Suny Downstate Med Ctr, New York, NY USA. RP Ecker, J (reprint author), Harvard Univ, Sch Med, Dept Obstet & Gynecol, Massachusetts Gen Hosp, Founders 420,33 Fruit St, Boston, MA 02114 USA. EM jecker@partners.org NR 14 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2011 VL 117 IS 5 BP 1179 EP 1182 DI 10.1097/AOG.0b013e3182167413 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 753KF UT WOS:000289771000022 PM 21508760 ER PT J AU Sharma, MR Werth, B Werth, VP AF Sharma, Meena R. Werth, Benjamin Werth, Victoria P. TI Animal Models of Acute Photodamage: Comparisons of Anatomic, Cellular and Molecular Responses in C57BL/6J, SKH1 and Balb/c Mice SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; SOLAR ULTRAVIOLET-RADIATION; NORMAL HUMAN SKIN; HAIRLESS MOUSE; TNF-ALPHA; IN-VIVO; DERMATAN SULFATE; HYALURONIC-ACID; FACTOR-BETA; IRRADIATION AB Human cutaneous photodamage is a major medical problem that includes premature aging and fragility of the skin. Nonxenografted animal models have not been comparatively evaluated for how well they resemble the changes seen in human skin. Here, we sought to identify a suitable mouse model that recapitulates key anatomic, cellular and molecular responses observed in human skin during acute UV exposure. Adult females from three strains of mice, C57BL/6J, SKH1 and Balb/c were exposed to UVB and then evaluated 3 or 20 h after the last irradiation. Skin from UVB-exposed C57BL/6J mice showed features resembling human photodamage, including epidermal thickening, infiltration of the dermis with inflammatory cells, induction of tumor necrosis factor-alpha (TNF-alpha) mRNA, accumulation of glycosaminoglycans, particularly hyaluronan in the epidermis and loss of collagen. Hairless SKH1 mouse skin responded similarly, but without any induction of TNF-alpha mRNA or chondroitin sulfate. Irradiated Balb/c mice were the least similar to humans. Our results in C57BL/6J mice and to a lesser extent in SKH1 mice, show cutaneous responses to a course of UVB-irradiation that mirror those seen in human skin. Proper choice of model is critical for investigating cellular and molecular mechanisms of photodamage and photoaging. C1 [Sharma, Meena R.; Werth, Benjamin; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Sharma, Meena R.; Werth, Benjamin; Werth, Victoria P.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Philadelphia VA Med Ctr, Philadelphia, PA USA. EM werth@mail.med.upenn.edu FU Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX This material is based upon work supported by a Merit Review Grant from the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. NR 42 TC 7 Z9 8 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY-JUN PY 2011 VL 87 IS 3 BP 690 EP 698 DI 10.1111/j.1751-1097.2011.00911.x PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 753LD UT WOS:000289774200026 PM 21332482 ER PT J AU St Denis, TG Huang, LY Dai, TH Hamblin, MR AF St Denis, Tyler G. Huang, Liyi Dai, Tianhong Hamblin, Michael R. TI Analysis of the Bacterial Heat Shock Response to Photodynamic Therapy-mediated Oxidative Stress SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; PROTEIN CARBONYLATION; STAPHYLOCOCCUS-AUREUS; ENTEROCOCCUS-FAECALIS; METHYLENE-BLUE; DNAK; GROEL; RESISTANCE; EXPRESSION; GENE AB Antimicrobial photodynamic therapy (PDT) has recently emerged as an effective modality for the selective destruction of bacteria and other pathogenic microorganisms. We investigated whether PDT induced protective responses such as heat shock proteins (HSPs) in bacteria. Using the photosensitizer Toluidine Blue O (TBO) at sublethal PDT conditions, a sevenfold increase in bacterial HSP GroEL and a three-fold increase in HSP DnaK were observed in Escherichia coli post PDT. Pretreatment with 50 degrees C heat for 30 min reduced PDT killing in both E. coli and in Enterococcus faecalis, with the most pronounced inhibition occurring at 50 mu M TBO with 5 J cm(-2) 635 nm light, where E. coli killing was reduced by 2 log(10) and E. faecalis killing was reduced by 4 log(10). Finally, inhibition of the highly conserved chaperone DnaK using a small molecule benzylidene lactam HSP inhibitor potentiated (but not significantly) the effect of PDT at a TBO concentration of 2.5 mu M in E. faecalis; however, this effect was not observed in E. coli presumably because inhibitor could not gain access due to Gram-negative permeability barrier. Induction of HSPs may be a mechanism whereby bacteria could become resistant to PDT and warrants the need for further study in the application of dual PDT-HSP-inhibition therapies. C1 [St Denis, Tyler G.; Huang, Liyi; Dai, Tianhong; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [St Denis, Tyler G.] John Jay High Sch, Cross River, NY USA. [Huang, Liyi; Dai, Tianhong; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Liyi] Guangxi Med Univ, Dept Infect Dis, Affiliated Coll & Hosp 1, Nanning, Peoples R China. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU US-NIH [R01AI50875, R01CA/AI838801, R01CA137108]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program in TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research [F9950-04-1-0079] FX The authors would like to thank Ursula Jakob and the Jakob Lab of the Department of Molecular, Cellular and Developmental Biology at the University of Michigan for advice on immunoblotting techniques. The authors would also like to thank Gitika Kharkwal and Sulbha K. Sharma of the Wellman Center for Photomedicine for assistance with SDS-PAGE. Research in the Hamblin laboratory is supported by the US-NIH (grants R01AI50875, R01CA/AI838801 to M. R. H. and R01CA137108 to Long Y. Chiang), the Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), the CDMRP Program in TBI (W81XWH-09-1-0514) and the Air Force Office of Scientific Research (F9950-04-1-0079). NR 51 TC 13 Z9 13 U1 1 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY-JUN PY 2011 VL 87 IS 3 BP 707 EP 713 DI 10.1111/j.1751-1097.2011.00902.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 753LD UT WOS:000289774200028 PM 21261628 ER PT J AU Sher, L AF Sher, L. TI Brain-derived neurotrophic factor and suicidal behavior SO QJM-AN INTERNATIONAL JOURNAL OF MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NEURODEGENERATIVE DISORDERS; GENE-EXPRESSION; BDNF; DEPRESSION; PATHOGENESIS; INJURY; 5-HT; AREA AB Studies of the neurobiology of suicidal behavior have become an important and integral part of psychiatric research. Over the past several years, studies of the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidality have attracted significant interest of researchers. Multiple lines of evidence including studies of levels of BDNF in blood cells and plasma of suicidal patients, postmortem brain studies in suicidal subjects with or without depression, and genetic association studies linking BDNF to suicide suggest that suicidal behavior may be associated with a decrease in BDNF functioning. Studies of the BDNF function are important for suicide research and prevention because of the multiple reasons including the following: (i) BDNF plays a role in the pathophysiology of depression, post-traumatic stress disorder, substance use disorders and other conditions associated with suicidal behavior. Treatment-induced enhancements of BDNF can facilitate neural integrity and recovery of function in psychiatric disorders, and consequently prevent suicidal behavior; (ii) abnormal BDNF function may be associated with elevated suicidality independently of psychiatric diagnoses. It is possible that treatment-induced improvement in the BDNF function prevents suicidal behavior independently of improvement in psychiatric disorders; (iii) BDNF may be a biological marker of suicidal behavior in certain patient populations. It is to be hoped that the studies of the neurobiology of suicidal behavior will lead to the development of new methods of suicide prevention. C1 James J Peters Vet Adm Med Ctr, Mt Sinai Sch Med, Dept Psychiat, New York, NY 10468 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, Mt Sinai Sch Med, Dept Psychiat, 130 W Kingsbridge Rd, New York, NY 10468 USA. EM drleosher@gmail.com NR 33 TC 12 Z9 14 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1460-2725 EI 1460-2393 J9 QJM-INT J MED JI QJM-An Int. J. Med. PD MAY PY 2011 VL 104 IS 5 BP 455 EP 458 DI 10.1093/qjmed/hcq207 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 754EY UT WOS:000289838200017 PM 21051476 ER PT J AU Ramadan, S Andronesi, OC Stanwell, P Lin, AP Sorensen, AG Mountford, CE AF Ramadan, Saadallah Andronesi, Ovidiu C. Stanwell, Peter Lin, Alexander P. Sorensen, A. Gregory Mountford, Carolyn E. TI Use of in Vivo Two-dimensional MR Spectroscopy to Compare the Biochemistry of the Human Brain to That of Glioblastoma SO RADIOLOGY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; MALIGNANT COLORECTAL CELLS; IDH2 MUTATIONS; COSY SPECTRA; PROTON MR; GLIOMAS; TUMORS; METABOLITES; CARCINOMA; GLUTAMATE AB Purpose: To develop an in vivo two-dimensional localized correlation spectroscopy technique with which to monitor the biochemistry of the human brain and the pathologic characteristics of diseases in a clinically applicable time, including ascertainment of appropriate postprocessing parameters with which to allow diagnostic and prognostic molecules to be measured, and to investigate how much of the chemical information, known to be available from malignant cultured cells, could be recorded in vivo from human brain. Materials and Methods: The study was approved by the institutional review board and was compliant with HIPAA. With use of a 3.0-T clinical magnetic resonance (MR) unit and a 32-channel head coil, localized correlation spectroscopy was performed in six healthy control subjects and six patients with glioblastoma multiforme (GBM) with an acquisition time of 11 minutes. Two-dimensional spectra were processed and analyzed and peak volume ratios were tabulated. The data used were proved to be normally distributed by passing the Shapiro-Wilk normality test. The first row of the spectra was extracted to examine diagnostic features. The pathologic characteristics and grade of each GBM were determined after biopsy or surgery. Statistically significant differences were assessed by using a t test. Results: The localized correlation spectroscopy method assigned biochemical species from the healthy human brain. The correlation spectra of GBM were of sufficiently high quality that many of the cross peaks, recorded previously from malignant cell models in vitro, were observed, demonstrating a statistically significant difference (P < .05) between the cross peak volumes measured for healthy subjects and those with GBM (which include lipid, alanine, N-acetylaspartate, gamma-aminobutyric acid, glutamine and glutamate, glutathione, aspartate, lysine, threonine, total choline, glycerophosphorylcholine, myo-inositol, imidazole, uridine diphosphate glucose, isocitrate, lactate, and fucose). The first row of the spectra was found to contain diagnostic features. Conclusion: Localized correlation spectroscopy of the human brain at 3.0 T with use of a 32-channel head coil was performed in 11 minutes and provided information about neurotransmitters, metabolites, lipids, and macromolecules. The method was able to help differentiate healthy brain from the biochemical signature of GBM in vivo. This method may, in the future, reduce the need for biopsy and is now applicable for the study of selected neurologic diseases. (C)RSNA, 2011 C1 [Ramadan, Saadallah; Stanwell, Peter; Lin, Alexander P.; Mountford, Carolyn E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Clin Spect,Dept Radiol, Boston, MA 02115 USA. [Andronesi, Ovidiu C.; Sorensen, A. Gregory] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Boston, MA 02115 USA. RP Mountford, CE (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Clin Spect,Dept Radiol, 4 Blackfan St,HIM 8-817, Boston, MA 02115 USA. RI Stanwell, Peter/F-9136-2012; OI Stanwell, Peter/0000-0002-4780-0393 FU National Institutes of Health [R01 1200-206456]; Australian Research Council [DP0663987]; Harvard Catalyst; Draper Laboratory; Siemens Healthcare; Siemens Medical; BayerScheringPharma; Bristol Meyers Squibb; Biogenidec; Merrimack Pharmaceuticals; Olea Medical; Mitsubishi Pharma; GE Healthcare; Regeneron; Novartis; Roche; Takeda; AstraZeneca; Kit; Medical Research Council; ACR-Image Metrix FX This research was supported by the National Institutes of Health (grant R01 1200-206456).; The authors thank the Australian Research Council for the Project Discovery Grant (DP0663987).; S.R. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. O.C.A. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. P.S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution received grants or grants are pending from Harvard Catalyst and Draper Laboratory; institution receives money for travel to other sites for technical support or collaborative research from Siemens Healthcare; institution receives research funds from Siemens Healthcare. Other relationships: none to disclose. A.P.L. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution received grants or grants are pending from Siemens Medical. Other relationships: none to disclose. A.G.S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: is on the board at ACR-Image Metrix; receives money for consultancy from BayerScheringPharma, Bristol Meyers Squibb, Biogenidec, Merrimack Pharmaceuticals, Olea Medical, Mitsubishi Pharma, GE Healthcare, Regeneron, Novartis, Roche, Siemens Medical, Takeda, and AstraZeneca; institution receives money for consultancy from Novartis, Roche, Takeda, and AstraZeneca; received money for expert testimony from Kit; institution received a grant or grants are pending from the Medical Research Council; receives payment for lectures including service on speakers bureaus from ACR-Image Metrix; has stock or stock options from Catalyst Medical and Breakaway Imaging. Other relationships: none to disclose. C.E.M. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution has grants/grants pending from Harvard Catalyst; institution receives money for travel to other sites for technical support or to undertake research from Siemens Healthcare; institution receives research funds from Siemens Healthcare. Other relationships: none to disclose. NR 48 TC 15 Z9 16 U1 0 U2 6 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 MAY PY 2011 VL 259 IS 2 BP 540 EP 549 DI 10.1148/radiol.11101123 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 752CZ UT WOS:000289667300029 PM 21357517 ER PT J AU Singh, S Kalra, MK Gilman, MD Hsieh, J Pien, HH Digumarthy, SR Shepard, JAO AF Singh, Sarabjeet Kalra, Mannudeep K. Gilman, Matthew D. Hsieh, Jiang Pien, Homer H. Digumarthy, Subba R. Shepard, Jo-Anne O. TI Adaptive Statistical Iterative Reconstruction Technique for Radiation Dose Reduction in Chest CT: A Pilot Study SO RADIOLOGY LA English DT Article ID RAY COMPUTED-TOMOGRAPHY; Z-AXIS MODULATION; IMAGE QUALITY; HELICAL CT; NOISE-REDUCTION; UNITED-STATES; PATIENT SIZE; BRONCHIECTASIS; OPTIMIZATION; FEASIBILITY AB Purpose: To compare lesion detection and image quality of chest computed tomographic (CT) images acquired at various tube current-time products (40-150 mAs) and reconstructed with adaptive statistical iterative reconstruction (ASIR) or filtered back projection (FBP). Materials and Methods: In this Institutional Review Board-approved HIPAA-compliant study, CT data from 23 patients (mean age, 63 years +/- 7.3 [standard deviation]; 10 men, 13 women) were acquired at varying tube current-time products (40, 75, 110, and 150 mAs) on a 64-row multidetector CT scanner with 10-cm scan length. All patients gave informed consent. Data sets were reconstructed at 30%, 50%, and 70% ASIR-FBP blending. Two thoracic radiologists assessed image noise, visibility of small structures, lesion conspicuity, and diagnostic confidence. Objective noise and CT number were measured in the thoracic aorta. CT dose index volume, dose-length product, weight, and transverse diameter were recorded. Data were analyzed by using analysis of variance and the Wilcoxon signed rank test. Results: FBP had unacceptable noise at 40 and 75 mAs in 17 and five patients, respectively, whereas ASIR had acceptable noise at 40-150 mAs. Objective noise with 30%, 50%, and 70% ASIR blending (11.8 +/- 3.8, 9.6 +/- 3.1, and 7.5 +/- 2.6, respectively) was lower than that with FBP (15.8 +/- 4.8) (P < .0001). No lesions were missed on FBP or ASIR images. Lesion conspicuity was graded as well seen on both FBP and ASIR images (P < .05). Mild pixilated blotchy texture was noticed with 70% blended ASIR images. Conclusion: Acceptable image quality can be obtained for chest CT images acquired at 40 mAs by using ASIR without any substantial artifacts affecting diagnostic confidence. (C)RSNA, 2011 C1 [Singh, Sarabjeet; Kalra, Mannudeep K.; Gilman, Matthew D.; Pien, Homer H.; Digumarthy, Subba R.; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hsieh, Jiang] GE Healthcare, Waukesha, WI USA. RP Singh, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,4th Floor,467C, Boston, MA 02114 USA. EM ssingh6@partners.org FU GE Healthcare; Siemens; Philips; GE Healthcare/RSNA FX S.S. No potential conflicts of interest to disclose. M.K.K. Financial activities related to the present article: institution has a grant from GE Healthcare, is a consultant for GE Healthcare. Financial activities not related to the present article: is a board member for GE Healthcare, is on the speakers bureau of GE Healthcare. Other relationships: none to disclose. M.D.G. No potential conflicts of interest to disclose. J.H. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: is an employee of GE Healthcare, receives payment for patents from GE Healthcare, owns stock in GE. Other relationships: none to disclose. H.H.P. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution has grants from Siemens and Philips for two studies for which the author is the principal investigator. Other relationships: none to disclose. S.R.D. No potential conflicts of interest to disclose. J.A.O.S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: has given expert testimony for Norman, Hanson & Detroy. Other relationships: none to disclose.; From the Department of Radiology, Massachusetts General Hospital, 25 New Chardon St, 4th Floor, 467C, Boston, MA 02114 (S.S., M.K.K., M.D.G., H.H.P., S.R.D., J.A.O.S.); and GE Healthcare, Waukesha, Wis (J.H.). Received July 20, 2010; revision requested October 11; revision received November 8; accepted November 19; final version accepted December 15. M.K.K. supported in part by 2010-2012 GE Healthcare/RSNA Education Scholar Grant. Address correspondence to S.S. (e-mail:ssingh6@partners.org). NR 29 TC 170 Z9 183 U1 1 U2 5 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 MAY PY 2011 VL 259 IS 2 BP 565 EP 573 DI 10.1148/radiol.11101450 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 752CZ UT WOS:000289667300032 PM 21386048 ER PT J AU Payabvash, S Souza, LCS Wang, YF Schaefer, PW Furie, KL Halpern, EF Gonzalez, G Lev, MH AF Payabvash, Seyedmehdi Souza, Leticia C. S. Wang, Yifei Schaefer, Pamela W. Furie, Karen L. Halpern, Elkan F. Gonzalez, R. Gilberto Lev, Michael H. TI Regional Ischemic Vulnerability of the Brain to Hypoperfusion The Need for Location Specific Computed Tomography Perfusion Thresholds in Acute Stroke Patients SO STROKE LA English DT Article DE computed tomography; magnetic resonance imaging; stroke ID CT PERFUSION; BLOOD-VOLUME; WHITE-MATTER; DIFFUSION; GRAY; INFARCTION AB Background and Purpose-To characterize the spatial pattern of cerebral ischemic vulnerability to hypoperfusion in stroke patients. Methods-We included 90 patients who underwent admission CT perfusion and MRI within 12 hours of ischemic stroke onset. Infarcted brain lesions ("core") were segmented from admission diffusion-weighted imaging and, along with the CT perfusion parameter maps, coregistered onto MNI-152 brain space, which was parcellated into 125 mirror cortical and subcortical regions per hemisphere. We tested the hypothesis that the percent infarction increment per unit of relative cerebral blood flow (rCBF) reduction differs statistically between regions using regression analysis to assess the interaction between regional rCBF and region variables. Next, for each patient, a "vulnerability index" map was constructed with voxel values equaling the product of that voxel's rCBF and infarction probability (derived from the MNI-152-transformed, binary, segmented, diffusion-weighted imaging lesions). Voxel-based rCBF threshold for core was determined within the upper 20(th) percentile of vulnerability index map voxel values. Results-Different regions had different percent infarction increase per unit rCBF reduction (P=0.001). The caudate body, putamen, insular ribbon, paracentral lobule, and precentral, middle, and inferior frontal gyri had the highest ischemic vulnerability to hypoperfusion. A voxel-based rCBF threshold of <0.42 optimally distinguished infarct core in the highly-vulnerable regions, whereas rCBF <0.16 distinguished core in the remainder of the brain. Conclusions-We demonstrated regional ischemic vulnerability of the brain to hypoperfusion in acute stroke patients. Location-specific, rather than whole-brain, rCBF thresholds may provide a more accurate metric for estimating infarct core using CT perfusion maps. (Stroke. 2011;42:1255-1260.) C1 [Payabvash, Seyedmehdi; Souza, Leticia C. S.; Schaefer, Pamela W.; Halpern, Elkan F.; Gonzalez, R. Gilberto; Lev, Michael H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Wang, Yifei] Univ Western Ontario, Schulich Sch Med & Dent, London, ON, Canada. [Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Gray 241H, Boston, MA 02114 USA. EM mlev@partners.org FU National Institute of Health (NIH) [P50 NS051343]; Agency for Healthcare Research and Quality [AHRQ R01 HS11392]; Massachusetts General Hospital Clinical Research Center, Harvard Clinical and Translational Science Center, from the National Center for Research Resources [1 UL1 RR025758-01]; GE Healthcare FX This work was supported by the Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) grant funded by the National Institute of Health (NIH; P50 NS051343), the Agency for Healthcare Research and Quality grant AHRQ R01 HS11392, and the Massachusetts General Hospital Clinical Research Center (1 UL1 RR025758-01), Harvard Clinical and Translational Science Center, from the National Center for Research Resources.; Michael H. Lev receives research support from GE Healthcare and is consultant to Co-Axia, GE Healthcare, and Millennium Pharmaceuticals. NR 15 TC 36 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2011 VL 42 IS 5 BP 1255 EP 1260 DI 10.1161/STROKEAHA.110.600940 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 754EK UT WOS:000289835900021 PM 21493917 ER PT J AU Muehlschlegel, S Rordorf, G Sims, J AF Muehlschlegel, Susanne Rordorf, Guy Sims, John TI Effects of a Single Dose of Dantrolene in Patients With Cerebral Vasospasm After Subarachnoid Hemorrhage A Prospective Pilot Study SO STROKE LA English DT Article DE calcium; cerebral vasospasm; dantrolene; neurocritical care; ryanodine receptor; subarachnoid hemorrhage; vasoconstriction ID AMERICAN-HEART-ASSOCIATION; CANINE BASILAR ARTERY; MALIGNANT HYPERTHERMIA; CONTROLLED-TRIAL; CELL-DEATH; ANGIOGRAPHY; MANAGEMENT; DIAGNOSIS; VASOCONSTRICTION; NIMODIPINE AB Background and Purpose-New therapies for cerebral vasospasm after subarachnoid hemorrhage are needed because of its high morbidity and mortality rates. We investigated the feasibility and safety of a single dose of intravenous dantrolene and its effect on transcranial Doppler in cerebral vasospasm after subarachnoid hemorrhage. Methods-In a prospective, open-label, single-dose ascending safety trial, 5 patients received intravenous dantrolene 1.25 mg/kg and the next 5 patients received 2.5 mg/kg over the course of 60 minutes. All other infusions were kept steady and hemodynamic parameters were recorded. Transcranial Doppler was performed at 0, 45, 90, and 135 minutes relative to infusion start. Basic chemistries, serum osmolality, arterial blood gas, and liver enzymes were measured before and after. Results-Laboratory values and hemodynamic parameters remained unchanged except for a decrease in the systolic blood pressure in the low-dose group (-8 mm Hg; 95% CI, -26 to 10 mm Hg; P = 0.027). After correcting for this decrease in blood pressure, peak systolic transcranial Doppler velocities decreased significantly (-26 cm/s; 95% CI, -47 to -5 cm/s; P = 0.02), with a borderline change in mean velocities in the low-dose group (-16 cm/s; 95% CI, -36 to 4 cm/s; P = 0.07) and peak systolic transcranial Doppler velocity in the high-dose group (-26 cm/s; 95% CI, -56 to 5 cm/s; P = 0.05). Conclusions-In this pilot study, a single dose of intravenous dantrolene in cerebral vasospasm after subarachnoid hemorrhage appears feasible while inhibiting vasoconstriction in the low-dose group, but it may lower blood pressure. Our study provides useful data for the design of larger future studies. C1 [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Neurol, Div Neurocrit Care, Worcester, MA 01655 USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Anesthesia Crit Care, Div Neurocrit Care, Worcester, MA 01655 USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Surg, Div Neurocrit Care, Worcester, MA 01655 USA. [Rordorf, Guy; Sims, John] Harvard Univ, Sch Med, Dept Neurol, Neurocrit Care Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sims, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. RP Muehlschlegel, S (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, Div Neurocrit Care, 55 Lake Ave N,S5-412, Worcester, MA 01655 USA. EM susanne.muehlschlegel@umassmemorial.org FU American Heart Association [09SDG2030022]; Worcester Research Foundation; National Institute of Health [NIH 1 K08 NS049241-01A2] FX This work was funded by the American Heart Association (Scientist Development grant 09SDG2030022 to Dr Muehlschlegel), the Worcester Research Foundation (2010 Award to Dr Muehlschlegel), the National Institute of Health (NIH 1 K08 NS049241-01A2 to Dr Sims), and private funds donated to Dr Guy Rordorf. The study drug dantrolene (Dantrium IV) was donated by Procter & Gamble Pharmaceuticals (Cincinnati, OH) and later by J.H.P. Pharmaceuticals (Parsippany, NJ). The study was entirely investigator-initiated and neither pharmaceutical company was part of the development, execution, and analysis of the study or drafting of the manuscript. NR 29 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 MAY PY 2011 VL 42 IS 5 BP 1301 EP 1306 DI 10.1161/STROKEAHA.110.603159 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 754EK UT WOS:000289835900028 PM 21454813 ER PT J AU Biffi, A Devan, WJ Anderson, CD Cortellini, L Furie, KL Rosand, J Rost, NS AF Biffi, Alessandro Devan, William J. Anderson, Christopher D. Cortellini, Lynelle Furie, Karen L. Rosand, Jonathan Rost, Natalia S. TI Statin Treatment and Functional Outcome After Ischemic Stroke Case-Control and Meta-Analysis SO STROKE LA English DT Article DE acute stroke; cerebral infarct; functional recovery; meta-analysis; outcomes; statins; stroke recovery ID PRETREATMENT; HETEROGENEITY; PREVENTION; DEMENTIA; SUBTYPE; DISEASE; VOLUME; BIAS AB Background and Purpose-Multiple studies suggest that statin use before acute ischemic stroke is associated with improved functional outcome. However, available evidence is conflicting, and several published reports are limited by small sample sizes. We therefore investigated the effect of antecedent use of statins on stroke outcome by performing a meta-analysis of all results from published studies as well as our own unpublished data. Methods-We performed a systematic literature search and meta-analysis of studies investigating the association between prestroke statin use and clinical outcome and included additional data from 126 prestroke statin users and 767 nonusers enrolled at our institution. A total of 12 studies, comprising 2013 statin users and 9682 nonusers, was meta-analyzed using a random effects model. We also meta-analyzed results for individual Trial of ORG 10172 in Acute Stroke Treatment stroke subtypes to determine whether the effect of statin use differed across subtypes using the Breslow-Day test. Results-Meta-analysis of all available data identified an association between prestroke statin use and improved functional outcome (OR, 1.62; 95% CI, 1.39 to 1.88), but we uncovered evidence of publication bias. The effect of statin use on functional outcome was found to be larger for small vessel strokes compared with other subtypes (Breslow-Day P = 0.008). Conclusions-Antecedent use of statins is associated with improved outcome in patients with acute ischemic stroke. This association appears to be stronger in patients with small vessel stroke subtype. However, evidence of publication bias in the existing literature suggests these findings should be interpreted with caution. (Stroke. 2011;42:1314-1319.) C1 [Biffi, Alessandro; Devan, William J.; Anderson, Christopher D.; Cortellini, Lynelle; Rosand, Jonathan; Rost, Natalia S.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA. [Biffi, Alessandro; Devan, William J.; Anderson, Christopher D.; Cortellini, Lynelle; Rosand, Jonathan; Rost, Natalia S.] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Dept Neurol, Boston, MA 02114 USA. RP Rost, NS (reprint author), Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org OI Anderson, Christopher/0000-0002-0053-2002 FU National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) [K23NS064052, 5R01NS059727, 5P50NS051343, R01NS063925, 5P50NS051343-04]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010N]; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke FX Supported by National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) K23NS064052 (N.S.R.); NIH-NINDS 5R01NS059727, 5P50NS051343, and R01NS063925 (J.R.); NIH-NINDS 5P50NS051343-04 (K. L. F.); American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N); and Deane Institute for Integrative Study of Atrial Fibrillation and Stroke. NR 23 TC 39 Z9 41 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 MAY PY 2011 VL 42 IS 5 BP 1314 EP 1319 DI 10.1161/STROKEAHA.110.605923 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 754EK UT WOS:000289835900030 PM 21415396 ER PT J AU Fujiwara, N Mandeville, ET Geng, XK Luo, YM Arai, K Wang, XY Ji, XM Singhal, AB Lo, EH AF Fujiwara, Norio Mandeville, Emiri T. Geng, Xiaokun Luo, Yumin Arai, Ken Wang, Xiaoying Ji, Xunming Singhal, Aneesh B. Lo, Eng H. TI Effect of Normobaric Oxygen Therapy in a Rat Model of Intracerebral Hemorrhage SO STROKE LA English DT Article DE acute stroke; intracranial hemorrhage; ischemia; neuroprotection ID FOCAL CEREBRAL-ISCHEMIA; EXPERIMENTAL STROKE; HYPEROXIA; MATRIX-METALLOPROTEINASE-9; REPERFUSION; INDUCTION; INJURY; EDEMA AB Background and Purpose-Normobaric oxygen (NBO) therapy may be neuroprotective in acute ischemic stroke. However, how NBO may affect intracerebral hemorrhage is unclear. We tested NBO in a rat model of striatal intracerebral hemorrhage. Methods-Intracerebral hemorrhage was induced by stereotactic injection of collagenase Type VII (0.5 U) into the right striatum of male Sprague-Dawley rats. One hour later, rats were randomized into controls (n = 13) versus NBO treatment (n = 13). NBO was applied for 2 hours. Hemorrhagic blood volume, brain water content, and neurological outcomes (forelimb placement test, forelimb asymmetry, neuroscore) were quantified at 72 hours. Experiments were repeated in a second independent laboratory to assess reproducibility in neurological outcomes (n = 10 per group). Results-NBO did not worsen hemorrhage severity or brain edema. There were no significant differences in hemorrhagic blood volumes (control, 6.4 +/- 0.9 mu L versus NBO, 7.0 +/- 2.1 mu L; P = 0.18) or brain water content (control, 81.9% +/- 1.1% versus NBO, 81.6% +/- 0.5%; P = 0.58). NBO did not affect any of the neurological outcome tests in the primary or secondary studies. Conclusions-NBO therapy may not worsen outcomes in intracerebral hemorrhage. (Stroke. 2011;42:1469-1472.) C1 [Fujiwara, Norio; Mandeville, Emiri T.; Arai, Ken; Wang, Xiaoying; Singhal, Aneesh B.; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Boston, MA 02114 USA. [Fujiwara, Norio; Mandeville, Emiri T.; Arai, Ken; Wang, Xiaoying; Singhal, Aneesh B.; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Boston, MA 02114 USA. [Geng, Xiaokun; Luo, Yumin; Ji, Xunming] Capital Med Univ, Xuanwu Hosp, Cerebrovasc Dis Res Inst, Beijing, Peoples R China. RP Singhal, AB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, ACC-729-C, Boston, MA 02114 USA. EM asinghal@partners.org FU National Institutes of Health [P50-NS51343, R01-NS51412, R01-NS56458] FX Supported in part by National Institutes of Health grants P50-NS51343, R01-NS51412, and R01-NS56458. NR 16 TC 13 Z9 14 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2011 VL 42 IS 5 BP 1469 EP 1472 DI 10.1161/STROKEAHA.110.593350 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 754EK UT WOS:000289835900053 PM 21415401 ER PT J AU Zhou, J Li, HB Fu, YY Shi, JL Hou, JX Zhang, YM Liu, XH Song, P AF Zhou, Jin Li, Huibo Fu, Yueyue Shi, Jialan Hou, Jinxiao Zhang, Yingmei Liu, Xiuhua Song, Peng TI Arsenic trioxide induces procoagulant activity through phosphatidylserine exposure and microparticle generation in endothelial cells SO THROMBOSIS RESEARCH LA English DT Article DE Arsenic trioxide; Endothelial cells; Phosphatidylserine; Lactadherin; Microparticles ID ACUTE PROMYELOCYTIC LEUKEMIA; TISSUE FACTOR ACTIVITY; IN-VIVO; ACTIVATED PLATELETS; THROMBIN GENERATION; LACTADHERIN; MEMBRANES; FAILURE; SURFACE; DEATH AB Background: Coagulopathy is a major cause of early death when arsenic trioxide (As(2)O(3)) therapy fails. In addition to the procoagulant properties of blast cells, the cytotoxic therapy may contribute to the coagulation disorders. The aim of the present study was to evaluate the possible impact of As(2)O(3) on membrane alterations, including phosphatidylserine (PS) exposure and microparticle generation, and the consequent procoagulant properties of endothelial cells. Methods: Procoagulant activity (PCA) of human umbilical vein endothelial cells (HUVECs) was assessed by measuring clotting time and through purified coagulation complex assays. PS exposure on HUVEC membrane was observed by confocal microscopy and quantified with flow cytometry. In addition, counts and PCA of endothelial microparticles were determined by flow cytometry and plasma coagulation assay. Results: As(2)O(3) increased the ability of HUVECs to accelerate coagulation process and promote formation of coagulation complexes. Procoagulant activity corresponded to PS exposed on HUVECs. In coincidence with the PS externalization, As(2)O(3) increased the production of PS-bearing microparticles, which then accelerated fibrin strand formation significantly. By blocking PS, lactadherin was able to inhibit over 90% of the intrinsic tenase/prothrombinase activity of As(2)O(3)-treated HUVECs, and restored coagulation times of As(2)O(3)-treated cells and microparticles to control levels. Conclusions: As(2)O(3) increases PCA of HUVECs through PS exposure and PS-bearing microparticle generation, which might cause thrombosis and act as a contributing factor in As(2)O(3) therapy-related coagulopathy. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Zhou, Jin; Li, Huibo; Fu, Yueyue; Shi, Jialan; Hou, Jinxiao; Zhang, Yingmei; Liu, Xiuhua; Song, Peng] Harbin Med Coll, Affiliated Hosp 1, Dept Med, Div Hematol, Harbin 150001, Peoples R China. [Shi, Jialan] Brigham & Womens Hosp, VA Boston Health care Syst, Dept Med, Boston, MA 02132 USA. [Shi, Jialan] Harvard Univ, Sch Med, Boston, MA 02132 USA. RP Zhou, J (reprint author), Harbin Med Coll, Affiliated Hosp 1, Dept Med, Div Hematol, 23 Youzheng St, Harbin 150001, Peoples R China. EM zhoujin1111@126.com FU National Natural Science Foundation of China [30871227]; International Cooperation Foundation [WH05C01]; National Traditional Chinese Medicine Bureau [06-07LP15]; Science Foundation of Heilongjiang Province [GB08C401-02]; Science Foundation of the First Affiliated Hospital of Harbin Medical University [2007091] FX This work was supported by grants of National Natural Science Foundation of China (30871227), the International Cooperation Foundation (WH05C01), the National Traditional Chinese Medicine Bureau (06-07LP15), the Science Foundation of Heilongjiang Province (GB08C401-02), and the Science Foundation of the First Affiliated Hospital of Harbin Medical University (2007091). NR 34 TC 4 Z9 5 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD MAY PY 2011 VL 127 IS 5 BP 466 EP 472 DI 10.1016/j.thromres.2011.01.003 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 753LJ UT WOS:000289774900013 PM 21272920 ER PT J AU Bleier, BS Wang, EW Vandergrift, WA Schlosser, RJ AF Bleier, Benjamin S. Wang, Eric W. Vandergrift, W. Alex, III Schlosser, Rodney J. TI Mucocele rate after endoscopic skull base reconstruction using vascularized pedicled flaps SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID NASOSEPTAL FLAP; SURGERY AB Background: Postoperative cerebrospinal fluid leak is a significant risk after endoscopic skull base surgery. Recently, novel reconstructive techniques using vascularized pedicled mucosal flaps have been applied to decrease this potential risk. Complete mucosal extirpation in the wound bed is not always feasible and the impact of insetting the flap over intact underlying mucosa is not clear. The purpose of this study was to determine the rate of mucocele formation after nasoseptal flap reconstruction without mucosal stripping. Methods: This is an Institutional Review Board approved, retrospective study consisting of 28 patients undergoing skull base reconstruction using a pedicled nasoseptal flap between 2008 and 2010 at a tertiary care hospital. In all cases the sinus or skull base mucosa surrounding the defect was left intact. Patients were followed postoperatively by endoscopy and/or imaging for evidence of mucocele formation in the reconstructive bed. Results: The total rate of mucocele formation was 3.6% (1 of 28, noted on postoperative day 46). The mean follow-up time was 243 +/- 174 days (range, 46-585 days). Eleven patients were followed for over I year. All flaps remained viable and well vascularized. Conclusion: The pedicled nasoseptal flap is an effective means of reconstruction after endoscopic skull base surgery. Avoidance of extensive stripping of the surrounding mucosa does not result in a significant rate of postoperative mucocele formation in the short term. Long-term follow-up is still indicated. (Am J Rhinol Allergy 25, 186-187, 2011; doi: 10.2500/ajra.2011.25.3587) C1 [Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. [Wang, Eric W.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Vandergrift, W. Alex, III] Med Univ S Carolina, Dept Neurosurg, Charleston, SC 29425 USA. RP Bleier, BS (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM bleierb@gmail.com OI Wang, Eric/0000-0002-1180-5854 NR 8 TC 21 Z9 21 U1 0 U2 3 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAY-JUN PY 2011 VL 25 IS 3 BP 186 EP 187 DI 10.2500/ajra.2011.25.3587 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA 783WZ UT WOS:000292116500010 PM 21679531 ER PT J AU Azim, HA Michiels, S Bedard, P Singhal, SK Haibe-Kains, B Piccart, M Sotiriou, C Loi, S AF Azim, H. A., Jr. Michiels, S. Bedard, P. Singhal, S. K. Haibe-Kains, B. Piccart, M. Sotiriou, C. Loi, S. TI THE PROGNOSTIC PERFORMANCE OF FIRST GENERATION GENE EXPRESSION SIGNATURES (FGS) IN YOUNG WOMEN WITH OPERABLE BREAST CANCER (BC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Conference on Improving Care and Knowledge through Translational Research (IMPAKT) Breast Cancer CY MAY 05-07, 2011 CL Brussels, BELGIUM C1 [Azim, H. A., Jr.; Michiels, S.; Singhal, S. K.; Sotiriou, C.; Loi, S.] Breast Canc Translat Res Lab, Brussels, Belgium. [Bedard, P.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Haibe-Kains, B.] Harvard Univ, Sch Publ Hlth, Comput Biol & Funct Genom Lab, Dana Farber Canc Inst, Boston, MA 02115 USA. [Piccart, M.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. RI Haibe-Kains, Benjamin/D-3702-2011; Michiels, Stefan/L-1516-2013; Loi, Sherene/H-1979-2016 OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Michiels, Stefan/0000-0002-6963-2968; 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 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2011 VL 22 SU 2 BP 61 EP 61 PG 1 WC Oncology SC Oncology GA 764EB UT WOS:000290610100128 ER PT J AU Miller, RM Ford, JM Shanbhag, H Mathalon, DH AF Miller, Ryan M. Ford, Judith M. Shanbhag, Harshad Mathalon, Daniel H. TI Negative Symptom Severity and Schizophrenia: Abnormal Entrainment of Dorsal Striatum in Default Mode Network SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 12-14, 2011 CL San Francisco, CA SP Soc Biol Psychiat C1 [Miller, Ryan M.; Ford, Judith M.; Shanbhag, Harshad; Mathalon, Daniel H.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2011 VL 69 IS 9 SU S MA 873 BP 263S EP 263S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764OR UT WOS:000290641800834 ER PT J AU Holmes, LB Westgate, MN AF Holmes, L. B. Westgate, M-N TI Using ICD-9 Codes in Discharge Diagnoses to Establish Prevalence of Malformations in Newborn Infants SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Holmes, L. B.; Westgate, M-N] MassGen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2011 VL 91 IS 5 SI SI BP 335 EP 335 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 762QQ UT WOS:000290494900055 ER PT J AU Holmes, LB AF Holmes, L. B. TI Controls for Pregnancy Registries SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Holmes, L. B.] MassGen Hosp Children, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2011 VL 91 IS 5 SI SI BP 386 EP 386 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 762QQ UT WOS:000290494900145 ER PT J AU Lin, AE AF Lin, A. E. TI Selecting Congenital Heart Defects in Birth Defects Research: Biology vs. Budget SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Lin, A. E.] MassGen Hosp Children, Genet Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2011 VL 91 IS 5 SI SI BP 388 EP 388 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 762QQ UT WOS:000290494900149 ER PT J AU Holmes, LB Westgate, MN AF Holmes, L. B. Westgate, M-N TI Using ICD-9 Codes in Discharge Diagnoses to Establish Prevalence of Malformations in Newborn Infants SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Holmes, L. B.; Westgate, M-N] MassGen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2011 VL 91 IS 5 SI SI BP 389 EP 389 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 762QQ UT WOS:000290494900151 ER PT J AU Meeks, TW Culberson, JW Horton, MS AF Meeks, Thomas W. Culberson, John W. Horton, Monica S. TI Medications in Long-Term Care: When Less is More SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Long-term care; Inappropriate prescribing; Polypharmacy; Psychotropics; Opiates; Sedatives ID NURSING-HOME RESIDENTS; ATYPICAL ANTIPSYCHOTIC-DRUGS; RANDOMIZED CONTROLLED-TRIALS; ELDERLY-PATIENTS; OLDER-ADULTS; MUSCULOSKELETAL PAIN; TARDIVE-DYSKINESIA; EXPLICIT CRITERIA; NONMALIGNANT PAIN; ALZHEIMER-DISEASE AB Attention has been drawn to the potential risks of several medications in the long-term care setting. Most of these medications deemed as inappropriate affect the central nervous system and are indicated only for select populations with specific conditions. Many of these drugs are prescribed without clear indications and continued indefinitely without critical decision-making about the potentially salutary effects of discontinuing medications. This article describes the increasing awareness of potentially inappropriate prescribing in the long-term care setting and reviews the rationale for why various types of medications are deemed inappropriate, with a focus on agents that affect central nervous system functioning. C1 [Meeks, Thomas W.] Univ Calif San Diego, Dept Psychiat, Div Geriatr Psychiat, San Diego, CA 92093 USA. [Culberson, John W.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Culberson, John W.] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Horton, Monica S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Horton, Monica S.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Meeks, TW (reprint author), 9300 Campus Point Dr,MC 7602, La Jolla, CA 92037 USA. EM tmeeks@ucsd.edu FU Geriatric Academic Career Awards [K01 HP00047-02, K01 HP00080-02, K01 HP00114-02] FX This work was supported by the following Geriatric Academic Career Awards: (1) K01 HP00047-02 (Dr. Meeks) (2) K01 HP00080-02 (Dr. Culberson) (3) K01 HP00114-02 (Dr. Horton). NR 67 TC 6 Z9 7 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2011 VL 27 IS 2 BP 171 EP + DI 10.1016/j.cger.2011.01.003 PG 23 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 784PQ UT WOS:000292169600005 PM 21641504 ER PT J AU Korc-Grodzicki, B Wallace, JA Rodin, MB Bernacki, RE AF Korc-Grodzicki, Beatriz Wallace, James A. Rodin, Miriam B. Bernacki, Rachelle E. TI Cancer in Long-Term Care SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Cancer; Long-term care; Nursing home; Geriatric ID NURSING-HOME RESIDENTS; ANDROGEN DEPRIVATION THERAPY; PROSTATE-SPECIFIC ANTIGEN; TERMINALLY-ILL PATIENTS; PRIMARY BREAST-CANCER; OLDER-ADULTS; COLORECTAL-CANCER; FUNCTIONAL DECLINE; 1-YEAR MORTALITY; ELDERLY-WOMEN AB This article describes the range of cancer patients in longterm care and provides a framework for clinical decision making. The benefits and burdens of providing standard therapy to a vulnerable population are discussed. To give more specific guidelines for advocates of treatment, skeptics, and others, the authors present best estimates of the current burden of cancer in the long-term care population and current screening guidelines that apply to the elderly under long-term care. Experience-based suggestions are offered for oncologists and clinicians involved in long-term care to help them respond to patient and family concerns about limitations of cancer care. C1 [Korc-Grodzicki, Beatriz] Mem Sloan Kettering Canc Ctr, Dept Med, Geriatr Serv, New York, NY 10065 USA. [Wallace, James A.] Univ Chicago Ongol Geriatr, SOCARE, Chicago, IL 60637 USA. [Rodin, Miriam B.] St Louis Univ, Sch Med, Dept Internal Med, Div Geriatr, St Louis, MO 63104 USA. [Bernacki, Rachelle E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Pain & Palliat Care Program, Boston, MA 02115 USA. RP Korc-Grodzicki, B (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Geriatr Serv, 1275 York Ave, New York, NY 10065 USA. EM korcgrob@mskcc.org OI Korc-Grodzicki, Beatriz/0000-0003-0673-4606 NR 101 TC 0 Z9 0 U1 9 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2011 VL 27 IS 2 BP 301 EP + DI 10.1016/j.cger.2011.03.011 PG 28 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 784PQ UT WOS:000292169600014 PM 21641513 ER PT J AU Ahluwalia, MS Wen, PY AF Ahluwalia, Manmeet S. Wen, Patrick Y. TI Antiangiogenic therapy for patients with glioblastoma: current challenges in imaging and future directions SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Editorial Material DE antiangiogenic agents; glioblastoma; imaging; response ID RECURRENT GLIOBLASTOMA; PROLONGS SURVIVAL; MALIGNANT GLIOMAS; TUMOR PROGRESSION; KINASE INHIBITOR; PHASE-II; BEVACIZUMAB; CEDIRANIB; CRITERIA; PROLIFERATION C1 [Ahluwalia, Manmeet S.] Cleveland Clin, Neurol Inst, Rose Ella Burkhardt Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA. [Ahluwalia, Manmeet S.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44195 USA. [Ahluwalia, Manmeet S.] Case Western Reserve Univ, Coll Med, Dept Med, Cleveland Clin Lerner, Cleveland, OH 44106 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Canc Neurol, Boston, MA 02115 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. RP Ahluwalia, MS (reprint author), Cleveland Clin, Neurol Inst, Rose Ella Burkhardt Brain Tumor & Neurooncol Ctr, 9500 Euclid Ave,S73, Cleveland, OH 44195 USA. EM ahluwam@ccf.org NR 20 TC 9 Z9 9 U1 1 U2 3 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 MAY PY 2011 VL 11 IS 5 BP 653 EP 656 DI 10.1586/ERA.11.35 PG 4 WC Oncology SC Oncology GA 782UG UT WOS:000292037000001 PM 21554035 ER PT J AU Singh, KK Gray, PK Wang, Y Fenton, T Trout, RN Spector, SA AF Singh, Kumud K. Gray, Ping Kathryn Wang, Yan Fenton, Terence Trout, Rodney N. Spector, Stephen A. TI HLA Alleles are Associated With Altered Risk for Disease Progression and Central Nervous System Impairment of HIV-Infected Children SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE children; CNS impairment; HLA alleles; HIV-1-related disease ID MAJOR HISTOCOMPATIBILITY COMPLEX; SLOW PROGRESSORS; VIRAL CONTROL; CASE-COHORT; 2 PARTS; SUSCEPTIBILITY; TRANSMISSION; POLYMORPHISM; IMMUNOLOGY; DIDANOSINE AB Objective: To examine the effects of human leukocyte antigen (HLA) alleles on HIV-1-related disease progression and central nervous system (CNS) impairment in children. Design: Five hundred seventy-two HIV-1-infected children, identified as disease progressors or nonprogressors, were selected from PACTG P152 and P300 through a case-cohort sampling scheme. Study endpoints were HIV-1-related disease progression-free survival and time to CNS impairment. Methods: DNA was genotyped for HLA alleles using a Luminex 100 platform. Weighted Kaplan-Meier methods, and Cox proportional hazards models were used to assess the effects of HLA alleles on study endpoints. Results: Presence of the B-27 allele (n = 20) was associated with complete protection against disease progression and CNS impairment over the median follow-up of 26 months (P < 0.0001 for both). These findings held in multivariate analyses controlling for baseline covariates including race, gender, age, log HIV-1 RNA, CD4(+) lymphocyte count and percent, weight for age z score and treatment, and for other genotypes shown to affect HIV-1-related disease progression. Also, although the Cw-2 allele protected against disease progression [ Hazard ratio (HR), 0.48; 95% confidence interval (CI): 0.28 to 0.81; P = 0.006], the A-24 allele was associated with more rapid CNS impairment (HR: 2.01; 95% CI: 1.04 to 3.88; P = 0.04). The HLA class II DQB1-2 allele was associated with a delayed disease progression (HR: 0.66; 95% CI: 0.47-0.92; P = 0.01) and CNS impairment (HR: 0.58; 95% CI: 0.36 to 0.93; P = 0.02). Conclusions: Presence of B-27, Cw-2, or DQB1-2 alleles was associated with delayed HIV-1 disease progression, while B-27, A-24, and DQB1-2 alleles were associated with altered progression to CNS impairment in children. C1 [Singh, Kumud K.; Trout, Rodney N.; Spector, Stephen A.] Univ Calif San Diego, Dept Pediat, Div Infect Dis, La Jolla, CA 92093 USA. [Gray, Ping Kathryn; Wang, Yan; Fenton, Terence] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Gray, Ping Kathryn] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Spector, Stephen A.] Rady Childrens Hosp San Diego, Div Infect Dis, Dept Pediat, San Diego, CA USA. RP Spector, SA (reprint author), Univ Calif San Diego, Dept Pediat, Div Infect Dis, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM kusingh@ucsd.edu; saspector@ucsd.edu FU National Institute of Allergy and Infectious Diseases; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network [AI-069536]; [5R01MH085608] FX Supported by grants from the National Institute of Allergy and Infectious Diseases, the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network (AI-069536) and 5R01MH085608. NR 37 TC 8 Z9 9 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 MAY 1 PY 2011 VL 57 IS 1 BP 32 EP 39 DI 10.1097/QAI.0b013e3182119244 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 749YU UT WOS:000289509100011 PM 21283014 ER PT J AU Banerji, D Martinez, F Abbara, S Truong, QA AF Banerji, Dahlia Martinez, Felipe Abbara, Suhny Truong, Quynh A. TI Turner Syndrome with aberrant right subclavian artery and partial anomalous pulmonary venous return SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Congenital heart disease; Turner syndrome; Aberrant right subclavian artery; Partial anomalous pulmonary venous return; Cardiac computed tomography; Esophagram AB We report the case of a 6 year old girl with Turner Syndrome and Aberrant Right Subclavian Artery with an incidental finding of PAPVR on contrast-enhanced, high-pitch, 128-slice, electrocardiographic-gated dual source CT. There is value of using high-pitch DSCT in pediatric patients for diagnostic images with minimal radiation exposure. (C) 2011 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Banerji, Dahlia; Martinez, Felipe; Abbara, Suhny; Truong, Quynh A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Cardiac MR PET CT Program, Boston, MA 02114 USA. [Truong, Quynh A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Truong, QA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM qtruong@partners.org FU NIH [K23HL098370, L30HL093896] FX Q.A.T. has received support from NIH grants K23HL098370 and L30HL093896. The other authors report no conflicts of interest. NR 1 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD MAY-JUN PY 2011 VL 5 IS 3 BP 189 EP 191 DI 10.1016/j.jcct.2011.01.008 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 035HD UT WOS:000310933100011 PM 21376695 ER PT J AU Andrews, J Cenzer, IS Yelin, E Covinsky, K AF Andrews, James Cenzer, Irena Stijacic Yelin, Ed Covinsky, Kenneth TI PAIN AND DISABILITY IN ELDERS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Andrews, James] Univ Calif San Francisco, Burlingame, CA USA. [Cenzer, Irena Stijacic; Covinsky, Kenneth] San Francisco VA Med Ctr, San Francisco, CA USA. [Yelin, Ed] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S51 EP S51 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812700088 ER PT J AU Arora, B Arora, B AF Arora, Bhaskar Arora, Bhaskar TI WEB BASED TOOL TO IMPROVE THROMBOEMBOLISM PROPHYLAXIS RATES IN HOSPITALIZED PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Arora, Bhaskar; Arora, Bhaskar] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S568 EP S568 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812703262 ER PT J AU Atlas, SJ Ashburner, J Chang, YC Grant, R Lester, W Chueh, H Barry, M AF Atlas, Steven J. Ashburner, Jeffrey Chang, Yuchiao Grant, Richard Lester, William Chueh, Henry Barry, Michael TI 3-YEAR FOLLOW-UP FROM A CLUSTER-RANDOMIZED TRIAL OF A PRIMARY CARE INFORMATICS-BASED SYSTEM FOR BREAST CANCER SCREENING SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Atlas, Steven J.; Ashburner, Jeffrey; Chang, Yuchiao; Grant, Richard; Lester, William; Chueh, Henry; Barry, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S31 EP S32 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812700051 ER PT J AU Atlas, SJ Ashburner, J Grant, R Percac-Lima, S Zai, A AF Atlas, Steven J. Ashburner, Jeffrey Grant, Richard Percac-Lima, Sanja Zai, Adrian TI IDENTIFYING PATIENTS AT INCREASED RISK FOR NOT COMPLETING PREVENTIVE CANCER SCREENING TESTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Atlas, Steven J.; Ashburner, Jeffrey; Grant, Richard; Percac-Lima, Sanja; Zai, Adrian] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S37 EP S37 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812700060 ER PT J AU Bachhuber, M Bachhuber, M AF Bachhuber, Melissa Bachhuber, Melissa TI DERMATOMYOSITIS IN A PATIENT WITH METASTATIC CHOLANGIOCARCINOMA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Bachhuber, Melissa; Bachhuber, Melissa] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S522 EP S523 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812703159 ER PT J AU Baggett, TP Rigotti, NA Stringfellow, E Hwang, SW Orav, EJ O'Connell, JJ AF Baggett, Travis P. Rigotti, Nancy A. Stringfellow, Erin Hwang, Stephen W. Orav, E. John O'Connell, James J. TI MORTALITY AND CAUSES OF DEATH AMONG HOMELESS ADULTS IN BOSTON SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Baggett, Travis P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. [Stringfellow, Erin; O'Connell, James J.] Boston Hlth Care Homeless Program, Boston, MA USA. [Hwang, Stephen W.] Univ Toronto, Toronto, ON, Canada. [Orav, E. John] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S234 EP S234 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812701197 ER PT J AU Bean-Mayberry, B Goldzweig, C Washington, DL Yano, E Batuman, F Huang, C Miake-Lye, I Shekelle, P AF Bean-Mayberry, Bevanne Goldzweig, Caroline Washington, Donna L. Yano, Elizabeth Batuman, Fatma Huang, Christine Miake-Lye, Isomi Shekelle, Paul TI UPDATED SYSTEMATIC REVIEW OF THE LITERATURE ON WOMEN VETERAN'S HEALTH SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Bean-Mayberry, Bevanne; Goldzweig, Caroline; Washington, Donna L.; Yano, Elizabeth; Batuman, Fatma; Huang, Christine; Miake-Lye, Isomi; Shekelle, Paul] VA Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S296 EP S297 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812702015 ER PT J AU Bitton, A Kincheloe, J Bates, D Weissman, J AF Bitton, Asaf Kincheloe, Jennifer Bates, David Weissman, Joel TI PATIENT EXPERIENCE WITH PATIENT-CENTERED MEDICAL HOMES AND ASSOCIATED QUALITY OF CARE IN MASSACHUSETTS, 2009 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Bitton, Asaf] Brigham & Womens Hosp, Div Gen Med, Brookline, MA USA. [Kincheloe, Jennifer] Kincheloe Hlth, Denver, CO USA. [Bates, David] Brigham & Womens Hosp, Boston, MA 02115 USA. [Weissman, Joel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S351 EP S352 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812702119 ER PT J AU Bokhour, B Fix, G Solomon, J Cohn, ES Cortes, DE Mueller, N Katz, L Borzecki, A Haidet, P Green, A Kressin, N AF Bokhour, Barbara Fix, Gemmae Solomon, Jeffrey Cohn, Ellen S. Cortes, Dharma E. Mueller, Nora Katz, Lois Borzecki, Ann Haidet, Paul Green, Alexander Kressin, Nancy TI RACIAL/ETHNIC DIFFERENCES IN EXPLANATORY MODELS, DAILY LIVED EXPERIENCE AND HTN MANAGEMENT BEHAVIORS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Bokhour, Barbara] ENRM VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Fix, Gemmae; Solomon, Jeffrey; Mueller, Nora; Borzecki, Ann] ENRM Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Cohn, Ellen S.] Boston Univ, Sargent Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. [Cortes, Dharma E.] Harvard Univ, Sch Med, Boston, MA USA. [Cortes, Dharma E.] Cambridge Hlth Alliance, Boston, MA USA. [Katz, Lois] New York Harbor VA Healthcare Syst, Larchmont, NY USA. [Haidet, Paul] Penn State Univ, Coll Med, Hershey, PA USA. [Green, Alexander] Massachusetts Gen Hosp, Cambridge, MA USA. [Kressin, Nancy] Boston Univ, Sch Med, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S270 EP S270 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812701269 ER PT J AU Borrero, S Mor, M Zhao, XH McNeil, M Ibrahim, S Hayes, P AF Borrero, Sonya Mor, Maria Zhao, Xinhua McNeil, Melissa Ibrahim, Said Hayes, Patricia TI CONTRACEPTIVE CARE IN THE VA HEALTHCARE SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Borrero, Sonya; McNeil, Melissa] Univ Pittsburgh, Pittsburgh, PA USA. [Mor, Maria; Zhao, Xinhua] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ibrahim, Said] Va Med Ctr, Philadelphia, PA USA. [Hayes, Patricia] Women Vet Hlth Strateg Hlth Care Grp, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S114 EP S114 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812700203 ER PT J AU Brooks, R Jasti, H AF Brooks, Robert Jasti, Harish TI TOWARD THE LEARNER-CENTERED PATIENT-CENTERED MEDICAL HOME: DIFFERENCES BETWEEN UNIVERSITY AND VA CLINICS IN FACTORS THAT AFFECT RESIDENT CONTINUITY WITH PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Brooks, Robert] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Jasti, Harish] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S339 EP S339 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812702096 ER PT J AU Buettner, C Rippberger, M Liang, MH AF Buettner, Catherine Rippberger, Matthew Liang, Matthew H. TI THE ASSOCIATION OF STATIN USE AND MUSCULOSKELETAL PAIN IN ADULTS WITH OSTEOARTHRITIS AND RHEUMATOID ARTHRITIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Buettner, Catherine; Rippberger, Matthew] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Buettner, Catherine; Liang, Matthew H.] Harvard Univ, Sch Med, Boston, MA USA. [Rippberger, Matthew] Boston Univ, Boston, MA 02215 USA. [Liang, Matthew H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Liang, Matthew H.] Boston VA Healthcare Syst, Boston, MA USA. [Liang, Matthew H.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S301 EP S301 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812702025 ER PT J AU Burgo-Black, L Hunt, SC Burgo-Black, L Spelman, J AF Burgo-Black, Lucille Hunt, Stephen C. Burgo-Black, Lucille Spelman, Juliette TI POST COMBAT CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Burgo-Black, Lucille; Spelman, Juliette] VA Connecticut Healthcare, West Haven, CT USA. [Hunt, Stephen C.] VA Puget Sound, Seattle, WA USA. [Burgo-Black, Lucille] VA Connectict Healthcare Syst, West Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S509 EP S510 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812703131 ER PT J AU Chatterjee, N He, YL Keating, NL AF Chatterjee, Neal He, Yulei Keating, Nancy L. TI RACIAL DISPARITIES IN BREAST CANCER STAGE AT DIAGNOSIS IN THE MAMMOGRAPHY ERA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Chatterjee, Neal] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [He, Yulei; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S24 EP S25 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812700039 ER PT J AU Clair, C Rigotti, NA Shrader, P Caroline Pencina, MSF Meigs, J AF Clair, Carole Rigotti, Nancy A. Shrader, Peter Caroline Pencina, Michael S. Fox Meigs, James TI EFFECTS OF SMOKING CESSATION AND WEIGHT CHANGE ON CARDIOVASCULAR DISEASE AMONG PEOPLE WITH AND WITHOUT DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Clair, Carole; Shrader, Peter; Caroline] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. [Pencina, Michael S. Fox] Boston Univ, NHLBI, Framingham Heart Study, Framingham, MA USA. [Meigs, James] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RI Clair, Carole/D-9786-2014 OI Clair, Carole/0000-0001-5281-0943 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S12 EP S14 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812700023 ER PT J AU Cohen, B O'Donovan, A Neylan, T Metzler, T Whooley, M AF Cohen, Beth O'Donovan, Aoife Neylan, Thomas Metzler, Thomas Whooley, Mary TI LIFETIME EXPOSURE TO TRAUMATIC PSYCHOLOGICAL STRESS IS ASSOCIATED WITH GREATER INCREASES IN INFLAMMATORY ACTIVITY OVER TIME IN PATIENTS WITH CARDIOVASCULAR DISEASE: PROSPECTIVE FINDINGS FROM THE HEART AND SOUL STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Cohen, Beth; O'Donovan, Aoife; Neylan, Thomas; Whooley, Mary] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Metzler, Thomas] San Francisco VA, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S288 EP S289 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812702003 ER PT J AU Cohen, M Shaykevich, S Cawthon, C Kripalani, S Paasche-Orlow, M Schnipper, J AF Cohen, Marya Shaykevich, Shimon Cawthon, Courtney Kripalani, Sunil Paasche-Orlow, Michael Schnipper, Jeffrey TI INCIDENCE AND PREDICTORS OF MEDICATION NON-ADHERENCE AFTER HOSPITALIZATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Cohen, Marya] Massachusetts Gen Hosp, Brookline, MA USA. [Shaykevich, Shimon] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cawthon, Courtney; Kripalani, Sunil] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Paasche-Orlow, Michael] Boston Med Ctr, Newton, MA USA. [Schnipper, Jeffrey] Brigham & Womens Hosp, Sharon, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S247 EP S248 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812701223 ER PT J AU Cordasco, KM Ryan, G Dominguez, BX Huynh, A Homeier, DC Derose, KP Sarkisian, CA AF Cordasco, Kristina M. Ryan, Gery Dominguez, Blanca X. Huynh, Alexis Homeier, Diana C. Derose, Kathyrn Pitkin Sarkisian, Catherine A. TI LITERACY-COMPENSATORY STRATEGIES AND RESOURCES OF OLDER LATINOS WITH DIABETES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Cordasco, Kristina M.; Sarkisian, Catherine A.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Cordasco, Kristina M.] RAND Corp, Los Angeles, CA USA. [Cordasco, Kristina M.; Sarkisian, Catherine A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Ryan, Gery; Dominguez, Blanca X.; Huynh, Alexis; Derose, Kathyrn Pitkin] RAND Corp, Santa Monica, CA USA. [Homeier, Diana C.] LAC USC Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S183 EP S183 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812701103 ER PT J AU Dodds, C Cooper, CM AF Dodds, Catherine Cooper, Cynthia Margaret TI WHITE HERRING: STEMI OR NOT? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Dodds, Catherine; Cooper, Cynthia Margaret] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2011 VL 26 SU 1 BP S494 EP S495 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V30JQ UT WOS:000208812703098 ER EF